Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock
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Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.
We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.
Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).
Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.
KeywordsVasopressors Hypotension Critical care Mean arterial blood pressure Individual patient data meta-analysis
We would like to thank Qi Zhou for additional input on the statistical analysis plan as well as nurses and physicians who contributed to both trials included in this analysis. We thank the Unité de Recherche Clinique et Épidémiologique (URCE) of the Centre de recherche du CHU de Sherbrooke for their support in coordinating the preparation and revisions of this manuscript.
FL and PA had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: FL, AGD, MOM, DJC, GHG, PA. Acquisition, analysis, or interpretation of data: FL, AGD, MOM, DJC, GHG, MH, PR, J-MC, NB, PH, FD, FM, PA. Drafting the manuscript: FL, PA. Critical revision of the manuscript for important intellectual content: FL, AGD, MOM, DJC, GHG, MH, PR, J-MC, NB, PH, FD, FM, PA. Statistical analysis: FD. Study supervision: FL.
Compliance with ethical standards
This analysis was funded by a grant from the Fonds de Recherche du Québec - Santé. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Conflicts of interest
The authors declare that they have no conflict of interest. Drs. Lamontagne and Asfar are the Principal Investigators of both trials included in this analysis.
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