Cardiovascular effects of a nifedipine infusion during fentanyl-nitrous oxide anesthesia in dogs

The hemodynamic effects of a nifedipine infusion were investigated in eight dogs given fentanyl/ pancuronium/nitrous oxide/oxygen anesthesia. Nifedipine (20 μg/kg) was given intravenously over two minutes immediately prior to each 30-minute infusion at 2 μg/kg/min, 4 μg/kg/min, and 6 μg/ kg/min. The range of plasma nifedipine levels obtained was 52.1 to 113.7 ng/mL. The predominant hemodynamic effects were significant reductions systemic vascular resistance (SVR) and mean aortic pressure (MAP), accompanied by a rise in cardiac index and heart rate (HR). Administration of calcium chloride (20 mg/kg) after the nifedipine infusion had no effect on SVR or MAP, but HR was significantly reduced. Serum epinephrine and norepinephrine levels increased after the infusion of nifedipine and suggested that fentanyl did not completely overcome the sympathetic response to the profound vasodilatation. The resulting tachycardia in combination with diastolic hypotension from nifedipine could have a detrimental effect on the myocardial oxygen balance.     

Anesthetic induction with fentanyl and intravenous lidocaine for coronary artery surgery

In a randomized, double-blind trial, 59 patients undergoing coronary artery surgery received fentanyl 10, 15, or 25 lag/kg infused over 5 minutes for anesthetic induction. Half of the patients received intravenous lidocaine, 1.5 mg/kg, 1 minute before laryngoscopy. Efficacy of induction as judged by loss of consciousness was evaluated, and hemodynamic values during induction, laryngoscopy, and tracheal intubation were recorded each minute for 10 minutes. Plasma fentanyl concentrations were determined after termination of the fentanyl infusion. Opioid induction with fentanyl was successful in 90% (18 of 20) of patients receiving 25 μg/kg, 89% (17 of 19) of patients receiving 15 μg/kg, but only 55% (11 of 20) of patients receiving 10 μg/kg (P < .01). While plasma fentanyl concentrations were proportional to the dose infused (25 ng/mL, 18 ng/mL, and 14 ng/mL in the 25, 15, and 10 μg/kg fentanyl groups, respectively), there was no relationship between plasma fentanyl concentration and hemodynamic response to laryngoscopy or intubation. Opioid induction caused a gradual decrease in blood pressure that was restored with intubation. Lidocaine partially blocked this restoration (systolic blood pressure 122 ± 5 v 138 ± 5 mmHg, lidocaine v placebo, 1 minute after laryngoscopy, P < .05). Fentanyl, 15 or 25 μg/kg, intravenously, is an effective induction agent for patients with coronary artery disease. Supplementation with intravenous lidocaine, 1.5 mg/kg, will obtund the increase in blood pressure that occurs with laryngoscopy and intubation and help prevent infrequent hypertensive responses seen with this opioid technique.     

Influence of high-dose opioid anesthesia on posterior tibial nerve somatosensory cortical evoked potentials: Effects of fentanyl,sufentanil, and alfentanil

The effects of high doses of fentanyl (group F), sufentanil (group S), and alfentanil (group A) on posterior tibial nerve somatosensory cortical evoked potentials were studied in 30 patients scheduled for elective valve replacement surgery. Anesthesia was induced with either fentanyl, 75 μg/kg, sufentanil, 5 μg/kg, or alfentanil, 125 μg/kg. The lungs were ventilated with oxygen/air. A bolus dose of fentanyl, 25 μg/kg, was given 30 minutes after induction of anesthesia in group F. Anesthesia was maintained with a continuous infusion of sufentanil, 5μg/kg/h, in group S, or alfentanil, 500 μg/kg/h, in group A. Latencies of the peaks of the primary cortical complex (P1, N1, 132) increased by 1 to 2 ms after induction of anesthesia, although this was significant (P < 0.01) only for P1 and N1 in groups F and S. N2 latency increased significantly (P < 0.01) by 6 to 10 ms in all groups. P1-N1 amplitude did not change after induction of anesthesia. N1-P2 amplitude decreased significantly (P < 0.01) to 60%–70% of preinduction values in groups F and S. P2-N2 amplitude decreased significantly (P < 0.01) to 60%–70% of preinduction values in all groups. P1, N1 and P2 latencies did not change significantly from the post-induction values in the period preceding cardiopulmonary bypass (75 ± 16 minutes) in groups F and S. In group A significant changes were observed only for N1 and P2 latency (P < 0.01). During this period there was a further gradual increase in N2 latency and amplitudes remained stable, except P1-N1 amplitude in group F, which decreased significantly (P < 0.05). A bolus dose of fentanyl, 25 μg/kg, given in group F at 30 minutes after induction of anesthesia did not change latencies and amplitudes. No significant differences in latency or amplitude were found at any time among the three study groups. It is concluded that anesthesia with high doses of fentanyl, sufentanil, or alfentanil is a suitable technique when intraoperative monitoring of posterior tibial nerve somatosensory cortical evoked potentials is indicated.     

右美托咪定对小儿先天性心脏病外科手术麻醉血流动力学的影响

目的探讨右美托咪定对小儿先天性心脏病外科手术麻醉过程中血流动力学的影响。方法将68例在体外循环下行心脏手术的先天性心脏病患儿按随机数字法随机分为咪达唑仑组(n=34)和右美托咪定组(n=34)。麻醉诱导:两组均给予咪达唑仑0.2 mg/kg、芬太尼10μg/kg、维库溴铵0.2 mg/kg行麻醉诱导。麻醉诱导后,行气管内插管,机械通气。麻醉维持:咪达唑仑组输注咪达唑仑0.2 mg.kg-1.h-1和芬太尼10μg.kg-1.h-1,1 h后分别以0.1μg.kg-1.h-1和5μg.kg-1.h-1维持;右美托咪定组输注右美托咪定1μg.kg-1.h-1和芬太尼10μg.kg-1.h-1,1 h后分别以0.5μg.kg-1.h-1和5μg.kg-1.h-1维持。必要时以0.4%～1.0%异氟醚吸入维持麻醉。监测并记录记录麻醉诱导前、麻醉后1 h、切皮前、切皮后即刻、手术结束即刻、手术结束后10 min的血压和心率。结果两组患儿在输注麻醉药物1 h后,收缩压和心率均显著降低,差异有统计学意义(均P<0.05);在切皮时,咪达唑仑组收缩压、舒张压和心率较切皮前明显增高,且明显高于右美托咪定组,差异有统计学意义(均P<0.05);右美托咪定组较少患儿需加用异氟醚,与咪达唑仑组比较,差异有统计学意义[35.3%(12/34)vs.85.3%(29/34),χ2=17.752,P=0.000]。结论与咪达唑仑比较,右美托咪定可更有效的维持小儿先天性心脏病外科手术麻醉过程中的血流动力学稳定。     

Catecholamine responses to anesthetic induction with fentanyl and sufentanil

In a randomized study, the authors examined the changes in plasma epinephrine and norepinephrine concentrations associated with induction of anesthesia and surgery in 33 patients with good ventricular function undergoing elective coronary artery surgery. After premedication with morphine and scopolamine, patients received either fentanyl, 100 μg/kg (n = 16), or sufentanil, 15 μg/kg, (n = 17), intravenously (IV), over 10 minutes to induce anesthesia. Metocurine, 0.42 mg/kg, IV, produced muscle relaxation. Arterial blood for plasma catecholamine determinations was drawn prior to induction, every two minutes throughout induction, one minute following endotracheal intubation, and one minute after sternotomy. Plasma epinephrine concentration was unchanged with either induction agent. Plasma norepinephrine concentration increased significantly after administration of either narcotic, peaked between six and ten minutes into induction, and returned to the preinduction value after intubation. Induction-related changes in arterial pressure and pulmonary capillary wedge pressure were significantly correlated with changes in the logarithm of plasma norepinephrine concentration. Similar degrees of endogenous norepinephrine release appear to accompany induction with equipotent doses of fentanyl and sufentanil in patients premedicated with morphine and scopolamine. Norepinephrine release may influence the hemodynamic response to induction with narcotics.     

不同肌肉松弛药对于先心病患者麻醉诱导时血压和心率的影响

目的 :研究不同肌肉松弛药用于先心病患者麻醉诱导时对血压和心率的影响。方法 :48例择期先天性心脏病矫形手术患者 ,心功能 ～ 级 ,随机分为 6组 ,每组 8例。泮库溴铵、阿曲库铵和维库溴铵 （剂量均为 0 .1mg/ kg）分别合用安定 （0 .2 m g/ kg）和小剂量芬太尼 （5 μg/ kg）或大剂量芬太尼 （10 μg/ kg）。记录插管前、后的血压、心率变化。结果 :与小剂量芬太尼合用进行麻醉诱导时 ,泮库溴铵有增快心率作用 （P<0 .0 1） ,对血压影响不明显 ,阿曲库铵有明显减慢心率作用和降压作用 （P<0 .0 5或 P<0 .0 1） ,维库溴铵有轻度减慢心率作用 （P<0 .0 1） ,对血压影响不大 ;与大剂量芬太尼合用时 ,泮库溴铵对心率的影响不显著 ,并引起血压轻度下降 （P<0 .0 5 ） ,阿曲库铵仍表现明显有减慢心率作用 （P<0 .0 5 ） ,其降压作用的时间有所延长 （P<0 .0 5或 P<0 .0 1） ,维库溴铵减慢心率作用时间有所延长 （P<0 .0 1） ,并使血压显著下降 （P<0 .0 5或 P<0 .0 1）。结论 :先心病矫治术麻醉诱导时宜选择泮库溴铵和较小剂量芬太尼 （5μg/ kg）合用 ,可减少诱导时心动过缓的发生率。     

A randomized double-blind comparison of fentanyl- and sufentanil-oxygen anesthesia for abdominal aortic surgery

Twenty-four patients undergoing abdominal aortic surgery for aneurysm or occlusive vascular disease entered a randomized, double-blind protocol comparing high-dose narcotic anesthesia with fentanyl (125 μg/kg) or sufentanil (25 μg/kg). All patients received perioperative β-adrenergic blockade therapy. Hemodynamic and electrocardiographic (leads 11 and V₅) responses to induction, intubation, skin incision, aortic cross-clamping, and declamping were studied. Sufentanil produced a transient decrease in mean arterial pressure and a significant reduction of systemic vascular resistance during induction. However, no significant hemodynamic differences were observed between the two groups during intubation, or at any other time during surgery. To maintain mean arterial pressure within 20% of the awake control value, the fentanyl group required an average infusion of 1.0 ± 1.1 μg/kg/min of nitroglycerin compared with 1.7 ± 2.8 μg/kg/min for the sufentanil group. Low-dose isoflurane was required in 30% of patients in the fentanyl group, compared with 41 % of the sufentanil group, for control of blood pressure. The multiple-bolus technique of narcotic administration resulted in a wide but parallel range of plasma concentrations from induction to the end of surgery with both narcotics. Mean plasma fentanyl concentrations varied between 7.2 ± 1.4 ng/mL and 26.5 ± 7.9 ng/mL, and mean sufentanil plasma concentrations varied between 1.0 ± 0.1 ng/mL and 10.6 ± 7.2 ng/mL throughout surgery. Within this range of narcotic serum levels, the authors were unable to identify a specific threshold level for either narcotic above which hemodynamic responses were consistently attenuated. A low incidence (4.5%) of intraoperative myocardial ischemia was observed. It is concluded that sufentanil and fentanyl are not different at blunting hemodynamic responses during aortic surgery. When supplemented by low doses of nitroglycerin and isoflurane, both narcotics provide anesthesia characterized by good hemodynamic control and a low incidence of myocardial ischemia.     

不同剂量芬太尼和依托咪酯复合诱导气管插管对神经外科患者脑血流动力学的影响研究

目的探讨不同剂量芬太尼和依托咪酯复合诱导气管插管对神经外科患者脑血流动力学的影响。方法选择2012—2013年我院神经外科收治的需气管插管全醉的成年患者64例,将其随机分为A组20例(芬太尼1μg/kg)、B组22例(芬太尼2μg/kg)、C组22例(芬太尼3μg/kg)。A、B、C组患者在1 min内分别静脉注射芬太尼1μg/kg、2μg/kg、3μg/kg,30 s后静脉给予依托咪酯0.3 mg/kg、维库溴胺0.1 mg/kg,3 min后进行气管插管。记录3组患者在手术室静卧(T0)、麻醉诱导前(T1)、插管即刻(T2)及插管1 min(T3)时的血流动力学指标〔收缩压(SBP)、舒张压(DBP)及心率(HR)〕和脑血流动力学指标〔收缩峰值血流速度(Vp)、舒张期血流速度(Vd)、平均血流速度(Vm)、搏动指数(PI)和阻力指数(RI)〕。结果 T0时各组Vp、Vd、Vm、PI和RI比较,差异无统计学意义(P0.05);T1、T2及T3时B和C组Vp、Vd、Vm低于A组,RI高于A组(P0.05)。T0时各组SBP、DBP和HR比较,差异无统计学意义(P0.05)。T1、T2和T3时B和C组SBP低于A组(P0.05)。结论不同剂量芬太尼和依托咪酯复合诱导气管插管对神经外科患者均有良好的效果,其中2~3μg/kg芬太尼麻醉诱导能更加有效地稳定患者脑血流动力学指标。     

Protective effects of felodipine and verapamil against imipramine-induced lethal cardiac conduction disturbances in the anaesthetized rat

The effect of verapamil and felodipine on imipramine-induced cardiac toxicity was assessed in anaesthetized rats. Rats received either infusion of saline (n = 13), or non-hypotensive doses of felodipine (n = 36) or verapamil (n = 36) over 40 minutes. In saline-pretreated rats IV bolus injection of imipramine (10 mg/kg) resulted in severe hypotension, bradycardia, electromechanical dissociation, and death within 3 minutes. Rats pretreated with nonhypotensive doses of felodipine (1, 3, 6, and 10 micrograms/kg/min) or verapamil (10, 30, 100, and 300 micrograms/kg/min) survived throughout the experiment, despite an initial fall in blood pressure within the first 5 minutes after imipramine administration. Blood pressure returned to baseline levels within 15 minutes. Intermittent ECG monitoring showed significant prolongation of QRS duration after imipramine in both saline (by 138%) and verapamil-pretreated rats (by 63%), whereas in the rats pretreated with felodipine no prolongation was observed (+3%). We conclude that, in our experimental model, felodipine, more than verapamil, protects against the cardiac effects of imipramine intoxication.     

Efficacy and tolerance of high-dose intravenous amiodarone for recurrent, refractory ventricular tachycardia

High-dose intravenous amiodarone was given to 35 patients with recurrent life-threatening ventricular tachycardia (VT) refractory to conventional antiarrhythmic agents. Intravenous amiodarone was given as a 5 mg/kg dose over 30 minutes followed by 20 to 30 mg/kg/day as a constant infusion for 5 days. Twenty-two (63%) patients responded to intravenous amiodarone. All 22 responders received oral amiodarone. Thirteen (59%) continue to receive oral amiodarone after an average follow-up of 19 months, 4 (18%) had sudden cardiac death on oral amiodarone, 2 (9%) died while receiving amiodarone, secondary to left ventricular failure, and 3 (14%) discontinued amiodarone because of side effects. Of the 13 (37%) nonresponders, 10 died in the hospital while receiving intravenous amiodarone, secondary to lethal arrhythmia. Three nonresponders were discharged from the hospital; 2 with automatic cardioverter/defibrillators and 1 receiving a combination of antiarrhythmic agents. Serious adverse events occurred in 13 (37%) patients during intravenous amiodarone therapy. These included hypotension in 8 patients, symptomatic bradycardia in 4 patients and sinus arrest with bradycardia and hypotension in 1 patient. Minor side effects occurred in 23 (66%) patients. In conclusion, high dose intravenous amiodarone is effective in most patients with recurrent, sustained VT but is associated with an unacceptably high incidence of serious adverse events. The optimal dose and duration of intravenous amiodarone for patients with recurrent, refractory sustained VT remain unknown.     

The incidence of awareness,and amnesia for perioperative events,after cardiac surgery with lorazepam and fentanyl anesthesia

One hundred patients (mean age 59 ± 10 years) were premedicated with morphine, 0.15 mg/kg, and scopolamine, 0.008 mg/kg. Anesthesia was induced with lorazepam, 50 μg/kg, followed by fentanyl, 50 μg/kg, oxygen and pancuronium, 0.15 mg/kg. Isoflurane was given for short periods before and after cardiopulmonary bypass to 57 patients when hypertension was uncontrolled by addition of fentanyl and/or nitroglycerin. Morphine was used as the sole sedative postoperatively. Patients were interviewed following discharge from the surgical intensive care unit to assess the incidence of operative awareness, and to assess amnesia for events occurring during four preoperative and two postoperative periods of the patients' hospital stay. During three preoperative periods (day of admission, evening before, and morning before operation), 1%, 3%, and 2% of patients had complete amnesia, and 19%, 41%, and 31% had partial amnesia of events. Fifty-five percent of patients exhibited complete, and 34% of patients exhibited partial amnesia to events occurring in the preinduction period. Two patients reported intra-operative awareness (noises, conversation) occurring at the end of the anesthetic. In the two postoperative periods (morning of the day after surgery and intensive care stay), 9% and 15% of patients had complete, and 35% and 47% of patients exhibited partial amnesia. Amnesia was statistically significantly greater in patients over 60 years of age in the preinduction period. Duration of cardiopulmonary bypass did not affect the incidence of amnesia.     

Clinical and electrophysiological effects of intravenous quinidine in man.

Quinidine gluconate (total dose 4-4 to 9-1 mg/kg) was infused intravenously over 22 minutes in 20 patients with either frequent premature ventricular contractions or supraventricular arrhythmias, 16 of whom had bundle-branch block. Therapeutic plasma quinidine levels (3 to 7 mg/l) were achieved in 15. Heart rate, atrioventricular nodal, and infranodal conduction times did not change significantly. The QRS duration increased significantly from 128+/-30 to 134+/-29 ms at peak plasma quinidine levels (P less than 0.01). Mild hypotension occurred during infusion in most patients. Two patients had a severe but transient toxic response characterised by hypotension, nausea, vomiting, and diaphoresis. Atrioventricular dissociation with escape His bundle or fascicular rhythm occurred in 1 patient with sinus bradycardia. Bundle-branch block does not contraindicate administration of quinidine. Quinidine gluconate administered intravenously (0-3 to 0-4 mg/kg per min) is frequently associated with hypotenstion and should be used only in an intensive care setting and with careful monitoring of blood pressure.     

Electrophysiologic testing of bretylium tosylate in sustained ventricular tachycardia

We used programmed ventricular stimulation to test intravenous bretylium tosylate in 10 consecutive patients with inducible sustained ventricular tachycardia (usually refractory to type I antiarrhythmic agents). These 10 patients had previously documented sustained ventricular tachycardia and/or ventricular fibrillation complicating stable heart disease. Following control inductions of sustained ventricular tachycardia, bretylium 10 mg/kg was infused over 30 minutes. Thirty minutes after this infusion, sustained ventricular tachycardia could be induced in 9 of the 10 patients (one of these nine patients also had bretylium-potentiated spontaneous ventricular tachycardia). Tachycardia induced in the nine patients after bretylium was similar to control tachycardia with respect to morphology and cycle length (333 +/- 16 msec after bretylium versus 330 +/- 16 msec during control). However, five of the nine patients tolerated induced tachycardia less well after bretylium (exacerbated hypotension). In one patient, ventricular tachycardia could not be induced after intravenous bretylium.     

Prebypass hemodynamic stability of sufentanil-O2, fentanyl-O2, and morphine-O2 anesthesia during cardiac surgery: A comparison of cardiovascular profiles

Cardiovascular responses and the need for intervention with vasoactive agents were measured prospectively in a randomized study of 50 adult patients receiving sufentanil (n = 20), fentanyl (n = 20), or morphine (n = 10) anesthesia for cardiac surgery. Measurements were recorded and compared during induction and prebypass at intervals during which airway or surgically induced stress responses were likely to be greatest. Randomized, double-blinded doses of opioids were administered slowly and titrated according to clinical responses (hemodynamics) and the electroencephalogram. Mean doses were as follows: from induction until time of incision, sufentanil, 9.1 μg/kg; fentanyl, 58 μg/kg; and morphine, 2.5 mg/kg; and total dose for surgery; sufentanil, 18.9 μg/kg; fentanyl, 95.4 μ/kg; and morphine, 4.4 mg/kg. Equi-anesthetic depth in patients receiving sufentanil or fentanyl was confirmed by continuous electroencephalographic monitoring. Patients anesthetized with sufentanil and fentanyl showed marked cardiovascular stability and rarely responded to stimuli. Systolic arterial pressure, mean arterial pressure, heart rate, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, stroke volume index, and stroke work index values were similar in the two groups. Patients receiving morphine experienced large changes in several variables. Pharmacologic intervention was made when systolic arterial pressure deviated more than 30% from pre-event values and was uncontrolled by additional opioids. Interventions were necessary more often in patients receiving morphine (nine of ten) or fentanyl (12 of 20) than in patients receiving sufentanil (six of 20), P < 0.05. Results from this study suggest that morphine is a relatively unsatisfactory anesthetic, while sufentanil and fentanyl, at equi-anesthetic depths, provide stable and satisfactory hemodynamics.     

Two-dimensional echocardiographic assessment of left ventricular papillary muscles in their long axes: A new cross-sectional approach

Although a single intravenous bolus of disopyramide is an effective antiarrhythmic, side effects occur in some patients. We tested the safety of multiple bolus loading for intravenous disopyramide in 10 patients with frequent premature ventricular beats. Concurrent with a 1.0 mg/kg/hr infusion, a bolus of 0.5 mg/kg of disopyramide was given over 5 minutes. Up to three additional boluses were given 5 minutes after the first bolus unless a 50% reduction in premature ventricular beats or side effects occurred. The infusion was continued for 3 hours and was then decreased to 0.4 mg/kg/hr for 15 hours. All patients had a 50% reduction in premature ventricular beats and attained therapeutic blood leveis. Three patients with a history of controlled congestive heart failure developed either hypotension or pulmonary edema. Hypotension and pulmonary edema following intravenous disopyramide is more related to the pharmacology of the drug than to the loading scheme employed.     

Alfentanil in infants and children with congenital heart defects

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 tag/kg, alfentanil, 20 μg/kg, was given, followed by a continuous infusion of 1 μgkg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 μ/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartments moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 ± 2. mL/kg/min and 6.3 ± 0.8 mL/kg/min, respectively. Distribution volume was 0.48 ± 0.12 L/kg and 0.31 ± 0.08 L/kg, and elimination half-life was 69 ± 25 min and 62 ± 9 min, respectively. It is concluded that a continuous infusion of alfentanil as a supplement to nitrous oxide-halothane anesthetic is a feasibly method of anesthesia in infants and children undergoing surgery for correction of congenital heart defects.     

Intravenous atenolol for ventricular arrhythmias

To determine the efficacy and safety of intravenous atenolol in patients with frequent and repetitive benign or potentially lethal ventricular arrhythmias, 40 patients received an open-label, single dose of 10 mg of intravenous atenolol, given in aliquots of 2.5 mg every 10 minutes. Twenty-four-hour Holter monitoring was performed on the day before, the day of, and the day after infusion of atenolol. A full 10-mg dose was given to 37 patients; asymptomatic bradycardia developed in 3 patients, and they were not included in the efficacy analysis. A single 10-mg dose of intravenous atenolol was effective rapidly in suppressing ventricular arrhythmias, with peak suppression occurring 1 to 2 hours after infusion and significant suppression lasting for 7 hours. Only 1 patient had symptoms (lightheadedness), plus hypotension lasting 45 minutes after the infusion was concluded. The mean plasma level of atenolol was 231 ng/ml 10 minutes after the infusion, with individual patient values of 148 to 457 ng/ml. Thus, a single intravenous dose of 10 mg of atenolol can significantly reduce the frequency of ventricular premature complexes and ventricular tachycardia within the first hour after infusion; suppression can last for 7 hours. Atenolol is well tolerated.     

Cardiovascular effects of nociceptin in unanesthetized mice

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of NC decreased mean blood pressure and heart rate. The hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more prolonged hypotension was evoked by 100 nmol/kg (from 114+/-3 to 97+/-2 mm Hg at 10 minutes, P<0.01). The latter dose reduced heart rate from 542+/-43 to 479+/-31 beats/min (P<0.05) and increased aortic blood flow by 41+/-5% (P<0.05). Hypotension and bradycardia were also evoked by NC(1-17)NH2 and NC(1-13)NH2 fragments, whereas NC(1-13)OH and NC(1-9)NH2 were ineffective. Thiorphan, an inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor, did not alter basal mean blood pressure or heart rate, but it prevented the hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In contrast, [F/G]NC(1-13)NH2 did not alter the hypotension induced by bradykinin or endomorphin-1 (a micro-receptor agonist), and the bradycardia induced by leu-enkephalin (a delta-receptor agonist) or U504885 (a synthetic kappa-receptor agonist). In conclusion, NC and some of its fragments cause hypotension and bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence being critical for these biological effects. Our results also demonstrate that the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC receptor in vivo.     

Compartmental analysis of lidocaine kinetics during extracorporeal circulation

The aim of this study was to measure the effects of extracorporeal circulation (ECC) on lidocaine disposition and to determine if therapeutic concentrations were achieved during ECC. Anesthesia was obtained by administration of fentanyl (50 μg/kg plus 0.3 μg/kg/min) and pancuronium bromide (0.1 mg/kg) along with controlled ventilation (10 mL/kg, PaCO₂, 30 to 34 mmHg). Lidocaine was administered to ten patients in bolus doses of 2 mg/kg at the time of endotracheal intubation and during ECC at aortic declamping. Samples were collected at 20 and 40 seconds, and at 1, 3,5,10.15,20,25, and 30 minutes after drug administration. Blood sampling was arterial during anesthesia induction and from the oxygenator during ECC. Blood levels of lidocaine were determined by the immunofluorescence method. The kinetic studies of lidocaine showed increases in plasma volume and in the volume of the peripheral compartment, along with decreased volume in the compartment of well-perfused tissues during ECC. The fraction of the dose of lidocaine administered during ECC behaved accordingly, showing a decrease in the quantity of drug in the well-perfused tissues, and an increase in the other two compartments when compared to values before ECC. The doses administered gave plasma concentrations of 1.55 μg/mL, which are considered therapeutic. Thus, it is not recommended to increase the lidocaine dosage during ECC.     

Comparison of sufentanil-oxygen and fentanyl-oxygen anesthesia for mitral and aortic valvular surgery

The cardiovascular responses, speed of anesthetic induction, incidence of chest wall rigidity, need for anesthetic supplements (phentolamine, N20, and nitroprusside) to control intraoperative hypertension, and speed of postoperative recovery were measured and compared in 44 patients undergoing aortic and mitral valvular replacement with fentanyl O₂ or sufentanil-O₂ anesthesia. After a lorazepamatropine premedication and pancuronium pretreatment, fentanyl was administered intravenously at a rate of 400 jig/min and sufentanil at 200 μg/min until patients were unconscious; at this time they were given succinylcholine and their tracheas were intubated. After intubation, an amount of fentanyl or sufentanil equal to the dose producing unconsciousness was infused over the next 30 minutes, at which time the operation began. Additional fentanyl or sufentanil was given whenever systolic arterial blood pressure (SBP) increased more than 15% over preanesthetic values. When three successive supplemental doses of the narcotic failed to effectively decrease SBP, phentolamine was used to control pressure before and during bypass; after bypass, N20 (25% to 50%) or, if N20 was ineffective, nitroprusside was used. Average time of induction was 3.4 ± 0.3 for fentanyl and 1.0 ± 0.2 min (mean ± SD) for sufentanil. Chest wall rigidity occurred in 36% of patients in both groups. Total doses of fentanyl and sufentanil required for the entire operation were 113 ± 11 and 9.0 ± 0.4 μg/kg (mean ± SD), respectively. Heart rate, cardiac output, and mean right atrial pressure remained unchanged throughout the study in both groups. Mean arterial blood pressure (MBP) and SBP were significantly decreased during induction and after intubation in patients receiving sufentanil, but not fentanyl. Arterial pressure returned to control values prior to incision in patients receiving sufentanil. Neither group experienced a significant change in SBP after incision, sternotomy, or sternal spread. However, phentolamine was required in 32% and 68% of patients receiving fentanyl before and during bypass, respectively, but in 0% to 5% of those having sufentanil. Thirty-two percent of fentanyl patients required N₂0, and 23% nitroprusside after bypass for blood pressure control. Fourteen percent of patients receiving sufentanil required N₂0, and only 5% needed nitroprusside after bypass. The results of this study demonstrate that anesthetic doses of sufentanil result in less need for supplements and vasodilators during operation, but produce more hypotension during induction than fentanyl in patients having valve replacement.