New Apnea Risk Study: RSV is Not the Only Culprit

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.

A large prospective study of infants hospitalized for bronchiolitis has revealed a number of previously unknown risk factors associated with apnea, a potentially life-threatening complication.

While high preadmission respiratory rates were found associated with increased apnea risk, so were low respiratory rates, a surprising finding that investigators could not explain. Low room air oxygen saturation was seen as contributing to risk. And one usual-suspect risk factor in apnea – respiratory syncytial virus – turned out not to be more dangerous than other viruses in terms of apnea risk.

Clinicians should not be reassured by either a low respiratory rate or infection with an organism other than RSV in assessing apnea risk, said Dr. Alan R. Schroeder of the Santa Clara Medical Center in San Jose, Calif., and his colleagues.

At 16 study sites nationwide starting in 2007, the researchers collected enrollment and outcome data on 2,156 children under age 2 (median age 4 months, with age corrected for birth at less than 37 weeks). The patients were admitted with bronchiolitis over three consecutive winter seasons. Of these children, 108 (5%) developed apnea while hospitalized, according to the study, which was published online Oct. 7 in Pediatrics (2013;132:1-8 [doi: 10.1542/peds.2013-1501]). The study was part of the Multicenter Airway Research Collaboration, a program of the Emergency Medicine Network.

The study confirmed the known risk factors of young corrected age, low birth weight, and previous apnea during the same bronchiolitis episode. Dr. Schroeder and his colleagues found that the statistically significant predictors of apnea included age of less than 2 weeks (odds ratio, 9.67) and 2-8 weeks (OR, 4.72), compared with age 6 months or older; birth weight of less than 2.3 kg (OR, 2.15), compared with birth weight of 3.2 kg or more; and previous apnea during the same bronchiolitis episode (OR, 3.63).

There also was risk associated with preadmission respiratory rates of less than 30 (OR, 4.05) and 30-39 (OR, 2.35), compared with 40-49, as well as a preadmission respiratory rate of 70 or more (OR, 2.26). Risk of apnea was also associated with having a preadmission room air oxygen saturation of less than 90% (OR, 1.60).

Apnea risk was shown to be similar across the major viral infections seen in the cohort. While more infants presented with RSV than with other viruses, there was roughly equal apnea risk seen among children infected with human rhinovirus, adenovirus, human metapneumovirus, enterovirus, coronavirus, and parainfluenza virus.

"These data suggest that using RSV status to drive admission decisions and admission locations (e.g., ward, step-down unit, ICU) due to apnea concerns may be misguided," Dr. Schroeder and his colleagues wrote in their analysis.

The study contained a number of other novel findings. While a recent, smaller study of 42 patients had suggested a possible protective effect associated with acetaminophen administered the week before hospitalization (Resuscitation 2012;83:440-46), the study by Dr. Schroeder and his colleagues found no such effect.

It also shed light on the timing of apnea during the course of bronchiolitis. While previous studies had shown apnea occurring early in the course of RSV infection, "our results challenge this notion," the authors wrote. One-third of the infants with apnea in the study began having difficulty breathing 4 or more days before the preadmission visit. "Furthermore, the time from the beginning of the ‘difficulty breathing’ to the preadmission visit was not different between children with and without apnea. Therefore, using the duration of symptoms to predict future risk of apnea or need for hospitalization may be problematic."

The investigators acknowledged as limitations of their study the possibility that the reported incidence of apnea may have been biased by oversampling of sicker patients, as the investigators recruited 20% of patients from intensive care. Some infants may have been included based on chart data that did not meet strict criteria for apnea, allowing for overreporting, they said, and apnea may have been harder to detect in intubated patients, leading to underreporting in this population.

The study was funded by the National Institutes of Health. Dr. Schroeder and his colleagues reported no disclosures.