François Lamontagne1,2,3, Maureen O Meade4,5, Paul C Hébert6, Pierre Asfar7, François Lauzier8,9,10, Andrew J E Seely11,12, Andrew G Day13, Sangeeta Mehta14, John Muscedere15, Sean M Bagshaw16, Niall D Ferguson14, Deborah J Cook4,5, Salmaan Kanji12, Alexis F Turgeon9,10, Margaret S Herridge14, Sanjay Subramanian17, Jacques Lacroix18, Neill K J Adhikari14,19, Damon C Scales14,19, Alison Fox-Robichaud4, Yoanna Skrobik20, Richard P Whitlock21,22, Robert S Green23, Karen K Y Koo24, Teddie Tanguay25, Sheldon Magder20, Daren K Heyland13. 1. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. francois.lamontagne@usherbrooke.ca. 2. Centre de Recherche du CHU de Sherbrooke, Sherbrooke, QC, Canada. francois.lamontagne@usherbrooke.ca. 3. Centre Hospitalier Universitaire de Sherbrooke, 3001 12e avenue N., Sherbrooke, QC, J1H 5N4, Canada. francois.lamontagne@usherbrooke.ca. 4. Department of Medicine, McMaster University, Hamilton, ON, Canada. 5. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. 6. Department of Medicine and Research Centre, Université de Montréal, Montreal, QC, Canada. 7. Department of Medical Intensive Care Medicine, University Hospital Angers, Angers, France. 8. Department of Medicine, Université Laval, Quebec, QC, Canada. 9. Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, Quebec, QC, Canada. 10. CHU de Québec - Université Laval Research Center, Population Health and Optimal Health Practices Research Unit (Trauma-Emergency-Critical Care Medicine), Université Laval, Quebec, QC, Canada. 11. Thoracic Surgery and Critical Care Medicine, University of Ottawa, Ottawa, ON, Canada. 12. Ottawa Hospital Research Institute, Ottawa, ON, Canada. 13. Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, Canada. 14. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 15. Department of Medicine, Kingston General Hospital, Queen's University, Kingston, ON, Canada. 16. Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 17. Department of Critical Care Medicine, Mercy St John's Medical Center, St Louis, MO, USA. 18. Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Quebec, Canada. 19. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 20. McGill University, Montreal, QC, Canada. 21. Department of Surgery, McMaster University, Hamilton, ON, Canada. 22. Population Health Research Institute, McMaster University, Hamilton, ON, Canada. 23. Department of Critical Care, Dalhousie University, Halifax, NS, Canada. 24. Department of Critical Care Medicine, Swedish Medical Center, Seattle, WA, USA. 25. Canadian Association of Critical Care Nurses, London, ON, Canada.
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.
RCT Entities:
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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