Clonidine in Patients Undergoing Noncardiac Surgery
Por:
Devereaux, PJ, Sessler, DI, Leslie, K, Kurz, A, Mrkobrada, M, Alonso-Coello, P, Villar, JC, Sigamani, A, Biccard, BM, Meyhoff, CS, Parlow, JL, Guyatt, G, Robinson, A, Garg, AX, Rodseth, RN, Botto, F, Buse, GL, Xavier, D, Chan, MTV, Tiboni, M, Cook, D, Kumar, PA, Forget, P, Malaga, G, Fleischmann, E, Amir, M, Eikelboom, J, Mizera, R, Torres, D, Wang, CY, VanHelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S
Publicada:
17 abr 2014
Resumen:
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.)
Filiaciones:
Devereaux, PJ:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
Sessler, DI:
Cleveland Clin, Dept Outcomes Res, Inst Anesthesiol, Cleveland, OH USA
Leslie, K:
Royal Melbourne Hosp, Dept Anaesthesia & Pain Management, Melbourne, Vic, Australia
Kurz, A:
Cleveland Clin, Dept Outcomes Res, Inst Anesthesiol, Cleveland, OH USA
Mrkobrada, M:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
London Hlth Sci Ctr, Dept Med, London, ON, Canada
Alonso-Coello, P:
Biomed Res Inst IIB St Pau, Iberoamer Cochrane Ctr, Barcelona, Spain
Villar, JC:
Univ Autonoma Bucaramanga, Bogota, Colombia
Fdn Cardioinfantil, Bogota, Colombia
Sigamani, A:
St Johns Natl Acad Hlth Sci, Dept Pharmacol, Div Clin Res & Training, Bangalore, Karnataka, India
Biccard, BM:
Univ KwaZulu Natal, Dept Anaesthet, Perioperat Res Grp, Nelson R Mandela Sch Med, Durban, South Africa
Meyhoff, CS:
Univ Copenhagen, Herlev Hosp, Dept Anesthesiol, DK-2730 Herlev, Denmark
Parlow, JL:
Kingston Gen Hosp, Dept Anesthesiol & Perioperat Med, Kingston, ON K7L 2V7, Canada
Queens Univ, Kingston, ON, Canada
Guyatt, G:
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
Robinson, A:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Garg, AX:
Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada
Rodseth, RN:
Univ KwaZulu Natal, Dept Anaesthet, Perioperat Res Grp, Nelson R Mandela Sch Med, Durban, South Africa
Botto, F:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Inst Cardiovasc Buenos Aires ICBA, Estudios Clin Latino Amer ECLA, Buenos Aires, DF, Argentina
Buse, GL:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Univ Basel Hosp, Dept Anesthesia, CH-4031 Basel, Switzerland
Xavier, D:
St Johns Natl Acad Hlth Sci, Dept Pharmacol, Div Clin Res & Training, Bangalore, Karnataka, India
Chan, MTV:
Chinese Univ Hong Kong, Dept Anaesthesia & Intens Care, Hong Kong, Hong Kong, Peoples R China
Tiboni, M:
McMaster Univ, Dept Med, Hamilton, ON, Canada
Cook, D:
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
Kumar, PA:
Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC USA
Forget, P:
Clin Univ St Luc, Brussels, Belgium
Malaga, G:
Univ Peruana Cayetano Heredia, Lima, Peru
Fleischmann, E:
Med Univ Vienna, Dept Anesthesia & Intens Care, Vienna, Austria
Amir, M:
Shifa Int Hosp, Dept Surg, Islamabad, Pakistan
Eikelboom, J:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
Mizera, R:
McMaster Univ, Dept Med, Hamilton, ON, Canada
Torres, D:
Clin Santa Maria, Dept Anesthesiol, Santiago, Chile
Wang, CY:
Univ Malaya, Dept Anesthesiol, Kuala Lumpur, Malaysia
VanHelder, T:
McMaster Univ, Dept Anesthesia, Hamilton, ON, Canada
Paniagua, P:
Biomed Res Inst IIB St Pau, Dept Anesthesiol, Barcelona, Spain
Berwanger, O:
Hosp Coracao, Res Inst HCor, Sao Paulo, Brazil
Srinathan, S:
Univ Manitoba, Dept Surg, Winnipeg, MB R3T 2N2, Canada
Graham, M:
Univ Alberta, Dept Med, Edmonton, AB, Canada
Pasin, L:
Ist Sci San Raffaele, I-20132 Milan, Italy
Le Manach, Y:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Anesthesia, Hamilton, ON, Canada
Gao, P:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Pogue, J:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
Whitlock, R:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada
McMaster Univ, Dept Crit Care, Hamilton, ON L8S 4L8, Canada
Lamy, A:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada
Kearon, C:
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
Chow, C:
George Inst Global Hlth, Sydney, NSW, Australia
Univ Sydney, Sydney, NSW 2006, Australia
Pettit, S:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Chrolavicius, S:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
Yusuf, S:
McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada
McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
McMaster Univ, Dept Med, Hamilton, ON, Canada
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