Pulmonary Health Hub

A 58-year-old man presented to the emergency department (ED) via emergency medical services (EMS) with shortness of breath, lightheadedness, and nausea. Upon arrival to the ED, most of his symptoms had resolved. The patient reported that he had taken a two-hour flight into town the previous day and had spent an uneventful evening at a local hotel. He said that he began experiencing shortness of breath and lightheadedness soon after entering his rental vehicle an hour prior to presentation, explaining that he felt as if he “could not get any air.”

He denied chest pain, leg pain or swelling, abdominal pain, or recent illness. Medical history was significant for hypertension, for which he was taking losartan and amlodipine. He had no drug allergies, surgical history, or smoking history. Of note, when the hotel clerk got in the same rental vehicle to move it, he developed symptoms similar to those of the patient. As with the patient, the clerk’s symptoms quickly resolved after he got out of the vehicle.

The patient’s vital signs at examination included an oral temperature of 97.5°F; pulse, 62 beats/min; respiratory rate (RR), 18 breaths/min; blood pressure, 133/83 mm Hg; and O₂ saturation, 100% on room air. He was alert and oriented, in no distress, easily conversational, and without diaphoresis. The lungs were clear to auscultation bilaterally, and there was no calf swelling, tenderness, or palpable cords. The remainder of the physical exam was normal.

Ancillary studies included a normal chest X-ray. An ECG demonstrated sinus bradycardia with a rate of 56 beats/min but no evidence of ischemia or right heart strain. Complete blood count, troponin I, D-dimer, and creatine phosphokinase (CPK) with MB fraction levels were all within normal limits. A serum chemistry panel was also within normal limits, except for a serum glucose level of 181 mg/dL. Venous co-oximetry showed a carboxyhemoglobin level of 0.0, and methemoglobin level of 0.5 gm% (normal range, 0.4-1.5).

Since both the patient’s and hotel clerk’s symptoms started when each was in the rental car, the patient was questioned about the vehicle and its contents. The car was a late-model rental in good condition per report. The patient informed the treating emergency physician that he worked as a decorative cake salesman and had brought cake samples with him to display at a trade show. He further stated that he had left these samples in the car overnight, packed in dry ice.

What's the solution to this unusual case?

Upon learning this information, EMS was contacted and instructed to return to the hotel and rental vehicle. The hotel room was noted to have normal levels of O₂ and carbon monoxide (CO) on measurement. Investigation of the car revealed normal levels of CO but O₂ levels too low to read on the sensor. The emergency team concluded that the dry ice (the solid form of carbon dioxide [CO₂]) sublimed to CO₂ gas overnight. This displaced the O₂ in the vehicle, resulting in severe hypoxia and the symptoms of both the patient and hotel clerk.

The patient was initially placed on 15 L of O₂ via a nonrebreather mask, then switched to 2 L of O₂ via nasal cannula. He was observed for a total of four hours after arrival; as he remained symptom-free, he was discharged home. Postdischarge follow-up information was not obtainable.

DISCUSSION
Carbon dioxide is prevalent in everyday life, from an agent in fire extinguishers and carbonation in beverages to byproducts of cellular metabolism. Similar to CO, it is a colorless and odorless gas.

Carbon dioxide is commonly used in the food industry as dry ice to keep items cold. In its solid state, CO₂ can cause severe frostbite with direct contact, similar to a burn. However, when dry ice is warmed and sublimated to a gaseous state, large amounts of CO₂ are generated, and this heavy gas can accumulate and displace air (ie, atmospheric O₂), especially in confined spaces. In low concentrations, gaseous CO₂ appears to have minimal toxicologic effects, but at higher concentrations it can cause tachycardia, tachypnea, dyspnea, visual disturbances, arrhythmias, impaired levels of consciousness, and death.

Carbon dioxide primarily acts as a simple asphyxiant, but it also dissolves in serum as carbonic acid, resulting in a metabolic acidosis. Compensation for this acidosis is accomplished by an increased RR (ie, respiratory alkalosis), which further worsens the intake of CO₂.^1,2

The normal concentration of CO₂ in the atmosphere is approximately 0.04% (396 ppm). The Occupational Safety and Health Administration (OSHA) has set a maximum safe exposure level of CO₂ at 0.5% (5,000 ppm) over an eight-hour day.³ Concentrations as low as 1% (10,000 ppm) may cause drowsiness. Exposure to concentrations of 7% to 10% for several minutes to an hour results in headache, tachycardia, dyspnea, and hyperventilation. At levels of 10% to 15%, dizziness, severe muscle twitching, and loss of consciousness can occur after only a few minutes. Death occurs within minutes at concentrations greater than 30%.²

Carbon dioxide also acts as a potent cerebral vasodilator, which may explain symptoms such as headache and dizziness.² The severity of symptoms is dependent on the concentration of CO₂, the length of the exposure, and the underlying health of the patient. Elevated concentrations of CO₂ can occur in areas where there is limited or poor ventilation, such as in a mine (where it is known as blackdamp, stythe, or choke damp),⁴ submarine, grain silo, or a sealed building without mechanical ventilation.

Continue for other case presentations >>

Other case presentations
Similar cases have been described in the literature. In one case, following Hurricane Ivan, a 34-year-old man placed four 25-pound blocks of dry ice wrapped in paper in the front seat of his truck with the windows closed.⁵ After driving less than one-quarter of a mile, he developed dyspnea and telephoned for help before losing consciousness. Fortunately, he was found in time and recovered soon after the doors to his truck were opened.⁵

In another case, a 59-year-old man entered a walk-in freezer that contained dry ice wrapped loosely in plastic. He was found inside the freezer 20 minutes later in cardiac arrest; resuscitation efforts were unsuccessful. Investigation of the freezer found an initial O₂ concentration of 13% (normal level, 20.93%) and an estimated CO₂ level of 40%.⁵

Similarly, a 35-year-old woman was inadvertently locked in a bank vault while storing receipts. In a bid for help, she pulled the fire alarm, which triggered a CO₂-based fire-extinguishing system. The fire department responded and found the woman dead in the vault 30 minutes later. The cause of death was labeled as CO₂ intoxication.⁶

Natural phenomena
There have also been documented cases of CO₂ toxicity associated with volcanic eruption and other natural phenomena; for example, the Lake Nyos, Cameroon, West Africa incident in 1986. In this event, a magma pocket underlying the lake saturated the water with CO₂ stored as carbonic acid in the water. When a landslide hit the lake, it caused the carbonic acid stored in the depths of the lake to be upheaved to the surface, where it turned back into CO₂ and was released into the atmosphere. Since CO₂ is heavier than O₂, it displaced the O₂ near the ground, resulting in the suffocation and death of 1,700 people in the surrounding villages.²

Next page: Differential diagnosis >>

Differential diagnosis
When CO₂ toxicity is suspected, other conditions should be considered, as there may be more than one process involved. For example, other causes of coma or dyspnea should be investigated, including trauma, hypoglycemia, CO, methemoglobinemia, or other metabolic processes. In addition, a patient may have a pre-existing condition, such as a trauma or an altered mental status due to drugs or alcohol, all of which can increase his or her susceptibility to the effects of CO₂.

Evaluation and treatment
Useful laboratory testing includes arterial blood gas, venous co-oximetry for carboxyhemoglobin, chemistry panels, ethanol testing, and radiographs or CT, as indicated.

Initial management of suspected CO₂ toxicity entails first removing the patient from the source of the gas. Rescuers must exercise caution so as to prevent a mass-casualty incident. Once out of the dangerous environment, as long as the patient is conscious and spontaneously breathing, supportive measures are generally all that are necessary. Oxygen should be applied, after which the spontaneously breathing patient without underlying lung disease should rapidly return to normal.

If there is marked decrease in mental status or poor respiratory drive despite O₂ administration, intubation with mechanical ventilation may be required. A higher-than-normal RR will help remove excessive CO₂ in this instance.

If a respiratory acidosis is present, IV sodium bicarbonate should be avoided, as this may increase the level of serum CO₂. IV fluids and other supportive measures, including treatment for any concurrent conditions, may be indicated.

REFERENCES
1. Nelson LS, Odujebe OA. Simple asphyxiants and pulmonary irritants. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies, 9th ed. New York, NY: McGraw-Hill; 2011:1644-1645.
2. Langford NJ. Carbon dioxide poisoning. Toxicol Rev. 2005;24(4):229-235.
3. Occupational Health and Safety Standards. Table Z-1, Limits for air contaminants. Occupational Safety and Health Administration Web site. www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=9992. Accessed January 19, 2015.
4. Hedlund FH. The extreme carbon dioxide outburst at the Menzengraben potash mine 7 July 1953. Safety Sci. 2012;50(3):537-553.
5. Dunford JV, Lucas J, Vent N, et al. Asphyxiation due to dry ice in a walk-in freezer. ­ J Emerg Med.­ 2009;36(4):353-356.
6. Gill JR, Ely SF, Hua Z. Environmental gas displacement: three accidental deaths in the workplace. Am J Forensic Med Pathol. 2002;23(1):26-30.

A 58-year-old man presented to the emergency department (ED) via emergency medical services (EMS) with shortness of breath, lightheadedness, and nausea. Upon arrival to the ED, most of his symptoms had resolved. The patient reported that he had taken a two-hour flight into town the previous day and had spent an uneventful evening at a local hotel. He said that he began experiencing shortness of breath and lightheadedness soon after entering his rental vehicle an hour prior to presentation, explaining that he felt as if he “could not get any air.”

He denied chest pain, leg pain or swelling, abdominal pain, or recent illness. Medical history was significant for hypertension, for which he was taking losartan and amlodipine. He had no drug allergies, surgical history, or smoking history. Of note, when the hotel clerk got in the same rental vehicle to move it, he developed symptoms similar to those of the patient. As with the patient, the clerk’s symptoms quickly resolved after he got out of the vehicle.

The patient’s vital signs at examination included an oral temperature of 97.5°F; pulse, 62 beats/min; respiratory rate (RR), 18 breaths/min; blood pressure, 133/83 mm Hg; and O₂ saturation, 100% on room air. He was alert and oriented, in no distress, easily conversational, and without diaphoresis. The lungs were clear to auscultation bilaterally, and there was no calf swelling, tenderness, or palpable cords. The remainder of the physical exam was normal.

Ancillary studies included a normal chest X-ray. An ECG demonstrated sinus bradycardia with a rate of 56 beats/min but no evidence of ischemia or right heart strain. Complete blood count, troponin I, D-dimer, and creatine phosphokinase (CPK) with MB fraction levels were all within normal limits. A serum chemistry panel was also within normal limits, except for a serum glucose level of 181 mg/dL. Venous co-oximetry showed a carboxyhemoglobin level of 0.0, and methemoglobin level of 0.5 gm% (normal range, 0.4-1.5).

Since both the patient’s and hotel clerk’s symptoms started when each was in the rental car, the patient was questioned about the vehicle and its contents. The car was a late-model rental in good condition per report. The patient informed the treating emergency physician that he worked as a decorative cake salesman and had brought cake samples with him to display at a trade show. He further stated that he had left these samples in the car overnight, packed in dry ice.

What's the solution to this unusual case?

Upon learning this information, EMS was contacted and instructed to return to the hotel and rental vehicle. The hotel room was noted to have normal levels of O₂ and carbon monoxide (CO) on measurement. Investigation of the car revealed normal levels of CO but O₂ levels too low to read on the sensor. The emergency team concluded that the dry ice (the solid form of carbon dioxide [CO₂]) sublimed to CO₂ gas overnight. This displaced the O₂ in the vehicle, resulting in severe hypoxia and the symptoms of both the patient and hotel clerk.

The patient was initially placed on 15 L of O₂ via a nonrebreather mask, then switched to 2 L of O₂ via nasal cannula. He was observed for a total of four hours after arrival; as he remained symptom-free, he was discharged home. Postdischarge follow-up information was not obtainable.

DISCUSSION
Carbon dioxide is prevalent in everyday life, from an agent in fire extinguishers and carbonation in beverages to byproducts of cellular metabolism. Similar to CO, it is a colorless and odorless gas.

Carbon dioxide is commonly used in the food industry as dry ice to keep items cold. In its solid state, CO₂ can cause severe frostbite with direct contact, similar to a burn. However, when dry ice is warmed and sublimated to a gaseous state, large amounts of CO₂ are generated, and this heavy gas can accumulate and displace air (ie, atmospheric O₂), especially in confined spaces. In low concentrations, gaseous CO₂ appears to have minimal toxicologic effects, but at higher concentrations it can cause tachycardia, tachypnea, dyspnea, visual disturbances, arrhythmias, impaired levels of consciousness, and death.

Carbon dioxide primarily acts as a simple asphyxiant, but it also dissolves in serum as carbonic acid, resulting in a metabolic acidosis. Compensation for this acidosis is accomplished by an increased RR (ie, respiratory alkalosis), which further worsens the intake of CO₂.^1,2

The normal concentration of CO₂ in the atmosphere is approximately 0.04% (396 ppm). The Occupational Safety and Health Administration (OSHA) has set a maximum safe exposure level of CO₂ at 0.5% (5,000 ppm) over an eight-hour day.³ Concentrations as low as 1% (10,000 ppm) may cause drowsiness. Exposure to concentrations of 7% to 10% for several minutes to an hour results in headache, tachycardia, dyspnea, and hyperventilation. At levels of 10% to 15%, dizziness, severe muscle twitching, and loss of consciousness can occur after only a few minutes. Death occurs within minutes at concentrations greater than 30%.²

Carbon dioxide also acts as a potent cerebral vasodilator, which may explain symptoms such as headache and dizziness.² The severity of symptoms is dependent on the concentration of CO₂, the length of the exposure, and the underlying health of the patient. Elevated concentrations of CO₂ can occur in areas where there is limited or poor ventilation, such as in a mine (where it is known as blackdamp, stythe, or choke damp),⁴ submarine, grain silo, or a sealed building without mechanical ventilation.

Continue for other case presentations >>

Other case presentations
Similar cases have been described in the literature. In one case, following Hurricane Ivan, a 34-year-old man placed four 25-pound blocks of dry ice wrapped in paper in the front seat of his truck with the windows closed.⁵ After driving less than one-quarter of a mile, he developed dyspnea and telephoned for help before losing consciousness. Fortunately, he was found in time and recovered soon after the doors to his truck were opened.⁵

In another case, a 59-year-old man entered a walk-in freezer that contained dry ice wrapped loosely in plastic. He was found inside the freezer 20 minutes later in cardiac arrest; resuscitation efforts were unsuccessful. Investigation of the freezer found an initial O₂ concentration of 13% (normal level, 20.93%) and an estimated CO₂ level of 40%.⁵

Similarly, a 35-year-old woman was inadvertently locked in a bank vault while storing receipts. In a bid for help, she pulled the fire alarm, which triggered a CO₂-based fire-extinguishing system. The fire department responded and found the woman dead in the vault 30 minutes later. The cause of death was labeled as CO₂ intoxication.⁶

Natural phenomena
There have also been documented cases of CO₂ toxicity associated with volcanic eruption and other natural phenomena; for example, the Lake Nyos, Cameroon, West Africa incident in 1986. In this event, a magma pocket underlying the lake saturated the water with CO₂ stored as carbonic acid in the water. When a landslide hit the lake, it caused the carbonic acid stored in the depths of the lake to be upheaved to the surface, where it turned back into CO₂ and was released into the atmosphere. Since CO₂ is heavier than O₂, it displaced the O₂ near the ground, resulting in the suffocation and death of 1,700 people in the surrounding villages.²

Next page: Differential diagnosis >>

Differential diagnosis
When CO₂ toxicity is suspected, other conditions should be considered, as there may be more than one process involved. For example, other causes of coma or dyspnea should be investigated, including trauma, hypoglycemia, CO, methemoglobinemia, or other metabolic processes. In addition, a patient may have a pre-existing condition, such as a trauma or an altered mental status due to drugs or alcohol, all of which can increase his or her susceptibility to the effects of CO₂.

Evaluation and treatment
Useful laboratory testing includes arterial blood gas, venous co-oximetry for carboxyhemoglobin, chemistry panels, ethanol testing, and radiographs or CT, as indicated.

Initial management of suspected CO₂ toxicity entails first removing the patient from the source of the gas. Rescuers must exercise caution so as to prevent a mass-casualty incident. Once out of the dangerous environment, as long as the patient is conscious and spontaneously breathing, supportive measures are generally all that are necessary. Oxygen should be applied, after which the spontaneously breathing patient without underlying lung disease should rapidly return to normal.

If there is marked decrease in mental status or poor respiratory drive despite O₂ administration, intubation with mechanical ventilation may be required. A higher-than-normal RR will help remove excessive CO₂ in this instance.

If a respiratory acidosis is present, IV sodium bicarbonate should be avoided, as this may increase the level of serum CO₂. IV fluids and other supportive measures, including treatment for any concurrent conditions, may be indicated.

REFERENCES
1. Nelson LS, Odujebe OA. Simple asphyxiants and pulmonary irritants. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies, 9th ed. New York, NY: McGraw-Hill; 2011:1644-1645.
2. Langford NJ. Carbon dioxide poisoning. Toxicol Rev. 2005;24(4):229-235.
3. Occupational Health and Safety Standards. Table Z-1, Limits for air contaminants. Occupational Safety and Health Administration Web site. www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=9992. Accessed January 19, 2015.
4. Hedlund FH. The extreme carbon dioxide outburst at the Menzengraben potash mine 7 July 1953. Safety Sci. 2012;50(3):537-553.
5. Dunford JV, Lucas J, Vent N, et al. Asphyxiation due to dry ice in a walk-in freezer. ­ J Emerg Med.­ 2009;36(4):353-356.
6. Gill JR, Ely SF, Hua Z. Environmental gas displacement: three accidental deaths in the workplace. Am J Forensic Med Pathol. 2002;23(1):26-30.

A 58-year-old man presented to the emergency department (ED) via emergency medical services (EMS) with shortness of breath, lightheadedness, and nausea. Upon arrival to the ED, most of his symptoms had resolved. The patient reported that he had taken a two-hour flight into town the previous day and had spent an uneventful evening at a local hotel. He said that he began experiencing shortness of breath and lightheadedness soon after entering his rental vehicle an hour prior to presentation, explaining that he felt as if he “could not get any air.”

He denied chest pain, leg pain or swelling, abdominal pain, or recent illness. Medical history was significant for hypertension, for which he was taking losartan and amlodipine. He had no drug allergies, surgical history, or smoking history. Of note, when the hotel clerk got in the same rental vehicle to move it, he developed symptoms similar to those of the patient. As with the patient, the clerk’s symptoms quickly resolved after he got out of the vehicle.

The patient’s vital signs at examination included an oral temperature of 97.5°F; pulse, 62 beats/min; respiratory rate (RR), 18 breaths/min; blood pressure, 133/83 mm Hg; and O₂ saturation, 100% on room air. He was alert and oriented, in no distress, easily conversational, and without diaphoresis. The lungs were clear to auscultation bilaterally, and there was no calf swelling, tenderness, or palpable cords. The remainder of the physical exam was normal.

Ancillary studies included a normal chest X-ray. An ECG demonstrated sinus bradycardia with a rate of 56 beats/min but no evidence of ischemia or right heart strain. Complete blood count, troponin I, D-dimer, and creatine phosphokinase (CPK) with MB fraction levels were all within normal limits. A serum chemistry panel was also within normal limits, except for a serum glucose level of 181 mg/dL. Venous co-oximetry showed a carboxyhemoglobin level of 0.0, and methemoglobin level of 0.5 gm% (normal range, 0.4-1.5).

Since both the patient’s and hotel clerk’s symptoms started when each was in the rental car, the patient was questioned about the vehicle and its contents. The car was a late-model rental in good condition per report. The patient informed the treating emergency physician that he worked as a decorative cake salesman and had brought cake samples with him to display at a trade show. He further stated that he had left these samples in the car overnight, packed in dry ice.

What's the solution to this unusual case?

Upon learning this information, EMS was contacted and instructed to return to the hotel and rental vehicle. The hotel room was noted to have normal levels of O₂ and carbon monoxide (CO) on measurement. Investigation of the car revealed normal levels of CO but O₂ levels too low to read on the sensor. The emergency team concluded that the dry ice (the solid form of carbon dioxide [CO₂]) sublimed to CO₂ gas overnight. This displaced the O₂ in the vehicle, resulting in severe hypoxia and the symptoms of both the patient and hotel clerk.

The patient was initially placed on 15 L of O₂ via a nonrebreather mask, then switched to 2 L of O₂ via nasal cannula. He was observed for a total of four hours after arrival; as he remained symptom-free, he was discharged home. Postdischarge follow-up information was not obtainable.

DISCUSSION
Carbon dioxide is prevalent in everyday life, from an agent in fire extinguishers and carbonation in beverages to byproducts of cellular metabolism. Similar to CO, it is a colorless and odorless gas.

Carbon dioxide is commonly used in the food industry as dry ice to keep items cold. In its solid state, CO₂ can cause severe frostbite with direct contact, similar to a burn. However, when dry ice is warmed and sublimated to a gaseous state, large amounts of CO₂ are generated, and this heavy gas can accumulate and displace air (ie, atmospheric O₂), especially in confined spaces. In low concentrations, gaseous CO₂ appears to have minimal toxicologic effects, but at higher concentrations it can cause tachycardia, tachypnea, dyspnea, visual disturbances, arrhythmias, impaired levels of consciousness, and death.

Carbon dioxide primarily acts as a simple asphyxiant, but it also dissolves in serum as carbonic acid, resulting in a metabolic acidosis. Compensation for this acidosis is accomplished by an increased RR (ie, respiratory alkalosis), which further worsens the intake of CO₂.^1,2

The normal concentration of CO₂ in the atmosphere is approximately 0.04% (396 ppm). The Occupational Safety and Health Administration (OSHA) has set a maximum safe exposure level of CO₂ at 0.5% (5,000 ppm) over an eight-hour day.³ Concentrations as low as 1% (10,000 ppm) may cause drowsiness. Exposure to concentrations of 7% to 10% for several minutes to an hour results in headache, tachycardia, dyspnea, and hyperventilation. At levels of 10% to 15%, dizziness, severe muscle twitching, and loss of consciousness can occur after only a few minutes. Death occurs within minutes at concentrations greater than 30%.²

Carbon dioxide also acts as a potent cerebral vasodilator, which may explain symptoms such as headache and dizziness.² The severity of symptoms is dependent on the concentration of CO₂, the length of the exposure, and the underlying health of the patient. Elevated concentrations of CO₂ can occur in areas where there is limited or poor ventilation, such as in a mine (where it is known as blackdamp, stythe, or choke damp),⁴ submarine, grain silo, or a sealed building without mechanical ventilation.

Continue for other case presentations >>

Other case presentations
Similar cases have been described in the literature. In one case, following Hurricane Ivan, a 34-year-old man placed four 25-pound blocks of dry ice wrapped in paper in the front seat of his truck with the windows closed.⁵ After driving less than one-quarter of a mile, he developed dyspnea and telephoned for help before losing consciousness. Fortunately, he was found in time and recovered soon after the doors to his truck were opened.⁵

In another case, a 59-year-old man entered a walk-in freezer that contained dry ice wrapped loosely in plastic. He was found inside the freezer 20 minutes later in cardiac arrest; resuscitation efforts were unsuccessful. Investigation of the freezer found an initial O₂ concentration of 13% (normal level, 20.93%) and an estimated CO₂ level of 40%.⁵

Similarly, a 35-year-old woman was inadvertently locked in a bank vault while storing receipts. In a bid for help, she pulled the fire alarm, which triggered a CO₂-based fire-extinguishing system. The fire department responded and found the woman dead in the vault 30 minutes later. The cause of death was labeled as CO₂ intoxication.⁶

Natural phenomena
There have also been documented cases of CO₂ toxicity associated with volcanic eruption and other natural phenomena; for example, the Lake Nyos, Cameroon, West Africa incident in 1986. In this event, a magma pocket underlying the lake saturated the water with CO₂ stored as carbonic acid in the water. When a landslide hit the lake, it caused the carbonic acid stored in the depths of the lake to be upheaved to the surface, where it turned back into CO₂ and was released into the atmosphere. Since CO₂ is heavier than O₂, it displaced the O₂ near the ground, resulting in the suffocation and death of 1,700 people in the surrounding villages.²

Next page: Differential diagnosis >>

Differential diagnosis
When CO₂ toxicity is suspected, other conditions should be considered, as there may be more than one process involved. For example, other causes of coma or dyspnea should be investigated, including trauma, hypoglycemia, CO, methemoglobinemia, or other metabolic processes. In addition, a patient may have a pre-existing condition, such as a trauma or an altered mental status due to drugs or alcohol, all of which can increase his or her susceptibility to the effects of CO₂.

Evaluation and treatment
Useful laboratory testing includes arterial blood gas, venous co-oximetry for carboxyhemoglobin, chemistry panels, ethanol testing, and radiographs or CT, as indicated.

Initial management of suspected CO₂ toxicity entails first removing the patient from the source of the gas. Rescuers must exercise caution so as to prevent a mass-casualty incident. Once out of the dangerous environment, as long as the patient is conscious and spontaneously breathing, supportive measures are generally all that are necessary. Oxygen should be applied, after which the spontaneously breathing patient without underlying lung disease should rapidly return to normal.

If there is marked decrease in mental status or poor respiratory drive despite O₂ administration, intubation with mechanical ventilation may be required. A higher-than-normal RR will help remove excessive CO₂ in this instance.

If a respiratory acidosis is present, IV sodium bicarbonate should be avoided, as this may increase the level of serum CO₂. IV fluids and other supportive measures, including treatment for any concurrent conditions, may be indicated.

REFERENCES
1. Nelson LS, Odujebe OA. Simple asphyxiants and pulmonary irritants. In: Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies, 9th ed. New York, NY: McGraw-Hill; 2011:1644-1645.
2. Langford NJ. Carbon dioxide poisoning. Toxicol Rev. 2005;24(4):229-235.
3. Occupational Health and Safety Standards. Table Z-1, Limits for air contaminants. Occupational Safety and Health Administration Web site. www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=9992. Accessed January 19, 2015.
4. Hedlund FH. The extreme carbon dioxide outburst at the Menzengraben potash mine 7 July 1953. Safety Sci. 2012;50(3):537-553.
5. Dunford JV, Lucas J, Vent N, et al. Asphyxiation due to dry ice in a walk-in freezer. ­ J Emerg Med.­ 2009;36(4):353-356.
6. Gill JR, Ely SF, Hua Z. Environmental gas displacement: three accidental deaths in the workplace. Am J Forensic Med Pathol. 2002;23(1):26-30.

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

PHOENIX – A pediatric ICU protocol to minimize sedation during intubation did not reduce ventilator days among children with acute respiratory failure, compared with usual care, in a randomized trial of 2,449 children across 31 ICUs.

The results were published online Jan. 20 in JAMA.

Seventeen pediatric ICUs (PICUs) followed a protocol that included sedation adjustment at least every 8 hours based on phase of illness; arousal assessments during titration and weaning; daily extubation readiness testing when spontaneously breathing; and weaning off opioids and benzodiazepines if patients were on them for 5 or more days, instead of simply discontinuing them.

The 1,225 children on the protocol were ventilated a median of 6.5 days, the same length as the 1,224 children in the 14 usual-care PICUs. There were no differences in sedation-related adverse events, including inadequate pain and sedation control, clinically significant drug withdrawal symptoms, and unplanned endotracheal tube removal (JAMA 2015 [doi:10.1001/jama.2014.18399])

It’s become clear in recent years that intubated adults do better with lighter sedation, and the PICU findings don’t necessarily mean that children are somehow different. A more likely explanation of the findings is that the control PICUs were using a lighter touch, too; prior to randomization, all the PICUs implemented the same pain, sedation, and withdrawal scales.

In any case, the study does show that “targeting a sedation goal of patients who are calm, easily aroused, and readily evaluated is attainable and safe in children,” wrote registered nurse Martha Curley, Ph.D., of the University of Pennsylvania, Philadelphia, and her associates . The study results were published to coincide with Dr. Curley’s presentation at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

The protocol patients had a median 9 days of opioids, versus 10 in the usual-care group, and they were awake and calm while intubated a median of 86% of days, versus 75% in the control group. However, intervention children had pain during about half of their days, while usual-care children reported pain during about quarter of their days. Intervention patients also had more agitation, and postextubation stridor, but fewer pressure sores. There were no differences in mortality between the groups.

Morphine was the primary protocol opioid, while fentanyl was used most often in the control group. Morphine was selected for the protocol because it has a longer duration of action, plus some sedative properties and less development of tolerance. The primary sedative in both groups was midazolam; about a quarter of protocol patients received dexmedetomidine, versus about half in the usual-care group.

Baseline patient characteristics were well matched between the two groups, except that the intervention group enrolled more patients younger than 2 years and more patients with bronchiolitis, both of whom are harder to sedate. Pneumonia, bronchiolitis, and acute respiratory failure due to sepsis were the most common diagnoses in both groups. The mean age of the children was 4.7 years.

The work, dubbed the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) study, was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research. The lead author had no disclosures. One coauthor is an advisor for Philips, and another reported consultant and other fees from Cerus, Quark Pharmaceuticals, Biogen, GlaxoSmithKline, and other companies.

[email protected]

PHOENIX – A pediatric ICU protocol to minimize sedation during intubation did not reduce ventilator days among children with acute respiratory failure, compared with usual care, in a randomized trial of 2,449 children across 31 ICUs.

The results were published online Jan. 20 in JAMA.

Seventeen pediatric ICUs (PICUs) followed a protocol that included sedation adjustment at least every 8 hours based on phase of illness; arousal assessments during titration and weaning; daily extubation readiness testing when spontaneously breathing; and weaning off opioids and benzodiazepines if patients were on them for 5 or more days, instead of simply discontinuing them.

The 1,225 children on the protocol were ventilated a median of 6.5 days, the same length as the 1,224 children in the 14 usual-care PICUs. There were no differences in sedation-related adverse events, including inadequate pain and sedation control, clinically significant drug withdrawal symptoms, and unplanned endotracheal tube removal (JAMA 2015 [doi:10.1001/jama.2014.18399])

It’s become clear in recent years that intubated adults do better with lighter sedation, and the PICU findings don’t necessarily mean that children are somehow different. A more likely explanation of the findings is that the control PICUs were using a lighter touch, too; prior to randomization, all the PICUs implemented the same pain, sedation, and withdrawal scales.

In any case, the study does show that “targeting a sedation goal of patients who are calm, easily aroused, and readily evaluated is attainable and safe in children,” wrote registered nurse Martha Curley, Ph.D., of the University of Pennsylvania, Philadelphia, and her associates . The study results were published to coincide with Dr. Curley’s presentation at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

The protocol patients had a median 9 days of opioids, versus 10 in the usual-care group, and they were awake and calm while intubated a median of 86% of days, versus 75% in the control group. However, intervention children had pain during about half of their days, while usual-care children reported pain during about quarter of their days. Intervention patients also had more agitation, and postextubation stridor, but fewer pressure sores. There were no differences in mortality between the groups.

Morphine was the primary protocol opioid, while fentanyl was used most often in the control group. Morphine was selected for the protocol because it has a longer duration of action, plus some sedative properties and less development of tolerance. The primary sedative in both groups was midazolam; about a quarter of protocol patients received dexmedetomidine, versus about half in the usual-care group.

Baseline patient characteristics were well matched between the two groups, except that the intervention group enrolled more patients younger than 2 years and more patients with bronchiolitis, both of whom are harder to sedate. Pneumonia, bronchiolitis, and acute respiratory failure due to sepsis were the most common diagnoses in both groups. The mean age of the children was 4.7 years.

The work, dubbed the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) study, was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research. The lead author had no disclosures. One coauthor is an advisor for Philips, and another reported consultant and other fees from Cerus, Quark Pharmaceuticals, Biogen, GlaxoSmithKline, and other companies.

[email protected]

PHOENIX – A pediatric ICU protocol to minimize sedation during intubation did not reduce ventilator days among children with acute respiratory failure, compared with usual care, in a randomized trial of 2,449 children across 31 ICUs.

The results were published online Jan. 20 in JAMA.

Seventeen pediatric ICUs (PICUs) followed a protocol that included sedation adjustment at least every 8 hours based on phase of illness; arousal assessments during titration and weaning; daily extubation readiness testing when spontaneously breathing; and weaning off opioids and benzodiazepines if patients were on them for 5 or more days, instead of simply discontinuing them.

The 1,225 children on the protocol were ventilated a median of 6.5 days, the same length as the 1,224 children in the 14 usual-care PICUs. There were no differences in sedation-related adverse events, including inadequate pain and sedation control, clinically significant drug withdrawal symptoms, and unplanned endotracheal tube removal (JAMA 2015 [doi:10.1001/jama.2014.18399])

It’s become clear in recent years that intubated adults do better with lighter sedation, and the PICU findings don’t necessarily mean that children are somehow different. A more likely explanation of the findings is that the control PICUs were using a lighter touch, too; prior to randomization, all the PICUs implemented the same pain, sedation, and withdrawal scales.

In any case, the study does show that “targeting a sedation goal of patients who are calm, easily aroused, and readily evaluated is attainable and safe in children,” wrote registered nurse Martha Curley, Ph.D., of the University of Pennsylvania, Philadelphia, and her associates . The study results were published to coincide with Dr. Curley’s presentation at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

The protocol patients had a median 9 days of opioids, versus 10 in the usual-care group, and they were awake and calm while intubated a median of 86% of days, versus 75% in the control group. However, intervention children had pain during about half of their days, while usual-care children reported pain during about quarter of their days. Intervention patients also had more agitation, and postextubation stridor, but fewer pressure sores. There were no differences in mortality between the groups.

Morphine was the primary protocol opioid, while fentanyl was used most often in the control group. Morphine was selected for the protocol because it has a longer duration of action, plus some sedative properties and less development of tolerance. The primary sedative in both groups was midazolam; about a quarter of protocol patients received dexmedetomidine, versus about half in the usual-care group.

Baseline patient characteristics were well matched between the two groups, except that the intervention group enrolled more patients younger than 2 years and more patients with bronchiolitis, both of whom are harder to sedate. Pneumonia, bronchiolitis, and acute respiratory failure due to sepsis were the most common diagnoses in both groups. The mean age of the children was 4.7 years.

The work, dubbed the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) study, was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research. The lead author had no disclosures. One coauthor is an advisor for Philips, and another reported consultant and other fees from Cerus, Quark Pharmaceuticals, Biogen, GlaxoSmithKline, and other companies.

[email protected]

Among older adults, hospitalization for pneumonia raises the short-term (1-month) and long-term (10-year) risk of cardiovascular disease events to a degree comparable to those of smoking, diabetes, and hypertension, according to a report published online Jan. 20 in JAMA.

“Our findings suggest that hospitalization for pneumonia should be considered an independent cardiovascular risk factor” and “should prompt clinical trials to test targeted strategies”’ to prevent the disease in this patient population, said Dr. Vicente F. Corrales-Medina of the University of Ottawa and the Ottawa Hospital Research Institute.

Courtesy NIH National Library of Medicine/Institute for Physical Education and Sport, University of Malta, Malta/Creative Commons License

The risk of cardiovascular disease (CVD) events within 30 days of severe infections, mainly those involving the respiratory tract, is well established, but the more lasting effects are uncertain. In what the researchers described as “the first study to document the temporal variation in the long-term risk of CVD ... using rigorous methods to adjust for many potential confounders,” they analyzed data from two multicenter population-based cohorts that were followed for 21 years.

The 591 participants in the Cardiovascular Health Study were 65 years of age or older and had been hospitalized for pneumonia. When researchers compared their outcomes to 1,182 matched controls without pneumonia, they found that in the pneumonia group the rate of CVD events was fourfold higher at 30 days, dropped to twofold higher throughout the rest of the first year, and leveled out at 1.5-fold higher for the remainder of the decade.

Researchers then verified this risk pattern in a cohort of 680 pneumonia patients aged 45-64 years and 1,360 matched controls in the Atherosclerosis Risk in Communities study. The increased risk conferred by hospitalization for pneumonia persisted after the data were adjusted to account for demographic traits, preexisting CVD risk factors, and measures of patient frailty; it also was robust to numerous sensitivity analyses, the researchers said (JAMA 2015 Jan. 20 [doi:10.1001/jama.2014.18229]).

Moreover, the magnitude of risk conferred by hospitalization for pneumonia “was similar or higher, compared with the risk of CVD associated with traditional risk factors such as smoking, diabetes, and hypertension,” wrote Dr. Corrales-Medina and his associates.

The Ottawa Hospital, the Ottawa Hospital Research Institute, and the Canadian National Institute of General Medical Sciences funded the study. Dr. Corrales-Medina reported having no financial disclosures; an associate reported ties to Biogen Idec, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, CardioNet, Daiichi Sankyo, diaDexus, Janssen, Merck/Organon, and Sanofi.

Among older adults, hospitalization for pneumonia raises the short-term (1-month) and long-term (10-year) risk of cardiovascular disease events to a degree comparable to those of smoking, diabetes, and hypertension, according to a report published online Jan. 20 in JAMA.

“Our findings suggest that hospitalization for pneumonia should be considered an independent cardiovascular risk factor” and “should prompt clinical trials to test targeted strategies”’ to prevent the disease in this patient population, said Dr. Vicente F. Corrales-Medina of the University of Ottawa and the Ottawa Hospital Research Institute.

Courtesy NIH National Library of Medicine/Institute for Physical Education and Sport, University of Malta, Malta/Creative Commons License

The risk of cardiovascular disease (CVD) events within 30 days of severe infections, mainly those involving the respiratory tract, is well established, but the more lasting effects are uncertain. In what the researchers described as “the first study to document the temporal variation in the long-term risk of CVD ... using rigorous methods to adjust for many potential confounders,” they analyzed data from two multicenter population-based cohorts that were followed for 21 years.

The 591 participants in the Cardiovascular Health Study were 65 years of age or older and had been hospitalized for pneumonia. When researchers compared their outcomes to 1,182 matched controls without pneumonia, they found that in the pneumonia group the rate of CVD events was fourfold higher at 30 days, dropped to twofold higher throughout the rest of the first year, and leveled out at 1.5-fold higher for the remainder of the decade.

Researchers then verified this risk pattern in a cohort of 680 pneumonia patients aged 45-64 years and 1,360 matched controls in the Atherosclerosis Risk in Communities study. The increased risk conferred by hospitalization for pneumonia persisted after the data were adjusted to account for demographic traits, preexisting CVD risk factors, and measures of patient frailty; it also was robust to numerous sensitivity analyses, the researchers said (JAMA 2015 Jan. 20 [doi:10.1001/jama.2014.18229]).

Moreover, the magnitude of risk conferred by hospitalization for pneumonia “was similar or higher, compared with the risk of CVD associated with traditional risk factors such as smoking, diabetes, and hypertension,” wrote Dr. Corrales-Medina and his associates.

The Ottawa Hospital, the Ottawa Hospital Research Institute, and the Canadian National Institute of General Medical Sciences funded the study. Dr. Corrales-Medina reported having no financial disclosures; an associate reported ties to Biogen Idec, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, CardioNet, Daiichi Sankyo, diaDexus, Janssen, Merck/Organon, and Sanofi.

Among older adults, hospitalization for pneumonia raises the short-term (1-month) and long-term (10-year) risk of cardiovascular disease events to a degree comparable to those of smoking, diabetes, and hypertension, according to a report published online Jan. 20 in JAMA.

“Our findings suggest that hospitalization for pneumonia should be considered an independent cardiovascular risk factor” and “should prompt clinical trials to test targeted strategies”’ to prevent the disease in this patient population, said Dr. Vicente F. Corrales-Medina of the University of Ottawa and the Ottawa Hospital Research Institute.

Courtesy NIH National Library of Medicine/Institute for Physical Education and Sport, University of Malta, Malta/Creative Commons License

The risk of cardiovascular disease (CVD) events within 30 days of severe infections, mainly those involving the respiratory tract, is well established, but the more lasting effects are uncertain. In what the researchers described as “the first study to document the temporal variation in the long-term risk of CVD ... using rigorous methods to adjust for many potential confounders,” they analyzed data from two multicenter population-based cohorts that were followed for 21 years.

The 591 participants in the Cardiovascular Health Study were 65 years of age or older and had been hospitalized for pneumonia. When researchers compared their outcomes to 1,182 matched controls without pneumonia, they found that in the pneumonia group the rate of CVD events was fourfold higher at 30 days, dropped to twofold higher throughout the rest of the first year, and leveled out at 1.5-fold higher for the remainder of the decade.

Researchers then verified this risk pattern in a cohort of 680 pneumonia patients aged 45-64 years and 1,360 matched controls in the Atherosclerosis Risk in Communities study. The increased risk conferred by hospitalization for pneumonia persisted after the data were adjusted to account for demographic traits, preexisting CVD risk factors, and measures of patient frailty; it also was robust to numerous sensitivity analyses, the researchers said (JAMA 2015 Jan. 20 [doi:10.1001/jama.2014.18229]).

Moreover, the magnitude of risk conferred by hospitalization for pneumonia “was similar or higher, compared with the risk of CVD associated with traditional risk factors such as smoking, diabetes, and hypertension,” wrote Dr. Corrales-Medina and his associates.

The Ottawa Hospital, the Ottawa Hospital Research Institute, and the Canadian National Institute of General Medical Sciences funded the study. Dr. Corrales-Medina reported having no financial disclosures; an associate reported ties to Biogen Idec, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, CardioNet, Daiichi Sankyo, diaDexus, Janssen, Merck/Organon, and Sanofi.

Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.

Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.

goa_novi/Thinkstock.com

“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.

The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.

Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”

Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.

“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.

Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.

[email protected]

Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.

Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.

goa_novi/Thinkstock.com

“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.

The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.

Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”

Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.

“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.

Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.

[email protected]

Patients with idiopathic pulmonary arterial hypertension did not respond to treatment with an acute vasodilator challenge because they were unable to recruit functional capillary surface area to accommodate increased blood flow to the lungs, according to the results of a study published Jan. 19 in Annals of Internal Medicine.

Dr. David Langleben of McGill University, Montreal, and Dr. Stylianos E. Orfanos of Attikon Hospital, Athens, hypothesized that the increased pulmonary vascular resistance (PVR) noted in responders would be based on vascular tone rather than cellular obstruction, and therefore responders should be capable of recruiting functional capillary surface area (CSA) during a vasodilator challenge.

goa_novi/Thinkstock.com

“Despite sharing the baseline hemodynamic profile of IPAH, responders and nonresponders [may] represent different vascular phenotypes and perhaps different diseases,” they wrote.

The investigators recruited 14 patients (12 female, 2 male) with IPAH, none of whom had previously received IPAH-specific therapy or had saline contrast evidence of intracardiac shunting on echocardiography. Each subject underwent a standardized right heart catheterization followed by insertion of a femoral artery sheath. After a 30-minute rest period, investigators measured baseline hemodynamics and pulmonary capillary, endothelium-bound, angiotensin-converting enzyme (PCEB-ACE) metabolic activity.

Subsequently, the researchers performed an acute vasodilator challenge on each patient using epoprostenol (Flolan, GlaxoSmithKline Canada), after which PCEB-ACE metabolic activity and hemodynamics were measured again at the peak epoprostenol dose – determined “individually by maximum hemodynamic response or adverse effects.”

Functional CSA was calculated and normalized to body surface area. Values among nonresponders before the vasodilator challenge and at the peak epoprostenol dose were compared using paired t-tests. Of the 14 subjects, 12 were found to be nonresponders to vasodilator challenge and 2 (1 female, 1 male) did respond to vasodilator challenge treatment. In nonresponders overall, mean pulmonary arterial pressure (mPAP) did not change significantly – 59.5 mm Hg to 58.1 mm Hg – but cardiac output increased and PVR decreased. In the two subjects who responded, cardiac output and PVR increased, but mPAP decreased 43.5 mm Hg to 31.5 mm Hg.

“These data show the inability of nonresponders with IPAH to open occluded arterioles and thus recruit more downstream capillaries to accommodate the observed increased lung blood volumes that should accompany vasodilator administration,” the researchers concluded.

Funding for this study was provided by the William and Ida Pencer Family Foundation, the Dimitrios Banousis Foundation, the Bank of Montreal Center for the Study of Heart Disease in Women, and the Jewish General Hospital Annual Walk for Pulmonary Hypertension, all at Jewish General Hospital. The authors disclosed no conflicts of interest.

[email protected]

So far this flu season, more than two-thirds of influenza A (H3N2) viruses differ from the components of the 2014-2015 influenza vaccine. In addition, the overall estimated effectiveness of the 2014-2015 influenza vaccine for preventing laboratory-confirmed influenza infection is only 23%.

Those are key findings from an analysis of 2,321 children and adults who presented to one of five study sites in the United States with acute respiratory illness between Nov. 10, 2014, and Jan. 2, 2015.

“Although influenza vaccines are the best tool for prevention of influenza currently available, more effective vaccines are needed,” wrote Brendan Flannery, Ph.D., of the influenza division at the CDC’s National Center for Immunization and Respiratory Disease, and his associates. The report is in the Jan. 16, 2015, issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2015 Jan. 16;64:10-15). “Antiviral medications are an important adjunct in the treatment and control of influenza for the 2014-2015 season and should be used as recommended, regardless of patient vaccination status.”

Targeted groups for antiviral treatment include any patient with suspected or confirmed influenza who is hospitalized, has severe or progressive illness, or is at high risk for complications from influenza, even if the illness seems mild. “Persons at high risk include young children (especially those younger than age 2), pregnant women, persons with chronic medical conditions like asthma, diabetes, or heart disease, and adults aged 65 years and older,” the researchers wrote. “Ideally, antiviral treatment should be initiated within 48 hours of symptom onset, when treatment is most effective.”

Though spot shortages of Tamiflu and other antiviral drugs have been reported in the United States, the CDC investigators noted that it may be necessary for physicians and patients to contact more than one pharmacy to fill a prescription. Updates on the supply of antiviral drugs can be found here.

Dr. Flannery and his associates acknowledged certain limitations of their analysis, including the fact that future estimates could differ as more data become available and that the current estimates “are limited to the prevention of outpatient medical visits, rather than more severe illness outcomes, such as hospitalization or death.”

The researchers reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

So far this flu season, more than two-thirds of influenza A (H3N2) viruses differ from the components of the 2014-2015 influenza vaccine. In addition, the overall estimated effectiveness of the 2014-2015 influenza vaccine for preventing laboratory-confirmed influenza infection is only 23%.

Those are key findings from an analysis of 2,321 children and adults who presented to one of five study sites in the United States with acute respiratory illness between Nov. 10, 2014, and Jan. 2, 2015.

“Although influenza vaccines are the best tool for prevention of influenza currently available, more effective vaccines are needed,” wrote Brendan Flannery, Ph.D., of the influenza division at the CDC’s National Center for Immunization and Respiratory Disease, and his associates. The report is in the Jan. 16, 2015, issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2015 Jan. 16;64:10-15). “Antiviral medications are an important adjunct in the treatment and control of influenza for the 2014-2015 season and should be used as recommended, regardless of patient vaccination status.”

Targeted groups for antiviral treatment include any patient with suspected or confirmed influenza who is hospitalized, has severe or progressive illness, or is at high risk for complications from influenza, even if the illness seems mild. “Persons at high risk include young children (especially those younger than age 2), pregnant women, persons with chronic medical conditions like asthma, diabetes, or heart disease, and adults aged 65 years and older,” the researchers wrote. “Ideally, antiviral treatment should be initiated within 48 hours of symptom onset, when treatment is most effective.”

Though spot shortages of Tamiflu and other antiviral drugs have been reported in the United States, the CDC investigators noted that it may be necessary for physicians and patients to contact more than one pharmacy to fill a prescription. Updates on the supply of antiviral drugs can be found here.

Dr. Flannery and his associates acknowledged certain limitations of their analysis, including the fact that future estimates could differ as more data become available and that the current estimates “are limited to the prevention of outpatient medical visits, rather than more severe illness outcomes, such as hospitalization or death.”

The researchers reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

So far this flu season, more than two-thirds of influenza A (H3N2) viruses differ from the components of the 2014-2015 influenza vaccine. In addition, the overall estimated effectiveness of the 2014-2015 influenza vaccine for preventing laboratory-confirmed influenza infection is only 23%.

Those are key findings from an analysis of 2,321 children and adults who presented to one of five study sites in the United States with acute respiratory illness between Nov. 10, 2014, and Jan. 2, 2015.

“Although influenza vaccines are the best tool for prevention of influenza currently available, more effective vaccines are needed,” wrote Brendan Flannery, Ph.D., of the influenza division at the CDC’s National Center for Immunization and Respiratory Disease, and his associates. The report is in the Jan. 16, 2015, issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2015 Jan. 16;64:10-15). “Antiviral medications are an important adjunct in the treatment and control of influenza for the 2014-2015 season and should be used as recommended, regardless of patient vaccination status.”

Targeted groups for antiviral treatment include any patient with suspected or confirmed influenza who is hospitalized, has severe or progressive illness, or is at high risk for complications from influenza, even if the illness seems mild. “Persons at high risk include young children (especially those younger than age 2), pregnant women, persons with chronic medical conditions like asthma, diabetes, or heart disease, and adults aged 65 years and older,” the researchers wrote. “Ideally, antiviral treatment should be initiated within 48 hours of symptom onset, when treatment is most effective.”

Though spot shortages of Tamiflu and other antiviral drugs have been reported in the United States, the CDC investigators noted that it may be necessary for physicians and patients to contact more than one pharmacy to fill a prescription. Updates on the supply of antiviral drugs can be found here.

Dr. Flannery and his associates acknowledged certain limitations of their analysis, including the fact that future estimates could differ as more data become available and that the current estimates “are limited to the prevention of outpatient medical visits, rather than more severe illness outcomes, such as hospitalization or death.”

The researchers reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

The approximate midpoint of the 2014-2015 flu season has been reached, disease remains widespread, and antiviral flu medications remain underutilized, according to the Centers for Disease Control and Prevention.

As predicted, this season is proving particularly severe due to the predominance of antigenically drifted H3N2 virus strains, and the CDC is urging clinicians to maintain a high index of suspicion for flu and to prescribe antivirals earlier and more aggressively for patients presenting with flulike illness – especially young children, those over age 65 years, and those with underlying conditions, even if their symptoms are mild, CDC Director Thomas R. Frieden said during a press briefing.

A health advisory on the topic was issued Jan. 9, he noted.

“The CDC has recommended the use of antiviral drugs as an adjunct to vaccination. They are the only medicines that can specifically treat influenza illness, and in the context of an H3N2 predominant season with a less effective vaccine, treatment with antiflu drugs is even more important than usual,” he said, referring to the two neuraminidase inhibitors currently approved for treating influenza: oseltamivir and zanamivir.

About two-thirds of the H3N2 viruses analyzed this season are different from the H3N2 virus included in this year’s vaccine, which is why the vaccine is expected to have reduced effectiveness, he explained.

This makes early antiviral treatment all the more important, he added, noting that treatment within 2 days of symptom onset is optimal, but later treatment can also offer benefit.

“CDC scientists have looked very carefully at the use of influenza drugs in the clinical setting, and the conclusion is clear: They work, but they aren’t being used nearly enough. They can reduce symptoms, shorten duration of illness, and prevent serious complications,” he said.

Continue for early treatments >>

Early treatment may help patients avoid hospitalization and could be life saving, he added.

Many patients are unaware that effective prescription treatments exist, and many doctors are not using the treatments as recommended. In one study, fewer than one in five eligible high-risk patients received treatment.

“So we’re expanding our efforts to reach clinicians about reminders about the importance of these drugs,” he said, noting that if high-risk patients with underlying conditions such as asthma, sickle cell disease, renal disease, or diabetes were treated, “tens of thousands of hospitalizations, and thousands of deaths could potentially be prevented.”

Dr. Frieden suggested that clinicians consider phone triage lines for high-risk patients to discuss symptoms over the phone and to “facilitate early initiation of treatment.”

An antiviral prescription can be provided without testing and before an office visit, he added.

The typical flu season lasts about 13 weeks on average, and the season began about 7 weeks ago. The continued high rate of H3N2 disease has had the greatest impact on older adults; that is typical of such seasons, which often involve a higher rate of hospitalizations and deaths.

In fact, hospitalization rates in the over 65 age group are rising sharply, Dr. Frieden said.

Last week the rate was 52 per 100,000 population, and this week the rate was 92 per 100,000 population. The cumulative rate 2 years ago when H3N2 viruses last predominated was 183 per 100,000, he noted.

“We wouldn’t be surprised to see something very similar this year,” he said.

Young children are also severely affected; thus far in the season there have been 26 reported pediatric flu-related deaths.

However, there are early signs that infection rates are declining in areas where the season started earlier, such as the Southeast, and the number of patients presenting to a doctor with flulike symptoms has also declined slightly, but it is too soon to tell whether disease activity has peaked, he said, stressing that “we still have several weeks of flu activity ahead.”

It’s not too late to get vaccinated, and despite the reduced efficacy of this year’s vaccine against the circulating H3N2 strains, vaccination may still offer some benefit.

“There are other strains out there as well,” he said, noting that a proportion of cases from other strains, such as influenza B, tend to occur late in the season, and this year’s vaccine offers a good match for influenza B viruses.

Pneumococcal vaccination is also important, particularly for older adults and those at high risk , he said.

Last September the CDC announced a new recommendation that all adults over age 65 years should get two different pneumococcal vaccines. Such vaccination may help prevent flu-related pneumonia.

Patients with the flu or flulike illness should be advised to cover their cough and to stay home from work or school to protect those who are most vulnerable to the flu, he said.

The approximate midpoint of the 2014-2015 flu season has been reached, disease remains widespread, and antiviral flu medications remain underutilized, according to the Centers for Disease Control and Prevention.

As predicted, this season is proving particularly severe due to the predominance of antigenically drifted H3N2 virus strains, and the CDC is urging clinicians to maintain a high index of suspicion for flu and to prescribe antivirals earlier and more aggressively for patients presenting with flulike illness – especially young children, those over age 65 years, and those with underlying conditions, even if their symptoms are mild, CDC Director Thomas R. Frieden said during a press briefing.

A health advisory on the topic was issued Jan. 9, he noted.

“The CDC has recommended the use of antiviral drugs as an adjunct to vaccination. They are the only medicines that can specifically treat influenza illness, and in the context of an H3N2 predominant season with a less effective vaccine, treatment with antiflu drugs is even more important than usual,” he said, referring to the two neuraminidase inhibitors currently approved for treating influenza: oseltamivir and zanamivir.

About two-thirds of the H3N2 viruses analyzed this season are different from the H3N2 virus included in this year’s vaccine, which is why the vaccine is expected to have reduced effectiveness, he explained.

This makes early antiviral treatment all the more important, he added, noting that treatment within 2 days of symptom onset is optimal, but later treatment can also offer benefit.

“CDC scientists have looked very carefully at the use of influenza drugs in the clinical setting, and the conclusion is clear: They work, but they aren’t being used nearly enough. They can reduce symptoms, shorten duration of illness, and prevent serious complications,” he said.

Continue for early treatments >>

Early treatment may help patients avoid hospitalization and could be life saving, he added.

Many patients are unaware that effective prescription treatments exist, and many doctors are not using the treatments as recommended. In one study, fewer than one in five eligible high-risk patients received treatment.

“So we’re expanding our efforts to reach clinicians about reminders about the importance of these drugs,” he said, noting that if high-risk patients with underlying conditions such as asthma, sickle cell disease, renal disease, or diabetes were treated, “tens of thousands of hospitalizations, and thousands of deaths could potentially be prevented.”

Dr. Frieden suggested that clinicians consider phone triage lines for high-risk patients to discuss symptoms over the phone and to “facilitate early initiation of treatment.”

An antiviral prescription can be provided without testing and before an office visit, he added.

The typical flu season lasts about 13 weeks on average, and the season began about 7 weeks ago. The continued high rate of H3N2 disease has had the greatest impact on older adults; that is typical of such seasons, which often involve a higher rate of hospitalizations and deaths.

In fact, hospitalization rates in the over 65 age group are rising sharply, Dr. Frieden said.

Last week the rate was 52 per 100,000 population, and this week the rate was 92 per 100,000 population. The cumulative rate 2 years ago when H3N2 viruses last predominated was 183 per 100,000, he noted.

“We wouldn’t be surprised to see something very similar this year,” he said.

Young children are also severely affected; thus far in the season there have been 26 reported pediatric flu-related deaths.

However, there are early signs that infection rates are declining in areas where the season started earlier, such as the Southeast, and the number of patients presenting to a doctor with flulike symptoms has also declined slightly, but it is too soon to tell whether disease activity has peaked, he said, stressing that “we still have several weeks of flu activity ahead.”

It’s not too late to get vaccinated, and despite the reduced efficacy of this year’s vaccine against the circulating H3N2 strains, vaccination may still offer some benefit.

“There are other strains out there as well,” he said, noting that a proportion of cases from other strains, such as influenza B, tend to occur late in the season, and this year’s vaccine offers a good match for influenza B viruses.

Pneumococcal vaccination is also important, particularly for older adults and those at high risk , he said.

Last September the CDC announced a new recommendation that all adults over age 65 years should get two different pneumococcal vaccines. Such vaccination may help prevent flu-related pneumonia.

Patients with the flu or flulike illness should be advised to cover their cough and to stay home from work or school to protect those who are most vulnerable to the flu, he said.

The approximate midpoint of the 2014-2015 flu season has been reached, disease remains widespread, and antiviral flu medications remain underutilized, according to the Centers for Disease Control and Prevention.

As predicted, this season is proving particularly severe due to the predominance of antigenically drifted H3N2 virus strains, and the CDC is urging clinicians to maintain a high index of suspicion for flu and to prescribe antivirals earlier and more aggressively for patients presenting with flulike illness – especially young children, those over age 65 years, and those with underlying conditions, even if their symptoms are mild, CDC Director Thomas R. Frieden said during a press briefing.

A health advisory on the topic was issued Jan. 9, he noted.

“The CDC has recommended the use of antiviral drugs as an adjunct to vaccination. They are the only medicines that can specifically treat influenza illness, and in the context of an H3N2 predominant season with a less effective vaccine, treatment with antiflu drugs is even more important than usual,” he said, referring to the two neuraminidase inhibitors currently approved for treating influenza: oseltamivir and zanamivir.

About two-thirds of the H3N2 viruses analyzed this season are different from the H3N2 virus included in this year’s vaccine, which is why the vaccine is expected to have reduced effectiveness, he explained.

This makes early antiviral treatment all the more important, he added, noting that treatment within 2 days of symptom onset is optimal, but later treatment can also offer benefit.

“CDC scientists have looked very carefully at the use of influenza drugs in the clinical setting, and the conclusion is clear: They work, but they aren’t being used nearly enough. They can reduce symptoms, shorten duration of illness, and prevent serious complications,” he said.

Continue for early treatments >>

Early treatment may help patients avoid hospitalization and could be life saving, he added.

Many patients are unaware that effective prescription treatments exist, and many doctors are not using the treatments as recommended. In one study, fewer than one in five eligible high-risk patients received treatment.

“So we’re expanding our efforts to reach clinicians about reminders about the importance of these drugs,” he said, noting that if high-risk patients with underlying conditions such as asthma, sickle cell disease, renal disease, or diabetes were treated, “tens of thousands of hospitalizations, and thousands of deaths could potentially be prevented.”

Dr. Frieden suggested that clinicians consider phone triage lines for high-risk patients to discuss symptoms over the phone and to “facilitate early initiation of treatment.”

An antiviral prescription can be provided without testing and before an office visit, he added.

The typical flu season lasts about 13 weeks on average, and the season began about 7 weeks ago. The continued high rate of H3N2 disease has had the greatest impact on older adults; that is typical of such seasons, which often involve a higher rate of hospitalizations and deaths.

In fact, hospitalization rates in the over 65 age group are rising sharply, Dr. Frieden said.

Last week the rate was 52 per 100,000 population, and this week the rate was 92 per 100,000 population. The cumulative rate 2 years ago when H3N2 viruses last predominated was 183 per 100,000, he noted.

“We wouldn’t be surprised to see something very similar this year,” he said.

Young children are also severely affected; thus far in the season there have been 26 reported pediatric flu-related deaths.

However, there are early signs that infection rates are declining in areas where the season started earlier, such as the Southeast, and the number of patients presenting to a doctor with flulike symptoms has also declined slightly, but it is too soon to tell whether disease activity has peaked, he said, stressing that “we still have several weeks of flu activity ahead.”

It’s not too late to get vaccinated, and despite the reduced efficacy of this year’s vaccine against the circulating H3N2 strains, vaccination may still offer some benefit.

“There are other strains out there as well,” he said, noting that a proportion of cases from other strains, such as influenza B, tend to occur late in the season, and this year’s vaccine offers a good match for influenza B viruses.

Pneumococcal vaccination is also important, particularly for older adults and those at high risk , he said.

Last September the CDC announced a new recommendation that all adults over age 65 years should get two different pneumococcal vaccines. Such vaccination may help prevent flu-related pneumonia.

Patients with the flu or flulike illness should be advised to cover their cough and to stay home from work or school to protect those who are most vulnerable to the flu, he said.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.