Russell James A, Lee Terry, Singer Joel, Boyd John H, Walley Keith R
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;45(6):940-948. doi: 10.1097/CCM.0000000000002323.
The 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.
Retrospective analysis of randomized controlled trial.
Multicenter ICUs.
We 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.
Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine.
Concealed vasopressin (0.03 U/min.) or norepinephrine infusions.
The 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.
The 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.
脓毒症休克3.0定义可能会改变脓毒症休克随机对照试验中的治疗比较。我们的第一个假设是，血管加压素与去甲肾上腺素的比较以及符合脓毒症休克3.0定义（乳酸>2 mmol/L）的患者的28天死亡率与血管加压素与去甲肾上腺素的比较以及血管加压素与脓毒症休克试验中的死亡率不同。我们的第二个假设是，在血管加压素与脓毒症休克试验中，乳酸小于或等于2 mmol/L与大于2 mmol/L的患者血浆细胞因子水平存在差异。
对随机对照试验的回顾性分析。
多中心重症监护病房。
我们比较了血管加压素与去甲肾上腺素组在血管加压素与脓毒症休克试验中乳酸亚组的28天和90天死亡率。我们测量了39种细胞因子，以比较乳酸小于或等于2 mmol/L与大于2 mmol/L的患者。
乳酸大于2 mmol/L或小于或等于2 mmol/L的脓毒症休克患者，随机分为血管加压素组或去甲肾上腺素组。
采用盲法输注血管加压素（0.03 U/分钟）或去甲肾上腺素。
脓毒症休克3.0定义会使样本量减少约一半。28天和90天死亡率比最初的血管加压素与脓毒症休克试验死亡率高10%-12%。在乳酸小于或等于2 mmol/L的患者中，血管加压素组的死亡率显著低于去甲肾上腺素组（p = 0.028），但在乳酸大于2 mmol/L的患者中，治疗组之间没有差异。乳酸大于2 mmol/L的患者几乎所有细胞因子水平均显著高于乳酸小于或等于2 mmol/L的患者。
脓毒症休克3.0定义使样本量减少一半，并使28天死亡率增加约10%。如果乳酸小于或等于2 mmol/L，血管加压素与去甲肾上腺素相比可降低死亡率。乳酸大于2 mmol/L的患者血浆细胞因子水平高于乳酸小于或等于2 mmol/L的患者，对感染的细胞因子反应更强烈。脓毒症休克3.0定义及我们的研究结果对脓毒症休克的试验设计具有重要意义。
