Efficacy and safety of non-invasive ventilation in pediatric care in low-income and middle-income countries: a systematic review

Abstract

Background Lower respiratory tract infections (LRTIs) are a leading cause of under-5 mortality in low-income and middle-income countries (LMICs) and interventions to reduce mortality are needed. Non-invasive ventilation has been shown to reduce mortality for neonates; however, data for children >1 month of age in LMICs are lacking. The objective of this study was to systematically review the available literature to determine if non-invasive ventilation as the primary modality of respiratory support is efficacious and safe for the management of respiratory distress in non-neonatal pediatric patients in LMICs. Methods We systematically reviewed all studies assessing the endpoints of efficacy, effectiveness, and safety of non-invasive ventilation for pediatric LRTIs in LMICs. A comprehensive search of Medline, Embase, LILACS, Web of Science, and Scopus was performed on April 7, 2020. Included studies assessed the safety, efficacy or effectiveness of non-invasive ventilation (NIV) in the hospital setting for pediatric patients with respiratory distress from 1 month - 15 years of age in LMICs. All study types, including case reports and case series were included. Studies focusing exclusively on neonates (<28 days old) were excluded. Mortality and rates of adverse events were extracted using Covidence by two independent reviewers. Risk of bias was assessed using GRADE criteria for randomized control trials and a standardized risk of bias assessment tool for observational studies. The study protocol was registered on PROSPERO (CRD42018084278). Findings A total of 2174 papers were screened and 20 met criteria for inclusion. There were 5 randomized control trials (RCTs), including 3 large, well-designed RCTs. The first RCT, the "Bangladesh trial," found that children who received bubble continuous positive airway pressure (bCPAP) compared to low-flow oxygen had a significantly lower risk of failure (6% in CPAP and 24% in low-flow oxygen, p=0.0026) and mortality (4% in CPAP and 15% in low-flow oxygen, p=0.022). A second RCT, the "Ghana trial," found no decrease in all-cause mortality between the CPAP and control arms (3% and 4% respectively, p=0.11); however, an adjusted secondary analysis demonstrated decreased mortality for children under 1 year of age (3% in CPAP and 7% in control group, p=0.01). The third RCT, the "Malawi trial," compared bCPAP to low flow oxygen and found higher mortality in the bCPAP arm (17% and 11% respectively, p=0.036). Among the non-RCT studies, mortality rates ranged from 0-55%. Interpretation The evidence of efficacy, effectiveness, and safety is mixed regarding the use of NIV in children with respiratory failure in LMICs. Our review of the literature suggests that CPAP for non-neonatal pediatric patients should be considered only in well-controlled, high acuity units with high provider-to-patient ratios and direct physician supervision. Until further data are available, CPAP use in LMICs should be limited to children less than 1 year of age. Further research is needed to determine best practices for CPAP prior to wide-spread implementation. Funding There was no funding source for this study.