脓毒性休克中的早期多模式血管加压药策略：TRICYCLE随机对照试验的结果。
摘要
背景：鉴于脓毒性休克中驱动血管扩张的多因素机制，早期联合使用多种具有互补作用机制的血管加压药（血管紧张素II、血管加压素和去甲肾上腺素）具有强有力的生理学依据。这种方法可能更有效地对抗脓毒性休克特有的复杂病理生理过程。在此，我们测试了早期多模式血管加压药策略在脓毒性休克患者中的生理和临床效应。…
正文 待译
BACKGROUND: Given multifactorial mechanisms driving vasodilation in septic shock, there is a strong physiological rationale for early initiation of multiple vasopressors (angiotensin II, vasopressin and norepinephrine) with complementary mechanisms of action. Such an approach could more effectively counteract the complex pathophysiological processes characteristic of septic shock. Here we tested the physiological and clinical effects of an early multimodal vasopressor strategy in patients with septic shock. METHODS: We randomly assigned patients with septic shock receiving ≥ 0.15 µg/kg/min of norepinephrine base to either intervention (early multimodal vasopressor administration: angiotensin II, vasopressin, and norepinephrine) group or control (classic stepwise vasopressor administration: norepinephrine dose increase followed by vasopressin and then by angiotensin II or other vasopressors) group. The primary outcome was change in plasma renin concentrations. This phase II trial was not powered to detect differences in mortality. RESULTS: A total of 79 patients were included (intervention group: n = 38, control group: n = 41). We observed a faster decline in plasma renin concentrations (2.61% per hour vs. 1.67% per hour; p = 0.015) and lactate concentrations (1.53% per hour vs. 1.01% per hour; p = 0.006) during the first 72 h in the intervention group compared to the control group. At 72 h, Sequential Organ Failure Assessment (SOFA) score was reduced by 3 points in the intervention group vs. 0 in the control group (p = 0.018). In the additional non-prespecified analyses, norepinephrine equivalent (NEE) dose decreased at a similar rate in the intervention and control groups over 72 h (- 5.41% per hour vs. -5.19% per hour; p = 0.47), whereas over the first 24 h, NEE dose decreased significantly faster in the intervention group (- 6.87% per hour vs. -3.03% per hour; p < 0.0004). The incidence of tachyarrhythmias was significantly lower in the intervention group (15.6% vs. 68.6%; p < 0.01). Intensive care unit mortality (26.3% vs. 41.5%; RR 0.635; 95% CI 0.33 to 1.21; p = 0.235) and 28-day mortality (36.8% vs. 46.3%; RR 0.795; 95% CI 0.47 to 1.35; p = 0.494) were similar. CONCLUSION: Early multimodal vasopressor therapy with Ang II, vasopressin and norepinephrine in patients with septic shock demonstrated promising physiological effects. These findings provide a rationale for a larger trial to assess whether early multimodal vasopressor therapy improves patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06155812. URL: https://clinicaltrials.gov/study/NCT06155812?term=NCT06155812&rank=1 . Trial registration date: 4 December 2023.
English
BACKGROUND: Given multifactorial mechanisms driving vasodilation in septic shock, there is a strong physiological rationale for early initiation of multiple vasopressors (angiotensin II, vasopressin and norepinephrine) with complementary mechanisms of action. Such an approach could more effectively counteract the complex pathophysiological processes characteristic of septic shock. Here we tested the physiological and clinical effects of an early multimodal vasopressor strategy in patients with septic shock.…