december 2017 • Cochrane Systematic Review

Nebulised hypertonic saline solution for acute bronchiolitis in infants

Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP

DOI: 10.1002/14651858.CD006458.pub4

Content curated by:Paulo Faria de Sousa

Key message

Esta revisão sistemática e meta-análise encontrou evidência de qualidade baixa a moderada que em crianças com bronquiolite aguda, a nebulização com soro hipertónico (>3%) parece reduzir ligeiramente a duração de internamento, reduzir as taxas de internamento e melhorar scores de sintomas respiratórios até 3 dias após tratamento. Pergunta de investigação: -População - Crianças com idade inferior a 2 anos com bronquiolite aguda em internamento ou serviço de urgência -Intervenção – Nebulização com soro hipertónico (>3%) isolado ou em conjunto com broncodilatadores -Comparadores – Nebulização com soro fisiológico ou tratamento habitual -Outcomes – Duração de internamento em crianças internadas e taxa de internamentos em serviço de urgência.

Analysis

Method

Revisão sistemática e meta-análise de efeitos aleatórios. Pesquisa ampla nas bases de dados habituais. Tentativas de minimizar viés de publicação. A selecção dos estudos, extracção de dados e avaliação de risco de viés foi realizada de forma independente por dois investigadores.

Results

- Total de 28 estudos com 4195 crianças incluídas. Destas, 2222 receberam tratamento com soro hipertónico nebulizado. - Duração de internamento (17 estudos || 1867 doentes || Qualidade GRADE Baixa) – O tratamento reduziu o internamento em 0.41 dias menos que o controlo (IC 95% ‐0.75 a ‐0.07)* - Escalas de sintomas respiratórios (9 estudos || 812 doentes || Qualidade GRADE Baixa) – Melhores resultados com o tratamento. Diferença de médias de 0.77 menos que o controlo (IC 95% ‐1.18 a ‐0.36), mantendo-se inferior no 3º dia após tratamento (-1.43, IC 95% ‐1.82 a ‐1.04). - Taxa de internamento (8 estudos || 1723 doentes || Qualidade GRADE Moderada) – O tratamento reduziu a taxa de internamento comparado com controlo. Risco relativo de 0.86 (IC 95% 0.76 a 0.98). - Efeitos adversos (24 estudos || 3723 doentes) – 13 estudos não reportaram algum efeito adverso e 11 estudos reportaram pelo menos um efeito adverso, na sua maioria ligeiro e autolimitado. *Esta estimativa foi reduzida na actualização desta revisão da Cochrane. Em 2013 era de -1.15 dias. Os estudos mais recentes não encontraram diferenças na duração de internamento.

Abstract

Background: Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and previously updated in 2010 and 2013. Objectives: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 11 August 2017. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 8 April 2017. Selection criteria: We included randomised controlled trials and quasi‐randomised controlled trials using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline, or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department trials was rate of hospitalisation. Data collection and analysis: Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random‐effects model meta‐analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics. Main results: We identified 26 new trials in this update, of which 9 await classification due to insufficient data for eligibility assessment, and 17 trials (N = 3105) met the inclusion criteria. We included a total of 28 trials involving 4195 infants with acute bronchiolitis, of whom 2222 infants received hypertonic saline. Hospitalised infants treated with nebulised hypertonic saline had a statistically significant shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD ‐0.41 days, 95% CI ‐0.75 to ‐0.07; P = 0.02, I² = 79%; 17 trials; 1867 infants) (GRADE quality of evidence: low). Infants who received hypertonic saline also had statistically significant lower post‐inhalation clinical scores than infants who received 0.9% saline in the first three days of treatment (day 1: MD ‐0.77, 95% CI ‐1.18 to ‐0.36, P < 0.001; day 2: MD ‐1.28, 95% CI ‐1.91 to ‐0.65, P < 0.001; day 3: MD ‐1.43, 95% CI ‐1.82 to ‐1.04, P < 0.001) (GRADE quality of evidence: low). Nebulised hypertonic saline reduced the risk of hospitalisation by 14% compared with nebulised 0.9% saline among infants who were outpatients and those treated in the emergency department (RR 0.86, 95% CI 0.76 to 0.98; P = 0.02, I² = 7%; 8 trials; 1723 infants) (GRADE quality of evidence: moderate). Twenty‐four trials presented safety data: 13 trials (1363 infants, 703 treated with hypertonic saline) did not report any adverse events, and 11 trials (2360 infants, 1265 treated with hypertonic saline) reported at least one adverse event, most of which were mild and resolved spontaneously. Authors' conclusions: Nebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate.