Preoperative alpha2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Perioperative sympatholysis. Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. McSPI--Europe Research Group. A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Efficacy and safety of low-dose propranolol versus diltiazem in the prophylaxis of supraventricular tachyarrhythmia after coronary artery bypass grafting. Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. A randomised, clinical study of the effect of low-dose dopamine on central and renal haemodynamics in infrarenal aortic surgery. A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial. A prospective randomized trial of preoperative "optimization" of cardiac function in patients undergoing elective peripheral vascular surgery. Hemodynamic effects and safety of sotalol in the prevention of supraventricular arrhythmias after coronary artery bypass surgery. Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery. beta-Blockade therapy for supraventricular tachyarrhythmias after coronary surgery: a propranolol withdrawal syndrome? Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent. Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids. Supraventricular tachyarrhythmias after coronary bypass surgery--a double blind randomized trial of prophylactic low dose propranolol. Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Efficacy of nadolol in preventing supraventricular tachycardia after coronary artery bypass grafting. Preoperative beta-blocker use reduces atrial fibrillation in off-pump coronary 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. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. Arrhythmia prophylaxis using propranolol after coronary artery surgery. Effect of low-dose amiodarone and magnesium combination on atrial fibrillation after coronary artery surgery. Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias: a prospective, randomized study. Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery. Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.
To evaluate the influence of the alpha2-adrenergic receptor agonist clonidine on creatinine clearance as a measure of renal function.
                Prospective, double-blind, randomized, placebo-controlled clinical trial.
                University hospital.
                Patients undergoing coronary artery bypass graft surgery (n = 48) with normal risk.
                Administration of clonidine (4 micrograms/kg iv)) or placebo 1 hr before induction of anesthesia.
                Induction and maintenance of anesthesia (etomidate, midazolam, and fentanyl) and cardiopulmonary bypass technique (nonpulsatile, normothermic, intermittent cold blood cardioplegia) were standardized in all patients. The night before surgery and the first and third night after surgery, creatinine clearance was calculated from a 12-hr urine collection period. Venous blood samples for determination of plasma antidiuretic hormone (ADH) concentrations were taken the evening before surgery, immediately before induction of anesthesia and the evening after surgery (n = 16). Arterial catecholamine plasma concentrations were determined (high-performance liquid chromatography) before induction, 15 mins after induction of anesthesia, immediately after sternotomy, before initiation of cardiopulmonary bypass, as well as 5, 15, and 30 mins after initiation of cardiopulmonary bypass (n = 16). The total amount of anesthetics, infusions, transfusions, diuresis, and blood loss was not different between the groups. Creatinine clearance decreased over the first postoperative night from 98 +/- 18 (preoperatively) to 68 +/- 19 mL/min (p < .05) in placebo-treated patients. Creatinine clearance remained unchanged in clonidine-treated patients (90 +/- 19 [preoperatively] to 92 +/- 17 mL/min). There was a significant difference in creatinine clearance between the groups during the first postoperative night (p < .05; Mann-Whitney U test). In the third postoperative night, mean creatinine clearance of both groups was not different (75 +/- 31 vs. 86 +/- 28 mL/min). ADH concentrations were not different between the groups at any time, while plasma catecholamine concentrations were always significantly lower in clonidine-treated patients.
                Preoperative treatment with clonidine (4 microgram/kilogram) prevents the deterioration of renal function after cardiac surgery. This effect might be due to clonidine-induced reduction in the sympathetic nervous system response to coronary artery bypass graft surgery. 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. We hypothesized that, in vascular surgery patients, the application of a goal-directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and/or inotropes required in such a goal-directed therapy depended on the general anaesthetic technique used.
                Patients undergoing peripheral arterial bypass grafting were randomly assigned to three groups. In group 1, haemodynamic management was performed according to routine clinical practice. In the two other groups (groups 2 and 3) a goal-directed therapy was applied aiming to maintain the pulse contour-derived cardiac index above 2.5 l m min. Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia. Haemodynamic variables, amount of fluid and administration of inotropes were assessed at different time intervals.
                The amount of fluid administered was not significantly different between the groups. Two patients in group 1, 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine (P < 0.001). None of the patients anaesthetized with sevoflurane (groups 1 and 2) experienced postoperative cardiovascular complications, whereas four patients in the total intravenous group (group 3) experienced major postoperative cardiovascular complications (P = 0.005).
                In the conditions of the present study, the application of a goal-directed therapy aiming to maintain the cardiac index above 2.5 l min m did not result in a higher tissue oxygen delivery than when applying the standard haemodynamic strategy nor did it depend on the anaesthetic technique used. 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. Supraventricular tachyarrhythmias (SVT) complicate postoperative management after coronary bypass surgery in about 30% of all patients. Though a prophylactic treatment both with beta-adrenergic blocking agents and the calcium antagonist diltiazem has been used for the prevention of post-operative SVT, no study yet has performed a prospective comparison of the efficacy of these therapies.
                To investigate the prophylactic effect of either a calcium antagonist (diltiazem, 0.1 mg/kg per h i.v.) or a beta-adrenergic blocking agent (propranolol, 10 mg every 6 h postoperatively), we randomized prospectively 103 consecutive patients into three groups, the third one serving as a control group. Anti-arrhythmic medication was started with the procedure and was continued until the 3rd postoperative day.
                Preoperative conditions were the same for the three groups concerning age, extent of coronary heart disease, ventricular function and heart-related medication. There were no differences in intraoperative parameters or postoperative enzyme patterns. Diltiazem was ineffective in preventing SVT, the incidence being exactly the same as in the control group (35%). Propranolol reduced the occurrence of SVT significantly (7%, P < 0.05). Furthermore, patients treated with diltiazem needed positive inotropic support more often in the first hours after surgery than patients of the control group (30% vs 5%, P < 0.01).
                The perioperative administration of low-dose propranolol is considered a safe and effective drug prophylaxis to avoid the occurrence of SVT after bypass surgery. Eighty-five patients receiving long-term propranolol therapy were randomized after aorta-coronary bypass grafting either to receive minidose propranolol (Group I) or to serve as controls (Group II). They were compared with 18 patients (Group III) who did not receive beta blocking agents prior to operation but were given propranolol postoperatively. Poor-risk patients (those having left ventricular aneurysms, low ejection fraction, or congestive heart failure) as well as patients who required catecholamines postoperatively were included in the study. All three groups were comparable with respect to all risk factors. Propranolol (5 to 10 mg/6 hr) was started through a nasogastric tube 6 hours after operation and continued orally in all patients in Groups I and III. Supraventricular tachyarrhythmia appeared in two of 37 patients in Group I (5%), 19 of 48 patients in Group II (40%), and five of 18 patients in Group III (27%). The incidence of supraventricular tachyarrhythmia was significantly lower in Group I than in Groups II and III (p less than 0.001, Group I versus Group II; p less than 0.01, Group I versus Group III). In conclusion, low-dose propranolol is very effective in preventing supraventricular tachyarrhythmia following aorta-coronary bypass in patients receiving beta blockers preoperatively. The increased tendency for postoperative supraventricular tachyarrhythmia to develop in these patients is attributed to hypersensitivity to adrenergic stimulation after propranolol withdrawal. The tachyarrhythmia can be prevented by early reinstitution of propranolol in low doses after the operation. To determine whether dopamine prevents deterioration of central haemodynamics and renal function in aortoiliac surgery.
                Prospective, randomised and placebo-controlled.
                University hospital.
                Thirty patients for elective vascular surgery with implantation of an aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h postoperatively. Thoracic epidural analgesia and general anaesthesia were used.
                Central haemodynamic measurements were registered. The effective renal plasma flow (ERPF), the glomerular filtration rate (GFR), angiotensin II, aldosterone, arginine vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin and excretion of water and electrolytes were measured preoperatively, 1 h postoperatively and 24 h postoperatively.
                During the operation the dopamine group had higher cardiac index and heart rate together with lower pulmonary artery wedge blood pressure. ERPF and GFR did not differ between the groups. In the dopamine group ERPF was increased in all patients at the first postoperative clearance. The fractional excretion of sodium, the per- and postoperative diuresis and AVP were increased in the dopamine group as compared to the placebo group. Postoperatively, ANP in the placebo group was raised as compared to the preoperative level.
                Peroperatively, dopamine counteracted depression of left ventricular function. The increased ERPF at the first postoperative clearance in the dopamine group indicates either improved peroperative haemodynamics or a synergistic effect between dopamine and epidural sympathetic blockade. Dopamine also improved diuresis and natriuresis. Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.
                We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.
                Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF. Previous investigations have suggested that preoperative invasive hemodynamic monitoring with "optimization" of cardiovascular function may favorably affect the outcome among patients undergoing peripheral vascular surgery. The purpose of this study was to evaluate the effect of preoperative optimization of hemodynamic parameters on outcome in patients undergoing aortic reconstruction (AR) or limb salvage procedures (LSP) in a randomized, prospective clinical trial.
                All 72 patients who consented to participate in this study were admitted to the intensive care unit at least 12 hours before operation for placement of a pulmonary artery catheter (PAC). Patients who were randomized to the treatment group (n = 32) were "optimized" by adjusting their hemoglobin concentration, oxygen saturation (SaO2), cardiac output, or afterload until the mixed venous O2 saturation (SvO2) was at least 65%. The control group (n = 40) underwent placement of a PAC and had oxygen transport parameters measured without any attempt to optimize SvO2.
                There were no significant differences between the treatment and control groups with respect to age, gender, type of operation, initial Acute Physiology and Chronic Health Evaluation (APACHE) II score, SvO2, pulmonary artery occlusion pressure, or cardiac index. All treatment patients achieved an SvO2 of at least 65% before operation. Comparing the treatment and control groups, postoperative cardiovascular complications occurred in 25% versus 27%, intraoperative complications in 28% versus 20%, and death in 9% versus 5%, respectively. None of these differences was statistically significant as a whole or within the subgroups undergoing AR or LSP.
                These data suggest that preoperative optimization of cardiovascular function by using achievement of SvO2 above 65% as the end point does not result in any reduction of intraoperative or perioperative cardiac complications in patients undergoing PVS. Further studies with alternative assessments and manipulation of different cardiopulmonary parameters may yield additional information. Sotalol is a beta-adrenergic blocking drug with the additional property of lengthening the cardiac action potential. These electrophysiologic properties render the drug attractive for use in the prevention of postoperative supraventricular arrhythmias (SVA), and previous studies have suggested that it was indeed effective. The hemodynamic response to sotalol and its safety early after coronary artery bypass graft (CABG) surgery were therefore studied. Forty-two patients undergoing CABG were randomly assigned either to receive sotalol to prevent postoperative SVA (25 patients) or to serve as controls (17 patients). Sotalol was started 6 hours after surgery if patients had a cardiac index > 2.8 L/min/m2 with a pulmonary capillary wedge pressure < 15 mmHg, and if they had no contraindications to the use of beta-blockers. The drug was given as a loading infusion of 1 mg/kg over 2 hours, followed by a maintenance infusion of 0.15 mg/kg/h for 24 hours. Three hours later, patients received the first oral dose of 80 mg to be repeated every 8 or 12 hours. Adverse effects necessitating discontinuation of the drug (bradycardia < 50 beats/min, systolic blood pressure < 90 mmHg, or cardiac index < 2.2 L/min/m2) occurred in six patients (24%) and were mainly related to the loading infusion. The hemodynamic data for patients who completed the study were characterized by a significant fall of the cardiac index caused by a lower heart rate without significant change of the stroke volume index. The incidence of supraventricular arrhythmias was not significantly different in the two groups (3/19 in the sotalol group, 5/17 in the control group).(ABSTRACT TRUNCATED AT 250 WORDS) Atrial fibrillation and atrial flutter (AF) frequently complicate coronary artery bypass surgery (CABG) and increase hospital stay as well as morbidity. Studies of drug prophylaxis to prevent AF with beta-adrenergic blocking agents administered in fixed doses have had conflicting results.
                One hundred patients were randomized to receive metoprolol or placebo following CABG. A dosing algorithm was used to achieve clinically significant beta-adrenergic blockade.
                There was no significant difference between the incidence of AF in the metoprolol (24%) and placebo (26%) groups. However, the incidence of AF in all patients having CABG at this institution declined over the period of the study from 31% to 23% (P < .025), in association with the adoption of a continuous technique of cardioplegia delivery.
                Metoprolol is not efficacious for the prevention of post-CABG AF even when dosage is titrated to achieve clinical evidence of beta blockade. It is likely that the adoption of a continuous cardioplegia technique caused a reduction in our incidence of post-CABG AF. A high incidence of cardiac arrhythmias and hypertension has been noted after coronary artery bypass surgery in patients previously treated with oral propranolol. Forty-two patients undergoing coronary bypass surgery had propranolol withdrawal 10 hours before surgery and were randomized into a group treated with propranolol immediately postoperatively, and a nontreatment group. Patients treated with prophylactic propranolol had a significantly lower incidence of postoperative supraventricular arrhythmias compared to patints who received no prophylaxis. All the arrhythmias responded rapidly to 1 mg of intravenous propranolol therapy, whether it was used as a primary treatment or as a supplement to prophylactic propranolol. The findings suggest that (1) there is a high incidence of supraventricular arrhythmias and sinus tachycardia after coronary artery bypass which might reflect an abrupt propranolol withdrawal, and (2) that perioperative prophylactic or supplementary propranolol therapy will successfully prevent or treat most of these arrhythmias. In a non-double-blind, prospective, randomized study, the intra-operative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beta-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication. Forty-four per cent of the untreated control patients and 61% of the patients pretreated with a beta-adrenergic blocking agent had normal preoperative electrocardiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a beta-adrenergic blocking agent (P less than 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untreated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beta-adrenergic blocking agent, given with pre-medication, can significantly reduce that risk. Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids. In the present study 75 patients were double blind randomized either to receive 10 mg propranolol orally 4 times a day (35 patients) or a placebo (40 patients). Episodes of clinically important supraventricular tachyarrhythmias were recorded in the first 4 postoperative days. They appeared in 5 of 35 patients receiving propranolol and in 5 of 40 patients receiving placebo (no statistically significant difference). In conclusion this study indicates the need for further evaluation to clarify if low-dose propranolol or any other drug is effective in reducing the frequency of SVT in the early postoperative period after coronary artery bypass surgery. To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery.
                Randomized, double-blind, placebo-controlled trial.
                A tertiary acute-care 500-bed university teaching hospital.
                Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied.
                Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass.
                Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia.
                Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period. 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. To investigate the efficacy of nadolol in the prevention of supraventricular arrhythmias after coronary artery bypass graft (CABG) surgery, 148 patients undergoing elective CABG were randomized in double-blind, placebo-controlled fashion to receive either nadolol or placebo. The test medication was started on the first postoperative morning and maintained as a single daily dose for 6 weeks. Aside from routine daily clinical evaluation and postoperative electrocardiographic monitoring, patients underwent 24-hour Holter recording once preoperatively and 3 times postoperatively. Seven patients were excluded from the evaluation of efficacy analysis because of insufficient postoperative data. There were no significant differences between the patients receiving nadolol (n = 67) and those receiving placebo (n = 74) with respect to age, preoperative heart rate, previous medications (including beta blockers), incidence of previous myocardial infarction, frequency of preoperative ventricular and supraventricular arrhythmias, concomitant valvular heart disease, mean cardiopulmonary bypass time, mean aortic cross-clamp time, use of blood and crystalloid cardioplegia, mean number of bypass grafts placed, postoperative use of inotropic agents and catecholamines and incidence of perioperative myocardial infarction. Analysis of postoperative Holter recordings showed that the heart rate was consistently and significantly higher in the placebo group throughout the period of the study (p less than 0.001). The average number of premature atrial contractions was significantly smaller in the nadolol group (p less than 0.05), and nadolol patients had fewer ventricular premature complexes, couplets and non-sustained ventricular tachycardias during the first week postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) Atrial fibrillation (AF) after coronary artery bypass graft surgery constitutes the most common sustained arrhythmia and results in many complications. The purpose of this study was to assess the effects of prophylactic use of beta-blockers against atrial fibrillation in off-pump surgery patients in the early postoperative period.
                From 2002 to 2005, 78 patients were enrolled and 41 patients received 50 mg metoprolol succinate daily, which was initiated minimum four days before surgery. Preoperative beta-blocking therapy was continued until the morning of surgery. Thirty-seven patients were free of beta-blocker therapy. Esmolol was used within same range of doses in both groups during operations. Both groups received metoprolol succinate following operations. The frequency of AF occurrence was analysed from the operation time to the sixth postoperative day. Results: Sixteen patients developed AF with an overall incidence of 22.5%. Four patients from the study group and three patients from the control group were excluded from the study because of transfer to on-pump surgery. There was no difference with regard to the number of grafts carried out, duration of operations and ventilation, intensive care unit stay and inotropic need among groups. Length of hospital stay did not differ among groups either. There was a higher incidence of postoperative AF in patients without beta-blocker prophylaxis (11.7-32.4% P=0.049).
                Low-dose postoperative beta-adrenergic blockade is valuable for patients who receive these medications before off-pump coronary artery bypass grafting procedures and may be beneficial against AF in all patients. 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. 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. To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.
                Randomised controlled trial with double blinding between inotrope groups. Setting: York District Hospital, England.
                138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.
                Hospital mortality and morbidity.
                Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.
                Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care. Sixty patients undergoing coronary artery bypass grafting operations with cold potassium cardioplegia as the method of myocardial preservation either received low-dose oral propranolol (10 mg every 6 hours; 28 patients) or served as controls (32 patients). The study period began after extubation and ended at the time of hospital discharge. On the fourth postoperative day, 24-hour Holter monitoring was performed to assess additional subtle differences in arrhythmias. The overall incidence of symptomatic postoperative arrhythmias was 31% in the control group: 6 patients (19%) had atrial fibrillation or flutter and 4 patients (12%), ventricular arrhythmias. By contrast, 1 patient (4%) in the propranolol group had atrial fibrillation, and no patient had ventricular arrhythmias. The difference in overall arrhythmia rates between the two groups is significant (p less than 0.025). Twenty-four-hour Holter monitoring demonstrated no additional differences in the frequency of simple or complex atrial or ventricular ectopy between the two groups. We conclude that the incidence of postoperative arrhythmias following coronary artery bypass operation is diminished by the oral administration of prophylactic low-dose propranolol. When compared with our previous study [1], in which the method of myocardial preservation was intermittent aortic cross-clamping and moderate hypothermia, there is no difference in the overall incidence of postoperative arrhythmias. To evaluate whether postoperative administration of intravenous low-dose amiodarone and magnesium sulfate (MgSO(4)) combination would reduce the incidence of atrial fibrillation following coronary artery bypass grafting (CABG) in normomagnesemic high-risk patients for postoperative atrial fibrillation (POAF).
                A total of 136 patients undergoing elective CABG and had > or =3 risk factors for POAF were prospectively randomized to one of three groups, to receive a single dose of amiodarone (5 mg/kg) and MgSO(4) (1.5 g) (combination group, n = 44), or an equal dose of amiodarone (amiodarone group, n = 44) or equal volumes of saline (control group, n = 48) at early postoperative period. Continuous electrocardiographic (ECG) monitoring was performed for the first 48 hours and an ECG was recorded every 8 hours later. POAF longer than 30 minutes or for any length requiring treatment, and the drug-related side effects were recorded.
                The study population showed a homogeneous distribution regarding risk factors for POAF and there was no significant difference in patient characteristics, echocardiographic variables, or operative variables among three groups. POAF developed in 4 patients in combination group, in 16 patients in amiodarone group and in 16 patients in control group, representing a 24% relative risk reduction between the combination group and control group (p = 0.023). No statistically significant difference regarding incidence of POAF was observed between amiodarone and control groups.
                Combined prophylactic therapy with amiodarone and MgSO(4) at the early postoperative period without a maintenance phase is an effective, simple, well-tolerated, and possibly cost-effective regimen to prevent POAF in normomagnesemic, high-risk patients. A prospective, randomized study was performed in 100 consecutive patients undergoing coronary artery bypass surgery to assess the efficacy of the early reinstitution of propranolol in reducing the incidence of postoperative supraventricular tachyarrhythmias (SVT). Patients were randomized to receive propranolol 10 mg every 6 hours enterally starting the morning after surgery (Group I, 50 patients) or to serve as controls (Group II, 50 patients). No patient was excluded because of poor ventricular function, need for urgent revascularization, or transient necessity for ionotropic support. Both groups had a comparable incidence of risk factors, previous infarction, unstable angina, and abnormal ventricular function. The extent of coronary disease, preoperative propranolol dose, and number of grafts performed were also similar. SVT occurred in 3/50 (6%) patients in Group I compared with 14/50 (28%) in Group II (p less than 0.01). There were no preoperative or intraoperative discriminators to predict the occurrence of SVT. In addition, perioperative infarction and the need for mechanical or pharmacologic circulatory support did not predispose to SVT. The data indicate that early administration of propranolol should be given to all patients after myocardial revascularization to decrease the incidence of these postoperative rhythm disturbances. 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. Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease.
                Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure.
                Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia.
                The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery. Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. An exaggerated inflammatory response has been proposed to be one etiological factor.
                To test whether intravenous corticosteroid administration after cardiac surgery prevents AF after cardiac surgery.
                A double-blind, randomized multicenter trial (study enrollment August 2005-June 2006) in 3 university hospitals in Finland of 241 consecutive patients without prior AF or flutter and scheduled to undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement.
                Patients were randomized to receive either 100-mg hydrocortisone or matching placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 hours during the next 3 days. In addition, all patients received oral metoprolol (50-150 mg/d) titrated to heart rate.
                Occurrence of AF during the first 84 hours after cardiac surgery.
                The incidence of postoperative AF was significantly lower in the hydrocortisone group (36/120 [30%]) than in the placebo group (58/121 [48%]; adjusted hazard ratio, 0.54; 95% confidence interval, 0.35-0.83; P = .004; number needed to treat, 5.6). Compared with placebo, patients receiving hydrocortisone did not have higher rates of superficial or deep wound infections, or other major complications.
                Intravenous hydrocortisone reduced the incidence of AF after cardiac surgery.
                clinicaltrials.gov Identifier: NCT00442494. Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.
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).