EFFECT OF COMBINATION TREATMENT APPROACH WITH EARLY INFUSION OF PARALYTICS, PRONING, AND LUNG PROTECTIVE VENTILATION ON MORTALITY IN PATIENTS WITH SEVERE ARDS: A SYSTEMIC REVIEW AND META-ANALYSIS

Abstract

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Prone positioning with lung-protective ventilation (LPV) has been shown to confer a mortality benefit in severe acute respiratory distress syndrome (ARDS) (1). A recently published randomized controlled trial (RCT) failed to show a survival benefit with the use of paralytics (2). However, this study utilized far less prone positioning, and excluded patients who had prior administration of paralytics (2). The reviewers of this metanalysis raised the hypothesis that a combination of proning; paralytics; and LPV, improved mortality in patients with severe ARDS. The analysis was conducted to evaluate the effect of early combination treatment with: proning; infusion of paralytics and LPV versus individual modalities on 28-day mortality. METHODS: We conducted a literature search using PUBMED, MEDLINE, and EMBASE for studies published until August 2019. Our inclusion criteria were as follows; severe ARDS, defined as PaO2/FiO2 <150 with positive end expiratory pressure > 5, used LPV, continuous paralytics for at least 48 hours, and early proning (initiated within 12 hours) for at least 16 hours daily. The primary outcome of the study was 28-day mortality. Secondary outcomes included ventilator free days, intensive care unit (ICU) length of stay (LOS) and pneumothorax. A random effects model was used for analyzing pooled data. Methodologic qualities of the RCTs and overall body of evidence were evaluated using the ‘Effective Public Health Practice Project’ (EPHPP) quality assessment tool and meta-XL, respectively. RESULTS: Thirteen RCTs met the inclusion criteria. The risk of bias was low across all trials. Statistical analysis for 28-day mortality included 3,650 patients (1,844, 50.4%) in intervention group and (1,806, 49.6%) in the control group.The pooled effect size for 28-day mortality was 0.27 {95% confidence interval [CI], 0.19-0.34} in the intervention group compared to 0.34 {95% CI, 0.29-0.38} in the control group.There was significant heterogeneity with I2 of 93% vs 77% in both groups. Ventilator free days at 28-days were 11.67 {95% CI; 8.81-14.48} vs 7.8 {95% CI; 5.7-9.96}, and ICU LOS was 15.86 {95% CI; 10.92-20.79} vs 16.86 {95% CI; 8.08-25.63}. Pneumothorax incidence rates were 0.03 {95 % CI; 0.01-0.04} vs 0.029 {95% CI; 0.02-0.03} in the intervention and control group, respectively. Pooled performance estimates of mortality with subgroups could not be performed due to data limitations. CONCLUSIONS: Our metanalysis revealed a significant 28-day mortality difference between combination treatment versus LPV alone. There were also notable differences in ventilator free days and ICU LOS between study groups without increase in pneumothorax incidence. However, the heterogeneity between the included studies limits interpretation of these results. CLINICAL IMPLICATIONS: Future randomized controlled trials combining modalities will be useful to further evaluate potential mortality improvement in severe ARDS. DISCLOSURES: No relevant relationships by Noah Cook, source=Web Response No relevant relationships by Rajany Dy, source=Web Response No relevant relationships by Hafiz Mahboob, source=Web Response