Elsevier

The Lancet

Volume 386, Issue 9998, 12–18 September 2015, Pages 1057-1065
The Lancet

Articles
Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial

https://doi.org/10.1016/S0140-6736(15)60249-5Get rights and content

Summary

Background

In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies.

Methods

This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759.

Findings

Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07–0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11–2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07–0·89; p=0·022).

Interpretation

Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology.

Funding

International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.

Introduction

In 2010, an estimated 120 million episodes of pneumonia in children younger than 5 years old, and 14 million cases progressed to severe pneumonia, as defined by WHO.1 In 2011, an estimated 1·3 million children died from pneumonia.1 Hypoxaemia is a major risk factor for death in children with pneumonia,2, 3 and effective management of severe pneumonia and hypoxaemia is a major challenge for clinicians in developing countries.4 In addition to antibiotics and supportive care, WHO recommends oxygen supplementation if the arterial oxygen saturation measured by pulse oximetry (SpO2) is less than 90%, or if a child has cyanosis, is unable to feed, or shows other danger signs.5 WHO recommends giving oxygen by nasal cannula at the following flow rates: 0·5–1 L/min for neonates, 1–2 L/min for infants and children younger than 2 years, and 2–4 L/min for children 2 years and older,5 and improving oxygen therapy has been shown to reduce mortality from severe pneumonia in developing countries.6 However, despite the provision of oxygen, antibiotics, and supportive care, case-fatality rates for severe pneumonia and hypoxaemia are high in many hospitals in developing countries (5–15% in observational studies).7, 8, 9, 10, 11, 12, 13, 14 We aimed to assess the role of other respiratory support, which could be given to the most severely ill children with pneumonia in resource-limited settings.

Continuous positive airway pressure (CPAP) is widely used for children with moderate or severe respiratory distress in intensive care units (ICU) in developed countries. The most common method to deliver CPAP is via a mechanical ventilator, which is not available in most health facilities in developing countries. However, bubble CPAP is possible using simple, low-cost material.15 This method generates positive-end-expiratory pressure by connecting the expiratory limb of a breathing circuit to a tube, which is submerged in water. The distance that the distal end of the expiratory tube is under water is equivalent to the pressure (in cm H2O) that will be generated in the upper airway if an adequate seal has been made in the patient interface and bubbles appear in the water bottle.15 Modified nasal oxygen prongs can be used, making it minimally invasive and almost as easy for nurses to apply as standard flow oxygen therapy. Bubble CPAP has been used successfully in neonatal care in developed countries since the 1970s, and is promoted for its simplicity, low cost, and potential applicability for neonatal care in low-resource settings.16, 17 However, the efficacy of bubble CPAP has not been assessed for children with pneumonia in developing countries.18

Another popularised method of respiratory support beyond standard flow oxygen supplementation uses a humidified high-flow mixture of air and oxygen via a nasal oxygen cannula. This method has also been used effectively for neonatal respiratory distress, acute viral bronchiolitis, and other disorders in developed countries.19, 20, 21, 22, 23 High-flow oxygen therapy has been shown to reduce the need for mechanical ventilation in ICUs, but as for bubble CPAP, has not been assessed in developing countries.

We aimed to assess whether respiratory support using bubble CPAP is more effective than standard low-flow oxygen therapy or high-flow oxygen therapy to reduce treatment failure or death in children with severe pneumonia.

Section snippets

Study design and patients

We did an open, randomised controlled trial of three methods of oxygen therapy for children with severe pneumonia and hypoxaemia in Bangladesh. Patients were treated with bubble CPAP, low-flow nasal cannula, or high-flow nasal cannula oxygen therapies in addition to WHO standard management of very severe pneumonia.

The study was undertaken at the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. The ICU of this hospital manages about 600 children with severe

Results

Between Aug 4, 2011, and July 17, 2013, 376 children younger than 5 years were admitted with severe pneumonia and hypoxaemia and assessed for eligibility. 151 (40%) children did not meet the study inclusion criteria (appendix). Of the 225 (60%) children who met the inclusion criteria and provided informed consent, 79 (35%) children were randomly allocated to receive bubble CPAP for provision of oxygen therapy, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. All

Discussion

Results of our randomised controlled trial in children with severe pneumonia in Bangladesh showed that fewer children who received bubble CPAP had treatment failure and death than did those who received standard low-flow nasal cannula oxygen therapy.

The recognition that hypoxaemia is the primary risk for mortality in children with pneumonia and the poor access to oxygen therapy in many settings has prompted calls for oxygen to be more widely available in developing countries. WHO has included

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