Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery. Dexmedetomidine does not improve patient satisfaction when compared with propofol during mechanical ventilation. Oral clonidine reduces myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery. Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT). Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis. Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements. Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Clonidine premedication in patients with sleep apnea syndrome: a randomized, double-blind, placebo-controlled study. Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery? The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens. Effect of clonidine on myocardial ischaemia: a double-blind pilot trial. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study. Effects of clonidine on variation of arterial blood pressure and heart rate during carotid artery surgery. Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Clonidine improves perioperative myocardial ischemia, reduces anesthetic requirement, and alters hemodynamic parameters in patients undergoing coronary artery bypass surgery. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Perioperative sympatholysis. Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. McSPI--Europe Research Group. Clonidine premedication for coronary artery bypass grafting under high-dose alfentanil anesthesia: intraoperative and postoperative hemodynamic study. Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial ischaemia and recovery. The effect of clonidine premedication on hemodynamic responses to microlaryngoscopy and rigid bronchoscopy. A prospective, double-blind, randomized, placebo-controlled study of dexmedetomidine as an adjunct to epidural analgesia after thoracic surgery.
Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio.
                A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded.
                Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03).
                A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease. Dexmedetomidine (DEX) may provide a sedation level that enables sleep and communication, with less amnesia and pain medication requirements, during mechanical ventilation. Our study directly assessed patient-perceived satisfaction with coronary artery bypass graft surgery after administration of DEX or propofol for intensive care unit (ICU) sedation.
                Prospective, randomized clinical study with subsequent questionnaire administration.
                Tertiary care surgical ICU.
                A total of 89 adult, nonemergent, coronary artery bypass graft patients with an expected length of intubation of <24 hrs.
                Patients were randomized to either DEX or propofol; drug administration was performed via standardized anesthesia and nursing protocols.
                Patients reported perceptions of their ICU experience after mechanical ventilation with a modified numerical-scale Hewitt questionnaire, validated specifically for ICU patients. Patients were questioned regarding awareness, recall, generalized comfort, level of pain, ability to interact with healthcare providers and family, feelings of agitation and anxiety, perceived ease of extubation, ability to sleep or rest, and satisfaction with ICU experience.
                Groups were well matched at baseline, with a mean +/- sd age of 63.0 +/- 10.4 yrs and weight of 88.7 +/- 16.7 kg. No difference was observed for length of surgery, length of intubation, or ICU stay (p > .05). DEX patients perceived a shorter length of intubation (p = .044). A deeper sedation level was found in the propofol group (p = .021), with similar morphine and midazolam requirements (p = .317). Patient-rated level of overall awareness as a marker of amnesia did not differ between groups (p = .653). The ability to rest or sleep trended toward significance favoring propofol (p = .051). On evaluation of questionnaire ratings, DEX patients expressed more discomfort (p = .046), pain (p = .096), and sleeping difficulty (p = .036). Similar comfort levels were reported during extubation (p = .179).
                Despite theoretical advantages of DEX to improve overall patient satisfaction, the two agents provide similar responses to amnesia and pain control. According to our findings, DEX does not seem to have any advantage compared with propofol for short-term sedation after coronary artery bypass graft surgery. To access the clinical effect of clonidine on reduction of myocardial ischemia events in patients with history of coronary artery disease undergoing noncardiac surgeries.
                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 micrograms/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, V2 and V5 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.
                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).
                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. Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting.
                Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs.
                Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients).
                Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension. Clonidine was administered intravenously in an attempt to limit sympatico-adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by-pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4 micrograms kg-1 before surgery, 2 micrograms kg-1 after cardiopulmonary by-pass and 1 microgram kg-1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower (P less than 0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group (P less than 0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/3 of those in the control group (P less than 0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico-adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico-adrenal hyperactivity must be important. Mivazerol is a drug with alpha2-agonist properties that reduces post-ganglionic noradrenaline availability and spinal efferent sympathetic output.
                A double-blind randomized placebo-controlled trial was conducted in 61 European centers during a 2.5-yr period on 2,854 patients: 1,897 with coronary heart disease and 957 patients without overt coronary heart disease but classified as at high risk for it. The present analysis was restricted to those patients with previous known coronary heart disease of whom 48% had vascular surgery, 32% non-vascular thoracic or abdominal surgery, and 20% orthopedic surgery. Mivazerol or placebo were given intravenously from the induction of anesthesia for up to 72 h.
                In the 1,897 patients with established coronary heart disease, mivazerol did not reduce the primary endpoint--the combination of myocardial infarction or death--or all-cause deaths significantly. A preplanned subgroup analysis of 904 patients with known coronary heart disease undergoing vascular surgery showed that there were fewer primary endpoints in those receiving mivazerol (risk ratio [RR], 0.67; 95% CL, 0.45-0.98; P = 0.037) and fewer cardiac deaths (6 of 454 vs. 18 of 450: RR, 0.33; 95% confidence limits, 0.13-0.82; P = 0.017). The all-cause death rate was also decreased (RR, 0.41; 95% CL, 0.18-0.91; P = 0.024), although there was no significant reduction in myocardial infarction.
                The alpha2-adrenergic agonist, mivazerol, did not alter the rates of myocardial infarction or cardiac death in patients with known coronary heart disease undergoing noncardiac surgery. However, it may have protected patients undergoing vascular surgery from further coronary events, and a specific study of such patients is now indicated. Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease.
                Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively.
                Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results.
                Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate. We studied 61 patients undergoing elective major non-cardiac 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 premedication 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 ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia. Thirty patients (ASA physical status II-III) with a history of arterial hypertension, whose blood pressure (BP) control varied from normotension to moderate hypertension (diastolic BP less than 110 mmHg), scheduled for elective surgery under general anesthesia, were randomly assigned to two groups. Group 1 was premedicated 90-120 min prior to induction with diazepam 0.15 mg X kg-1 po; group 2, in addition, received clonidine 5 micrograms X kg-1 po. Anesthetic depth was assessed by on-line aperiodic analysis of the electroencephalogram. Following lidocaine 1 mg X kg-1 and fentanyl 2 micrograms X kg-1 (group 1 only), anesthesia was induced with thiopental 3-4 mg X kg-1 and vecuronium 0.1 mg X kg-1 was used to facilitate endotracheal intubation. Anesthesia was maintained with isoflurane in N2O/O2 and supplemented by fentanyl. In group 2, clonidine produced a rapid preoperative control of systolic and diastolic BP from 166 +/- 32/95 +/- 14 to 136 +/- 80 +/- 11 (P less than 0.01), was more effective in blunting the reflex tachycardia associated with laryngoscopy and endotracheal intubation than lidocaine-fentanyl pretreatment. It significantly reduced the intraoperative lability (coefficient of variation) of systolic (P less than 0.01) and diastolic BP and heart rate (HR) (P less than 0.05), and resulted in significantly slower HR during recovery (P less than 0.01). Anesthetic requirements for isoflurane were reduced 40% (P less than 0.01) in group 2; narcotic supplementation was also significantly reduced (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) The effects of clonidine, a centrally acting alpha 2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3-4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard premedication, or Group 2 (n = 12), who received clonidine 5 micrograms X kg-1 po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor). Fentanyl was administered in 250-micrograms increments to shift the EEG to the 0.5-3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1, 44 +/- 9 ml X beat-1 X m-2 compared with Group 2, 35 +/- 3.3 ml X beat-1 X m-2 (P less than 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 +/- 23 to 61 +/- 19 micrograms X kg-1 (P less than 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5-3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and alpha 2-adrenoceptor agonists on central sympathetic outflow. 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.
                In a prospective, double-blinded, clinical trial, we studied 190 patients with or at risk for coronary artery disease in two study groups with a 2:1 ratio (clonidine, n = 125 vs. placebo, n = 65) to test the hypothesis that prophylactic clonidine reduces the incidence of perioperative myocardial ischemia and postoperative death in patients undergoing noncardiac surgery. Clonidine (0.2 mg orally as well as a patch) or placebo (tablet and patch) was administered the night before surgery, and clonidine (0.2 mg orally) or placebo (tablet) was administered on the morning of surgery. The patch or placebo remained on the patient for 4 days and was then removed.
                The incidence of perioperative myocardial ischemia was significantly reduced with clonidine (intraoperative and postoperative, 18 of 125, 14% vs. placebo, 20 of 65, 31%; P = 0.01). Prophylactic clonidine administration had minimal hemodynamic effects. Clonidine reduced the incidence of postoperative mortality for up to 2 yr (clonidine, 19 of 125 [15%] vs. placebo, 19 of 65 [29%]; relative risk = 0.43 [confidence interval, 0.21-0.89]; P = 0.035).
                Perioperative administration of clonidine for 4 days to patients at risk for coronary artery disease significantly reduces the incidence of perioperative myocardial ischemia and postoperative death. Patients with sleep apnea often present with cardiac diseases and breathing difficulties, with a high risk of postoperative respiratory depression. We conducted a randomized, double-blind, prospective study in 30 adult patients with obstructive sleep apnea, undergoing elective ear-nose-throat surgery. The patients were randomly assigned to receive placebo or clonidine (2 microg/kg oral) the night before and the next morning 2 h before surgery. Spo2, heart rate, mean arterial blood pressure, snoring, and oronasal airflow were monitored for 36 h. A standard anesthesia was used consisting of propofol and remifentanil. Anesthetic drug consumption, postoperative analgesics, and pain score were recorded. In the clonidine group, mean arterial blood pressures were significantly lower during induction, operation, and emergence from anesthesia. Both propofol dose required for induction (190 +/- 32.2 mg) and anesthesia (6.3 +/- 1.3 mg . kg(-1).h(-1)) during surgery were significantly reduced in the clonidine group compared with the placebo group (induction 218 +/- 32.4, anesthesia 7.70 +/- 1.5; P < 0.05). Piritramide consumption (7.4 +/- 5.1 versus 14.2 +/- 8.5 mg; P < 0.05) and analgesia scores were significantly reduced in the clonidine group. Apnea and desaturation index were not different between the groups, whereas the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo than in the clonidine group (76.7% +/- 8.0% versus 82.4% +/- 5.8%; P < 0.05). We conclude that oral clonidine premedication stabilizes hemodynamic variables during induction, maintenance, and emergence from anesthesia and reduces the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation. To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery.
                Prospective randomised controlled trial.
                Clinical investigation in a cardiac anaesthesia department of a university hospital.
                88 consecutive patients undergoing coronary artery bypass surgery.
                After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass.
                The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days.
                Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml).
                In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury. Dexmedetomidine was evaluated for sedation of 401 post-surgical patients in this double-blind, randomized, placebo-controlled, multicenter trial. Dexmedetomidine or saline was started on arrival in the intensive care unit (ICU) (1.0 mcg/kg for 10 minutes), then titrated at 0.2 to 0.7 mcg/kg/h to effect. Patients could be given propofol if necessary. Morphine was administered for pain. Sixty percent of the dexmedetomidine patients required no other sedative to maintain an RSS > or = 3; 21% required < 50 mg propofol. In contrast, 76% of the control group received propofol; 59% required > or = 50 mg. Dexmedetomidine patients required significantly less morphine for pain relief (P <.001). Continuously given throughout the ICU stay, dexmedetomidine had no effect on respiratory rate, oxygen saturation, duration of weaning, or times to extubation. Nurses judged the dexmedetomidine patients were easier to manage. Later, fewer dexmedetomidine patients remembered pain or discomfort. The majority of dexmedetomidine patients maintained blood pressures within normal range, without rebound. Hypertension, atelectasis, and rigors occurred more frequently in the control group, while hypotension and bradycardia occurred more frequently in the dexmedetomidine group. Preoperative cardiovascular conditions were not risk factors for dexmedetomidine patients. The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures. Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation. To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU).
                Randomized, open label.
                Twenty-five centers in the United States and Canada.
                Two hundred ninety-five adults undergoing CABG surgery.
                At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice.
                Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001).
                Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics. nan We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia.
                The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients. To compare dexmedetomidine vs. placebo with respect to the amount of additional propofol and morphine used for bispectral index-guided sedation and analgesia in mechanically ventilated, intensive care patients after surgery.
                Prospective, randomized, double blind, placebo-controlled, phase II clinical trial.
                General surgical and cardiac surgical intensive care units.
                Thirty patients scheduled for major surgery requiring mechanical ventilation for a minimum of 6 hrs were included in the study.
                Patients were assigned randomly to receive either dexmedetomidine (loading infusion, 6.0 microg x kg(-1) x hr(-1) for 10 mins; maintenance infusion, 0.1-0.7 microg x kg(-1) x hr(-1)) or placebo after intensive care unit admission.
                Sedation was guided by using the electroencephalographic parameter bispectral index, a new noninvasive method to estimate the level of sedation. We aimed at maintaining bispectral index ranges between 60 and 70 during mechanical ventilation before starting weaning, 65 and 95 during weaning, and 85 to 95 postextubation. Additional sedative and analgesic medication was given (propofol and morphine) as clinically indicated and within the previously mentioned bispectral index ranges. Patients receiving dexmedetomidine required significantly less propofol during mechanical ventilation (0.87 +/- 0.21 vs. 1.52 +/- 0.30 mg x kg(-1) x hr(-1); p <.01) and weaning (0.17 +/- 0.06 vs. 0.62 +/- 0.21 mg x kg(-1) x hr(-1); p <.001) to maintain the target bispectral index range. During study drug administration, morphine requirements for dexmedetomidine-treated patients were reduced by 58% (p =.05). Hemodynamic stability during weaning and after extubation was better maintained in patients receiving dexmedetomidine.
                Dexmedetomidine reduced propofol requirements and improved hemodynamic stability during bispectral index-guided intensive care unit sedation. The effect of oral premedication with 300 micrograms of clonidine on systemic arterial pressure, heart rate, and plasma norepinephrine levels was assessed in a double-blinded, placebo-controlled study conducted in 29 patients subjected to carotid artery surgery (CAS). Anesthesia was induced with thiopental, 6 mg/kg, and alfentanil, 0.05 mg/kg, and maintained with alfentanil and 0.6% isoflurane in 50% N20/O2. The study was divided into five periods as follows: (1) anesthesia to start of surgery; (2) surgery to carotid artery clamping; (3) carotid artery clamping to unclamping; (4) carotid artery unclamping to the end of surgery; and (5) the first 4 postoperative hours in the recovery room. In the clonidine group (n = 14), plasma norepinephrine concentrations were significantly lower before induction of anesthesia and during the operative period. Heart rate and systemic arterial pressure were lower (P less than 0.01) in the clonidine group at 3 different time intervals (control, carotid clamping, carotid unclamping). However, during each of the previously defined periods, the variability of heart rate and systemic arterial pressure, assessed by the coefficient of variation, was not different between the two groups. The lability of these hemodynamic parameters, expressed as the percentage of values, which increased or decreased more than 20% of control values during the corresponding period, was also comparable between the two groups. The number of patients who experienced at least one episode of hypertension (systolic arterial pressure greater than 180 mm Hg), hypotension (systolic arterial pressure less than 100 mm Hg), or bradycardia less than 45 beats/min was not different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) The alpha2 agonist dexmedetomidine is a new sedative and analgesic agent which is licensed in the USA for post-operative intensive care sedation. We compared dexmedetomidine with propofol in patients requiring sedation in intensive care. Twenty adult patients expected to require a minimum of 8 h artificial ventilation after surgery were randomized to receive sedation with either dexmedetomidine or propofol infusions. Additional analgesia, if required, was provided by an alfentanil infusion. Depth of sedation was monitored using both the Ramsay sedation score (RSS) and the bispectral index (BIS). Cardiovascular, respiratory, biochemical and haematological data were obtained. Patients' perceptions of their intensive care stay were assessed using the Hewitt questionnaire. Sedation was equivalent in the two groups [median (interquartile range): RSS, propofol group 5 (4-5), dexmedetomidine group 5 (4-6) (P=0.68); BIS, propofol group 53 (41-64), dexmedetomidine group 46 (36-58); P=0.32], but the propofol group received three times more alfentanil compared with patients sedated with dexmedetomidine [2.5 (2.2-2.9) mg h(-1) versus 0.8 (0.65-1.2) mg h(-1) (P=0.004)]. No differences were found in arterial pressures between the groups, but heart rate was significantly lower in the dexmedetomidine group [mean (SD) 75 (6) vs 90 (4) beats min(-1)]. Extubation times were similar and rapid with the use of both sedative agents [median (range) 28 (20-50) and 29 (15-50) min (P=0.63) respectively for the propofol and dexmedetomidine groups]. No adverse events related to the sedative infusions occurred in either group. Despite ventilation and intubation, patients sedated with dexmedetomidine could be easily roused to cooperate with procedures (e.g. physiotherapy, radiology) without showing irritation. From the clinician's and patient's perspectives, dexmedetomidine is a safe and acceptable sedative agent for those requiring intensive care. The rate pressure product is reduced in patients receiving dexmedetomidine, which may protect against myocardial ischaemia. Dexmedetomidine reduces the requirement for opioid analgesia. The purpose of this study was to determine if clonidine reduces myocardial ischemia or alters anesthetic requirement and perioperative hemodynamic parameters during coronary artery bypass grafting (CABG) surgery. Forty-three patients were randomized in a prospective, double-blind fashion to receive either clonidine (5 micrograms/kg) or placebo. Anesthetic induction and maintenance was accomplished with intravenous sufentanil-midazolam (S-M) in a 1:20 ratio; up to 1.0% enflurane was added during surgery when repeated boluses of S-M failed to maintain the blood pressure within 20% of preinduction values. Continuous ST segment analysis of leads II and V5 was performed throughout surgery with maximal ST segment deflection from baseline recorded every 5 minutes. Catecholamine levels were measured intermittently throughout the perioperative period and myocardial lactate use or excretion was determined just prior to cardiopulmonary bypass (CPB) and at 1, 5, 10, 30, and 60 minutes after release of the aortic cross-clamp. Patients who received clonidine required significantly less sufentanil for their surgical procedure (11.82 +/- 0.66 micrograms/kg v 14.55 +/- 0.90 micrograms/kg, P < 0.05) and also needed less enflurane for blood pressure control, particularly during CPB (P < 0.05). Baseline hemodynamic parameters were similar for both groups prior to induction. In the period between anesthetic induction and the initiation of CPB, patients treated with clonidine had a significantly slower heart rate (HR) (P < 0.01), a lower cardiac output (CO) (P < 0.05), and transiently higher systemic vascular resistance (SVR) (P < 0.05) than placebo-treated patients. Immediately after CPB, patients receiving clonidine continued to have a significantly lower CO (P < 0.01) and a higher SVR (P < 0.01) than placebo-treated patients. Clonidine treatment significantly increased the percentage of patients who required pacing after CPB (P < 0.05). In the intensive care unit, clonidine-treated patients displayed a persistently increased requirement for pacing (P < 0.01), decreased systolic blood pressures, and reduced sodium nitroprusside requirements relative to patients treated with placebo. Epinephrine and norepinephrine levels were lower in clonidine-treated patients throughout the perioperative procedure with significant differences noted immediately following sternotomy and release of the aortic cross-clamp (P < 0.05). Critical ST segment depression was significantly less in clonidine-treated patients for the period from sternotomy until application of the aortic cross-clamp (P < 0.01). Following CPB, absolute deviation of ST segments from isoelectric baseline was significantly less in the clonidine-treated group (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. Implications: Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting. Mivazerol hydrochloride is a new alpha 2-adrenoceptor agonist. In vitro and animal studies have demonstrated both sympatholytic and antiischemic properties. To evaluate the safety and efficacy of mivazerol in patients during perioperative stress, this multicenter phase II clinical trial studied hemodynamic stability and myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery.
                Three hundred patients, from twenty-three European medical institutions, participated in this placebo-controlled, double-blind, randomized, parallel-group trial. Ninety-eight were given high-dose mivazerol (1.5 micrograms.kg-1.h-1); 99, low-dose mivazerol (0.75 microgram.kg-1.h-1); and 103, placebo, continuously intraoperatively and for 72 h postoperatively. Blood pressure and heart rate were monitored for 96 h. Myocardial ischemia was assessed by Holter electrocardiography for at least 8 h before induction of anesthesia until 96 h after surgery. Twelve-lead electrocardiograms and creatine kinase myocardial band isoenzyme levels were obtained before and serially after surgery. Adverse cardiac events were assessed for the intraoperative, early postoperative (0-24 h), and late postoperative (24-72 h) periods.
                The incidence of tachycardia was significantly lower with high-dose mivazerol (vs. placebo) during the intraoperative (30% vs. 51%; P = 0.002), early postoperative (29% vs. 50%; P = 0.002), and late postoperative periods (46% vs. 70%; P = 0.001). Also, the percentage of patients treated for tachycardia was significantly lower with the high dose (vs. placebo) during the early (10% vs. 20%; P = 0.043) and late (6% vs. 15%; P = 0.024) postoperative periods. The incidence of hypertension was significantly lower with both high and low doses (vs. placebo) during the intraoperative period (46% and 43%, respectively, vs. 63%; P = 0.010); treatment was similar at both high and low doses (33% and 34%, respectively, vs. 46%; P = 0.066). The incidence of bradycardia was significantly higher at both dose levels than with placebo during and after drug administration (intraoperatively-3%, 7%, and 9%; early postoperative-0%, 5%, and 6%; late postoperative-0%, 4%, and 6%; after drug-0%, 6%, and 6%; placebo, low-dose, high-dose, respectively), but the need for treatment did not differ for the groups. The incidence of, and treatment for, hypotension were similar for the three groups. Intraoperative myocardial ischemia was significantly lower with high-dose mivazerol than with placebo (20% vs. 34%, respectively, P = 0.026). When intraoperative data were subdivided into emergence vs. nonemergence periods (post boc analysis), the incidence of myocardial ischemia was significantly lower with high-dose mivazerol than with placebo during emergence (11% vs. 30%; P = 0.001). Regarding blood pressure, heart rate, and ischemia, no rebound response occurred in the 12 h after discontinuation of mivazerol. The high-dose, low-dose, and placebo groups did not differ in the incidence of adverse cardiac outcomes (3%, 2%, and 8%, respectively) or the diagnosis of myocardial infarction (2%, 1%, and 6%, respectively).
                Continuous, 72-h perioperative administration of mivazerol to high-risk patients appears to be relatively safe, producing no significant hypotension or adverse events but some evidence of bradycardia not associated with adverse clinical events. Mivazerol decreased the incidence of, and treatment for, tachycardia, hypertension, and myocardial ischemia, particularly during high stress periods. Therefore, these salutary effects of mivazerol indicate further study in large-scale trials that assess mivazerol's effects on adverse cardiac outcomes, including death and myocardial infarction. The purpose of this study was to assess the efficacy of clonidine in achieving perioperative hemodynamic stability in patients undergoing coronary artery bypass grafting performed under high-dose alfentanil anesthesia. Twenty-four patients with left ventricular ejection fraction greater than 0.5 were prospectively studied in a double-blind manner; those requiring emergency procedures were excluded. They were randomized to receive either oral clonidine or placebo together with their premedication. Induction of anesthesia was achieved with 10 mg of alfentanil infused over 5 minutes followed by a continuous infusion of 60 mg/h during 1 hour, or until sternotomy, and then 30 mg/h until the end of surgery. Hemodynamic responses to noxious stimuli were treated with additional alfentanil boluses and isoflurane when these were unsuccessful. Intraoperative hemodynamic profile analyses showed a continuous increase in systemic vascular resistance and mean arterial pressure in the clonidine group from the time of skin incision until the onset of bypass, whereas the cardiac output profiles remained similar in the two groups. The number of additional alfentanil boluses was similar. Isoflurane requirements (1/11 v 4/13) were not significantly different, but only a few patients required this therapy. The postbypass hemodynamic profiles were similar. Severe hemodynamic impairment occurred in the clonidine group during warming in the postoperative period: this group showed a drop in systemic vascular resistance index (1276 +/- 347 v 1757 +/- 415 dyn.sec.cm-5.m2) that could not be compensated for by an increase in cardiac output despite normal filling pressures, causing hypotension (66 +/- 10 v 79 +/- 16 mmHg). This hemodynamic status led to greater requirements for vasoactive agents and inotropics in this group.(ABSTRACT TRUNCATED AT 250 WORDS) Clonidine may have beneficial effects in patients undergoing major surgery. We enrolled 156 patients having elective CABG surgery in a double-blind, randomized trial. Patients were randomized to receive either two doses of placebo (Group PP) or clonidine 5 micrograms/kg (Group CC). Perioperative measurements included haemodynamics, anaesthetic and analgesic drug usage, creatinine clearance, cortisol excretion, recovery times and quality of life (SF-36) after surgery. Overall, there was no significant difference with time to tracheal extubation (median [10-90 centile]): CC 7.1 (3.4-18) h vs PP 8.0 (4.3-17) h, P = 0.70; but there was a higher proportion of patients extubated within four hours: CC 20% vs. PP 8%, P = 0.038. Clonidine resulted in a number of significant (P < 0.05) haemodynamic changes, particularly pre-CPB: less tachycardia and hypertension, more bradycardia and hypotension. Clonidine was associated with a significant (P < 0.05) reduction in anaesthetic drug usage, higher creatinine clearance, lower cortisol excretion and improvement in some aspects of quality of life. This study lends support to consideration of clonidine therapy in patients undergoing CABG surgery. The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in heart rate and arterial blood pressure. Previous work has reported that 10%-18% of the patients develop ischemic ST segment changes during the procedure. Therefore, we performed a prospective, randomized, double-blinded study in 36 patients scheduled for elective microlaryngeal and bronchoscopic surgical procedures to evaluate the effects of 300-microg oral clonidine premedication (n = 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by using continuous electrocardiographic monitoring, beginning 30 min before, and lasting until 24 h after the operation. During the procedure, patients receiving placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure (the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15 to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose of 300-microg clonidine blunted the hemodynamic response to endoscopy. Ventricular arrhythmias were more frequent in patients who were not premedicated with clonidine. Two patients in the control group, but none in the clonidine group, had evidence of myocardial ischemia. These data should encourage routine premedication with clonidine in patients undergoing microlaryngoscopic and bronchoscopic procedures. The purpose of this study was to test the hypothesis that after thoracic surgery, the supplementation of a low-dose thoracic epidural (ED) bupivacaine (0.125%) infusion by intravenous (IV) dexmedetomidine decreases analgesic requirement without causing respiratory depression. The primary endpoint was the need for additional ED bupivacaine administered through patient-controlled epidural analgesia (PCEA). Secondary endpoints included the requirement for supplemental opioids and the impact of dexmedetomidine on CO2 retention.
                A prospective, randomized, double-blinded study.
                A major US tertiary care university hospital.
                Twenty-eight patients scheduled to undergo elective thoracotomy for wedge resection, lobectomy, or pneumonectomy.
                On intensive care unit arrival, the thoracic ED catheter was loaded with 0.125% bupivacaine to a T4 sensory level and a continuous infusion of 0.125% bupivacaine without opioid was commenced at 4 mL/h. Patients were then randomized into 1 of 2 groups. The dexmedetomidine group received an IV loading dose of dexmedetomidine of 0.5 microg/kg over 20 minutes, followed by continuous IV infusion at 0.4 microg/kg/h. The placebo group received IV saline at the same calculated loading and infusion rates by volume. If necessary, supplemental analgesia (increased ED rate, ED fentanyl, ketorolac [IV]) was provided to ensure a visual analog scale (VAS) score of < or =3.
                The analgesic effect was monitored by the VAS, and the requirement for PCEA dosing and additional analgesics was recorded. Heart rate, blood pressure, and blood gases were also monitored.
                There was no significant difference in PCEA use and VAS score between the 2 groups, but requirement for supplemental ED fentanyl analgesia was significantly greater in the placebo group (66.1 +/- 95.6 v 5.3 +/- 17.1 microg, p = 0.039). Mean PaCO2 was also significantly greater in the placebo group (40.3 +/- 4.1 v 43.9 +/- 4.3 mmHg, p = 0.04). Patients in the dexmedetomidine group exhibited significantly decreased heart rate (1 patient required and responded to atropine) and blood pressure (4 patients required and readily responded to IV fluid) compared with the placebo group.
                The authors conclude that in postthoracotomy patients, IV dexmedetomidine is a potentially effective analgesic adjunct to thoracic ED bupivacaine infusion and may decrease the requirement for opioids and potential for respiratory depression.
Our study provides encouraging evidence that α-2 adrenergic agonists may reduce cardiac risk, especially during vascular surgery. Nonetheless, these data remain insufficient to make firm conclusions about their efficacy and safety. A large randomized trial of α-2 adrenergic agonists is therefore warranted. Additionally, future research must determine which specific α-2 adrenergic agonist should be used, and whether it is safe to combine them with other perioperative interventions (for example β-adrenergic blockade).