Applicability of Vasopressor Trials in Adult Critical Care: A Prospective Multicentre Meta-Epidemiologic Cohort Study

Abstract

Nina Buchtele,1 Michael Schwameis,2 Dominik Roth,2 Franz Schwameis,3 Felix Kraft,4 Roman Ullrich,4 Jakob Mühlbacher,5 Roberta Laggner,6 Gunnar Gamper,7 Georg Semmler,8 Christian Schoergenhofer,9 Thomas Staudinger,1 Harald Herkner2 1Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, Vienna, Austria; 2Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria; 3Department of Anaesthesiology and Intensive Care Medicine, Landesklinikum Baden, Vienna, Austria; 4Department of Anaesthesia, Critical Care and Pain Medicine, Medical University of Vienna, Vienna, Austria; 5Department of General Surgery, Medical University of Vienna, Vienna, Austria; 6Department of Orthopaedics and Trauma-Surgery, Medical University of Vienna, Vienna, Austria; 7Department of Cardiology, Universitätsklinikum Sankt Pölten, Vienna, Austria; 8Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 9Department of Clinical Pharmacology, Medical University of Vienna, Vienna, AustriaCorrespondence: Michael Schwameis, Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria, Tel [phone], Fax [phone], Email [email protected]: To assess the applicability of evidence from landmark randomized controlled trials (RCTs) of vasopressor treatment in critically ill adults.Study Design and Setting: This prospective, multi-center cohort study was conducted at five medical and surgical intensive care units at three tertiary care centers. Consecutive cases of newly initiated vasopressor treatment were included. The primary end point was the proportion of patients (≥ 18 years) who met the eligibility criteria of 25 RCTs of vasopressor therapy in critically ill adults included in the most recent Cochrane review. Multilevel Poisson regression was used to estimate the eligibility proportions with 95% confidence intervals for each trial. Secondary end points included the eligibility criteria that contributed most to trial ineligibility, and the relationship between eligibility proportions and (i) the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) score, and (ii) the recruitment-to-screening ratio of each RCT. The PRECIS-2 score was used to assess the degree of pragmatism of each trial.Results: Between January 1, 2017, and January 1, 2019, a total of 1189 cases of newly initiated vasopressor therapy were included. The median proportion of cases meeting eligibility criteria for all 25 RCTs ranged from 1.3% to 6.0%. The eligibility criteria contributing most to trial ineligibility were the exceedance of a specific norepinephrine dose, the presence of a particular shock type, and the drop below a particular blood pressure value. Eligibility proportions increased with the PRECIS-2 score but not with the recruitment-to-screening ratio of the trials.Conclusion: The applicability of evidence from available trials on vasopressor treatment in critically ill adults to patients receiving vasopressors in daily practice is limited. Applicability increases with the degree of study pragmatism but is not reflected in a high recruitment-to-screening ratio. Our findings may help researchers design vasopressor trials and promote standardized assessment and reporting of the degree of pragmatism achieved.Graphical Abstract: Keywords: real-world data, randomized controlled trials, critical illness, vasoconstrictor agents

Keywords

• real-world data
• randomized controlled trials
• critical illness
• vasoconstrictor agents