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2014, New England Journal of Medicine
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10 pages
1 file
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.
Background: Perioperative myocardial ischemia occurs in 20 -40% of patients at risk for cardiac morbidity and is associated with a ninefold increase in risk of cardiac morbidity.
2002
Background : To access the clinical effect of clonidine on reduction of myocardial ischemia events in patients with history of coronary artery disease undergoing noncardiac surgeries. Methods : Sixty ASA class III patients with coronary artery disease were allotted at random to two groups in a prospective, double-blind study to receive either clonidine (3 g/kg) or placebo (control group) 90 minutes before arrival at the operating room. Continuous EKG monitoring (Holter monitor) was performed to analyze the ST segment in lead II, V 2 and V 5 during the preoperative (since late hours the night before operation), intraoperative and early postoperative periods (total monitoring time = 24 hours). The episode of myocardial ischemia defined as the magnitude of ST segment depression of at least 1 mm, occurring 60 ms after the J point and persisting for three minutes or more was recorded. Perioperative hemodynamic data were analyzed with two-way ANOVA with repeated measures. Student's t-test for unpaired data was used for analysis of demographics. Chi-square test was used for ST segment changes. Results are expressed as mean ± SD and P < 0.05 was considered to be statistically significant. Results : In the control group, 9 patients (30%) were noted to have episodes of ischemia preoperatively, 7 patients (23.3%) intraoperatively, and 12 patients (40%) postoperatively. The occurrence of myocardial ischemia peaked in the early postoperative period (P < 0.05). On the contrary, in the clonidine group, 10 patients (33.3%) saw ischemic episodes preoperatively, 3 patients (10%) intraoperatively and 5 patients (16.7%) postoperatively. The incidence of myocardial ischemia in clonidine group was significantly lower than that in placebo group in intraoperative and postoperative periods. The mean arterial pressure was significantly lower in some clonidine-treated patients during perioperative periods (P < 0.05). A number of patients in clonidine group suffered from drowsiness (66.7%) after operation (P < 0.05), but they could be easily aroused. In regard to dryness of mouth, nausea and vomiting clonidine and control groups did not differ much (P > 0.05). Demerol consumption was significantly lower in clonidine group (43.7 ± 4.6 mg) than in control group (76.3 ± 3.7 mg, P < 0.05). Conclusions : We conclude that premedication with oral clonidine can significantly reduce the incidence of perioperative myocardial ischemia in patients with CAD undergoing noncardiac surgeries. The incidence of myocardial ischemia in these patients is rather high during perioperative period, which deserves our exceptional caution.
… and intensive care, 1999
1. Anaesth Intensive Care. 1999 Apr;27(2):137-47. Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial ischaemia and recovery. Myles PS, Hunt JO, Holdgaard HO, McRae R, Buckland MR, Moloney ...
Anesthesiology, 2020
Background The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. Methods The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. Results Neither aspirin nor clonidine had a significant effect on the pri...
Anesthesiology, 2002
Background There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard. Methods Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as od...
Anesthesia and Analgesia, 1994
We studied 61 patients undergoing elective major noncardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received prernedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ubstantial morbidity, mortality, and costs are associated with coronary artery disease (CAD) in S elderly surgical patients, particularly in those who have vascular surgery (1 ). Electrocardiogram (ECG) monitoring has been used to document that patients with CAD are more likely to manifest myocardial ischemia after surgery rather than before surgery (2). Clonidine is an a,-adrenergic agonist with the potential to improve outcome in high-risk patients undergoing noncardiac surgery (3,4).
Journal of Clinical Anesthesia, 1995
Study Objective': Determine the hemodynamic consequences of intraoperative clonidine during major abdominal surgery. Design: Prospective open trial. Setting: Teaching hospital. Patients: 402 consecutive patients scheduled for major abdominal surgery. Interventions: 350 consecutive patients received intravenous (IV) clonidine (loading dose of 4 p.glkg in 20 minutes at anesthesia induction, followed by a continuous infmion of 2 p.glkglh until the end of surgery). Fifty-two additional patients served as controls. Anesthetic technique consisted of balanced anesthesia (isoflurane, fentanyl, atracurium). ECG, invasive arterial blood pressure (BP), expiratory PCO, and pulse oximetry were continuously recorded. Hemodynamic events {HEs) were defined as moderate for a 20% reduction of the baseline systolic blood pressure (SBP) or a heart rate (HR) decreasing between 50 beats per minute (bpm) and 40 bpm. A 30% reduction of the baseline SBP or a HR below 40 bpm was considered an important HE. The rate and duration of these events were recorded from induction to recovery. HEs requiring a specific treatment were noted. Central venous pressure, volume of fluid infused, and urinary output were also recorded. Measurements and Main Results: 21% of control patients and 31% of clonidine patients had no adverse HEs. A moderate reduction of the baseline BP was the most common episode in both groups. The incidence of the HEs (moderate and important) was similar in both groups but the duration HEs was signaficantly longer in the clonidine patients (p < 0.05). 4OYo of the control patients and 13% of the clonidine patients required specific management for their HEs (p < 0.05), the most common of which was hypotension without bradycardia. Neither coexisting pathology nor preoperative medications influenced the incidence of HEs. Conclusion: IV clonidine can be used routinely during anesthesia for major abdominal surgery.
Vascular and Endovascular Surgery, 2011
We investigated the role of low-dose clonidine intravenous (IV) premedication in arterial pressure variation during and after carotid endarterectomy (CEA). A total of 84 patients, American Society of Anesthesiologists (ASA) II-III, scheduled for elective CEA under general anesthesia participated in this study. The patients were divided into 2 groups: group P (n ¼ 42) and group C (n ¼ 42) and received N/S 0.9% (placebo) or clonidine 1 mg/kg IV, respectively, 15 minutes before induction of anesthesia. Recovery times, number of patients needed to be treated for circulatory events (hypertension, hypotension, and bradycardia), number of circulatory events per patient, and consumption of vasoactive drugs (nitroglycerine, phenylphrine, and atropine) intraoperatively and the first 6 hours postoperatively were recorded. Significantly less hypertensive episodes were observed intraoperatively, but more hypotensive episodes were observed postoperatively in patients receiving clonidine. Intravenous premedication with lowdose clonidine (1 mg/kg) seems to be effective in preventing hypertensive episodes during CEA under general anesthesia but seems to increase the incidence of hypotension postoperatively.
Brazilian Journal of Anesthesiology (English Edition), 2014
Objective: Evaluate the ability of clonidine to reduce pulmonary arterial pressure in patients with pulmonary hypertension undergoing heart surgery, either by reducing the pressure values from the direct measurement of pulmonary arterial pressure or by reducing or eliminating the need for intraoperative dobutamine and nitroprusside. Method: Randomized, double-blind, placebo-controlled, comparative study conducted in 30 patients with pulmonary arterial hypertension type 2 undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of dobutamine and sodium nitroprusside were assessed four times: before intravenous administration of clonidine (2 g/kg) or placebo (T0), 30 min after tested treatment and before cardiopulmonary bypass (T1), immediately after CPB (T2), 10 min after protamine injection (T3). Results: There were no significant differences regarding mean pulmonary arterial pressure at any time of evaluation. There was no significant difference between groups regarding other variables, such as mean systemic arterial pressure, heart rate, total dose of dobutamine, total dose of sodium nitroprusside, and need for fentanyl. Conclusion: Data analysis from patients included in this study allows us to conclude that intravenous clonidine (2 g/kg) was not able to reduce the mean pulmonary arterial pressure in patients with pulmonary hypertension in group 2 (pulmonary venous hypertension), undergoing heart surgery, or reduce or eliminate the need for intraoperative administration of dobutamine and sodium nitroprusside.
Anesthesia and Analgesia, 1993
Clonidine premedication in a dose of 5 micrograms/kg may be particularly well suited for elderly patients. To pursue this approach, sedation, intraocular pressure (IOP), and the hemodynamic profile of two doses of oral clonidine premedication were compared in 60 elderly patients, aged 65-82 yr, who underwent elective ophthalmic surgery under local anesthesia. Group 1 (n = 20) received placebo, Group 2 (n = 20) 150 micrograms of clonidine (2-2.5 micrograms/kg), and Group 3 (n = 20) 300 micrograms of clonidine (4-4.5 micrograms/kg) in a randomized, double-blind fashion. Decreases in mean arterial blood pressure were more pronounced and occurred earlier after 300 micrograms of clonidine (31.4 +/- 12.1%, P < 0.001) as compared to 150 micrograms of clonidine (18.1 +/- 10.9%, P < 0.001). Throughout the study, six patients (30%) in Group 3 (300 micrograms clonidine-treated group), but no patient in Groups 1 or 2, were treated at least once for hypotension (P < 0.05). Heart rate decreased significantly 18.5 +/- 8.1% (P < 0.001) only after 300 micrograms of clonidine. Clonidine 150 micrograms and 300 micrograms decreased IOP 32.1 +/- 14.3% (P < 0.001) and 47.8 +/- 17.2% (P < 0.001), respectively. After 150 micrograms of clonidine patients were significantly more sedated as compared to those given placebo (P < 0.01) but significantly less sedated than after 300 micrograms of clonidine (P < 0.01), where sedation persisted more than 6 h postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
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