SGEM #379 Heigh Ho High Flow versus CPAP in Acutely Ill Children

Date: September 15, 2022 Reference:  Ramnarayan P et al. Effect of high-flow nasal cannula therapy vs continuous positive airway pressure therapy on liberation from respiratory support in acutely ill children admitted to pediatric critical care units: a randomized clinical trial. JAMA July 2022 Dr. Spyridon Karageorgos Guest Skeptic: Dr. Spyridon Karageorgos is a Pediatric Resident at Aghia Sophia Childrens’ Hospital, Athens, Greece and a MSc student in Pediatric Emergency Medicine at Queen Mary University London. Case: A 10-month-old male infant presents to the emergency department (ED) with a low-grade fever, rhinorrhea and reduced feeding during the last two days. On exam, you notice increased work of breathing, nasal flaring, grunting with subcostal and intercostal retractions. He’s breathing at a rate of 75 per minute with oxygen saturations of 86% on room air. You make a clinical diagnosis of severe bronchiolitis. You start with low-flow O2 therapy but there is no clinical improvement. You discuss with the family the possibility that the child may need to be admitted in the pediatric intensive care unit (PICU) and require escalation of respiratory support with another modality of non-invasive ventilation. Parents look worried and ask you what kind of non-invasive support are you planning to start? Background: The use of High-Flow Nasal Cannula (HFNC) has increased in both PICU and in the Pediatric ED, especially for infants presenting acutely ill with respiratory distress requiring non-invasive ventilation (NIV). Despite the rise in popularity, there is a lack of high-quality evidence surrounding the use of high flow nasal cannula. Most studies are observational studies rather than randomized control trials (RCTs) [1-3]. Randomized control trials performed demonstrated that the early initiation of high flow nasal cannula led to lower rates of treatment failure/escalation…to high flow nasal cannula[4]. Even results from meta-analyses are mixed [5-6]. The SGEM covered the use of high flow nasal oxygen for bronchiolitis with Dr. Ben Lawton on SGEM #228. The bottom line for that episode was: "High flow oxygen therapy is not required for every child in hospital with bronchiolitis. It will continue to have a role in supporting those with more severe disease, but the potential benefits and harms will need to be considered within the context of where it is being used." There are a few proposed mechanisms for HFNC: Positive pressure Reduced upper airway resistance Washout of dead space in the nasopharynx More comfort from humidified air However, data regarding the clinical effectiveness of HFNC compared to continuous positive airway pressure (CPAP) is limited. In 2018, Ramnarayan et al. performed a multicentre pilot randomised controlled trial of HFNC vs CPAP in paediatric critical care that confirmed the feasibility of performing a large multicenter trial on HFNC vs CPAP in PICU [7]. The FIRST-ABC master protocol included two RCTs, one in acutely ill children requiring respiratory support (Step-Up RCT) and one in children requiring respiratory support after extubation from invasive ventilation (Step-Down RCT), with the aim of assessing the clinical and cost-effectiveness of HFNC as the first-line mode of non-invasive respiratory support in critically ill children. We’re focusing on the Step-Up RCT for today’s episode. Clinical Question: In acutely ill pediatric patients requiring non-invasive ventilation in the PICU, is High Flow Nasal Cannula (HFNC) noninferior to Continuous Positive Airway Pressure (CPAP) in terms of time to liberation from all forms of respiratory support? Reference:  Ramnarayan P et al. Effect of high-flow nasal cannula therapy vs continuous positive airway pressure therapy on liberation from respiratory support in acutely ill children admitted to pediatric critical care units: a randomized clinical trial. JAMA July 2022 Population: Children between 36 weeks (corrected gestational age) and less than 16 years requiring non-invasive respiratory support for acute illness from 24 PICUs and HDUs in the UK between August 2019 and November 2021 Exclusion: Clinical decision to initiate other mode of ventilation (intubation, invasive ventilation), tracheostomy in place, receipt of CPAP or HFNC for >2 hours in the prior to randomization, supplemented O2 at home, presence of air-leak, midfacial/craniofacial anomalies, previously recruited to the FIRST-ABC trial Intervention: HFNC based on body weight Comparison: CPAP of 7 to 8 cm H2 Outcome: Primary Outcome: Time from randomization to liberation from respiratory support which was defined as the start of the 48-hour period during which the child was free from any respiratory support, excluding supplemental oxygen. Secondary Outcomes: Mortality at critical care discharge Rate of intubation at 48 hours Duration of critical care and acute hospital stay Patient comfort Sedation during noninvasive respiratory support Parental stress Adverse events up to 48 hours after liberation from respiratory support Trial: unblinded, multicenter, parallel-group, randomized, non-inferiority trial. Authors’ Conclusions: “Among acutely ill children clinically assessed to require non-invasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. Yes. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure. Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure. Financial conflicts of interest. The lead author reported receiving personal fees from two healthcare companies, but we do not think this impacted the results of the article. Results: 600 children (41% of those eligible) were randomized. 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis. 533 children (HFNC: 288; CPAP: 245) were included in the per-protocol analysis. Median age for both groups was around 9 months and 40% were female. Key Result: There were no statistical differences between the HFNC and CPAP groups with regards to time from randomization to liberation from respiratory support. Primary Outcome: The median time to liberation in the HFNC group was 52.7 hours (95% CI, 45.0-60.1 hours) vs 45.4 hours (95% CI, 40.2-53.7 hours) in the CPAP group Absolute difference, 7.3 hours [95% CI –7.3 to 22.2 hours] Adjusted hazard ratio 1.03 [0.86-1.2] Secondary Outcomes:  There was no difference between groups regarding mortality at critical care discharge, patient comfort and parental stress scale. Sedation use was lower in the HFNC group compared to the CPAP group (28% vs 39.2%) Non-invasive Ventilation Devices: This study was attempting to compare HFNC versus CPAP across multiple institutions. However, not all institutions used the same device or interface of delivering HFNC or CPAP. There were 7 different types of devices used across the institutions to deliver HFNC or CPAP. There were 5 or 6 difference CPAP interfaces used. It is hard to guarantee that with this variation, the patients received the same or consistent respiratory support within the same group. The modality of CPAP used may also have impacted patient comfort and decision to switch modalities. Heterogeneous Disease Processes: While most previous HFNC studies have looked specifically at application to children with bronchiolitis, this study includes a patient population with a variety of disease processes including upper airway problems, asthma, cardiac, neurologic, or sepsis/infection. This both a strength and weakness of this study. Including a heterogeneous group may make the results more generalizable. However, it leaves much more (appropriate) flexibility on behalf of the clinician as to what modality of NIV to use. For example, a patient for whom we may want to optimize preload, we may prefer a modality that avoids excessive positive pressure, leading to decrease systemic venous return. Disclaimer: I am skeptical of the ability for HFNC to deliver consistent PEEP especially in children, given that it is an open system, variability to size of cannula and nares, and little control over whether a pediatric patient keeps their mouth open or closed.[8] Selection Bias: As mentioned prior only 41% of eligible patients were randomized in the study. Of the group of that were eligible but not randomized, 35% (325 out of 849) were due to “clinical decision.” The authors cite reasons including preference for HFNC or CPAP, unavailability of PICU (could not initiate CPAP), availability of CPAP masks, cardiac disease, wheeze and unsuitability of CPAP, or unspecified reasons. This may have led to selection bias. Switching between HFNC and CPAP: The decision to switch from HFNC and CPAP and vice versa was based on clinician’s judgement. Even though there were specific criteria for switching, a high rate of patients initially randomized to CPAP group were switched to HFNC (31%), mainly due to discomfort.