Oxygen saturation targets in infants with bronchiolitis
2015; Elsevier BV; Volume: 386; Issue: 9998 Linguagem: Inglês
10.1016/s0140-6736(15)00155-5
ISSN1474-547X
AutoresClaire Wainwright, Nitin Kapur,
Tópico(s)Neonatal Respiratory Health Research
ResumoAcute viral bronchiolitis is associated with lower respiratory tract infections in infants. Although generally self-limiting and managed in the community, acute viral bronchiolitis is the most common cause of hospital admission in infants younger than 12 months of age, and is associated with substantial morbidity and health-care costs. Admissions of infants to hospital for bronchiolitis have increased in the past 20 years for reasons that might be multifactorial, although the use of pulse oximeters and insufficient evidence and clarity about levels of tolerable hypoxaemia are thought to be associated with increased admission rates.1Schuh S Freedman S Coates A et al.Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical trial.JAMA. 2014; 312: 712-718Crossref PubMed Scopus (66) Google Scholar Additionally, duration of hospital stay seems to be determined by the requirement for oxygen supplementation, even when feeding problems have resolved.2Unger S Cunningham S Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis.Pediatrics. 2008; 121: 470-475Crossref PubMed Scopus (83) Google Scholar National guidelines in the USA3American Academy of Pediatrics subcommittee on diagnosis and management of bronchiolitisDiagnosis and management of bronchiolitis.Pediatrics. 2006; 118: 1774-1793Crossref PubMed Scopus (853) Google Scholar and UK4Scottish Intercollegiate Guidelines Network. Bronchiolitis in children (SIGN 91). NHS Quality improvement. Scotland, 2006.Google Scholar differ in their recommendations for supplemental oxygen to target acceptable saturations (SpO2) of 90% or higher, or 94% or higher, respectively. An observational study in bronchiolitis5Cunningham S McMurray A Observational study of two oxygen saturation targets for discharge in bronchiolitis.Arch Dis Child. 2012; 97: 361-363Crossref PubMed Scopus (28) Google Scholar previously suggested that length of stay could be reduced when lower oxygen cutoffs were chosen, setting the stage for the randomised BIDS trial now reported by Steve Cunningham and colleagues in The Lancet,6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar which provides welcome evidence about the use of supplemental oxygen and oxygen saturation targets in bronchiolitis.BIDS reports findings from a multicentre randomised equivalence trial of 615 infants aged between 6 weeks and 12 months, who presented to eight paediatric hospitals in the UK with bronchiolitis. These infants were randomly assigned to be monitored either by standard oximeters (n=308), or by modified oximeters (n=307) which had a skewed algorithm that displayed an SpO2 reading of 94% when the measured value was 90% (with adjusted values for SpO2 85–100%). Supplemental oxygen was given to all infants with an SpO2 reading lower than 94% on their assigned oximeter.The median time of resolution of cough (the primary outcome) was 15 days for both groups (95% CI for difference −1 to 2), which was within the limits of equivalence. As expected, compared with the standard group, fewer infants in the modified oximeter group needed supplemental oxygen (169 [56%] vs 223 [73%]), and, when required, supplementation was for a significantly shorter duration (5·7 h vs 27·6 h) and the infants were fit for discharge significantly earlier (30·2 h vs 44·2 h). More unexpectedly, infants in the modified group returned to adequate feeding a median of 2·7 h sooner, were perceived to return to normal by their parents 1 day earlier, and had fewer readmissions to hospital within 28 days compared with those in the standard group. Adverse events did not differ between groups. The authors conclude that children with bronchiolitis could be managed with an oxygen saturation target of 90% or higher, instead of 94% or higher, with no short-term safety implications. This would result in earlier discharge home from hospital with the potential for health-care-cost reduction and improved quality of life for parents.The primary outcome chosen by Cunningham and colleagues6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar (resolution of cough) was unusual for clinical trials of bronchiolitis, although duration of cough is perceived to be important by families.7Hay AD Wilson A Fahey T Peters TJ The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study.Fam Pract. 2003; 20: 696-705Crossref PubMed Scopus (121) Google Scholar The association between duration of cough and degree of hypoxaemia is not established, and it is interesting to speculate whether the results of cough duration would have been any different if an even lower saturation cutoff was chosen. Cunningham and colleagues suggest a potential interaction with airway inflammation, and it is also possible that cough might become more frequent with worsening hypoxia given the association between cough frequency and altitude8Mason NP Barry PW Despiau G Gardette B Richalet JP Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude.Eur Respir J. 1999; 13: 508-513Crossref PubMed Scopus (29) Google Scholar and the as yet unexplained association between nocturnal cough and obstructive sleep apnoea reported in adults.9Sundar KM Daly SE Pearce MJ Alward WT Chronic cough and obstructive sleep apnea in a community-based pulmonary practice.Cough. 2010; 6: 2Crossref PubMed Scopus (52) Google Scholar Of the other outcomes measured, the time to sufficient feeding and frequency of apnoea were possibly more discerning outcomes that could have been affected by hypoxia. The parental perception of return to normalcy might be biased by early discharge home, but, like readmission to hospital, would also reflect the parental level of concern about the infant.Although Cunningham and colleagues' study6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar provides convincing evidence that reduced oxygen saturation targets in bronchiolitis are safe in the short term, unfortunately the longer-term neurocognitive and behavioural outcomes are unknown. On one hand, the likely safety of the lower oxygen saturation target is supported from a physiological perspective because the oxygen–haemoglobin dissociation curve predicts that the actual oxygen delivered to tissues is unlikely to be very different with an oxygen saturation target of 90% instead of 94%, although risk factors such as fever and acidosis need to be taken into account. In addition, intermittent desaturation episodes of short duration (up to 6 s) have no adverse consequences in infancy.10Hunt CE Corwin MJ Lister G et al.for the Collaborative Home Infant Monitoring Evaluation (CHIME) Study GroupLongitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age.J Pediatr. 1999; 135: 580-586Summary Full Text Full Text PDF PubMed Scopus (103) Google ScholarOn the other hand, intermittent hypoxia over a prolonged period of months to years, as in sleep disordered breathing and long-term hypoxaemia due to altitude or congenital heart disease, has been associated with detrimental effects on long-term neurocognitive outcomes in children.11Bass JL Corwin M Gozal D et al.The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence.Pediatrics. 2004; 114: 805-816Crossref PubMed Scopus (350) Google Scholar The resulting quandary is in clinical situations such as bronchiolitis or asthma, which lie somewhere between these two ends of the spectrum in terms of duration of lower saturations, when the longer-term safety of lower saturation targets falls into an evidence-free zone. When the American Academy of Pediatrics bronchiolitis guidelines3American Academy of Pediatrics subcommittee on diagnosis and management of bronchiolitisDiagnosis and management of bronchiolitis.Pediatrics. 2006; 118: 1774-1793Crossref PubMed Scopus (853) Google Scholar were published in 2007 suggesting 90% as the acceptable saturation cutoff, Bass and Gozal12Bass JL Gozal D Oxygen therapy for bronchiolitis.Pediatrics. 2007; 119: 611Crossref PubMed Scopus (18) Google Scholar raised concerns about the potential detrimental effects on cognitive and behavioural outcomes, and concerns among paediatricians continue to be raised.13Walsh P Rothenberg SJ American Academy of Pediatrics 2014 bronchiolitis guidelines: bonfire of the evidence.West J Emerg Med. 2015; 16: 85-88Crossref PubMed Scopus (11) Google ScholarFindings from BIDS6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar also raise questions about the use of supplemental oxygen in other acute hypoxic states, such as exacerbations of asthma and community-acquired pneumonia. The decision about acceptable oxygen saturations for these disorders is also based on expert opinion and becomes a matter of clinical judgment, availability of health-care resources, and cost implications. Cunningham and colleagues have done a commendable job in bringing robust evidence with far-reaching implications to an area previously governed by expert opinion; however, we urge consideration of long-term neurobehavioural follow-up of randomised trials such as BIDS, to shed light on the nagging question that remains.This online publication has been corrected. The corrected version first appeared at thelancet.com on October 9, 2015CEW has received honoraria, travel expenses, and consulting fees from Vertex Pharmaceuticals, honoraria and travel expenses from Novartis Pharmaceuticals, is a member of the international advisory board for Vertex Pharmaceuticals, and has been an investigator and received funding on a per-patient basis derived from pharmaceutical studies sponsored by Vertex Pharmaceuticals and Boehringer Ingelheim. She has taken part in studies sponsored by Vertex Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, and GlaxoSmithKline. NK declares no competing interests. Acute viral bronchiolitis is associated with lower respiratory tract infections in infants. Although generally self-limiting and managed in the community, acute viral bronchiolitis is the most common cause of hospital admission in infants younger than 12 months of age, and is associated with substantial morbidity and health-care costs. Admissions of infants to hospital for bronchiolitis have increased in the past 20 years for reasons that might be multifactorial, although the use of pulse oximeters and insufficient evidence and clarity about levels of tolerable hypoxaemia are thought to be associated with increased admission rates.1Schuh S Freedman S Coates A et al.Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical trial.JAMA. 2014; 312: 712-718Crossref PubMed Scopus (66) Google Scholar Additionally, duration of hospital stay seems to be determined by the requirement for oxygen supplementation, even when feeding problems have resolved.2Unger S Cunningham S Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis.Pediatrics. 2008; 121: 470-475Crossref PubMed Scopus (83) Google Scholar National guidelines in the USA3American Academy of Pediatrics subcommittee on diagnosis and management of bronchiolitisDiagnosis and management of bronchiolitis.Pediatrics. 2006; 118: 1774-1793Crossref PubMed Scopus (853) Google Scholar and UK4Scottish Intercollegiate Guidelines Network. Bronchiolitis in children (SIGN 91). NHS Quality improvement. Scotland, 2006.Google Scholar differ in their recommendations for supplemental oxygen to target acceptable saturations (SpO2) of 90% or higher, or 94% or higher, respectively. An observational study in bronchiolitis5Cunningham S McMurray A Observational study of two oxygen saturation targets for discharge in bronchiolitis.Arch Dis Child. 2012; 97: 361-363Crossref PubMed Scopus (28) Google Scholar previously suggested that length of stay could be reduced when lower oxygen cutoffs were chosen, setting the stage for the randomised BIDS trial now reported by Steve Cunningham and colleagues in The Lancet,6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar which provides welcome evidence about the use of supplemental oxygen and oxygen saturation targets in bronchiolitis. BIDS reports findings from a multicentre randomised equivalence trial of 615 infants aged between 6 weeks and 12 months, who presented to eight paediatric hospitals in the UK with bronchiolitis. These infants were randomly assigned to be monitored either by standard oximeters (n=308), or by modified oximeters (n=307) which had a skewed algorithm that displayed an SpO2 reading of 94% when the measured value was 90% (with adjusted values for SpO2 85–100%). Supplemental oxygen was given to all infants with an SpO2 reading lower than 94% on their assigned oximeter. The median time of resolution of cough (the primary outcome) was 15 days for both groups (95% CI for difference −1 to 2), which was within the limits of equivalence. As expected, compared with the standard group, fewer infants in the modified oximeter group needed supplemental oxygen (169 [56%] vs 223 [73%]), and, when required, supplementation was for a significantly shorter duration (5·7 h vs 27·6 h) and the infants were fit for discharge significantly earlier (30·2 h vs 44·2 h). More unexpectedly, infants in the modified group returned to adequate feeding a median of 2·7 h sooner, were perceived to return to normal by their parents 1 day earlier, and had fewer readmissions to hospital within 28 days compared with those in the standard group. Adverse events did not differ between groups. The authors conclude that children with bronchiolitis could be managed with an oxygen saturation target of 90% or higher, instead of 94% or higher, with no short-term safety implications. This would result in earlier discharge home from hospital with the potential for health-care-cost reduction and improved quality of life for parents. The primary outcome chosen by Cunningham and colleagues6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar (resolution of cough) was unusual for clinical trials of bronchiolitis, although duration of cough is perceived to be important by families.7Hay AD Wilson A Fahey T Peters TJ The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study.Fam Pract. 2003; 20: 696-705Crossref PubMed Scopus (121) Google Scholar The association between duration of cough and degree of hypoxaemia is not established, and it is interesting to speculate whether the results of cough duration would have been any different if an even lower saturation cutoff was chosen. Cunningham and colleagues suggest a potential interaction with airway inflammation, and it is also possible that cough might become more frequent with worsening hypoxia given the association between cough frequency and altitude8Mason NP Barry PW Despiau G Gardette B Richalet JP Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude.Eur Respir J. 1999; 13: 508-513Crossref PubMed Scopus (29) Google Scholar and the as yet unexplained association between nocturnal cough and obstructive sleep apnoea reported in adults.9Sundar KM Daly SE Pearce MJ Alward WT Chronic cough and obstructive sleep apnea in a community-based pulmonary practice.Cough. 2010; 6: 2Crossref PubMed Scopus (52) Google Scholar Of the other outcomes measured, the time to sufficient feeding and frequency of apnoea were possibly more discerning outcomes that could have been affected by hypoxia. The parental perception of return to normalcy might be biased by early discharge home, but, like readmission to hospital, would also reflect the parental level of concern about the infant. Although Cunningham and colleagues' study6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar provides convincing evidence that reduced oxygen saturation targets in bronchiolitis are safe in the short term, unfortunately the longer-term neurocognitive and behavioural outcomes are unknown. On one hand, the likely safety of the lower oxygen saturation target is supported from a physiological perspective because the oxygen–haemoglobin dissociation curve predicts that the actual oxygen delivered to tissues is unlikely to be very different with an oxygen saturation target of 90% instead of 94%, although risk factors such as fever and acidosis need to be taken into account. In addition, intermittent desaturation episodes of short duration (up to 6 s) have no adverse consequences in infancy.10Hunt CE Corwin MJ Lister G et al.for the Collaborative Home Infant Monitoring Evaluation (CHIME) Study GroupLongitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age.J Pediatr. 1999; 135: 580-586Summary Full Text Full Text PDF PubMed Scopus (103) Google Scholar On the other hand, intermittent hypoxia over a prolonged period of months to years, as in sleep disordered breathing and long-term hypoxaemia due to altitude or congenital heart disease, has been associated with detrimental effects on long-term neurocognitive outcomes in children.11Bass JL Corwin M Gozal D et al.The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence.Pediatrics. 2004; 114: 805-816Crossref PubMed Scopus (350) Google Scholar The resulting quandary is in clinical situations such as bronchiolitis or asthma, which lie somewhere between these two ends of the spectrum in terms of duration of lower saturations, when the longer-term safety of lower saturation targets falls into an evidence-free zone. When the American Academy of Pediatrics bronchiolitis guidelines3American Academy of Pediatrics subcommittee on diagnosis and management of bronchiolitisDiagnosis and management of bronchiolitis.Pediatrics. 2006; 118: 1774-1793Crossref PubMed Scopus (853) Google Scholar were published in 2007 suggesting 90% as the acceptable saturation cutoff, Bass and Gozal12Bass JL Gozal D Oxygen therapy for bronchiolitis.Pediatrics. 2007; 119: 611Crossref PubMed Scopus (18) Google Scholar raised concerns about the potential detrimental effects on cognitive and behavioural outcomes, and concerns among paediatricians continue to be raised.13Walsh P Rothenberg SJ American Academy of Pediatrics 2014 bronchiolitis guidelines: bonfire of the evidence.West J Emerg Med. 2015; 16: 85-88Crossref PubMed Scopus (11) Google Scholar Findings from BIDS6Cunningham S Rodriguez A Adams T et al.for the Bronchiolitis of Infancy Discharge Study (BIDS) groupOxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial.Lancet. 2015; 386: 1041-1048Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar also raise questions about the use of supplemental oxygen in other acute hypoxic states, such as exacerbations of asthma and community-acquired pneumonia. The decision about acceptable oxygen saturations for these disorders is also based on expert opinion and becomes a matter of clinical judgment, availability of health-care resources, and cost implications. Cunningham and colleagues have done a commendable job in bringing robust evidence with far-reaching implications to an area previously governed by expert opinion; however, we urge consideration of long-term neurobehavioural follow-up of randomised trials such as BIDS, to shed light on the nagging question that remains. This online publication has been corrected. The corrected version first appeared at thelancet.com on October 9, 2015 This online publication has been corrected. The corrected version first appeared at thelancet.com on October 9, 2015 This online publication has been corrected. The corrected version first appeared at thelancet.com on October 9, 2015 CEW has received honoraria, travel expenses, and consulting fees from Vertex Pharmaceuticals, honoraria and travel expenses from Novartis Pharmaceuticals, is a member of the international advisory board for Vertex Pharmaceuticals, and has been an investigator and received funding on a per-patient basis derived from pharmaceutical studies sponsored by Vertex Pharmaceuticals and Boehringer Ingelheim. She has taken part in studies sponsored by Vertex Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, and GlaxoSmithKline. NK declares no competing interests. Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trialManagement of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce. Full-Text PDF Open AccessDepartment of ErrorWainwright CE, Kapur N. Oxygen saturation targets in infants with bronchiolitis. Lancet 2015; 386: 1016–18—In this Comment (Sept 12), the addresses for the authors should read: Department of Respiratory and Sleep Medicine, Lady Cilento Children's Hospital, Brisbane, QLD 4101, Australia (CEW, NK); and School of Medicine, University of Queensland, QLD, Australia (CEW). This correction has been made to the online version as of Oct 9, 2015. Full-Text PDF
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