Outcome in early vs late intubation among COVID-19 patients with acute respiratory distress syndrome: an updated systematic review and meta-analysis

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Abstract
Timing of endotracheal intubation in COVID-19 patients with acute respiratory distress syndrome (ARDS) remains controversial regarding its risk and benefit in patient outcomes. Our study aims to elucidate early versus late intubation outcomes among COVID-19 patients with ARDS. A protocol of this study is registered at the international prospective register of systematic reviews (PROSPERO) (CRD42021230272). We report our systematic review based on PRISMA and MOOSE guidelines. We searched the Cochrane Library, EBSCOhost, EMBASE, Grey Literature Report, OpenGrey, ProQuest, PubMed, and ScienceDirect from inception until 4 December 2021. Titles and abstracts were reviewed for their relevance. The risk of bias in each study was evaluated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) guideline. Trial sequential analysis is done to elucidate firm evidence. We retrieved 20 observational studies that assessed an intervention (early vs. late intubation). Meta-analysis for in-hospital mortality reduction showed 119 fewer deaths per 1000 patients in early intubation. Early intubation reduces 2.81 days of ICU length of stay (LOS) and 2.12 days of ventilation duration. Benefits for mortality and ICU LOS reduction were based on studies with low to moderate risk of bias while ventilation duration was based on low disease burden setting. According to the contextualized approach, the benefit of mortality reduction showed a trivial effect, while ICU LOS and ventilation duration showed a small effect. GRADE certainty of evidence for mortality reduction in early intubation is moderate. The certainty of evidence for ICU length of stay, ventilation duration, ventilator-free days, and continuous renal replacement therapy are very low. This updated systematic review provided new evidence that early intubation might provide benefits in treating COVID-19 patients with ARDS. The benefits of early intubation appear to have an important but small effect based on contextualized approach for ICU LOS and ventilation duration. In reducing in-hospital mortality, the early intubation effect was present but only trivial based on contextualized approach. TSA showed that more studies are needed to elucidate firmer evidence.

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