Toxicology

Case

A 16-year-old girl, who recently emigrated from Haiti, was brought to the pediatric ED by her mother for evaluation of a 2-hour history of gastric discomfort. Upon arrival at the ED waiting area, the patient experienced a sudden onset of generalized tonic-clonic movement with altered sensorium, though she did not fall to the ground and was not injured. Vital signs from triage were: blood pressure, 110/76 mm Hg; heart rate, 112 beats/min; respiratory rate, 22 breaths/min; and temperature, 97°F. Oxygen saturation was 98% on room air.

The patient was immediately attached to a cardiac monitor, given oxygen via a face mask, and received airway suctioning. Despite receiving a total of 4 mg of lorazepam, the seizure continued. Physical examination revealed no signs of external injury, but the ongoing generalized status epilepticus made the examination difficult.

What are the causes of refractory seizures in an adolescent patient?

The differential diagnosis for pediatric patients presenting with refractory seizure is the same as that for adult patients and should include treatment noncompliance, infection, vascular event (eg, stroke, hemorrhage), trauma (eg, cerebral contusions), metabolic and electrolyte disturbances, anticonvulsant toxicity, and exposure to a convulsant toxin.

While certain drugs (eg, cocaine) may cause status epilepticus through a secondary effect such as ischemia or a bleed, some drugs can directly cause refractory seizures. A few drugs and toxins are responsible for the majority of such seizures: bupropion; carbon monoxide; diphenhydramine; ethanol (withdrawal); hypoglycemics; lead; theophylline; tramadol; and certain antibiotics, including cephalosporins, penicillins, quinolones, and, in particular, isoniazid (INH).¹

Case Continuation

Upon further history-taking, the patient’s mother informed the ED staff that during a recent visit to a local clinic, her daughter tested positive on routine screening for tuberculosis and was given “some medications.” The patient’s mother further noted that her daughter was scheduled for a follow-up appointment at the same clinic later this morning. She believed the patient had taken “a few” of the prescribed pills at once to “catch-up” on missed doses prior to that appointment, and provided the ED staff with an empty bottle of INH that she had found in her daughter’s purse.

What are the signs and symptoms of acute isoniazid toxicity?

Isoniazid toxicity should be suspected in any patient who has access to INH—even if the drug was prescribed for someone other than the patient. Acute toxicity develops rapidly after the ingestion of supratherapeutic doses of INH and includes nausea, abdominal discomfort, vomiting, dizziness, and excessive fatigue or lethargy. Patients can present with tachycardia, stupor, agitation, mydriasis, increased anion gap metabolic acidosis, and encephalopathy.

Seizures occur due to an INH-induced functional pyridoxine deficiency. Isoniazid inhibits pyridoxine phosphokinase, the enzyme that converts pyridoxine (vitamin B₆) to its physiologically active form, pyridoxal 5’-phosphate (PLP). Because the conversion of glutamate (an excitatory neurotransmitter) to gamma-aminobutyric acid (GABA; the body’s main inhibitory neurotransmitter) is dependent on PLP, an excess of glutamate and a deficiency of GABA occurs following INH overdose. The result is neuroexcitation, which manifests as generalized seizures in affected patients.

The most consequential effect of INH overdose, however, is the development of seizure refractory to conventional therapy, such as benzodiazepines. This occurs because benzodiazepines are indirect-acting GABA agonists, and require the presence of GABA to elicit their effect. Therefore, due to the impairment of GABA synthesis, benzodiazepines are limited or ineffective as anticonvulsants. Although INH doses in excess of 20 mg/kg may result in neuroexcitation, refractory seizures are uncommon with doses <70 mg/kg.

Complications of chronic INH use include hepatotoxicity, and patients will present with jaundice, hepatomegaly, and right upper quadrant pain and tenderness. Isoniazid must be discontinued rapidly in patients demonstrating hepatotoxicity, and the risk/benefit of treatment reconsidered. Patients can also develop peripheral neuropathy while using INH therapeutically, and prophylactic vitamin B₆ supplementation is recommended for certain at-risk patients, such as those who are pregnant or breastfeeding.² Supplementation, however, neither reduces the risk of hepatotoxicity nor prevents onset of seizure following an INH overdose (the B₆ dose is not sufficient enough to exert this effect).

How is acute isoniazid-induced seizure managed?

Management of patients with refractory seizure should initially include an assessment and management of the patient’s airway, breathing, and circulation. Although seizures induced by INH toxicity are often resistant to benzodiazepines, these agents remain the first-line therapy. For patients who fail to respond to a reasonable trial of benzodiazepines (eg, lorazepam 6 mg intravenously [IV]), pyridoxine should be administered.³ The recommended dose is 1 g pyridoxine per every 1 g of INH ingested—if the initial dose ingested is known—with a maximum dose of 5 g pyridoxine. If the initial dose of INH is not known, 70 mg/kg of pyridoxine, up to 5 g, is recommended. Repeated doses of pyridoxine can be administered if the seizure continues, up to a total dose of 10 g in an adult. At extremely high doses, pyridoxine itself can be neurotoxic, limiting the maximal antidotal dose.

Rapid initiation of pyridoxine is a challenge since typical stocks in most EDs are not in an adequate supply required for treatment. Additionally, a typical vial of pyridoxine contains 100 mg, highlighting the rare need to open dozens of vials for a single patient. Drawing up adequate doses of the IV formulation can be a challenge and time-consuming.

Regardless, the most reliable and rapid route of administration for pyridoxine is IV, at a rate of 0.5 to 1 g/min. Even if the seizure resolves prior to completion of the initial dose, the remaining doses should still be administered over a 4- to 6-hour period. Oral or (more likely) nasogastric administration of pyridoxine can be administered if the IV formulation is not available, but neither are optimal routes of delivery. Every effort should be made to stock pyridoxine in the antidote supply in the ED to avoid time delays involving finding, preparing, and administering the drug in these scenarios. Previous studies have found that most EDs are not prepared to handle pyridoxine replacement.^4,5

Since benzodiazepines and barbiturates are GABA agonists with complementary mechanisms of actions to pyridoxine, they should be administered to potentiate the antiseizure effect of pyridoxine. If the seizure does not terminate, the use of propofol or general anesthesia may be required. Once the seizure is terminated, oral activated charcoal can be administered if the ingestion occurred within several hours of presentation. Given the rapid onset of effect of a large dose of INH, most patients will develop seizure shortly after exposure, limiting the benefits of both aggressive gastrointestinal decontamination and delayed activated charcoal. Charcoal also can be used for patients who overdose on INH but do not develop seizures.

Although the utility of a head computed tomography (CT) scan or laboratory studies is limited given the context of the exposure, these are generally obtained for patients with new-onset seizure. Since many patients with INH toxicity do not seize, such a patient may have a lower seizure threshold due to the existence of a subclinical cerebral lesion or metabolic abnormality.

Case Conclusion

The patient’s INH-induced refractory seizure was treated with pyridoxine. Her history suggested that she had ingested an unknown number of INH tablets within an hour. On this initial basis, an IV dose of 5,000 mg of pyridoxine was administered. The patient’s seizures terminated within 2 minutes of the infusion, and no additional doses of pyridoxine were required. Given the lack of concern for self-harm, an acetaminophen concentration was not obtained. A urine toxicology screen was negative for cocaine and amphetamines, and a CT scan of the head was negative for any abnormality. The patient was admitted to the pediatric intensive care unit for status epileptics and was discharged home on hospital day 2 after an uneventful stay.

Case

A 16-year-old girl, who recently emigrated from Haiti, was brought to the pediatric ED by her mother for evaluation of a 2-hour history of gastric discomfort. Upon arrival at the ED waiting area, the patient experienced a sudden onset of generalized tonic-clonic movement with altered sensorium, though she did not fall to the ground and was not injured. Vital signs from triage were: blood pressure, 110/76 mm Hg; heart rate, 112 beats/min; respiratory rate, 22 breaths/min; and temperature, 97°F. Oxygen saturation was 98% on room air.

The patient was immediately attached to a cardiac monitor, given oxygen via a face mask, and received airway suctioning. Despite receiving a total of 4 mg of lorazepam, the seizure continued. Physical examination revealed no signs of external injury, but the ongoing generalized status epilepticus made the examination difficult.

What are the causes of refractory seizures in an adolescent patient?

The differential diagnosis for pediatric patients presenting with refractory seizure is the same as that for adult patients and should include treatment noncompliance, infection, vascular event (eg, stroke, hemorrhage), trauma (eg, cerebral contusions), metabolic and electrolyte disturbances, anticonvulsant toxicity, and exposure to a convulsant toxin.

While certain drugs (eg, cocaine) may cause status epilepticus through a secondary effect such as ischemia or a bleed, some drugs can directly cause refractory seizures. A few drugs and toxins are responsible for the majority of such seizures: bupropion; carbon monoxide; diphenhydramine; ethanol (withdrawal); hypoglycemics; lead; theophylline; tramadol; and certain antibiotics, including cephalosporins, penicillins, quinolones, and, in particular, isoniazid (INH).¹

Case Continuation

Upon further history-taking, the patient’s mother informed the ED staff that during a recent visit to a local clinic, her daughter tested positive on routine screening for tuberculosis and was given “some medications.” The patient’s mother further noted that her daughter was scheduled for a follow-up appointment at the same clinic later this morning. She believed the patient had taken “a few” of the prescribed pills at once to “catch-up” on missed doses prior to that appointment, and provided the ED staff with an empty bottle of INH that she had found in her daughter’s purse.

What are the signs and symptoms of acute isoniazid toxicity?

Isoniazid toxicity should be suspected in any patient who has access to INH—even if the drug was prescribed for someone other than the patient. Acute toxicity develops rapidly after the ingestion of supratherapeutic doses of INH and includes nausea, abdominal discomfort, vomiting, dizziness, and excessive fatigue or lethargy. Patients can present with tachycardia, stupor, agitation, mydriasis, increased anion gap metabolic acidosis, and encephalopathy.

Seizures occur due to an INH-induced functional pyridoxine deficiency. Isoniazid inhibits pyridoxine phosphokinase, the enzyme that converts pyridoxine (vitamin B₆) to its physiologically active form, pyridoxal 5’-phosphate (PLP). Because the conversion of glutamate (an excitatory neurotransmitter) to gamma-aminobutyric acid (GABA; the body’s main inhibitory neurotransmitter) is dependent on PLP, an excess of glutamate and a deficiency of GABA occurs following INH overdose. The result is neuroexcitation, which manifests as generalized seizures in affected patients.

The most consequential effect of INH overdose, however, is the development of seizure refractory to conventional therapy, such as benzodiazepines. This occurs because benzodiazepines are indirect-acting GABA agonists, and require the presence of GABA to elicit their effect. Therefore, due to the impairment of GABA synthesis, benzodiazepines are limited or ineffective as anticonvulsants. Although INH doses in excess of 20 mg/kg may result in neuroexcitation, refractory seizures are uncommon with doses <70 mg/kg.

Complications of chronic INH use include hepatotoxicity, and patients will present with jaundice, hepatomegaly, and right upper quadrant pain and tenderness. Isoniazid must be discontinued rapidly in patients demonstrating hepatotoxicity, and the risk/benefit of treatment reconsidered. Patients can also develop peripheral neuropathy while using INH therapeutically, and prophylactic vitamin B₆ supplementation is recommended for certain at-risk patients, such as those who are pregnant or breastfeeding.² Supplementation, however, neither reduces the risk of hepatotoxicity nor prevents onset of seizure following an INH overdose (the B₆ dose is not sufficient enough to exert this effect).

How is acute isoniazid-induced seizure managed?

Management of patients with refractory seizure should initially include an assessment and management of the patient’s airway, breathing, and circulation. Although seizures induced by INH toxicity are often resistant to benzodiazepines, these agents remain the first-line therapy. For patients who fail to respond to a reasonable trial of benzodiazepines (eg, lorazepam 6 mg intravenously [IV]), pyridoxine should be administered.³ The recommended dose is 1 g pyridoxine per every 1 g of INH ingested—if the initial dose ingested is known—with a maximum dose of 5 g pyridoxine. If the initial dose of INH is not known, 70 mg/kg of pyridoxine, up to 5 g, is recommended. Repeated doses of pyridoxine can be administered if the seizure continues, up to a total dose of 10 g in an adult. At extremely high doses, pyridoxine itself can be neurotoxic, limiting the maximal antidotal dose.

Rapid initiation of pyridoxine is a challenge since typical stocks in most EDs are not in an adequate supply required for treatment. Additionally, a typical vial of pyridoxine contains 100 mg, highlighting the rare need to open dozens of vials for a single patient. Drawing up adequate doses of the IV formulation can be a challenge and time-consuming.

Regardless, the most reliable and rapid route of administration for pyridoxine is IV, at a rate of 0.5 to 1 g/min. Even if the seizure resolves prior to completion of the initial dose, the remaining doses should still be administered over a 4- to 6-hour period. Oral or (more likely) nasogastric administration of pyridoxine can be administered if the IV formulation is not available, but neither are optimal routes of delivery. Every effort should be made to stock pyridoxine in the antidote supply in the ED to avoid time delays involving finding, preparing, and administering the drug in these scenarios. Previous studies have found that most EDs are not prepared to handle pyridoxine replacement.^4,5

Since benzodiazepines and barbiturates are GABA agonists with complementary mechanisms of actions to pyridoxine, they should be administered to potentiate the antiseizure effect of pyridoxine. If the seizure does not terminate, the use of propofol or general anesthesia may be required. Once the seizure is terminated, oral activated charcoal can be administered if the ingestion occurred within several hours of presentation. Given the rapid onset of effect of a large dose of INH, most patients will develop seizure shortly after exposure, limiting the benefits of both aggressive gastrointestinal decontamination and delayed activated charcoal. Charcoal also can be used for patients who overdose on INH but do not develop seizures.

Although the utility of a head computed tomography (CT) scan or laboratory studies is limited given the context of the exposure, these are generally obtained for patients with new-onset seizure. Since many patients with INH toxicity do not seize, such a patient may have a lower seizure threshold due to the existence of a subclinical cerebral lesion or metabolic abnormality.

Case Conclusion

The patient’s INH-induced refractory seizure was treated with pyridoxine. Her history suggested that she had ingested an unknown number of INH tablets within an hour. On this initial basis, an IV dose of 5,000 mg of pyridoxine was administered. The patient’s seizures terminated within 2 minutes of the infusion, and no additional doses of pyridoxine were required. Given the lack of concern for self-harm, an acetaminophen concentration was not obtained. A urine toxicology screen was negative for cocaine and amphetamines, and a CT scan of the head was negative for any abnormality. The patient was admitted to the pediatric intensive care unit for status epileptics and was discharged home on hospital day 2 after an uneventful stay.

Case

A 16-year-old girl, who recently emigrated from Haiti, was brought to the pediatric ED by her mother for evaluation of a 2-hour history of gastric discomfort. Upon arrival at the ED waiting area, the patient experienced a sudden onset of generalized tonic-clonic movement with altered sensorium, though she did not fall to the ground and was not injured. Vital signs from triage were: blood pressure, 110/76 mm Hg; heart rate, 112 beats/min; respiratory rate, 22 breaths/min; and temperature, 97°F. Oxygen saturation was 98% on room air.

The patient was immediately attached to a cardiac monitor, given oxygen via a face mask, and received airway suctioning. Despite receiving a total of 4 mg of lorazepam, the seizure continued. Physical examination revealed no signs of external injury, but the ongoing generalized status epilepticus made the examination difficult.

What are the causes of refractory seizures in an adolescent patient?

The differential diagnosis for pediatric patients presenting with refractory seizure is the same as that for adult patients and should include treatment noncompliance, infection, vascular event (eg, stroke, hemorrhage), trauma (eg, cerebral contusions), metabolic and electrolyte disturbances, anticonvulsant toxicity, and exposure to a convulsant toxin.

While certain drugs (eg, cocaine) may cause status epilepticus through a secondary effect such as ischemia or a bleed, some drugs can directly cause refractory seizures. A few drugs and toxins are responsible for the majority of such seizures: bupropion; carbon monoxide; diphenhydramine; ethanol (withdrawal); hypoglycemics; lead; theophylline; tramadol; and certain antibiotics, including cephalosporins, penicillins, quinolones, and, in particular, isoniazid (INH).¹

Case Continuation

Upon further history-taking, the patient’s mother informed the ED staff that during a recent visit to a local clinic, her daughter tested positive on routine screening for tuberculosis and was given “some medications.” The patient’s mother further noted that her daughter was scheduled for a follow-up appointment at the same clinic later this morning. She believed the patient had taken “a few” of the prescribed pills at once to “catch-up” on missed doses prior to that appointment, and provided the ED staff with an empty bottle of INH that she had found in her daughter’s purse.

What are the signs and symptoms of acute isoniazid toxicity?

Isoniazid toxicity should be suspected in any patient who has access to INH—even if the drug was prescribed for someone other than the patient. Acute toxicity develops rapidly after the ingestion of supratherapeutic doses of INH and includes nausea, abdominal discomfort, vomiting, dizziness, and excessive fatigue or lethargy. Patients can present with tachycardia, stupor, agitation, mydriasis, increased anion gap metabolic acidosis, and encephalopathy.

Seizures occur due to an INH-induced functional pyridoxine deficiency. Isoniazid inhibits pyridoxine phosphokinase, the enzyme that converts pyridoxine (vitamin B₆) to its physiologically active form, pyridoxal 5’-phosphate (PLP). Because the conversion of glutamate (an excitatory neurotransmitter) to gamma-aminobutyric acid (GABA; the body’s main inhibitory neurotransmitter) is dependent on PLP, an excess of glutamate and a deficiency of GABA occurs following INH overdose. The result is neuroexcitation, which manifests as generalized seizures in affected patients.

The most consequential effect of INH overdose, however, is the development of seizure refractory to conventional therapy, such as benzodiazepines. This occurs because benzodiazepines are indirect-acting GABA agonists, and require the presence of GABA to elicit their effect. Therefore, due to the impairment of GABA synthesis, benzodiazepines are limited or ineffective as anticonvulsants. Although INH doses in excess of 20 mg/kg may result in neuroexcitation, refractory seizures are uncommon with doses <70 mg/kg.

Complications of chronic INH use include hepatotoxicity, and patients will present with jaundice, hepatomegaly, and right upper quadrant pain and tenderness. Isoniazid must be discontinued rapidly in patients demonstrating hepatotoxicity, and the risk/benefit of treatment reconsidered. Patients can also develop peripheral neuropathy while using INH therapeutically, and prophylactic vitamin B₆ supplementation is recommended for certain at-risk patients, such as those who are pregnant or breastfeeding.² Supplementation, however, neither reduces the risk of hepatotoxicity nor prevents onset of seizure following an INH overdose (the B₆ dose is not sufficient enough to exert this effect).

How is acute isoniazid-induced seizure managed?

Management of patients with refractory seizure should initially include an assessment and management of the patient’s airway, breathing, and circulation. Although seizures induced by INH toxicity are often resistant to benzodiazepines, these agents remain the first-line therapy. For patients who fail to respond to a reasonable trial of benzodiazepines (eg, lorazepam 6 mg intravenously [IV]), pyridoxine should be administered.³ The recommended dose is 1 g pyridoxine per every 1 g of INH ingested—if the initial dose ingested is known—with a maximum dose of 5 g pyridoxine. If the initial dose of INH is not known, 70 mg/kg of pyridoxine, up to 5 g, is recommended. Repeated doses of pyridoxine can be administered if the seizure continues, up to a total dose of 10 g in an adult. At extremely high doses, pyridoxine itself can be neurotoxic, limiting the maximal antidotal dose.

Rapid initiation of pyridoxine is a challenge since typical stocks in most EDs are not in an adequate supply required for treatment. Additionally, a typical vial of pyridoxine contains 100 mg, highlighting the rare need to open dozens of vials for a single patient. Drawing up adequate doses of the IV formulation can be a challenge and time-consuming.

Regardless, the most reliable and rapid route of administration for pyridoxine is IV, at a rate of 0.5 to 1 g/min. Even if the seizure resolves prior to completion of the initial dose, the remaining doses should still be administered over a 4- to 6-hour period. Oral or (more likely) nasogastric administration of pyridoxine can be administered if the IV formulation is not available, but neither are optimal routes of delivery. Every effort should be made to stock pyridoxine in the antidote supply in the ED to avoid time delays involving finding, preparing, and administering the drug in these scenarios. Previous studies have found that most EDs are not prepared to handle pyridoxine replacement.^4,5

Since benzodiazepines and barbiturates are GABA agonists with complementary mechanisms of actions to pyridoxine, they should be administered to potentiate the antiseizure effect of pyridoxine. If the seizure does not terminate, the use of propofol or general anesthesia may be required. Once the seizure is terminated, oral activated charcoal can be administered if the ingestion occurred within several hours of presentation. Given the rapid onset of effect of a large dose of INH, most patients will develop seizure shortly after exposure, limiting the benefits of both aggressive gastrointestinal decontamination and delayed activated charcoal. Charcoal also can be used for patients who overdose on INH but do not develop seizures.

Although the utility of a head computed tomography (CT) scan or laboratory studies is limited given the context of the exposure, these are generally obtained for patients with new-onset seizure. Since many patients with INH toxicity do not seize, such a patient may have a lower seizure threshold due to the existence of a subclinical cerebral lesion or metabolic abnormality.

Case Conclusion

The patient’s INH-induced refractory seizure was treated with pyridoxine. Her history suggested that she had ingested an unknown number of INH tablets within an hour. On this initial basis, an IV dose of 5,000 mg of pyridoxine was administered. The patient’s seizures terminated within 2 minutes of the infusion, and no additional doses of pyridoxine were required. Given the lack of concern for self-harm, an acetaminophen concentration was not obtained. A urine toxicology screen was negative for cocaine and amphetamines, and a CT scan of the head was negative for any abnormality. The patient was admitted to the pediatric intensive care unit for status epileptics and was discharged home on hospital day 2 after an uneventful stay.

Risks of Electronic Cigarettes Include Unintentional Ingestion of Liquid Nicotine

BY JEFF BAUER

A recent case report of a 6-year-old girl who developed severe toxicity and required intubation after an unintentional exposure to liquid nicotine emphasizes a potential danger of commercially available liquid nicotine, which is highly concentrated, unreliably packaged, and poorly regulated.

Liquid nicotine is commonly sold in concentrated “refill” solutions intended for electronic cigarette users to dilute themselves. Previous studies have found that these refill products have unreliable commercial labeling, and that the actual nicotine concentration of these solutions can vary widely from the advertised concentration.

In this case report, the girl’s mother had purchased a concentrated nicotine solution online and had used an empty ibuprofen bottle, which she relabeled as “NIC,” to dilute the solution. Afterward, the patient’s father gave his daughter a 10-mL dose of the liquid from the repurposed bottle, believing it to be ibuprofen. Immediately upon consumption, the girl experienced a burning sensation in her mouth and throat. When the father tasted the liquid, he realized it contained the nicotine solution.

Within 5 minutes of the ingestion, the patient’s father called the regional poison control center and emergency medical services, while the girl’s mother attempted to manually induce vomiting, which produced only a small amount of emesis. When the paramedics arrived, the girl was conscious and breathing spontaneously, but she did not respond to questions or follow commands. The only intervention the paramedics performed was insertion of a peripheral intravenous line.

The girl arrived at the ED approximately 25 minutes after having ingested the nicotine. Her vital signs were: temperature, 95.4°F; heart rate (HR), 140 to 150 beats/min; and blood pressure, 93/70 mm Hg. Oxygen saturation was 95% on room air. She was alternately agitated and unresponsive. Her HR decreased to 60 beats/min, and she developed vomiting, diaphoresis, fasciculations, obtundation, and copious secretions. She was given ondansetron (0.1 mg/kg) and lorazepam (0.05 mg/kg), and within 6 minutes from arrival, she was sedated and intubated. Activated charcoal (25 g) was administered via nasogastric tube, and she was admitted to the pediatric intensive care unit.

Laboratory results from blood drawn upon the girl’s arrival at the ED indicated elevated lactate, creatinine, and potassium levels. A serum sample obtained 60 minutes after the girl had ingested the liquid was notable for elevated levels of nicotine (348 ng/mL). With the parents’ permission, the liquid in the ibuprofen container was analyzed and found to contain nicotine, 70.3 mg/mL, which meant the girl had consumed 703 mg of nicotine, or 35 mg/kg. A recent review suggested a fatal nicotine dose of 500 to 1,000 mg in adults. Assuming the mother had correctly diluted the liquid nicotine by half as she had intended to, the original product’s nicotine concentration was 140.6 mg/mL, or 234% of the amount listed on the package (60 mg/mL).

The girl remained sedated and intubated overnight without requiring additional medication or treatment. She was extubated the next morning. Her lactate, creatinine, and potassium levels returned to normal, and electrocardiography and chest radiography results were normal. She was discharged home in stable condition. The Department of Human Services conducted a brief investigation, which they closed when the patient was discharged.

The authors of this case report concluded that emergency physicians (EPs) should be aware of the widespread availability of liquid nicotine products, and the potential of severe toxicity from ingestion of liquid nicotine.

Noble MJ, Longstreet B, Hendrickson RG, Gerona R. Unintentional pediatric ingestion of electronic cigarette nicotine refill liquid necessitating intubation. Ann Emerg Med. 2017;69(1):94-97. doi:10.1016/j.annemergmed.2016.08.448.

Emergency Radiologists’ Job Satisfaction Tied to How Often They Have to Work Overnight Shifts

BY JEFF BAUER

According to a recent survey of emergency radiologists, those who frequently work overnight shifts are less likely to be satisfied with their job than counterparts who work fewer or no overnight shifts.

Approximately 1,100 emergency radiologists received an e-mail invitation to complete an online survey; 327 did so (29.6% response rate). Seventy-three percent of respondents were male, 69% were age 40 years or older, and 87% practiced full-time. Respondents were asked to rate statements such as “I enjoy my job” and “At times I feel overwhelmed at work” on a Likert scale from “disagree or strongly disagree” to “agree or strongly agree.”

Overall, 81% of respondents reported some measure of job enjoyment. There was an association between the average number of overnight shifts performed per year and job enjoyment. Emergency radiologists who did no overnight shifts were 2.21 times more likely to report enjoying their job than those who worked 17 weeks or more of overnight shifts a year.

Hanna TN, Shekhani H, Lamoureux C, et al. Emergency radiology practice patterns: shifts, schedules, and job satisfaction. J Am Coll Radiol. 2016. Dec 4. [Epub ahead of print]. doi:10.1016/j.jacr.2016.09.018.

Discharging Select Diverticulitis Patients From the ED May Be Acceptable

DOUG BRUNK

FRONTLINE MEDICAL NEWS

Among patients diagnosed with diverticulitis via computed tomography (CT) scan in the ED who were discharged home, only 13% required a return visit to the hospital, results from a long-term retrospective analysis demonstrated.

“In select patients whose assessment includes a CT scan, discharge to home from the emergency department with treatment for diverticulitis is safe,” study author Anne-Marie Sirany, MD, said at the annual meeting of the Western Surgical Association.

According to Dr Sirany, a general surgery resident at Hennepin County Medical Center, Minneapolis, diverticulitis accounts for about 150,000 hospital admissions per year in the United States, and only 15% of these patients require surgical intervention. However, between 2006 and 2011, ED visits for diverticulitis increased by 21%, and the annual direct medical cost related to the condition is estimated to exceed $1.8 billion. At the same time, medical literature regarding uncomplicated diverticulitis is scarce. “Most of the literature focuses on complicated diverticulitis, which includes episodes associated with extraluminal air, free perforation, abscess, fistula, obstruction, and stricture,” Dr Sirany said.

A few years ago, researchers conducted a randomized trial to evaluate the treatment of uncomplicated diverticulitis. Patients were diagnosed with diverticulitis in the ED and randomized to either hospital admission or outpatient management at home. The investigators found no significant differences between the readmission rates of the inpatient and outpatient groups, but the health care costs were three times lower in the outpatient group. Dr Sirany and her associates set out to compare the outcomes of patients diagnosed with and treated for diverticulitis in the ED who were discharged to home, versus those who were admitted to the hospital. They reviewed the medical records of 240 patients with a primary diagnosis of diverticulitis by CT scan who were evaluated in the ED at one of four hospitals and one academic medical center from September 2010 to January 2012. The primary outcome was hospital readmission or return to the ED within 30 days, while the secondary outcomes were recurrent diverticulitis or surgical resection for diverticulitis.

The mean age of the 240 patients was 59 years, 45% were men, 22% had a Charlson Comorbidity Index (CCI) of >2, and 7.5% were on corticosteroids or immunosuppressant medications. More than half (62%) were admitted to the hospital, while the remaining 38% were discharged home on oral antibiotics. Compared with patients discharged home, those admitted to the hospital were more likely to be older than 65 years (43% vs 24%, respectively; P = .003), have a CCI of 2 or greater (28% vs 13%; P = .007), were more likely to be on immunosuppressant or steroid medications (11% vs 1%; P = .003), show extraluminal air on CT (30% vs 7%; P < .001), or show abscess on CT (19% vs 1%; P < .001). “Of note: We did not have any patients who had CT scan findings of pneumoperitoneum who were discharged home, and 48% of patients admitted to the hospital had uncomplicated diverticulitis,” she said.

After a median follow-up of 37 months, no significant differences were observed between patients discharged to home and those admitted to the hospital in readmission or return to the ED (13% vs 14%), recurrent diverticulitis (23% in each group), or in colon resection at subsequent encounter (16% vs 19%). “Among patients discharged to home, only one patient required emergency surgery, and this was 20 months after their index admission,” Dr Sirany said. “We think that the low rate of readmission in patients discharged home demonstrates that this is a safe approach to management of patients with diverticulitis, when using information from the CT scan.”

Closer analysis of patients who were discharged home revealed that six patients had extraluminal air on CT scan, three of whom returned to the ED or were admitted to the hospital. In addition, 11% of those with uncomplicated diverticulitis returned to the ED or were admitted to the hospital.

Dr Sirany acknowledged certain limitations of the study, including its retrospective design, a lack of complete follow-up for all patients, and the fact that it included patients with recurrent diverticulitis. “Despite the limitations, we recommend that young, relatively healthy patients with uncomplicated findings on CT scan can be discharged to home and managed as an outpatient,” she said. “In an era where there’s increasing attention to health care costs, we need to think more critically about which patients need to be admitted for management of uncomplicated diverticulitis.”

Microsensor Perfectly Distinguished Coagulopathy Patients From Controls

AMY KARON

FRONTLINE MEDICAL NEWS

Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in <15 minutes and perfectly distinguished various coagulopathies from normal blood samples—handily beating the results from both activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care (POC) assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.

Existing POC coagulation assays have several shortcomings, Dr Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.

To develop an alternative, Dr Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.

To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.

Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes—significantly exceeding those of healthy controls (P = .002).

By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver-operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, while neither aPTT nor PT did.

Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E₂ to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time-to-peak values were the same in both groups. This finding confirms the chip can identify abnormal platelet function, Dr Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.

The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.

Survey: Overprescribing Is the Cause of the Opioid Crisis

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Almost a third of doctors blamed overprescribing as the cause of the opioid crisis, according to a survey of 225 US primary care, emergency medicine, and pain management physicians by InCrowd, an online physician survey company.

Respondents said their and other physicians’ overprescribing is the single biggest factor fueling the leap in opioid abuse over the past 5 years.

“We were told…that [opioids] wouldn’t be addictive in the great majority of patients. This was obviously wrong,” said a Utah EP in practice for 38 years. Meanwhile, 24% of the respondents cited aggressive patient drug-seeking as the primary cause, and 18% blamed drug dealers.

In short, the survey pointed out what front-line doctors think needs to be fixed as the nation combats prescription opioid abuse and the subsequent heroin epidemic. Their insights “should be a rallying cry” for changes in 2017, said epidemiologist Diane Hayes, PhD, president and cofounder of InCrowd.

Making pain the “fifth vital sign” and allowing patients to downgrade doctors on surveys if they don’t prescribe or refill opioid prescriptions compounded the situation. Lengthy waits for specialists with better pain options, many of whom are not covered by Medicaid or the Affordable Care Act, also added to the problem, survey respondents said.

“We’re caught in the middle” between the Joint Commission on Accreditation of Healthcare Organization’s fifth vital sign and overprescribing, a primary care physician (PCP) said.

Seventy-three percent of survey respondents said that they want opioid alternatives, noting exasperation with nonsteroidal anti-inflammatory drugs, physical therapy, and exercise. About half recommend behavioral health interventions, while 20% recommend vitamin and herbal supplements. Only 10% recommend medical marijuana, probably because it is inaccessible to most US patients. Meanwhile, the respondents said they want opioid prescribing “hemmed in.” Almost two-thirds wanted refill limits and more frequent refill evaluations, and many agreed that there needs to be a weaning protocol before the drugs are even started. Some wanted to limit advertising.

Easton Jackson, MD, a PCP in West Valley City, Utah, who answered the survey, helped make the answers real by sharing his thoughts.

“We need to recognize that…people don’t set out to get addicted to opioids….We need to educate [patients] and assist them with their expectations. They need to understand that they’re going to have pain from surgery and injuries. Our goal isn’t to make them pain-free. It’s to manage their pain,” he said.

“We as physicians need to write for fewer pills and in lower doses. We need to see our patients back sooner. If it’s not working, stop increasing the dose and instead taper the patient off the medication. We need to be familiar with the adjuvant therapies. As easy as it is to say, ‘send them all to the pain specialist,’ there simply aren’t enough of them around,” Dr Jackson said.

Physician respondents to InCrowd’s opioid survey have practiced an average of 25 years, and were scattered around the United States. They filled out the four-question survey during October 27 to 28, 2016. They signed up to receive and answer InCrowd’s questions, and were paid nominally for their time.

Half (50%) of respondents estimated that they prescribed opioids to <10% of their patients; 38% said they prescribed to less than half of their patients; and 12% estimated they prescribed opioids to more than half of their patients.

Adding Respiratory Rate to Triage Criteria Improves Accurate Staging of Chest Trauma Patients

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Adding respiratory rate (RR) and suspected blunt chest injury to a trauma assessment in the field significantly improved the appropriate triaging of level III trauma patients.

When the assessment specifically evaluated for tachypnea in the setting of blunt chest injury, undertriaging improved by 1.2%, John Yonge, MD, said at the annual clinical congress of the American College of Surgeons.

“When we applied this new criteria to our 10-year study, we identified 661 patients who should have been activated as a level I or level II,” but instead were assessed as less critically injured, Dr Yonge said in an interview. This initial misstep significantly extended the time before patients could have critical surgical procedures and was related to higher mortality among them.

Dr Yonge, a surgical fellow at Oregon Health & Science University (OHSU), Portland, and his mentor Martin Schreiber, MD, conducted the retrospective study of 7,880 trauma patients admitted at level III activation from 2004 to 2014. The OHSU trauma system has three activation levels.

• Level I activations are reserved for the most critically injured patients; attending trauma surgeon and anesthesiologist presence is mandatory.
• Level II activations capture moderate-to-severe injuries; trauma surgeon and respiratory therapist presence is mandated.
• Level III activations are designed to capture patients who do not require an immediate lifesaving intervention; the presence of the trauma surgery chief resident and attending emergency medicine physician is mandatory.

Patients were considered undertriaged if they were admitted as level III activations, but then required a critical intervention (chest tube placement, intubation, needle thoracostomy, or intracranial pressure monitoring) in the ED or ultimately met level I or II activation criteria.

Among all the level III patients, 466 (6%) were undertriaged: 390 were undertriaged based on the existing level I or II activation criteria, and 76 were considered undertriaged based on the need for a critical intervention.

Most of the undertriaged patients (65%) met criteria for level I activation; the rest should have been triaged as level II patients. Compared with appropriately staged level III patients, mortality among the undertriaged patients was significantly higher (3.2% vs 0.6%). Undertriaged patients also experienced longer delays before initiation of major emergency surgery: a mean of 147 minutes, compared with 106 minutes for appropriately triaged level I patients and 62 minutes for appropriately triaged level II patients.

Dr Yonge then looked for clinical measures that would improve triage. Tachypnea (RR >20 breaths/min) in the field stood out as a significant factor. Tachypneic patients who had a suspected chest injury were 70% more likely to be undertriaged than were those with a normal RR. Tachypnea was significantly associated with a diagnosis of flail chest, ED intubation, and chest-tube placement.

The team then constructed a new triage criterion for patients with suspected chest injury—tachypnea combined with suspected blunt thoracic injury. By applying that model to their study population of level III patients, they determined that the level III undertriage rate would be reduced by 1.2%.

Tying the physiological marker of tachypnea to a suspected clinical diagnosis is a key factor, Dr Yonge noted. “Just adding tachypnea doesn’t help us. In fact, it would overwhelm us, because a trauma patient could very well be tachypneic because he’s experiencing panic. But tying it to a suspected clinical diagnosis gives us a meaningful result.”

He confirmed this linkage with an additional analysis. “We looked to see how severely injured these patients were and found that 71% of them had an Abbreviated Injury Score (AIS) to the chest of 3 or more, indicating a severe chest injury. Only 29% had an AIS of 2 or less. So this proves that respiratory rate is a valid triage criterion and can be used to identify patients who need a higher level of trauma care.”

The challenge now, Dr Yonge said, is incorporating the marker into clinical practice. “It doesn’t matter how many statistics you do, if you can’t educate the prehospital providers in this, it’s useless. They are the crux of the trauma system.”

Although national guidelines do recommend assessing RR as part of field triage, it often isn’t recorded or is only estimated, Dr Yonge said. That’s one reason he used the 20 breaths/min cutoff rate. “It doesn’t even take a full minute to assess this, but it can make a big improvement in care.”

Risks of Electronic Cigarettes Include Unintentional Ingestion of Liquid Nicotine

BY JEFF BAUER

A recent case report of a 6-year-old girl who developed severe toxicity and required intubation after an unintentional exposure to liquid nicotine emphasizes a potential danger of commercially available liquid nicotine, which is highly concentrated, unreliably packaged, and poorly regulated.

Liquid nicotine is commonly sold in concentrated “refill” solutions intended for electronic cigarette users to dilute themselves. Previous studies have found that these refill products have unreliable commercial labeling, and that the actual nicotine concentration of these solutions can vary widely from the advertised concentration.

In this case report, the girl’s mother had purchased a concentrated nicotine solution online and had used an empty ibuprofen bottle, which she relabeled as “NIC,” to dilute the solution. Afterward, the patient’s father gave his daughter a 10-mL dose of the liquid from the repurposed bottle, believing it to be ibuprofen. Immediately upon consumption, the girl experienced a burning sensation in her mouth and throat. When the father tasted the liquid, he realized it contained the nicotine solution.

Within 5 minutes of the ingestion, the patient’s father called the regional poison control center and emergency medical services, while the girl’s mother attempted to manually induce vomiting, which produced only a small amount of emesis. When the paramedics arrived, the girl was conscious and breathing spontaneously, but she did not respond to questions or follow commands. The only intervention the paramedics performed was insertion of a peripheral intravenous line.

The girl arrived at the ED approximately 25 minutes after having ingested the nicotine. Her vital signs were: temperature, 95.4°F; heart rate (HR), 140 to 150 beats/min; and blood pressure, 93/70 mm Hg. Oxygen saturation was 95% on room air. She was alternately agitated and unresponsive. Her HR decreased to 60 beats/min, and she developed vomiting, diaphoresis, fasciculations, obtundation, and copious secretions. She was given ondansetron (0.1 mg/kg) and lorazepam (0.05 mg/kg), and within 6 minutes from arrival, she was sedated and intubated. Activated charcoal (25 g) was administered via nasogastric tube, and she was admitted to the pediatric intensive care unit.

Laboratory results from blood drawn upon the girl’s arrival at the ED indicated elevated lactate, creatinine, and potassium levels. A serum sample obtained 60 minutes after the girl had ingested the liquid was notable for elevated levels of nicotine (348 ng/mL). With the parents’ permission, the liquid in the ibuprofen container was analyzed and found to contain nicotine, 70.3 mg/mL, which meant the girl had consumed 703 mg of nicotine, or 35 mg/kg. A recent review suggested a fatal nicotine dose of 500 to 1,000 mg in adults. Assuming the mother had correctly diluted the liquid nicotine by half as she had intended to, the original product’s nicotine concentration was 140.6 mg/mL, or 234% of the amount listed on the package (60 mg/mL).

The girl remained sedated and intubated overnight without requiring additional medication or treatment. She was extubated the next morning. Her lactate, creatinine, and potassium levels returned to normal, and electrocardiography and chest radiography results were normal. She was discharged home in stable condition. The Department of Human Services conducted a brief investigation, which they closed when the patient was discharged.

The authors of this case report concluded that emergency physicians (EPs) should be aware of the widespread availability of liquid nicotine products, and the potential of severe toxicity from ingestion of liquid nicotine.

Noble MJ, Longstreet B, Hendrickson RG, Gerona R. Unintentional pediatric ingestion of electronic cigarette nicotine refill liquid necessitating intubation. Ann Emerg Med. 2017;69(1):94-97. doi:10.1016/j.annemergmed.2016.08.448.

Emergency Radiologists’ Job Satisfaction Tied to How Often They Have to Work Overnight Shifts

BY JEFF BAUER

According to a recent survey of emergency radiologists, those who frequently work overnight shifts are less likely to be satisfied with their job than counterparts who work fewer or no overnight shifts.

Approximately 1,100 emergency radiologists received an e-mail invitation to complete an online survey; 327 did so (29.6% response rate). Seventy-three percent of respondents were male, 69% were age 40 years or older, and 87% practiced full-time. Respondents were asked to rate statements such as “I enjoy my job” and “At times I feel overwhelmed at work” on a Likert scale from “disagree or strongly disagree” to “agree or strongly agree.”

Overall, 81% of respondents reported some measure of job enjoyment. There was an association between the average number of overnight shifts performed per year and job enjoyment. Emergency radiologists who did no overnight shifts were 2.21 times more likely to report enjoying their job than those who worked 17 weeks or more of overnight shifts a year.

Hanna TN, Shekhani H, Lamoureux C, et al. Emergency radiology practice patterns: shifts, schedules, and job satisfaction. J Am Coll Radiol. 2016. Dec 4. [Epub ahead of print]. doi:10.1016/j.jacr.2016.09.018.

Discharging Select Diverticulitis Patients From the ED May Be Acceptable

DOUG BRUNK

FRONTLINE MEDICAL NEWS

Among patients diagnosed with diverticulitis via computed tomography (CT) scan in the ED who were discharged home, only 13% required a return visit to the hospital, results from a long-term retrospective analysis demonstrated.

“In select patients whose assessment includes a CT scan, discharge to home from the emergency department with treatment for diverticulitis is safe,” study author Anne-Marie Sirany, MD, said at the annual meeting of the Western Surgical Association.

According to Dr Sirany, a general surgery resident at Hennepin County Medical Center, Minneapolis, diverticulitis accounts for about 150,000 hospital admissions per year in the United States, and only 15% of these patients require surgical intervention. However, between 2006 and 2011, ED visits for diverticulitis increased by 21%, and the annual direct medical cost related to the condition is estimated to exceed $1.8 billion. At the same time, medical literature regarding uncomplicated diverticulitis is scarce. “Most of the literature focuses on complicated diverticulitis, which includes episodes associated with extraluminal air, free perforation, abscess, fistula, obstruction, and stricture,” Dr Sirany said.

A few years ago, researchers conducted a randomized trial to evaluate the treatment of uncomplicated diverticulitis. Patients were diagnosed with diverticulitis in the ED and randomized to either hospital admission or outpatient management at home. The investigators found no significant differences between the readmission rates of the inpatient and outpatient groups, but the health care costs were three times lower in the outpatient group. Dr Sirany and her associates set out to compare the outcomes of patients diagnosed with and treated for diverticulitis in the ED who were discharged to home, versus those who were admitted to the hospital. They reviewed the medical records of 240 patients with a primary diagnosis of diverticulitis by CT scan who were evaluated in the ED at one of four hospitals and one academic medical center from September 2010 to January 2012. The primary outcome was hospital readmission or return to the ED within 30 days, while the secondary outcomes were recurrent diverticulitis or surgical resection for diverticulitis.

The mean age of the 240 patients was 59 years, 45% were men, 22% had a Charlson Comorbidity Index (CCI) of >2, and 7.5% were on corticosteroids or immunosuppressant medications. More than half (62%) were admitted to the hospital, while the remaining 38% were discharged home on oral antibiotics. Compared with patients discharged home, those admitted to the hospital were more likely to be older than 65 years (43% vs 24%, respectively; P = .003), have a CCI of 2 or greater (28% vs 13%; P = .007), were more likely to be on immunosuppressant or steroid medications (11% vs 1%; P = .003), show extraluminal air on CT (30% vs 7%; P < .001), or show abscess on CT (19% vs 1%; P < .001). “Of note: We did not have any patients who had CT scan findings of pneumoperitoneum who were discharged home, and 48% of patients admitted to the hospital had uncomplicated diverticulitis,” she said.

After a median follow-up of 37 months, no significant differences were observed between patients discharged to home and those admitted to the hospital in readmission or return to the ED (13% vs 14%), recurrent diverticulitis (23% in each group), or in colon resection at subsequent encounter (16% vs 19%). “Among patients discharged to home, only one patient required emergency surgery, and this was 20 months after their index admission,” Dr Sirany said. “We think that the low rate of readmission in patients discharged home demonstrates that this is a safe approach to management of patients with diverticulitis, when using information from the CT scan.”

Closer analysis of patients who were discharged home revealed that six patients had extraluminal air on CT scan, three of whom returned to the ED or were admitted to the hospital. In addition, 11% of those with uncomplicated diverticulitis returned to the ED or were admitted to the hospital.

Dr Sirany acknowledged certain limitations of the study, including its retrospective design, a lack of complete follow-up for all patients, and the fact that it included patients with recurrent diverticulitis. “Despite the limitations, we recommend that young, relatively healthy patients with uncomplicated findings on CT scan can be discharged to home and managed as an outpatient,” she said. “In an era where there’s increasing attention to health care costs, we need to think more critically about which patients need to be admitted for management of uncomplicated diverticulitis.”

Microsensor Perfectly Distinguished Coagulopathy Patients From Controls

AMY KARON

FRONTLINE MEDICAL NEWS

Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in <15 minutes and perfectly distinguished various coagulopathies from normal blood samples—handily beating the results from both activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care (POC) assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.

Existing POC coagulation assays have several shortcomings, Dr Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.

To develop an alternative, Dr Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.

To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.

Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes—significantly exceeding those of healthy controls (P = .002).

By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver-operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, while neither aPTT nor PT did.

Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E₂ to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time-to-peak values were the same in both groups. This finding confirms the chip can identify abnormal platelet function, Dr Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.

The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.

Survey: Overprescribing Is the Cause of the Opioid Crisis

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Almost a third of doctors blamed overprescribing as the cause of the opioid crisis, according to a survey of 225 US primary care, emergency medicine, and pain management physicians by InCrowd, an online physician survey company.

Respondents said their and other physicians’ overprescribing is the single biggest factor fueling the leap in opioid abuse over the past 5 years.

“We were told…that [opioids] wouldn’t be addictive in the great majority of patients. This was obviously wrong,” said a Utah EP in practice for 38 years. Meanwhile, 24% of the respondents cited aggressive patient drug-seeking as the primary cause, and 18% blamed drug dealers.

In short, the survey pointed out what front-line doctors think needs to be fixed as the nation combats prescription opioid abuse and the subsequent heroin epidemic. Their insights “should be a rallying cry” for changes in 2017, said epidemiologist Diane Hayes, PhD, president and cofounder of InCrowd.

Making pain the “fifth vital sign” and allowing patients to downgrade doctors on surveys if they don’t prescribe or refill opioid prescriptions compounded the situation. Lengthy waits for specialists with better pain options, many of whom are not covered by Medicaid or the Affordable Care Act, also added to the problem, survey respondents said.

“We’re caught in the middle” between the Joint Commission on Accreditation of Healthcare Organization’s fifth vital sign and overprescribing, a primary care physician (PCP) said.

Seventy-three percent of survey respondents said that they want opioid alternatives, noting exasperation with nonsteroidal anti-inflammatory drugs, physical therapy, and exercise. About half recommend behavioral health interventions, while 20% recommend vitamin and herbal supplements. Only 10% recommend medical marijuana, probably because it is inaccessible to most US patients. Meanwhile, the respondents said they want opioid prescribing “hemmed in.” Almost two-thirds wanted refill limits and more frequent refill evaluations, and many agreed that there needs to be a weaning protocol before the drugs are even started. Some wanted to limit advertising.

Easton Jackson, MD, a PCP in West Valley City, Utah, who answered the survey, helped make the answers real by sharing his thoughts.

“We need to recognize that…people don’t set out to get addicted to opioids….We need to educate [patients] and assist them with their expectations. They need to understand that they’re going to have pain from surgery and injuries. Our goal isn’t to make them pain-free. It’s to manage their pain,” he said.

“We as physicians need to write for fewer pills and in lower doses. We need to see our patients back sooner. If it’s not working, stop increasing the dose and instead taper the patient off the medication. We need to be familiar with the adjuvant therapies. As easy as it is to say, ‘send them all to the pain specialist,’ there simply aren’t enough of them around,” Dr Jackson said.

Physician respondents to InCrowd’s opioid survey have practiced an average of 25 years, and were scattered around the United States. They filled out the four-question survey during October 27 to 28, 2016. They signed up to receive and answer InCrowd’s questions, and were paid nominally for their time.

Half (50%) of respondents estimated that they prescribed opioids to <10% of their patients; 38% said they prescribed to less than half of their patients; and 12% estimated they prescribed opioids to more than half of their patients.

Adding Respiratory Rate to Triage Criteria Improves Accurate Staging of Chest Trauma Patients

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Adding respiratory rate (RR) and suspected blunt chest injury to a trauma assessment in the field significantly improved the appropriate triaging of level III trauma patients.

When the assessment specifically evaluated for tachypnea in the setting of blunt chest injury, undertriaging improved by 1.2%, John Yonge, MD, said at the annual clinical congress of the American College of Surgeons.

“When we applied this new criteria to our 10-year study, we identified 661 patients who should have been activated as a level I or level II,” but instead were assessed as less critically injured, Dr Yonge said in an interview. This initial misstep significantly extended the time before patients could have critical surgical procedures and was related to higher mortality among them.

Dr Yonge, a surgical fellow at Oregon Health & Science University (OHSU), Portland, and his mentor Martin Schreiber, MD, conducted the retrospective study of 7,880 trauma patients admitted at level III activation from 2004 to 2014. The OHSU trauma system has three activation levels.

• Level I activations are reserved for the most critically injured patients; attending trauma surgeon and anesthesiologist presence is mandatory.
• Level II activations capture moderate-to-severe injuries; trauma surgeon and respiratory therapist presence is mandated.
• Level III activations are designed to capture patients who do not require an immediate lifesaving intervention; the presence of the trauma surgery chief resident and attending emergency medicine physician is mandatory.

Patients were considered undertriaged if they were admitted as level III activations, but then required a critical intervention (chest tube placement, intubation, needle thoracostomy, or intracranial pressure monitoring) in the ED or ultimately met level I or II activation criteria.

Among all the level III patients, 466 (6%) were undertriaged: 390 were undertriaged based on the existing level I or II activation criteria, and 76 were considered undertriaged based on the need for a critical intervention.

Most of the undertriaged patients (65%) met criteria for level I activation; the rest should have been triaged as level II patients. Compared with appropriately staged level III patients, mortality among the undertriaged patients was significantly higher (3.2% vs 0.6%). Undertriaged patients also experienced longer delays before initiation of major emergency surgery: a mean of 147 minutes, compared with 106 minutes for appropriately triaged level I patients and 62 minutes for appropriately triaged level II patients.

Dr Yonge then looked for clinical measures that would improve triage. Tachypnea (RR >20 breaths/min) in the field stood out as a significant factor. Tachypneic patients who had a suspected chest injury were 70% more likely to be undertriaged than were those with a normal RR. Tachypnea was significantly associated with a diagnosis of flail chest, ED intubation, and chest-tube placement.

The team then constructed a new triage criterion for patients with suspected chest injury—tachypnea combined with suspected blunt thoracic injury. By applying that model to their study population of level III patients, they determined that the level III undertriage rate would be reduced by 1.2%.

Tying the physiological marker of tachypnea to a suspected clinical diagnosis is a key factor, Dr Yonge noted. “Just adding tachypnea doesn’t help us. In fact, it would overwhelm us, because a trauma patient could very well be tachypneic because he’s experiencing panic. But tying it to a suspected clinical diagnosis gives us a meaningful result.”

He confirmed this linkage with an additional analysis. “We looked to see how severely injured these patients were and found that 71% of them had an Abbreviated Injury Score (AIS) to the chest of 3 or more, indicating a severe chest injury. Only 29% had an AIS of 2 or less. So this proves that respiratory rate is a valid triage criterion and can be used to identify patients who need a higher level of trauma care.”

The challenge now, Dr Yonge said, is incorporating the marker into clinical practice. “It doesn’t matter how many statistics you do, if you can’t educate the prehospital providers in this, it’s useless. They are the crux of the trauma system.”

Although national guidelines do recommend assessing RR as part of field triage, it often isn’t recorded or is only estimated, Dr Yonge said. That’s one reason he used the 20 breaths/min cutoff rate. “It doesn’t even take a full minute to assess this, but it can make a big improvement in care.”

Risks of Electronic Cigarettes Include Unintentional Ingestion of Liquid Nicotine

BY JEFF BAUER

A recent case report of a 6-year-old girl who developed severe toxicity and required intubation after an unintentional exposure to liquid nicotine emphasizes a potential danger of commercially available liquid nicotine, which is highly concentrated, unreliably packaged, and poorly regulated.

Liquid nicotine is commonly sold in concentrated “refill” solutions intended for electronic cigarette users to dilute themselves. Previous studies have found that these refill products have unreliable commercial labeling, and that the actual nicotine concentration of these solutions can vary widely from the advertised concentration.

In this case report, the girl’s mother had purchased a concentrated nicotine solution online and had used an empty ibuprofen bottle, which she relabeled as “NIC,” to dilute the solution. Afterward, the patient’s father gave his daughter a 10-mL dose of the liquid from the repurposed bottle, believing it to be ibuprofen. Immediately upon consumption, the girl experienced a burning sensation in her mouth and throat. When the father tasted the liquid, he realized it contained the nicotine solution.

Within 5 minutes of the ingestion, the patient’s father called the regional poison control center and emergency medical services, while the girl’s mother attempted to manually induce vomiting, which produced only a small amount of emesis. When the paramedics arrived, the girl was conscious and breathing spontaneously, but she did not respond to questions or follow commands. The only intervention the paramedics performed was insertion of a peripheral intravenous line.

The girl arrived at the ED approximately 25 minutes after having ingested the nicotine. Her vital signs were: temperature, 95.4°F; heart rate (HR), 140 to 150 beats/min; and blood pressure, 93/70 mm Hg. Oxygen saturation was 95% on room air. She was alternately agitated and unresponsive. Her HR decreased to 60 beats/min, and she developed vomiting, diaphoresis, fasciculations, obtundation, and copious secretions. She was given ondansetron (0.1 mg/kg) and lorazepam (0.05 mg/kg), and within 6 minutes from arrival, she was sedated and intubated. Activated charcoal (25 g) was administered via nasogastric tube, and she was admitted to the pediatric intensive care unit.

Laboratory results from blood drawn upon the girl’s arrival at the ED indicated elevated lactate, creatinine, and potassium levels. A serum sample obtained 60 minutes after the girl had ingested the liquid was notable for elevated levels of nicotine (348 ng/mL). With the parents’ permission, the liquid in the ibuprofen container was analyzed and found to contain nicotine, 70.3 mg/mL, which meant the girl had consumed 703 mg of nicotine, or 35 mg/kg. A recent review suggested a fatal nicotine dose of 500 to 1,000 mg in adults. Assuming the mother had correctly diluted the liquid nicotine by half as she had intended to, the original product’s nicotine concentration was 140.6 mg/mL, or 234% of the amount listed on the package (60 mg/mL).

The girl remained sedated and intubated overnight without requiring additional medication or treatment. She was extubated the next morning. Her lactate, creatinine, and potassium levels returned to normal, and electrocardiography and chest radiography results were normal. She was discharged home in stable condition. The Department of Human Services conducted a brief investigation, which they closed when the patient was discharged.

The authors of this case report concluded that emergency physicians (EPs) should be aware of the widespread availability of liquid nicotine products, and the potential of severe toxicity from ingestion of liquid nicotine.

Noble MJ, Longstreet B, Hendrickson RG, Gerona R. Unintentional pediatric ingestion of electronic cigarette nicotine refill liquid necessitating intubation. Ann Emerg Med. 2017;69(1):94-97. doi:10.1016/j.annemergmed.2016.08.448.

Emergency Radiologists’ Job Satisfaction Tied to How Often They Have to Work Overnight Shifts

BY JEFF BAUER

According to a recent survey of emergency radiologists, those who frequently work overnight shifts are less likely to be satisfied with their job than counterparts who work fewer or no overnight shifts.

Approximately 1,100 emergency radiologists received an e-mail invitation to complete an online survey; 327 did so (29.6% response rate). Seventy-three percent of respondents were male, 69% were age 40 years or older, and 87% practiced full-time. Respondents were asked to rate statements such as “I enjoy my job” and “At times I feel overwhelmed at work” on a Likert scale from “disagree or strongly disagree” to “agree or strongly agree.”

Overall, 81% of respondents reported some measure of job enjoyment. There was an association between the average number of overnight shifts performed per year and job enjoyment. Emergency radiologists who did no overnight shifts were 2.21 times more likely to report enjoying their job than those who worked 17 weeks or more of overnight shifts a year.

Hanna TN, Shekhani H, Lamoureux C, et al. Emergency radiology practice patterns: shifts, schedules, and job satisfaction. J Am Coll Radiol. 2016. Dec 4. [Epub ahead of print]. doi:10.1016/j.jacr.2016.09.018.

Discharging Select Diverticulitis Patients From the ED May Be Acceptable

DOUG BRUNK

FRONTLINE MEDICAL NEWS

Among patients diagnosed with diverticulitis via computed tomography (CT) scan in the ED who were discharged home, only 13% required a return visit to the hospital, results from a long-term retrospective analysis demonstrated.

“In select patients whose assessment includes a CT scan, discharge to home from the emergency department with treatment for diverticulitis is safe,” study author Anne-Marie Sirany, MD, said at the annual meeting of the Western Surgical Association.

According to Dr Sirany, a general surgery resident at Hennepin County Medical Center, Minneapolis, diverticulitis accounts for about 150,000 hospital admissions per year in the United States, and only 15% of these patients require surgical intervention. However, between 2006 and 2011, ED visits for diverticulitis increased by 21%, and the annual direct medical cost related to the condition is estimated to exceed $1.8 billion. At the same time, medical literature regarding uncomplicated diverticulitis is scarce. “Most of the literature focuses on complicated diverticulitis, which includes episodes associated with extraluminal air, free perforation, abscess, fistula, obstruction, and stricture,” Dr Sirany said.

A few years ago, researchers conducted a randomized trial to evaluate the treatment of uncomplicated diverticulitis. Patients were diagnosed with diverticulitis in the ED and randomized to either hospital admission or outpatient management at home. The investigators found no significant differences between the readmission rates of the inpatient and outpatient groups, but the health care costs were three times lower in the outpatient group. Dr Sirany and her associates set out to compare the outcomes of patients diagnosed with and treated for diverticulitis in the ED who were discharged to home, versus those who were admitted to the hospital. They reviewed the medical records of 240 patients with a primary diagnosis of diverticulitis by CT scan who were evaluated in the ED at one of four hospitals and one academic medical center from September 2010 to January 2012. The primary outcome was hospital readmission or return to the ED within 30 days, while the secondary outcomes were recurrent diverticulitis or surgical resection for diverticulitis.

The mean age of the 240 patients was 59 years, 45% were men, 22% had a Charlson Comorbidity Index (CCI) of >2, and 7.5% were on corticosteroids or immunosuppressant medications. More than half (62%) were admitted to the hospital, while the remaining 38% were discharged home on oral antibiotics. Compared with patients discharged home, those admitted to the hospital were more likely to be older than 65 years (43% vs 24%, respectively; P = .003), have a CCI of 2 or greater (28% vs 13%; P = .007), were more likely to be on immunosuppressant or steroid medications (11% vs 1%; P = .003), show extraluminal air on CT (30% vs 7%; P < .001), or show abscess on CT (19% vs 1%; P < .001). “Of note: We did not have any patients who had CT scan findings of pneumoperitoneum who were discharged home, and 48% of patients admitted to the hospital had uncomplicated diverticulitis,” she said.

After a median follow-up of 37 months, no significant differences were observed between patients discharged to home and those admitted to the hospital in readmission or return to the ED (13% vs 14%), recurrent diverticulitis (23% in each group), or in colon resection at subsequent encounter (16% vs 19%). “Among patients discharged to home, only one patient required emergency surgery, and this was 20 months after their index admission,” Dr Sirany said. “We think that the low rate of readmission in patients discharged home demonstrates that this is a safe approach to management of patients with diverticulitis, when using information from the CT scan.”

Closer analysis of patients who were discharged home revealed that six patients had extraluminal air on CT scan, three of whom returned to the ED or were admitted to the hospital. In addition, 11% of those with uncomplicated diverticulitis returned to the ED or were admitted to the hospital.

Dr Sirany acknowledged certain limitations of the study, including its retrospective design, a lack of complete follow-up for all patients, and the fact that it included patients with recurrent diverticulitis. “Despite the limitations, we recommend that young, relatively healthy patients with uncomplicated findings on CT scan can be discharged to home and managed as an outpatient,” she said. “In an era where there’s increasing attention to health care costs, we need to think more critically about which patients need to be admitted for management of uncomplicated diverticulitis.”

Microsensor Perfectly Distinguished Coagulopathy Patients From Controls

AMY KARON

FRONTLINE MEDICAL NEWS

Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in <15 minutes and perfectly distinguished various coagulopathies from normal blood samples—handily beating the results from both activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care (POC) assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.

Existing POC coagulation assays have several shortcomings, Dr Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.

To develop an alternative, Dr Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.

To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.

Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes—significantly exceeding those of healthy controls (P = .002).

By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver-operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, while neither aPTT nor PT did.

Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E₂ to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time-to-peak values were the same in both groups. This finding confirms the chip can identify abnormal platelet function, Dr Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.

The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.

Survey: Overprescribing Is the Cause of the Opioid Crisis

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Almost a third of doctors blamed overprescribing as the cause of the opioid crisis, according to a survey of 225 US primary care, emergency medicine, and pain management physicians by InCrowd, an online physician survey company.

Respondents said their and other physicians’ overprescribing is the single biggest factor fueling the leap in opioid abuse over the past 5 years.

“We were told…that [opioids] wouldn’t be addictive in the great majority of patients. This was obviously wrong,” said a Utah EP in practice for 38 years. Meanwhile, 24% of the respondents cited aggressive patient drug-seeking as the primary cause, and 18% blamed drug dealers.

In short, the survey pointed out what front-line doctors think needs to be fixed as the nation combats prescription opioid abuse and the subsequent heroin epidemic. Their insights “should be a rallying cry” for changes in 2017, said epidemiologist Diane Hayes, PhD, president and cofounder of InCrowd.

Making pain the “fifth vital sign” and allowing patients to downgrade doctors on surveys if they don’t prescribe or refill opioid prescriptions compounded the situation. Lengthy waits for specialists with better pain options, many of whom are not covered by Medicaid or the Affordable Care Act, also added to the problem, survey respondents said.

“We’re caught in the middle” between the Joint Commission on Accreditation of Healthcare Organization’s fifth vital sign and overprescribing, a primary care physician (PCP) said.

Seventy-three percent of survey respondents said that they want opioid alternatives, noting exasperation with nonsteroidal anti-inflammatory drugs, physical therapy, and exercise. About half recommend behavioral health interventions, while 20% recommend vitamin and herbal supplements. Only 10% recommend medical marijuana, probably because it is inaccessible to most US patients. Meanwhile, the respondents said they want opioid prescribing “hemmed in.” Almost two-thirds wanted refill limits and more frequent refill evaluations, and many agreed that there needs to be a weaning protocol before the drugs are even started. Some wanted to limit advertising.

Easton Jackson, MD, a PCP in West Valley City, Utah, who answered the survey, helped make the answers real by sharing his thoughts.

“We need to recognize that…people don’t set out to get addicted to opioids….We need to educate [patients] and assist them with their expectations. They need to understand that they’re going to have pain from surgery and injuries. Our goal isn’t to make them pain-free. It’s to manage their pain,” he said.

“We as physicians need to write for fewer pills and in lower doses. We need to see our patients back sooner. If it’s not working, stop increasing the dose and instead taper the patient off the medication. We need to be familiar with the adjuvant therapies. As easy as it is to say, ‘send them all to the pain specialist,’ there simply aren’t enough of them around,” Dr Jackson said.

Physician respondents to InCrowd’s opioid survey have practiced an average of 25 years, and were scattered around the United States. They filled out the four-question survey during October 27 to 28, 2016. They signed up to receive and answer InCrowd’s questions, and were paid nominally for their time.

Half (50%) of respondents estimated that they prescribed opioids to <10% of their patients; 38% said they prescribed to less than half of their patients; and 12% estimated they prescribed opioids to more than half of their patients.

Adding Respiratory Rate to Triage Criteria Improves Accurate Staging of Chest Trauma Patients

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Adding respiratory rate (RR) and suspected blunt chest injury to a trauma assessment in the field significantly improved the appropriate triaging of level III trauma patients.

When the assessment specifically evaluated for tachypnea in the setting of blunt chest injury, undertriaging improved by 1.2%, John Yonge, MD, said at the annual clinical congress of the American College of Surgeons.

“When we applied this new criteria to our 10-year study, we identified 661 patients who should have been activated as a level I or level II,” but instead were assessed as less critically injured, Dr Yonge said in an interview. This initial misstep significantly extended the time before patients could have critical surgical procedures and was related to higher mortality among them.

Dr Yonge, a surgical fellow at Oregon Health & Science University (OHSU), Portland, and his mentor Martin Schreiber, MD, conducted the retrospective study of 7,880 trauma patients admitted at level III activation from 2004 to 2014. The OHSU trauma system has three activation levels.

• Level I activations are reserved for the most critically injured patients; attending trauma surgeon and anesthesiologist presence is mandatory.
• Level II activations capture moderate-to-severe injuries; trauma surgeon and respiratory therapist presence is mandated.
• Level III activations are designed to capture patients who do not require an immediate lifesaving intervention; the presence of the trauma surgery chief resident and attending emergency medicine physician is mandatory.

Patients were considered undertriaged if they were admitted as level III activations, but then required a critical intervention (chest tube placement, intubation, needle thoracostomy, or intracranial pressure monitoring) in the ED or ultimately met level I or II activation criteria.

Among all the level III patients, 466 (6%) were undertriaged: 390 were undertriaged based on the existing level I or II activation criteria, and 76 were considered undertriaged based on the need for a critical intervention.

Most of the undertriaged patients (65%) met criteria for level I activation; the rest should have been triaged as level II patients. Compared with appropriately staged level III patients, mortality among the undertriaged patients was significantly higher (3.2% vs 0.6%). Undertriaged patients also experienced longer delays before initiation of major emergency surgery: a mean of 147 minutes, compared with 106 minutes for appropriately triaged level I patients and 62 minutes for appropriately triaged level II patients.

Dr Yonge then looked for clinical measures that would improve triage. Tachypnea (RR >20 breaths/min) in the field stood out as a significant factor. Tachypneic patients who had a suspected chest injury were 70% more likely to be undertriaged than were those with a normal RR. Tachypnea was significantly associated with a diagnosis of flail chest, ED intubation, and chest-tube placement.

The team then constructed a new triage criterion for patients with suspected chest injury—tachypnea combined with suspected blunt thoracic injury. By applying that model to their study population of level III patients, they determined that the level III undertriage rate would be reduced by 1.2%.

Tying the physiological marker of tachypnea to a suspected clinical diagnosis is a key factor, Dr Yonge noted. “Just adding tachypnea doesn’t help us. In fact, it would overwhelm us, because a trauma patient could very well be tachypneic because he’s experiencing panic. But tying it to a suspected clinical diagnosis gives us a meaningful result.”

He confirmed this linkage with an additional analysis. “We looked to see how severely injured these patients were and found that 71% of them had an Abbreviated Injury Score (AIS) to the chest of 3 or more, indicating a severe chest injury. Only 29% had an AIS of 2 or less. So this proves that respiratory rate is a valid triage criterion and can be used to identify patients who need a higher level of trauma care.”

The challenge now, Dr Yonge said, is incorporating the marker into clinical practice. “It doesn’t matter how many statistics you do, if you can’t educate the prehospital providers in this, it’s useless. They are the crux of the trauma system.”

Although national guidelines do recommend assessing RR as part of field triage, it often isn’t recorded or is only estimated, Dr Yonge said. That’s one reason he used the 20 breaths/min cutoff rate. “It doesn’t even take a full minute to assess this, but it can make a big improvement in care.”

‘Twas the night before New Year, when all through the land
Every ED was busy—Can you give us a hand?

Treating chest pains, and traumas, and hot swollen knees,
While clinics were shuttered, along with UCs.

The handoffs were done with hardly a frown,
In hopes that the volume soon would slow down.

Babies were nestled all snug in a sheet,
Watching sutures applied to their hands and their feet.

And amateur athletes unpadded, uncapped,
Had brains that were rattled after balls had been snapped.

When out on the deck there arose such a clatter
We sprang from the doc box to help with the matter.

To Resusc room 1 we flew in a flash,
Tearing open the curtain before the patient could crash.

The leads on the breast of the now-fallen fellow,
Made lustrous white circles near sclerae bright yellow.

When what to our wondering ears did we hear,
But an overhead page that inspired some fear:

Notifications of a Level 1 trauma,
And several ODs, to add to the drama.

More rapid than eagles the new patients came,
All victims of poisons with rather strange names:

Poinsettia, and holly, and dried mistletoe,
Angel hair, leaded tinsel, polyacrylate snow.

And a man who was tarnished with ashes and soot,
With a cherry red color from his head to his foot.

Smoke inhalation and a toxic epoxide?
Or alcohol, cyanide, carbon monoxide?

But “Holiday Poisonings” on the pages ahead,
Soon reassured us we had nothing to dread…

When patients were discharged to families waiting,

They promised to give us all a good rating.

So to all EMTs, NPs, and PAs,
RNs, and EPs who work holidays,

And to all ED staffs who “fight the good fight,”
Have a Happy New Year, and a nice quiet night!

—Neal Flomenbaum, MD

‘Twas the night before New Year, when all through the land
Every ED was busy—Can you give us a hand?

Treating chest pains, and traumas, and hot swollen knees,
While clinics were shuttered, along with UCs.

The handoffs were done with hardly a frown,
In hopes that the volume soon would slow down.

Babies were nestled all snug in a sheet,
Watching sutures applied to their hands and their feet.

And amateur athletes unpadded, uncapped,
Had brains that were rattled after balls had been snapped.

When out on the deck there arose such a clatter
We sprang from the doc box to help with the matter.

To Resusc room 1 we flew in a flash,
Tearing open the curtain before the patient could crash.

The leads on the breast of the now-fallen fellow,
Made lustrous white circles near sclerae bright yellow.

When what to our wondering ears did we hear,
But an overhead page that inspired some fear:

Notifications of a Level 1 trauma,
And several ODs, to add to the drama.

More rapid than eagles the new patients came,
All victims of poisons with rather strange names:

Poinsettia, and holly, and dried mistletoe,
Angel hair, leaded tinsel, polyacrylate snow.

And a man who was tarnished with ashes and soot,
With a cherry red color from his head to his foot.

Smoke inhalation and a toxic epoxide?
Or alcohol, cyanide, carbon monoxide?

But “Holiday Poisonings” on the pages ahead,
Soon reassured us we had nothing to dread…

When patients were discharged to families waiting,

They promised to give us all a good rating.

So to all EMTs, NPs, and PAs,
RNs, and EPs who work holidays,

And to all ED staffs who “fight the good fight,”
Have a Happy New Year, and a nice quiet night!

—Neal Flomenbaum, MD

‘Twas the night before New Year, when all through the land
Every ED was busy—Can you give us a hand?

Treating chest pains, and traumas, and hot swollen knees,
While clinics were shuttered, along with UCs.

The handoffs were done with hardly a frown,
In hopes that the volume soon would slow down.

Babies were nestled all snug in a sheet,
Watching sutures applied to their hands and their feet.

And amateur athletes unpadded, uncapped,
Had brains that were rattled after balls had been snapped.

When out on the deck there arose such a clatter
We sprang from the doc box to help with the matter.

To Resusc room 1 we flew in a flash,
Tearing open the curtain before the patient could crash.

The leads on the breast of the now-fallen fellow,
Made lustrous white circles near sclerae bright yellow.

When what to our wondering ears did we hear,
But an overhead page that inspired some fear:

Notifications of a Level 1 trauma,
And several ODs, to add to the drama.

More rapid than eagles the new patients came,
All victims of poisons with rather strange names:

Poinsettia, and holly, and dried mistletoe,
Angel hair, leaded tinsel, polyacrylate snow.

And a man who was tarnished with ashes and soot,
With a cherry red color from his head to his foot.

Smoke inhalation and a toxic epoxide?
Or alcohol, cyanide, carbon monoxide?

But “Holiday Poisonings” on the pages ahead,
Soon reassured us we had nothing to dread…

When patients were discharged to families waiting,

They promised to give us all a good rating.

So to all EMTs, NPs, and PAs,
RNs, and EPs who work holidays,

And to all ED staffs who “fight the good fight,”
Have a Happy New Year, and a nice quiet night!

—Neal Flomenbaum, MD

The holiday season, a time of warmth, joy, and good cheer, is upon us. Yet with this most wonderful time of the year comes the possibility of poisoning and hazards in the home. As emergency physicians (EPs), we must ask ourselves: Which holiday items are potentially toxic to our patients? How do we evaluate and manage poisonings that result from exposure to these items? In this article, we review several plants and decorations that are unique to the holiday season. We discuss recommendations for evaluation and management of holiday poisonings that will avoid inappropriate work-ups and interventions while increasing recognition of truly dangerous ingestions, thus help keeping the season safe and merry.

Plants

Plant exposures are the fourth most common cause for calls to poison centers.¹ In 2012, US Poison Control Centers reported more than 30,000 toxic plant exposures in children younger than age 5 years.² Not surprisingly, toxic plant ingestions occur most commonly in early childhood. The highest rate of mortality, however, takes place during the teenaged years, when suicide attempts are common.² The most common plant ingestions reported in the United States include peace lily, holly, philodendron, and poinsettia.³ These and the other frequently ingested potentially poisonous plants produce very little, if any, toxic effects. Approximately 95% of unintentional potentially toxic plant ingestions reported in the United States are managed safely at home.³

Poinsettia

The poinsettia is a large, prominent plant that was introduced to the United States in 1825 by Joel Poinsett, the US ambassador to Mexico. The poinsettia is one of the most commonly researched plants, and studies show the plant is not actually toxic.^4,5 The myth of poinsettia toxicity is a widely held, yet false, belief. The legend involves a young child of an army officer stationed in Hawaii in 1919 who reportedly died after eating poinsettia leaves.⁴ However, the reality is that the poinsettia plant was not actually involved in the child’s death. In fact, the wild plant involved in this case probably had little resemblance to the popular plant cultivated domestically in North America today.⁶

A majority of poinsettia exposures will be asymptomatic, or involve simple nausea and vomiting. Krenzelok et al⁵ reviewed 22,793 cases of poinsettia exposures from 1985 to 1992. Almost all of these exposures (98.9%) were accidental poisonings.⁵ Not surprisingly, 93.3% of poinsettia exposures involved children; most importantly, 96.1% of these patients did not require treatment at a health care facility,and there were no fatalities.⁵ Another study could not identify an LD50 (lethal dose, 50%—ie, the amount of an ingested substance that kills 50% of the test sample) in rats.⁴

The majority of patients presenting to the ED with symptoms from poinsettia exposure will have gastrointestinal (GI) upset. Most patients require only symptomatic care. Those who do present to the ED do not require gastric emptying.

Interestingly, there is a crossreactivity of poinsettia sap in latex-allergic vulnerable patients.⁶ Poinsettia is part of the same plant family as natural rubber latex, and patients can present with symptoms of contact dermatitis, especially if they have a latex allergy.⁴ Washing the area thoroughly with soap and water and avoiding future contact is all that is required for most patients with contact dermatitis.

Holly

Holly exposure accounted for the third highest rate of genus-specific human plant exposure calls to poison centers in 2010.⁴ In the United States, there are two common forms of holly: English holly and American holly. The berries of both varieties contain saponin, a toxin that can cause erythrocyte hemolysis and changes in the permeability of small intestinal mucosal cells.⁴ Most holly berry ingestions cause minor or no symptoms. The prickly leaves of the holly plant are nontoxic but consumption may result in minor injury. When symptoms do occur, they can include nausea, vomiting, abdominal cramping, and possible dermatitis.⁵ Mydriasis, hyperthermia, and drowsiness are rare but possible symptoms.⁴

For symptoms to develop, children need to have eaten only five berries, while adults reportedly must consume at least 20 to 30 berries.⁴ A study by Wax et al⁷ done at the University of Rochester reviewed 103 cases of toxic berry ingestion in children aged 9 months to 5 years, with children who swallowed six or fewer berries of holly, yew, or nightshade. Investigators compared home observation alone versus ipecac administration with home observation. Every patient treated with ipecac had emesis at home with increased sedation and diarrhea, while there was no emesis in the group with home observation alone.⁷ These results suggest the symptoms were due to the ipecac rather than plant toxicity.⁷ Thus, ipecac is not recommended, and patients should be treated symptomatically.

Bittersweet and Jerusalem Cherry

Bittersweet, also known as the woody nightshade, and Jerusalem cherry, or Christmas orange, are the most dangerous of the holiday plants. While there is little evidence to support serious toxicity to adults, ingestion may be dangerous to children. Bittersweet has purple and yellow flowers, spreading petals, and red, ovoid berries.⁴ Both plants are part of the genus Solanum. In both plants, the immature fruit is more poisonous than ripened fruit due to the glycoalkaloid solanine via hypothetical alteration of mitochondrial potassium and calcium transport.⁴ Case reports document the rare anticholinergic effects of these plants, likely due to dulcamarine.⁴

The largest case series included 319 ingestions of bittersweet or Jerusalem cherry.⁴ Of these, 295 patients were under age 10 years, and only nine experienced solanine-related symptoms; none required hospitalization.⁴ The symptoms of ingestion were primarily nausea and vomiting and abdominal cramping, possibly due to anticholinergic effects. Symptoms typically occur several hours after ingestion and may last for days.

Historically, induced emesis was recommended for ingestion in children, but this is no longer recommended. Prolonged observation may be necessary for children in the setting of high likelihood of ingestion. Management includes rehydration with intravenous (IV) fluids, antiemetics, and physostigmine if clinically warranted.⁴

Mistletoe

Mistletoe, a perennial with white or translucent berries, has traditionally been associated with kissing, fertility, and vitality. The American mistletoe is known as Phoradendron serotinum and the European mistletoe as Viscum album. Both the American and European mistletoe contain the toxalbumins phoratoxin and viscotoxin, which are associated with inhibiting cellular synthesis, thereby affecting cells with rapid turnover, including the GI mucosa.⁴

After several hours, clinical effects are primarily GI upset with potential sloughing of portions of the intestinal tract.⁴ Bradycardia, delirium, and hepatic, central nervous system, kidney, and adrenal gland toxicities can also occur.⁸ The American species has a lower toxicity compared to the European species. Cases involving death likely related to P serotinum usually occur due to excessive, concentrated herbal use, such as brewing mistletoe in tea.⁹ Placing the plant in hot water may result in larger amounts of ingested toxin. The only two reported deaths from ingestion of mistletoe were in patients who consumed brewed teas.⁴

A case review of 14 patients with American mistletoe leaf or berry ingestions failed to find any toxic symptoms.⁴ Krenzelok et al¹⁰ compiled the largest case review of 1,754 exposures from 1985 to 1992. In this review, patient outcomes were good. There were no fatalities, and 99% of patients experienced no morbidity. Outcomes were not influenced by GI decontamination.¹⁰

Another study by Spiller et al¹¹ described 92 American mistletoe exposures involving ingestions of up to 20 berries and five leaves. In cases where five or more berries were consumed, none of the patients had symptoms.¹¹ Three of the 11 patients (27%) who swallowed one to five leaves developed GI upset. One child had a seizure, likely not related to the mistletoe. The study concluded that severe toxic symptoms are uncommon.¹¹

Management in the ED should involve supportive care for dehydration and vomiting, typically IV rehydration with normal saline or Ringer’s lactate and IV antiemetics. According to multiple case reviews, GI decontamination is not believed to alter patient outcome and is not recommended.⁴ An observation period of 6 hours is reasonable.^4,10,11

Christmas Cactus

Christmas cactus is an old-time favorite. It is made of arching, drooping branches and spineless joints. Christmas cactus is essentially nontoxic, and patients and family can be reassured of its safety.

Holiday Decorations

Artificial Snow

Fake snow sprays, powders, and granules are popular decorative additions used in holiday games and celebrations. The “snow” typically consists of a polymer of sodium polyacrylate, both of which can cause injury to the eyes. Repeatedly inhaling the aerosol spray can cause breathing problems, especially in patients who have asthma or other underlying bronchospastic disease.

Devastating outcomes may occur from ocular alkaline injury. When mixed with water, the fake snow absorbs the water and expands as a gel material that may stick to the ocular surface, resulting in a change in pH and osmolarity.¹² A case report by Al-Amry and Al-Ghadeer¹² recently described a 7-year-old boy with corneal epitheliopathy due to a chemical burn injury following ocular contact with fake snow.The case was later managed with multiple debridements over 3 days, topical antibiotics, and bandage contact lenses. The child had complete resolution at 1 week follow-up.¹²

Some fake snow-product sprays contain acetone or methylene chloride, which is harmful when inhaled and can cause nausea, lightheadedness, and headache.¹³ Methylene chloride can be metabolized to carbon monoxide, but the quantity required for such an exposure is unknown and has not been reported in this context. Emergency physicians should consider ordering carboxyhemoglobin levels in symptomatic patients.

Tinsel

Tinsel, which gets its name from the Old French word “estincele,” translated as sparkle, used to be made of actual silver, and was affordable only for wealthy individuals. However, in the early 1900s, manufacturers began to make tinsel from metals such as aluminum and copper. These materials did not tarnish and could be reused annually. However, during World War I, copper became difficult to buy, while aluminum proved to be flammable and dangerous. Thus, manufacturers began to produce tinsel from lead. Tinsel was made with lead until the 1970s, when the US Food and Drug Administration realized the toxic risks of lead exposure, especially in young children. Today, tinsel is made of plastic; though a poor imitation of the previous tinsel, it is relatively harmless.¹⁴

Angel Hair

Angel hair is finely spun glass that can be irritating to the skin, eyes, and throat, especially if swallowed.¹³ The greatest danger is airway obstruction if a patient attempts to eat the angel hair and it becomes lodged in the oropharynx. For contact irritation, thoroughly washing and irrigating affected areas are recommended.

Snow Globes

Snow globes are popular holiday decorations that are available in a range of sizes. While the majority of globes made in the United States are filled with water, those manufactured overseas many contain a small amount of ethylene glycol (EG) (ie, antifreeze) to prevent freezing and breakage during shipping. Fortunately, the amount of EG is not usually sufficient to cause symptoms if ingested. For globes made in the United States, the water can be contaminated with bacteria, and drinking it can cause GI upset. The snow in these globes is typically made of inert material and does not cause toxicity. If a child does exhibit symptoms after ingesting any portion of a snow globe, parents are advised to call their local poison center.

Ethanol

While alcohol is not unique to the holiday season, its availability and use are more pronounced during this time of year, and the incidence of alcohol poisoning increases during the holiday season. Some traditional holiday drinks containing alcohol, such as egg nog, can entice young children. Children may often imitate adults and drink from partially filled leftover glasses.

Therefore, families with young children must ensure that all alcoholic beverages are placed out of children’s reach.

A common presentation of alcohol poisoning is seen in the child who is brought to the ED by parents concerned because their child is acting strangely. On examination, the child may appear dazed and have tachycardia, tachypnea, and hypotension, depending on the amount of alcohol ingested. Hypoglycemia in an alcohol-intoxicated pediatric patient is a concern, but it appears the effects of alcohol on glucose regulation in infants is unpredictable.¹⁵

Intravenous access should be obtained in any patient presenting with altered mental status, and rapid blood glucose level determined. Blood samples should be sent to assess ethanol concentration. Other laboratory and imaging studies should be obtained as clinically indicated, including electrolytes, serum osmolality, acetaminophen level, urine drug screen, X-ray, and computed tomography scan of the head. Treatment of respiratory depression, hypoglycemia, hypovolemia, and hypothermia are the key interventions to ensure good outcomes.¹⁶ Supportive care is the mainstay of therapy for pediatric patients, who rarely require thiamine supplementation.¹⁶ Medical evaluation is recommended for all symptomatic children; hourly observation for 6 hours is recommended for asymptomatic children.¹⁷

Alcohol is also associated with cardiac arrhythmias. Alcohol-induced atrial arrhythmias, most commonly atrial fibrillation (AF), are referred to as “holiday heart syndrome.” This should be considered early in the differential diagnosis of new-onset AF in young adults. Consuming massive quantities of alcohol or binge drinking can also result in metabolic and electrolyte alterations. Treatment includes rehydration with IV fluids, electrolyte replacement, and IV diltiazem or cardioversion for AF with rapid ventricular response.¹⁸

Conclusion

During the holiday season, it is easy to overlook the fact that some of the most unsuspecting items in the home can pose real hazards (Table). In addition, many holiday plants are used as table decorations, which can confuse small children, who may assume the colorful berries must be edible if they are on the dining room table.

It is vital that patients, parents, and physicians know what to do when someone ingests a potential toxin. Parents often try to induce vomiting, but ipecac and other forms of gastric emptying are no longer recommended.⁶ Instead, the recommended action is to separate the patient from the plant, remove plant material that may cause a sensitivity reaction, and consult a poison control center, which can save unnecessary interventions—including an ED visit.⁶

Fortunately, most holiday toxicities are relatively nonthreatening. Holiday-related toxic ingestions primarily occur in children, and most are asymptomatic, innocuous, and treated with symptomatic care as necessary. The most poisonous holiday-related toxins are bittersweet and Jerusalem cherry. Work-ups for holiday-plant ingestions are usually limited to severe gastroenteritis, which may require IV fluids and evaluation of electrolytes.

Holiday decorations, such as artificial snow and angel hair, present hazards that should be treated on a case-by-case basis. Finally, alcohol intoxication should be considered in the differential diagnosis for pediatric patients presenting with altered mental status, or the otherwise healthy binge drinker who presents with palpitations and new-onset AF.

The holiday season, a time of warmth, joy, and good cheer, is upon us. Yet with this most wonderful time of the year comes the possibility of poisoning and hazards in the home. As emergency physicians (EPs), we must ask ourselves: Which holiday items are potentially toxic to our patients? How do we evaluate and manage poisonings that result from exposure to these items? In this article, we review several plants and decorations that are unique to the holiday season. We discuss recommendations for evaluation and management of holiday poisonings that will avoid inappropriate work-ups and interventions while increasing recognition of truly dangerous ingestions, thus help keeping the season safe and merry.

Plants

Plant exposures are the fourth most common cause for calls to poison centers.¹ In 2012, US Poison Control Centers reported more than 30,000 toxic plant exposures in children younger than age 5 years.² Not surprisingly, toxic plant ingestions occur most commonly in early childhood. The highest rate of mortality, however, takes place during the teenaged years, when suicide attempts are common.² The most common plant ingestions reported in the United States include peace lily, holly, philodendron, and poinsettia.³ These and the other frequently ingested potentially poisonous plants produce very little, if any, toxic effects. Approximately 95% of unintentional potentially toxic plant ingestions reported in the United States are managed safely at home.³

Poinsettia

The poinsettia is a large, prominent plant that was introduced to the United States in 1825 by Joel Poinsett, the US ambassador to Mexico. The poinsettia is one of the most commonly researched plants, and studies show the plant is not actually toxic.^4,5 The myth of poinsettia toxicity is a widely held, yet false, belief. The legend involves a young child of an army officer stationed in Hawaii in 1919 who reportedly died after eating poinsettia leaves.⁴ However, the reality is that the poinsettia plant was not actually involved in the child’s death. In fact, the wild plant involved in this case probably had little resemblance to the popular plant cultivated domestically in North America today.⁶

A majority of poinsettia exposures will be asymptomatic, or involve simple nausea and vomiting. Krenzelok et al⁵ reviewed 22,793 cases of poinsettia exposures from 1985 to 1992. Almost all of these exposures (98.9%) were accidental poisonings.⁵ Not surprisingly, 93.3% of poinsettia exposures involved children; most importantly, 96.1% of these patients did not require treatment at a health care facility,and there were no fatalities.⁵ Another study could not identify an LD50 (lethal dose, 50%—ie, the amount of an ingested substance that kills 50% of the test sample) in rats.⁴

The majority of patients presenting to the ED with symptoms from poinsettia exposure will have gastrointestinal (GI) upset. Most patients require only symptomatic care. Those who do present to the ED do not require gastric emptying.

Interestingly, there is a crossreactivity of poinsettia sap in latex-allergic vulnerable patients.⁶ Poinsettia is part of the same plant family as natural rubber latex, and patients can present with symptoms of contact dermatitis, especially if they have a latex allergy.⁴ Washing the area thoroughly with soap and water and avoiding future contact is all that is required for most patients with contact dermatitis.

Holly

Holly exposure accounted for the third highest rate of genus-specific human plant exposure calls to poison centers in 2010.⁴ In the United States, there are two common forms of holly: English holly and American holly. The berries of both varieties contain saponin, a toxin that can cause erythrocyte hemolysis and changes in the permeability of small intestinal mucosal cells.⁴ Most holly berry ingestions cause minor or no symptoms. The prickly leaves of the holly plant are nontoxic but consumption may result in minor injury. When symptoms do occur, they can include nausea, vomiting, abdominal cramping, and possible dermatitis.⁵ Mydriasis, hyperthermia, and drowsiness are rare but possible symptoms.⁴

For symptoms to develop, children need to have eaten only five berries, while adults reportedly must consume at least 20 to 30 berries.⁴ A study by Wax et al⁷ done at the University of Rochester reviewed 103 cases of toxic berry ingestion in children aged 9 months to 5 years, with children who swallowed six or fewer berries of holly, yew, or nightshade. Investigators compared home observation alone versus ipecac administration with home observation. Every patient treated with ipecac had emesis at home with increased sedation and diarrhea, while there was no emesis in the group with home observation alone.⁷ These results suggest the symptoms were due to the ipecac rather than plant toxicity.⁷ Thus, ipecac is not recommended, and patients should be treated symptomatically.

Bittersweet and Jerusalem Cherry

Bittersweet, also known as the woody nightshade, and Jerusalem cherry, or Christmas orange, are the most dangerous of the holiday plants. While there is little evidence to support serious toxicity to adults, ingestion may be dangerous to children. Bittersweet has purple and yellow flowers, spreading petals, and red, ovoid berries.⁴ Both plants are part of the genus Solanum. In both plants, the immature fruit is more poisonous than ripened fruit due to the glycoalkaloid solanine via hypothetical alteration of mitochondrial potassium and calcium transport.⁴ Case reports document the rare anticholinergic effects of these plants, likely due to dulcamarine.⁴

The largest case series included 319 ingestions of bittersweet or Jerusalem cherry.⁴ Of these, 295 patients were under age 10 years, and only nine experienced solanine-related symptoms; none required hospitalization.⁴ The symptoms of ingestion were primarily nausea and vomiting and abdominal cramping, possibly due to anticholinergic effects. Symptoms typically occur several hours after ingestion and may last for days.

Historically, induced emesis was recommended for ingestion in children, but this is no longer recommended. Prolonged observation may be necessary for children in the setting of high likelihood of ingestion. Management includes rehydration with intravenous (IV) fluids, antiemetics, and physostigmine if clinically warranted.⁴

Mistletoe

Mistletoe, a perennial with white or translucent berries, has traditionally been associated with kissing, fertility, and vitality. The American mistletoe is known as Phoradendron serotinum and the European mistletoe as Viscum album. Both the American and European mistletoe contain the toxalbumins phoratoxin and viscotoxin, which are associated with inhibiting cellular synthesis, thereby affecting cells with rapid turnover, including the GI mucosa.⁴

After several hours, clinical effects are primarily GI upset with potential sloughing of portions of the intestinal tract.⁴ Bradycardia, delirium, and hepatic, central nervous system, kidney, and adrenal gland toxicities can also occur.⁸ The American species has a lower toxicity compared to the European species. Cases involving death likely related to P serotinum usually occur due to excessive, concentrated herbal use, such as brewing mistletoe in tea.⁹ Placing the plant in hot water may result in larger amounts of ingested toxin. The only two reported deaths from ingestion of mistletoe were in patients who consumed brewed teas.⁴

A case review of 14 patients with American mistletoe leaf or berry ingestions failed to find any toxic symptoms.⁴ Krenzelok et al¹⁰ compiled the largest case review of 1,754 exposures from 1985 to 1992. In this review, patient outcomes were good. There were no fatalities, and 99% of patients experienced no morbidity. Outcomes were not influenced by GI decontamination.¹⁰

Another study by Spiller et al¹¹ described 92 American mistletoe exposures involving ingestions of up to 20 berries and five leaves. In cases where five or more berries were consumed, none of the patients had symptoms.¹¹ Three of the 11 patients (27%) who swallowed one to five leaves developed GI upset. One child had a seizure, likely not related to the mistletoe. The study concluded that severe toxic symptoms are uncommon.¹¹

Management in the ED should involve supportive care for dehydration and vomiting, typically IV rehydration with normal saline or Ringer’s lactate and IV antiemetics. According to multiple case reviews, GI decontamination is not believed to alter patient outcome and is not recommended.⁴ An observation period of 6 hours is reasonable.^4,10,11

Christmas Cactus

Christmas cactus is an old-time favorite. It is made of arching, drooping branches and spineless joints. Christmas cactus is essentially nontoxic, and patients and family can be reassured of its safety.

Holiday Decorations

Artificial Snow

Fake snow sprays, powders, and granules are popular decorative additions used in holiday games and celebrations. The “snow” typically consists of a polymer of sodium polyacrylate, both of which can cause injury to the eyes. Repeatedly inhaling the aerosol spray can cause breathing problems, especially in patients who have asthma or other underlying bronchospastic disease.

Devastating outcomes may occur from ocular alkaline injury. When mixed with water, the fake snow absorbs the water and expands as a gel material that may stick to the ocular surface, resulting in a change in pH and osmolarity.¹² A case report by Al-Amry and Al-Ghadeer¹² recently described a 7-year-old boy with corneal epitheliopathy due to a chemical burn injury following ocular contact with fake snow.The case was later managed with multiple debridements over 3 days, topical antibiotics, and bandage contact lenses. The child had complete resolution at 1 week follow-up.¹²

Some fake snow-product sprays contain acetone or methylene chloride, which is harmful when inhaled and can cause nausea, lightheadedness, and headache.¹³ Methylene chloride can be metabolized to carbon monoxide, but the quantity required for such an exposure is unknown and has not been reported in this context. Emergency physicians should consider ordering carboxyhemoglobin levels in symptomatic patients.

Tinsel

Tinsel, which gets its name from the Old French word “estincele,” translated as sparkle, used to be made of actual silver, and was affordable only for wealthy individuals. However, in the early 1900s, manufacturers began to make tinsel from metals such as aluminum and copper. These materials did not tarnish and could be reused annually. However, during World War I, copper became difficult to buy, while aluminum proved to be flammable and dangerous. Thus, manufacturers began to produce tinsel from lead. Tinsel was made with lead until the 1970s, when the US Food and Drug Administration realized the toxic risks of lead exposure, especially in young children. Today, tinsel is made of plastic; though a poor imitation of the previous tinsel, it is relatively harmless.¹⁴

Angel Hair

Angel hair is finely spun glass that can be irritating to the skin, eyes, and throat, especially if swallowed.¹³ The greatest danger is airway obstruction if a patient attempts to eat the angel hair and it becomes lodged in the oropharynx. For contact irritation, thoroughly washing and irrigating affected areas are recommended.

Snow Globes

Snow globes are popular holiday decorations that are available in a range of sizes. While the majority of globes made in the United States are filled with water, those manufactured overseas many contain a small amount of ethylene glycol (EG) (ie, antifreeze) to prevent freezing and breakage during shipping. Fortunately, the amount of EG is not usually sufficient to cause symptoms if ingested. For globes made in the United States, the water can be contaminated with bacteria, and drinking it can cause GI upset. The snow in these globes is typically made of inert material and does not cause toxicity. If a child does exhibit symptoms after ingesting any portion of a snow globe, parents are advised to call their local poison center.

Ethanol

While alcohol is not unique to the holiday season, its availability and use are more pronounced during this time of year, and the incidence of alcohol poisoning increases during the holiday season. Some traditional holiday drinks containing alcohol, such as egg nog, can entice young children. Children may often imitate adults and drink from partially filled leftover glasses.

Therefore, families with young children must ensure that all alcoholic beverages are placed out of children’s reach.

A common presentation of alcohol poisoning is seen in the child who is brought to the ED by parents concerned because their child is acting strangely. On examination, the child may appear dazed and have tachycardia, tachypnea, and hypotension, depending on the amount of alcohol ingested. Hypoglycemia in an alcohol-intoxicated pediatric patient is a concern, but it appears the effects of alcohol on glucose regulation in infants is unpredictable.¹⁵

Intravenous access should be obtained in any patient presenting with altered mental status, and rapid blood glucose level determined. Blood samples should be sent to assess ethanol concentration. Other laboratory and imaging studies should be obtained as clinically indicated, including electrolytes, serum osmolality, acetaminophen level, urine drug screen, X-ray, and computed tomography scan of the head. Treatment of respiratory depression, hypoglycemia, hypovolemia, and hypothermia are the key interventions to ensure good outcomes.¹⁶ Supportive care is the mainstay of therapy for pediatric patients, who rarely require thiamine supplementation.¹⁶ Medical evaluation is recommended for all symptomatic children; hourly observation for 6 hours is recommended for asymptomatic children.¹⁷

Alcohol is also associated with cardiac arrhythmias. Alcohol-induced atrial arrhythmias, most commonly atrial fibrillation (AF), are referred to as “holiday heart syndrome.” This should be considered early in the differential diagnosis of new-onset AF in young adults. Consuming massive quantities of alcohol or binge drinking can also result in metabolic and electrolyte alterations. Treatment includes rehydration with IV fluids, electrolyte replacement, and IV diltiazem or cardioversion for AF with rapid ventricular response.¹⁸

Conclusion

During the holiday season, it is easy to overlook the fact that some of the most unsuspecting items in the home can pose real hazards (Table). In addition, many holiday plants are used as table decorations, which can confuse small children, who may assume the colorful berries must be edible if they are on the dining room table.

It is vital that patients, parents, and physicians know what to do when someone ingests a potential toxin. Parents often try to induce vomiting, but ipecac and other forms of gastric emptying are no longer recommended.⁶ Instead, the recommended action is to separate the patient from the plant, remove plant material that may cause a sensitivity reaction, and consult a poison control center, which can save unnecessary interventions—including an ED visit.⁶

Fortunately, most holiday toxicities are relatively nonthreatening. Holiday-related toxic ingestions primarily occur in children, and most are asymptomatic, innocuous, and treated with symptomatic care as necessary. The most poisonous holiday-related toxins are bittersweet and Jerusalem cherry. Work-ups for holiday-plant ingestions are usually limited to severe gastroenteritis, which may require IV fluids and evaluation of electrolytes.

Holiday decorations, such as artificial snow and angel hair, present hazards that should be treated on a case-by-case basis. Finally, alcohol intoxication should be considered in the differential diagnosis for pediatric patients presenting with altered mental status, or the otherwise healthy binge drinker who presents with palpitations and new-onset AF.

The holiday season, a time of warmth, joy, and good cheer, is upon us. Yet with this most wonderful time of the year comes the possibility of poisoning and hazards in the home. As emergency physicians (EPs), we must ask ourselves: Which holiday items are potentially toxic to our patients? How do we evaluate and manage poisonings that result from exposure to these items? In this article, we review several plants and decorations that are unique to the holiday season. We discuss recommendations for evaluation and management of holiday poisonings that will avoid inappropriate work-ups and interventions while increasing recognition of truly dangerous ingestions, thus help keeping the season safe and merry.

Plants

Plant exposures are the fourth most common cause for calls to poison centers.¹ In 2012, US Poison Control Centers reported more than 30,000 toxic plant exposures in children younger than age 5 years.² Not surprisingly, toxic plant ingestions occur most commonly in early childhood. The highest rate of mortality, however, takes place during the teenaged years, when suicide attempts are common.² The most common plant ingestions reported in the United States include peace lily, holly, philodendron, and poinsettia.³ These and the other frequently ingested potentially poisonous plants produce very little, if any, toxic effects. Approximately 95% of unintentional potentially toxic plant ingestions reported in the United States are managed safely at home.³

Poinsettia

The poinsettia is a large, prominent plant that was introduced to the United States in 1825 by Joel Poinsett, the US ambassador to Mexico. The poinsettia is one of the most commonly researched plants, and studies show the plant is not actually toxic.^4,5 The myth of poinsettia toxicity is a widely held, yet false, belief. The legend involves a young child of an army officer stationed in Hawaii in 1919 who reportedly died after eating poinsettia leaves.⁴ However, the reality is that the poinsettia plant was not actually involved in the child’s death. In fact, the wild plant involved in this case probably had little resemblance to the popular plant cultivated domestically in North America today.⁶

A majority of poinsettia exposures will be asymptomatic, or involve simple nausea and vomiting. Krenzelok et al⁵ reviewed 22,793 cases of poinsettia exposures from 1985 to 1992. Almost all of these exposures (98.9%) were accidental poisonings.⁵ Not surprisingly, 93.3% of poinsettia exposures involved children; most importantly, 96.1% of these patients did not require treatment at a health care facility,and there were no fatalities.⁵ Another study could not identify an LD50 (lethal dose, 50%—ie, the amount of an ingested substance that kills 50% of the test sample) in rats.⁴

The majority of patients presenting to the ED with symptoms from poinsettia exposure will have gastrointestinal (GI) upset. Most patients require only symptomatic care. Those who do present to the ED do not require gastric emptying.

Interestingly, there is a crossreactivity of poinsettia sap in latex-allergic vulnerable patients.⁶ Poinsettia is part of the same plant family as natural rubber latex, and patients can present with symptoms of contact dermatitis, especially if they have a latex allergy.⁴ Washing the area thoroughly with soap and water and avoiding future contact is all that is required for most patients with contact dermatitis.

Holly

Holly exposure accounted for the third highest rate of genus-specific human plant exposure calls to poison centers in 2010.⁴ In the United States, there are two common forms of holly: English holly and American holly. The berries of both varieties contain saponin, a toxin that can cause erythrocyte hemolysis and changes in the permeability of small intestinal mucosal cells.⁴ Most holly berry ingestions cause minor or no symptoms. The prickly leaves of the holly plant are nontoxic but consumption may result in minor injury. When symptoms do occur, they can include nausea, vomiting, abdominal cramping, and possible dermatitis.⁵ Mydriasis, hyperthermia, and drowsiness are rare but possible symptoms.⁴

For symptoms to develop, children need to have eaten only five berries, while adults reportedly must consume at least 20 to 30 berries.⁴ A study by Wax et al⁷ done at the University of Rochester reviewed 103 cases of toxic berry ingestion in children aged 9 months to 5 years, with children who swallowed six or fewer berries of holly, yew, or nightshade. Investigators compared home observation alone versus ipecac administration with home observation. Every patient treated with ipecac had emesis at home with increased sedation and diarrhea, while there was no emesis in the group with home observation alone.⁷ These results suggest the symptoms were due to the ipecac rather than plant toxicity.⁷ Thus, ipecac is not recommended, and patients should be treated symptomatically.

Bittersweet and Jerusalem Cherry

Bittersweet, also known as the woody nightshade, and Jerusalem cherry, or Christmas orange, are the most dangerous of the holiday plants. While there is little evidence to support serious toxicity to adults, ingestion may be dangerous to children. Bittersweet has purple and yellow flowers, spreading petals, and red, ovoid berries.⁴ Both plants are part of the genus Solanum. In both plants, the immature fruit is more poisonous than ripened fruit due to the glycoalkaloid solanine via hypothetical alteration of mitochondrial potassium and calcium transport.⁴ Case reports document the rare anticholinergic effects of these plants, likely due to dulcamarine.⁴

The largest case series included 319 ingestions of bittersweet or Jerusalem cherry.⁴ Of these, 295 patients were under age 10 years, and only nine experienced solanine-related symptoms; none required hospitalization.⁴ The symptoms of ingestion were primarily nausea and vomiting and abdominal cramping, possibly due to anticholinergic effects. Symptoms typically occur several hours after ingestion and may last for days.

Historically, induced emesis was recommended for ingestion in children, but this is no longer recommended. Prolonged observation may be necessary for children in the setting of high likelihood of ingestion. Management includes rehydration with intravenous (IV) fluids, antiemetics, and physostigmine if clinically warranted.⁴

Mistletoe

Mistletoe, a perennial with white or translucent berries, has traditionally been associated with kissing, fertility, and vitality. The American mistletoe is known as Phoradendron serotinum and the European mistletoe as Viscum album. Both the American and European mistletoe contain the toxalbumins phoratoxin and viscotoxin, which are associated with inhibiting cellular synthesis, thereby affecting cells with rapid turnover, including the GI mucosa.⁴

After several hours, clinical effects are primarily GI upset with potential sloughing of portions of the intestinal tract.⁴ Bradycardia, delirium, and hepatic, central nervous system, kidney, and adrenal gland toxicities can also occur.⁸ The American species has a lower toxicity compared to the European species. Cases involving death likely related to P serotinum usually occur due to excessive, concentrated herbal use, such as brewing mistletoe in tea.⁹ Placing the plant in hot water may result in larger amounts of ingested toxin. The only two reported deaths from ingestion of mistletoe were in patients who consumed brewed teas.⁴

A case review of 14 patients with American mistletoe leaf or berry ingestions failed to find any toxic symptoms.⁴ Krenzelok et al¹⁰ compiled the largest case review of 1,754 exposures from 1985 to 1992. In this review, patient outcomes were good. There were no fatalities, and 99% of patients experienced no morbidity. Outcomes were not influenced by GI decontamination.¹⁰

Another study by Spiller et al¹¹ described 92 American mistletoe exposures involving ingestions of up to 20 berries and five leaves. In cases where five or more berries were consumed, none of the patients had symptoms.¹¹ Three of the 11 patients (27%) who swallowed one to five leaves developed GI upset. One child had a seizure, likely not related to the mistletoe. The study concluded that severe toxic symptoms are uncommon.¹¹

Management in the ED should involve supportive care for dehydration and vomiting, typically IV rehydration with normal saline or Ringer’s lactate and IV antiemetics. According to multiple case reviews, GI decontamination is not believed to alter patient outcome and is not recommended.⁴ An observation period of 6 hours is reasonable.^4,10,11

Christmas Cactus

Christmas cactus is an old-time favorite. It is made of arching, drooping branches and spineless joints. Christmas cactus is essentially nontoxic, and patients and family can be reassured of its safety.

Holiday Decorations

Artificial Snow

Fake snow sprays, powders, and granules are popular decorative additions used in holiday games and celebrations. The “snow” typically consists of a polymer of sodium polyacrylate, both of which can cause injury to the eyes. Repeatedly inhaling the aerosol spray can cause breathing problems, especially in patients who have asthma or other underlying bronchospastic disease.

Devastating outcomes may occur from ocular alkaline injury. When mixed with water, the fake snow absorbs the water and expands as a gel material that may stick to the ocular surface, resulting in a change in pH and osmolarity.¹² A case report by Al-Amry and Al-Ghadeer¹² recently described a 7-year-old boy with corneal epitheliopathy due to a chemical burn injury following ocular contact with fake snow.The case was later managed with multiple debridements over 3 days, topical antibiotics, and bandage contact lenses. The child had complete resolution at 1 week follow-up.¹²

Some fake snow-product sprays contain acetone or methylene chloride, which is harmful when inhaled and can cause nausea, lightheadedness, and headache.¹³ Methylene chloride can be metabolized to carbon monoxide, but the quantity required for such an exposure is unknown and has not been reported in this context. Emergency physicians should consider ordering carboxyhemoglobin levels in symptomatic patients.

Tinsel

Tinsel, which gets its name from the Old French word “estincele,” translated as sparkle, used to be made of actual silver, and was affordable only for wealthy individuals. However, in the early 1900s, manufacturers began to make tinsel from metals such as aluminum and copper. These materials did not tarnish and could be reused annually. However, during World War I, copper became difficult to buy, while aluminum proved to be flammable and dangerous. Thus, manufacturers began to produce tinsel from lead. Tinsel was made with lead until the 1970s, when the US Food and Drug Administration realized the toxic risks of lead exposure, especially in young children. Today, tinsel is made of plastic; though a poor imitation of the previous tinsel, it is relatively harmless.¹⁴

Angel Hair

Angel hair is finely spun glass that can be irritating to the skin, eyes, and throat, especially if swallowed.¹³ The greatest danger is airway obstruction if a patient attempts to eat the angel hair and it becomes lodged in the oropharynx. For contact irritation, thoroughly washing and irrigating affected areas are recommended.

Snow Globes

Snow globes are popular holiday decorations that are available in a range of sizes. While the majority of globes made in the United States are filled with water, those manufactured overseas many contain a small amount of ethylene glycol (EG) (ie, antifreeze) to prevent freezing and breakage during shipping. Fortunately, the amount of EG is not usually sufficient to cause symptoms if ingested. For globes made in the United States, the water can be contaminated with bacteria, and drinking it can cause GI upset. The snow in these globes is typically made of inert material and does not cause toxicity. If a child does exhibit symptoms after ingesting any portion of a snow globe, parents are advised to call their local poison center.

Ethanol

While alcohol is not unique to the holiday season, its availability and use are more pronounced during this time of year, and the incidence of alcohol poisoning increases during the holiday season. Some traditional holiday drinks containing alcohol, such as egg nog, can entice young children. Children may often imitate adults and drink from partially filled leftover glasses.

Therefore, families with young children must ensure that all alcoholic beverages are placed out of children’s reach.

A common presentation of alcohol poisoning is seen in the child who is brought to the ED by parents concerned because their child is acting strangely. On examination, the child may appear dazed and have tachycardia, tachypnea, and hypotension, depending on the amount of alcohol ingested. Hypoglycemia in an alcohol-intoxicated pediatric patient is a concern, but it appears the effects of alcohol on glucose regulation in infants is unpredictable.¹⁵

Intravenous access should be obtained in any patient presenting with altered mental status, and rapid blood glucose level determined. Blood samples should be sent to assess ethanol concentration. Other laboratory and imaging studies should be obtained as clinically indicated, including electrolytes, serum osmolality, acetaminophen level, urine drug screen, X-ray, and computed tomography scan of the head. Treatment of respiratory depression, hypoglycemia, hypovolemia, and hypothermia are the key interventions to ensure good outcomes.¹⁶ Supportive care is the mainstay of therapy for pediatric patients, who rarely require thiamine supplementation.¹⁶ Medical evaluation is recommended for all symptomatic children; hourly observation for 6 hours is recommended for asymptomatic children.¹⁷

Alcohol is also associated with cardiac arrhythmias. Alcohol-induced atrial arrhythmias, most commonly atrial fibrillation (AF), are referred to as “holiday heart syndrome.” This should be considered early in the differential diagnosis of new-onset AF in young adults. Consuming massive quantities of alcohol or binge drinking can also result in metabolic and electrolyte alterations. Treatment includes rehydration with IV fluids, electrolyte replacement, and IV diltiazem or cardioversion for AF with rapid ventricular response.¹⁸

Conclusion

During the holiday season, it is easy to overlook the fact that some of the most unsuspecting items in the home can pose real hazards (Table). In addition, many holiday plants are used as table decorations, which can confuse small children, who may assume the colorful berries must be edible if they are on the dining room table.

It is vital that patients, parents, and physicians know what to do when someone ingests a potential toxin. Parents often try to induce vomiting, but ipecac and other forms of gastric emptying are no longer recommended.⁶ Instead, the recommended action is to separate the patient from the plant, remove plant material that may cause a sensitivity reaction, and consult a poison control center, which can save unnecessary interventions—including an ED visit.⁶

Fortunately, most holiday toxicities are relatively nonthreatening. Holiday-related toxic ingestions primarily occur in children, and most are asymptomatic, innocuous, and treated with symptomatic care as necessary. The most poisonous holiday-related toxins are bittersweet and Jerusalem cherry. Work-ups for holiday-plant ingestions are usually limited to severe gastroenteritis, which may require IV fluids and evaluation of electrolytes.

Holiday decorations, such as artificial snow and angel hair, present hazards that should be treated on a case-by-case basis. Finally, alcohol intoxication should be considered in the differential diagnosis for pediatric patients presenting with altered mental status, or the otherwise healthy binge drinker who presents with palpitations and new-onset AF.

Case

A 68-year-old woman presented to the ED 5 days after receiving onabotulinumtoxinA cosmetic injections for wrinkles of the face and neck. She stated that she was unable to raise her head while in a supine position and that her head felt heavy when standing. She also experienced spasms and strain of the posterior cervical neck muscles. In addition, the patient described a constant need to swallow forcefully throughout the day, and felt an intermittent heavy sensation over her larynx that was associated with stridor. She noted these symptoms began 5 days after the onabotulinumtoxinA injections and had peaked 2 days prior to presentation. She also complained of dysphagia without odynophagia, but denied any changes in her voice.

The patient first began onabotulinumtoxinA injections 12 years earlier for aesthetic treatment of glabellar and peri-orbital wrinkles. She initially received the injections at a regular interval of 90 to 100 days. During the course of the first 2 years of treatment, the patient was under the care of a plastic surgeon; thereafter, she sought treatment at a physician-owned medical spa because it offered onabotulinumtoxinA at a lower price. The injections at the medical spa were administered by a physician assistant (PA). The patient stated that although the PA had steadily increased the dose of onabotulinumtoxinA to maintain the desired aesthetic effect, this was the first time she had experienced any side effects from the treatment.

The ED staff contacted the medical spa provider, who reviewed the patient’s medical record over the telephone. The PA stated that he had been the only practitioner at the facility to administer the onabotulinumtoxinA injections to the patient over her past 10 years there as a client. He further informed the emergency physician (EP) that 12 days prior to presentation, he had given the patient a total of 50 IU of onabotulinumtoxinA, in five separate injections, into the mid frontalis muscle; a total of 35 IU, in seven separate injections, into the glabellar region (procerus and corrugator muscles bilaterally); 20 IU into the lateral and inferior-lateral orbicularis oculi bilaterally, in four separate injections per side, (40 IU total); and a total of 100 IU in the anterior platysma, in 20 separate injections, for a total 1-day onabotulinumtoxinA dose of 225 IU.

The PA explained to the EP that he mixed the onabotulinumtoxinA in the patient’s room and had shown her the vials and dilution standard as recommended by the manufacturer because she had been requiring increased dosages and had previously questioned whether the onabotulinumtoxinA was diluted. The PA denied any other patients experiencing similar adverse events as those of the patient’s.

Over the last 10 years, the patient had received onabotulinumtoxinA in the nasolabial folds, upper and lower lip wrinkles, mentalis, depressor angular oris, buccal, nasalis, lateral brow, masseter, and calf muscles. The dosage of onabotulinumtoxinA at this most recent injection cycle was unchanged from her previous visit 3 months prior. According to the PA, the practice did not use abobotulinumtoxinA or incobotulinumtoxinA.

Regarding the patient’s medical history, she had no health issues suggestive of myasthenia gravis, multiple sclerosis, or Guillain-Barré syndrome. Examination of the face revealed decreased muscle excursion of the frontalis muscle from mid-brow to mid-brow, and stair-step wrinkle formation bilaterally. The procerus muscle was very weak, and the corrugator muscles were moderately diminished in strength. The lateral orbicularis oculi were very weak at each canthus. The extra-ocular muscles were intact. She had full mandibular excursion, and powerful movement of the tongue. The oropharynx and floor of the mouth were normal. She was noted to purposefully swallow and extend her neck every 90 to 120 seconds to “clear her throat,” though she did not drool and was able to handle her secretions and swallow fluids without aspiration. Her voice was normal and she was able to recite the letters “KKKKK,” “OOOOO,” and “EEEEE” in rapid fashion without breathiness or stridor. The rest of her facial muscles were normal.

While supine, the patient strained to lift her head and complained of a suffocating sensation over the larynx. She had no rashes or edema, and the remainder of the physical examination, vital signs, and pulse oximetry were normal. Laboratory evaluation, which included a complete blood count and serum electrolytes, was also normal.

An otolaryngologist consultation for laryngoscopy was obtained. After reviewing the patient’s case, the otolaryngologist concluded that given the patient’s history, intermittent stridor, and an absence of signs or symptoms suggestive of an impending upper airway obstruction (UAO), laryngoscopy was not warranted.

A plastic surgery consultation was then obtained. The patient’s examination was as noted above, and her vital signs and pulse oximetry remained normal throughout her ED stay. Although botulinum and botulinum antibody titers were ordered, the patient refused testing due to cost concerns. She was discharged home by plastic surgery services with a diagnosis of floppy neck and dysphagia secondary to aesthetic botulinum toxin paralysis of the bilateral sternocleidomastoid muscles and platysma. She was given a prescription for metoclopramide hydrochloride to stimulate motility of the upper gastrointestinal tract and to potentially improve swallowing.¹⁰

The patient was scheduled for a follow-up evaluation with the plastic surgeon 2 days after discharge. She was instructed to call 911 if she experienced stridor, shortness of breath, drooling, or if any airway issues arose. The patient did not return for her follow-up appointment with the plastic surgeon.

Discussion

Clostridium Botulinum Toxins

Clostridium botulinum is a gram-positive spore-forming anaerobic bacterium that produces extremely potent neuro-exotoxins. C botulinum is found in soil, contaminated foods, and in illicit injectable drugs (eg, heroin). Seven distinct antigenic botulinum toxins (A, B, C1, D, E, F, and G) are produced by several strains of C botulinum. Systemically, each neurotoxin is able to produce severe morbidity and mortality by causing generalized muscle paralysis and death by respiratory failure. The lethal dose of these agents is approximating 10(-9) g/kg body weight. Botulinum toxin type A is the most potent.^1,2

Nonetheless, botulinum toxin has been used clinically since the early 1970s. Currently, there are three FDA-approved botulinum toxin type A agents and one type B formulation (rimabotulinumtoxinB) (Table). Each formulation is unique, proprietary, and differs in molecular weight, toxin-complex size, protein content, and inactive ingredients. The effectiveness and adverse event profile for these four botulinum toxins is individually dependent upon the different dilutions and potency, onset of action, duration of effect, diffusion, and migration potential. Hence, the effective dose of one botulinum toxin does not equate to any other, resulting in a lack of interchangeability between botulinum toxins (eg, 5 IU of incobotulinumtoxinA does not equal 5 IU of onabotulinumtoxinA).

Aesthetic Indications

Historically, the use of botulinum toxin for aesthetic treatment of wrinkles and platysmal bands was first reported by Blitzer³ in 1993.Subsequently, the use of botulinum toxin for the aesthetic treatment of facial wrinkles, hypertrophic platysmal bands and horizontal neck lines gained popularity within the public and medical community.^3-5

Anatomically, the platysma is a thin sheet-like muscle that originates in the superior fascia of the pectoralis and deltoid fascia, and extends over the full length of the neck up past the mandible and continuing into the submuscular aponeurotic system. The platysma is innervated by the seventh cranial nerve and functions to pull the jaw downward. The platysma muscle is attached directly to the skin. With normal aging, the anterior neck skin becomes flaccid, the central platysmal bands thicken and contract—forming bands, horizontal wrinkles, and loss of definition of the neck noticed at rest and with contraction of the platysma muscle. These vertical bands are known as platysmal bands. The platysmal bands are benign consequences of aging and as such are targets of correction through surgery or botulinum toxin injection.^6,7

Mechanism of Action

Platysmal band and horizontal line injection techniques with botulinum toxin have been reported in the literature with dosages ranging from 15 IU to 200 IU used to block the Soluble N-ethylmaleimide-sensitive factor activating protein receptors. Typical onset of action begins at 3 days, with full paralytic effect at 7 days. Repeat injections every 3 to 4 months are required with prolonged effects seen with each subsequent injection due to chemodenervation-induced muscle atrophy.^4,7,8

Adverse Effects

Commercial botulinum toxin type A has been associated with minor and transient side effects. Moderate complications seen in the neck region include transient soft-tissue edema, dermal ecchymoses, intramuscular hematoma, diffuse muscle soreness, neck flexor weakness, and headaches.^4,8,9

The use of botulinum toxin for chemodenervation of the platysma can produce significant weakness of other neck muscles, including the sternocleidomastoid, cricothyroid, sternothyroid, and sternohyoid. Floppy neck and dysphagia may be due to diffusion of the toxin into the muscles of deglutition of the larynx; injection directly into the sternocleidomastoid muscle; or a result of the systemic effects of large dosages. Hoarseness, breathiness, and dysphagia may occur 3 to 4 days after injection, especially with doses over 75 IU.¹⁰

The recommended concentration of botulinum toxin type A causes a diffusion average of 1 cm in all directions from the injection sites. However, as the dilution increases, so does the zone of diffusion. Typical discharge instructions for platysma treatment include the overuse of the neck muscles for 2 to 4 hours after injection to encourage the botulinum toxin uptake for optimal result. Site manipulation (rubbing or massaging) also increases diffusion. For botulinum toxin type B, the zone of diffusion is greater because its molecular weight is less than the type A toxins, thus making it an undesirable agent for aesthetic facial chemodenervation.^4,11

Toxin Resistance

Botulinum toxin resistance is a known complication that occurs normally as a result of the body recognizing the neurotoxin as a foreign substance and producing neutralizing antibodies (NAb). Primary botulinum toxin failure is known in patients who require high doses of the neurotoxin for treatment of neuromuscular disorders.¹² Complete secondary therapy failure is known to occur in cosmetic patients after a single dose and those who have been receiving low-dose botulinum toxin regularly. The risk of NAb development increases with long-term treatment and high doses.^12-18

Floppy Neck and Dysphagia

As previously noted, floppy neck and dysphagia are adverse clinical findings of botulinum toxin effect on the platysma, sternocleidomastoid, or the paralaryngeal muscles. In this case, the patient was fortunate to have only sustained weakness of the platysma and sternocleidomastoid muscles despite both a large neck and total body dose. Paralaryngeal muscle paralysis is not life-threatening, but the distress may precipitate paradoxical vocal cord motion and stridor.

Stridor

Stridor is typically a symptom of an upper airway obstruction (UAO) process. Typical UAO conditions encountered in the ED are infections (eg, epiglottitis, croup), foreign body, allergy, and laryngeal trauma. The age of the patient, onset of stridor, course of the stridor (ie, intermittent, continuous, worsening), associated symptoms (eg, fever, rash, swelling of oral soft tissues), and bruising must be ascertained.

In differentiating the etiology of stridor, the EP should observe the patient for any associated change in voice, inability to handle secretions, and position of comfort. Patients with stridor require admission and evaluation by an otolaryngologist as expeditiously as possible because impending UAO may quickly progress to complete UAO necessitating emergent intubation.

An atypical presentation of stridor to the ED is sporadic stridor. Sporadic attacks of stridor during activity have been associated with the entity of paradoxical vocal cord motion. Patients usually describe a choking sensation with inability to breathe resulting in an audible inspiratory and/or expiratory sound—ie, stridor. Wheezing may or may not be present. Patients may also describe tightness in the neck and sometimes in the chest. The attacks are usually seconds to minutes in duration. More often, there is a precipitating or an inducing factor such as hyperventilation, cough, panting, phonatory tasks, or the inhalation of irritants or perfume, or an oropharyngeal or laryngeal manipulation prior or postextubation. The feeling of stress alone is commonly reported prior to the attacks. When evaluating patients presenting with floppy neck, dysphagia, and stridor, it is imperative that the clinician conduct a thorough history and physical examination to determine if the symptoms are secondary to a systemic or local effect, and whether the patient will progress to an acute UAO (vocal cord paralysis) necessitating intubation in the ED and subsequent tracheostomy.^19,20

Conclusion

The ready availability of botulinum toxins and their low-cost-benefit ratio continue to promote over-utilization for treatment of facial wrinkles, platysmal bands, and horizontal lines; migraine headache; and hyperhidrosis. Complications associated with overuse of botulinum toxins are due to either administration of a large single dose or from regional diffusion. With the increasing number of patients receiving botulinum injections, EPs should be aware of the four available toxin types onset of action, adverse events, and potential life-threatening complications of regional neck injections.

Case

A 68-year-old woman presented to the ED 5 days after receiving onabotulinumtoxinA cosmetic injections for wrinkles of the face and neck. She stated that she was unable to raise her head while in a supine position and that her head felt heavy when standing. She also experienced spasms and strain of the posterior cervical neck muscles. In addition, the patient described a constant need to swallow forcefully throughout the day, and felt an intermittent heavy sensation over her larynx that was associated with stridor. She noted these symptoms began 5 days after the onabotulinumtoxinA injections and had peaked 2 days prior to presentation. She also complained of dysphagia without odynophagia, but denied any changes in her voice.

The patient first began onabotulinumtoxinA injections 12 years earlier for aesthetic treatment of glabellar and peri-orbital wrinkles. She initially received the injections at a regular interval of 90 to 100 days. During the course of the first 2 years of treatment, the patient was under the care of a plastic surgeon; thereafter, she sought treatment at a physician-owned medical spa because it offered onabotulinumtoxinA at a lower price. The injections at the medical spa were administered by a physician assistant (PA). The patient stated that although the PA had steadily increased the dose of onabotulinumtoxinA to maintain the desired aesthetic effect, this was the first time she had experienced any side effects from the treatment.

The ED staff contacted the medical spa provider, who reviewed the patient’s medical record over the telephone. The PA stated that he had been the only practitioner at the facility to administer the onabotulinumtoxinA injections to the patient over her past 10 years there as a client. He further informed the emergency physician (EP) that 12 days prior to presentation, he had given the patient a total of 50 IU of onabotulinumtoxinA, in five separate injections, into the mid frontalis muscle; a total of 35 IU, in seven separate injections, into the glabellar region (procerus and corrugator muscles bilaterally); 20 IU into the lateral and inferior-lateral orbicularis oculi bilaterally, in four separate injections per side, (40 IU total); and a total of 100 IU in the anterior platysma, in 20 separate injections, for a total 1-day onabotulinumtoxinA dose of 225 IU.

The PA explained to the EP that he mixed the onabotulinumtoxinA in the patient’s room and had shown her the vials and dilution standard as recommended by the manufacturer because she had been requiring increased dosages and had previously questioned whether the onabotulinumtoxinA was diluted. The PA denied any other patients experiencing similar adverse events as those of the patient’s.

Over the last 10 years, the patient had received onabotulinumtoxinA in the nasolabial folds, upper and lower lip wrinkles, mentalis, depressor angular oris, buccal, nasalis, lateral brow, masseter, and calf muscles. The dosage of onabotulinumtoxinA at this most recent injection cycle was unchanged from her previous visit 3 months prior. According to the PA, the practice did not use abobotulinumtoxinA or incobotulinumtoxinA.

Regarding the patient’s medical history, she had no health issues suggestive of myasthenia gravis, multiple sclerosis, or Guillain-Barré syndrome. Examination of the face revealed decreased muscle excursion of the frontalis muscle from mid-brow to mid-brow, and stair-step wrinkle formation bilaterally. The procerus muscle was very weak, and the corrugator muscles were moderately diminished in strength. The lateral orbicularis oculi were very weak at each canthus. The extra-ocular muscles were intact. She had full mandibular excursion, and powerful movement of the tongue. The oropharynx and floor of the mouth were normal. She was noted to purposefully swallow and extend her neck every 90 to 120 seconds to “clear her throat,” though she did not drool and was able to handle her secretions and swallow fluids without aspiration. Her voice was normal and she was able to recite the letters “KKKKK,” “OOOOO,” and “EEEEE” in rapid fashion without breathiness or stridor. The rest of her facial muscles were normal.

While supine, the patient strained to lift her head and complained of a suffocating sensation over the larynx. She had no rashes or edema, and the remainder of the physical examination, vital signs, and pulse oximetry were normal. Laboratory evaluation, which included a complete blood count and serum electrolytes, was also normal.

An otolaryngologist consultation for laryngoscopy was obtained. After reviewing the patient’s case, the otolaryngologist concluded that given the patient’s history, intermittent stridor, and an absence of signs or symptoms suggestive of an impending upper airway obstruction (UAO), laryngoscopy was not warranted.

A plastic surgery consultation was then obtained. The patient’s examination was as noted above, and her vital signs and pulse oximetry remained normal throughout her ED stay. Although botulinum and botulinum antibody titers were ordered, the patient refused testing due to cost concerns. She was discharged home by plastic surgery services with a diagnosis of floppy neck and dysphagia secondary to aesthetic botulinum toxin paralysis of the bilateral sternocleidomastoid muscles and platysma. She was given a prescription for metoclopramide hydrochloride to stimulate motility of the upper gastrointestinal tract and to potentially improve swallowing.¹⁰

The patient was scheduled for a follow-up evaluation with the plastic surgeon 2 days after discharge. She was instructed to call 911 if she experienced stridor, shortness of breath, drooling, or if any airway issues arose. The patient did not return for her follow-up appointment with the plastic surgeon.

Discussion

Clostridium Botulinum Toxins

Clostridium botulinum is a gram-positive spore-forming anaerobic bacterium that produces extremely potent neuro-exotoxins. C botulinum is found in soil, contaminated foods, and in illicit injectable drugs (eg, heroin). Seven distinct antigenic botulinum toxins (A, B, C1, D, E, F, and G) are produced by several strains of C botulinum. Systemically, each neurotoxin is able to produce severe morbidity and mortality by causing generalized muscle paralysis and death by respiratory failure. The lethal dose of these agents is approximating 10(-9) g/kg body weight. Botulinum toxin type A is the most potent.^1,2

Nonetheless, botulinum toxin has been used clinically since the early 1970s. Currently, there are three FDA-approved botulinum toxin type A agents and one type B formulation (rimabotulinumtoxinB) (Table). Each formulation is unique, proprietary, and differs in molecular weight, toxin-complex size, protein content, and inactive ingredients. The effectiveness and adverse event profile for these four botulinum toxins is individually dependent upon the different dilutions and potency, onset of action, duration of effect, diffusion, and migration potential. Hence, the effective dose of one botulinum toxin does not equate to any other, resulting in a lack of interchangeability between botulinum toxins (eg, 5 IU of incobotulinumtoxinA does not equal 5 IU of onabotulinumtoxinA).

Aesthetic Indications

Historically, the use of botulinum toxin for aesthetic treatment of wrinkles and platysmal bands was first reported by Blitzer³ in 1993.Subsequently, the use of botulinum toxin for the aesthetic treatment of facial wrinkles, hypertrophic platysmal bands and horizontal neck lines gained popularity within the public and medical community.^3-5

Anatomically, the platysma is a thin sheet-like muscle that originates in the superior fascia of the pectoralis and deltoid fascia, and extends over the full length of the neck up past the mandible and continuing into the submuscular aponeurotic system. The platysma is innervated by the seventh cranial nerve and functions to pull the jaw downward. The platysma muscle is attached directly to the skin. With normal aging, the anterior neck skin becomes flaccid, the central platysmal bands thicken and contract—forming bands, horizontal wrinkles, and loss of definition of the neck noticed at rest and with contraction of the platysma muscle. These vertical bands are known as platysmal bands. The platysmal bands are benign consequences of aging and as such are targets of correction through surgery or botulinum toxin injection.^6,7

Mechanism of Action

Platysmal band and horizontal line injection techniques with botulinum toxin have been reported in the literature with dosages ranging from 15 IU to 200 IU used to block the Soluble N-ethylmaleimide-sensitive factor activating protein receptors. Typical onset of action begins at 3 days, with full paralytic effect at 7 days. Repeat injections every 3 to 4 months are required with prolonged effects seen with each subsequent injection due to chemodenervation-induced muscle atrophy.^4,7,8

Adverse Effects

Commercial botulinum toxin type A has been associated with minor and transient side effects. Moderate complications seen in the neck region include transient soft-tissue edema, dermal ecchymoses, intramuscular hematoma, diffuse muscle soreness, neck flexor weakness, and headaches.^4,8,9

The use of botulinum toxin for chemodenervation of the platysma can produce significant weakness of other neck muscles, including the sternocleidomastoid, cricothyroid, sternothyroid, and sternohyoid. Floppy neck and dysphagia may be due to diffusion of the toxin into the muscles of deglutition of the larynx; injection directly into the sternocleidomastoid muscle; or a result of the systemic effects of large dosages. Hoarseness, breathiness, and dysphagia may occur 3 to 4 days after injection, especially with doses over 75 IU.¹⁰

The recommended concentration of botulinum toxin type A causes a diffusion average of 1 cm in all directions from the injection sites. However, as the dilution increases, so does the zone of diffusion. Typical discharge instructions for platysma treatment include the overuse of the neck muscles for 2 to 4 hours after injection to encourage the botulinum toxin uptake for optimal result. Site manipulation (rubbing or massaging) also increases diffusion. For botulinum toxin type B, the zone of diffusion is greater because its molecular weight is less than the type A toxins, thus making it an undesirable agent for aesthetic facial chemodenervation.^4,11

Toxin Resistance

Botulinum toxin resistance is a known complication that occurs normally as a result of the body recognizing the neurotoxin as a foreign substance and producing neutralizing antibodies (NAb). Primary botulinum toxin failure is known in patients who require high doses of the neurotoxin for treatment of neuromuscular disorders.¹² Complete secondary therapy failure is known to occur in cosmetic patients after a single dose and those who have been receiving low-dose botulinum toxin regularly. The risk of NAb development increases with long-term treatment and high doses.^12-18

Floppy Neck and Dysphagia

As previously noted, floppy neck and dysphagia are adverse clinical findings of botulinum toxin effect on the platysma, sternocleidomastoid, or the paralaryngeal muscles. In this case, the patient was fortunate to have only sustained weakness of the platysma and sternocleidomastoid muscles despite both a large neck and total body dose. Paralaryngeal muscle paralysis is not life-threatening, but the distress may precipitate paradoxical vocal cord motion and stridor.

Stridor

Stridor is typically a symptom of an upper airway obstruction (UAO) process. Typical UAO conditions encountered in the ED are infections (eg, epiglottitis, croup), foreign body, allergy, and laryngeal trauma. The age of the patient, onset of stridor, course of the stridor (ie, intermittent, continuous, worsening), associated symptoms (eg, fever, rash, swelling of oral soft tissues), and bruising must be ascertained.

In differentiating the etiology of stridor, the EP should observe the patient for any associated change in voice, inability to handle secretions, and position of comfort. Patients with stridor require admission and evaluation by an otolaryngologist as expeditiously as possible because impending UAO may quickly progress to complete UAO necessitating emergent intubation.

An atypical presentation of stridor to the ED is sporadic stridor. Sporadic attacks of stridor during activity have been associated with the entity of paradoxical vocal cord motion. Patients usually describe a choking sensation with inability to breathe resulting in an audible inspiratory and/or expiratory sound—ie, stridor. Wheezing may or may not be present. Patients may also describe tightness in the neck and sometimes in the chest. The attacks are usually seconds to minutes in duration. More often, there is a precipitating or an inducing factor such as hyperventilation, cough, panting, phonatory tasks, or the inhalation of irritants or perfume, or an oropharyngeal or laryngeal manipulation prior or postextubation. The feeling of stress alone is commonly reported prior to the attacks. When evaluating patients presenting with floppy neck, dysphagia, and stridor, it is imperative that the clinician conduct a thorough history and physical examination to determine if the symptoms are secondary to a systemic or local effect, and whether the patient will progress to an acute UAO (vocal cord paralysis) necessitating intubation in the ED and subsequent tracheostomy.^19,20

Conclusion

The ready availability of botulinum toxins and their low-cost-benefit ratio continue to promote over-utilization for treatment of facial wrinkles, platysmal bands, and horizontal lines; migraine headache; and hyperhidrosis. Complications associated with overuse of botulinum toxins are due to either administration of a large single dose or from regional diffusion. With the increasing number of patients receiving botulinum injections, EPs should be aware of the four available toxin types onset of action, adverse events, and potential life-threatening complications of regional neck injections.

Case

A 68-year-old woman presented to the ED 5 days after receiving onabotulinumtoxinA cosmetic injections for wrinkles of the face and neck. She stated that she was unable to raise her head while in a supine position and that her head felt heavy when standing. She also experienced spasms and strain of the posterior cervical neck muscles. In addition, the patient described a constant need to swallow forcefully throughout the day, and felt an intermittent heavy sensation over her larynx that was associated with stridor. She noted these symptoms began 5 days after the onabotulinumtoxinA injections and had peaked 2 days prior to presentation. She also complained of dysphagia without odynophagia, but denied any changes in her voice.

The patient first began onabotulinumtoxinA injections 12 years earlier for aesthetic treatment of glabellar and peri-orbital wrinkles. She initially received the injections at a regular interval of 90 to 100 days. During the course of the first 2 years of treatment, the patient was under the care of a plastic surgeon; thereafter, she sought treatment at a physician-owned medical spa because it offered onabotulinumtoxinA at a lower price. The injections at the medical spa were administered by a physician assistant (PA). The patient stated that although the PA had steadily increased the dose of onabotulinumtoxinA to maintain the desired aesthetic effect, this was the first time she had experienced any side effects from the treatment.

The ED staff contacted the medical spa provider, who reviewed the patient’s medical record over the telephone. The PA stated that he had been the only practitioner at the facility to administer the onabotulinumtoxinA injections to the patient over her past 10 years there as a client. He further informed the emergency physician (EP) that 12 days prior to presentation, he had given the patient a total of 50 IU of onabotulinumtoxinA, in five separate injections, into the mid frontalis muscle; a total of 35 IU, in seven separate injections, into the glabellar region (procerus and corrugator muscles bilaterally); 20 IU into the lateral and inferior-lateral orbicularis oculi bilaterally, in four separate injections per side, (40 IU total); and a total of 100 IU in the anterior platysma, in 20 separate injections, for a total 1-day onabotulinumtoxinA dose of 225 IU.

The PA explained to the EP that he mixed the onabotulinumtoxinA in the patient’s room and had shown her the vials and dilution standard as recommended by the manufacturer because she had been requiring increased dosages and had previously questioned whether the onabotulinumtoxinA was diluted. The PA denied any other patients experiencing similar adverse events as those of the patient’s.

Over the last 10 years, the patient had received onabotulinumtoxinA in the nasolabial folds, upper and lower lip wrinkles, mentalis, depressor angular oris, buccal, nasalis, lateral brow, masseter, and calf muscles. The dosage of onabotulinumtoxinA at this most recent injection cycle was unchanged from her previous visit 3 months prior. According to the PA, the practice did not use abobotulinumtoxinA or incobotulinumtoxinA.

Regarding the patient’s medical history, she had no health issues suggestive of myasthenia gravis, multiple sclerosis, or Guillain-Barré syndrome. Examination of the face revealed decreased muscle excursion of the frontalis muscle from mid-brow to mid-brow, and stair-step wrinkle formation bilaterally. The procerus muscle was very weak, and the corrugator muscles were moderately diminished in strength. The lateral orbicularis oculi were very weak at each canthus. The extra-ocular muscles were intact. She had full mandibular excursion, and powerful movement of the tongue. The oropharynx and floor of the mouth were normal. She was noted to purposefully swallow and extend her neck every 90 to 120 seconds to “clear her throat,” though she did not drool and was able to handle her secretions and swallow fluids without aspiration. Her voice was normal and she was able to recite the letters “KKKKK,” “OOOOO,” and “EEEEE” in rapid fashion without breathiness or stridor. The rest of her facial muscles were normal.

While supine, the patient strained to lift her head and complained of a suffocating sensation over the larynx. She had no rashes or edema, and the remainder of the physical examination, vital signs, and pulse oximetry were normal. Laboratory evaluation, which included a complete blood count and serum electrolytes, was also normal.

An otolaryngologist consultation for laryngoscopy was obtained. After reviewing the patient’s case, the otolaryngologist concluded that given the patient’s history, intermittent stridor, and an absence of signs or symptoms suggestive of an impending upper airway obstruction (UAO), laryngoscopy was not warranted.

A plastic surgery consultation was then obtained. The patient’s examination was as noted above, and her vital signs and pulse oximetry remained normal throughout her ED stay. Although botulinum and botulinum antibody titers were ordered, the patient refused testing due to cost concerns. She was discharged home by plastic surgery services with a diagnosis of floppy neck and dysphagia secondary to aesthetic botulinum toxin paralysis of the bilateral sternocleidomastoid muscles and platysma. She was given a prescription for metoclopramide hydrochloride to stimulate motility of the upper gastrointestinal tract and to potentially improve swallowing.¹⁰

The patient was scheduled for a follow-up evaluation with the plastic surgeon 2 days after discharge. She was instructed to call 911 if she experienced stridor, shortness of breath, drooling, or if any airway issues arose. The patient did not return for her follow-up appointment with the plastic surgeon.

Discussion

Clostridium Botulinum Toxins

Clostridium botulinum is a gram-positive spore-forming anaerobic bacterium that produces extremely potent neuro-exotoxins. C botulinum is found in soil, contaminated foods, and in illicit injectable drugs (eg, heroin). Seven distinct antigenic botulinum toxins (A, B, C1, D, E, F, and G) are produced by several strains of C botulinum. Systemically, each neurotoxin is able to produce severe morbidity and mortality by causing generalized muscle paralysis and death by respiratory failure. The lethal dose of these agents is approximating 10(-9) g/kg body weight. Botulinum toxin type A is the most potent.^1,2

Nonetheless, botulinum toxin has been used clinically since the early 1970s. Currently, there are three FDA-approved botulinum toxin type A agents and one type B formulation (rimabotulinumtoxinB) (Table). Each formulation is unique, proprietary, and differs in molecular weight, toxin-complex size, protein content, and inactive ingredients. The effectiveness and adverse event profile for these four botulinum toxins is individually dependent upon the different dilutions and potency, onset of action, duration of effect, diffusion, and migration potential. Hence, the effective dose of one botulinum toxin does not equate to any other, resulting in a lack of interchangeability between botulinum toxins (eg, 5 IU of incobotulinumtoxinA does not equal 5 IU of onabotulinumtoxinA).

Aesthetic Indications

Historically, the use of botulinum toxin for aesthetic treatment of wrinkles and platysmal bands was first reported by Blitzer³ in 1993.Subsequently, the use of botulinum toxin for the aesthetic treatment of facial wrinkles, hypertrophic platysmal bands and horizontal neck lines gained popularity within the public and medical community.^3-5

Anatomically, the platysma is a thin sheet-like muscle that originates in the superior fascia of the pectoralis and deltoid fascia, and extends over the full length of the neck up past the mandible and continuing into the submuscular aponeurotic system. The platysma is innervated by the seventh cranial nerve and functions to pull the jaw downward. The platysma muscle is attached directly to the skin. With normal aging, the anterior neck skin becomes flaccid, the central platysmal bands thicken and contract—forming bands, horizontal wrinkles, and loss of definition of the neck noticed at rest and with contraction of the platysma muscle. These vertical bands are known as platysmal bands. The platysmal bands are benign consequences of aging and as such are targets of correction through surgery or botulinum toxin injection.^6,7

Mechanism of Action

Platysmal band and horizontal line injection techniques with botulinum toxin have been reported in the literature with dosages ranging from 15 IU to 200 IU used to block the Soluble N-ethylmaleimide-sensitive factor activating protein receptors. Typical onset of action begins at 3 days, with full paralytic effect at 7 days. Repeat injections every 3 to 4 months are required with prolonged effects seen with each subsequent injection due to chemodenervation-induced muscle atrophy.^4,7,8

Adverse Effects

Commercial botulinum toxin type A has been associated with minor and transient side effects. Moderate complications seen in the neck region include transient soft-tissue edema, dermal ecchymoses, intramuscular hematoma, diffuse muscle soreness, neck flexor weakness, and headaches.^4,8,9

The use of botulinum toxin for chemodenervation of the platysma can produce significant weakness of other neck muscles, including the sternocleidomastoid, cricothyroid, sternothyroid, and sternohyoid. Floppy neck and dysphagia may be due to diffusion of the toxin into the muscles of deglutition of the larynx; injection directly into the sternocleidomastoid muscle; or a result of the systemic effects of large dosages. Hoarseness, breathiness, and dysphagia may occur 3 to 4 days after injection, especially with doses over 75 IU.¹⁰

The recommended concentration of botulinum toxin type A causes a diffusion average of 1 cm in all directions from the injection sites. However, as the dilution increases, so does the zone of diffusion. Typical discharge instructions for platysma treatment include the overuse of the neck muscles for 2 to 4 hours after injection to encourage the botulinum toxin uptake for optimal result. Site manipulation (rubbing or massaging) also increases diffusion. For botulinum toxin type B, the zone of diffusion is greater because its molecular weight is less than the type A toxins, thus making it an undesirable agent for aesthetic facial chemodenervation.^4,11

Toxin Resistance

Botulinum toxin resistance is a known complication that occurs normally as a result of the body recognizing the neurotoxin as a foreign substance and producing neutralizing antibodies (NAb). Primary botulinum toxin failure is known in patients who require high doses of the neurotoxin for treatment of neuromuscular disorders.¹² Complete secondary therapy failure is known to occur in cosmetic patients after a single dose and those who have been receiving low-dose botulinum toxin regularly. The risk of NAb development increases with long-term treatment and high doses.^12-18

Floppy Neck and Dysphagia

As previously noted, floppy neck and dysphagia are adverse clinical findings of botulinum toxin effect on the platysma, sternocleidomastoid, or the paralaryngeal muscles. In this case, the patient was fortunate to have only sustained weakness of the platysma and sternocleidomastoid muscles despite both a large neck and total body dose. Paralaryngeal muscle paralysis is not life-threatening, but the distress may precipitate paradoxical vocal cord motion and stridor.

Stridor

Stridor is typically a symptom of an upper airway obstruction (UAO) process. Typical UAO conditions encountered in the ED are infections (eg, epiglottitis, croup), foreign body, allergy, and laryngeal trauma. The age of the patient, onset of stridor, course of the stridor (ie, intermittent, continuous, worsening), associated symptoms (eg, fever, rash, swelling of oral soft tissues), and bruising must be ascertained.

In differentiating the etiology of stridor, the EP should observe the patient for any associated change in voice, inability to handle secretions, and position of comfort. Patients with stridor require admission and evaluation by an otolaryngologist as expeditiously as possible because impending UAO may quickly progress to complete UAO necessitating emergent intubation.

An atypical presentation of stridor to the ED is sporadic stridor. Sporadic attacks of stridor during activity have been associated with the entity of paradoxical vocal cord motion. Patients usually describe a choking sensation with inability to breathe resulting in an audible inspiratory and/or expiratory sound—ie, stridor. Wheezing may or may not be present. Patients may also describe tightness in the neck and sometimes in the chest. The attacks are usually seconds to minutes in duration. More often, there is a precipitating or an inducing factor such as hyperventilation, cough, panting, phonatory tasks, or the inhalation of irritants or perfume, or an oropharyngeal or laryngeal manipulation prior or postextubation. The feeling of stress alone is commonly reported prior to the attacks. When evaluating patients presenting with floppy neck, dysphagia, and stridor, it is imperative that the clinician conduct a thorough history and physical examination to determine if the symptoms are secondary to a systemic or local effect, and whether the patient will progress to an acute UAO (vocal cord paralysis) necessitating intubation in the ED and subsequent tracheostomy.^19,20

Conclusion

The ready availability of botulinum toxins and their low-cost-benefit ratio continue to promote over-utilization for treatment of facial wrinkles, platysmal bands, and horizontal lines; migraine headache; and hyperhidrosis. Complications associated with overuse of botulinum toxins are due to either administration of a large single dose or from regional diffusion. With the increasing number of patients receiving botulinum injections, EPs should be aware of the four available toxin types onset of action, adverse events, and potential life-threatening complications of regional neck injections.

Case

A 14-year-old girl with no known medical history presented to the ED via emergency medical services (EMS) approximately 1.5 hours after intentionally ingesting what she described as “a handful or two” of her mother’s lupus prescription medication in a suicide attempt. Initial vital signs and physical examination were normal, and her only complaint was nausea.

Thirty minutes after presentation, the patient suffered acute cardiovascular (CV) collapse: blood pressure, 57/39 mm Hg; heart rate, 90 beats/min. An initial electrocardiogram (ECG) revealed QRS duration of 123 milliseconds and QTc duration of 510 milliseconds, along with nonspecific T-wave abnormalities. A 150-mEq intravenous (IV) bolus of sodium bicarbonate and a 40-mEq potassium chloride IV infusion were administered, and both epinephrine and norepinephrine IV infusions were also initiated. A basic metabolic panel obtained prior to medication administration showed a potassium concentration of 1.9 mmol/L.

What is the differential diagnosis of toxicological hypokalemia?

Hypokalemia may be reflective of diminished whole body potassium stores or a transient alteration of intravascular potassium concentrations. In acute ingestions and overdose, the etiology of the hypokalemia is often electrolyte redistribution through either blockade of constitutive outward potassium leakage (eg, barium, insulin, quinine) or through increased activity of the Na⁺/K⁺-ATPase pump (eg, catecholamines, insulin, methylxanthines). This activity has little effect on whole body potassium stores, but can result in a profound fall in the serum potassium. While mild hypokalemia is generally well tolerated, more severe potassium abnormalities can cause muscular weakness, areflexic paralysis, respiratory failure, and life-threatening dysrhythmias. Common ECG findings include decreased T-wave amplitudes, ST-segment depression, and the presence or amplification of U waves.

Case Continuation

While the emergency physicians were stabilizing the patient, her mother provided additional information. Approximately 30 minutes after the exposure, the patient had become nauseated and told her mother what she had done. Her mother called EMS, and the patient was transported to the hospital, where she rapidly became symptomatic. Despite CV decompensation, she remained neurologically intact. On further questioning, the patient admitted to ingesting 6 g of her mother’s prescription of hydroxychloroquine (HCQ) in a suicide attempt but denied taking any other medications. She was stabilized on vasopressors and admitted to the intensive care unit.

What characterizes hydroxychloroquine toxicity?

Hydroxychloroquine is an aminoquinoline antibiotic that is classically used as an antimalarial to treat infection with Plasmodium vivax, P ovale, P malariae, and susceptible strains of P falciparum. In the United States, it is more commonly used to manage both rheumatoid arthritis and systemic lupus erythematosus (SLE), debilitating diseases which are estimated to affect anywhere from 161,000 to 322,000 Americans.¹ Hydroxychloroquine is considered first-line therapy for SLE, but its mechanism of action in treating SLE-associated arthralgias is unclear.

Hydroxychloroquine is structurally similar to quinine and chloroquine (CQ), and not surprisingly exerts quinidine-like effects on the CV system with resultant negative inotropy and vasodilation. Its toxicity is characterized by rapid onset of clinical effects including central nervous system depression, seizures, apnea, hypotension, and arrhythmia. After large overdoses, cardiac arrest and death can occur within hours.

Hypokalemia is another hallmark of HCQ toxicity. It is thought to develop secondary to potassium channel blockade, which slows the constitutive release of potassium from the myocytes.² As noted, the hypokalemia is transient and does not reflect whole-body depletion. With CQ, which is considered more toxic, there appears to be a correlation between the quantity of CQ ingested and both the degree of hypokalemia and the severity of the outcome. It is reasonable to assume the same for HCQ. There are little data to support that hypokalemia itself causes cardiotoxicity in patients with CQ or HCQ overdose.

Although lethal doses are not well established, animal studies suggest that HCQ is much less toxic than CQ, for which the clinical toxicity is better understood due to its more widespread use in overdose abroad.³ In children, the reported therapeutic dose is 10 mg/kg, but the minimum reported lethal dose was a single 300-mg tablet (30 mg/kg in a toddler). In adults, the toxic dose is reported as 20 mg/kg with lethal doses suggested to be as low as 30 mg/kg.

What are the treatment modalities for patients with hydroxychloroquine toxicity?

By analogy with the treatment of CQ poisoning, the mainstay of HCQ therapy is supportive care, including early intubation and ventilation to minimize metabolic demand. Direct-acting inotropes and vasopressors should be administered after saline to treat hypotension. Because of its large volume of distribution, extracorporeal removal has not proved to be of clinical value.^4,5 Though data are sparse to determine its efficacy, there may be a role for giving activated charcoal, particularly following large overdoses—if it is given early after exposure and the patient has normal consciousness. If the patient is intubated and aspiration risk is minimized, gastric lavage may also be beneficial—especially when performed within an hour of the overdose. Syrup of ipecac should not be used.

High-dose diazepam is typically recommended, again by analogy with CQ, although there is no clear mechanism of action and its use remains controversial. Its protective effect in patients with CQ overdose is based on swine and rat models that demonstrated dose dependent relationships between diazepam and survival.^6,7 A prospective study of CQ toxicity in humans reported improved survival rates when high-dose diazepam was given in combination with epinephrine.⁸ However, this study is limited by its comparison of prospectively studied patients with a retrospective control. A subsequent prospective study of moderately CQ-intoxicated patients did not find a benefit from treatment with diazepam.⁹ Furthermore, it remains unclear if the proposed benefit from high-dose diazepam in CQ toxicity may be extrapolated to HCQ, and cases of even massive HCQ ingestions report good outcomes without the use of high-dose diazepam.¹⁰

How aggressively should hypokalemia in hydroxychloroquine toxicity be treated?

As noted earlier, hypokalemia resulting from HCQ toxicity is transient, and aggressive repletion may result in rebound hyperkalemia once toxicity resolves. However, these dangers should be balanced with risks of hypokalemia-induced ventricular arrhythmias. Additionally, hypokalemia may be worsened by sodium bicarbonate that is administered to correct QRS prolongations, increasing the risk of dysrhythmia. Correction of hypokalemia in these cases is necessary but should be done with care and monitoring of serum potassium concentrations to minimize risk of hyperkalemia-induced ventricular arrhythmia.¹¹

Case Conclusion

Throughout treatment, the patient remained neurologically intact. She did not receive benzodiazepines. The epinephrine and norepinephrine infusions were weaned, and she was discharged on hospital day 3 with no neurological or cardiac sequelae. She received an inpatient psychiatric evaluation and was referred to outpatient services for ongoing care.  

Case

A 14-year-old girl with no known medical history presented to the ED via emergency medical services (EMS) approximately 1.5 hours after intentionally ingesting what she described as “a handful or two” of her mother’s lupus prescription medication in a suicide attempt. Initial vital signs and physical examination were normal, and her only complaint was nausea.

Thirty minutes after presentation, the patient suffered acute cardiovascular (CV) collapse: blood pressure, 57/39 mm Hg; heart rate, 90 beats/min. An initial electrocardiogram (ECG) revealed QRS duration of 123 milliseconds and QTc duration of 510 milliseconds, along with nonspecific T-wave abnormalities. A 150-mEq intravenous (IV) bolus of sodium bicarbonate and a 40-mEq potassium chloride IV infusion were administered, and both epinephrine and norepinephrine IV infusions were also initiated. A basic metabolic panel obtained prior to medication administration showed a potassium concentration of 1.9 mmol/L.

What is the differential diagnosis of toxicological hypokalemia?

Hypokalemia may be reflective of diminished whole body potassium stores or a transient alteration of intravascular potassium concentrations. In acute ingestions and overdose, the etiology of the hypokalemia is often electrolyte redistribution through either blockade of constitutive outward potassium leakage (eg, barium, insulin, quinine) or through increased activity of the Na⁺/K⁺-ATPase pump (eg, catecholamines, insulin, methylxanthines). This activity has little effect on whole body potassium stores, but can result in a profound fall in the serum potassium. While mild hypokalemia is generally well tolerated, more severe potassium abnormalities can cause muscular weakness, areflexic paralysis, respiratory failure, and life-threatening dysrhythmias. Common ECG findings include decreased T-wave amplitudes, ST-segment depression, and the presence or amplification of U waves.

Case Continuation

While the emergency physicians were stabilizing the patient, her mother provided additional information. Approximately 30 minutes after the exposure, the patient had become nauseated and told her mother what she had done. Her mother called EMS, and the patient was transported to the hospital, where she rapidly became symptomatic. Despite CV decompensation, she remained neurologically intact. On further questioning, the patient admitted to ingesting 6 g of her mother’s prescription of hydroxychloroquine (HCQ) in a suicide attempt but denied taking any other medications. She was stabilized on vasopressors and admitted to the intensive care unit.

What characterizes hydroxychloroquine toxicity?

Hydroxychloroquine is an aminoquinoline antibiotic that is classically used as an antimalarial to treat infection with Plasmodium vivax, P ovale, P malariae, and susceptible strains of P falciparum. In the United States, it is more commonly used to manage both rheumatoid arthritis and systemic lupus erythematosus (SLE), debilitating diseases which are estimated to affect anywhere from 161,000 to 322,000 Americans.¹ Hydroxychloroquine is considered first-line therapy for SLE, but its mechanism of action in treating SLE-associated arthralgias is unclear.

Hydroxychloroquine is structurally similar to quinine and chloroquine (CQ), and not surprisingly exerts quinidine-like effects on the CV system with resultant negative inotropy and vasodilation. Its toxicity is characterized by rapid onset of clinical effects including central nervous system depression, seizures, apnea, hypotension, and arrhythmia. After large overdoses, cardiac arrest and death can occur within hours.

Hypokalemia is another hallmark of HCQ toxicity. It is thought to develop secondary to potassium channel blockade, which slows the constitutive release of potassium from the myocytes.² As noted, the hypokalemia is transient and does not reflect whole-body depletion. With CQ, which is considered more toxic, there appears to be a correlation between the quantity of CQ ingested and both the degree of hypokalemia and the severity of the outcome. It is reasonable to assume the same for HCQ. There are little data to support that hypokalemia itself causes cardiotoxicity in patients with CQ or HCQ overdose.

Although lethal doses are not well established, animal studies suggest that HCQ is much less toxic than CQ, for which the clinical toxicity is better understood due to its more widespread use in overdose abroad.³ In children, the reported therapeutic dose is 10 mg/kg, but the minimum reported lethal dose was a single 300-mg tablet (30 mg/kg in a toddler). In adults, the toxic dose is reported as 20 mg/kg with lethal doses suggested to be as low as 30 mg/kg.

What are the treatment modalities for patients with hydroxychloroquine toxicity?

By analogy with the treatment of CQ poisoning, the mainstay of HCQ therapy is supportive care, including early intubation and ventilation to minimize metabolic demand. Direct-acting inotropes and vasopressors should be administered after saline to treat hypotension. Because of its large volume of distribution, extracorporeal removal has not proved to be of clinical value.^4,5 Though data are sparse to determine its efficacy, there may be a role for giving activated charcoal, particularly following large overdoses—if it is given early after exposure and the patient has normal consciousness. If the patient is intubated and aspiration risk is minimized, gastric lavage may also be beneficial—especially when performed within an hour of the overdose. Syrup of ipecac should not be used.

High-dose diazepam is typically recommended, again by analogy with CQ, although there is no clear mechanism of action and its use remains controversial. Its protective effect in patients with CQ overdose is based on swine and rat models that demonstrated dose dependent relationships between diazepam and survival.^6,7 A prospective study of CQ toxicity in humans reported improved survival rates when high-dose diazepam was given in combination with epinephrine.⁸ However, this study is limited by its comparison of prospectively studied patients with a retrospective control. A subsequent prospective study of moderately CQ-intoxicated patients did not find a benefit from treatment with diazepam.⁹ Furthermore, it remains unclear if the proposed benefit from high-dose diazepam in CQ toxicity may be extrapolated to HCQ, and cases of even massive HCQ ingestions report good outcomes without the use of high-dose diazepam.¹⁰

How aggressively should hypokalemia in hydroxychloroquine toxicity be treated?

As noted earlier, hypokalemia resulting from HCQ toxicity is transient, and aggressive repletion may result in rebound hyperkalemia once toxicity resolves. However, these dangers should be balanced with risks of hypokalemia-induced ventricular arrhythmias. Additionally, hypokalemia may be worsened by sodium bicarbonate that is administered to correct QRS prolongations, increasing the risk of dysrhythmia. Correction of hypokalemia in these cases is necessary but should be done with care and monitoring of serum potassium concentrations to minimize risk of hyperkalemia-induced ventricular arrhythmia.¹¹

Case Conclusion

Throughout treatment, the patient remained neurologically intact. She did not receive benzodiazepines. The epinephrine and norepinephrine infusions were weaned, and she was discharged on hospital day 3 with no neurological or cardiac sequelae. She received an inpatient psychiatric evaluation and was referred to outpatient services for ongoing care.  

Case

A 14-year-old girl with no known medical history presented to the ED via emergency medical services (EMS) approximately 1.5 hours after intentionally ingesting what she described as “a handful or two” of her mother’s lupus prescription medication in a suicide attempt. Initial vital signs and physical examination were normal, and her only complaint was nausea.

Thirty minutes after presentation, the patient suffered acute cardiovascular (CV) collapse: blood pressure, 57/39 mm Hg; heart rate, 90 beats/min. An initial electrocardiogram (ECG) revealed QRS duration of 123 milliseconds and QTc duration of 510 milliseconds, along with nonspecific T-wave abnormalities. A 150-mEq intravenous (IV) bolus of sodium bicarbonate and a 40-mEq potassium chloride IV infusion were administered, and both epinephrine and norepinephrine IV infusions were also initiated. A basic metabolic panel obtained prior to medication administration showed a potassium concentration of 1.9 mmol/L.

What is the differential diagnosis of toxicological hypokalemia?

Hypokalemia may be reflective of diminished whole body potassium stores or a transient alteration of intravascular potassium concentrations. In acute ingestions and overdose, the etiology of the hypokalemia is often electrolyte redistribution through either blockade of constitutive outward potassium leakage (eg, barium, insulin, quinine) or through increased activity of the Na⁺/K⁺-ATPase pump (eg, catecholamines, insulin, methylxanthines). This activity has little effect on whole body potassium stores, but can result in a profound fall in the serum potassium. While mild hypokalemia is generally well tolerated, more severe potassium abnormalities can cause muscular weakness, areflexic paralysis, respiratory failure, and life-threatening dysrhythmias. Common ECG findings include decreased T-wave amplitudes, ST-segment depression, and the presence or amplification of U waves.

Case Continuation

While the emergency physicians were stabilizing the patient, her mother provided additional information. Approximately 30 minutes after the exposure, the patient had become nauseated and told her mother what she had done. Her mother called EMS, and the patient was transported to the hospital, where she rapidly became symptomatic. Despite CV decompensation, she remained neurologically intact. On further questioning, the patient admitted to ingesting 6 g of her mother’s prescription of hydroxychloroquine (HCQ) in a suicide attempt but denied taking any other medications. She was stabilized on vasopressors and admitted to the intensive care unit.

What characterizes hydroxychloroquine toxicity?

Hydroxychloroquine is an aminoquinoline antibiotic that is classically used as an antimalarial to treat infection with Plasmodium vivax, P ovale, P malariae, and susceptible strains of P falciparum. In the United States, it is more commonly used to manage both rheumatoid arthritis and systemic lupus erythematosus (SLE), debilitating diseases which are estimated to affect anywhere from 161,000 to 322,000 Americans.¹ Hydroxychloroquine is considered first-line therapy for SLE, but its mechanism of action in treating SLE-associated arthralgias is unclear.

Hydroxychloroquine is structurally similar to quinine and chloroquine (CQ), and not surprisingly exerts quinidine-like effects on the CV system with resultant negative inotropy and vasodilation. Its toxicity is characterized by rapid onset of clinical effects including central nervous system depression, seizures, apnea, hypotension, and arrhythmia. After large overdoses, cardiac arrest and death can occur within hours.

Hypokalemia is another hallmark of HCQ toxicity. It is thought to develop secondary to potassium channel blockade, which slows the constitutive release of potassium from the myocytes.² As noted, the hypokalemia is transient and does not reflect whole-body depletion. With CQ, which is considered more toxic, there appears to be a correlation between the quantity of CQ ingested and both the degree of hypokalemia and the severity of the outcome. It is reasonable to assume the same for HCQ. There are little data to support that hypokalemia itself causes cardiotoxicity in patients with CQ or HCQ overdose.

Although lethal doses are not well established, animal studies suggest that HCQ is much less toxic than CQ, for which the clinical toxicity is better understood due to its more widespread use in overdose abroad.³ In children, the reported therapeutic dose is 10 mg/kg, but the minimum reported lethal dose was a single 300-mg tablet (30 mg/kg in a toddler). In adults, the toxic dose is reported as 20 mg/kg with lethal doses suggested to be as low as 30 mg/kg.

What are the treatment modalities for patients with hydroxychloroquine toxicity?

By analogy with the treatment of CQ poisoning, the mainstay of HCQ therapy is supportive care, including early intubation and ventilation to minimize metabolic demand. Direct-acting inotropes and vasopressors should be administered after saline to treat hypotension. Because of its large volume of distribution, extracorporeal removal has not proved to be of clinical value.^4,5 Though data are sparse to determine its efficacy, there may be a role for giving activated charcoal, particularly following large overdoses—if it is given early after exposure and the patient has normal consciousness. If the patient is intubated and aspiration risk is minimized, gastric lavage may also be beneficial—especially when performed within an hour of the overdose. Syrup of ipecac should not be used.

High-dose diazepam is typically recommended, again by analogy with CQ, although there is no clear mechanism of action and its use remains controversial. Its protective effect in patients with CQ overdose is based on swine and rat models that demonstrated dose dependent relationships between diazepam and survival.^6,7 A prospective study of CQ toxicity in humans reported improved survival rates when high-dose diazepam was given in combination with epinephrine.⁸ However, this study is limited by its comparison of prospectively studied patients with a retrospective control. A subsequent prospective study of moderately CQ-intoxicated patients did not find a benefit from treatment with diazepam.⁹ Furthermore, it remains unclear if the proposed benefit from high-dose diazepam in CQ toxicity may be extrapolated to HCQ, and cases of even massive HCQ ingestions report good outcomes without the use of high-dose diazepam.¹⁰

How aggressively should hypokalemia in hydroxychloroquine toxicity be treated?

As noted earlier, hypokalemia resulting from HCQ toxicity is transient, and aggressive repletion may result in rebound hyperkalemia once toxicity resolves. However, these dangers should be balanced with risks of hypokalemia-induced ventricular arrhythmias. Additionally, hypokalemia may be worsened by sodium bicarbonate that is administered to correct QRS prolongations, increasing the risk of dysrhythmia. Correction of hypokalemia in these cases is necessary but should be done with care and monitoring of serum potassium concentrations to minimize risk of hyperkalemia-induced ventricular arrhythmia.¹¹

Case Conclusion

Throughout treatment, the patient remained neurologically intact. She did not receive benzodiazepines. The epinephrine and norepinephrine infusions were weaned, and she was discharged on hospital day 3 with no neurological or cardiac sequelae. She received an inpatient psychiatric evaluation and was referred to outpatient services for ongoing care.  

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

[email protected]

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

[email protected]

Labeling for prescription opioid pain or cough medicines and benzodiazepines will now carry the strongest available warning regarding serious side effects and death associated with their combined use, according to the Food and Drug Administration.

The new boxed warnings urge health care professionals to limit prescribing opioid pain medicines with benzodiazepines or other central nervous system depressants only to patients for whom alternative treatment options are inadequate, and to limit dosages and treatment duration to the minimum possible while achieving the desired clinical effect.

“First, the FDA is requiring companies to update their product labeling for ... benzodiazepines and opioids to include possible harms when they are used together. Second, we are requiring new or updated medication guides for these drugs reflecting those same warnings,” said Doug Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, during a telebriefing.

Opioids will include a warning regarding prescribing with benzodiazepines and other central nervous system depressants, including alcohol. Benzodiazepines will include a warning regarding prescribing with opioids.

In addition, the FDA has issued a safety communication to “warn the public about the serious risk of taking these products together to help make doctors more cautious and patients better informed,” Dr. Throckmorton said.

The action comes amid ongoing efforts to address an epidemic of opioid addiction across the United States, and in response to a first-of-its-kind “citizen petition” calling for the boxed warnings.

A coalition of health officials from multiple cities, states, and U.S. territories initiated that petition in February, and thousands of concerned community members started an additional online petition. Those petitions were in response to both the increasing combined use of opioids and benzodiazepines and a concomitant increase in the risk of serious side effects and deaths associated with their combined use, according to Baltimore City Health Commissioner Leana Wen, MD.

As an emergency physician, Dr. Wen said that she has seen firsthand the alarming trends; one in three unintentional overdose deaths from prescribed opioids also involve benzodiazepines, she noted.

“In my state of Maryland in 2014, benzodiazepines were associated with 19% of prescription opioid deaths, and 59% of benzodiazepine-associated deaths involved prescription opioids. We also noted the growing biological evidence that combining these medications caused sleepiness and slowed breathing, increasing the likelihood of a fatal overdose,” she said.

Dr. Throckmorton further noted that emergency department visits and deaths involving patients prescribed both opioids and benzodiazepines have increased significantly over time. From 2004 to 2011, the rate of nonmedical use–related emergency department visits increased significantly each year, and overdose deaths involving both drug classes during that period nearly tripled on an annual basis.

“Communities have been seeing this trend for some time, but ultimately we needed data in order to act today,” FDA Commissioner Robert Califf, MD, said during the telebriefing.

The current action is just “one part of a larger effort to address this epidemic.

“We remain focused and deeply committed to contributing to the comprehensive effort to address the opioid epidemic,” Dr. Califf said. The FDA “will continue to monitor these products carefully and take additional actions as needed, and will share updates with the public as necessary as we work to address this public health crisis.”

Dr. Califf noted that the current action is part of the FDA’s Opioids Action Plan, which is “importantly not meant just to cover illicit or abusive use of opioids.”

“So, you’ll be hearing a lot more from us, because this is a national crisis that is not going away. We’re making progress on the prescribing, and we’re seeing a reduction in the use of opioids now,” he noted. “But we’re still seeing many overdoses.

“This is a continuum, and we’ll continue to try to do everything we can to address the epidemic,” Dr. Califf concluded.

[email protected]

SAN FRANCISCO – The opioid overdose crisis in the United States is now plainly evident in intensive care units (ICUs), finds a study of hospitals in 44 states conducted between 2009 and 2015.

During the study period, ICU admissions for opioid overdoses increased by almost half, investigators reported in a session and related press briefing an international conference of the American Thoracic Society. Furthermore, ICU deaths from this cause roughly doubled.

Susan London/Frontline Medical News

“This means the opioid use epidemic has probably reached a new level of crisis,” said lead investigator Jennifer P. Stevens, MD, an instructor in medicine at Harvard Medical School, and an adult intensive care physician at Beth Israel Deaconess Medical Center, both in Boston. “And this means that in spite of everything that we can do in the ICU – keeping them alive on ventilators, doing life support, doing acute dialysis, doing round-the-clock care, round-the-clock board-certified intensivist care – we are still not able to make a difference in that mortality.”

Dr. Stevens added that any ICU admission for overdose from opioids is a preventable admission. “So if we have an increase in mortality of this population, we have a number of patients who have preventable deaths in our ICU,” she said.

Efforts to track this epidemic on a national level are important, she said, and the U.S. Centers for Disease Control and Prevention has been investigating opioid overdoses in some cities, including Boston, as they would any epidemic.

The factors driving the observed trends could not be determined from the study data, Dr. Stevens said. But state-specific patterns that show, for example, higher baseline rates and greater increases over time in ICU admissions for opioid overdose in Massachusetts and Indiana may be a starting point for investigation.

Certain practices in the ICU may also be inadvertently contributing. “I imagine that a patient who comes in with an opioid overdose can cause harm to themselves in a number of ways, and the things that we try to do to help them might cause harm in other ways as well,” she said. “So in an effort to try to maintain them in a safe, ventilated state, we might give them a ton of sedation that then prolongs their time on the ventilator. That’s sort of a simple example of how the two could intersect to have a multiplicative effect of harm.”

The idea for the study arose because ICU staff anecdotally noticed an uptick in admissions for opioid use disorder. “Not only were we seeing more people coming in, but we were seeing sicker people coming in, and with the associated tragedy that comes with a lot of young people coming in with opioid use disorder,” Dr. Stevens said. “We wanted to see if this was happening nationally... We asked, is this epidemic now reaching the most technologically advanced parts of our health care system?”

The investigators studied hospitals providing data to Vizient (formerly the University HealthSystem Consortium) between 2009 and 2015. The included hospitals – about 200 for each study year – were predominantly urban and university affiliated, but representation of community hospitals increased during the study period.

Ultimately, analyses were based on a total of 28.2 million hospital discharges of patients aged 18 years or older, which included 4.9 million ICU admissions.

Results reported at the meeting showed that 27,325 patients were admitted to the study hospitals’ ICUs with opioid overdose during the study period, as ascertained from billing codes.

Opioid overdose was seen in 45 patients per 10,000 ICU admissions in 2009 but rose to 65 patients per 10,000 ICU admissions in 2015, a 46% increase.

Furthermore, ICU deaths due to opioid overdose rose by 87% during the same time period, and mortality among patients admitted to the unit with overdose rose at a pace of 0.5% per month.

“This is somewhat unusual because a lot of times, when we are admitting more people to our ICUs or examining [a trend] further, mortality actually goes down. This is partly because maybe we are doing more for them and we are taking care of them in an aggressive way. But it’s also because we are admitting less sick people because we are more aware of the issue,” Dr. Stevens said. “And we saw the opposite of this – we saw that the mortality was going up.”

The use of billing data was a specific means but not a sensitive means of identifying opioid overdoses, she noted. Therefore, the observed values are likely underestimates of these outcomes.

Addressing the opioid overdose epidemic will require a multifaceted approach, according to Dr. Stevens, who disclosed that she had no relevant conflicts of interest.

“Folks are doing very impressive work in the community trying to make sure EMTs and other first responders have access to the tools that they need in those settings,” she said. “But one thing we haven’t approached before is the care that we provide in the ICU, and maybe that’s a space that we need to think more prospectively about.”

SAN FRANCISCO – The opioid overdose crisis in the United States is now plainly evident in intensive care units (ICUs), finds a study of hospitals in 44 states conducted between 2009 and 2015.

During the study period, ICU admissions for opioid overdoses increased by almost half, investigators reported in a session and related press briefing an international conference of the American Thoracic Society. Furthermore, ICU deaths from this cause roughly doubled.

Susan London/Frontline Medical News

“This means the opioid use epidemic has probably reached a new level of crisis,” said lead investigator Jennifer P. Stevens, MD, an instructor in medicine at Harvard Medical School, and an adult intensive care physician at Beth Israel Deaconess Medical Center, both in Boston. “And this means that in spite of everything that we can do in the ICU – keeping them alive on ventilators, doing life support, doing acute dialysis, doing round-the-clock care, round-the-clock board-certified intensivist care – we are still not able to make a difference in that mortality.”

Dr. Stevens added that any ICU admission for overdose from opioids is a preventable admission. “So if we have an increase in mortality of this population, we have a number of patients who have preventable deaths in our ICU,” she said.

Efforts to track this epidemic on a national level are important, she said, and the U.S. Centers for Disease Control and Prevention has been investigating opioid overdoses in some cities, including Boston, as they would any epidemic.

The factors driving the observed trends could not be determined from the study data, Dr. Stevens said. But state-specific patterns that show, for example, higher baseline rates and greater increases over time in ICU admissions for opioid overdose in Massachusetts and Indiana may be a starting point for investigation.

Certain practices in the ICU may also be inadvertently contributing. “I imagine that a patient who comes in with an opioid overdose can cause harm to themselves in a number of ways, and the things that we try to do to help them might cause harm in other ways as well,” she said. “So in an effort to try to maintain them in a safe, ventilated state, we might give them a ton of sedation that then prolongs their time on the ventilator. That’s sort of a simple example of how the two could intersect to have a multiplicative effect of harm.”

The idea for the study arose because ICU staff anecdotally noticed an uptick in admissions for opioid use disorder. “Not only were we seeing more people coming in, but we were seeing sicker people coming in, and with the associated tragedy that comes with a lot of young people coming in with opioid use disorder,” Dr. Stevens said. “We wanted to see if this was happening nationally... We asked, is this epidemic now reaching the most technologically advanced parts of our health care system?”

The investigators studied hospitals providing data to Vizient (formerly the University HealthSystem Consortium) between 2009 and 2015. The included hospitals – about 200 for each study year – were predominantly urban and university affiliated, but representation of community hospitals increased during the study period.

Ultimately, analyses were based on a total of 28.2 million hospital discharges of patients aged 18 years or older, which included 4.9 million ICU admissions.

Results reported at the meeting showed that 27,325 patients were admitted to the study hospitals’ ICUs with opioid overdose during the study period, as ascertained from billing codes.

Opioid overdose was seen in 45 patients per 10,000 ICU admissions in 2009 but rose to 65 patients per 10,000 ICU admissions in 2015, a 46% increase.

Furthermore, ICU deaths due to opioid overdose rose by 87% during the same time period, and mortality among patients admitted to the unit with overdose rose at a pace of 0.5% per month.

“This is somewhat unusual because a lot of times, when we are admitting more people to our ICUs or examining [a trend] further, mortality actually goes down. This is partly because maybe we are doing more for them and we are taking care of them in an aggressive way. But it’s also because we are admitting less sick people because we are more aware of the issue,” Dr. Stevens said. “And we saw the opposite of this – we saw that the mortality was going up.”

The use of billing data was a specific means but not a sensitive means of identifying opioid overdoses, she noted. Therefore, the observed values are likely underestimates of these outcomes.

Addressing the opioid overdose epidemic will require a multifaceted approach, according to Dr. Stevens, who disclosed that she had no relevant conflicts of interest.

“Folks are doing very impressive work in the community trying to make sure EMTs and other first responders have access to the tools that they need in those settings,” she said. “But one thing we haven’t approached before is the care that we provide in the ICU, and maybe that’s a space that we need to think more prospectively about.”

SAN FRANCISCO – The opioid overdose crisis in the United States is now plainly evident in intensive care units (ICUs), finds a study of hospitals in 44 states conducted between 2009 and 2015.

During the study period, ICU admissions for opioid overdoses increased by almost half, investigators reported in a session and related press briefing an international conference of the American Thoracic Society. Furthermore, ICU deaths from this cause roughly doubled.

Susan London/Frontline Medical News

“This means the opioid use epidemic has probably reached a new level of crisis,” said lead investigator Jennifer P. Stevens, MD, an instructor in medicine at Harvard Medical School, and an adult intensive care physician at Beth Israel Deaconess Medical Center, both in Boston. “And this means that in spite of everything that we can do in the ICU – keeping them alive on ventilators, doing life support, doing acute dialysis, doing round-the-clock care, round-the-clock board-certified intensivist care – we are still not able to make a difference in that mortality.”

Dr. Stevens added that any ICU admission for overdose from opioids is a preventable admission. “So if we have an increase in mortality of this population, we have a number of patients who have preventable deaths in our ICU,” she said.

Efforts to track this epidemic on a national level are important, she said, and the U.S. Centers for Disease Control and Prevention has been investigating opioid overdoses in some cities, including Boston, as they would any epidemic.

The factors driving the observed trends could not be determined from the study data, Dr. Stevens said. But state-specific patterns that show, for example, higher baseline rates and greater increases over time in ICU admissions for opioid overdose in Massachusetts and Indiana may be a starting point for investigation.

Certain practices in the ICU may also be inadvertently contributing. “I imagine that a patient who comes in with an opioid overdose can cause harm to themselves in a number of ways, and the things that we try to do to help them might cause harm in other ways as well,” she said. “So in an effort to try to maintain them in a safe, ventilated state, we might give them a ton of sedation that then prolongs their time on the ventilator. That’s sort of a simple example of how the two could intersect to have a multiplicative effect of harm.”

The idea for the study arose because ICU staff anecdotally noticed an uptick in admissions for opioid use disorder. “Not only were we seeing more people coming in, but we were seeing sicker people coming in, and with the associated tragedy that comes with a lot of young people coming in with opioid use disorder,” Dr. Stevens said. “We wanted to see if this was happening nationally... We asked, is this epidemic now reaching the most technologically advanced parts of our health care system?”

The investigators studied hospitals providing data to Vizient (formerly the University HealthSystem Consortium) between 2009 and 2015. The included hospitals – about 200 for each study year – were predominantly urban and university affiliated, but representation of community hospitals increased during the study period.

Ultimately, analyses were based on a total of 28.2 million hospital discharges of patients aged 18 years or older, which included 4.9 million ICU admissions.

Results reported at the meeting showed that 27,325 patients were admitted to the study hospitals’ ICUs with opioid overdose during the study period, as ascertained from billing codes.

Opioid overdose was seen in 45 patients per 10,000 ICU admissions in 2009 but rose to 65 patients per 10,000 ICU admissions in 2015, a 46% increase.

Furthermore, ICU deaths due to opioid overdose rose by 87% during the same time period, and mortality among patients admitted to the unit with overdose rose at a pace of 0.5% per month.

“This is somewhat unusual because a lot of times, when we are admitting more people to our ICUs or examining [a trend] further, mortality actually goes down. This is partly because maybe we are doing more for them and we are taking care of them in an aggressive way. But it’s also because we are admitting less sick people because we are more aware of the issue,” Dr. Stevens said. “And we saw the opposite of this – we saw that the mortality was going up.”

The use of billing data was a specific means but not a sensitive means of identifying opioid overdoses, she noted. Therefore, the observed values are likely underestimates of these outcomes.

Addressing the opioid overdose epidemic will require a multifaceted approach, according to Dr. Stevens, who disclosed that she had no relevant conflicts of interest.

“Folks are doing very impressive work in the community trying to make sure EMTs and other first responders have access to the tools that they need in those settings,” she said. “But one thing we haven’t approached before is the care that we provide in the ICU, and maybe that’s a space that we need to think more prospectively about.”

Case

A 27-year-old man presented to an ED after experiencing a syncopal episode. His vital signs at presentation were normal. Physical examination was generally normal except that there were blisters on the patient’s abdomen, left hand, and right arm, as well as a hypertrophic nodule on the right elbow (Figure) and hard growths on the digits of the right hand. The patient stated the growths started 5 months ago and had been increasing in size. On further questioning, the patient admitted to “huffing” (ie, inhaling) at least six cans of pressurized dust-removal keyboard cleaning spray daily for the past 11 months.

Why do patients abuse keyboard cleaning spray?

The propellant used in certain liquefied compressed gas products is 1,1-difluoroethane (1,1-DFE), a fluorinated hydrocarbon. It is a member of a broad class of related compounds that are present in spray paints, glues, nail polish removers, fuels, hair sprays, and air-freshening products. These 1,1-DFE-containing products are abused for their rapid and short-acting central nervous system (CNS) depressant effects—not unlike that of ethanol. Typically, the vapor of a volatile hydrocarbon is inhaled directly from the open container (“sniffing”), from a bag (“bagging”), or from a soaked rag (huffing). Not only are such hydrocarbon-containing products easy to conceal, they are also highly accessible and inexpensive. Moreover, there are generally no direct legal consequences resulting from abuse of these substances.

All of the aforementioned factors make hydrocarbons a popular drug of abuse among adolescents. Approximately 75% of the population abusing hydrocarbons is younger than age 18 years, half of whom reported first use prior to age 13 years.^1,2 Though inhalant abuse rarely continues into adulthood, 0.1% of individuals between the ages of 18 and 30 years report having an inhalant-use disorder.

Hydrocarbons and their halogenated derivatives are lipophilic compounds that are rapidly absorbed after inhalation and rapidly distributed to CNS and cardiac tissue. The brain concentration of 1,1-DFE likely peaks higher than concentrations in other organs and is cleared more rapidly.³ Hydrocarbons produce CNS depression secondary to multiple mechanisms, including gamma-aminobutyric acid agonism, dopamine modulation, and N-methyl-D-aspartate-receptor antagonism.^4,5

What causes skin lesions on the abdomen and arms?

The lesions on the patient’s abdomen and extremities were consistent with frostbite. The liquefied compressed gas in computer-cleaning and related products is housed in a pressurized canister. The pressure is released when the spray nozzle is depressed; this causes the liquid to rapidly expand to a gas as it is released, resulting in a quick decrease in the temperature of the metal canister. This process, referred to as adiabatic cooling, demonstrates the first law of thermodynamics. The cold temperature of both the liquid and the canister can cause frostbite in the digits and other parts of the body with which the canister or liquid comes into contact.⁶

Why did the patient have syncope?

Halogenated hydrocarbons inhibit the cardiac delayed rectifier potassium channels involved in the repolarization of cardiac myocytes, causing a delay in repolarization that is manifested as prolongation of the QT interval on an electrocardiogram. This condition places patients at an increased risk of developing torsades de pointes (TdP).⁷ In most cases, TdP is self-terminating; however, if TdP persists, degeneration to ventricular fibrillation will result. Deaths caused in this fashion have been referred to as “sudden sniffing death syndrome,” and account for half of all hydrocarbon-related deaths.^6,8 In addition to the cardiac effects, hydrocarbons are simple asphyxiants that act by displacing oxygen from inspired air, which also contributes to syncope.

It is important to note that epinephrine and other catecholamines increase the risk for dysrhythmias such as TdP in the setting of hydrocarbon abuse.⁹ For this reason, epinephrine should be used with caution in the setting of a hydrocarbon-induced arrhythmia. Beta-adrenergic antagonists such as esmolol and propranolol are preferable because they reduce the incidence of ectopia that may trigger TdP.¹⁰

What is the significance of the masses noted on the examination and radiograph?

Fluorosis is associated with abnormalities of skeletal and dental tissue. Skeletal fluorosis causes osteosclerosis of the axial skeleton, periosteal new bone formation, ligamentous and tendinous ossification, and osteophyte formation. Dental fluorosis causes a yellow/brown discoloration of the teeth with horizontal streaking (mottling), pitting, and chipping.¹¹ Fluorosis is well-described in regions where water fluoride concentrations are high due to industrial exposure; from consumption of fluorinated wine or chronic overconsumption of tea (especially green or black tea); or from fluoridated toothpaste.^12-14 More recently, fluorosis has been described in patients treated for an extended duration of time with voriconazole, a fluorinated antifungal agent.¹⁵ Unlike other hydrocarbon products, fluorinated hydrocarbons such as 1,1-DFE can significantly increase systemic fluoride concentrations with excessive use. Rapid skeletal fluorosis is not well described, but has been reported after chronic abuse of fluorinated hydrocarbons.¹⁶

How is fluorosis diagnosed and managed?

The lack of rapid laboratory testing available for serum, urine, and bone fluoride concentrations makes the initial diagnosis of fluorosis a clinical one. Imaging studies are generally highly suggestive of fluorosis and can be used to support the diagnosis. A dual energy X-ray absorptiometry scan of the spine, hip, femur, and distal portions of the radii can reveal elevated T-scores consistent with osteosclerosis.¹⁴ These findings, in conjunction with bone or joint pain, reduced range of motion, or kyphosis, should prompt clinicians to conduct further testing—even without a confirmed fluoride source. A serum fluoride (reference range, 0.2-3.2 mg/L) and 24-hour urine fluoride (reference range, 0.2-3.2 mg/dL) and creatinine evaluation can be used to diagnose fluorosis. However, a bone biopsy with quantitative bone ash fluoride analysis remains the gold standard for the diagnosis of skeletal fluorosis.¹⁶ Laboratory evaluation should also include an assessment of electrolytes, specifically calcium, 25-hydroxyvitamin D, and alkaline phosphatase. The differential diagnosis should include hemoglobinopathies, renal osteodystrophy, Paget disease, hypothyroidism, and skeletal metastases.¹⁶

Treatment of fluorosis is largely symptomatic and supportive, with identification and discontinuation of the fluoride source. Patients should be referred to an orthopedist for evaluation and management as needed. Evaluation by an endocrinologist should also be considered because patients may have chronic vitamin D and calcium deficiencies as a result of systemic fluorosis.
 

Case Conclusion

The patient’s laboratory assessment was notable for the following: alkaline phosphatase, 624 U/L (reference range, 44-147 IU/L); vitamin D, 10 ng/mL (reference range, 20-40 ng/mL); serum fluoride, 0.3 mg/L (reference range, 0.2-3.2 mg/L); urine fluoride, 52 mg/dL (0.2-3.2 mg/dL); and urine creatinine, 1 g/L (reference range, 0.3-3 g/L). Imaging studies noted periosteal bone formation on the lateral epicondyle of the distal right humerus, as well as similar osseous abnormalities in other locations. A bone biopsy was scheduled. The patient was treated with oral vitamin D and educated about the importance of discontinuing the huffing of all hydrocarbons.

Case

A 27-year-old man presented to an ED after experiencing a syncopal episode. His vital signs at presentation were normal. Physical examination was generally normal except that there were blisters on the patient’s abdomen, left hand, and right arm, as well as a hypertrophic nodule on the right elbow (Figure) and hard growths on the digits of the right hand. The patient stated the growths started 5 months ago and had been increasing in size. On further questioning, the patient admitted to “huffing” (ie, inhaling) at least six cans of pressurized dust-removal keyboard cleaning spray daily for the past 11 months.

Why do patients abuse keyboard cleaning spray?

The propellant used in certain liquefied compressed gas products is 1,1-difluoroethane (1,1-DFE), a fluorinated hydrocarbon. It is a member of a broad class of related compounds that are present in spray paints, glues, nail polish removers, fuels, hair sprays, and air-freshening products. These 1,1-DFE-containing products are abused for their rapid and short-acting central nervous system (CNS) depressant effects—not unlike that of ethanol. Typically, the vapor of a volatile hydrocarbon is inhaled directly from the open container (“sniffing”), from a bag (“bagging”), or from a soaked rag (huffing). Not only are such hydrocarbon-containing products easy to conceal, they are also highly accessible and inexpensive. Moreover, there are generally no direct legal consequences resulting from abuse of these substances.

All of the aforementioned factors make hydrocarbons a popular drug of abuse among adolescents. Approximately 75% of the population abusing hydrocarbons is younger than age 18 years, half of whom reported first use prior to age 13 years.^1,2 Though inhalant abuse rarely continues into adulthood, 0.1% of individuals between the ages of 18 and 30 years report having an inhalant-use disorder.

Hydrocarbons and their halogenated derivatives are lipophilic compounds that are rapidly absorbed after inhalation and rapidly distributed to CNS and cardiac tissue. The brain concentration of 1,1-DFE likely peaks higher than concentrations in other organs and is cleared more rapidly.³ Hydrocarbons produce CNS depression secondary to multiple mechanisms, including gamma-aminobutyric acid agonism, dopamine modulation, and N-methyl-D-aspartate-receptor antagonism.^4,5

What causes skin lesions on the abdomen and arms?

The lesions on the patient’s abdomen and extremities were consistent with frostbite. The liquefied compressed gas in computer-cleaning and related products is housed in a pressurized canister. The pressure is released when the spray nozzle is depressed; this causes the liquid to rapidly expand to a gas as it is released, resulting in a quick decrease in the temperature of the metal canister. This process, referred to as adiabatic cooling, demonstrates the first law of thermodynamics. The cold temperature of both the liquid and the canister can cause frostbite in the digits and other parts of the body with which the canister or liquid comes into contact.⁶

Why did the patient have syncope?

Halogenated hydrocarbons inhibit the cardiac delayed rectifier potassium channels involved in the repolarization of cardiac myocytes, causing a delay in repolarization that is manifested as prolongation of the QT interval on an electrocardiogram. This condition places patients at an increased risk of developing torsades de pointes (TdP).⁷ In most cases, TdP is self-terminating; however, if TdP persists, degeneration to ventricular fibrillation will result. Deaths caused in this fashion have been referred to as “sudden sniffing death syndrome,” and account for half of all hydrocarbon-related deaths.^6,8 In addition to the cardiac effects, hydrocarbons are simple asphyxiants that act by displacing oxygen from inspired air, which also contributes to syncope.

It is important to note that epinephrine and other catecholamines increase the risk for dysrhythmias such as TdP in the setting of hydrocarbon abuse.⁹ For this reason, epinephrine should be used with caution in the setting of a hydrocarbon-induced arrhythmia. Beta-adrenergic antagonists such as esmolol and propranolol are preferable because they reduce the incidence of ectopia that may trigger TdP.¹⁰

What is the significance of the masses noted on the examination and radiograph?

Fluorosis is associated with abnormalities of skeletal and dental tissue. Skeletal fluorosis causes osteosclerosis of the axial skeleton, periosteal new bone formation, ligamentous and tendinous ossification, and osteophyte formation. Dental fluorosis causes a yellow/brown discoloration of the teeth with horizontal streaking (mottling), pitting, and chipping.¹¹ Fluorosis is well-described in regions where water fluoride concentrations are high due to industrial exposure; from consumption of fluorinated wine or chronic overconsumption of tea (especially green or black tea); or from fluoridated toothpaste.^12-14 More recently, fluorosis has been described in patients treated for an extended duration of time with voriconazole, a fluorinated antifungal agent.¹⁵ Unlike other hydrocarbon products, fluorinated hydrocarbons such as 1,1-DFE can significantly increase systemic fluoride concentrations with excessive use. Rapid skeletal fluorosis is not well described, but has been reported after chronic abuse of fluorinated hydrocarbons.¹⁶

How is fluorosis diagnosed and managed?

The lack of rapid laboratory testing available for serum, urine, and bone fluoride concentrations makes the initial diagnosis of fluorosis a clinical one. Imaging studies are generally highly suggestive of fluorosis and can be used to support the diagnosis. A dual energy X-ray absorptiometry scan of the spine, hip, femur, and distal portions of the radii can reveal elevated T-scores consistent with osteosclerosis.¹⁴ These findings, in conjunction with bone or joint pain, reduced range of motion, or kyphosis, should prompt clinicians to conduct further testing—even without a confirmed fluoride source. A serum fluoride (reference range, 0.2-3.2 mg/L) and 24-hour urine fluoride (reference range, 0.2-3.2 mg/dL) and creatinine evaluation can be used to diagnose fluorosis. However, a bone biopsy with quantitative bone ash fluoride analysis remains the gold standard for the diagnosis of skeletal fluorosis.¹⁶ Laboratory evaluation should also include an assessment of electrolytes, specifically calcium, 25-hydroxyvitamin D, and alkaline phosphatase. The differential diagnosis should include hemoglobinopathies, renal osteodystrophy, Paget disease, hypothyroidism, and skeletal metastases.¹⁶

Treatment of fluorosis is largely symptomatic and supportive, with identification and discontinuation of the fluoride source. Patients should be referred to an orthopedist for evaluation and management as needed. Evaluation by an endocrinologist should also be considered because patients may have chronic vitamin D and calcium deficiencies as a result of systemic fluorosis.
 

Case Conclusion

The patient’s laboratory assessment was notable for the following: alkaline phosphatase, 624 U/L (reference range, 44-147 IU/L); vitamin D, 10 ng/mL (reference range, 20-40 ng/mL); serum fluoride, 0.3 mg/L (reference range, 0.2-3.2 mg/L); urine fluoride, 52 mg/dL (0.2-3.2 mg/dL); and urine creatinine, 1 g/L (reference range, 0.3-3 g/L). Imaging studies noted periosteal bone formation on the lateral epicondyle of the distal right humerus, as well as similar osseous abnormalities in other locations. A bone biopsy was scheduled. The patient was treated with oral vitamin D and educated about the importance of discontinuing the huffing of all hydrocarbons.

Case

A 27-year-old man presented to an ED after experiencing a syncopal episode. His vital signs at presentation were normal. Physical examination was generally normal except that there were blisters on the patient’s abdomen, left hand, and right arm, as well as a hypertrophic nodule on the right elbow (Figure) and hard growths on the digits of the right hand. The patient stated the growths started 5 months ago and had been increasing in size. On further questioning, the patient admitted to “huffing” (ie, inhaling) at least six cans of pressurized dust-removal keyboard cleaning spray daily for the past 11 months.

Why do patients abuse keyboard cleaning spray?

The propellant used in certain liquefied compressed gas products is 1,1-difluoroethane (1,1-DFE), a fluorinated hydrocarbon. It is a member of a broad class of related compounds that are present in spray paints, glues, nail polish removers, fuels, hair sprays, and air-freshening products. These 1,1-DFE-containing products are abused for their rapid and short-acting central nervous system (CNS) depressant effects—not unlike that of ethanol. Typically, the vapor of a volatile hydrocarbon is inhaled directly from the open container (“sniffing”), from a bag (“bagging”), or from a soaked rag (huffing). Not only are such hydrocarbon-containing products easy to conceal, they are also highly accessible and inexpensive. Moreover, there are generally no direct legal consequences resulting from abuse of these substances.

All of the aforementioned factors make hydrocarbons a popular drug of abuse among adolescents. Approximately 75% of the population abusing hydrocarbons is younger than age 18 years, half of whom reported first use prior to age 13 years.^1,2 Though inhalant abuse rarely continues into adulthood, 0.1% of individuals between the ages of 18 and 30 years report having an inhalant-use disorder.

Hydrocarbons and their halogenated derivatives are lipophilic compounds that are rapidly absorbed after inhalation and rapidly distributed to CNS and cardiac tissue. The brain concentration of 1,1-DFE likely peaks higher than concentrations in other organs and is cleared more rapidly.³ Hydrocarbons produce CNS depression secondary to multiple mechanisms, including gamma-aminobutyric acid agonism, dopamine modulation, and N-methyl-D-aspartate-receptor antagonism.^4,5

What causes skin lesions on the abdomen and arms?

The lesions on the patient’s abdomen and extremities were consistent with frostbite. The liquefied compressed gas in computer-cleaning and related products is housed in a pressurized canister. The pressure is released when the spray nozzle is depressed; this causes the liquid to rapidly expand to a gas as it is released, resulting in a quick decrease in the temperature of the metal canister. This process, referred to as adiabatic cooling, demonstrates the first law of thermodynamics. The cold temperature of both the liquid and the canister can cause frostbite in the digits and other parts of the body with which the canister or liquid comes into contact.⁶

Why did the patient have syncope?

Halogenated hydrocarbons inhibit the cardiac delayed rectifier potassium channels involved in the repolarization of cardiac myocytes, causing a delay in repolarization that is manifested as prolongation of the QT interval on an electrocardiogram. This condition places patients at an increased risk of developing torsades de pointes (TdP).⁷ In most cases, TdP is self-terminating; however, if TdP persists, degeneration to ventricular fibrillation will result. Deaths caused in this fashion have been referred to as “sudden sniffing death syndrome,” and account for half of all hydrocarbon-related deaths.^6,8 In addition to the cardiac effects, hydrocarbons are simple asphyxiants that act by displacing oxygen from inspired air, which also contributes to syncope.

It is important to note that epinephrine and other catecholamines increase the risk for dysrhythmias such as TdP in the setting of hydrocarbon abuse.⁹ For this reason, epinephrine should be used with caution in the setting of a hydrocarbon-induced arrhythmia. Beta-adrenergic antagonists such as esmolol and propranolol are preferable because they reduce the incidence of ectopia that may trigger TdP.¹⁰

What is the significance of the masses noted on the examination and radiograph?

Fluorosis is associated with abnormalities of skeletal and dental tissue. Skeletal fluorosis causes osteosclerosis of the axial skeleton, periosteal new bone formation, ligamentous and tendinous ossification, and osteophyte formation. Dental fluorosis causes a yellow/brown discoloration of the teeth with horizontal streaking (mottling), pitting, and chipping.¹¹ Fluorosis is well-described in regions where water fluoride concentrations are high due to industrial exposure; from consumption of fluorinated wine or chronic overconsumption of tea (especially green or black tea); or from fluoridated toothpaste.^12-14 More recently, fluorosis has been described in patients treated for an extended duration of time with voriconazole, a fluorinated antifungal agent.¹⁵ Unlike other hydrocarbon products, fluorinated hydrocarbons such as 1,1-DFE can significantly increase systemic fluoride concentrations with excessive use. Rapid skeletal fluorosis is not well described, but has been reported after chronic abuse of fluorinated hydrocarbons.¹⁶

How is fluorosis diagnosed and managed?

The lack of rapid laboratory testing available for serum, urine, and bone fluoride concentrations makes the initial diagnosis of fluorosis a clinical one. Imaging studies are generally highly suggestive of fluorosis and can be used to support the diagnosis. A dual energy X-ray absorptiometry scan of the spine, hip, femur, and distal portions of the radii can reveal elevated T-scores consistent with osteosclerosis.¹⁴ These findings, in conjunction with bone or joint pain, reduced range of motion, or kyphosis, should prompt clinicians to conduct further testing—even without a confirmed fluoride source. A serum fluoride (reference range, 0.2-3.2 mg/L) and 24-hour urine fluoride (reference range, 0.2-3.2 mg/dL) and creatinine evaluation can be used to diagnose fluorosis. However, a bone biopsy with quantitative bone ash fluoride analysis remains the gold standard for the diagnosis of skeletal fluorosis.¹⁶ Laboratory evaluation should also include an assessment of electrolytes, specifically calcium, 25-hydroxyvitamin D, and alkaline phosphatase. The differential diagnosis should include hemoglobinopathies, renal osteodystrophy, Paget disease, hypothyroidism, and skeletal metastases.¹⁶

Treatment of fluorosis is largely symptomatic and supportive, with identification and discontinuation of the fluoride source. Patients should be referred to an orthopedist for evaluation and management as needed. Evaluation by an endocrinologist should also be considered because patients may have chronic vitamin D and calcium deficiencies as a result of systemic fluorosis.
 

Case Conclusion

The patient’s laboratory assessment was notable for the following: alkaline phosphatase, 624 U/L (reference range, 44-147 IU/L); vitamin D, 10 ng/mL (reference range, 20-40 ng/mL); serum fluoride, 0.3 mg/L (reference range, 0.2-3.2 mg/L); urine fluoride, 52 mg/dL (0.2-3.2 mg/dL); and urine creatinine, 1 g/L (reference range, 0.3-3 g/L). Imaging studies noted periosteal bone formation on the lateral epicondyle of the distal right humerus, as well as similar osseous abnormalities in other locations. A bone biopsy was scheduled. The patient was treated with oral vitamin D and educated about the importance of discontinuing the huffing of all hydrocarbons.

The incidence of exposure to nicotine and tobacco products in children less than 6 years old increased significantly from 2012 to 2015, according to Alisha Kamboj and her associates.

From January 2012 to April 2015, the National Poison Data System received 29,141 reports of nicotine and tobacco product exposure in children under 6 years of age, averaging 729 children per month. The annual rate of exposure increased from 3.0/100,000 children in 2012 to 4.2/100,000 in 2014. A dramatic increase in exposure to e-cigarettes drove the overall increase, with monthly reports of e-cigarette use rising nearly 1,500% from January 2012 to April 2015.

Carpe89/ThinkStock

Nearly 80% of children exposed were younger than 2 years old, and the median age of exposed children was 1.1 years. Children younger than 2 accounted for 44.1% of e-cigarette exposures, 91.6% of cigarette exposures, and 75.4% of exposures to other tobacco products, the investigators noted.

Children exposed to e-cigarettes were significantly more likely to be admitted to a health care facility and to have severe outcomes than were children exposed to cigarettes, with odds ratios of 5.19 and 2.6, respectively. One death – of a 1-year-old child – was associated with nicotine liquid.

“Educating child caregivers about potential clinical effects and outcomes associated with nicotine exposure may help motivate adoption of safety behaviors and aid in identification of symptoms in the event of an exposure. Adults in households with children [younger than] 6 years should be counseled on vaping cessation and strongly encouraged not to use or store e-cigarettes, e-liquid, and related products in the home,” the investigators recommended.

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0041).

[email protected]

The incidence of exposure to nicotine and tobacco products in children less than 6 years old increased significantly from 2012 to 2015, according to Alisha Kamboj and her associates.

From January 2012 to April 2015, the National Poison Data System received 29,141 reports of nicotine and tobacco product exposure in children under 6 years of age, averaging 729 children per month. The annual rate of exposure increased from 3.0/100,000 children in 2012 to 4.2/100,000 in 2014. A dramatic increase in exposure to e-cigarettes drove the overall increase, with monthly reports of e-cigarette use rising nearly 1,500% from January 2012 to April 2015.

Carpe89/ThinkStock

Nearly 80% of children exposed were younger than 2 years old, and the median age of exposed children was 1.1 years. Children younger than 2 accounted for 44.1% of e-cigarette exposures, 91.6% of cigarette exposures, and 75.4% of exposures to other tobacco products, the investigators noted.

Children exposed to e-cigarettes were significantly more likely to be admitted to a health care facility and to have severe outcomes than were children exposed to cigarettes, with odds ratios of 5.19 and 2.6, respectively. One death – of a 1-year-old child – was associated with nicotine liquid.

“Educating child caregivers about potential clinical effects and outcomes associated with nicotine exposure may help motivate adoption of safety behaviors and aid in identification of symptoms in the event of an exposure. Adults in households with children [younger than] 6 years should be counseled on vaping cessation and strongly encouraged not to use or store e-cigarettes, e-liquid, and related products in the home,” the investigators recommended.

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0041).

[email protected]

The incidence of exposure to nicotine and tobacco products in children less than 6 years old increased significantly from 2012 to 2015, according to Alisha Kamboj and her associates.

From January 2012 to April 2015, the National Poison Data System received 29,141 reports of nicotine and tobacco product exposure in children under 6 years of age, averaging 729 children per month. The annual rate of exposure increased from 3.0/100,000 children in 2012 to 4.2/100,000 in 2014. A dramatic increase in exposure to e-cigarettes drove the overall increase, with monthly reports of e-cigarette use rising nearly 1,500% from January 2012 to April 2015.

Carpe89/ThinkStock

Nearly 80% of children exposed were younger than 2 years old, and the median age of exposed children was 1.1 years. Children younger than 2 accounted for 44.1% of e-cigarette exposures, 91.6% of cigarette exposures, and 75.4% of exposures to other tobacco products, the investigators noted.

Children exposed to e-cigarettes were significantly more likely to be admitted to a health care facility and to have severe outcomes than were children exposed to cigarettes, with odds ratios of 5.19 and 2.6, respectively. One death – of a 1-year-old child – was associated with nicotine liquid.

“Educating child caregivers about potential clinical effects and outcomes associated with nicotine exposure may help motivate adoption of safety behaviors and aid in identification of symptoms in the event of an exposure. Adults in households with children [younger than] 6 years should be counseled on vaping cessation and strongly encouraged not to use or store e-cigarettes, e-liquid, and related products in the home,” the investigators recommended.

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0041).

[email protected]