Robert Harrington, MD, recently was tabbed as chief medical officer of SurveyVitals, a health care analytics company specializing in digital patient-experience surveys. Dr. Harrington has 20 years experience, including CMO roles with Reliant Post–Acute Care Solutions and Locum Leaders, a hospitalist staffing firm.

David Northington, DO, has been named the new chief medical officer at Stone County Hospital in Wiggins, Miss. The former hospitalist comes to Stone County after working as chief of staff and chief medical information officer at Memorial Hospital in Gulfport, Miss., where he was also medical director of the hospitalist program.

In addition to his new role, Dr. Northington will serve as medical director of the Woodland Village Nursing Center in Diamondhead, Miss., and the Stone County Nursing and Rehabilitation Center in Wiggins.
 

Schuyler K. Geller, MD, has been recognized by Continental Who’s Who as a Pinnacle Lifetime Member in the medical field. Dr. Geller works as a full-time hospitalist and a principal consultant for The CopperRidge Group, which provides guidance to patients in health, wellness, and fitness services and products.

In addition to his work at the CopperRidge Group, Dr. Geller is a member of Civil Vision International’s board of directors. He has extensive civilian and military-based experience in the United States, Africa, the Middle East, and South Asia.

A physician leader in the U.S. Air Force, Dr. Geller earned White House Medical Unit commendations for planning and leading the surgical and intensive care unit teams to support President Clinton’s trips to Vietnam and Africa in 2000.
 

Nikhil Sharma, MD, recently was selected by the International Association of HealthCare Professionals to be part of the Leading Physicians of the World. Dr. Sharma is a hospitalist serving at the Ochsner Health System in New Orleans.

Dr. Sharma, a member of the Southern Hospital Association and the Louisiana Medical Association, began his medical career in 2009 with a residency and fellowship at Ochsner, where he has remained ever since. He specializes in internal medicine and transplants.
 

I. Carol Nwelue, MD, a longtime hospitalist and the medical director of the Sparrow Medical Group Adult Hospitalist Service, recently received the Sparrow Physician Leadership Award. The award goes to an emerging leader who provides outstanding work in areas such as safety, clinical or service excellence, research, teaching, publishing, teamwork, and innovation.

Dr. Nwelue completed the Sparrow Physician Leadership Academy program, earning recognition for innovation in leadership, as well as practice management.
 

Laura Jin, MD, recently was promoted to medical director for utilization management at the University of Maryland Shore Regional Health. In her new role, Dr. Jin will identify and facilitate the resolution of utilization issues; in so doing, she will serve as a consultant leader to the health care system, its physicians, its advance practice providers, and the care management team.

Dr. Jin will remain as a hospitalist at Digestive Health Associates while fulfilling the duties in her new position at Shore Regional. She will guide the center on issues such as compliance, level of care, length of stay, resource management, reimbursement, emergency department throughput, and more.
 

Business Moves

The Mount Sinai Health System and The New Jewish Home, both based in New York City, have extended their relationship to improve care of hospitalized patients who require specialized post-acute or long-term care at a skilled nursing facility. Through the Mount Sinai-New Jewish Home Hospitalist Program, Mount Sinai hospitalists will be charged with providing a seamless transition to The New Jewish Home for patients who need nursing care.

This model will buoy communication and ensure the sharing of vital information between the two venues, reducing the risk of rehospitalization.
 

Gryphon Investors, based in San Francisco, recently announced it will acquire OB Hospitalist Group, one of the nation’s leading providers of obstetric hospital medicine. The deal with OBHG’s current partner, Ares Management, was finalized in late July.

OBHG, based out of Mauldin, S.C., has a national network of more than 550 OB hospitalists, covering more than 120 hospitals in 28 states. OBHG’s hospitalist program features an obstetric emergency department, providing expectant mothers at partner hospitals with 24/7/365 access to medical care.
 

Envision Healthcare, based in Nashville, Tenn., and Greenwood Village, Colo., a provider of physician-led services and ambulatory surgery services, has acquired Milwaukee-based Infinity Healthcare. Infinity’s group-physician practice includes more than 340 physicians and providers delivering emergency and hospital medicine, anesthesia, and radiology services.

Robert Harrington, MD, recently was tabbed as chief medical officer of SurveyVitals, a health care analytics company specializing in digital patient-experience surveys. Dr. Harrington has 20 years experience, including CMO roles with Reliant Post–Acute Care Solutions and Locum Leaders, a hospitalist staffing firm.

David Northington, DO, has been named the new chief medical officer at Stone County Hospital in Wiggins, Miss. The former hospitalist comes to Stone County after working as chief of staff and chief medical information officer at Memorial Hospital in Gulfport, Miss., where he was also medical director of the hospitalist program.

In addition to his new role, Dr. Northington will serve as medical director of the Woodland Village Nursing Center in Diamondhead, Miss., and the Stone County Nursing and Rehabilitation Center in Wiggins.
 

Schuyler K. Geller, MD, has been recognized by Continental Who’s Who as a Pinnacle Lifetime Member in the medical field. Dr. Geller works as a full-time hospitalist and a principal consultant for The CopperRidge Group, which provides guidance to patients in health, wellness, and fitness services and products.

In addition to his work at the CopperRidge Group, Dr. Geller is a member of Civil Vision International’s board of directors. He has extensive civilian and military-based experience in the United States, Africa, the Middle East, and South Asia.

A physician leader in the U.S. Air Force, Dr. Geller earned White House Medical Unit commendations for planning and leading the surgical and intensive care unit teams to support President Clinton’s trips to Vietnam and Africa in 2000.
 

Nikhil Sharma, MD, recently was selected by the International Association of HealthCare Professionals to be part of the Leading Physicians of the World. Dr. Sharma is a hospitalist serving at the Ochsner Health System in New Orleans.

Dr. Sharma, a member of the Southern Hospital Association and the Louisiana Medical Association, began his medical career in 2009 with a residency and fellowship at Ochsner, where he has remained ever since. He specializes in internal medicine and transplants.
 

I. Carol Nwelue, MD, a longtime hospitalist and the medical director of the Sparrow Medical Group Adult Hospitalist Service, recently received the Sparrow Physician Leadership Award. The award goes to an emerging leader who provides outstanding work in areas such as safety, clinical or service excellence, research, teaching, publishing, teamwork, and innovation.

Dr. Nwelue completed the Sparrow Physician Leadership Academy program, earning recognition for innovation in leadership, as well as practice management.
 

Laura Jin, MD, recently was promoted to medical director for utilization management at the University of Maryland Shore Regional Health. In her new role, Dr. Jin will identify and facilitate the resolution of utilization issues; in so doing, she will serve as a consultant leader to the health care system, its physicians, its advance practice providers, and the care management team.

Dr. Jin will remain as a hospitalist at Digestive Health Associates while fulfilling the duties in her new position at Shore Regional. She will guide the center on issues such as compliance, level of care, length of stay, resource management, reimbursement, emergency department throughput, and more.
 

Business Moves

The Mount Sinai Health System and The New Jewish Home, both based in New York City, have extended their relationship to improve care of hospitalized patients who require specialized post-acute or long-term care at a skilled nursing facility. Through the Mount Sinai-New Jewish Home Hospitalist Program, Mount Sinai hospitalists will be charged with providing a seamless transition to The New Jewish Home for patients who need nursing care.

This model will buoy communication and ensure the sharing of vital information between the two venues, reducing the risk of rehospitalization.
 

Gryphon Investors, based in San Francisco, recently announced it will acquire OB Hospitalist Group, one of the nation’s leading providers of obstetric hospital medicine. The deal with OBHG’s current partner, Ares Management, was finalized in late July.

OBHG, based out of Mauldin, S.C., has a national network of more than 550 OB hospitalists, covering more than 120 hospitals in 28 states. OBHG’s hospitalist program features an obstetric emergency department, providing expectant mothers at partner hospitals with 24/7/365 access to medical care.
 

Envision Healthcare, based in Nashville, Tenn., and Greenwood Village, Colo., a provider of physician-led services and ambulatory surgery services, has acquired Milwaukee-based Infinity Healthcare. Infinity’s group-physician practice includes more than 340 physicians and providers delivering emergency and hospital medicine, anesthesia, and radiology services.

Robert Harrington, MD, recently was tabbed as chief medical officer of SurveyVitals, a health care analytics company specializing in digital patient-experience surveys. Dr. Harrington has 20 years experience, including CMO roles with Reliant Post–Acute Care Solutions and Locum Leaders, a hospitalist staffing firm.

David Northington, DO, has been named the new chief medical officer at Stone County Hospital in Wiggins, Miss. The former hospitalist comes to Stone County after working as chief of staff and chief medical information officer at Memorial Hospital in Gulfport, Miss., where he was also medical director of the hospitalist program.

In addition to his new role, Dr. Northington will serve as medical director of the Woodland Village Nursing Center in Diamondhead, Miss., and the Stone County Nursing and Rehabilitation Center in Wiggins.
 

Schuyler K. Geller, MD, has been recognized by Continental Who’s Who as a Pinnacle Lifetime Member in the medical field. Dr. Geller works as a full-time hospitalist and a principal consultant for The CopperRidge Group, which provides guidance to patients in health, wellness, and fitness services and products.

In addition to his work at the CopperRidge Group, Dr. Geller is a member of Civil Vision International’s board of directors. He has extensive civilian and military-based experience in the United States, Africa, the Middle East, and South Asia.

A physician leader in the U.S. Air Force, Dr. Geller earned White House Medical Unit commendations for planning and leading the surgical and intensive care unit teams to support President Clinton’s trips to Vietnam and Africa in 2000.
 

Nikhil Sharma, MD, recently was selected by the International Association of HealthCare Professionals to be part of the Leading Physicians of the World. Dr. Sharma is a hospitalist serving at the Ochsner Health System in New Orleans.

Dr. Sharma, a member of the Southern Hospital Association and the Louisiana Medical Association, began his medical career in 2009 with a residency and fellowship at Ochsner, where he has remained ever since. He specializes in internal medicine and transplants.
 

I. Carol Nwelue, MD, a longtime hospitalist and the medical director of the Sparrow Medical Group Adult Hospitalist Service, recently received the Sparrow Physician Leadership Award. The award goes to an emerging leader who provides outstanding work in areas such as safety, clinical or service excellence, research, teaching, publishing, teamwork, and innovation.

Dr. Nwelue completed the Sparrow Physician Leadership Academy program, earning recognition for innovation in leadership, as well as practice management.
 

Laura Jin, MD, recently was promoted to medical director for utilization management at the University of Maryland Shore Regional Health. In her new role, Dr. Jin will identify and facilitate the resolution of utilization issues; in so doing, she will serve as a consultant leader to the health care system, its physicians, its advance practice providers, and the care management team.

Dr. Jin will remain as a hospitalist at Digestive Health Associates while fulfilling the duties in her new position at Shore Regional. She will guide the center on issues such as compliance, level of care, length of stay, resource management, reimbursement, emergency department throughput, and more.
 

Business Moves

The Mount Sinai Health System and The New Jewish Home, both based in New York City, have extended their relationship to improve care of hospitalized patients who require specialized post-acute or long-term care at a skilled nursing facility. Through the Mount Sinai-New Jewish Home Hospitalist Program, Mount Sinai hospitalists will be charged with providing a seamless transition to The New Jewish Home for patients who need nursing care.

This model will buoy communication and ensure the sharing of vital information between the two venues, reducing the risk of rehospitalization.
 

Gryphon Investors, based in San Francisco, recently announced it will acquire OB Hospitalist Group, one of the nation’s leading providers of obstetric hospital medicine. The deal with OBHG’s current partner, Ares Management, was finalized in late July.

OBHG, based out of Mauldin, S.C., has a national network of more than 550 OB hospitalists, covering more than 120 hospitals in 28 states. OBHG’s hospitalist program features an obstetric emergency department, providing expectant mothers at partner hospitals with 24/7/365 access to medical care.
 

Envision Healthcare, based in Nashville, Tenn., and Greenwood Village, Colo., a provider of physician-led services and ambulatory surgery services, has acquired Milwaukee-based Infinity Healthcare. Infinity’s group-physician practice includes more than 340 physicians and providers delivering emergency and hospital medicine, anesthesia, and radiology services.

Evaluating pediatric patients presenting to the ED with head trauma can be a challenging task for emergency physicians (EPs). Specifically, identifying a nondisplaced skull fracture is not always possible through physical examination alone.¹ However, point-of-care (POC) ultrasound permits rapid identification of skull fractures, which in turn assists the EP to determine if advanced imaging studies such as computed tomography (CT) are necessary.

Case

A previously healthy 10-month-old male infant presented to the ED with his mother for evaluation of rhinorrhea, cough, and fever, the onset of which began 24 hours prior to presentation. The patient’s mother reported that the infant continually tugged at his right ear throughout the previous evening and was increasingly irritable, but not inconsolable.

Initial vital signs at presentation were: blood pressure, 95/54 mm Hg; heart rate, 146 beats/min; respiratory rate, 36 beats/min, and temperature, 101.8°F. Oxygen saturation was 96% on room air. The physical examination was notable for an alert well-appearing infant who had a tender nonecchymotic scalp hematoma superior to the right pinna, clear tympanic membranes, crusted mucous bilaterally at the nares, nonlabored respirations, and wheezing throughout the lung fields.

Imaging Technique

To evaluate for skull fractures using POC ultrasound, the area of localized trauma must first be identified.^2,3 Evidence of trauma includes an area of focal tenderness, abrasion, soft-tissue swelling, and hematoma.^2,3 The presence of any depressed and open cranial injuries are contraindications to ultrasound. In which case, a physician should consult a neurosurgical specialist and obtain a CT scan of the head.

A high-frequency linear probe (5-10 MHz) is used to scan the area of localized trauma; this should be performed in two perpendicular planes using copious gel and light pressure (Figures 2a-2c).

Discussion

Closed head trauma is one of the most common pediatric injuries, accounting for roughly 1.4 million ED visits annually in the United States.⁵ Four to 12% percent of these minor traumas result in an intracranial injury,² and the presence of a skull fracture is associated with a 4- to 20-fold increase in risk of underlying intracranial hemorrhage.³

Clinical assessment alone is not always reliable in predicting skull fracture and intracranial injury, especially in children younger than 2 years of age.^2,3 Ultrasound is safe, noninvasive, expedient, cost-effective, and well tolerated in the pediatric population for identifying skull fractures,³ and can obviate the need for skull radiographs⁴ or procedural sedation. Moreover, POC ultrasound can serve as an adjunct to the Pediatric Emergency Care Applied Research Network head injury algorithm for head CT use decision rules if the fracture is not palpable on examination.

Several prospective studies and case reports have demonstrated the usefulness of POC ultrasound in diagnosing pediatric skull fractures in the ED.^1-4 Two of the four cases published represented cases in which the EP identified an undisclosed nonaccidental trauma through POC ultrasound. Rabiner et al,³ estimates a combined sensitivity and specificity of 94% and 96%, respectively. It is important to remember that intracranial injury can still occur without an associated skull fracture. As our case demonstrates, POC ultrasound is a useful tool in risk-stratifying minor head trauma in children.

Case Conclusion

The head CT study confirmed a nondisplaced, oblique, and acute-appearing linear fracture of the right parietal bone extending from the squamosal to the lambdoid suture. There was no associated intracranial hemorrhage. The patient was admitted to the hospital for a nonaccidental trauma evaluation. The Department of Children and Family Services was contacted and the patient was discharged in the temporary custody of his maternal grandmother.

Summary

Point-of-care ultrasound is a useful diagnostic tool to rapidly evaluate for, and diagnose skull fractures in pediatric patients. Given its high sensitivity and specificity, ultrasound can help EPs identify occult nondisplaced skull fractures in children.

Evaluating pediatric patients presenting to the ED with head trauma can be a challenging task for emergency physicians (EPs). Specifically, identifying a nondisplaced skull fracture is not always possible through physical examination alone.¹ However, point-of-care (POC) ultrasound permits rapid identification of skull fractures, which in turn assists the EP to determine if advanced imaging studies such as computed tomography (CT) are necessary.

Case

A previously healthy 10-month-old male infant presented to the ED with his mother for evaluation of rhinorrhea, cough, and fever, the onset of which began 24 hours prior to presentation. The patient’s mother reported that the infant continually tugged at his right ear throughout the previous evening and was increasingly irritable, but not inconsolable.

Initial vital signs at presentation were: blood pressure, 95/54 mm Hg; heart rate, 146 beats/min; respiratory rate, 36 beats/min, and temperature, 101.8°F. Oxygen saturation was 96% on room air. The physical examination was notable for an alert well-appearing infant who had a tender nonecchymotic scalp hematoma superior to the right pinna, clear tympanic membranes, crusted mucous bilaterally at the nares, nonlabored respirations, and wheezing throughout the lung fields.

Imaging Technique

To evaluate for skull fractures using POC ultrasound, the area of localized trauma must first be identified.^2,3 Evidence of trauma includes an area of focal tenderness, abrasion, soft-tissue swelling, and hematoma.^2,3 The presence of any depressed and open cranial injuries are contraindications to ultrasound. In which case, a physician should consult a neurosurgical specialist and obtain a CT scan of the head.

A high-frequency linear probe (5-10 MHz) is used to scan the area of localized trauma; this should be performed in two perpendicular planes using copious gel and light pressure (Figures 2a-2c).

Discussion

Closed head trauma is one of the most common pediatric injuries, accounting for roughly 1.4 million ED visits annually in the United States.⁵ Four to 12% percent of these minor traumas result in an intracranial injury,² and the presence of a skull fracture is associated with a 4- to 20-fold increase in risk of underlying intracranial hemorrhage.³

Clinical assessment alone is not always reliable in predicting skull fracture and intracranial injury, especially in children younger than 2 years of age.^2,3 Ultrasound is safe, noninvasive, expedient, cost-effective, and well tolerated in the pediatric population for identifying skull fractures,³ and can obviate the need for skull radiographs⁴ or procedural sedation. Moreover, POC ultrasound can serve as an adjunct to the Pediatric Emergency Care Applied Research Network head injury algorithm for head CT use decision rules if the fracture is not palpable on examination.

Several prospective studies and case reports have demonstrated the usefulness of POC ultrasound in diagnosing pediatric skull fractures in the ED.^1-4 Two of the four cases published represented cases in which the EP identified an undisclosed nonaccidental trauma through POC ultrasound. Rabiner et al,³ estimates a combined sensitivity and specificity of 94% and 96%, respectively. It is important to remember that intracranial injury can still occur without an associated skull fracture. As our case demonstrates, POC ultrasound is a useful tool in risk-stratifying minor head trauma in children.

Case Conclusion

The head CT study confirmed a nondisplaced, oblique, and acute-appearing linear fracture of the right parietal bone extending from the squamosal to the lambdoid suture. There was no associated intracranial hemorrhage. The patient was admitted to the hospital for a nonaccidental trauma evaluation. The Department of Children and Family Services was contacted and the patient was discharged in the temporary custody of his maternal grandmother.

Summary

Point-of-care ultrasound is a useful diagnostic tool to rapidly evaluate for, and diagnose skull fractures in pediatric patients. Given its high sensitivity and specificity, ultrasound can help EPs identify occult nondisplaced skull fractures in children.

Evaluating pediatric patients presenting to the ED with head trauma can be a challenging task for emergency physicians (EPs). Specifically, identifying a nondisplaced skull fracture is not always possible through physical examination alone.¹ However, point-of-care (POC) ultrasound permits rapid identification of skull fractures, which in turn assists the EP to determine if advanced imaging studies such as computed tomography (CT) are necessary.

Case

A previously healthy 10-month-old male infant presented to the ED with his mother for evaluation of rhinorrhea, cough, and fever, the onset of which began 24 hours prior to presentation. The patient’s mother reported that the infant continually tugged at his right ear throughout the previous evening and was increasingly irritable, but not inconsolable.

Initial vital signs at presentation were: blood pressure, 95/54 mm Hg; heart rate, 146 beats/min; respiratory rate, 36 beats/min, and temperature, 101.8°F. Oxygen saturation was 96% on room air. The physical examination was notable for an alert well-appearing infant who had a tender nonecchymotic scalp hematoma superior to the right pinna, clear tympanic membranes, crusted mucous bilaterally at the nares, nonlabored respirations, and wheezing throughout the lung fields.

Imaging Technique

To evaluate for skull fractures using POC ultrasound, the area of localized trauma must first be identified.^2,3 Evidence of trauma includes an area of focal tenderness, abrasion, soft-tissue swelling, and hematoma.^2,3 The presence of any depressed and open cranial injuries are contraindications to ultrasound. In which case, a physician should consult a neurosurgical specialist and obtain a CT scan of the head.

A high-frequency linear probe (5-10 MHz) is used to scan the area of localized trauma; this should be performed in two perpendicular planes using copious gel and light pressure (Figures 2a-2c).

Discussion

Closed head trauma is one of the most common pediatric injuries, accounting for roughly 1.4 million ED visits annually in the United States.⁵ Four to 12% percent of these minor traumas result in an intracranial injury,² and the presence of a skull fracture is associated with a 4- to 20-fold increase in risk of underlying intracranial hemorrhage.³

Clinical assessment alone is not always reliable in predicting skull fracture and intracranial injury, especially in children younger than 2 years of age.^2,3 Ultrasound is safe, noninvasive, expedient, cost-effective, and well tolerated in the pediatric population for identifying skull fractures,³ and can obviate the need for skull radiographs⁴ or procedural sedation. Moreover, POC ultrasound can serve as an adjunct to the Pediatric Emergency Care Applied Research Network head injury algorithm for head CT use decision rules if the fracture is not palpable on examination.

Several prospective studies and case reports have demonstrated the usefulness of POC ultrasound in diagnosing pediatric skull fractures in the ED.^1-4 Two of the four cases published represented cases in which the EP identified an undisclosed nonaccidental trauma through POC ultrasound. Rabiner et al,³ estimates a combined sensitivity and specificity of 94% and 96%, respectively. It is important to remember that intracranial injury can still occur without an associated skull fracture. As our case demonstrates, POC ultrasound is a useful tool in risk-stratifying minor head trauma in children.

Case Conclusion

The head CT study confirmed a nondisplaced, oblique, and acute-appearing linear fracture of the right parietal bone extending from the squamosal to the lambdoid suture. There was no associated intracranial hemorrhage. The patient was admitted to the hospital for a nonaccidental trauma evaluation. The Department of Children and Family Services was contacted and the patient was discharged in the temporary custody of his maternal grandmother.

Summary

Point-of-care ultrasound is a useful diagnostic tool to rapidly evaluate for, and diagnose skull fractures in pediatric patients. Given its high sensitivity and specificity, ultrasound can help EPs identify occult nondisplaced skull fractures in children.

An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Sports-related injuries to the larynx and related structures are uncommon.^6,7

Case

A 38-year-old man presented with a complaint of throat pain after wrestling at home, in horseplay, with his 15-year-old son. He reported that when his son placed a choke hold on him, he felt a "crack" in the area of his neck, and soon afterwards felt throat pain with swallowing, along with discomfort with breathing. He also felt a sensation of "fluid building up in his throat." There were no changes noted with his voice and the patient was speaking in full sentences. There was no wheezing or stridor. He denied shortness of breath or any other complaints. He denied pain over the posterior elements of his cervical spine. At the time of the incident, there was no loss of consciousness. Palpation of the neck and chest did not elicit any crepitance to suggest subcutaneous emphysema. The trachea was midline. There was no pain overlying the carotids bilaterally, and the patient had no bruits. The neck examination did not show any surface abnormalities to suggest trauma, such as ecchymosis or swelling. He did have slight tenderness to palpation over the thyroid cartilage.

The patient was sent for a computed tomography (CT) scan of the soft-tissue neck with intravenous (IV) contrast, and a CT scan of the cervical spine. The results showed no cervical spine fracture. However, there was a minimally displaced fracture of the left thyroid cartilage, with soft-tissue swelling that was noted, along with minimal narrowing of the subglottic trachea. There were no abnormal enhancements or fluid collections. No evidence of vocal cord abnormality or asymmetry was seen, and there was no evidence of airway compromise (Figure).

Discussion

Our patient sustained an isolated thyroid cartilage fracture. A thyroid cartilage fracture is a type of laryngeal fracture. Using an anatomic system in which such injuries are classified by location (supraglottic, glottis, or infraglottic), a thyroid cartilage fracture is classified as a supraglottic laryngeal injury.^1,2 In our case, the fracture was due to a blunt force mechanism. Most blunt force laryngeal fractures are associated with multiple trauma.⁸ An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature.

Sports-related injuries to the larynx and related structures are uncommon.^6,7 When reported, significant force is usually involved. For example, Tasca et al⁶ reported a thyroid cartilage fracture from direct blunt trauma (rugby, opponent stamped on patient’s throat) in which the patient presented with pain with swallowing and a lowering of the pitch of his voice. Rejali et al⁹ reported the case of a midair collision in a soccer match, resulting in an obvious mandibular fracture, but with an arytenoid cartilage fracture that was not initially identified. A football struck a 17-year-old boy with a resulting fracture of the superior cornu of the larynx and a puncture of the laryngeal mucosal wall in a case reported by Saab and Birkinshaw.¹⁰ The patient presented with neck pain and dysphagia, as well as subcutaneous air.¹⁰ A 21-year-old collegiate basketball player was struck in the neck by a teammate’s head while jumping for a rebound. He sustained a fracture of the thyroid cartilage and a fracture of the anterior cricoid ring.³Patients with such injuries "may appear deceptively normal when seeking medical attention."⁸ Kragha² refers to such injuries as "rare but potentially deadly."

Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, and even subcutaneous emphysema. There may be loss of prominence of the thyroid cartilage.³ Tracheal deviation and stridor can occur.^10,11 Computed tomography scan and laryngoscopy can be helpful in the diagnostic process; 3-dimensional (3-D) reconstructions may be needed.

Various classification systems have been proposed with related treatment strategies. Percevik et al¹¹ summarized a five-part clinical classification. Group 1 (hematoma, no fracture) and Group 2 (non-displaced fracture) may be treated conservatively. Group 3 (stable, displaced fracture), Group 4 (unstable, displaced fracture), and Group 5 (laryngotracheal disinsertion) are more likely to be treated with surgery.¹¹ Surgical techniques vary and have been refined over time.¹²

In this case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible that this injury may have involved neck hyperflexion, rather than direct compressive force. Lin et al,¹ described a case of neck hyperflexion in an unrestrained driver, with a resulting isolated thyroid cartilage fracture without direct impact to the neck. Walsh and Trotter⁵ presented a case of a motorcyclist with a blow to the back of the head, with resulting neck hyperflexion, which resulted in a fracture of the thyroid cartilage. Beato-Martínez et al,¹³ reported a case of thyroid cartilage fracture following a sneezing episode. The patient presented with odynophagia, dysphonia and neck pain.¹³ In our review of the literature, we found that only one other similar case has been reported. In that case, a patient experienced a feeling of a neck click, followed by neck pain and hoarseness. He sustained a fracture of the thyroid cartilage.¹⁴

In reviewing the hyperflexion mechanism, Lin et al¹ noted that isolated thyroid cartilage fractures are rare and that "most of these are caused by direct injury to the neck, except for two patients reported in the literature who sustained isolated thyroid cartilage fractures after sneezing." Lin et al¹ proposed an interesting hypothesis—that "the mechanism causing thyroid cartilage fracture during impaction may be the same with sneezing." Sneezing can be associated with sudden and forceful flexion of the neck.

It is certainly possible that this hyperflexion mechanism was involved in our case, given there was no history of significant blunt force to the neck, as in the sports-related injuries discussed. Wrestling holds can produce hyperflexion. The patient described a feeling of a "crack", which is similar to the clicking sound described in one of the sneezing-related cases. An isolated thyroid cartilage fracture is rare in the absence of major trauma. However, as noted by Rejali et al,⁹ this can create a potential management pitfall. "In the context of non-contact sports, the attendant doctor may not realize the significance of apparently minor head and neck trauma."⁹

There are no series data to provide us with an exact incidence of airway compromise. However, seemingly minor insults to the anterior neck can cause posterior compression of the larynx and can result in airway compromise.^9-11

The CT scan is described as an important imaging modality to rule out cervical spine fracture. Although there was no significant blunt force, the cervical spine was exposed to hyperflexion forces. Another important potential consequence is long-term injury to the vocal cords, with subsequent speech difficulties.¹¹ Computed tomography can visualize the thyroid fracture, but many authors point out that visualization of the vocal cords, with nasopharyngeal laryngoscopy or other modality, is an important adjunct to the CT scan.^9-11

Otolaryngologist consultation should be strongly considered. This patient was transferred to a tertiary care center with expertise in thyroid fractures, and planned nasopharyngeal laryngoscopy to be performed at the receiving institution.

Conclusion

Our patient sustained an isolated thyroid cartilage fracture. Most blunt force laryngeal fractures are associated with multiple trauma. An isolated thyroid cartilage fracture is very rare. An isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, or even subcutaneous emphysema. There may be loss of the prominence of the thyroid cartilage, tracheal deviation, and stridor. Computed tomography scan imaging with 3-D reconstructions and laryngoscopy can be helpful in the diagnostic process. In our case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible this injury may have involved neck hyperflexion, rather than direct compressive forces, similar to that described by Lin et al.¹ Certainly, there was no history of significant blunt force to the neck on the level of the sports-related injuries discussed.

An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Sports-related injuries to the larynx and related structures are uncommon.^6,7

Case

A 38-year-old man presented with a complaint of throat pain after wrestling at home, in horseplay, with his 15-year-old son. He reported that when his son placed a choke hold on him, he felt a "crack" in the area of his neck, and soon afterwards felt throat pain with swallowing, along with discomfort with breathing. He also felt a sensation of "fluid building up in his throat." There were no changes noted with his voice and the patient was speaking in full sentences. There was no wheezing or stridor. He denied shortness of breath or any other complaints. He denied pain over the posterior elements of his cervical spine. At the time of the incident, there was no loss of consciousness. Palpation of the neck and chest did not elicit any crepitance to suggest subcutaneous emphysema. The trachea was midline. There was no pain overlying the carotids bilaterally, and the patient had no bruits. The neck examination did not show any surface abnormalities to suggest trauma, such as ecchymosis or swelling. He did have slight tenderness to palpation over the thyroid cartilage.

The patient was sent for a computed tomography (CT) scan of the soft-tissue neck with intravenous (IV) contrast, and a CT scan of the cervical spine. The results showed no cervical spine fracture. However, there was a minimally displaced fracture of the left thyroid cartilage, with soft-tissue swelling that was noted, along with minimal narrowing of the subglottic trachea. There were no abnormal enhancements or fluid collections. No evidence of vocal cord abnormality or asymmetry was seen, and there was no evidence of airway compromise (Figure).

Discussion

Our patient sustained an isolated thyroid cartilage fracture. A thyroid cartilage fracture is a type of laryngeal fracture. Using an anatomic system in which such injuries are classified by location (supraglottic, glottis, or infraglottic), a thyroid cartilage fracture is classified as a supraglottic laryngeal injury.^1,2 In our case, the fracture was due to a blunt force mechanism. Most blunt force laryngeal fractures are associated with multiple trauma.⁸ An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature.

Sports-related injuries to the larynx and related structures are uncommon.^6,7 When reported, significant force is usually involved. For example, Tasca et al⁶ reported a thyroid cartilage fracture from direct blunt trauma (rugby, opponent stamped on patient’s throat) in which the patient presented with pain with swallowing and a lowering of the pitch of his voice. Rejali et al⁹ reported the case of a midair collision in a soccer match, resulting in an obvious mandibular fracture, but with an arytenoid cartilage fracture that was not initially identified. A football struck a 17-year-old boy with a resulting fracture of the superior cornu of the larynx and a puncture of the laryngeal mucosal wall in a case reported by Saab and Birkinshaw.¹⁰ The patient presented with neck pain and dysphagia, as well as subcutaneous air.¹⁰ A 21-year-old collegiate basketball player was struck in the neck by a teammate’s head while jumping for a rebound. He sustained a fracture of the thyroid cartilage and a fracture of the anterior cricoid ring.³Patients with such injuries "may appear deceptively normal when seeking medical attention."⁸ Kragha² refers to such injuries as "rare but potentially deadly."

Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, and even subcutaneous emphysema. There may be loss of prominence of the thyroid cartilage.³ Tracheal deviation and stridor can occur.^10,11 Computed tomography scan and laryngoscopy can be helpful in the diagnostic process; 3-dimensional (3-D) reconstructions may be needed.

Various classification systems have been proposed with related treatment strategies. Percevik et al¹¹ summarized a five-part clinical classification. Group 1 (hematoma, no fracture) and Group 2 (non-displaced fracture) may be treated conservatively. Group 3 (stable, displaced fracture), Group 4 (unstable, displaced fracture), and Group 5 (laryngotracheal disinsertion) are more likely to be treated with surgery.¹¹ Surgical techniques vary and have been refined over time.¹²

In this case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible that this injury may have involved neck hyperflexion, rather than direct compressive force. Lin et al,¹ described a case of neck hyperflexion in an unrestrained driver, with a resulting isolated thyroid cartilage fracture without direct impact to the neck. Walsh and Trotter⁵ presented a case of a motorcyclist with a blow to the back of the head, with resulting neck hyperflexion, which resulted in a fracture of the thyroid cartilage. Beato-Martínez et al,¹³ reported a case of thyroid cartilage fracture following a sneezing episode. The patient presented with odynophagia, dysphonia and neck pain.¹³ In our review of the literature, we found that only one other similar case has been reported. In that case, a patient experienced a feeling of a neck click, followed by neck pain and hoarseness. He sustained a fracture of the thyroid cartilage.¹⁴

In reviewing the hyperflexion mechanism, Lin et al¹ noted that isolated thyroid cartilage fractures are rare and that "most of these are caused by direct injury to the neck, except for two patients reported in the literature who sustained isolated thyroid cartilage fractures after sneezing." Lin et al¹ proposed an interesting hypothesis—that "the mechanism causing thyroid cartilage fracture during impaction may be the same with sneezing." Sneezing can be associated with sudden and forceful flexion of the neck.

It is certainly possible that this hyperflexion mechanism was involved in our case, given there was no history of significant blunt force to the neck, as in the sports-related injuries discussed. Wrestling holds can produce hyperflexion. The patient described a feeling of a "crack", which is similar to the clicking sound described in one of the sneezing-related cases. An isolated thyroid cartilage fracture is rare in the absence of major trauma. However, as noted by Rejali et al,⁹ this can create a potential management pitfall. "In the context of non-contact sports, the attendant doctor may not realize the significance of apparently minor head and neck trauma."⁹

There are no series data to provide us with an exact incidence of airway compromise. However, seemingly minor insults to the anterior neck can cause posterior compression of the larynx and can result in airway compromise.^9-11

The CT scan is described as an important imaging modality to rule out cervical spine fracture. Although there was no significant blunt force, the cervical spine was exposed to hyperflexion forces. Another important potential consequence is long-term injury to the vocal cords, with subsequent speech difficulties.¹¹ Computed tomography can visualize the thyroid fracture, but many authors point out that visualization of the vocal cords, with nasopharyngeal laryngoscopy or other modality, is an important adjunct to the CT scan.^9-11

Otolaryngologist consultation should be strongly considered. This patient was transferred to a tertiary care center with expertise in thyroid fractures, and planned nasopharyngeal laryngoscopy to be performed at the receiving institution.

Conclusion

Our patient sustained an isolated thyroid cartilage fracture. Most blunt force laryngeal fractures are associated with multiple trauma. An isolated thyroid cartilage fracture is very rare. An isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, or even subcutaneous emphysema. There may be loss of the prominence of the thyroid cartilage, tracheal deviation, and stridor. Computed tomography scan imaging with 3-D reconstructions and laryngoscopy can be helpful in the diagnostic process. In our case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible this injury may have involved neck hyperflexion, rather than direct compressive forces, similar to that described by Lin et al.¹ Certainly, there was no history of significant blunt force to the neck on the level of the sports-related injuries discussed.

An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Sports-related injuries to the larynx and related structures are uncommon.^6,7

Case

A 38-year-old man presented with a complaint of throat pain after wrestling at home, in horseplay, with his 15-year-old son. He reported that when his son placed a choke hold on him, he felt a "crack" in the area of his neck, and soon afterwards felt throat pain with swallowing, along with discomfort with breathing. He also felt a sensation of "fluid building up in his throat." There were no changes noted with his voice and the patient was speaking in full sentences. There was no wheezing or stridor. He denied shortness of breath or any other complaints. He denied pain over the posterior elements of his cervical spine. At the time of the incident, there was no loss of consciousness. Palpation of the neck and chest did not elicit any crepitance to suggest subcutaneous emphysema. The trachea was midline. There was no pain overlying the carotids bilaterally, and the patient had no bruits. The neck examination did not show any surface abnormalities to suggest trauma, such as ecchymosis or swelling. He did have slight tenderness to palpation over the thyroid cartilage.

The patient was sent for a computed tomography (CT) scan of the soft-tissue neck with intravenous (IV) contrast, and a CT scan of the cervical spine. The results showed no cervical spine fracture. However, there was a minimally displaced fracture of the left thyroid cartilage, with soft-tissue swelling that was noted, along with minimal narrowing of the subglottic trachea. There were no abnormal enhancements or fluid collections. No evidence of vocal cord abnormality or asymmetry was seen, and there was no evidence of airway compromise (Figure).

Discussion

Our patient sustained an isolated thyroid cartilage fracture. A thyroid cartilage fracture is a type of laryngeal fracture. Using an anatomic system in which such injuries are classified by location (supraglottic, glottis, or infraglottic), a thyroid cartilage fracture is classified as a supraglottic laryngeal injury.^1,2 In our case, the fracture was due to a blunt force mechanism. Most blunt force laryngeal fractures are associated with multiple trauma.⁸ An isolated thyroid cartilage fracture is very rare.^1-5 More interestingly, an isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature.

Sports-related injuries to the larynx and related structures are uncommon.^6,7 When reported, significant force is usually involved. For example, Tasca et al⁶ reported a thyroid cartilage fracture from direct blunt trauma (rugby, opponent stamped on patient’s throat) in which the patient presented with pain with swallowing and a lowering of the pitch of his voice. Rejali et al⁹ reported the case of a midair collision in a soccer match, resulting in an obvious mandibular fracture, but with an arytenoid cartilage fracture that was not initially identified. A football struck a 17-year-old boy with a resulting fracture of the superior cornu of the larynx and a puncture of the laryngeal mucosal wall in a case reported by Saab and Birkinshaw.¹⁰ The patient presented with neck pain and dysphagia, as well as subcutaneous air.¹⁰ A 21-year-old collegiate basketball player was struck in the neck by a teammate’s head while jumping for a rebound. He sustained a fracture of the thyroid cartilage and a fracture of the anterior cricoid ring.³Patients with such injuries "may appear deceptively normal when seeking medical attention."⁸ Kragha² refers to such injuries as "rare but potentially deadly."

Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, and even subcutaneous emphysema. There may be loss of prominence of the thyroid cartilage.³ Tracheal deviation and stridor can occur.^10,11 Computed tomography scan and laryngoscopy can be helpful in the diagnostic process; 3-dimensional (3-D) reconstructions may be needed.

Various classification systems have been proposed with related treatment strategies. Percevik et al¹¹ summarized a five-part clinical classification. Group 1 (hematoma, no fracture) and Group 2 (non-displaced fracture) may be treated conservatively. Group 3 (stable, displaced fracture), Group 4 (unstable, displaced fracture), and Group 5 (laryngotracheal disinsertion) are more likely to be treated with surgery.¹¹ Surgical techniques vary and have been refined over time.¹²

In this case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible that this injury may have involved neck hyperflexion, rather than direct compressive force. Lin et al,¹ described a case of neck hyperflexion in an unrestrained driver, with a resulting isolated thyroid cartilage fracture without direct impact to the neck. Walsh and Trotter⁵ presented a case of a motorcyclist with a blow to the back of the head, with resulting neck hyperflexion, which resulted in a fracture of the thyroid cartilage. Beato-Martínez et al,¹³ reported a case of thyroid cartilage fracture following a sneezing episode. The patient presented with odynophagia, dysphonia and neck pain.¹³ In our review of the literature, we found that only one other similar case has been reported. In that case, a patient experienced a feeling of a neck click, followed by neck pain and hoarseness. He sustained a fracture of the thyroid cartilage.¹⁴

In reviewing the hyperflexion mechanism, Lin et al¹ noted that isolated thyroid cartilage fractures are rare and that "most of these are caused by direct injury to the neck, except for two patients reported in the literature who sustained isolated thyroid cartilage fractures after sneezing." Lin et al¹ proposed an interesting hypothesis—that "the mechanism causing thyroid cartilage fracture during impaction may be the same with sneezing." Sneezing can be associated with sudden and forceful flexion of the neck.

It is certainly possible that this hyperflexion mechanism was involved in our case, given there was no history of significant blunt force to the neck, as in the sports-related injuries discussed. Wrestling holds can produce hyperflexion. The patient described a feeling of a "crack", which is similar to the clicking sound described in one of the sneezing-related cases. An isolated thyroid cartilage fracture is rare in the absence of major trauma. However, as noted by Rejali et al,⁹ this can create a potential management pitfall. "In the context of non-contact sports, the attendant doctor may not realize the significance of apparently minor head and neck trauma."⁹

There are no series data to provide us with an exact incidence of airway compromise. However, seemingly minor insults to the anterior neck can cause posterior compression of the larynx and can result in airway compromise.^9-11

The CT scan is described as an important imaging modality to rule out cervical spine fracture. Although there was no significant blunt force, the cervical spine was exposed to hyperflexion forces. Another important potential consequence is long-term injury to the vocal cords, with subsequent speech difficulties.¹¹ Computed tomography can visualize the thyroid fracture, but many authors point out that visualization of the vocal cords, with nasopharyngeal laryngoscopy or other modality, is an important adjunct to the CT scan.^9-11

Otolaryngologist consultation should be strongly considered. This patient was transferred to a tertiary care center with expertise in thyroid fractures, and planned nasopharyngeal laryngoscopy to be performed at the receiving institution.

Conclusion

Our patient sustained an isolated thyroid cartilage fracture. Most blunt force laryngeal fractures are associated with multiple trauma. An isolated thyroid cartilage fracture is very rare. An isolated thyroid cartilage fracture from a wrestling injury, especially in a non-sports competition context, such as horseplay, has not been previously reported in the literature. Symptoms can include neck pain, voice changes, pain with swallowing, and shortness of breath. Signs can include tenderness, ecchymosis, or even subcutaneous emphysema. There may be loss of the prominence of the thyroid cartilage, tracheal deviation, and stridor. Computed tomography scan imaging with 3-D reconstructions and laryngoscopy can be helpful in the diagnostic process. In our case, the patient sustained a thyroid cartilage fracture without the energy and force involved in a motor vehicle collision and without significant sports-related force. It is possible this injury may have involved neck hyperflexion, rather than direct compressive forces, similar to that described by Lin et al.¹ Certainly, there was no history of significant blunt force to the neck on the level of the sports-related injuries discussed.

Case

A 90-year-old woman with chronic obstructive pulmonary disease; hypertension; chronic kidney disease; diastolic dysfunction; severe tricuspid regurgitation; and atrial fibrillation (AF), for which she was taking rivaroxaban, presented to the ED for evaluation of injuries she sustained during a fall. The patient’s family stated that she fell while walking with the assistance of a walker and landed on her face. There was no reported loss of consciousness. Upon arrival at the ED, the patient’s vital signs were: blood pressure, 188/105 mm Hg; heart rate, 91 beats/min; respiratory rate, 20 breaths/min; and temperature, 97.88°F (36.6°C). Oxygen (O₂) saturation was 90% on room air, but increased to 98% after the patient received 10 L/min of O₂ through a non-rebreather mask.

On physical examination, the patient was awake, alert, and oriented to person, place, and time, with a Glasgow Coma Scale score of 15. She was able to move all four extremities and had 4/5 motor strength in the upper extremities bilaterally, and 3/5 motor strength in the bilateral lower limbs, which her family reported was the same as her baseline. On pulmonary examination, the lungs were clear to auscultation bilaterally and had no stridor. On auscultation she had a regular rate, with no murmurs or rubs.

The patient had nasal bone tenderness with epistaxis that resolved spontaneously and did not require packing; she had no other facial tenderness. The oropharynx was clear. There was mild posterior midline tenderness over C5 and C6, but no skin ecchymosis or neck swelling. Along with the non-rebreather mask, the patient was placed in a neck collar while she awaited transport to radiology for computed tomography (CT) studies.

The CT scan of the cervical spine demonstrated a minimally displaced fracture of the right anterior arch, both sides of the posterior arch of C1, and a comminuted minimally displaced fracture involving the posterior arch and spinous process of C5, with mild retrolisthesis of C5 over C6.

Based on the CT findings, the patient was taken to the operating room (OR) where she underwent awake fiberoptic laryngoscopy. During transfer to the OR, the patient’s O₂ dropped to 87%; however, after successful intubation without complication, O₂ saturation improved to 95%. After intubation, the patient was admitted to the intensive care unit for observation, and rivaroxaban therapy was discontinued.

A CT scan of the neck postintubation showed a mild interval decrease in the retropharyngeal hematoma, but an increase in the anterior disc space at C5-C6 with mild retrolisthesis, which raised suspicion for an anterior longitudinal ligamentous injury. A repeat CT scan on hospital day 4 revealed a new bleed within the old retropharyngeal hematoma, with no increase in thickness or size of the initial hematoma. The head and neck surgical team kept the patient intubated while awaiting resolution of the hematoma, with no plan of surgery.

On hospital day 6, the patient was transferred to another facility for continued long-term care. She was transitioned to a tracheostomy 4 days later. Follow-up approximately 2 weeks after presentation confirmed complete resolution of the hematoma, and no surgical intervention was required.

Discussion

Overview

Retropharyngeal hematomas are infrequent, but potentially life-threatening complications of cervical fractures, foreign body trauma, infection, violent coughing, and anticoagulation therapy.¹ Although retropharyngeal hematomas associated with warfarin have been well described, to our knowledge, there are no reported cases associated with a direct oral anticoagulant (DOAC).²

Though multiple studies have supported the effectiveness and safety of DOACs for prevention of stroke and systemic embolism in patients with AF, the risk of hemorrhage still exists.³ Postmarketing surveillance studies of DOACs report an overall risk of bleeding comparable to warfarin. Gastrointestinal bleeding was found to be slightly higher in patients taking a DOAC compared to those on warfarin, but the risk of intracranial bleeding from DOACs was notably lower.³ With limited effective reversal agents, DOACs present a tremendous challenge in managing acute life-threatening hemorrhage.⁴

Signs and Symptoms

Patients with retropharyngeal hematomas can present with dyspnea, sore throat, dysphagia, or odynophagia. Neck tenderness and swelling can suggest a retropharyngeal hematoma.⁵ The diagnosis of a retropharyngeal hemorrhage is of clinical importance because of the possible threat of airway obstruction—which may not be initially detectable clinically, and depends on how quickly the blood fills the retropharyngeal space.^1,6

Diagnosis

Computed tomography with intravenous contrast is the imaging study of choice for diagnosing retropharyngeal hematomas in the emergent care setting, and can detect the presence of any associated vertebral facture.^5,7,8 Lateral neck X-ray imaging can detect prevertebral swelling, but is not as sensitive as CT and may underestimate the extent of spinal injury; moreover, lesions or early bleeding may be missed.⁹ In the absence of vertebral fracture on CT imaging, magnetic resonance imaging should be considered to evaluate for possible associated ligamentous injury.⁹

Treatment and Management

Airway Management. Given the risk of progression to complete airway obstruction, the first step in managing retropharyngeal hematomas is to secure the patient’s airway. Even though the published literature recommends either endotracheal intubation or tracheostomy, the latter should only be considered as a last resort for patients on DOACs because of the increased risk of bleeding.

The fiberoptic approach to endotracheal intubation minimizes the risk of further trauma and rupture of the hematoma.^1,10 Once the patient’s airway is secure, the hematoma can be managed conservatively with spinal immobilization and observation for resolution, which may take 2 to 3 weeks.^6,11

Surgical Intervention. Some clinicians believe early surgical intervention leads to early recovery and a shorter hospitalization.¹² Surgical intervention using a transoral or anterior cervical approach is recommended for large hematomas that fail to regress.⁶ Surgical intervention may be considered for patients taking warfarin after successful anticoagulation reversal is achieved using fresh frozen plasma (FFP) and vitamin K. However, due to the increased bleeding potential and limited reversal options, there is an increased risk of surgical complications in patients on DOACs.⁵

Direct Oral Anticoagulation Reversal

The anticoagulation effect of DOACs resolves after five half-lives from the last administered dose, which in the case of rivaroxaban, is between 1 to 2 days.¹³ Therefore, when emergent surgical intervention is required for a retropharyngeal hematoma, understanding the options and limitations of reversal agents is necessary.

Idarucizumab. Currently the only DOAC anticoagulation reversal agent approved by the US Food and Drug Administration, idarucizumab is only effective for reversing the anticoagulation effects of dabigatran.^4,14

Prothrombin Complex Concentrate. Also referred to as factor IX complex, prothrombin complex concentrate (PCC) has been shown to correct prolonged prothrombin time in experimental models of bleeding. Although there is no clinical evidence for its use in DOAC-associated bleeding, PCC should be considered in life-threatening cases, including large or expanding prevertebral hematoma, or other cases in which the potential benefit outweighs the potential risk of thrombosis associated with PCC.⁴

Fresh Frozen Plasma. In the absence of PCC, FFP may be considered, though there are no data supporting its use as a reversal agent for rivaroxaban.¹⁵

Conclusion

Although a rare entity, retropharyngeal hematoma should be suspected in patients with cervical fractures or trauma, especially in the setting of anticoagulation. Early airway management should be considered in a patient with a retropharyngeal hematoma, as symptoms of airway obstruction may be insidious. In patients on DOACs, the potential benefit of earlier resolution with surgical intervention must be strongly weighed against the increased risk of bleeding.

Case

A 90-year-old woman with chronic obstructive pulmonary disease; hypertension; chronic kidney disease; diastolic dysfunction; severe tricuspid regurgitation; and atrial fibrillation (AF), for which she was taking rivaroxaban, presented to the ED for evaluation of injuries she sustained during a fall. The patient’s family stated that she fell while walking with the assistance of a walker and landed on her face. There was no reported loss of consciousness. Upon arrival at the ED, the patient’s vital signs were: blood pressure, 188/105 mm Hg; heart rate, 91 beats/min; respiratory rate, 20 breaths/min; and temperature, 97.88°F (36.6°C). Oxygen (O₂) saturation was 90% on room air, but increased to 98% after the patient received 10 L/min of O₂ through a non-rebreather mask.

On physical examination, the patient was awake, alert, and oriented to person, place, and time, with a Glasgow Coma Scale score of 15. She was able to move all four extremities and had 4/5 motor strength in the upper extremities bilaterally, and 3/5 motor strength in the bilateral lower limbs, which her family reported was the same as her baseline. On pulmonary examination, the lungs were clear to auscultation bilaterally and had no stridor. On auscultation she had a regular rate, with no murmurs or rubs.

The patient had nasal bone tenderness with epistaxis that resolved spontaneously and did not require packing; she had no other facial tenderness. The oropharynx was clear. There was mild posterior midline tenderness over C5 and C6, but no skin ecchymosis or neck swelling. Along with the non-rebreather mask, the patient was placed in a neck collar while she awaited transport to radiology for computed tomography (CT) studies.

The CT scan of the cervical spine demonstrated a minimally displaced fracture of the right anterior arch, both sides of the posterior arch of C1, and a comminuted minimally displaced fracture involving the posterior arch and spinous process of C5, with mild retrolisthesis of C5 over C6.

Based on the CT findings, the patient was taken to the operating room (OR) where she underwent awake fiberoptic laryngoscopy. During transfer to the OR, the patient’s O₂ dropped to 87%; however, after successful intubation without complication, O₂ saturation improved to 95%. After intubation, the patient was admitted to the intensive care unit for observation, and rivaroxaban therapy was discontinued.

A CT scan of the neck postintubation showed a mild interval decrease in the retropharyngeal hematoma, but an increase in the anterior disc space at C5-C6 with mild retrolisthesis, which raised suspicion for an anterior longitudinal ligamentous injury. A repeat CT scan on hospital day 4 revealed a new bleed within the old retropharyngeal hematoma, with no increase in thickness or size of the initial hematoma. The head and neck surgical team kept the patient intubated while awaiting resolution of the hematoma, with no plan of surgery.

On hospital day 6, the patient was transferred to another facility for continued long-term care. She was transitioned to a tracheostomy 4 days later. Follow-up approximately 2 weeks after presentation confirmed complete resolution of the hematoma, and no surgical intervention was required.

Discussion

Overview

Retropharyngeal hematomas are infrequent, but potentially life-threatening complications of cervical fractures, foreign body trauma, infection, violent coughing, and anticoagulation therapy.¹ Although retropharyngeal hematomas associated with warfarin have been well described, to our knowledge, there are no reported cases associated with a direct oral anticoagulant (DOAC).²

Though multiple studies have supported the effectiveness and safety of DOACs for prevention of stroke and systemic embolism in patients with AF, the risk of hemorrhage still exists.³ Postmarketing surveillance studies of DOACs report an overall risk of bleeding comparable to warfarin. Gastrointestinal bleeding was found to be slightly higher in patients taking a DOAC compared to those on warfarin, but the risk of intracranial bleeding from DOACs was notably lower.³ With limited effective reversal agents, DOACs present a tremendous challenge in managing acute life-threatening hemorrhage.⁴

Signs and Symptoms

Patients with retropharyngeal hematomas can present with dyspnea, sore throat, dysphagia, or odynophagia. Neck tenderness and swelling can suggest a retropharyngeal hematoma.⁵ The diagnosis of a retropharyngeal hemorrhage is of clinical importance because of the possible threat of airway obstruction—which may not be initially detectable clinically, and depends on how quickly the blood fills the retropharyngeal space.^1,6

Diagnosis

Computed tomography with intravenous contrast is the imaging study of choice for diagnosing retropharyngeal hematomas in the emergent care setting, and can detect the presence of any associated vertebral facture.^5,7,8 Lateral neck X-ray imaging can detect prevertebral swelling, but is not as sensitive as CT and may underestimate the extent of spinal injury; moreover, lesions or early bleeding may be missed.⁹ In the absence of vertebral fracture on CT imaging, magnetic resonance imaging should be considered to evaluate for possible associated ligamentous injury.⁹

Treatment and Management

Airway Management. Given the risk of progression to complete airway obstruction, the first step in managing retropharyngeal hematomas is to secure the patient’s airway. Even though the published literature recommends either endotracheal intubation or tracheostomy, the latter should only be considered as a last resort for patients on DOACs because of the increased risk of bleeding.

The fiberoptic approach to endotracheal intubation minimizes the risk of further trauma and rupture of the hematoma.^1,10 Once the patient’s airway is secure, the hematoma can be managed conservatively with spinal immobilization and observation for resolution, which may take 2 to 3 weeks.^6,11

Surgical Intervention. Some clinicians believe early surgical intervention leads to early recovery and a shorter hospitalization.¹² Surgical intervention using a transoral or anterior cervical approach is recommended for large hematomas that fail to regress.⁶ Surgical intervention may be considered for patients taking warfarin after successful anticoagulation reversal is achieved using fresh frozen plasma (FFP) and vitamin K. However, due to the increased bleeding potential and limited reversal options, there is an increased risk of surgical complications in patients on DOACs.⁵

Direct Oral Anticoagulation Reversal

The anticoagulation effect of DOACs resolves after five half-lives from the last administered dose, which in the case of rivaroxaban, is between 1 to 2 days.¹³ Therefore, when emergent surgical intervention is required for a retropharyngeal hematoma, understanding the options and limitations of reversal agents is necessary.

Idarucizumab. Currently the only DOAC anticoagulation reversal agent approved by the US Food and Drug Administration, idarucizumab is only effective for reversing the anticoagulation effects of dabigatran.^4,14

Prothrombin Complex Concentrate. Also referred to as factor IX complex, prothrombin complex concentrate (PCC) has been shown to correct prolonged prothrombin time in experimental models of bleeding. Although there is no clinical evidence for its use in DOAC-associated bleeding, PCC should be considered in life-threatening cases, including large or expanding prevertebral hematoma, or other cases in which the potential benefit outweighs the potential risk of thrombosis associated with PCC.⁴

Fresh Frozen Plasma. In the absence of PCC, FFP may be considered, though there are no data supporting its use as a reversal agent for rivaroxaban.¹⁵

Conclusion

Although a rare entity, retropharyngeal hematoma should be suspected in patients with cervical fractures or trauma, especially in the setting of anticoagulation. Early airway management should be considered in a patient with a retropharyngeal hematoma, as symptoms of airway obstruction may be insidious. In patients on DOACs, the potential benefit of earlier resolution with surgical intervention must be strongly weighed against the increased risk of bleeding.

Case

A 90-year-old woman with chronic obstructive pulmonary disease; hypertension; chronic kidney disease; diastolic dysfunction; severe tricuspid regurgitation; and atrial fibrillation (AF), for which she was taking rivaroxaban, presented to the ED for evaluation of injuries she sustained during a fall. The patient’s family stated that she fell while walking with the assistance of a walker and landed on her face. There was no reported loss of consciousness. Upon arrival at the ED, the patient’s vital signs were: blood pressure, 188/105 mm Hg; heart rate, 91 beats/min; respiratory rate, 20 breaths/min; and temperature, 97.88°F (36.6°C). Oxygen (O₂) saturation was 90% on room air, but increased to 98% after the patient received 10 L/min of O₂ through a non-rebreather mask.

On physical examination, the patient was awake, alert, and oriented to person, place, and time, with a Glasgow Coma Scale score of 15. She was able to move all four extremities and had 4/5 motor strength in the upper extremities bilaterally, and 3/5 motor strength in the bilateral lower limbs, which her family reported was the same as her baseline. On pulmonary examination, the lungs were clear to auscultation bilaterally and had no stridor. On auscultation she had a regular rate, with no murmurs or rubs.

The patient had nasal bone tenderness with epistaxis that resolved spontaneously and did not require packing; she had no other facial tenderness. The oropharynx was clear. There was mild posterior midline tenderness over C5 and C6, but no skin ecchymosis or neck swelling. Along with the non-rebreather mask, the patient was placed in a neck collar while she awaited transport to radiology for computed tomography (CT) studies.

The CT scan of the cervical spine demonstrated a minimally displaced fracture of the right anterior arch, both sides of the posterior arch of C1, and a comminuted minimally displaced fracture involving the posterior arch and spinous process of C5, with mild retrolisthesis of C5 over C6.

Based on the CT findings, the patient was taken to the operating room (OR) where she underwent awake fiberoptic laryngoscopy. During transfer to the OR, the patient’s O₂ dropped to 87%; however, after successful intubation without complication, O₂ saturation improved to 95%. After intubation, the patient was admitted to the intensive care unit for observation, and rivaroxaban therapy was discontinued.

A CT scan of the neck postintubation showed a mild interval decrease in the retropharyngeal hematoma, but an increase in the anterior disc space at C5-C6 with mild retrolisthesis, which raised suspicion for an anterior longitudinal ligamentous injury. A repeat CT scan on hospital day 4 revealed a new bleed within the old retropharyngeal hematoma, with no increase in thickness or size of the initial hematoma. The head and neck surgical team kept the patient intubated while awaiting resolution of the hematoma, with no plan of surgery.

On hospital day 6, the patient was transferred to another facility for continued long-term care. She was transitioned to a tracheostomy 4 days later. Follow-up approximately 2 weeks after presentation confirmed complete resolution of the hematoma, and no surgical intervention was required.

Discussion

Overview

Retropharyngeal hematomas are infrequent, but potentially life-threatening complications of cervical fractures, foreign body trauma, infection, violent coughing, and anticoagulation therapy.¹ Although retropharyngeal hematomas associated with warfarin have been well described, to our knowledge, there are no reported cases associated with a direct oral anticoagulant (DOAC).²

Though multiple studies have supported the effectiveness and safety of DOACs for prevention of stroke and systemic embolism in patients with AF, the risk of hemorrhage still exists.³ Postmarketing surveillance studies of DOACs report an overall risk of bleeding comparable to warfarin. Gastrointestinal bleeding was found to be slightly higher in patients taking a DOAC compared to those on warfarin, but the risk of intracranial bleeding from DOACs was notably lower.³ With limited effective reversal agents, DOACs present a tremendous challenge in managing acute life-threatening hemorrhage.⁴

Signs and Symptoms

Patients with retropharyngeal hematomas can present with dyspnea, sore throat, dysphagia, or odynophagia. Neck tenderness and swelling can suggest a retropharyngeal hematoma.⁵ The diagnosis of a retropharyngeal hemorrhage is of clinical importance because of the possible threat of airway obstruction—which may not be initially detectable clinically, and depends on how quickly the blood fills the retropharyngeal space.^1,6

Diagnosis

Computed tomography with intravenous contrast is the imaging study of choice for diagnosing retropharyngeal hematomas in the emergent care setting, and can detect the presence of any associated vertebral facture.^5,7,8 Lateral neck X-ray imaging can detect prevertebral swelling, but is not as sensitive as CT and may underestimate the extent of spinal injury; moreover, lesions or early bleeding may be missed.⁹ In the absence of vertebral fracture on CT imaging, magnetic resonance imaging should be considered to evaluate for possible associated ligamentous injury.⁹

Treatment and Management

Airway Management. Given the risk of progression to complete airway obstruction, the first step in managing retropharyngeal hematomas is to secure the patient’s airway. Even though the published literature recommends either endotracheal intubation or tracheostomy, the latter should only be considered as a last resort for patients on DOACs because of the increased risk of bleeding.

The fiberoptic approach to endotracheal intubation minimizes the risk of further trauma and rupture of the hematoma.^1,10 Once the patient’s airway is secure, the hematoma can be managed conservatively with spinal immobilization and observation for resolution, which may take 2 to 3 weeks.^6,11

Surgical Intervention. Some clinicians believe early surgical intervention leads to early recovery and a shorter hospitalization.¹² Surgical intervention using a transoral or anterior cervical approach is recommended for large hematomas that fail to regress.⁶ Surgical intervention may be considered for patients taking warfarin after successful anticoagulation reversal is achieved using fresh frozen plasma (FFP) and vitamin K. However, due to the increased bleeding potential and limited reversal options, there is an increased risk of surgical complications in patients on DOACs.⁵

Direct Oral Anticoagulation Reversal

The anticoagulation effect of DOACs resolves after five half-lives from the last administered dose, which in the case of rivaroxaban, is between 1 to 2 days.¹³ Therefore, when emergent surgical intervention is required for a retropharyngeal hematoma, understanding the options and limitations of reversal agents is necessary.

Idarucizumab. Currently the only DOAC anticoagulation reversal agent approved by the US Food and Drug Administration, idarucizumab is only effective for reversing the anticoagulation effects of dabigatran.^4,14

Prothrombin Complex Concentrate. Also referred to as factor IX complex, prothrombin complex concentrate (PCC) has been shown to correct prolonged prothrombin time in experimental models of bleeding. Although there is no clinical evidence for its use in DOAC-associated bleeding, PCC should be considered in life-threatening cases, including large or expanding prevertebral hematoma, or other cases in which the potential benefit outweighs the potential risk of thrombosis associated with PCC.⁴

Fresh Frozen Plasma. In the absence of PCC, FFP may be considered, though there are no data supporting its use as a reversal agent for rivaroxaban.¹⁵

Conclusion

Although a rare entity, retropharyngeal hematoma should be suspected in patients with cervical fractures or trauma, especially in the setting of anticoagulation. Early airway management should be considered in a patient with a retropharyngeal hematoma, as symptoms of airway obstruction may be insidious. In patients on DOACs, the potential benefit of earlier resolution with surgical intervention must be strongly weighed against the increased risk of bleeding.

Case

A 55-year-old previously healthy woman with an insignificant medical history presented to the ED for evaluation of right-sided numbness, tingling, and inability to sense temperature. The patient stated the numbness and tingling first began in her right leg and thigh 2 months earlier, and had progressively worsened to her entire right-side. She said she first experienced the thermoanesthesia while taking a shower the morning of presentation. While showering, the patient noted that she could not feel any hot or cold sensation on the right side of her body, including her right leg and arm. She also reported decreased sensation to her extremities on the right side.

She denied any new weakness, headache, chest pain, shortness of breath, fever, chills, nausea, vomiting, back pain, neck pain, or any other symptoms. In addition, she denied any difficulty swallowing, speaking, blurry vision, or double vision. Regarding her social history, the patient denied a history of sexually transmitted diseases, including syphilis; or any tobacco, alcohol, or illicit drug use. The patient confirmed that she had never experienced any of the presenting symptoms prior to 2 months ago. There was no history of trauma or falls. A review of systems was otherwise negative.

Vital signs at presentation were: blood pressure, 129/88 mm Hg; heart rate, 99 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.5°F. Oxygen saturation was 98% on room air. Physical examination revealed a middle-aged woman who was awake, alert, and oriented. Her head was normocephalic and atraumatic, and her pupils were 5 mm, equal, round, and reactive to light bilaterally. Her cranial nerves II through XII were intact. She had normal 5/5 strength in both her upper and lower extremities bilaterally, and had 2+ and equal bilateral patella and Achilles deep tendon reflexes. The patient had no truncal ataxia, and she had a normal gait on ambulation. She was unable to sense temperature (assessed by touching a cold metal tray with her right hand). There was no neck or back midline tenderness to palpation of her spine.

Initial laboratory studies included a complete blood count (CBC); basic metabolic panel (BMP), including blood urea nitrogen; and urine drug screen (UDS). The CBC and BMP were within normal limits, except for an elevated creatine kinase of 249 U/L. The UDS was positive for cocaine. A head computed tomography (CT) scan without contrast was unremarkable.

The patient was admitted to the hospital for further evaluation. Additional laboratory workup during the inpatient stay included nonreactive treponemal immunoglobulin G/immunoglobulin M; nonreactive HIV antigen antibody assay; normal thyroid stimulating hormone; normal free thyroxine, folate, and vitamin B₁₂ levels; normal erythrocyte sedimentation rate, and C-reactive protein levels. The patient’s hemoglobin A_1C was also within normal range.

Other imaging studies, which included MR angiography (MRA) of the head and neck, and MRI of the thoracic and lumbar spine, were unremarkable, with the exception of some chronic spondylitic changes.

Due to the significant C3-C4 stenosis, orthopedic surgery services were consulted for a spinal surgery workup. The orthopedic examination identified a few beats of clonus, intact proprioception, and no dysmetria. The patient had decreased sensation to fine touch in the distribution of C7 at the level of the triceps, midphalangeal joints to distal fingertips on the right, fourth, and fifth fingers on the left and right lateral lower extremity. A Hoffmann sign was positive bilaterally. A CT scan of the cervical spine showed severe canal stenosis at the C3-C4 level secondary to a large C3-C4 left paracentral disc protrusion with AP dimensions of the canal measured at 4 to 5 mm. There was no evidence of acute cervical spine fracture or subluxation.

The patient was offered operative and nonoperative management options, including anterior cervical discectomy and fusion vs conservative management with corticosteroid therapy. She agreed to conservative management and received intravenous (IV) dexamethasone with subjective improvement in her symptoms. The patient was discharged home on hospital day 3, with instructions to follow-up with a spine surgeon in 2 weeks. She was also counseled on abstaining from further cocaine or other illicit drug use.

The patient eventually returned for an elective anterior cervical discectomy and fusion 2 months later, after several outpatient visits and progression of symptoms. She was discharged home on postoperative day 1 with pain well-controlled and was able to ambulate without assistance. On follow-up, she reported 15% improvement in her symptoms.

Discussion

Cervical spondylotic myelopathy (CSM) is the most common myelopathy in patients aged 55 years and older. Immediate neuroimaging studies followed by spinal surgery consultation are recommended for patients presenting with acute symptoms suggestive of cord compression.^1,2

Diagnosis and Differential Diagnosis

Diagnosis of CSM can be made with a thorough patient history, neurological examination, and MRI/MRA. However, because cases of cervical disc herniation (CDH) are often atraumatic, the patient history may not always be contributory to the diagnosis and severity of the offending cause.

During our patient’s hospital course, there was initially a concern for Brown-Séquard syndrome (BSS) due to the lateralizing symptoms and radiographic findings. This is a rare condition that can occur in the setting of spinal trauma, unilateral disc herniation, tumors, epidural hematomas, and spinal cord ischemia.^3,4 In one retrospective case review by Sayer et al,⁴ the incidence of CDH causing BSS was only 0.21% (5 per 2,350 patients), and 67% of the cases involved C5-C6 or C6-C7.

Although disc herniation usually presents with symptoms on the ipsilateral side in patients with BSS, there are rare case reports of patients with contralateral symptoms in the form of complete or incomplete BSS manifesting as ipsilateral motor deficit and/or loss of contralateral pain and temperature due to an incomplete spinal cord compression.^5-7 We were able to rule-out BSS in our patient due to the absence of motor symptoms.

Treatment

Corticosteroid Therapy. High-dose IV corticosteroids should be given to all patients with CSM prior to surgery to reduce cord edema caused by spinal cord injury. In one randomized control trial by Bracken et al,⁸ patients given methylprednisolone within 8 hours of spinal cord injury had improvement in motor function, sensation to pinprick, and touch at 6 months when compared to placebo. When the aforementioned steps are taken in the emergent care setting, they may significantly improve patient outcomes.

Surgical Intervention. All cases of CSM in the review literature were treated surgically with laminectomy or hemilaminectomy, anterior discectomy with or without fusion, or corpectomy followed by interbody fusion, with the goal of achieving cord decompression. A large majority of patients underwent anterior discectomy with interbody fusion, and all of the cases recommend early surgical intervention in severe CSM to prevent rapidly worsening symptoms, including permanent hemiparesis.

Early surgical intervention is positively correlated with better outcomes, most often resulting in significant improvement of symptoms to full recovery.^3,4,6,7,9-12 In one case report, surgical intervention did not result in a significant improvement, and the patient had been suffering from progressive symptoms for 7 years prior to diagnosis and treatment.¹¹

Conservative Management. Conservative management of CSM includes immobilization, activity modification, pain management, and/or corticosteroids therapy.¹³ However, for patients undergoing surgical decompression, 50% to 80% reported symptom improvement.^14,15 This evidence strongly supports management of CSM with early diagnosis and surgical intervention. Despite delays in diagnosis and treatment, surgical intervention can still offer significant relief of weakness and sensory deficits associated with severe CSM.¹¹

Conclusion

Cervical spondylotic myelopathy is the most common myelopathy in patients aged 55 years and older. Common symptoms involve upper extremity sensation, gait disturbances, and deterioration of hand use¹⁶; however, there is a large differential for patients presenting to the ED with these symptoms, including mass effect, infection, vascular conditions, metabolic disorders, inflammatory conditions, and trauma.

Our patient with CSM presented with signs of an incomplete cord syndrome with lateralizing features caused by asymmetric disc herniation. This case is unique in that though our patient had some symptom resolution with corticosteroids therapy alone, she ultimately returned for definitive surgical decompression after symptom progression.

Case

A 55-year-old previously healthy woman with an insignificant medical history presented to the ED for evaluation of right-sided numbness, tingling, and inability to sense temperature. The patient stated the numbness and tingling first began in her right leg and thigh 2 months earlier, and had progressively worsened to her entire right-side. She said she first experienced the thermoanesthesia while taking a shower the morning of presentation. While showering, the patient noted that she could not feel any hot or cold sensation on the right side of her body, including her right leg and arm. She also reported decreased sensation to her extremities on the right side.

She denied any new weakness, headache, chest pain, shortness of breath, fever, chills, nausea, vomiting, back pain, neck pain, or any other symptoms. In addition, she denied any difficulty swallowing, speaking, blurry vision, or double vision. Regarding her social history, the patient denied a history of sexually transmitted diseases, including syphilis; or any tobacco, alcohol, or illicit drug use. The patient confirmed that she had never experienced any of the presenting symptoms prior to 2 months ago. There was no history of trauma or falls. A review of systems was otherwise negative.

Vital signs at presentation were: blood pressure, 129/88 mm Hg; heart rate, 99 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.5°F. Oxygen saturation was 98% on room air. Physical examination revealed a middle-aged woman who was awake, alert, and oriented. Her head was normocephalic and atraumatic, and her pupils were 5 mm, equal, round, and reactive to light bilaterally. Her cranial nerves II through XII were intact. She had normal 5/5 strength in both her upper and lower extremities bilaterally, and had 2+ and equal bilateral patella and Achilles deep tendon reflexes. The patient had no truncal ataxia, and she had a normal gait on ambulation. She was unable to sense temperature (assessed by touching a cold metal tray with her right hand). There was no neck or back midline tenderness to palpation of her spine.

Initial laboratory studies included a complete blood count (CBC); basic metabolic panel (BMP), including blood urea nitrogen; and urine drug screen (UDS). The CBC and BMP were within normal limits, except for an elevated creatine kinase of 249 U/L. The UDS was positive for cocaine. A head computed tomography (CT) scan without contrast was unremarkable.

The patient was admitted to the hospital for further evaluation. Additional laboratory workup during the inpatient stay included nonreactive treponemal immunoglobulin G/immunoglobulin M; nonreactive HIV antigen antibody assay; normal thyroid stimulating hormone; normal free thyroxine, folate, and vitamin B₁₂ levels; normal erythrocyte sedimentation rate, and C-reactive protein levels. The patient’s hemoglobin A_1C was also within normal range.

Other imaging studies, which included MR angiography (MRA) of the head and neck, and MRI of the thoracic and lumbar spine, were unremarkable, with the exception of some chronic spondylitic changes.

Due to the significant C3-C4 stenosis, orthopedic surgery services were consulted for a spinal surgery workup. The orthopedic examination identified a few beats of clonus, intact proprioception, and no dysmetria. The patient had decreased sensation to fine touch in the distribution of C7 at the level of the triceps, midphalangeal joints to distal fingertips on the right, fourth, and fifth fingers on the left and right lateral lower extremity. A Hoffmann sign was positive bilaterally. A CT scan of the cervical spine showed severe canal stenosis at the C3-C4 level secondary to a large C3-C4 left paracentral disc protrusion with AP dimensions of the canal measured at 4 to 5 mm. There was no evidence of acute cervical spine fracture or subluxation.

The patient was offered operative and nonoperative management options, including anterior cervical discectomy and fusion vs conservative management with corticosteroid therapy. She agreed to conservative management and received intravenous (IV) dexamethasone with subjective improvement in her symptoms. The patient was discharged home on hospital day 3, with instructions to follow-up with a spine surgeon in 2 weeks. She was also counseled on abstaining from further cocaine or other illicit drug use.

The patient eventually returned for an elective anterior cervical discectomy and fusion 2 months later, after several outpatient visits and progression of symptoms. She was discharged home on postoperative day 1 with pain well-controlled and was able to ambulate without assistance. On follow-up, she reported 15% improvement in her symptoms.

Discussion

Cervical spondylotic myelopathy (CSM) is the most common myelopathy in patients aged 55 years and older. Immediate neuroimaging studies followed by spinal surgery consultation are recommended for patients presenting with acute symptoms suggestive of cord compression.^1,2

Diagnosis and Differential Diagnosis

Diagnosis of CSM can be made with a thorough patient history, neurological examination, and MRI/MRA. However, because cases of cervical disc herniation (CDH) are often atraumatic, the patient history may not always be contributory to the diagnosis and severity of the offending cause.

During our patient’s hospital course, there was initially a concern for Brown-Séquard syndrome (BSS) due to the lateralizing symptoms and radiographic findings. This is a rare condition that can occur in the setting of spinal trauma, unilateral disc herniation, tumors, epidural hematomas, and spinal cord ischemia.^3,4 In one retrospective case review by Sayer et al,⁴ the incidence of CDH causing BSS was only 0.21% (5 per 2,350 patients), and 67% of the cases involved C5-C6 or C6-C7.

Although disc herniation usually presents with symptoms on the ipsilateral side in patients with BSS, there are rare case reports of patients with contralateral symptoms in the form of complete or incomplete BSS manifesting as ipsilateral motor deficit and/or loss of contralateral pain and temperature due to an incomplete spinal cord compression.^5-7 We were able to rule-out BSS in our patient due to the absence of motor symptoms.

Treatment

Corticosteroid Therapy. High-dose IV corticosteroids should be given to all patients with CSM prior to surgery to reduce cord edema caused by spinal cord injury. In one randomized control trial by Bracken et al,⁸ patients given methylprednisolone within 8 hours of spinal cord injury had improvement in motor function, sensation to pinprick, and touch at 6 months when compared to placebo. When the aforementioned steps are taken in the emergent care setting, they may significantly improve patient outcomes.

Surgical Intervention. All cases of CSM in the review literature were treated surgically with laminectomy or hemilaminectomy, anterior discectomy with or without fusion, or corpectomy followed by interbody fusion, with the goal of achieving cord decompression. A large majority of patients underwent anterior discectomy with interbody fusion, and all of the cases recommend early surgical intervention in severe CSM to prevent rapidly worsening symptoms, including permanent hemiparesis.

Early surgical intervention is positively correlated with better outcomes, most often resulting in significant improvement of symptoms to full recovery.^3,4,6,7,9-12 In one case report, surgical intervention did not result in a significant improvement, and the patient had been suffering from progressive symptoms for 7 years prior to diagnosis and treatment.¹¹

Conservative Management. Conservative management of CSM includes immobilization, activity modification, pain management, and/or corticosteroids therapy.¹³ However, for patients undergoing surgical decompression, 50% to 80% reported symptom improvement.^14,15 This evidence strongly supports management of CSM with early diagnosis and surgical intervention. Despite delays in diagnosis and treatment, surgical intervention can still offer significant relief of weakness and sensory deficits associated with severe CSM.¹¹

Conclusion

Cervical spondylotic myelopathy is the most common myelopathy in patients aged 55 years and older. Common symptoms involve upper extremity sensation, gait disturbances, and deterioration of hand use¹⁶; however, there is a large differential for patients presenting to the ED with these symptoms, including mass effect, infection, vascular conditions, metabolic disorders, inflammatory conditions, and trauma.

Our patient with CSM presented with signs of an incomplete cord syndrome with lateralizing features caused by asymmetric disc herniation. This case is unique in that though our patient had some symptom resolution with corticosteroids therapy alone, she ultimately returned for definitive surgical decompression after symptom progression.

Case

A 55-year-old previously healthy woman with an insignificant medical history presented to the ED for evaluation of right-sided numbness, tingling, and inability to sense temperature. The patient stated the numbness and tingling first began in her right leg and thigh 2 months earlier, and had progressively worsened to her entire right-side. She said she first experienced the thermoanesthesia while taking a shower the morning of presentation. While showering, the patient noted that she could not feel any hot or cold sensation on the right side of her body, including her right leg and arm. She also reported decreased sensation to her extremities on the right side.

She denied any new weakness, headache, chest pain, shortness of breath, fever, chills, nausea, vomiting, back pain, neck pain, or any other symptoms. In addition, she denied any difficulty swallowing, speaking, blurry vision, or double vision. Regarding her social history, the patient denied a history of sexually transmitted diseases, including syphilis; or any tobacco, alcohol, or illicit drug use. The patient confirmed that she had never experienced any of the presenting symptoms prior to 2 months ago. There was no history of trauma or falls. A review of systems was otherwise negative.

Vital signs at presentation were: blood pressure, 129/88 mm Hg; heart rate, 99 beats/min; respiratory rate, 18 breaths/min; and temperature, 98.5°F. Oxygen saturation was 98% on room air. Physical examination revealed a middle-aged woman who was awake, alert, and oriented. Her head was normocephalic and atraumatic, and her pupils were 5 mm, equal, round, and reactive to light bilaterally. Her cranial nerves II through XII were intact. She had normal 5/5 strength in both her upper and lower extremities bilaterally, and had 2+ and equal bilateral patella and Achilles deep tendon reflexes. The patient had no truncal ataxia, and she had a normal gait on ambulation. She was unable to sense temperature (assessed by touching a cold metal tray with her right hand). There was no neck or back midline tenderness to palpation of her spine.

Initial laboratory studies included a complete blood count (CBC); basic metabolic panel (BMP), including blood urea nitrogen; and urine drug screen (UDS). The CBC and BMP were within normal limits, except for an elevated creatine kinase of 249 U/L. The UDS was positive for cocaine. A head computed tomography (CT) scan without contrast was unremarkable.

The patient was admitted to the hospital for further evaluation. Additional laboratory workup during the inpatient stay included nonreactive treponemal immunoglobulin G/immunoglobulin M; nonreactive HIV antigen antibody assay; normal thyroid stimulating hormone; normal free thyroxine, folate, and vitamin B₁₂ levels; normal erythrocyte sedimentation rate, and C-reactive protein levels. The patient’s hemoglobin A_1C was also within normal range.

Other imaging studies, which included MR angiography (MRA) of the head and neck, and MRI of the thoracic and lumbar spine, were unremarkable, with the exception of some chronic spondylitic changes.

Due to the significant C3-C4 stenosis, orthopedic surgery services were consulted for a spinal surgery workup. The orthopedic examination identified a few beats of clonus, intact proprioception, and no dysmetria. The patient had decreased sensation to fine touch in the distribution of C7 at the level of the triceps, midphalangeal joints to distal fingertips on the right, fourth, and fifth fingers on the left and right lateral lower extremity. A Hoffmann sign was positive bilaterally. A CT scan of the cervical spine showed severe canal stenosis at the C3-C4 level secondary to a large C3-C4 left paracentral disc protrusion with AP dimensions of the canal measured at 4 to 5 mm. There was no evidence of acute cervical spine fracture or subluxation.

The patient was offered operative and nonoperative management options, including anterior cervical discectomy and fusion vs conservative management with corticosteroid therapy. She agreed to conservative management and received intravenous (IV) dexamethasone with subjective improvement in her symptoms. The patient was discharged home on hospital day 3, with instructions to follow-up with a spine surgeon in 2 weeks. She was also counseled on abstaining from further cocaine or other illicit drug use.

The patient eventually returned for an elective anterior cervical discectomy and fusion 2 months later, after several outpatient visits and progression of symptoms. She was discharged home on postoperative day 1 with pain well-controlled and was able to ambulate without assistance. On follow-up, she reported 15% improvement in her symptoms.

Discussion

Cervical spondylotic myelopathy (CSM) is the most common myelopathy in patients aged 55 years and older. Immediate neuroimaging studies followed by spinal surgery consultation are recommended for patients presenting with acute symptoms suggestive of cord compression.^1,2

Diagnosis and Differential Diagnosis

Diagnosis of CSM can be made with a thorough patient history, neurological examination, and MRI/MRA. However, because cases of cervical disc herniation (CDH) are often atraumatic, the patient history may not always be contributory to the diagnosis and severity of the offending cause.

During our patient’s hospital course, there was initially a concern for Brown-Séquard syndrome (BSS) due to the lateralizing symptoms and radiographic findings. This is a rare condition that can occur in the setting of spinal trauma, unilateral disc herniation, tumors, epidural hematomas, and spinal cord ischemia.^3,4 In one retrospective case review by Sayer et al,⁴ the incidence of CDH causing BSS was only 0.21% (5 per 2,350 patients), and 67% of the cases involved C5-C6 or C6-C7.

Although disc herniation usually presents with symptoms on the ipsilateral side in patients with BSS, there are rare case reports of patients with contralateral symptoms in the form of complete or incomplete BSS manifesting as ipsilateral motor deficit and/or loss of contralateral pain and temperature due to an incomplete spinal cord compression.^5-7 We were able to rule-out BSS in our patient due to the absence of motor symptoms.

Treatment

Corticosteroid Therapy. High-dose IV corticosteroids should be given to all patients with CSM prior to surgery to reduce cord edema caused by spinal cord injury. In one randomized control trial by Bracken et al,⁸ patients given methylprednisolone within 8 hours of spinal cord injury had improvement in motor function, sensation to pinprick, and touch at 6 months when compared to placebo. When the aforementioned steps are taken in the emergent care setting, they may significantly improve patient outcomes.

Surgical Intervention. All cases of CSM in the review literature were treated surgically with laminectomy or hemilaminectomy, anterior discectomy with or without fusion, or corpectomy followed by interbody fusion, with the goal of achieving cord decompression. A large majority of patients underwent anterior discectomy with interbody fusion, and all of the cases recommend early surgical intervention in severe CSM to prevent rapidly worsening symptoms, including permanent hemiparesis.

Early surgical intervention is positively correlated with better outcomes, most often resulting in significant improvement of symptoms to full recovery.^3,4,6,7,9-12 In one case report, surgical intervention did not result in a significant improvement, and the patient had been suffering from progressive symptoms for 7 years prior to diagnosis and treatment.¹¹

Conservative Management. Conservative management of CSM includes immobilization, activity modification, pain management, and/or corticosteroids therapy.¹³ However, for patients undergoing surgical decompression, 50% to 80% reported symptom improvement.^14,15 This evidence strongly supports management of CSM with early diagnosis and surgical intervention. Despite delays in diagnosis and treatment, surgical intervention can still offer significant relief of weakness and sensory deficits associated with severe CSM.¹¹

Conclusion

Cervical spondylotic myelopathy is the most common myelopathy in patients aged 55 years and older. Common symptoms involve upper extremity sensation, gait disturbances, and deterioration of hand use¹⁶; however, there is a large differential for patients presenting to the ED with these symptoms, including mass effect, infection, vascular conditions, metabolic disorders, inflammatory conditions, and trauma.

Our patient with CSM presented with signs of an incomplete cord syndrome with lateralizing features caused by asymmetric disc herniation. This case is unique in that though our patient had some symptom resolution with corticosteroids therapy alone, she ultimately returned for definitive surgical decompression after symptom progression.

Case

An otherwise healthy 20-month-old boy presented to the ED for evaluation after his father witnessed the child ingest a model race car fuel additive. According to the patient’s father, the boy was playing with several closed bottles that were stored in the garage, when he witnessed the boy open up and take a sip of a pink-colored fuel additive, which the father believed to contain 100% methanol. The patient’s father further noted that immediately after drinking the fluid, the patient spat and drooled, and had one episode of nonbloody emesis prior to arrival at the ED.

Initial vital signs at presentation were: blood pressure, 84/54 mm Hg; heart rate, 97 beats/min; respiratory rate, 24 breaths/min; and temperature 98°F. Oxygen saturation was 99% on room air. Physical examination was notable for mild erythema in the posterior oropharynx. Otherwise, the patient was acting appropriately for his age and in no acute distress. Laboratory studies were within normal limits, except for the following: serum anion gap, 18 mEq/L (reference range for children < 3 years old, 10-14 mEq/L); serum bicarbonate, 19 mmol/L (reference range for children 12-24 months, 17-25 mmol/L); and serum creatinine, 2.8 mg/dL (reference range for children 12 to 24 months, 0.2-0.5 mg/dL). A repeat creatinine test taken after bolus of fluid administration was 2.4 mg/dL. A renal ultrasound, performed to investigate the cause of the renal failure, was unremarkable.

What toxic exposures are of concern based on the clinical history?

The history of exposure to a liquid stored in a garage raises the likelihood of exposure to an automobile-related item such as diethylene glycol, ethylene glycol (EG), and methanol.

Diethylene Glycol. Diethylene glycol is an ingredient in brake and power steering fluids, and has toxic properties qualitatively similar to EG.

Ethylene Glycol. A clear, colorless, odorless fluid with a sweet taste, EG is an ingredient in radiator antifreeze, refrigerant fluid, coolants, and pesticides. Like methylene, EG reaches peak plasma concentration within 1 to 4 hours, but toxic clinical findings do not occur for 3 to 6 hours.¹

Methanol. Methanol is a clear, colorless, alcohol found in antifreeze, windshield washer fluid, and race car fuel.² Although methanol reaches peak plasma concentration in about 30 to 60 minutes, signs of systemic toxicity (ie, metabolic acidosis) typically take 6 to 12 hours to manifest.¹

In both EG and methanol, there is a delay in toxic clinical findings because the parent compounds are not toxic in their initial form; rather, major toxicity is derived from their metabolites: formic acid and oxalic acid, respectively.

Other Toxins. Many other potentially toxic liquids are associated with a homeowner’s occupation or avocational interests. These include painting supplies (eg, industrial paints containing lead), gardening materials (eg, pesticides containing organophosphates), fuels (eg, gasoline, polychlorinated biphenyls in coolant, and lubricants), and cleaning supplies (eg, caustics, detergents, and air freshener).

Case Continuation

Since the patient’s elevated anion gap raised concerns for methanol or EG exposure, he was given fomepizole and transferred to a tertiary care children’s hospital for further management and possible hemodialysis. Upon arrival at the receiving hospital, the patient’s vital signs and physical examination remained unchanged. Repeat laboratory studies were notable for a creatinine level of 0.3 mg/dL. The patient’s father was instructed to retrieve the implicated bottle from home. An inspection of the bottle’s ingredients was notable for nitromethane, castor oil, and methanol.

What is nitromethane and what are its uses?

Nitromethane, the simplest nitro compound, is a colorless, viscous, lipid-soluble fluid.³ The polarity of nitromethane permits its use as a stabilizer in a number of chemical solvents, such as dry cleaning fluid, degreasers, and "super glue."^4,5 Nitromethane is also commonly added to model-engine and drag-race fuels, which also contain methanol and castor oil.³ In this capacity, nitromethane functions as an oxygen carrier, allowing more efficient fuel use in combustion cylinders (compared to gasoline), thereby increasing the horsepower of the vehicle.⁶ It is therefore commonly added to fuel for drag racers, radio-controlled cars, and model aircrafts.⁴ In the small concentrations typically inadvertently ingested, the clinical effects of nitromethane itself are inconsequential.

What is the differential for creatinine elevation?

Creatinine itself is a normal breakdown product of muscle metabolism produced by spontaneous conversion from creatine and is found at a fairly constant serum level in proportion to muscle mass.⁷ Thus, as people age and muscle mass decreases, their baseline creatinine levels decrease proportionally.

Elimination. The majority of creatinine (85%-90%) is filtered and excreted by the kidneys, with the remaining 10% to 15% secreted by the tubules, allowing creatinine to be a surrogate measure of the glomerular filtration rate.⁷ Exogenous sources of creatine or creatinine include meat and creatine supplements, the latter of which are used as an "energy source" to enhance athletic performance.

Etiology. The etiology for an elevated serum creatinine concentration includes renal failure, both acute and chronic; volume depletion; hemorrhage (low blood volume); and medications, including diuretics, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, nonsteroidal anti-inflammatory drugs, and certain antibiotics. These etiologies can also be categorized as processes that increase creatinine production, decrease elimination (H₂ antagonist and trimethoprim both inhibit the cation secretory pump in the tubules), or interfere with the creatinine assay (ketones, keto acids, lipemia, hemolysis, cephalosporins).⁷

Because creatinine is filtered so efficiently by the kidney, neither exogenous nor endogenous creatinine sources are expected to increase serum creatinine in the absence of renal dysfunction. However, transient elevation may occur in body builders who use extreme doses of creatine. Patients with rhabdomyolysis often develop elevated creatinine concentrations, but nearly always in the setting of myoglobinuric renal failure.

Jaffe Reaction and Enzymatic Methods. Serum creatinine can be measured using either the Jaffe reaction or the enzymatic method. In the Jaffe reaction, creatinine reacts with alkaline sodium picrate to form a red-orange chromophore, which absorbs light in the range of 470 to 550 nanometers on spectroscopy.^6,8,9 The active methylene group on nitromethane also reacts with alkaline sodium picrate to form a chromophore which absorbs light in the same wavelength range.¹⁰ Thus, serum creatinine measurements via the Jaffe reaction are falsely elevated due to the cross-reactivity between nitromethane and alkaline sodium picrate. In some reported cases, there is a 20-fold increase in the measured serum creatinine in the presence of nitromethane; renal function, however, remains normal.⁵

This false reading seen in the Jaffe reaction can be avoided by utilizing the enzymatic method of creatinine measurement, a three-step process that ultimately produces hydrogen peroxide, which is measured and accurately correlates with serum creatinine—even in the presence of nitromethane.⁸ This distinction explains the dramatically different creatinine concentrations measured at the two institutions in this case.

Case Conclusion

The patient was monitored overnight at the children’s hospital. Repeat laboratory studies in the morning showed a normal creatinine level of 0.3 mg/dL and a negative methanol level. The patient was discharged home in the care of his father, who was instructed to follow-up with his son’s pediatrician. The father also received counseling on safe storage practices for dangerous chemicals.

Case

An otherwise healthy 20-month-old boy presented to the ED for evaluation after his father witnessed the child ingest a model race car fuel additive. According to the patient’s father, the boy was playing with several closed bottles that were stored in the garage, when he witnessed the boy open up and take a sip of a pink-colored fuel additive, which the father believed to contain 100% methanol. The patient’s father further noted that immediately after drinking the fluid, the patient spat and drooled, and had one episode of nonbloody emesis prior to arrival at the ED.

Initial vital signs at presentation were: blood pressure, 84/54 mm Hg; heart rate, 97 beats/min; respiratory rate, 24 breaths/min; and temperature 98°F. Oxygen saturation was 99% on room air. Physical examination was notable for mild erythema in the posterior oropharynx. Otherwise, the patient was acting appropriately for his age and in no acute distress. Laboratory studies were within normal limits, except for the following: serum anion gap, 18 mEq/L (reference range for children < 3 years old, 10-14 mEq/L); serum bicarbonate, 19 mmol/L (reference range for children 12-24 months, 17-25 mmol/L); and serum creatinine, 2.8 mg/dL (reference range for children 12 to 24 months, 0.2-0.5 mg/dL). A repeat creatinine test taken after bolus of fluid administration was 2.4 mg/dL. A renal ultrasound, performed to investigate the cause of the renal failure, was unremarkable.

What toxic exposures are of concern based on the clinical history?

The history of exposure to a liquid stored in a garage raises the likelihood of exposure to an automobile-related item such as diethylene glycol, ethylene glycol (EG), and methanol.

Diethylene Glycol. Diethylene glycol is an ingredient in brake and power steering fluids, and has toxic properties qualitatively similar to EG.

Ethylene Glycol. A clear, colorless, odorless fluid with a sweet taste, EG is an ingredient in radiator antifreeze, refrigerant fluid, coolants, and pesticides. Like methylene, EG reaches peak plasma concentration within 1 to 4 hours, but toxic clinical findings do not occur for 3 to 6 hours.¹

Methanol. Methanol is a clear, colorless, alcohol found in antifreeze, windshield washer fluid, and race car fuel.² Although methanol reaches peak plasma concentration in about 30 to 60 minutes, signs of systemic toxicity (ie, metabolic acidosis) typically take 6 to 12 hours to manifest.¹

In both EG and methanol, there is a delay in toxic clinical findings because the parent compounds are not toxic in their initial form; rather, major toxicity is derived from their metabolites: formic acid and oxalic acid, respectively.

Other Toxins. Many other potentially toxic liquids are associated with a homeowner’s occupation or avocational interests. These include painting supplies (eg, industrial paints containing lead), gardening materials (eg, pesticides containing organophosphates), fuels (eg, gasoline, polychlorinated biphenyls in coolant, and lubricants), and cleaning supplies (eg, caustics, detergents, and air freshener).

Case Continuation

Since the patient’s elevated anion gap raised concerns for methanol or EG exposure, he was given fomepizole and transferred to a tertiary care children’s hospital for further management and possible hemodialysis. Upon arrival at the receiving hospital, the patient’s vital signs and physical examination remained unchanged. Repeat laboratory studies were notable for a creatinine level of 0.3 mg/dL. The patient’s father was instructed to retrieve the implicated bottle from home. An inspection of the bottle’s ingredients was notable for nitromethane, castor oil, and methanol.

What is nitromethane and what are its uses?

Nitromethane, the simplest nitro compound, is a colorless, viscous, lipid-soluble fluid.³ The polarity of nitromethane permits its use as a stabilizer in a number of chemical solvents, such as dry cleaning fluid, degreasers, and "super glue."^4,5 Nitromethane is also commonly added to model-engine and drag-race fuels, which also contain methanol and castor oil.³ In this capacity, nitromethane functions as an oxygen carrier, allowing more efficient fuel use in combustion cylinders (compared to gasoline), thereby increasing the horsepower of the vehicle.⁶ It is therefore commonly added to fuel for drag racers, radio-controlled cars, and model aircrafts.⁴ In the small concentrations typically inadvertently ingested, the clinical effects of nitromethane itself are inconsequential.

What is the differential for creatinine elevation?

Creatinine itself is a normal breakdown product of muscle metabolism produced by spontaneous conversion from creatine and is found at a fairly constant serum level in proportion to muscle mass.⁷ Thus, as people age and muscle mass decreases, their baseline creatinine levels decrease proportionally.

Elimination. The majority of creatinine (85%-90%) is filtered and excreted by the kidneys, with the remaining 10% to 15% secreted by the tubules, allowing creatinine to be a surrogate measure of the glomerular filtration rate.⁷ Exogenous sources of creatine or creatinine include meat and creatine supplements, the latter of which are used as an "energy source" to enhance athletic performance.

Etiology. The etiology for an elevated serum creatinine concentration includes renal failure, both acute and chronic; volume depletion; hemorrhage (low blood volume); and medications, including diuretics, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, nonsteroidal anti-inflammatory drugs, and certain antibiotics. These etiologies can also be categorized as processes that increase creatinine production, decrease elimination (H₂ antagonist and trimethoprim both inhibit the cation secretory pump in the tubules), or interfere with the creatinine assay (ketones, keto acids, lipemia, hemolysis, cephalosporins).⁷

Because creatinine is filtered so efficiently by the kidney, neither exogenous nor endogenous creatinine sources are expected to increase serum creatinine in the absence of renal dysfunction. However, transient elevation may occur in body builders who use extreme doses of creatine. Patients with rhabdomyolysis often develop elevated creatinine concentrations, but nearly always in the setting of myoglobinuric renal failure.

Jaffe Reaction and Enzymatic Methods. Serum creatinine can be measured using either the Jaffe reaction or the enzymatic method. In the Jaffe reaction, creatinine reacts with alkaline sodium picrate to form a red-orange chromophore, which absorbs light in the range of 470 to 550 nanometers on spectroscopy.^6,8,9 The active methylene group on nitromethane also reacts with alkaline sodium picrate to form a chromophore which absorbs light in the same wavelength range.¹⁰ Thus, serum creatinine measurements via the Jaffe reaction are falsely elevated due to the cross-reactivity between nitromethane and alkaline sodium picrate. In some reported cases, there is a 20-fold increase in the measured serum creatinine in the presence of nitromethane; renal function, however, remains normal.⁵

This false reading seen in the Jaffe reaction can be avoided by utilizing the enzymatic method of creatinine measurement, a three-step process that ultimately produces hydrogen peroxide, which is measured and accurately correlates with serum creatinine—even in the presence of nitromethane.⁸ This distinction explains the dramatically different creatinine concentrations measured at the two institutions in this case.

Case Conclusion

The patient was monitored overnight at the children’s hospital. Repeat laboratory studies in the morning showed a normal creatinine level of 0.3 mg/dL and a negative methanol level. The patient was discharged home in the care of his father, who was instructed to follow-up with his son’s pediatrician. The father also received counseling on safe storage practices for dangerous chemicals.

Case

An otherwise healthy 20-month-old boy presented to the ED for evaluation after his father witnessed the child ingest a model race car fuel additive. According to the patient’s father, the boy was playing with several closed bottles that were stored in the garage, when he witnessed the boy open up and take a sip of a pink-colored fuel additive, which the father believed to contain 100% methanol. The patient’s father further noted that immediately after drinking the fluid, the patient spat and drooled, and had one episode of nonbloody emesis prior to arrival at the ED.

Initial vital signs at presentation were: blood pressure, 84/54 mm Hg; heart rate, 97 beats/min; respiratory rate, 24 breaths/min; and temperature 98°F. Oxygen saturation was 99% on room air. Physical examination was notable for mild erythema in the posterior oropharynx. Otherwise, the patient was acting appropriately for his age and in no acute distress. Laboratory studies were within normal limits, except for the following: serum anion gap, 18 mEq/L (reference range for children < 3 years old, 10-14 mEq/L); serum bicarbonate, 19 mmol/L (reference range for children 12-24 months, 17-25 mmol/L); and serum creatinine, 2.8 mg/dL (reference range for children 12 to 24 months, 0.2-0.5 mg/dL). A repeat creatinine test taken after bolus of fluid administration was 2.4 mg/dL. A renal ultrasound, performed to investigate the cause of the renal failure, was unremarkable.

What toxic exposures are of concern based on the clinical history?

The history of exposure to a liquid stored in a garage raises the likelihood of exposure to an automobile-related item such as diethylene glycol, ethylene glycol (EG), and methanol.

Diethylene Glycol. Diethylene glycol is an ingredient in brake and power steering fluids, and has toxic properties qualitatively similar to EG.

Ethylene Glycol. A clear, colorless, odorless fluid with a sweet taste, EG is an ingredient in radiator antifreeze, refrigerant fluid, coolants, and pesticides. Like methylene, EG reaches peak plasma concentration within 1 to 4 hours, but toxic clinical findings do not occur for 3 to 6 hours.¹

Methanol. Methanol is a clear, colorless, alcohol found in antifreeze, windshield washer fluid, and race car fuel.² Although methanol reaches peak plasma concentration in about 30 to 60 minutes, signs of systemic toxicity (ie, metabolic acidosis) typically take 6 to 12 hours to manifest.¹

In both EG and methanol, there is a delay in toxic clinical findings because the parent compounds are not toxic in their initial form; rather, major toxicity is derived from their metabolites: formic acid and oxalic acid, respectively.

Other Toxins. Many other potentially toxic liquids are associated with a homeowner’s occupation or avocational interests. These include painting supplies (eg, industrial paints containing lead), gardening materials (eg, pesticides containing organophosphates), fuels (eg, gasoline, polychlorinated biphenyls in coolant, and lubricants), and cleaning supplies (eg, caustics, detergents, and air freshener).

Case Continuation

Since the patient’s elevated anion gap raised concerns for methanol or EG exposure, he was given fomepizole and transferred to a tertiary care children’s hospital for further management and possible hemodialysis. Upon arrival at the receiving hospital, the patient’s vital signs and physical examination remained unchanged. Repeat laboratory studies were notable for a creatinine level of 0.3 mg/dL. The patient’s father was instructed to retrieve the implicated bottle from home. An inspection of the bottle’s ingredients was notable for nitromethane, castor oil, and methanol.

What is nitromethane and what are its uses?

Nitromethane, the simplest nitro compound, is a colorless, viscous, lipid-soluble fluid.³ The polarity of nitromethane permits its use as a stabilizer in a number of chemical solvents, such as dry cleaning fluid, degreasers, and "super glue."^4,5 Nitromethane is also commonly added to model-engine and drag-race fuels, which also contain methanol and castor oil.³ In this capacity, nitromethane functions as an oxygen carrier, allowing more efficient fuel use in combustion cylinders (compared to gasoline), thereby increasing the horsepower of the vehicle.⁶ It is therefore commonly added to fuel for drag racers, radio-controlled cars, and model aircrafts.⁴ In the small concentrations typically inadvertently ingested, the clinical effects of nitromethane itself are inconsequential.

What is the differential for creatinine elevation?

Creatinine itself is a normal breakdown product of muscle metabolism produced by spontaneous conversion from creatine and is found at a fairly constant serum level in proportion to muscle mass.⁷ Thus, as people age and muscle mass decreases, their baseline creatinine levels decrease proportionally.

Elimination. The majority of creatinine (85%-90%) is filtered and excreted by the kidneys, with the remaining 10% to 15% secreted by the tubules, allowing creatinine to be a surrogate measure of the glomerular filtration rate.⁷ Exogenous sources of creatine or creatinine include meat and creatine supplements, the latter of which are used as an "energy source" to enhance athletic performance.

Etiology. The etiology for an elevated serum creatinine concentration includes renal failure, both acute and chronic; volume depletion; hemorrhage (low blood volume); and medications, including diuretics, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, nonsteroidal anti-inflammatory drugs, and certain antibiotics. These etiologies can also be categorized as processes that increase creatinine production, decrease elimination (H₂ antagonist and trimethoprim both inhibit the cation secretory pump in the tubules), or interfere with the creatinine assay (ketones, keto acids, lipemia, hemolysis, cephalosporins).⁷

Because creatinine is filtered so efficiently by the kidney, neither exogenous nor endogenous creatinine sources are expected to increase serum creatinine in the absence of renal dysfunction. However, transient elevation may occur in body builders who use extreme doses of creatine. Patients with rhabdomyolysis often develop elevated creatinine concentrations, but nearly always in the setting of myoglobinuric renal failure.

Jaffe Reaction and Enzymatic Methods. Serum creatinine can be measured using either the Jaffe reaction or the enzymatic method. In the Jaffe reaction, creatinine reacts with alkaline sodium picrate to form a red-orange chromophore, which absorbs light in the range of 470 to 550 nanometers on spectroscopy.^6,8,9 The active methylene group on nitromethane also reacts with alkaline sodium picrate to form a chromophore which absorbs light in the same wavelength range.¹⁰ Thus, serum creatinine measurements via the Jaffe reaction are falsely elevated due to the cross-reactivity between nitromethane and alkaline sodium picrate. In some reported cases, there is a 20-fold increase in the measured serum creatinine in the presence of nitromethane; renal function, however, remains normal.⁵

This false reading seen in the Jaffe reaction can be avoided by utilizing the enzymatic method of creatinine measurement, a three-step process that ultimately produces hydrogen peroxide, which is measured and accurately correlates with serum creatinine—even in the presence of nitromethane.⁸ This distinction explains the dramatically different creatinine concentrations measured at the two institutions in this case.

Case Conclusion

The patient was monitored overnight at the children’s hospital. Repeat laboratory studies in the morning showed a normal creatinine level of 0.3 mg/dL and a negative methanol level. The patient was discharged home in the care of his father, who was instructed to follow-up with his son’s pediatrician. The father also received counseling on safe storage practices for dangerous chemicals.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, approximately 468,000 persons in the United States are on dialysis—a number that continues to grow annually.¹ The 1-year rate for hemorrhagic complications from arteriovenous fistulas (AVFs) is estimated to be 0.4%.² One study by Ellingson et al³ reported 1,654 deaths secondary to fatal vascular access hemorrhage over a 6-year period, accounting for 0.4% of all deaths of hemodialysis (HD) patients in that study.³

Nonhemorrhagic vascular access-related complications also contribute to the morbidity and mortality associated with AVFs and arteriovenous grafts (AVGs). Venous stenosis resulting in thrombosis has been estimated to occur in 24.7% of AVGs and 9.0% of AVFs, both of which are common causes of access failure.

Infection is reported to be the second leading cause of death in dialysis patients, and vascular access-related infection rates are reported to occur in 9.5% of AVGs vs 0.4% to 0.9% of AVFs.^2,4 Pseudoaneurysms and aneurysms range from 30% to 60% for AVFs,^2,5 and contribute to morbidity by limiting available areas to cannulate for dialysis, occasionally requiring surgical revision to restore access function or prevent access rupture.

Steal phenomena, including dialysis access-induced steal syndrome (DASS) and ischemic monomelic neuropathy, as well as heart failure secondary to high output are additional contributors to morbidity and mortality.

With the growing rate of end-stage renal disease (ESRD) in the United States and the contribution to morbidity and mortality by bleeding and other complications, it is essential to understand how to evaluate and treat these patients in the ED. This article reviews the evaluation and treatment of vascular access emergencies, as well as risk factors that contribute to complications in the ESRD patient population.

Hemorrhagic Complications of Vascular Access

Risk Factors

Many patients with ESRD have multiple comorbidities such as coronary artery disease and atrial fibrillation that require anticoagulation, antiplatelet medications, or both. Studies have shown that ESRD patients taking warfarin have an increase in major bleeding episodes of 3.1% per person-year and 4.4% per person-year for those taking aspirin alone, while those taking both medications have an increased bleeding risk of 6.3% per person-year.⁶ A recent systematic review by Elliott et al⁷ has suggested a 2-fold increase in bleeding rates in HD patients anticoagulated with warfarin as compared to HD patients not on warfarin.

While uremia secondary to chronic kidney disease (CKD) is a well-known facilitator of bleeding complications, the underlying pathophysiology is not yet completely delineated. However, there are some general underlying principles that may help in understanding the best treatment modalities available at this time. As the kidneys fail, uremic toxins accumulate in the bloodstream. These toxins include urea, creatinine, and phenolic acids, which are believed to interfere with primary hemostasis by effecting platelet adherence to endothelium, platelet activation, and aggregation.⁸ Functional defects are created in the interactions between the glycoprotein Ib (GPIb) receptor and von Willebrand factor (vWF), which are essential to endothelial adhesion of platelets.⁹ Additionally, these toxins impair the up regulation of the GPIIbIIIa receptor which is integral to platelet aggregation.¹⁰ Platelet activation normally leads to platelet aggregation by increasing production of thromboxane A2 (TXA2) and serotonin that are released from storage granules.¹⁰ Some toxins may increase nitric oxide (NO) synthesis, effectively reducing aggregation by decreasing TXA2 and adenosine diphosphate (ADP) levels.¹¹ In addition, elevated levels of fibrinogen fragments have also recently been shown to inhibit platelet function by competing with fibrinogen for the GPIIbIIIa receptor with decreasing levels demonstrated after HD.¹²

Finally, increased pressure in the venous outflow segment also increases persistent bleeding from puncture sites. These pressures may be exaggerated secondary to venous thrombosis, venous stenosis, pseudoaneurysm, aneurysm, or infection.¹³ The following sections further describe the evaluation and treatment of these complications.

Clinical Presentation

Patients presenting with bleeding from the vascular access site may present with slow continuous oozing from the needle puncture-site itself or with life-threatening hemorrhage secondary to AVF or AVG rupture.¹⁴ The incidence of vascular access rupture is unknown, but it appears the majority of ruptures occur in patients with AVG vs AVF.³ However, several case reports have also described hemorrhagic complications of AVF ruptures.^15-17 The risk of rupture may be associated with the development of aneurysms or pseudoaneuryms.¹⁸ Possible impending perforation may be signaled by skin thinning or a shiny appearance overlying the aneurysm, or evidence of infection overlying the access site.³ Many patients were shown to have complications such as stenosis, thrombosis, or infection within 6 months prior to rupture.³ Education of patients is also important as most hemorrhages occur prior to hospital arrival.^3,19

Evaluation in the ED

As with any patient presenting to the ED, the initial evaluation of an unstable patient experiencing bleeding from a vascular access site includes assessing the airway, breathing, and circulation as a first priority—paying special attention to the area of bleeding while simultaneously preparing for possible intervention. It is also important to determine when the patient last underwent dialysis and if he or she was able to complete HD. This information will identify patients who are candidates for reversing the heparin load likely given during dialysis.

It is also important to note that some patients undergoing HD who have already been identified as having an increased risk of bleeding may not receive heparin or may undergo local heparinization, minimal heparinization, or regional citrate anticoagulation during dialysis, in which case protamine is not indicated.¹⁴ The emergency physician (EP) must also determine if the patient is on any antiplatelet or anticoagulation agents.

The vascular access site should be inspected for evidence of aneurysmal changes, infection, and skin thinning as these factors increase the risk of bleeding and vascular rupture. Additionally auscultation and palpation of the vascular access site should be performed to evaluate for other potential complications such as stenosis and thrombosis. Lastly, the EP should anticipate the patient’s need for HD in the setting of a potentially unavailable AVG or AVF to determine whether the patient may need an alternative access.

Treatment and Management

The primary responsibility during the initial treatment of a bleeding access site is to stop further blood loss by utilizing methods that employ direct pressure or, in extreme cases, application of a tourniquet, followed by other interventions such as fluid and blood-product resuscitation; coagulopathy reversal; consideration of desmopressin, cryoprecipitate, tranexamic acid (TXA); HD; and vascular repair.

Control of a bleeding dialysis access-site is a balancing act of adequately controlling the bleeding while maintaining the integrity of the fistula. Overly aggressive management may cause thrombosis in the vascular access site, which is associated with morbidity—eg, site revisions, potential for the need to create a new access site. On the opposite end of the spectrum, failing to adequately control bleeding can lead to significant anemia ranging from minimal symptoms to hemodynamic compromise and death.

Peripheral Venous Access

While peripheral venous access is notoriously difficult in patients with ESRD, it is essential for the resuscitation of hemorrhaging patients. Ideally, two large bore peripheral intravenous (IV) lines should be placed in the proximal upper extremities. If peripheral venous access is not achieved, central venous access or interosseous access placement is indicated (Figure).

Direct Pressure

With low-volume bleeding, the first attempt to control the bleeding is simple direct pressure. Except in the instance of trauma or self-inflicted injury, bleeding usually occurs at the site of cannulation of the vascular access post-HD. Direct pressure should be light and limited to as small of an area as possible to prevent thrombosis; the force and area encompassed by direct pressure can be expanded as needed for bleeding that is more difficult to control. In cases of higher volume bleeding, pressure should be placed both proximally and distally to the shunt due to its bidirectional flow. Another possible temporizing measure is to place an upright gallipot or cup over the bleeding site on top of a folded piece of gauze and then securing it with tape.²¹

Topical Hemostatic Agents

Second simple direct pressure, topical hemostatic agents may be a good adjunct to help obtain hemostasis. There is a wide range of products available, from procoagulants (eg, Combat Gauze, topical thrombin) to factor concentrators (eg, QuikClot). These can be used directly on the bleeding site and only in conjunction with direct pressure.

In addition to topical hemostatic agents, another option is skin glue, which should be applied generously after bleeding has been temporized, with pressure both proximally and distally to the site.

Anticoagulation Reversal

As previously mentioned, it is important to determine when the patient’s last HD was. Heparin is used during dialysis to prevent clotting within the circuit, and although clotting times are monitored during dialysis to guide anticoagulation, it is possible that a patient bleeding after dialysis could still have therapeutic levels of heparin requiring reversal with protamine.

The recommended dose of protamine is 1 mg for every 100 U of heparin given during dialysis; protamine should be administered over 10 minutes. Alternatively, a 10- to 20-mg dose of protamine can be given if the amount of heparin administered during HD is unknown. Additionally, the patient’s medication list, as with any ED presentation, should be carefully reviewed as many dialysis patients have comorbidities requiring anticoagulation with potentially reversible agents.

Hemodialysis to Improve Platelet Dysfunction

It is thought that long-term exposure of platelets to the dialysis membrane can lead to chronic platelet activation leading to platelet dysfunction. There is conflicting data regarding the effects of HD on improving bleeding in renal patients.^9,22,23 Hemodialysis is thought to be beneficial, at least partially, through reversing uremia, thus improving platelet function.²⁴ Therefore, in the stable bleeding patient who missed a scheduled dialysis, initiating HD in the ED setting could be beneficial. If the vascular access site is deemed unsafe for HD, another access site must be obtained, for example, by placing a temporary central venous catheter that will allow for successful HD.

Desmopressin

Desmopressin acetate has been shown to reduce bleeding time in uremic patients by releasing vWF and factor VIII into plasma, taking effect within 1 hour and lasting 4 to 8 hours.^25-27 Desmopressin has also been shown to reduce blood loss and bleeding times in patients with platelet dysfunction undergoing cardiac surgery.²⁸ While the underlying mechanism is unclear, desmopressin acetate is thought to help with platelet adhesion to the endothelial wall.

Alternatively, one study by Soslau et al²⁹ has suggested that desmopressin may increase serotonin uptake by platelets and increase adenosine triphosphate release, thereby facilitating platelet aggregation. The dosing of desmopressin is 0.2 to 0.3 mcg/kg IV.³⁰ Adverse effects include facial flushing, mild headache, and transient small decrease in blood pressure (BP) with increase in heart rate. Historically, it was thought that desmopressin could lead to water retention, volume overload, congestive heart failure, and hyponatremia; however, these adverse effects have not been seen in uremic patients.³⁰ Tachyphylaxis may occur after just a few doses of desmopressin are given.³¹ Additionally, hyponatremia and seizures have been seen after repeated administration in children.³¹

Anemia and Low Hematocrit

As mentioned earlier, anemia and low hematocrit (HCT) may actually exacerbate bleeding tendencies by decreasing the number of platelets exposed to the vessel wall. Red blood cells (RBCs) also produce TXA2 and ADP, both of which play vital roles in normal platelet aggregation. Secondly, RBCs have been shown to increase NO uptake. Nitric oxide is a potent vasodilator and inhibitor of platelet aggregation. The degree of uptake appears to be augmented by increasing HCT levels.³² A goal HCT of greater than 30% has been suggested and demonstrated benefit.³³

Cryoprecipitate

Cryoprecipitate is rich in fibrinogen and vWF. Its mechanism is thought to be secondary to increasing functional vWF levels and possibly fibrinogen levels. While the overall effects appear to be variable, studies suggest 10 U of cryoprecipitate is adequate to reverse significant bleeding with resolution of effect at 24 hours.^34,35 Given the risks of adverse reactions, variable responses, and risks of hepatitis C and HIV transmission, this therapy must be used cautiously with risk-benefit analysis.

Tranexamic Acid

Tranexamic acid is an antifibrinolytic agent that binds to fibrinogen as a competitive inhibitor of plasmin, inhibiting plasminogen activation. The trauma literature has shown TXA to significantly reduce all-cause mortality.³⁶ It has also been shown to be beneficial in the bleeding uremic patient.^37-39

However, it is important to keep in mind that the clearance of TXA in patients with renal disease is unclear. One study by Andersson et al⁴⁰ demonstrated that TXA has increased plasma concentrations in patients with renal impairment, and a generally accepted practice is to renal-dose this medication. This study recommended a dose of 10 mg/kg IV at varying intervals, such as once daily, twice daily, or every 48 hours depending on the creatinine value, compared to patients with no renal impairment.⁴⁰ Another study by Sabovic et al³⁹ that evaluated the effects of TXA on gastrointestinal bleeding in patients with renal impairment used a 20-mg IV loading dose of TXA followed by 10 mg/kg orally every 48 hours. Though no adverse events occurred in this study, the study group was small. Other studies have not shown an increase in thromboembolic risk in patients who have no renal disease.^36,41

At this time, there is no consensus on the exact dosing of TXA in this patient population. Therefore, this therapy should only be considered if others have failed and the patient continues to have significant blood loss.

Life-threatening Hemorrhage

If a patient is experiencing life-threatening blood loss, more aggressive measures must be employed regardless of risk of damage to the access. In such cases, a consultation with vascular surgery services should be obtained as early as possible. If none of the previously discussed measures are ineffective, the EP may be required to place sutures in the vascular access itself or apply a tourniquet. Again, these interventions may cause permanent damage to the access; however, in the setting of life-threatening hemorrhage such interventions clearly outweigh the risks associated with continued blood loss.

As blood can flow bidirectionally within a fistula, a tourniquet should be placed both proximally and distally to the fistula to obtain adequate hemostasis. Once the tourniquets are in place, if there is no immediate surgical consultation available, the EP may need to temporarily repair the defect to allow minimal tourniquet time. There are a few considerations when placing sutures. Ideally, a noncutting needle should be used to minimize damage. An adequate-sized suture, such as a 3-0 nylon suture, should be used to maintain strength in the high-pressure system. A figure-8 suture or purse-string suture may be placed around the defect. Adequate repair should allow for tourniquet removal.

Hemodynamic Status

The EP must remain aware of the patient’s hemodynamic status. Massive transfusion protocols may need to be initiated. Best current evidence dictates that this should be done in a 1:1:1 ratio of packed red blood cells, platelets, and fresh frozen plasma respectively.⁴² In our experience, the EP should consider permissive hypotension as aggressive resuscitation and increasing BP can compromise the vascular repair.

Lastly, transfer for definitive management should be arranged if not available at the EP’s institution. The patient should travel with tourniquets in place (although not tightened) in the event of further bleeding.

Nonhemorrhagic Complications of AVF or AVG

Stenosis/Thrombosis

Prolonged bleeding from the cannulation site may suggest outflow stenosis.⁴³ Stenosis with or without subsequent thrombosis is a common cause of vascular access failure. Access failure has also been implicated secondary to poor vascular mapping, resulting in undetected pre-existing stenosis of the inflow artery, outflow vein, or juxta-anastomosis. However, development of stenosis may occur at any time throughout the life of the vascular access. One study by Schild et al⁴ reported thrombosis rates of 24.7% for grafts and 9.0% for fistula. Additionally, AVGs have a higher reported stenosis rate than AVFs, which is a risk factor for thrombosis.^44,45

There has been much debate regarding routine surveillance to prevent clinically significant stenosis with subsequent thrombosis. Surveillance includes a clinical examination, Doppler imaging studies, and flow measurements during dialysis. A recent systematic review from 2016 by Ravani et al,⁴⁶ demonstrated no difference in risk of access loss in preemptive stenosis correction in AVF or AVG without evidence of access dysfunction. However, on subgroup analysis this review did demonstrate a small benefit regarding risk of thrombosis and access loss in the AVF group.⁴⁶

The physical examination may indicate evidence of vascular access stenosis or thrombosis. Evidence of stenosis may be indicated by failure of the outflow vein to collapse on arm raise test (distal stenosis), hyperpulsatility or hypopulsatility, loss of the diastolic component of the normal continuous thrill and bruit with only systolic components appreciated, and arm edema (central vein stenosis).^43,47 Thrombosis of the vein may be evidenced by complete loss of the thrill and pulsatility on palpation. Sensitivity and specificity of the physical examination for inflow or outflow stenosis has been reported to be between 70% to 92% and 71% to 100%, respectively.^48-50

While evidence may or may not support preemptive correction of stenosis, interventions are usually required when the stenosis is more than 50% and interferes with dialysis, decreased flow, abnormal physical examination, or elevated venous pressures.⁵¹ If stenosis is associated with interference of effective dialysis or thrombosis is suspected, ultrasound imaging and consultation with a vascular surgeon or interventional radiologist are indicated. Treatment of AVF or AVG stenosis and thrombosis includes percutaneous and surgical interventions.⁵²

A systematic review by Tanner and da Silva⁵³ evaluating adjuvant medical treatments for increasing patency rates of AVF and AVG found no therapy had any improvement in patency rates at 1 month. Another review from 2015 by Palmer et al⁵⁴ suggested antiplatelet therapy may be protective for stenosis and thrombosis in AVF, but not AVG.

Infection

Infection in patients with ESRD is a major cause of morbidity and mortality, and 24% of these infections may be attributed to the vascular access itself, including central venous catheters (CVC).⁵⁵ Central venous catheters are associated with the highest rate of infection, followed by AVGs, then AVFs.^4,54 Studies have reported 9.5% vs 0.4% to 0.9% infection rates for AVG and AVF, respectively.^2,4 These infections are usually due to gram-positive organisms, with the Staphylococcus species being the most common organism involved.^55-57 However, infections caused by gram-negative organisms are possible, and broad-spectrum antibiotics should be initiated in the ED if infection is suspected. Patients may present with localized infection with increased risk of rupture of access to profound sepsis. Definitive treatment of an infected graft or fistula usually requires removal of the infected access or at least partial excision with possible interposition of additional graft material.⁵⁸

Pseudoaneurysm/Aneurysm

Pseudoaneuryms are usually caused by hematoma development after needle puncture or in juxta-anastomic segments postoperatively. Pseudoaneurysms do not have a true wall and may secondarily become infected.⁵⁹ Pseudoaneurysms occur more frequently in AVG, and are usually reported along with true aneurysms. One study by Al-Thani et al⁶⁰ detected pseudoaneurysms in 15% of clinically significant aneurysms.

Approximately 30% to 60% of patients with AVFs will develop an aneurysm.^2,5 One study by Al-Thani et al⁶⁰ reported the need for surgical intervention in 31% of patients with an AVF in whom an aneurysm was detected. The risk for developing an aneurysm is highest for those patients on high flux membrane type HD and polycystic kidney disease.⁵ As discussed earlier in this article, cannulation sites and techniques may also influence aneurysmal changes in the fistula. Aneurysm formation at the site of previous cannulation site should not be re-cannulated.¹⁸ Aneurysmal changes can contribute to other complications including high-output heart failure, thrombosis with fistula or graft failure, increased risk of bleeding, ineffective HD when associated with thrombosis or stenosis, pain and peripheral neuropathies secondary to compression of nearby nerves, and interference with functional HD.

Many asymptomatic aneurysmal changes to vascular access may not compromise access function. If a patient is identified with a vascular access pseudoaneurysm or aneurysmal changes with high-risk features, early referral to vascular surgeon for surgical interventions is imperative. High-risk features include any of the complications previously discussed—infection, threatened overlying skin, or shiny appearance. The EP should consider duplex imaging to assist with evaluation. Treatment may include ligation of the AVF, partial resection, stenting, or grafting of the aneurysm with hopes of salvaging the vascular access.^61,62

Ischemic Monomelic Neuropathy

Ischemic monomelic neuropathy may result secondary to a type of steal phenomenon, thereby inducing ischemia to supplied nerves. Ischemic monomelic neuropathy has been described in many case reports and narrative reviews.^63-67 It has been described as ischemia or infarction of the blood supply to the nerves (vasa nervosa) in the lower arm.⁶⁸ Ischemic monomelic neuropathy typically occurs immediately after the vascular access creation in the postoperative period. Therefore, it is unlikely to be seen in the ED but as patients may have sequelae of this complication, EPs should be aware of its existence. Patients with ischemic monomelic neuropathy will have severe pain, paresthesia, and weakness immediately after placement of a vascular access. Patients also typically have sensorimotor deficits in the radial, ulnar, and median nerves. Pulses should be preserved. Severe neuropathic pain will develop and may limit the examination. Clinical diagnosis may be difficult immediately after surgery because patients will often have minor deficits secondary to the surgical procedure itself or secondary to the regional block provided by anesthesia, but nerve-conduction studies usually reveal the diagnosis. The treatment is ligation of the access immediately and prognosis is variable, depending on the severity and duration of ischemia, and may result in complete loss of function of the hand.

Steal Syndrome

Dialysis access-associated steal syndrome is a type of distal ischemia secondary to the vascular access site with a reported incidence of 6.2%, and appears to occur more frequently in AVF than AVGs.^69,70 Diabetes appears to be a strong risk factor for developing DASS.⁷¹ Patients with DASS can present with classic ischemic symptoms such as pain, paresthesia, claudication, pallor, and diminished or absent arterial pulse. Pain may be present only while undergoing dialysis or exercising, or symptoms may be persistent.^68,72 There are several possible causes of DASS, including arterial occlusion or insufficiency proximal or distal to the anastomosis, increased flow through the conduit (true steal), or increased flow diverted through collateral vessels.^73,74 One clue to the diagnosis is a diminished or absent radial pulse that should improve with compression of the access site.

Once DASS is suspected, diagnosis should be confirmed using venous duplex scanning with finger pressure waveform analysis or arteriogram. Definitive management is surgical intervention with ligation of the access or banding.

High-Output Heart Failure

Changes in cardiac output (CO) are a well-documented effect of AVF placement, with one small study by Korsheed et al⁷⁵ demonstrating an average increase in CO of 17% only 2 weeks after AVF placement. The increase in CO is thought to be secondary to alterations in systemic vascular resistance and sympathetic activity. While an increase in CO can ultimately lead to high-output heart failure, this is typically only seen in patients with pre-existing cardiac dysfunction.⁷⁶ Patients are at an increased risk of high-output heart failure when flow through the AVF exceeds 2 L/min; flows below this rate are typically not associated with adverse cardiac effects.⁷⁷ Another objective measurement for identifying patients at risk of high-output heart failure is the ratio of flow in the fistula (Qa) to cardiac output ratio. Patients with a Qa:CO ratio greater than 0.3 have a significantly increased risk of high-output heart failure.⁷⁸ There is thought to be no difference in risk of heart failure between AVF and AVG.⁷⁹

Once overt heart failure has developed, it should be treated in the usual fashion, with IV fluid management and standard pharmacological therapies. If standard conservative heart failure treatment is ineffective, several surgical options are available, including banding, changing the location of the anastomosis, and ultimately closing the fistula.⁸⁰

Conclusion

While life-threatening bleeding and vascular access rupture are uncommon complications of AVFs and AVGs, it is essential for the EP to rapidly treat the potentially catastrophic hemorrhagic vascular access complications. Depending on the severity and stability of the patient, it is reasonable to begin in a stepwise fashion as presented in this article for patients with minor bleeding, while more severe or persistent bleeding may require several interventions simultaneously to gain control of the bleeding.

Patients with hemodynamic instability requiring transfusion will need a vascular surgery consult and admission. Disposition for stable patients, without evidence of impending aneurysmal related rupture and concern for overlying infection or other complication requiring immediate intervention, will depend on clinical judgment, patient-specific factors and family support, follow-up, and proximity of the patient to medical care.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, approximately 468,000 persons in the United States are on dialysis—a number that continues to grow annually.¹ The 1-year rate for hemorrhagic complications from arteriovenous fistulas (AVFs) is estimated to be 0.4%.² One study by Ellingson et al³ reported 1,654 deaths secondary to fatal vascular access hemorrhage over a 6-year period, accounting for 0.4% of all deaths of hemodialysis (HD) patients in that study.³

Nonhemorrhagic vascular access-related complications also contribute to the morbidity and mortality associated with AVFs and arteriovenous grafts (AVGs). Venous stenosis resulting in thrombosis has been estimated to occur in 24.7% of AVGs and 9.0% of AVFs, both of which are common causes of access failure.

Infection is reported to be the second leading cause of death in dialysis patients, and vascular access-related infection rates are reported to occur in 9.5% of AVGs vs 0.4% to 0.9% of AVFs.^2,4 Pseudoaneurysms and aneurysms range from 30% to 60% for AVFs,^2,5 and contribute to morbidity by limiting available areas to cannulate for dialysis, occasionally requiring surgical revision to restore access function or prevent access rupture.

Steal phenomena, including dialysis access-induced steal syndrome (DASS) and ischemic monomelic neuropathy, as well as heart failure secondary to high output are additional contributors to morbidity and mortality.

With the growing rate of end-stage renal disease (ESRD) in the United States and the contribution to morbidity and mortality by bleeding and other complications, it is essential to understand how to evaluate and treat these patients in the ED. This article reviews the evaluation and treatment of vascular access emergencies, as well as risk factors that contribute to complications in the ESRD patient population.

Hemorrhagic Complications of Vascular Access

Risk Factors

Many patients with ESRD have multiple comorbidities such as coronary artery disease and atrial fibrillation that require anticoagulation, antiplatelet medications, or both. Studies have shown that ESRD patients taking warfarin have an increase in major bleeding episodes of 3.1% per person-year and 4.4% per person-year for those taking aspirin alone, while those taking both medications have an increased bleeding risk of 6.3% per person-year.⁶ A recent systematic review by Elliott et al⁷ has suggested a 2-fold increase in bleeding rates in HD patients anticoagulated with warfarin as compared to HD patients not on warfarin.

While uremia secondary to chronic kidney disease (CKD) is a well-known facilitator of bleeding complications, the underlying pathophysiology is not yet completely delineated. However, there are some general underlying principles that may help in understanding the best treatment modalities available at this time. As the kidneys fail, uremic toxins accumulate in the bloodstream. These toxins include urea, creatinine, and phenolic acids, which are believed to interfere with primary hemostasis by effecting platelet adherence to endothelium, platelet activation, and aggregation.⁸ Functional defects are created in the interactions between the glycoprotein Ib (GPIb) receptor and von Willebrand factor (vWF), which are essential to endothelial adhesion of platelets.⁹ Additionally, these toxins impair the up regulation of the GPIIbIIIa receptor which is integral to platelet aggregation.¹⁰ Platelet activation normally leads to platelet aggregation by increasing production of thromboxane A2 (TXA2) and serotonin that are released from storage granules.¹⁰ Some toxins may increase nitric oxide (NO) synthesis, effectively reducing aggregation by decreasing TXA2 and adenosine diphosphate (ADP) levels.¹¹ In addition, elevated levels of fibrinogen fragments have also recently been shown to inhibit platelet function by competing with fibrinogen for the GPIIbIIIa receptor with decreasing levels demonstrated after HD.¹²

Finally, increased pressure in the venous outflow segment also increases persistent bleeding from puncture sites. These pressures may be exaggerated secondary to venous thrombosis, venous stenosis, pseudoaneurysm, aneurysm, or infection.¹³ The following sections further describe the evaluation and treatment of these complications.

Clinical Presentation

Patients presenting with bleeding from the vascular access site may present with slow continuous oozing from the needle puncture-site itself or with life-threatening hemorrhage secondary to AVF or AVG rupture.¹⁴ The incidence of vascular access rupture is unknown, but it appears the majority of ruptures occur in patients with AVG vs AVF.³ However, several case reports have also described hemorrhagic complications of AVF ruptures.^15-17 The risk of rupture may be associated with the development of aneurysms or pseudoaneuryms.¹⁸ Possible impending perforation may be signaled by skin thinning or a shiny appearance overlying the aneurysm, or evidence of infection overlying the access site.³ Many patients were shown to have complications such as stenosis, thrombosis, or infection within 6 months prior to rupture.³ Education of patients is also important as most hemorrhages occur prior to hospital arrival.^3,19

Evaluation in the ED

As with any patient presenting to the ED, the initial evaluation of an unstable patient experiencing bleeding from a vascular access site includes assessing the airway, breathing, and circulation as a first priority—paying special attention to the area of bleeding while simultaneously preparing for possible intervention. It is also important to determine when the patient last underwent dialysis and if he or she was able to complete HD. This information will identify patients who are candidates for reversing the heparin load likely given during dialysis.

It is also important to note that some patients undergoing HD who have already been identified as having an increased risk of bleeding may not receive heparin or may undergo local heparinization, minimal heparinization, or regional citrate anticoagulation during dialysis, in which case protamine is not indicated.¹⁴ The emergency physician (EP) must also determine if the patient is on any antiplatelet or anticoagulation agents.

The vascular access site should be inspected for evidence of aneurysmal changes, infection, and skin thinning as these factors increase the risk of bleeding and vascular rupture. Additionally auscultation and palpation of the vascular access site should be performed to evaluate for other potential complications such as stenosis and thrombosis. Lastly, the EP should anticipate the patient’s need for HD in the setting of a potentially unavailable AVG or AVF to determine whether the patient may need an alternative access.

Treatment and Management

The primary responsibility during the initial treatment of a bleeding access site is to stop further blood loss by utilizing methods that employ direct pressure or, in extreme cases, application of a tourniquet, followed by other interventions such as fluid and blood-product resuscitation; coagulopathy reversal; consideration of desmopressin, cryoprecipitate, tranexamic acid (TXA); HD; and vascular repair.

Control of a bleeding dialysis access-site is a balancing act of adequately controlling the bleeding while maintaining the integrity of the fistula. Overly aggressive management may cause thrombosis in the vascular access site, which is associated with morbidity—eg, site revisions, potential for the need to create a new access site. On the opposite end of the spectrum, failing to adequately control bleeding can lead to significant anemia ranging from minimal symptoms to hemodynamic compromise and death.

Peripheral Venous Access

While peripheral venous access is notoriously difficult in patients with ESRD, it is essential for the resuscitation of hemorrhaging patients. Ideally, two large bore peripheral intravenous (IV) lines should be placed in the proximal upper extremities. If peripheral venous access is not achieved, central venous access or interosseous access placement is indicated (Figure).

Direct Pressure

With low-volume bleeding, the first attempt to control the bleeding is simple direct pressure. Except in the instance of trauma or self-inflicted injury, bleeding usually occurs at the site of cannulation of the vascular access post-HD. Direct pressure should be light and limited to as small of an area as possible to prevent thrombosis; the force and area encompassed by direct pressure can be expanded as needed for bleeding that is more difficult to control. In cases of higher volume bleeding, pressure should be placed both proximally and distally to the shunt due to its bidirectional flow. Another possible temporizing measure is to place an upright gallipot or cup over the bleeding site on top of a folded piece of gauze and then securing it with tape.²¹

Topical Hemostatic Agents

Second simple direct pressure, topical hemostatic agents may be a good adjunct to help obtain hemostasis. There is a wide range of products available, from procoagulants (eg, Combat Gauze, topical thrombin) to factor concentrators (eg, QuikClot). These can be used directly on the bleeding site and only in conjunction with direct pressure.

In addition to topical hemostatic agents, another option is skin glue, which should be applied generously after bleeding has been temporized, with pressure both proximally and distally to the site.

Anticoagulation Reversal

As previously mentioned, it is important to determine when the patient’s last HD was. Heparin is used during dialysis to prevent clotting within the circuit, and although clotting times are monitored during dialysis to guide anticoagulation, it is possible that a patient bleeding after dialysis could still have therapeutic levels of heparin requiring reversal with protamine.

The recommended dose of protamine is 1 mg for every 100 U of heparin given during dialysis; protamine should be administered over 10 minutes. Alternatively, a 10- to 20-mg dose of protamine can be given if the amount of heparin administered during HD is unknown. Additionally, the patient’s medication list, as with any ED presentation, should be carefully reviewed as many dialysis patients have comorbidities requiring anticoagulation with potentially reversible agents.

Hemodialysis to Improve Platelet Dysfunction

It is thought that long-term exposure of platelets to the dialysis membrane can lead to chronic platelet activation leading to platelet dysfunction. There is conflicting data regarding the effects of HD on improving bleeding in renal patients.^9,22,23 Hemodialysis is thought to be beneficial, at least partially, through reversing uremia, thus improving platelet function.²⁴ Therefore, in the stable bleeding patient who missed a scheduled dialysis, initiating HD in the ED setting could be beneficial. If the vascular access site is deemed unsafe for HD, another access site must be obtained, for example, by placing a temporary central venous catheter that will allow for successful HD.

Desmopressin

Desmopressin acetate has been shown to reduce bleeding time in uremic patients by releasing vWF and factor VIII into plasma, taking effect within 1 hour and lasting 4 to 8 hours.^25-27 Desmopressin has also been shown to reduce blood loss and bleeding times in patients with platelet dysfunction undergoing cardiac surgery.²⁸ While the underlying mechanism is unclear, desmopressin acetate is thought to help with platelet adhesion to the endothelial wall.

Alternatively, one study by Soslau et al²⁹ has suggested that desmopressin may increase serotonin uptake by platelets and increase adenosine triphosphate release, thereby facilitating platelet aggregation. The dosing of desmopressin is 0.2 to 0.3 mcg/kg IV.³⁰ Adverse effects include facial flushing, mild headache, and transient small decrease in blood pressure (BP) with increase in heart rate. Historically, it was thought that desmopressin could lead to water retention, volume overload, congestive heart failure, and hyponatremia; however, these adverse effects have not been seen in uremic patients.³⁰ Tachyphylaxis may occur after just a few doses of desmopressin are given.³¹ Additionally, hyponatremia and seizures have been seen after repeated administration in children.³¹

Anemia and Low Hematocrit

As mentioned earlier, anemia and low hematocrit (HCT) may actually exacerbate bleeding tendencies by decreasing the number of platelets exposed to the vessel wall. Red blood cells (RBCs) also produce TXA2 and ADP, both of which play vital roles in normal platelet aggregation. Secondly, RBCs have been shown to increase NO uptake. Nitric oxide is a potent vasodilator and inhibitor of platelet aggregation. The degree of uptake appears to be augmented by increasing HCT levels.³² A goal HCT of greater than 30% has been suggested and demonstrated benefit.³³

Cryoprecipitate

Cryoprecipitate is rich in fibrinogen and vWF. Its mechanism is thought to be secondary to increasing functional vWF levels and possibly fibrinogen levels. While the overall effects appear to be variable, studies suggest 10 U of cryoprecipitate is adequate to reverse significant bleeding with resolution of effect at 24 hours.^34,35 Given the risks of adverse reactions, variable responses, and risks of hepatitis C and HIV transmission, this therapy must be used cautiously with risk-benefit analysis.

Tranexamic Acid

Tranexamic acid is an antifibrinolytic agent that binds to fibrinogen as a competitive inhibitor of plasmin, inhibiting plasminogen activation. The trauma literature has shown TXA to significantly reduce all-cause mortality.³⁶ It has also been shown to be beneficial in the bleeding uremic patient.^37-39

However, it is important to keep in mind that the clearance of TXA in patients with renal disease is unclear. One study by Andersson et al⁴⁰ demonstrated that TXA has increased plasma concentrations in patients with renal impairment, and a generally accepted practice is to renal-dose this medication. This study recommended a dose of 10 mg/kg IV at varying intervals, such as once daily, twice daily, or every 48 hours depending on the creatinine value, compared to patients with no renal impairment.⁴⁰ Another study by Sabovic et al³⁹ that evaluated the effects of TXA on gastrointestinal bleeding in patients with renal impairment used a 20-mg IV loading dose of TXA followed by 10 mg/kg orally every 48 hours. Though no adverse events occurred in this study, the study group was small. Other studies have not shown an increase in thromboembolic risk in patients who have no renal disease.^36,41

At this time, there is no consensus on the exact dosing of TXA in this patient population. Therefore, this therapy should only be considered if others have failed and the patient continues to have significant blood loss.

Life-threatening Hemorrhage

If a patient is experiencing life-threatening blood loss, more aggressive measures must be employed regardless of risk of damage to the access. In such cases, a consultation with vascular surgery services should be obtained as early as possible. If none of the previously discussed measures are ineffective, the EP may be required to place sutures in the vascular access itself or apply a tourniquet. Again, these interventions may cause permanent damage to the access; however, in the setting of life-threatening hemorrhage such interventions clearly outweigh the risks associated with continued blood loss.

As blood can flow bidirectionally within a fistula, a tourniquet should be placed both proximally and distally to the fistula to obtain adequate hemostasis. Once the tourniquets are in place, if there is no immediate surgical consultation available, the EP may need to temporarily repair the defect to allow minimal tourniquet time. There are a few considerations when placing sutures. Ideally, a noncutting needle should be used to minimize damage. An adequate-sized suture, such as a 3-0 nylon suture, should be used to maintain strength in the high-pressure system. A figure-8 suture or purse-string suture may be placed around the defect. Adequate repair should allow for tourniquet removal.

Hemodynamic Status

The EP must remain aware of the patient’s hemodynamic status. Massive transfusion protocols may need to be initiated. Best current evidence dictates that this should be done in a 1:1:1 ratio of packed red blood cells, platelets, and fresh frozen plasma respectively.⁴² In our experience, the EP should consider permissive hypotension as aggressive resuscitation and increasing BP can compromise the vascular repair.

Lastly, transfer for definitive management should be arranged if not available at the EP’s institution. The patient should travel with tourniquets in place (although not tightened) in the event of further bleeding.

Nonhemorrhagic Complications of AVF or AVG

Stenosis/Thrombosis

Prolonged bleeding from the cannulation site may suggest outflow stenosis.⁴³ Stenosis with or without subsequent thrombosis is a common cause of vascular access failure. Access failure has also been implicated secondary to poor vascular mapping, resulting in undetected pre-existing stenosis of the inflow artery, outflow vein, or juxta-anastomosis. However, development of stenosis may occur at any time throughout the life of the vascular access. One study by Schild et al⁴ reported thrombosis rates of 24.7% for grafts and 9.0% for fistula. Additionally, AVGs have a higher reported stenosis rate than AVFs, which is a risk factor for thrombosis.^44,45

There has been much debate regarding routine surveillance to prevent clinically significant stenosis with subsequent thrombosis. Surveillance includes a clinical examination, Doppler imaging studies, and flow measurements during dialysis. A recent systematic review from 2016 by Ravani et al,⁴⁶ demonstrated no difference in risk of access loss in preemptive stenosis correction in AVF or AVG without evidence of access dysfunction. However, on subgroup analysis this review did demonstrate a small benefit regarding risk of thrombosis and access loss in the AVF group.⁴⁶

The physical examination may indicate evidence of vascular access stenosis or thrombosis. Evidence of stenosis may be indicated by failure of the outflow vein to collapse on arm raise test (distal stenosis), hyperpulsatility or hypopulsatility, loss of the diastolic component of the normal continuous thrill and bruit with only systolic components appreciated, and arm edema (central vein stenosis).^43,47 Thrombosis of the vein may be evidenced by complete loss of the thrill and pulsatility on palpation. Sensitivity and specificity of the physical examination for inflow or outflow stenosis has been reported to be between 70% to 92% and 71% to 100%, respectively.^48-50

While evidence may or may not support preemptive correction of stenosis, interventions are usually required when the stenosis is more than 50% and interferes with dialysis, decreased flow, abnormal physical examination, or elevated venous pressures.⁵¹ If stenosis is associated with interference of effective dialysis or thrombosis is suspected, ultrasound imaging and consultation with a vascular surgeon or interventional radiologist are indicated. Treatment of AVF or AVG stenosis and thrombosis includes percutaneous and surgical interventions.⁵²

A systematic review by Tanner and da Silva⁵³ evaluating adjuvant medical treatments for increasing patency rates of AVF and AVG found no therapy had any improvement in patency rates at 1 month. Another review from 2015 by Palmer et al⁵⁴ suggested antiplatelet therapy may be protective for stenosis and thrombosis in AVF, but not AVG.

Infection

Infection in patients with ESRD is a major cause of morbidity and mortality, and 24% of these infections may be attributed to the vascular access itself, including central venous catheters (CVC).⁵⁵ Central venous catheters are associated with the highest rate of infection, followed by AVGs, then AVFs.^4,54 Studies have reported 9.5% vs 0.4% to 0.9% infection rates for AVG and AVF, respectively.^2,4 These infections are usually due to gram-positive organisms, with the Staphylococcus species being the most common organism involved.^55-57 However, infections caused by gram-negative organisms are possible, and broad-spectrum antibiotics should be initiated in the ED if infection is suspected. Patients may present with localized infection with increased risk of rupture of access to profound sepsis. Definitive treatment of an infected graft or fistula usually requires removal of the infected access or at least partial excision with possible interposition of additional graft material.⁵⁸

Pseudoaneurysm/Aneurysm

Pseudoaneuryms are usually caused by hematoma development after needle puncture or in juxta-anastomic segments postoperatively. Pseudoaneurysms do not have a true wall and may secondarily become infected.⁵⁹ Pseudoaneurysms occur more frequently in AVG, and are usually reported along with true aneurysms. One study by Al-Thani et al⁶⁰ detected pseudoaneurysms in 15% of clinically significant aneurysms.

Approximately 30% to 60% of patients with AVFs will develop an aneurysm.^2,5 One study by Al-Thani et al⁶⁰ reported the need for surgical intervention in 31% of patients with an AVF in whom an aneurysm was detected. The risk for developing an aneurysm is highest for those patients on high flux membrane type HD and polycystic kidney disease.⁵ As discussed earlier in this article, cannulation sites and techniques may also influence aneurysmal changes in the fistula. Aneurysm formation at the site of previous cannulation site should not be re-cannulated.¹⁸ Aneurysmal changes can contribute to other complications including high-output heart failure, thrombosis with fistula or graft failure, increased risk of bleeding, ineffective HD when associated with thrombosis or stenosis, pain and peripheral neuropathies secondary to compression of nearby nerves, and interference with functional HD.

Many asymptomatic aneurysmal changes to vascular access may not compromise access function. If a patient is identified with a vascular access pseudoaneurysm or aneurysmal changes with high-risk features, early referral to vascular surgeon for surgical interventions is imperative. High-risk features include any of the complications previously discussed—infection, threatened overlying skin, or shiny appearance. The EP should consider duplex imaging to assist with evaluation. Treatment may include ligation of the AVF, partial resection, stenting, or grafting of the aneurysm with hopes of salvaging the vascular access.^61,62

Ischemic Monomelic Neuropathy

Ischemic monomelic neuropathy may result secondary to a type of steal phenomenon, thereby inducing ischemia to supplied nerves. Ischemic monomelic neuropathy has been described in many case reports and narrative reviews.^63-67 It has been described as ischemia or infarction of the blood supply to the nerves (vasa nervosa) in the lower arm.⁶⁸ Ischemic monomelic neuropathy typically occurs immediately after the vascular access creation in the postoperative period. Therefore, it is unlikely to be seen in the ED but as patients may have sequelae of this complication, EPs should be aware of its existence. Patients with ischemic monomelic neuropathy will have severe pain, paresthesia, and weakness immediately after placement of a vascular access. Patients also typically have sensorimotor deficits in the radial, ulnar, and median nerves. Pulses should be preserved. Severe neuropathic pain will develop and may limit the examination. Clinical diagnosis may be difficult immediately after surgery because patients will often have minor deficits secondary to the surgical procedure itself or secondary to the regional block provided by anesthesia, but nerve-conduction studies usually reveal the diagnosis. The treatment is ligation of the access immediately and prognosis is variable, depending on the severity and duration of ischemia, and may result in complete loss of function of the hand.

Steal Syndrome

Dialysis access-associated steal syndrome is a type of distal ischemia secondary to the vascular access site with a reported incidence of 6.2%, and appears to occur more frequently in AVF than AVGs.^69,70 Diabetes appears to be a strong risk factor for developing DASS.⁷¹ Patients with DASS can present with classic ischemic symptoms such as pain, paresthesia, claudication, pallor, and diminished or absent arterial pulse. Pain may be present only while undergoing dialysis or exercising, or symptoms may be persistent.^68,72 There are several possible causes of DASS, including arterial occlusion or insufficiency proximal or distal to the anastomosis, increased flow through the conduit (true steal), or increased flow diverted through collateral vessels.^73,74 One clue to the diagnosis is a diminished or absent radial pulse that should improve with compression of the access site.

Once DASS is suspected, diagnosis should be confirmed using venous duplex scanning with finger pressure waveform analysis or arteriogram. Definitive management is surgical intervention with ligation of the access or banding.

High-Output Heart Failure

Changes in cardiac output (CO) are a well-documented effect of AVF placement, with one small study by Korsheed et al⁷⁵ demonstrating an average increase in CO of 17% only 2 weeks after AVF placement. The increase in CO is thought to be secondary to alterations in systemic vascular resistance and sympathetic activity. While an increase in CO can ultimately lead to high-output heart failure, this is typically only seen in patients with pre-existing cardiac dysfunction.⁷⁶ Patients are at an increased risk of high-output heart failure when flow through the AVF exceeds 2 L/min; flows below this rate are typically not associated with adverse cardiac effects.⁷⁷ Another objective measurement for identifying patients at risk of high-output heart failure is the ratio of flow in the fistula (Qa) to cardiac output ratio. Patients with a Qa:CO ratio greater than 0.3 have a significantly increased risk of high-output heart failure.⁷⁸ There is thought to be no difference in risk of heart failure between AVF and AVG.⁷⁹

Once overt heart failure has developed, it should be treated in the usual fashion, with IV fluid management and standard pharmacological therapies. If standard conservative heart failure treatment is ineffective, several surgical options are available, including banding, changing the location of the anastomosis, and ultimately closing the fistula.⁸⁰

Conclusion

While life-threatening bleeding and vascular access rupture are uncommon complications of AVFs and AVGs, it is essential for the EP to rapidly treat the potentially catastrophic hemorrhagic vascular access complications. Depending on the severity and stability of the patient, it is reasonable to begin in a stepwise fashion as presented in this article for patients with minor bleeding, while more severe or persistent bleeding may require several interventions simultaneously to gain control of the bleeding.

Patients with hemodynamic instability requiring transfusion will need a vascular surgery consult and admission. Disposition for stable patients, without evidence of impending aneurysmal related rupture and concern for overlying infection or other complication requiring immediate intervention, will depend on clinical judgment, patient-specific factors and family support, follow-up, and proximity of the patient to medical care.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, approximately 468,000 persons in the United States are on dialysis—a number that continues to grow annually.¹ The 1-year rate for hemorrhagic complications from arteriovenous fistulas (AVFs) is estimated to be 0.4%.² One study by Ellingson et al³ reported 1,654 deaths secondary to fatal vascular access hemorrhage over a 6-year period, accounting for 0.4% of all deaths of hemodialysis (HD) patients in that study.³

Nonhemorrhagic vascular access-related complications also contribute to the morbidity and mortality associated with AVFs and arteriovenous grafts (AVGs). Venous stenosis resulting in thrombosis has been estimated to occur in 24.7% of AVGs and 9.0% of AVFs, both of which are common causes of access failure.

Infection is reported to be the second leading cause of death in dialysis patients, and vascular access-related infection rates are reported to occur in 9.5% of AVGs vs 0.4% to 0.9% of AVFs.^2,4 Pseudoaneurysms and aneurysms range from 30% to 60% for AVFs,^2,5 and contribute to morbidity by limiting available areas to cannulate for dialysis, occasionally requiring surgical revision to restore access function or prevent access rupture.

Steal phenomena, including dialysis access-induced steal syndrome (DASS) and ischemic monomelic neuropathy, as well as heart failure secondary to high output are additional contributors to morbidity and mortality.

With the growing rate of end-stage renal disease (ESRD) in the United States and the contribution to morbidity and mortality by bleeding and other complications, it is essential to understand how to evaluate and treat these patients in the ED. This article reviews the evaluation and treatment of vascular access emergencies, as well as risk factors that contribute to complications in the ESRD patient population.

Hemorrhagic Complications of Vascular Access

Risk Factors

Many patients with ESRD have multiple comorbidities such as coronary artery disease and atrial fibrillation that require anticoagulation, antiplatelet medications, or both. Studies have shown that ESRD patients taking warfarin have an increase in major bleeding episodes of 3.1% per person-year and 4.4% per person-year for those taking aspirin alone, while those taking both medications have an increased bleeding risk of 6.3% per person-year.⁶ A recent systematic review by Elliott et al⁷ has suggested a 2-fold increase in bleeding rates in HD patients anticoagulated with warfarin as compared to HD patients not on warfarin.

While uremia secondary to chronic kidney disease (CKD) is a well-known facilitator of bleeding complications, the underlying pathophysiology is not yet completely delineated. However, there are some general underlying principles that may help in understanding the best treatment modalities available at this time. As the kidneys fail, uremic toxins accumulate in the bloodstream. These toxins include urea, creatinine, and phenolic acids, which are believed to interfere with primary hemostasis by effecting platelet adherence to endothelium, platelet activation, and aggregation.⁸ Functional defects are created in the interactions between the glycoprotein Ib (GPIb) receptor and von Willebrand factor (vWF), which are essential to endothelial adhesion of platelets.⁹ Additionally, these toxins impair the up regulation of the GPIIbIIIa receptor which is integral to platelet aggregation.¹⁰ Platelet activation normally leads to platelet aggregation by increasing production of thromboxane A2 (TXA2) and serotonin that are released from storage granules.¹⁰ Some toxins may increase nitric oxide (NO) synthesis, effectively reducing aggregation by decreasing TXA2 and adenosine diphosphate (ADP) levels.¹¹ In addition, elevated levels of fibrinogen fragments have also recently been shown to inhibit platelet function by competing with fibrinogen for the GPIIbIIIa receptor with decreasing levels demonstrated after HD.¹²

Finally, increased pressure in the venous outflow segment also increases persistent bleeding from puncture sites. These pressures may be exaggerated secondary to venous thrombosis, venous stenosis, pseudoaneurysm, aneurysm, or infection.¹³ The following sections further describe the evaluation and treatment of these complications.

Clinical Presentation

Patients presenting with bleeding from the vascular access site may present with slow continuous oozing from the needle puncture-site itself or with life-threatening hemorrhage secondary to AVF or AVG rupture.¹⁴ The incidence of vascular access rupture is unknown, but it appears the majority of ruptures occur in patients with AVG vs AVF.³ However, several case reports have also described hemorrhagic complications of AVF ruptures.^15-17 The risk of rupture may be associated with the development of aneurysms or pseudoaneuryms.¹⁸ Possible impending perforation may be signaled by skin thinning or a shiny appearance overlying the aneurysm, or evidence of infection overlying the access site.³ Many patients were shown to have complications such as stenosis, thrombosis, or infection within 6 months prior to rupture.³ Education of patients is also important as most hemorrhages occur prior to hospital arrival.^3,19

Evaluation in the ED

As with any patient presenting to the ED, the initial evaluation of an unstable patient experiencing bleeding from a vascular access site includes assessing the airway, breathing, and circulation as a first priority—paying special attention to the area of bleeding while simultaneously preparing for possible intervention. It is also important to determine when the patient last underwent dialysis and if he or she was able to complete HD. This information will identify patients who are candidates for reversing the heparin load likely given during dialysis.

It is also important to note that some patients undergoing HD who have already been identified as having an increased risk of bleeding may not receive heparin or may undergo local heparinization, minimal heparinization, or regional citrate anticoagulation during dialysis, in which case protamine is not indicated.¹⁴ The emergency physician (EP) must also determine if the patient is on any antiplatelet or anticoagulation agents.

The vascular access site should be inspected for evidence of aneurysmal changes, infection, and skin thinning as these factors increase the risk of bleeding and vascular rupture. Additionally auscultation and palpation of the vascular access site should be performed to evaluate for other potential complications such as stenosis and thrombosis. Lastly, the EP should anticipate the patient’s need for HD in the setting of a potentially unavailable AVG or AVF to determine whether the patient may need an alternative access.

Treatment and Management

The primary responsibility during the initial treatment of a bleeding access site is to stop further blood loss by utilizing methods that employ direct pressure or, in extreme cases, application of a tourniquet, followed by other interventions such as fluid and blood-product resuscitation; coagulopathy reversal; consideration of desmopressin, cryoprecipitate, tranexamic acid (TXA); HD; and vascular repair.

Control of a bleeding dialysis access-site is a balancing act of adequately controlling the bleeding while maintaining the integrity of the fistula. Overly aggressive management may cause thrombosis in the vascular access site, which is associated with morbidity—eg, site revisions, potential for the need to create a new access site. On the opposite end of the spectrum, failing to adequately control bleeding can lead to significant anemia ranging from minimal symptoms to hemodynamic compromise and death.

Peripheral Venous Access

While peripheral venous access is notoriously difficult in patients with ESRD, it is essential for the resuscitation of hemorrhaging patients. Ideally, two large bore peripheral intravenous (IV) lines should be placed in the proximal upper extremities. If peripheral venous access is not achieved, central venous access or interosseous access placement is indicated (Figure).

Direct Pressure

With low-volume bleeding, the first attempt to control the bleeding is simple direct pressure. Except in the instance of trauma or self-inflicted injury, bleeding usually occurs at the site of cannulation of the vascular access post-HD. Direct pressure should be light and limited to as small of an area as possible to prevent thrombosis; the force and area encompassed by direct pressure can be expanded as needed for bleeding that is more difficult to control. In cases of higher volume bleeding, pressure should be placed both proximally and distally to the shunt due to its bidirectional flow. Another possible temporizing measure is to place an upright gallipot or cup over the bleeding site on top of a folded piece of gauze and then securing it with tape.²¹

Topical Hemostatic Agents

Second simple direct pressure, topical hemostatic agents may be a good adjunct to help obtain hemostasis. There is a wide range of products available, from procoagulants (eg, Combat Gauze, topical thrombin) to factor concentrators (eg, QuikClot). These can be used directly on the bleeding site and only in conjunction with direct pressure.

In addition to topical hemostatic agents, another option is skin glue, which should be applied generously after bleeding has been temporized, with pressure both proximally and distally to the site.

Anticoagulation Reversal

As previously mentioned, it is important to determine when the patient’s last HD was. Heparin is used during dialysis to prevent clotting within the circuit, and although clotting times are monitored during dialysis to guide anticoagulation, it is possible that a patient bleeding after dialysis could still have therapeutic levels of heparin requiring reversal with protamine.

The recommended dose of protamine is 1 mg for every 100 U of heparin given during dialysis; protamine should be administered over 10 minutes. Alternatively, a 10- to 20-mg dose of protamine can be given if the amount of heparin administered during HD is unknown. Additionally, the patient’s medication list, as with any ED presentation, should be carefully reviewed as many dialysis patients have comorbidities requiring anticoagulation with potentially reversible agents.

Hemodialysis to Improve Platelet Dysfunction

It is thought that long-term exposure of platelets to the dialysis membrane can lead to chronic platelet activation leading to platelet dysfunction. There is conflicting data regarding the effects of HD on improving bleeding in renal patients.^9,22,23 Hemodialysis is thought to be beneficial, at least partially, through reversing uremia, thus improving platelet function.²⁴ Therefore, in the stable bleeding patient who missed a scheduled dialysis, initiating HD in the ED setting could be beneficial. If the vascular access site is deemed unsafe for HD, another access site must be obtained, for example, by placing a temporary central venous catheter that will allow for successful HD.

Desmopressin

Desmopressin acetate has been shown to reduce bleeding time in uremic patients by releasing vWF and factor VIII into plasma, taking effect within 1 hour and lasting 4 to 8 hours.^25-27 Desmopressin has also been shown to reduce blood loss and bleeding times in patients with platelet dysfunction undergoing cardiac surgery.²⁸ While the underlying mechanism is unclear, desmopressin acetate is thought to help with platelet adhesion to the endothelial wall.

Alternatively, one study by Soslau et al²⁹ has suggested that desmopressin may increase serotonin uptake by platelets and increase adenosine triphosphate release, thereby facilitating platelet aggregation. The dosing of desmopressin is 0.2 to 0.3 mcg/kg IV.³⁰ Adverse effects include facial flushing, mild headache, and transient small decrease in blood pressure (BP) with increase in heart rate. Historically, it was thought that desmopressin could lead to water retention, volume overload, congestive heart failure, and hyponatremia; however, these adverse effects have not been seen in uremic patients.³⁰ Tachyphylaxis may occur after just a few doses of desmopressin are given.³¹ Additionally, hyponatremia and seizures have been seen after repeated administration in children.³¹

Anemia and Low Hematocrit

As mentioned earlier, anemia and low hematocrit (HCT) may actually exacerbate bleeding tendencies by decreasing the number of platelets exposed to the vessel wall. Red blood cells (RBCs) also produce TXA2 and ADP, both of which play vital roles in normal platelet aggregation. Secondly, RBCs have been shown to increase NO uptake. Nitric oxide is a potent vasodilator and inhibitor of platelet aggregation. The degree of uptake appears to be augmented by increasing HCT levels.³² A goal HCT of greater than 30% has been suggested and demonstrated benefit.³³

Cryoprecipitate

Cryoprecipitate is rich in fibrinogen and vWF. Its mechanism is thought to be secondary to increasing functional vWF levels and possibly fibrinogen levels. While the overall effects appear to be variable, studies suggest 10 U of cryoprecipitate is adequate to reverse significant bleeding with resolution of effect at 24 hours.^34,35 Given the risks of adverse reactions, variable responses, and risks of hepatitis C and HIV transmission, this therapy must be used cautiously with risk-benefit analysis.

Tranexamic Acid

Tranexamic acid is an antifibrinolytic agent that binds to fibrinogen as a competitive inhibitor of plasmin, inhibiting plasminogen activation. The trauma literature has shown TXA to significantly reduce all-cause mortality.³⁶ It has also been shown to be beneficial in the bleeding uremic patient.^37-39

However, it is important to keep in mind that the clearance of TXA in patients with renal disease is unclear. One study by Andersson et al⁴⁰ demonstrated that TXA has increased plasma concentrations in patients with renal impairment, and a generally accepted practice is to renal-dose this medication. This study recommended a dose of 10 mg/kg IV at varying intervals, such as once daily, twice daily, or every 48 hours depending on the creatinine value, compared to patients with no renal impairment.⁴⁰ Another study by Sabovic et al³⁹ that evaluated the effects of TXA on gastrointestinal bleeding in patients with renal impairment used a 20-mg IV loading dose of TXA followed by 10 mg/kg orally every 48 hours. Though no adverse events occurred in this study, the study group was small. Other studies have not shown an increase in thromboembolic risk in patients who have no renal disease.^36,41

At this time, there is no consensus on the exact dosing of TXA in this patient population. Therefore, this therapy should only be considered if others have failed and the patient continues to have significant blood loss.

Life-threatening Hemorrhage

If a patient is experiencing life-threatening blood loss, more aggressive measures must be employed regardless of risk of damage to the access. In such cases, a consultation with vascular surgery services should be obtained as early as possible. If none of the previously discussed measures are ineffective, the EP may be required to place sutures in the vascular access itself or apply a tourniquet. Again, these interventions may cause permanent damage to the access; however, in the setting of life-threatening hemorrhage such interventions clearly outweigh the risks associated with continued blood loss.

As blood can flow bidirectionally within a fistula, a tourniquet should be placed both proximally and distally to the fistula to obtain adequate hemostasis. Once the tourniquets are in place, if there is no immediate surgical consultation available, the EP may need to temporarily repair the defect to allow minimal tourniquet time. There are a few considerations when placing sutures. Ideally, a noncutting needle should be used to minimize damage. An adequate-sized suture, such as a 3-0 nylon suture, should be used to maintain strength in the high-pressure system. A figure-8 suture or purse-string suture may be placed around the defect. Adequate repair should allow for tourniquet removal.

Hemodynamic Status

The EP must remain aware of the patient’s hemodynamic status. Massive transfusion protocols may need to be initiated. Best current evidence dictates that this should be done in a 1:1:1 ratio of packed red blood cells, platelets, and fresh frozen plasma respectively.⁴² In our experience, the EP should consider permissive hypotension as aggressive resuscitation and increasing BP can compromise the vascular repair.

Lastly, transfer for definitive management should be arranged if not available at the EP’s institution. The patient should travel with tourniquets in place (although not tightened) in the event of further bleeding.

Nonhemorrhagic Complications of AVF or AVG

Stenosis/Thrombosis

Prolonged bleeding from the cannulation site may suggest outflow stenosis.⁴³ Stenosis with or without subsequent thrombosis is a common cause of vascular access failure. Access failure has also been implicated secondary to poor vascular mapping, resulting in undetected pre-existing stenosis of the inflow artery, outflow vein, or juxta-anastomosis. However, development of stenosis may occur at any time throughout the life of the vascular access. One study by Schild et al⁴ reported thrombosis rates of 24.7% for grafts and 9.0% for fistula. Additionally, AVGs have a higher reported stenosis rate than AVFs, which is a risk factor for thrombosis.^44,45

There has been much debate regarding routine surveillance to prevent clinically significant stenosis with subsequent thrombosis. Surveillance includes a clinical examination, Doppler imaging studies, and flow measurements during dialysis. A recent systematic review from 2016 by Ravani et al,⁴⁶ demonstrated no difference in risk of access loss in preemptive stenosis correction in AVF or AVG without evidence of access dysfunction. However, on subgroup analysis this review did demonstrate a small benefit regarding risk of thrombosis and access loss in the AVF group.⁴⁶

The physical examination may indicate evidence of vascular access stenosis or thrombosis. Evidence of stenosis may be indicated by failure of the outflow vein to collapse on arm raise test (distal stenosis), hyperpulsatility or hypopulsatility, loss of the diastolic component of the normal continuous thrill and bruit with only systolic components appreciated, and arm edema (central vein stenosis).^43,47 Thrombosis of the vein may be evidenced by complete loss of the thrill and pulsatility on palpation. Sensitivity and specificity of the physical examination for inflow or outflow stenosis has been reported to be between 70% to 92% and 71% to 100%, respectively.^48-50

While evidence may or may not support preemptive correction of stenosis, interventions are usually required when the stenosis is more than 50% and interferes with dialysis, decreased flow, abnormal physical examination, or elevated venous pressures.⁵¹ If stenosis is associated with interference of effective dialysis or thrombosis is suspected, ultrasound imaging and consultation with a vascular surgeon or interventional radiologist are indicated. Treatment of AVF or AVG stenosis and thrombosis includes percutaneous and surgical interventions.⁵²

A systematic review by Tanner and da Silva⁵³ evaluating adjuvant medical treatments for increasing patency rates of AVF and AVG found no therapy had any improvement in patency rates at 1 month. Another review from 2015 by Palmer et al⁵⁴ suggested antiplatelet therapy may be protective for stenosis and thrombosis in AVF, but not AVG.

Infection

Infection in patients with ESRD is a major cause of morbidity and mortality, and 24% of these infections may be attributed to the vascular access itself, including central venous catheters (CVC).⁵⁵ Central venous catheters are associated with the highest rate of infection, followed by AVGs, then AVFs.^4,54 Studies have reported 9.5% vs 0.4% to 0.9% infection rates for AVG and AVF, respectively.^2,4 These infections are usually due to gram-positive organisms, with the Staphylococcus species being the most common organism involved.^55-57 However, infections caused by gram-negative organisms are possible, and broad-spectrum antibiotics should be initiated in the ED if infection is suspected. Patients may present with localized infection with increased risk of rupture of access to profound sepsis. Definitive treatment of an infected graft or fistula usually requires removal of the infected access or at least partial excision with possible interposition of additional graft material.⁵⁸

Pseudoaneurysm/Aneurysm

Pseudoaneuryms are usually caused by hematoma development after needle puncture or in juxta-anastomic segments postoperatively. Pseudoaneurysms do not have a true wall and may secondarily become infected.⁵⁹ Pseudoaneurysms occur more frequently in AVG, and are usually reported along with true aneurysms. One study by Al-Thani et al⁶⁰ detected pseudoaneurysms in 15% of clinically significant aneurysms.

Approximately 30% to 60% of patients with AVFs will develop an aneurysm.^2,5 One study by Al-Thani et al⁶⁰ reported the need for surgical intervention in 31% of patients with an AVF in whom an aneurysm was detected. The risk for developing an aneurysm is highest for those patients on high flux membrane type HD and polycystic kidney disease.⁵ As discussed earlier in this article, cannulation sites and techniques may also influence aneurysmal changes in the fistula. Aneurysm formation at the site of previous cannulation site should not be re-cannulated.¹⁸ Aneurysmal changes can contribute to other complications including high-output heart failure, thrombosis with fistula or graft failure, increased risk of bleeding, ineffective HD when associated with thrombosis or stenosis, pain and peripheral neuropathies secondary to compression of nearby nerves, and interference with functional HD.

Many asymptomatic aneurysmal changes to vascular access may not compromise access function. If a patient is identified with a vascular access pseudoaneurysm or aneurysmal changes with high-risk features, early referral to vascular surgeon for surgical interventions is imperative. High-risk features include any of the complications previously discussed—infection, threatened overlying skin, or shiny appearance. The EP should consider duplex imaging to assist with evaluation. Treatment may include ligation of the AVF, partial resection, stenting, or grafting of the aneurysm with hopes of salvaging the vascular access.^61,62

Ischemic Monomelic Neuropathy

Ischemic monomelic neuropathy may result secondary to a type of steal phenomenon, thereby inducing ischemia to supplied nerves. Ischemic monomelic neuropathy has been described in many case reports and narrative reviews.^63-67 It has been described as ischemia or infarction of the blood supply to the nerves (vasa nervosa) in the lower arm.⁶⁸ Ischemic monomelic neuropathy typically occurs immediately after the vascular access creation in the postoperative period. Therefore, it is unlikely to be seen in the ED but as patients may have sequelae of this complication, EPs should be aware of its existence. Patients with ischemic monomelic neuropathy will have severe pain, paresthesia, and weakness immediately after placement of a vascular access. Patients also typically have sensorimotor deficits in the radial, ulnar, and median nerves. Pulses should be preserved. Severe neuropathic pain will develop and may limit the examination. Clinical diagnosis may be difficult immediately after surgery because patients will often have minor deficits secondary to the surgical procedure itself or secondary to the regional block provided by anesthesia, but nerve-conduction studies usually reveal the diagnosis. The treatment is ligation of the access immediately and prognosis is variable, depending on the severity and duration of ischemia, and may result in complete loss of function of the hand.

Steal Syndrome

Dialysis access-associated steal syndrome is a type of distal ischemia secondary to the vascular access site with a reported incidence of 6.2%, and appears to occur more frequently in AVF than AVGs.^69,70 Diabetes appears to be a strong risk factor for developing DASS.⁷¹ Patients with DASS can present with classic ischemic symptoms such as pain, paresthesia, claudication, pallor, and diminished or absent arterial pulse. Pain may be present only while undergoing dialysis or exercising, or symptoms may be persistent.^68,72 There are several possible causes of DASS, including arterial occlusion or insufficiency proximal or distal to the anastomosis, increased flow through the conduit (true steal), or increased flow diverted through collateral vessels.^73,74 One clue to the diagnosis is a diminished or absent radial pulse that should improve with compression of the access site.

Once DASS is suspected, diagnosis should be confirmed using venous duplex scanning with finger pressure waveform analysis or arteriogram. Definitive management is surgical intervention with ligation of the access or banding.

High-Output Heart Failure

Changes in cardiac output (CO) are a well-documented effect of AVF placement, with one small study by Korsheed et al⁷⁵ demonstrating an average increase in CO of 17% only 2 weeks after AVF placement. The increase in CO is thought to be secondary to alterations in systemic vascular resistance and sympathetic activity. While an increase in CO can ultimately lead to high-output heart failure, this is typically only seen in patients with pre-existing cardiac dysfunction.⁷⁶ Patients are at an increased risk of high-output heart failure when flow through the AVF exceeds 2 L/min; flows below this rate are typically not associated with adverse cardiac effects.⁷⁷ Another objective measurement for identifying patients at risk of high-output heart failure is the ratio of flow in the fistula (Qa) to cardiac output ratio. Patients with a Qa:CO ratio greater than 0.3 have a significantly increased risk of high-output heart failure.⁷⁸ There is thought to be no difference in risk of heart failure between AVF and AVG.⁷⁹

Once overt heart failure has developed, it should be treated in the usual fashion, with IV fluid management and standard pharmacological therapies. If standard conservative heart failure treatment is ineffective, several surgical options are available, including banding, changing the location of the anastomosis, and ultimately closing the fistula.⁸⁰

Conclusion

While life-threatening bleeding and vascular access rupture are uncommon complications of AVFs and AVGs, it is essential for the EP to rapidly treat the potentially catastrophic hemorrhagic vascular access complications. Depending on the severity and stability of the patient, it is reasonable to begin in a stepwise fashion as presented in this article for patients with minor bleeding, while more severe or persistent bleeding may require several interventions simultaneously to gain control of the bleeding.

Patients with hemodynamic instability requiring transfusion will need a vascular surgery consult and admission. Disposition for stable patients, without evidence of impending aneurysmal related rupture and concern for overlying infection or other complication requiring immediate intervention, will depend on clinical judgment, patient-specific factors and family support, follow-up, and proximity of the patient to medical care.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

Following the successful use of ambulances during the Civil War to transport wounded soldiers from the battlefield to safer and better equipped field hospital facilities, many communities adopted the practice for their civilian populations. Between the Civil War and World War II (WWII) "teaching hospitals" sent interns on their ambulances both to improve patient care at the scene, and to further their interns’ postgraduate education. However, as described by Ryan Corbett Bell in his book The Ambulance (Jefferson, NC: McFarland; 2009), by the 1930s, relatively poor reimbursement for ambulance calls followed by the severe doctor shortage due to WWII, effectively ended this practice. Though the interns were initially replaced by "ambulance attendants" or "orderlies," since the 1960s, ambulances have been staffed by trained EMTs and (later) paramedics to provide basic and advanced prehospital care both at the scene and during transport. For almost half a century, paramedics operating with standing protocols and physician medical control have conclusively demonstrated their ability to improve care and save lives.

At present, the increased demand for access to medical care brought about by the Affordable Care Act, an aging homebound population, overcrowded EDs, and inpatient services filled to capacity, along with, in some areas, insufficient numbers of visiting nurses, NPs, and PAs to provide needed home care services, prompted many to consider expanding the role of paramedics and EMTs to provide "community paramedicine," without afterward requiring them to transport patients to hospitals.

Community paramedicine was defined in 2012 by the US Department of Health and Human Services Administration as "an emerging field in health care where EMTs and Paramedics operate in expanded roles in an effort to connect underutilized resources to underserved populations" (https://www.hrsa.gov). A standard curriculum consisting of 114 hours of education in social determinants of health, public health, and tailored learning about chronic diseases, together with 200 hours of laboratory and clinical experiences has been developed and made available free of charge to colleges and universities (https://www.ruralhealthinfo.org).

Among the many individuals and organizations weighing in on the subject of community paramedicine, the American College of Emergency Physicians 2015 policy statement supports the development of properly designed expanded scope of practice programs for EMS personnel with medical oversight, that do not compromise existing emergency response systems (https://www.acep.org/). Dr Bryan Bledsoe, an editorial board member of JEMS (Journal of Emergency Medical Services), provides a thoughtful analysis of the pros and cons of community paramedicine (http://www.jems.com), hile Iyah K. Romm and colleagues, writing in the NEJM Catalyst, offer concrete evidence of the effectiveness of one such mobile integrated healthcare and community paramedicine program (http://catalyst.nejm.org).

Properly trained, experienced paramedics with careful supervision by emergency medical control physicians and consultation with the patients’ primary care physicians, supported by telemedicine and bedside diagnostic tests, can provide essential care in a patient’s home environment. Depending on local circumstances, EMTs and paramedics can provide that care 24/7, supplementing other available home health care to support posthospital-discharge care for congestive heart failure, wound healing, etc, obviating the need for repeated ED and clinic visits or hospitalizations.

In addition to patient benefits, community paramedicine offers an opportunity for experienced paramedics to extend their years of practice similar to the way urgent care clinics have enabled experienced EPs to extend theirs. For all of these reasons, we support an expanded role for EMTs and paramedics in safe, carefully planned community paramedicine programs.

Following the successful use of ambulances during the Civil War to transport wounded soldiers from the battlefield to safer and better equipped field hospital facilities, many communities adopted the practice for their civilian populations. Between the Civil War and World War II (WWII) "teaching hospitals" sent interns on their ambulances both to improve patient care at the scene, and to further their interns’ postgraduate education. However, as described by Ryan Corbett Bell in his book The Ambulance (Jefferson, NC: McFarland; 2009), by the 1930s, relatively poor reimbursement for ambulance calls followed by the severe doctor shortage due to WWII, effectively ended this practice. Though the interns were initially replaced by "ambulance attendants" or "orderlies," since the 1960s, ambulances have been staffed by trained EMTs and (later) paramedics to provide basic and advanced prehospital care both at the scene and during transport. For almost half a century, paramedics operating with standing protocols and physician medical control have conclusively demonstrated their ability to improve care and save lives.

At present, the increased demand for access to medical care brought about by the Affordable Care Act, an aging homebound population, overcrowded EDs, and inpatient services filled to capacity, along with, in some areas, insufficient numbers of visiting nurses, NPs, and PAs to provide needed home care services, prompted many to consider expanding the role of paramedics and EMTs to provide "community paramedicine," without afterward requiring them to transport patients to hospitals.

Community paramedicine was defined in 2012 by the US Department of Health and Human Services Administration as "an emerging field in health care where EMTs and Paramedics operate in expanded roles in an effort to connect underutilized resources to underserved populations" (https://www.hrsa.gov). A standard curriculum consisting of 114 hours of education in social determinants of health, public health, and tailored learning about chronic diseases, together with 200 hours of laboratory and clinical experiences has been developed and made available free of charge to colleges and universities (https://www.ruralhealthinfo.org).

Among the many individuals and organizations weighing in on the subject of community paramedicine, the American College of Emergency Physicians 2015 policy statement supports the development of properly designed expanded scope of practice programs for EMS personnel with medical oversight, that do not compromise existing emergency response systems (https://www.acep.org/). Dr Bryan Bledsoe, an editorial board member of JEMS (Journal of Emergency Medical Services), provides a thoughtful analysis of the pros and cons of community paramedicine (http://www.jems.com), hile Iyah K. Romm and colleagues, writing in the NEJM Catalyst, offer concrete evidence of the effectiveness of one such mobile integrated healthcare and community paramedicine program (http://catalyst.nejm.org).

Properly trained, experienced paramedics with careful supervision by emergency medical control physicians and consultation with the patients’ primary care physicians, supported by telemedicine and bedside diagnostic tests, can provide essential care in a patient’s home environment. Depending on local circumstances, EMTs and paramedics can provide that care 24/7, supplementing other available home health care to support posthospital-discharge care for congestive heart failure, wound healing, etc, obviating the need for repeated ED and clinic visits or hospitalizations.

In addition to patient benefits, community paramedicine offers an opportunity for experienced paramedics to extend their years of practice similar to the way urgent care clinics have enabled experienced EPs to extend theirs. For all of these reasons, we support an expanded role for EMTs and paramedics in safe, carefully planned community paramedicine programs.

Following the successful use of ambulances during the Civil War to transport wounded soldiers from the battlefield to safer and better equipped field hospital facilities, many communities adopted the practice for their civilian populations. Between the Civil War and World War II (WWII) "teaching hospitals" sent interns on their ambulances both to improve patient care at the scene, and to further their interns’ postgraduate education. However, as described by Ryan Corbett Bell in his book The Ambulance (Jefferson, NC: McFarland; 2009), by the 1930s, relatively poor reimbursement for ambulance calls followed by the severe doctor shortage due to WWII, effectively ended this practice. Though the interns were initially replaced by "ambulance attendants" or "orderlies," since the 1960s, ambulances have been staffed by trained EMTs and (later) paramedics to provide basic and advanced prehospital care both at the scene and during transport. For almost half a century, paramedics operating with standing protocols and physician medical control have conclusively demonstrated their ability to improve care and save lives.

At present, the increased demand for access to medical care brought about by the Affordable Care Act, an aging homebound population, overcrowded EDs, and inpatient services filled to capacity, along with, in some areas, insufficient numbers of visiting nurses, NPs, and PAs to provide needed home care services, prompted many to consider expanding the role of paramedics and EMTs to provide "community paramedicine," without afterward requiring them to transport patients to hospitals.

Community paramedicine was defined in 2012 by the US Department of Health and Human Services Administration as "an emerging field in health care where EMTs and Paramedics operate in expanded roles in an effort to connect underutilized resources to underserved populations" (https://www.hrsa.gov). A standard curriculum consisting of 114 hours of education in social determinants of health, public health, and tailored learning about chronic diseases, together with 200 hours of laboratory and clinical experiences has been developed and made available free of charge to colleges and universities (https://www.ruralhealthinfo.org).

Among the many individuals and organizations weighing in on the subject of community paramedicine, the American College of Emergency Physicians 2015 policy statement supports the development of properly designed expanded scope of practice programs for EMS personnel with medical oversight, that do not compromise existing emergency response systems (https://www.acep.org/). Dr Bryan Bledsoe, an editorial board member of JEMS (Journal of Emergency Medical Services), provides a thoughtful analysis of the pros and cons of community paramedicine (http://www.jems.com), hile Iyah K. Romm and colleagues, writing in the NEJM Catalyst, offer concrete evidence of the effectiveness of one such mobile integrated healthcare and community paramedicine program (http://catalyst.nejm.org).

Properly trained, experienced paramedics with careful supervision by emergency medical control physicians and consultation with the patients’ primary care physicians, supported by telemedicine and bedside diagnostic tests, can provide essential care in a patient’s home environment. Depending on local circumstances, EMTs and paramedics can provide that care 24/7, supplementing other available home health care to support posthospital-discharge care for congestive heart failure, wound healing, etc, obviating the need for repeated ED and clinic visits or hospitalizations.

In addition to patient benefits, community paramedicine offers an opportunity for experienced paramedics to extend their years of practice similar to the way urgent care clinics have enabled experienced EPs to extend theirs. For all of these reasons, we support an expanded role for EMTs and paramedics in safe, carefully planned community paramedicine programs.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.