Philippa Clery & Megan Collins What are the acceptable oxygen saturation limits in babies with bronchiolitis? Philippa Clery & Megan Collins Year 4 Medical Students King’s College London

What does current guidance say? 2015 NICE Give oxygen supplementation if saturation is persistently less than 92% Before discharge ensure child has maintained oxygen saturation over 92% in air for 4 hours SpO2 value decided on consensus of Guideline Committee 2006 UK SIGN Recommend a normoxic saturation of 94% or higher (removed) 2014 American Academy of Pediatrics Physicians may choose not to administer supplemental oxygen to children with oxygen saturations of 90% or greater 2013 WHO Recommended saturation target of 90% or higher in infants with LRTI

Evidence 1 Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial. The Lancet 2015 1 “To our knowledge this is the first RCT of oxygen saturation targets of children with bronchiolitis” Randomised, double-blind 615 subjects, 6 weeks – 12 months 8 paediatric hospital units, UK Aim: To assess whether a 90% saturation target for management of oxygen supplementation was equivalent to a normoxic 94% target in infants admitted to hospital with bronchiolitis. Outcomes: Primary: Time to resolution of cough. Other: adverse events; admission to HDU rates; readmission rate; back to normal; returned to adequate feeding Conclusion: Cough resolved by 15 days (median) in both groups; adverse events did not differ significantly between the group; modified group returned to feeding 2.7hrs sooner and normal 1 day sooner Management of infants with bronchiolitis to an oxygen saturation of 90% or higher is as safe and clinically effective as 94% or higher. 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.

Critical Appraisal Strengths Weaknesses Correct demographics (age-range, UK, inpatient) SIGN 91 criteria for diagnosis Blinding Not generalisable to patients with chronic comorbidities Randomisation Primary outcome measure subjective Sufficient sample size Didn’t assess neurocognitive and behavioural outcomes Small attrition bias Assessed up to six months – could there be longer term consequences of 90% saturations? Multiple outcome measures Primary outcome of cough is a weird one to choose and was perceived/recorded by families – might be influenced by early discharge for example i.e. if child is discharged from hospital earlier the parent might be positively biased into thinking their child’s cough is getting better.

Evidence 2 Observational study of two oxygen saturation targets for discharge in bronchiolitis. Archive of Diseases in Childhood 20122. Prospective observational study 68 subjects, up to 18 months old Tertiary hospital, UK Aim: To assess effect of two oxygen saturation recommendations (90% and 94%) on recovering from bronchiolitis Outcomes: Time from admission to re-establishment of feeding Time from admission for SpO2 to become stable for 4 hours (at ≥90% or ≥94%) Conclusion: Time for infants to achieve a stable SpO2 of ≥90% and resolve feeding difficulties was a median of 22 hours sooner than the equivalent for a stable SpO2 of ≥94% Limitations: Small sample size; chronic condition exclusions Uses SIGN91 as 94% guide The main conclusion was more about timings and early discharge (important to consider), but didn’t measure feeding times separately in groups All but 20 infants (29%) had re-established feeding by the time they reached 90% saturations.

Evidence 3 Effect of Oxygen desaturations on subsequent medical visits in infants discharged from the Emergency Department with bronchiolitis. JAMA Pediatrics 2016 3. Prospective cohort study Canada 118 subjects from 2008 to 2013 Aim: To see if there’s a difference in the proportion of unscheduled medical visits within 72 hours of being discharged from the ED in infants with bronchiolitis who desaturated to below 90% for at least 1 minute during home oximetry monitoring compared to those who did not. Outcomes: Unscheduled medical visits / readmission within 72 hours of discharge Conclusion: Majority of infants experienced recurrent or sustained desaturations after discharge home. Infants with and without desaturations had comparable rates of return for care with no difference in unscheduled return hospital visits. Pulse oximetry is not an effective tool to predicting subsequent return to care Limitations: No information past 72 hours Performed in ED – not necessarily generalizable to inpatient population Not applicable to chronic desaturations or infants with co-morbid chronic respiratory In this prospective cohort study from 2016, researchers studied outcomes of infants discharged home with acute bronchiolitis from the paediatric emergency department at the Hospital for Sick Children in Toronto, Canada, comparing those who experienced desaturation with those who did not. They studied a total of 118 infants (mean age 4.5 months) seen at the centre from 6 February 2008 to 30 April 2013, and followed up to see if there was a difference in readmissions or seeking of medical care in the group that desaturated vs the one that didn’t. The majority of infants with mild bronchiolitis experienced recurrent or sustained desaturations after discharge home. Children with and without desaturations had comparable rates of return for care, with no difference in unscheduled return medical visits and delayed hospitalizations Before discharge, nurses attached a saturation probe to each infant’s foot, and parents were asked to keep this on at home. They were followed up by telephone 72 hours after discharge to check for further unscheduled medical visits for bronchiolitis.

Evidence 4 Effect of Oximetry on Hospitalization in Bronchiolitis A Randomized Clinical Trial. JAMA 2014 4 RCT 213 subjects, aged 4 weeks to 12 months Canada Aim: To examine if infants with bronchiolitis whose oximetry measurements had been artificially elevated to 3 percentage points above true values, experience less hospitalisation Outcome: Hospitalization Conclusion: Those with artificially elevated pulse oximetry were less likely to be admitted than those in the true value oximetry group (despite being the same clinically) Suggests that pulse oximetry should not be the main factor in decision on admitting and discharging Echoed by experts in field – concern of rise in hospitalisation rates when routine oximetry was introduced5 This study focuses more on the hospitalisation of patients with bronchiolitis, but raises a concern that is echoed by experts thorughout the field – that is of relying so heavily on pulse oximetry as a tool for decision on admitting and discharging pts e.g. since introduction of routine oximetry there was a rise in hospitalization rate of bronchiolitis. Experts feel that this increase in hospital admissions may have happened owing to a high reliance on oximetry. A retrospective study in 2004 also shows that hospitalisation of some infants with bronchiolitis are prolonged by a perceived need for supplemental oxygen therapy based on pulse oximetry readins alone.

Conclusions 90% is as good as 94% Perhaps better according to study outcomes Perhaps better because oxygen therapy has limitations A lower target approach is associated with cost savings for the NHS But we don’t know the long-term behavioural or neurocognitive effects of managing the infant to a lower target of 90% Pulse oximetry may not be the most effective tool to use when assessing for discharge Re-establishment of oral feeding may be better Future directions Longer term studies Intermittent vs continuous monitoring The BIDS trial found that “when managed with an SpO2 target of 90% as expected, fewer pts needed oxygen, those that did needed it for a shorter duration, and the infants were discharged home sooner> Infants might also regain satisfactory feeding and be back to normal sooner and have fewer readmissions to hospital” 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% i addition, intermittent desaturation episodes of short duration (up to 6 s) have no adverse consequences in infancy

References Cunningham, S, Rodriguez, A, Adams, et al. for the Bronchiolitis of Infancy Discharge Study (BIDS) group. Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial. Lancet. 2015; 386: 1041–1048 Cunningham, S and McMurray, A. Observational study of two oxygen saturation targets for discharge in bronchiolitis. Arch Dis Child. 2012; 97: 361–363 Principi T, Coates A, Parkin P. Effect of Oxygen Desaturations on Subsequent Medical Visits in Infants Discharged From the Emergency Department With Bronchiolitis. JAMA Pediatr. 2016;170(6):602-608 Schuh, S, Freedman, S, Coates, A et al. Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical trial. JAMA. 2014; 312: 712–718 Langley JM, LeBlanc JC, Smith B, Wang EE. Increasing incidence of hospitalization for bronchiolitis among Canadian children, 1980-2000.J Infect Dis. 2003;188(11):1764-1767