may 2020 • JAMA Pediatr

Evaluating the Placebo Status of Nebulized Normal Saline in Patients With Acute Viral Bronchiolitis - A Systematic Review and Meta-analysis

House SA, Gadomski AM, Ralston SL

DOI: 10.1001/jamapediatrics.2019.5195.

Content curated by:Paulo Faria de Sousa

Key message

O tratamento com nebulização de soro fisiológico em doentes com Bronquiolite aguda melhora significativamente a frequência respiratória e scores respiratórios mas não a hipoxemia. Comparativamente com outros placebos, a nebulização com soro fisiológico apresenta melhorias superiores. O soro fisiológico aerossolizado pode ser um tratamento activo para bronquiolite aguda, sendo necessários estudos posteriores para confirmar este achado. #Contexto A melhoria clínica consistente observada nos doentes com Bronquiolite Aguda tratados com soro fisiológico nebulizado levanta a questão se este será de facto um placebo ou um tratamento activo. #Pergunta de Investigação -População - crianças com bronquiolite aguda -Intervenção – Nebulização com soro fisiológico -Comparadores – outros placebos e comparação com estado prévio ao tratamento -Outcomes – Medição de parâmetros respiratórios – escalas de sintomas respiratórios, frequência respiratória, saturação de O2 após 60 min do início do tratamento

Analysis

Method

Revisão sistemática e meta-análise. Foram pesquisados ensaios clínicos envolvendo crianças com < 2 anos com Bronquiolite Aguda tratados com soro fisiológico nebulizado. Estudos envolvendo outros placebos foram incluídos para efeitos de comparadores. Foram extraídos dados dos estudos obtidos e analisados recorrendo a modelos meta-analíticos de comparações indirectas.

Results

29 estudos com total de 1583 doentes. - Comparações directas – 3 estudos com > 200 doentes. Após 60min de tratamento, a nebulização com Soro Fisiológico mostrou uma melhoria superior de scores respiratórios comparativamente com outros placebos - Diferenças de médias estandardizadas de -0.9 pontos (IC 95% -1.2 a -0.6). Não existiram diferenças na frequência respiratória nem saturação de O2. - Comparação antes e após tratamento – Melhoria nos scores respiratórios −0.7 (IC 95%, −0.7 a− 0.6; I2 = 62%); melhoria na frequência respiratória de 5.5 ciclos por minuto (IC 95%, −6.3 a −4.6 cpm; I2 = 24%); alteração da Sat O2 de −0.4% (IC 95%, −0.6% a −0.2%; I2 = 79%).

Abstract

Importance In therapeutic trials for acute viral bronchiolitis, consistent clinical improvement in groups that received nebulized normal saline (NS) as placebo raises the question of whether nebulized NS acts as a treatment rather than a placebo. Objective To measure the short-term association of nebulized NS with physiologic measures of respiratory status in children with bronchiolitis by analyzing the changes in these measures between the use of nebulized NS and the use of other placebos and the changes before and after nebulized NS treatment. Data Sources MEDLINE and Scopus were searched through March 2019, as were bibliographies of included studies and relevant systematic reviews, for randomized clinical trials evaluating nebulized therapies in bronchiolitis. Study Selection Randomized clinical trials comparing children 2 years or younger with bronchiolitis who were treated with nebulized NS were included. Studies enrolling a treatment group receiving an alternative placebo were included for comparison of NS with other placebos. Data Extraction and Synthesis Data abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used. Main Outcomes and Measures Pooled estimates of the association with respiratory scores, respiratory rates, and oxygen saturation within 60 minutes of treatment were generated for nebulized NS vs another placebo and for change before and after receiving nebulized NS. Results A total of 29 studies including 1583 patients were included. Standardized mean differences in respiratory scores for nebulized NS vs other placebo (3 studies) favored nebulized NS by −0.9 points (95% CI, −1.2 to −0.6 points) at 60 minutes after treatment (P < .001). There were no differences in respiratory rate or oxygen saturation comparing nebulized NS with other placebo. The standardized mean difference in respiratory score (25 studies) after nebulized NS was −0.7 (95% CI, −0.7 to −0.6; I2 = 62%). The weighted mean difference in respiratory scores using a consistent scale (13 studies) after nebulized NS was −1.6 points (95% CI, −1.9 to −1.3 points; I2 = 72%). The weighted mean difference in respiratory rate (17 studies) after nebulized NS was −5.5 breaths per minute (95% CI, −6.3 to −4.6 breaths per minute; I2 = 24%). The weighted mean difference in oxygen saturation (23 studies) after nebulized NS was −0.4% (95% CI, −0.6% to −0.2%; I2 = 79%). Conclusions and Relevance Nebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.