Abstract
Purpose
In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.
Methods
We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60–65 mmHg) versus a higher (75–80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.
Results
A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7–11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36 %, p = 0.07) and hospital mortality (30 versus 33 %, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %, p = 0.03) but not in younger patients.
Conclusions
This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.
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Acknowledgments
We would like to express our gratitude for the contribution and support of Janet Overvelde, Shawna Froese, Jesse Gadon, the Institute for Safer Medication Practices Canada, the Canadian Critical Care Society, the Canadian Society of Hospital Pharmacists, the Canadian Association of Emergency Physicians, the Canadian Association of Critical Care Nurses and the intensive care unit nurses and physicians who collaborated on this work. Dr. Tom Stelfox conducted the internal review of this manuscript for the Canadian Critical Care Trials Group. We are also indebted to Dr. Andreas Laupacis (Chair), Dr. Lauren Griffiths and Dr. Scott Halpern who constituted the Data Monitoring Committee for this trial. This study would not have been feasible without the outstanding participation of (in alphabetical order) Sarah-Judith Breton, Katia Cauchon, Paulina Farais, Susan Fleury, Brittany Giacomino, Marnie Jakab, Lisa Julien, Catherine Krause, Chantal Langevin, Heather Langlois, Nicole Marinoff, Andrea Matte, Tracy McArdle, Katie O'Brien, Rebecca Porteus, , Sumesh Shah, Samantha Taylor, and Irene Watpool.
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Take-home message: This pilot study supports the feasibility of a larger trial comparing MAP targets below those applied in the SEPSISPAM trial. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.
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Lamontagne, F., Meade, M.O., Hébert, P.C. et al. Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med 42, 542–550 (2016). https://doi.org/10.1007/s00134-016-4237-3
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DOI: https://doi.org/10.1007/s00134-016-4237-3