Critical care (London, England) · 2026
Early multimodal vasopressor strategy in septic shock: results of the TRICYCLE randomized controlled trial.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kalamar Žiga, Landoni Giovanni, Gorenjak Mario, Cestar Iva, Fluher Jure, Horvat Marko, Jerenec Katja, Kit Barbara, Marinšek Martin, Puklavec Nina, Svenšek Franc, Radonić Radovan, Šundalić Sara, Brajković Ana Vujaklija, Vujević Andro, Erjavc Nina, Petek Davor, Košir Alenka Strdin, Homšak Evgenija, Knehtl Maja Cvikl, Markota Andrej
Аннотация
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.
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.