An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock

被引：0

作者：

Daniel E. Leisman ^{[1
]}

Patrick M. Wieruszewski ^{[2
]}

Laurence W. Busse ^{[3
]}

Lakhmir S. Chawla ^{[4
]}

Kathryn A. Hibbert ^{[5
]}

Damian R. Handisides ^{[6
]}

Ashish K. Khanna ^{[7
]}

Marlies Ostermann ^{[1
]}

Michael T. McCurdy ^{[8
]}

Christopher D. Adams ^{[9
]}

Tony N. Hodges ^{[10
]}

Rinaldo Bellomo ^{[11
]}

机构：

[1] Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, 55 Fruit St., Bulfinch 148, Boston, MA

[2] Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, 02114, MA

[3] Department of Pharmacy, Mayo Clinic, Rochester, MN

[4] Department of Anesthesiology, Mayo Clinic, Rochester, MN

[5] Department of Medicine, Emory University, Atlanta, GA

[6] Emory Critical Care Center, Emory Healthcare, Atlanta, GA

[7] Department of Medicine, Veterans Affairs Medical Center, San Diego, CA

[8] Innoviva Specialty Therapeutics, Inc - an Affiliate of La Jolla Pharmaceutical Company, Waltham, MA

[9] Department of Anesthesiology, Section On Critical Care Medicine, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC

[10] Perioperative Outcomes and Informatics Collaborative (POIC), Winston-Salem, NC

[11] Outcomes Research Consortium, Cleveland, OH

[12] Department of Critical Care, King’s College London, Guy’s & St Thomas’ Hospital, London

[13] Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD

[14] Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD

[15] Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne

[16] Department of Critical Care, Melbourne Medical School, University of Melbourne, Austin Hospital, Melbourne

[17] Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital, Melbourne

[18] Department of Intensive Care Medicine, Austin Hospital, Melbourne

[19] The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE), Melbourne

[20] Intensive Care Unit, Royal Melbourne Hospital, Melbourne, VIC

来源：

Critical Care | / 29卷 / 1期

关键词：

Angiotensin II; Norepinephrine; Renin-angiotensin system; Septic; Shock;

D O I：

10.1186/s13054-025-05311-z

中图分类号：

学科分类号：

摘要：

Background: No standardized index exists to assess cardiovascular responsiveness to angiotensin-II. We hypothesized that a standardized index of initial blood pressure response to angiotensin-II treatment would be associated with clinical outcomes. Methods: Using data from the Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we developed an Angiotensin-II Initial MAP Response Index of Treatment Effect (AIMRITE) defined as (MAP at hr1 – MAP at baseline)/study drug dose. We assessed AIMRITE continuously and, based on observed distributions, we additionally categorized patients as “responsive” or “resistant”, with responsiveness defined by an AIMRITE ≥ 0.90 mmHg/ng/kg/min. The primary clinical outcome was 28-day mortality. Secondary outcomes included days alive and vasopressor- or ventilator- or renal replacement therapy-free at day-7. Biological outcomes included baseline renin, angiotensin-II, and renin/angiotensin-II ratio, and their change at hr3. Results: Of 158 placebo patients, as expected, 157 (99%) had AIMRITE < 0.90 mmHg/ng/kg/min (median AIMRITE 0.02; IQR − 0.03–0.10). In contrast, 163 patients assigned to angiotensin-II had a median AIMRITE of 1.43 mmHg/ng/kg/min (IQR 0.35–2.83). Of these, 97 (60%) were responsive (median AIMRITE 2.55; IQR 1.66–4.12) and 66 (40%) were resistant (median AIMRITE 0.24; IQR 0.10–0.52). Each 1.0-unit increase in AIMRITE was associated with a 16% lower hazard of death (HR: 0.84 per-mmHg/ng/kg/min [95% CI 0.74–0.95], p = 0.0062). Responsive patients had half the mortality hazard than resistant patients (HR: 0.50 [95% CI 0.32–0.78], p = 0.0026) and placebo patients (HR 0.58 [95% CI 0.40–0.86], p = 0.0064). Resistant patients had a similar mortality hazard to placebo (HR 1.17 [95% CI 0.80–1.72], p = 0.41). Compared to resistant patients, responsive patients had lower baseline renin and renin/angiotensin-II ratio, but a greater decrease in both at hr3. When stratified by baseline renin level, mortality was highest in placebo patients with high renin (69%) and angiotensin-II resistant patients with low renin (61%). Conclusions: Among patients with catecholamine-refractory vasodilatory shock treated with angiotensin-II, the AIMRITE was associated with mortality at day-28. Responsive angiotensin-II patients had higher survival versus both angiotensin-II resistant patients and those treated with placebo plus standard vasopressors. This index may serve as a prognostic indicator and early identifier of patients most likely to benefit from angiotensin-II. © The Author(s) 2025.

引用

共 27 条

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