Clonidine in Patients Undergoing Noncardiac Surgery

被引：239

作者：

Devereaux, P. J. ^{[1
,2
,3
]}

Sessler, D. I. ^{[13
]}

Leslie, K. ^{[14
]}

Kurz, A. ^{[13
]}

Mrkobrada, M. ^{[1
,7
]}

Alonso-Coello, P. ^{[15
]}

Villar, J. C. ^{[17
,18
]}

Sigamani, A. ^{[19
]}

Biccard, B. M. ^{[20
]}

Meyhoff, C. S. ^{[21
]}

Parlow, J. L. ^{[8
,9
]}

Guyatt, G. ^{[2
,3
]}

Robinson, A. ^{[1
]}

Garg, A. X. ^{[10
]}

Rodseth, R. N. ^{[20
]}

Botto, F. ^{[1
,22
]}

Buse, G. Lurati ^{[1
,23
]}

Xavier, D. ^{[19
]}

Chan, M. T. V. ^{[24
]}

Tiboni, M. ^{[3
]}

Cook, D. ^{[2
,3
]}

Kumar, P. A. ^{[25
]}

Forget, P. ^{[26
]}

Malaga, G. ^{[27
]}

Fleischmann, E. ^{[28
]}

Amir, M. ^{[29
]}

Eikelboom, J. ^{[1
,2
,3
]}

Mizera, R. ^{[3
]}

Torres, D. ^{[30
]}

Wang, C. Y. ^{[31
]}

VanHelder, T. ^{[4
]}

Paniagua, P. ^{[16
]}

Berwanger, O. ^{[32
]}

Srinathan, S. ^{[11
]}

Graham, M. ^{[12
]}

Pasin, L. ^{[33
]}

Le Manach, Y. ^{[1
,2
,4
]}

Gao, P. ^{[1
]}

Pogue, J. ^{[1
,2
]}

Whitlock, R. ^{[1
,5
,6
]}

Lamy, A. ^{[1
,5
]}

Kearon, C. ^{[2
,3
]}

Chow, C. ^{[34
,35
]}

Pettit, S. ^{[1
]}

Chrolavicius, S. ^{[1
]}

Yusuf, S. ^{[1
,2
,3
]}

机构：

[1] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[2] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada

[3] McMaster Univ, Dept Med, Hamilton, ON, Canada

[4] McMaster Univ, Dept Anesthesia, Hamilton, ON, Canada

[5] McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada

[6] McMaster Univ, Dept Crit Care, Hamilton, ON L8S 4L8, Canada

[7] London Hlth Sci Ctr, Dept Med, London, ON, Canada

[8] Kingston Gen Hosp, Dept Anesthesiol & Perioperat Med, Kingston, ON K7L 2V7, Canada

[9] Queens Univ, Kingston, ON, Canada

[10] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada

[11] Univ Manitoba, Dept Surg, Winnipeg, MB R3T 2N2, Canada

[12] Univ Alberta, Dept Med, Edmonton, AB, Canada

[13] Cleveland Clin, Dept Outcomes Res, Inst Anesthesiol, Cleveland, OH USA

[14] Royal Melbourne Hosp, Dept Anaesthesia & Pain Management, Melbourne, Vic, Australia

[15] Biomed Res Inst IIB St Pau, Iberoamer Cochrane Ctr, Barcelona, Spain

[16] Biomed Res Inst IIB St Pau, Dept Anesthesiol, Barcelona, Spain

[17] Univ Autonoma Bucaramanga, Bogota, Colombia

[18] Fdn Cardioinfantil, Bogota, Colombia

[19] St Johns Natl Acad Hlth Sci, Dept Pharmacol, Div Clin Res & Training, Bangalore, Karnataka, India

[20] Univ KwaZulu Natal, Dept Anaesthet, Perioperat Res Grp, Nelson R Mandela Sch Med, Durban, South Africa

[21] Univ Copenhagen, Herlev Hosp, Dept Anesthesiol, DK-2730 Herlev, Denmark

[22] Inst Cardiovasc Buenos Aires ICBA, Estudios Clin Latino Amer ECLA, Buenos Aires, DF, Argentina

[23] Univ Basel Hosp, Dept Anesthesia, CH-4031 Basel, Switzerland

[24] Chinese Univ Hong Kong, Dept Anaesthesia & Intens Care, Hong Kong, Hong Kong, Peoples R China

[25] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA

[26] Clin Univ St Luc, Brussels, Belgium

[27] Univ Peruana Cayetano Heredia, Lima, Peru

[28] Med Univ Vienna, Dept Anesthesia & Intens Care, Vienna, Austria

[29] Shifa Int Hosp, Dept Surg, Islamabad, Pakistan

[30] Clin Santa Maria, Dept Anesthesiol, Santiago, Chile

[31] Univ Malaya, Dept Anesthesiol, Kuala Lumpur, Malaysia

[32] Hosp Coracao, Res Inst HCor, Sao Paulo, Brazil

[33] Ist Sci San Raffaele, I-20132 Milan, Italy

[34] George Inst Global Hlth, Sydney, NSW, Australia

[35] Univ Sydney, Sydney, NSW 2006, Australia

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2014年 / 370卷 / 16期

基金：

加拿大健康研究院; 英国医学研究理事会;

关键词：

PERIOPERATIVE MYOCARDIAL-INFARCTION; TRANSDERMAL CLONIDINE; VASCULAR-SURGERY; CARDIAC RISK; EFFICACY; STRESS; METAANALYSIS; RESPONSES; ISCHEMIA; TRIALS;

D O I：

10.1056/NEJMoa1401106

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02). Conclusions: Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.)

引用

页码：1504 / 1513

页数：10

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