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.
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.
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).