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N Engl J Med. 2014 Apr 17;370(16):1504-13. doi: 10.1056/NEJMoa1401106. Epub 2014 Mar 31.

Clonidine in patients undergoing noncardiac surgery.

Collaborators (338)

DeBeer J, Mizera R, Patel A, VanHelder T, Cook D, Dechert W, Jackson P, Tiboni M, Allard R, Dumerton-Shore D, McCourt J, Parlow JL, Jones PM, Lavi R, Lavi S, Moor R, Dresser GK, Garg AX, Gros ML, Schumann VC, Baur M, MacDonald C, Wirzba B, Regalado O, Srinathan SK, Ong DD, Todd A, Abbas S, Beattie WS, Chan VW, Chin KJ, Wijeysundera DN, Graham MM, Irwin M, Jacka M, El Beheiry H, McMullen SM, MacDonald P, Akhtar Z, Ayad S, Buttar M, Deroee A, Eshraghi Y, Fergany A, Finnigan P, Fu A, Grady M, Helper S, Hesler B, Honar H, Hutcherson M, Krebs V, Kurz A, Lee J, Malik M, Podolyak A, Salmasi V, Sessler DI, Arora H, Coombs RF, Kumar PA, Martinelli SM, Bergese SD, Melibary SB, Uribe AA, Jordan M, Miller SA, Cata JP, Nemergut EC, Candiotti KA, Memtsoudis SG, McKay RE, Montes FR, Parra GA, Rojas MF, Plata R, Vásquez SM, Sarquis T, Haider Z, Jane NB, Lanjewar PP, Rahate PV, Mehra BR, Premendaran B, Abraham V, George P, Kumar P, Gaikwad SB, Mohan NV, Sidhu G, Alvarez J, Gonzalez R, Maestre M, Popova E, Urrutia G, de Nadal M, González-Suárez S, González-Tallada A, Plou P, Mena E, Riveira C, del Valle S, Tena B, Lang SA, Ludbrook GL, Painter TW, Terblanche NC, Osborne C, Mahood JR, Leslie K, Myles PS, Sivalingam P, Riedel B, Elhalawani I, Biccard BM, Drummond L, Mugabi A, Naidoo P, Myburgh AL, Porrill OS, Diedericks BJ, Turton EW, Bøgeskov M, Dahl RM, Madsen MV, Søndergaard ES, Bauer NE, Martinsen KR, Chan MT, Choi GY, Gin T, Ng SS, Bidgoli SJ, Van der Linden PJ, De Kock M, Forget P, Fleischmann E, Kabon B, Luf F, Radonic M, Amir M, Ishtiaq O, Safdar J, Acuna-Villaorduna A, Barrionuevo P, Castaneda-Guarderas A, Caballero JA, Lau VE, Aphang-Lam MR, Lembo R, Pasin L, Gossetti B, Jara X, Leon P, Torres D, Ong G, Wang CY, Lee HS, Seeberger EE, Seeberger MD, Alfonsi P, Coriat P, Piriou V, Vizcaychipi MP, Rech RL, Bergo RR, Walker S, Devereaux PJ, Sessler DI, Kurz A, Mrkobrada M, Lurati Buse G, Botto F, Rodseth R, Robinson A, Guyatt G, LeManach Y, Pogue J, Pettit S, Chrolavicius S, Yusuf S, Botto F, Díaz R, Leslie K, Fleischmann E, Forget P, Berwanger O, Devereaux PJ, Mrkobrada M, Torres D, Villar JC, Cortés OL, Meyhoff CS, Wetterslev J, Alfonsi P, Hoeft A, Wittmann M, Chan M, Sigamani A, Xavier D, Landoni G, Wang CY, Ishtiaq O, Malaga G, Biccard BM, Alonso-Coello P, Conen D, Balaji P, Kurz A, Robinson A, Sovereign T, Blake L, Sephton J, Serra A, Agrippa C, Lawrence M, Gao P, Pettit S, Chrolavicius S, Leslie K, Alonso-Coello P, Biccard B, Chan M, Meyhoff CS, Villar JC, Xavier D, Wang CY, Landoni G, Berwanger O, Jacka M, Malaga G, Chow C, Gluud C, Baigent C, Karthikeyan G, Devereaux PJ, Alfonsi P, Alonso-Coello P, Auerbach A, Baigent C, Balaji P, Beattie S, Berwanger O, Biccard BM, Botto F, Buckley N, Chan M, Chow C, Chrolavicius S, Conen D, Cook D, Douketis J, Eikelboom J, Forget P, Garg AX, Gerstein H, Ghali W, Graham M, Guyatt G, Hart R, Hill M, Hoeft A, Jacka M, Karthikeyan G, Kearon C, Kurz A, Lamy A, Landoni G, LeManach Y, Leslie K, Lurati Buse G, Malaga G, McAlister F, McAuley D, Meyhoff CS, Miller S, Mrkobrada M, O'Donnell M, Pais P, Parlow J, Pogue J, Robinson A, Rodseth R, Schricker T, Sessler D, Simunovic M, Srinathan S, Teoh K, Torres D, Urrutia G, Villar JC, Walsh M, Wang CY, Wetterslev J, Whitlock R, Wijeysundera D, Xavier D, Yang H, Yusuf S, Guyatt G, Botto F, Alonso-Coello P, Alshalash S, Alvarez J, Bessissow A, Douketis J, Duceppe E, Fleischmann E, Hart R, Hill M, Khalid Z, Khan J, Kurz A, Lauw M, Le Manach Y, Lurati Buse G, Martinsen K, Meyhoff CS, Mrkobrada M, Neary J, Oczkowski W, O'Donnell M, Paniagua P, Papina M, Pasin L, Popova E, Rodseth R, Seeberger M, Tandon V, Thomas S, Tiboni M, Torres D, Wetterslev J, Friedman L, Cheng D, Johnstone D, Lowenstein E, Roberts R.

Author information

1
The authors' affiliations are listed in the Appendix.

Abstract

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.).

PMID:
24679061
DOI:
10.1056/NEJMoa1401106
[Indexed for MEDLINE]
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