Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Eleni Papoutsi,Christina Routsi,Eleni Xourgia,Anastasia Kotanidou,Vassilis G Giannakoulis,Ilias I Siempos

doi:10.1186/s13054-021-03540-6

Abstract

BackgroundAlthough several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis.MethodsPubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147).ResultsA total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08).ConclusionsThe synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

Highlights

Several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial
Since the birth of critical care, the optimal timing of intubation of patients with severe acute hypoxemic respiratory failure seems to be a matter of debate. This debate is reinforced during the ongoing epidemic of coronavirus disease 2019 (COVID-19)
There was no statistically detectable difference between patients undergoing early versus late intubation regarding all-cause mortality (3981 deaths; 45.4% versus 39.1%; risk ratio (RR) 1.07, 95% confidence intervals (CI) 0.99–1.15, p = 0.08; Fig. 2)

Summary

Introduction

Several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Since the birth of critical care, the optimal timing of intubation of patients with severe acute hypoxemic respiratory failure seems to be a matter of debate. This debate is reinforced during the ongoing epidemic of coronavirus disease 2019 (COVID-19). Experts of clinical respiratory physiology seemed to back this approach with notions that early intubation might prevent ensuing patient self-inflicted lung injury [6].

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