Bubble CPAP in resource-poor settings: friend or foe?
Authors: Patrick T Wilson
Journal: The Lancet Respiratory Medicine (2019)

The results of McCollum and colleagues' study in Malawi highlight several important points surrounding the use of non-invasive ventilation in low-income and middle-income countries (LMICs).1McCollum ED Mvalo T Eckerle M et al.Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label randomised controlled trial.Lancet Respir Med. 2019; published online Sept 24. https://doi.org/10.1016/S2213-2600(19)30243-7Summary Full Text Full Text PDF Scopus (31) Google Scholar Bubble continuous positive airway pressure (bCPAP), a form of non-invasive ventilation, has been used for decades in high-income countries in both neonatal and paediatric patients with acute respiratory distress. In LMICs the use of bCPAP has also increased as a result of its perceived safety, reduced invasiveness and technical skill requirements, and relatively low cost compared with invasive mechanical ventilation.2Duke T CPAP and high-flow oxygen to address high mortality of very severe pneumonia in low-income countries - keeping it in perspective.Paediatr Int Child Health. 2019; 39: 155-159Crossref PubMed Scopus (2) Google Scholar, 3Jayashree M KiranBabu HB Singhi S Nallasamy K Use of nasal bubble CPAP in children with hypoxemic clinical pneumonia-report from a resource limited set-up.J Trop Pediatr. 2016; 62: 69-74Crossref PubMed Scopus (25) Google Scholar, 4Thukral A Sankar MJ Chandrasekaran A Agarwal R Paul VK Efficacy and safety of CPAP in low- and middle-income countries.J Perinatol. 2016; 36: S21-S28Crossref PubMed Scopus (52) Google Scholar, 5Martin S Duke T Davis P Efficacy and safety of bubble CPAP in neonatal care in low and middle income countries: a systematic review.Arch Dis Child Fetal Neonatal Ed. 2014; 99: F495-F504Crossref PubMed Scopus (87) Google Scholar, 6Kawaza K Machen HE Brown J et al.Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in a neonatal ward in Malawi.PLoS One. 2014; 9: e86327Crossref PubMed Scopus (23) Google Scholar However, safety and effectiveness data on bCPAP in LMIC are less robust, emphasising the importance of the McCollum study. Two published randomised, controlled trials in Bangladesh (a tertiary centre) and Ghana (two district level hospitals) showed physiological and mortality benefits with the use of bCPAP in select paediatric populations under 5 years of age.7Chisti MJ Salam MA Smith JH et al.Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial.Lancet. 2015; 386: 1057-1065Summary Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 8Wilson PT Baiden F Brooks JC et al.Continuous positive airway pressure for children with undifferentiated respiratory distress in Ghana: an open label, cluster, crossover trial.Lancet Glob Health. 2017; 5: e615-ee23Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar The Bangladesh trial (n=146) was stopped early due to the significant reduction in mortality (15% vs 4%) in children receiving bCPAP for severe hypoxaemic pneumonia as compared with low flow oxygen. The clinical trial in Ghana (n=2182) showed significant improvement in respiratory rate in all age groups and decreased mortality (7% vs 3%) in children under 1 year of age with the application of bCPAP in undifferentiated acute respiratory distress. A meta-analysis pooled a neonatal and the two paediatric studies above suggesting safety and overall favourable benefit with the use of bCPAP in LMIC.9Ekhaguere OA Mairami AB Kirpalani H Risk and benefits of bubble continuous positive airway pressure for neonatal and childhood respiratory diseases in low- and middle-Income countries.Paediatr Respir Rev. 2019; 29: 31-36PubMed Google Scholar In contrast to previous studies, the Malawi study (n=644) showed an increase in mortality (11% vs 17%) with the use of bCPAP, and the trial was stopped early. These findings represent a sentinel event and deserve to be examined thoroughly. It is uncommon for well-designed, successfully implemented and closely monitored paediatric clinical trials to show harm in the context of previous research and clinical practice supporting the effectiveness and safety of a medical intervention. Given the study's successful randomisation and treatment allocation one must conclude that the findings are an effect of post-randomisation factors leading to harm. The authors offer several potential explanations for the increased mortality seen in their specific population: aspiration events, pneumothoraces, nasal airway obstruction, oxygen toxicity, absence of physician supervision, and equipment contamination. Further investigation is warranted to determine the exact cause of death to prevent harm in future patients. Even in low-resource settings verbal autopsies, small group sessions with local health-care providers who participated in the study, and critical reviews by outside experts can assist in root-cause analyses to determine the exact mechanism of death. Given the dramatically different results between the three published paediatric clinical trials, it is imperative to review key structural differences amongst them. The Ghana and Bangladesh trials both excluded children with impending respiratory failure, asthma, and upper-airway obstruction and the Ghana trial also excluded children with the inability to protect the airway, persistent emesis, unresponsiveness or coma, and hypotension. The only exclusion criterion in the Malawi study was previous participation in the study. The lack of exclusion criteria is a concern as many clinicians would avoid using non-invasive ventilation in patients with impending respiratory failure, inability to protect the airway, excessive emesis, and hypotension, even in highly monitored settings. Non-vented nasal mask interfaces were used in most patients in the Malawi study whereas the Bangladesh and Ghana trials only used nasal prongs. Different interfaces come with varying risks and the possibility of nasal masks occluding the nares, leading to hypoxaemic or hypercapneic respiratory failure, or both is a substantial concern if it is not feasible to monitor patients closely. Interface type, appropriate fit and close monitoring are essential in minimising the known risks of bCPAP in paediatric patients. Over 95% of patients in the Malawi study were eligible for nasogastric tube insertion per the study protocol but only 13% of patients receiving bCPAP were documented as having them placed. Feeding patients orally while in respiratory distress can lead to aspiration events and bCPAP could increase this risk further via gastric distension. Nasogastric feeds bypass the upper airway and might decompress the stomach avoiding further gastric distention. The Ghana study did not allow children to take feeds by mouth while in respiratory distress and most patients in Bangladesh received nasogastric tubes while on bCPAP. Both the Ghana and Bangladesh studies started bCPAP at 5 cm H2O, whereas the Malawi trial initiated bCPAP at 7 cm H2O or 8 cm H2O, possibly increasing the risk of aspiration. Although task shifting is reasonable in certain settings, the lack of physician oversight in the Malawi study was in direct contrast to the Ghana and Bangladesh studies. Although bCPAP is non-invasive, the absence of physician oversight could lead to delays in crucial medical decision making. It raises an important question of whether research should be done in settings where adequate medical supervision cannot be guaranteed during the trial. The authors are to be applauded for stopping the study early and reporting their findings. They correctly conclude that future studies are needed to definitively establish which specific patient populations could benefit from bCPAP in various settings. In conclusion, the Malawi study highlights the importance of appropriate exclusion criteria, protocol adherence, and close patient monitoring when implementing bCPAP in any setting and serves as an important reminder of the multiple challenges associated with doing research in critically ill paediatric patients in resource-poor settings. I declare no competing interests. Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trialbCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care. Full-Text PDF Open Access