James A Russell1, Terry Lee2, Joel Singer3, Daniel De Backer4, Djillali Annane5. 1. Centre for Heart Lung Innovation (HLI), St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada; Division of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Electronic address: Jim.Russell@hli.ubc.ca. 2. Centre for Health Evaluation and Outcome Science (CHEOS), St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Electronic address: tlee@hivnet.ubc.ca. 3. Centre for Health Evaluation and Outcome Science (CHEOS), St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Electronic address: jsinger@hivnet.ubc.ca. 4. Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, 35 Rue Wayez, 1420 Braine L'Alleud, Belgium. Electronic address: ddebacke@ulb.ac.be. 5. Service de reanimation medicale, Hopital R. Poincare, 104 Bd Raymond Poincare, 92380 Garches, France. Electronic address: djillali.annane@rpc.aphp.fr.
Abstract
PURPOSE: RCTs in septic shock negative for mortality may show organ dysfunction benefits. We hypothesized that RCTs in septic shock show significant differences between treatment groups in organ support despite no mortality differences. METHODS: RCTs of epinephrine vs. norepinephrine plus dobutamine, norepinephrine vs. dopamine and vasopressin vs. norepinephrine reported days alive and free ("DAF") of vasopressors, ventilation and RRT, by subtracting days with support from the lesser of 28 or days to death. We also assigned zero DAF to non-survivors ("DAF and Mortality") and calculated the composite "DAF vasopressors, ventilation and RRT". RESULTS: Using "DAF", norepinephrine was better than dopamine for vasopressors. In contrast, using "DAF and Mortality", norepinephrine was better than dopamine for vasopressors, ventilation and RRT; norepinephrine + dobutamine was better than epinephrine for ventilation. Using the novel composite "DAF vasopressors, ventilation and RRT", norepinephrine + dobutamine was better than epinephrine (p = 0.033), norepinephrine better than dopamine (p = 0.03), and vasopressin better than norepinephrine in less severe shock (p = 0.03). CONCLUSIONS: Differences between treatment groups in organ dysfunction in RCTs in septic shock occur despite lack of mortality differences depending on calculation method. If standardized and validated further, DAF could become the primary endpoint of RCTs in septic shock.
PURPOSE: RCTs in septic shock negative for mortality may show organ dysfunction benefits. We hypothesized that RCTs in septic shock show significant differences between treatment groups in organ support despite no mortality differences. METHODS: RCTs of epinephrine vs. norepinephrine plus dobutamine, norepinephrine vs. dopamine and vasopressin vs. norepinephrine reported days alive and free ("DAF") of vasopressors, ventilation and RRT, by subtracting days with support from the lesser of 28 or days to death. We also assigned zero DAF to non-survivors ("DAF and Mortality") and calculated the composite "DAF vasopressors, ventilation and RRT". RESULTS: Using "DAF", norepinephrine was better than dopamine for vasopressors. In contrast, using "DAF and Mortality", norepinephrine was better than dopamine for vasopressors, ventilation and RRT; norepinephrine + dobutamine was better than epinephrine for ventilation. Using the novel composite "DAF vasopressors, ventilation and RRT", norepinephrine + dobutamine was better than epinephrine (p = 0.033), norepinephrine better than dopamine (p = 0.03), and vasopressin better than norepinephrine in less severe shock (p = 0.03). CONCLUSIONS: Differences between treatment groups in organ dysfunction in RCTs in septic shock occur despite lack of mortality differences depending on calculation method. If standardized and validated further, DAF could become the primary endpoint of RCTs in septic shock.
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