Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: A systematic review and meta-analysis.

BACKGROUND: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries. METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365. FINDINGS: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p = 0.714 and Begg&Mazumdar test with p = 0.334. INTERPRETATION: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.

Extracorporeal membrane oxygenation (ECMO) in patients with severe COVID-19 adult respiratory distress syndrome: a systematic review and meta-analysis

BACKGROUND: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for COVID-associated ARDS to study its outcome. MATERIALS AND METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from inception to May 28, 2020. Studies reporting five or more patients with COVID 19 infection treated venovenous with ECMO were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. The validity of all the included observational studies was appraised with the Newcastle Ottawa scale. Meta-regression and publication bias were tested. This trial was registered with PROSPERO under registration number CRD42020183861. RESULTS: From 1647 initial citations, 34 full text articles were analysed and 12 studies were selected, including 194 patients with confirmed COVID 19 infection requiring ICU admission and venovenous ECMO treatment. Median New Castle Ottawa scale was 6 indicating acceptable study validity. 136 patients reached an endpoint of weaning from ECMO or death while the rest were still on ECMO. The median Berlin score for ARDS prior to starting ECMO was III. Patients received mechanical ventilation before ECMO implementation for a median of four days and ECMO was maintained for a median of 13 days. In hospital and short-term mortality were highly variable among the included studies ranging between 0% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.49 (95% confidence interval 0.259 to 0.721;I2 = 94%). Subgroup analysis according to country of origin showed persistent heterogeneity only in the 7 Chinese studies with pooled estimate mortality risk ratio of 0.66 (I2 = 87%) (95% CI = 0.39-0.93), while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.41 (95% CI 0.28-0.53) with homogeneity (p=0.67) similar to France with a pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86). Meta-regression showed only younger age as a predictor of mortality (p=0.02). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p=0.566 and Begg&Mazumdar test with p=0.373. CONCLUSION: The study included the largest number of patients with outcome findings of ECMO in this current pandemic. Our findings showed that the use of venovenous ECMO at high-volume ECMO centres may be beneficial for selected COVID 19 patients with severe ARDS. However, none of the included studies involve prospective randomized analyses;and therefore, all the included studies were of low or moderate quality according to the Newcastle-Ottawa scale. In the current era and environment of the pandemic, it will likely be very challenging to conduct a prospective randomized trial of ECMO versus no-ECMO for COVID-19. Therefore, the information contained in this systematic review of the literature is valuable and provides important guidance.