Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial

François Lamontagne, Maureen O. Meade, Paul C. Hébert, Pierre Asfar, François Lauzier, Andrew J.E. Seely, Andrew G. Day, Sangeeta Mehta, John Muscedere, Sean M. Bagshaw, Niall D. Ferguson, Deborah J. Cook, Salmaan Kanji, Alexis F. Turgeon, Margaret S. Herridge, Sanjay Subramanian, Jacques Lacroix, Neill K.J. Adhikari, Damon C. Scales, Alison Fox-Robichaud, Yoanna Skrobik, Richard P. Whitlock, Robert S. Green, Karen K.Y. Koo, Teddie Tanguay, Sheldon Magder, Daren K. Heyland, for the Canadian Critical Care Trials Group.

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. 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. 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. 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.