Angiotensin II for the Treatment of Vasodilatory Shock

被引：596

作者：

Khanna, Ashish ^{[1
,2
]}

English, Shane W. ^{[3
,4
]}

Wang, Xueyuan S. ^{[5
]}

Ham, Kealy ^{[6
]}

Tumlin, James ^{[7
]}

Szerlip, Harold ^{[8
]}

Busse, Laurence W. ^{[9
]}

Altaweel, Laith ^{[10
]}

Albertson, Timothy E. ^{[11
]}

Mackey, Caleb ^{[14
]}

McCurdy, Michael T. ^{[15
]}

Boldt, David W. ^{[12
]}

Chock, Stefan ^{[16
]}

Young, Paul J. ^{[17
,18
]}

Krell, Kenneth ^{[19
]}

Wunderink, Richard G. ^{[20
]}

Ostermann, Marlies ^{[21
]}

Murugan, Raghavan ^{[22
]}

Gong, Michelle N. ^{[23
,24
]}

Panwar, Rakshit ^{[25
,26
]}

Hastbacka, Johanna ^{[31
,32
]}

Favory, Raphael ^{[33
,34
]}

Venkatesh, Balasubramanian ^{[27
,28
]}

Thompson, B. Taylor ^{[35
]}

Bellomo, Rinaldo ^{[29
]}

Jensen, Jeffrey ^{[13
]}

Kroll, Stew ^{[13
]}

Chawla, Lakhmir S. ^{[13
]}

Tidmarsh, George F. ^{[13
]}

Deane, Adam M. ^{[30
]}

机构：

[1] Cleveland Clin, Ctr Crit Care, Inst Anesthesiol, Cleveland, OH 44106 USA

[2] Cleveland Clin, Dept Outcomes Res, Cleveland, OH 44106 USA

[3] Univ Ottawa, Dept Med Crit Care, Ottawa, ON, Canada

[4] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada

[5] Duke Univ, Med Ctr, Dept Anesthesiol, Div Crit Care Med, Durham, NC 27710 USA

[6] Reg Hosp, St Paul, MN USA

[7] Univ Tennessee, Coll Med, Chattanooga, TN USA

[8] Baylor Univ, Med Ctr, Div Nephrol, Dallas, TX USA

[9] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA

[10] Inova Med Ctr, Falls Church, VA USA

[11] Univ Calif Davis, Sch Med, Dept Internal Med, Sacramento, CA 95817 USA

[12] Univ Calif Los Angeles, Dept Anesthesiol, Div Crit Care, Los Angeles, CA 90024 USA

[13] La Jolla Pharmaceut Co, San Diego, CA USA

[14] Riverside Methodist Hosp, Dept Pulm & Crit Care Med, Columbus, OH 43214 USA

[15] Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA

[16] Sunrise Hosp, Dept Surg, Las Vegas, NV USA

[17] Wellington Hosp, Intens Care Unit, Wellington, New Zealand

[18] Med Res Inst New Zealand, Wellington, New Zealand

[19] Eastern Idaho Reg Med Ctr, Dept Med, Div Crit Care, Idaho Falls, ID USA

[20] Northwestern Univ, Feinberg Sch Med, Dept Med Pulm & Crit Care, Chicago, IL 60611 USA

[21] Kings Coll London, Guys & St Thomas Hosp, Dept Crit Care & Nephrol, London, England

[22] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA

[23] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA

[24] Montefiore Med Ctr, Div Crit Care Med, 111 E 210th St, Bronx, NY 10467 USA

[25] John Hunter Hosp, New Lambton Hts, Australia

[26] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia

[27] Univ Queensland, Wesley Hosp, Dept Intens Care, St Lucia, Qld, Australia

[28] Univ Queensland, Princess Alexandra Hosp, St Lucia, Qld, Australia

[29] Univ Melbourne, Sch Med, Parkville, Vic, Australia

[30] Univ Melbourne, Royal Melbourne Hosp, Intens Care Unit, Melbourne, Vic, Australia

[31] Univ Helsinki, Dept Anesthesiol Intens Care & Pain Med, Div Intens Care Med, Helsinki, Finland

[32] Helsinki Univ Hosp, Helsinki, Finland

[33] Ctr Hosp Univ Lille, Crit Care Ctr, LIRIC Lille Inflammat Res Ctr, INSERM,UMR 995, Lille, France

[34] Univ Lille, Sch Med, Lille, France

[35] Harvard Med Sch, Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2017年 / 377卷 / 05期

关键词：

SEPTIC SHOCK; MANAGEMENT; SURVIVAL; SEPSIS;

D O I：

10.1056/NEJMoa1704154

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P< 0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)

引用

页码：419 / 430

页数：12

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