• James A Russell, Terry Lee, Joel Singer, John H Boyd, Keith R Walley, and Vasopressin and Septic Shock Trial (VASST) Group.
• 1Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.2Division of Critical Care Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.3Centre for Health Evaluation and Outcome Science (CHEOS), St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
• Crit. Care Med. 2017 Jun 1; 45 (6): 940-948.

ObjectivesThe Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L.DesignRetrospective analysis of randomized controlled trial.SettingMulticenter ICUs.MethodsWe compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L.PatientsPatients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine.InterventionsConcealed vasopressin (0.03 U/min.) or norepinephrine infusions.Measurements And Main ResultsThe Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L.ConclusionsThe Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic Shock 3.0 definition and our findings have important implications for trial design in septic shock.

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