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PubMedDate not supplied

[Isoflurane versus propofol for sedation after heart surgery].

OBJECTIVE: To compare isoflurane and propofol as the principal sedatives in ventilated patients after cardiac surgery with extracorporeal circulation (ECC). PATIENTS AND METHODS: Forty consecutive, randomized patients undergoing cardiac surgery with ECC were studied prospectively. Patients were assigned to receive either isoflurane or propofol. Variables recorded were level of sedation, adaptation to the respirator and hemodynamic stability. RESULTS: Each group included 20 patients. The mean dose of isoflurane was 0.39% +/- 0.06% of end-tidal concentration. The mean propofol dose was 2.11 +/- 0.55 mg/kg/h. Statistically significant differences were found for stabilization of sedation time (4 min +/- 1.17 for isoflurane and 11.7 min +/- 4.78 for propofol) and time to endotracheal extubation (56.2 min +/- 20.47 for isoflurane and 72.65 min +/- 30.90 for propofol), number of times dosage had to be changed (2.20 +/- 0.89 with isoflurane and 7.05 +/- 2.58 with propofol) and time of administration had to be interrupted (8.45 min +/- 8.73 with propofol and 0.75 min +/- 1.94 with isoflurane). CONCLUSIONS: In comparison with propofol, isoflurane offers advantages of rapid stabilization of sedation, ease of use and shorter time to endotracheal extubation.

Aged↗
PubMed1994

Effect of medetomidine on the pharmacokinetics of propofol in dogs.

Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 micrograms/kg of body weight) on these kinetics was investigated using a two-way crossover design. On 2 occasions, dogs received either a bolus dose of propofol sufficient to allow endotracheal intubation, followed by an infusion of propofol (0.4 mg/kg/min) for 120 minutes, or medetomidine (10 micrograms/kg, IM), 15 minutes prior to induction of anesthesia as described, followed by infusion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atipamezole (50 micrograms/kg, IM) at the end of the 120-minute propofol infusion. Blood propofol concentration was measured, using high-performance liquid chromatography with fluorescence detection. Mean elimination half-life, blood clearance, mean residence time, and mean volume of distribution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minutes, and 6.04 L/kg, respectively, in the absence of medetomidine, and 136.9 minutes, 36.2 ml/kg/min, 215.1 minutes, and 3.38 L/kg, respectively, in the presence of medetomidine. Mean time to walking without ataxia was 174 minutes in the nonpremedicated dogs (with a median blood propofol concentration of 2.2 micrograms/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 microgram/ml.

Adrenergic alpha-Agonists↗
PubMed1993

Cardiovascular effects of propofol during coronary ligation in anesthetized dogs.

Under different infusion rates in normal hearts and hearts with coronary ligation, the hemodynamic effects of propofol were measured in a coronary artery ligation model in twelve mongrel dogs. Propofol was given by 10 mg/kg intravenous bolus followed by 30 min infusion in succession with 20 mg/kg/hr, 40 mg/kg/hr and 80 mg/kg/hr in both normal hearts and hearts with coronary ligation. The range of blood concentrations in our study is 2.19 +/- 0.56 microgram/ml to 15.78 +/- 3.31 micrograms/ml. After ligation at 1 cm below first diagonal branch of left anterior descending artery (LAD) obvious cardiovascular changes were seen in a few seconds. However, non-significant hemodynamic changes were demonstrated between pre-ligated and 30 min after ligation. With increasing blood propofol concentrations, there was significant negative correlation (p < 0.01) in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) but central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) decreased non-significantly with increasing propofol concentrations in both non-ligated and ligated groups. Propofol infusion up to 80 mg/kg/hr did not decrease MAP, CO and systemic vascular resistance (SVR) further in hearts with coronary ligation than normal hearts in our study. SVR and pulmonary vascular resistance (PVR) changed non-significantly between each groups even in blood concentration as high as 15 micrograms/ml. We conclude that propofol depresses myocardial function associated with increasing blood propofol concentrations despite stable SVR and PVR. The hemodynamic effects of propofol were similar in the normal hearts and hearts with coronary ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1993

[Propofol in general anesthesia in children].

For a long period of time propofol has been in use for total intravenous anesthesia in adults. In our literature there are no data on the use of propofol in pediatric anesthesia. The aim of the study was to compare effects of propofol for the induction of anesthesia, maintenance and recovery after anesthesia, with barbiturate, that is, inhalation anesthesia during spontaneous breathing. 50 children underwent propofol anesthesia. A control group comprised 50 children who underwent thiopentone and halothane anesthesia. The average propofol dose was 2.38 mg/kg/tt. Monitoring of cardiovascular parameters revealed statistically significant variations in systolic and diastolic pressure in both groups, but a more significant decrease was recorded in the propofol group. The decrease, recorded only during the initiation of anesthesia, stabilized afterwards. Side effects (pain during the initiation, apnea, spontaneous movements) were present in the propofol anesthesia, while in the halothane group they were reduced. In the propofol group period of recovery was short, indicating advantages of this anesthetic in day care centers.

Adolescent↗
PubMed1993

The initial clinical experience of 1819 physicians in maintaining anesthesia with propofol: characteristics associated with prolonged time to awakening.

In October 1989, propofol underwent Phase IV Food and Drug Administration testing that involved 25,981 patients, 1722 institutions, and 1819 anesthesiologists. Participants were 18-80 yr of age and ASA physical status I-III; they could not have a continuing pregnancy or prior adverse anesthetic experience. Anesthesiologists completed detailed forms to describe their use of propofol in this three-step study: propofol for induction only (Step 1), for induction and then maintenance by intermittent bolus injection (Step 2), or for continuous infusion (Step 3). In early 1992, our group of anesthesiologists and epidemiologists analyzed the resulting data base. We evaluated data from 14,882 patients (8095 given bolus injections and 6787 given continuous infusion) to determine factors predicting prolonged time (> 15 min after cessation of all anesthesia) to awakening, one measure of recovery from anesthesia. The incidence of prolonged awakening was 6.8% (1016 patients); the median and mean (+/- SD) times to awakening were, respectively, 5 min and 7.2 +/- 7.3 min. The following variables were associated (P < 0.05) with prolonged awakening from propofol maintenance anesthesia: a total dose of propofol > 8 mg/kg, male gender, endotracheal intubation, age > 65 yr, abdominal surgery, continuous infusion of propofol, and concomitant use of isoflurane or benzodiazepines. These results support the clinical impression that recovery from propofol anesthesia is remarkably rapid; although the vast majority of physicians participating in this study were using propofol for maintenance for the first time, only 6.8% of patients had awakening times exceeding 15 min.

Adolescent↗
PubMed1993

[Propofol versus diazepam. Sedation in ophthalmologic surgery under local anesthesia].

This prospective study was designed to evaluate the sedative effect of two different anaesthetic drugs in patients undergoing ophthalmic surgery. Propofol is an intravenous hypnotic agent with a short half-life of about 30 min. A constant high oxygen saturation in continuous pulse oximetry was achieved in previous studies using propofol for sedation. Furthermore, an IOP-lowering effect was proved. Propofol was compared to diazepam, a well-established sedative, which has been used for many years for sedation of patients in local anaesthesia. METHOD. One hundred patients of comparable anaesthesiologic risk (ASA classes 2-4) undergoing identical surgical procedures received either propofol (n = 50), or diazepam (n = 50). Propofol was infused at a rate of 0.8-3.0 mg/kg/h, while diazepam was given as a slow intravenous bolus of 5 mg before surgery. All patients were monitored by continuous pulse oximetry. RESULTS. Oxygen saturation of patients receiving propofol was never less than 96%. In contrast, oxygen saturation of patients sedated by diazepam dropped to 85%, especially for the first 5 min following administration, before improving to 95% during the next 10 min. None of the patients who received propofol showed signs of motor unrest, a great handicap in ophthalmic surgery, while four patients who received diazepam were restless enough to hamper the procedure. None of the patients who received propofol developed respiratory depression. In contrast, marked respiratory depression, motor agitation, and postoperative fatigue slowing mobilization were common in patients who received diazepam.

Aged↗
PubMed1995

The pulmonary vascular response to propofol in the isolated perfused rat lung.

This study investigated the effect of propofol on the pulmonary vascular bed of the rat. Propofol (5 x 10(-6) to 5 x 10(-4) M) did not alter the basal perfusion pressure in isolated rat lungs perfused at a constant flow (0.03 mL g body wt-1 min-1) with Krebs-Henseleit solution. When perfusion pressure was elevated by raising the K+ concentration to 30 mM (depolarizing Krebs-Henseleit solution), propofol decreased it in a concentration-dependent manner. Indomethacin (3 x 10(-6) M) and NG-nitro-L-arginine methyl ester (10(-4) M) did not affect the response to propofol, which excluded the role of cyclo-oxygenase metabolites and nitric oxide, respectively. The ATP-sensitive K+ (K+ATP) channel blocker glibenclamide (3 x 10(-6) and 10(-5) M) inhibited the vasodilator effect of propofol. When lungs were perfused with Ca(2+)-free depolarizing Krebs-Henseleit solution, 0.1-2.5 mM Ca+2 produced a concentration-dependent pressor response. Propofol (5 x 10(-5) M) attenuated the vasopressor response to Ca2+ significantly. In conclusion, the activation of K+ATP channels is probably the major mechanism of the vasodilator effect of propofol, at clinically relevant concentrations, in the rat lung. The Ca2+ antagonistic property of propofol is evident only at higher concentrations.

Anesthetics, Intravenous↗
PubMedDate not supplied

The influence of selected antiarrhythmic drugs on the hemodynamic parameters in rabbits during anesthesia. Part I. Propofol anesthesia.

Cardiac arrhythmia can be a serious complication during general anesthesia. On the other hand, there is a need for general anesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which procainamide, N-acetyl-procainamide, verapamil and propranolol influence hemodynamic parameters of rabbits during propofol anesthesia. The experiments were performed on rabbits. Heart rate was counted from ECG. Blood pressure was measured directly in the carotid artery. Cardiac output, stroke volume, and total peripheral resistance were estimated using the method of human Cr51 albumin dilution. Hepatic blood flow was estimated after single injection of 99mTc/Sn Hepida. Renal blood flow was estimated after a single injection of 125J-hippurate. Propofol decreases renal and hepatic blood flows, decreases blood pressure and peripheral vascular resistance. Propranolol given alone or in combination with propofol decreases hepatic blood flow. The administration of antiarrhythmic drugs during propofol anesthesia decreases renal blood flow. Propofol decreases blood pressure in rabbits as a result of decreased peripheral vascular resistance. It also decreased RBF and HBF. Disadvantages of interactions of propofol and antiarrhythmic drugs concern mainly with RBF and HBF. Propranolol (given alone or in combination with propofol) strongly decreases HBF. NAPA given during P anesthesia exerts a weaker effect on HBF. The administration of antiarrhythmic drugs during propofol anesthesia decreases RBF. The strongest disadvantageous action is exerted by propranolol, the slightest one--by verapamil.

Anesthetics, Intravenous↗
PubMed1996

Comparative responses to propofol anaesthesia alone and with alpha 2-adrenergic medications in a canine model.

Cardiovascular and pulmonary effects of propofol, a relatively new nonbarbiturate intravenous anaesthetic, were assessed and compared in 22 male and female dogs. Dogs in group 1 did not receive any premedication prior to 6.6 mg/kg IV propofol, group 2 was premedicated with atropine (0.02 mg/kg IM) and the alpha 2-agonist medetomidine (10 micrograms/kg IM), and group 3 received the same premedication agents as group 2, but the medetomidine effects were reversed by the alpha 2-antagonist atipamezole (30 micrograms/kg IV) after 30 min of anaesthesia. Each dog in groups 2 and 3 received a propofol induction dose of 2.2 mg/kg IV. The anaesthetic duration was shortest with propofol alone and prolonged with medetomidine as a premedication which was reversible with atipamezole. In group 1, the most prominent effects were a temporary drop in diastolic arterial blood pressure (26% and 24%) at 2 and 5 min post-propofol, respectively and a drop in respiratory frequency (41%) 2 min after propofol induction. Similar respiratory depression was observed in groups 2 and 3 (20% and 48%, respectively) at the same time. Apnea was not observed. An increase in systemic arterial blood pressure was observed throughout the trial in groups 2 and 3 until dogs recovered or were reversed with atipamezole. Medetomidine significantly reduces propofol dosage requirements. Safe and effective injectable anaesthesia was produced by propofol in this group of dogs. The frequency of respiratory depression would suggest in clinical usage, the practitioner should be aware oxygen supplementation is the treatment of choice should apnea occur.

Adjuvants, Anesthesia↗
PubMed1996

[A comparative study of the use of sevoflurane and propofol in ambulatory surgery].

UNLABELLED: Cost-containment strategies increase the demand for day-case surgery. In outpatients, a short time of stay in the post-anaesthesia care unit and a short interval to discharge home are of great importance. After general anaesthesia, mental and psychomotor functions are impaired to varying degrees by different anaesthetics. Therefore, the choice of anaesthetic may influence the discharge times of outpatients. In this study, the recovery characteristics of sevoflurane versus propofol anaesthesia were compared in adult outpatients. METHODS: With ethics committee approval and written informed consent, a total of 50 patients undergoing day-case ophthalmological or urological surgery were randomised into two groups. After a priming dose of vecuronium 0.015 mg/kg, anaesthesia was induced in all patients with propofol 2.0-2.5 mg/kg and fentanyl 2 micrograms/kg. Suxamethonium 1 mg/kg was used to provide muscle relaxation for endotracheal intubation. According to the randomisation, anaesthesia was maintained with either sevoflurane 1-3 vol.% (group 1, n = 25) or propofol (group 2, n = 25). The immediate postoperative recovery was assessed by the time to the appropriate response to different verbal commands. The quality of the overall postoperative recovery was classified by visual analogue scales, the digit-symbol substitution test (DSST), a modified Aldrete score, and the time until the ability to sit upright and walk. Overall side effects and postoperative behaviour were evaluated by a telephone interview on the day after surgery. RESULTS: Neither the study groups nor the duration of surgical procedures differed significantly. The total doses of anaesthetic used were 1.7 +/- 1.1 MAC-h sevoflurane and 631 +/- 261 mg propofol, respectively. The time intervals from the end of anaesthesia to extubation of the trachea were significantly shorter after sevoflurane than after propofol (6.6 +/- 2 min vs. 9.8 +/- 6 min). Similar results were obtained for the intervals to eye opening (7.2 +/- 2 min vs. 12.6 +/- 9 min) and hand squeezing (8 +/- 2 min vs. 13.8 +/- 11 min). The recovery of cognitive functions was significantly faster after sevoflurane when compared to propofol as evidenced by the DSST. The modified Aldrete score was significantly better in the sevoflurane group at all assessment times. Except for 30 min after anaesthesia, when sevoflurane patients complained of significantly more nausea, VAS scores were not different. No significant difference in the ability to sit and walk was found. The side effects did not differ between both groups. CONCLUSION: The results indicate that in urological and ophthalmological day surgery, the early recovery and the return of mental and psychomotor function in the first 60 min after anaesthesia is faster following sevoflurane than after propofol. No differences in ambulation times became evident. Sevoflurane may offer clinical advantages over propofol when used for maintenance of anaesthesia during outpatient surgical procedures.

Adult↗
PubMed1996

Effectiveness of a manually controlled infusion scheme of propofol and alfentanil mixture for endotracheal intubation in hypertensive patients: in comparison with thiamylal and nifedipine plus thiamylal.

BACKGROUND: Bolus administration of propofol for induction causes hypotension, especially in elderly hypertensive patient. Carefully titrated infusion of propofol minimizes adverse effects, such as hypotension, and permits a rapid recovery of its central effects. The objective of this study was to investigate the effect of a manually controlled infusion scheme of propofol and alfentanil mixture on hemodynamic stability during induction and endotracheal intubation for hypertensive patient. At the same time, the effectiveness of this scheme was compared with two other induction regimens (thiamylal or nifedipine plus thiamylal). METHODS: Sixty hypertensive patients undergoing orthopedic surgery were randomized into 3 groups (n = 20 per each group), None of the patients received premedication. Anesthesia was induced in group 1 (G1) with alfentanil 10 micrograms/kg. 30 s later, manual infusion of a mixture of propofol (10-12 mg/kg/h) and alfentanil (25 micrograms/kg/h) was performed for 2 min, followed by atracurium (5 mg) and propofol (1-1.5 mg/kg) as a bolus induction dose over 20 s, and then Suxamethonium (1.5 mg/kg) at 30-40 s later. Intubation was done while giving a continuous infusion of propofol and alfentanil. After intubation, the infusion rate was adjusted according to the blood pressure (BP) variation. Group 2 patients (G2) were induced with fentanyl (2 micrograms/kg), thiamylal (4-5 mg/kg), atracurium (5 mg) and succinylcholine (1.5 mg/kg). Induction of anesthesia in group 3 patients (G3) was the same as for G2, with additional sublingual nifedipine (1/2 capsule) 10 min prior to induction. Extra bolus dose of propofol (20 mg) or thiamylal (20 mg) was given at every 15 s if the systolic BP was still higher than 160 mmHg after induction by the above 3 regimens. The radial arterial pressure and electrocardiogram were continuously recorded for evaluation of hemodynamic changes. RESULTS: Post-intubation peak mean arterial pressure (MAP) in G1 and G3 were below to awake baseline values, while MAP of G2 was significantly higher than over awake baseline level (p < 0.001). The lowest MAP of G3 at post-intubation period before surgical stimulation were significantly lower than those of G1 and G2 (p < 0.001). Peak tachycardiac response to intubation in G2 was significantly higher than G1 (p < 0.05). After intubation, the peak rate pressure product were significantly higher in G2 compared with that in G1 (p < 0.05) and G3 (p < 0.001). CONCLUSIONS: The proposed manual infusion scheme of propofol and alfentanil mixture performed during induction and intubation attenuated the subsequent peak pressor response to incubation and reduced the hypotensive effect, in comparison to thiamylal or thiamylal plus nifedipine treatment, during post-intubation period. The same infusion scheme also attenuated the tachycardiac response to intubation.

Aged↗
PubMed1997

[Effects of midazolam and propofol on dopamine release from rat striatal slice using a fast-cyclic voltammetry system].

In order to evaluate the difference in pharmacological mechanism between midazolam and propofol, we focused on the interaction between dopaminergic and GABAergic neurons in the striatum because of its important role in the regulation of motor system and arousal response, and examined these inhibitory effects on dopamine (DA) release induced by high-K from the rat striatal slice using the fast-cyclic voltammetry method. Between 0.1 and 200 nmol, the standard curve of DA was linear. The peak and the sensitivity of DA oxidation were different from those of norepinephrine and DA main metabolites. The dosages between 0.1 and 10 micro M of propofol significantly blocked the high-K evoked DA release, although the dosage of larger than 50 micro M of propofol potentiated DA release. In case of midazolam, the dosages between 0.1 and 50 micro M markedly suppressed DA release induced by high-K in a dose-dependent manner. The recovery time of DA release after removal of midazolam from incubation medium was longer than that seen in the treatment of propofol. In conclusion, propofol and midazolam inhibited high-K evoked DA release from striatal slice, although these efficacies were dissimilar. Furthermore the pharmacological effects of larger dosage of propofol was different from those obtained by its smaller dosages. These results suggest that the anesthetic actions of propofol and midazolam are partially related to inhibition of DA neuron A1 activity and that the excitatory symptom induced by a larger dose of propofol may be related to its potantiation of DA release.

Anesthetics, Intravenous↗
PubMed1997

Cardiopulmonary and anesthetic effects of propofol in wild turkeys.

OBJECTIVE: To determine safety, anesthetic variables, and cardiopulmonary effects of i.v. infusion of propofol for induction and maintenance of anesthesia in wild turkeys. ANIMALS: 10 healthy, adult wild turkeys. PROCEDURE: Anesthesia was induced by i.v. administration of propofol (5 mg/kg of body weight) over 20 seconds and was maintained for 30 minutes by constant i.v. infusion of propofol at a rate of 0.5 mg/kg/min. Heart and respiratory rates, arterial blood pressures, and arterial blood gas tensions were obtained prior to propofol administration (baseline values) and again at 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes after induction of anesthesia. All birds were intubated immediately after induction of anesthesia, and end-tidal CO2 concentration was determined at the same time intervals. Supplemental oxygen was not provided. RESULTS: Apnea was observed for 10 to 30 seconds after propofol administration, which induced a decrease in heart rate; however, the changes were not significant. Compared with baseline values, respiratory rate was significantly decreased at 4 minutes after administration of propofol and thereafter. Systolic, mean, and diastolic pressures decreased over the infusion period, but the changes were not significant. Mean arterial blood pressure decreased by 30% after 15 minutes of anesthesia; end-tidal CO2 concentration increased from baseline values after 30 minutes; PO2 was significantly decreased at 5 minutes after induction and thereafter; PCO2 was significantly (P < 0.05) increased after 15 minutes of anesthesia; and arterial oxygen saturation was significantly (P < 0.05) decreased at the end of anesthesia. Two male turkeys developed severe transient hypoxemia, 1 at 5 and the other at 15 minutes after induction. Time to standing after discontinuation of propofol infusion was 11 +/- 6 minutes. Recovery was smooth and unremarkable. CONCLUSION: Propofol is an effective agent for i.v. induction and maintenance of anesthesia in wild turkeys, and is useful for short procedures or where the use of inhalational agents is contraindicated.

Anesthesia, Intravenous↗
PubMed1998

[The duration of action of vecuronium is unchanged when administered with propofol].

We examined the difference in the duration of action of vecuronium injected through a venous line infused with propofol and the duration of vecuronium infused into another venous line without propofol, in order to investigate the interaction between vecuronium and propofol within the intravenous lines. The subjects of the study are 8 patients, (ASA grade 1 or 2, aged from 20 to 50 years, 6 males and 2 females), who had undergone elective operations under general anesthesia. The mean duration of action of vecuronium injected through the venous line infused with propofol was 32.3 +/- 9.0 (min), while that for vecuronium injected through the venous line without propofol was 32.1 +/- 8.6 (min). There was no significant difference in the duration of action of vecuronium between the two conditions. We conclude that since vecuronium can be injected through the venous lines infused with propofol without interaction, there is no need for an additional venous line without propofol when vecuronium is administered under propofol anesthesia.

Adult↗
PubMed1998

Long-term continuous infusion of propofol as a means of sedation for patients in intensive care unit: relationship between dosage and serum concentration.

BACKGROUND: We studied the effect of long-term continuous propofol infusion in patients who were utilizing mechanical ventilation in intensive care unit. The purpose of our study was to identify the appropriate dosage of propofol and to monitor the relating serum level that would provide satisfactory sedative and hypnotic effects to the patients, i.e., to procure a Ramsay Sedation Scale (RSS) value between 2 and 3. METHODS: Ten mechanically ventilated ICU patients were studied. The syringe pump was set to deliver propofol at a rate of 1 mg/kg/h without an initial loading dose. After continuous infusion of propofol for 24 h, in each patient 5 ml of whole blood was sampled daily for one week. All samples were analyzed for serum level of propofol by high performance liquid chromatography. RESULTS: When the Ramsay Sedation Scale (RSS) value was between 2 and 3, the mean dosage of infused propofol was 0.71 +/- 0.31 mg/kg/h (ranging from 0.58 to 1.27 mg/kg/h) and the mean plasma concentration was 0.58 +/- 0.22 microgram/ml (ranging from 0.20 to 0.86 microgram/ml). The lipid serum level was measured in three patients whose infusion duration was greater than 14 days. The respective level was 321 mg/dl, 139 mg/dl, and 99 mg/dl. The first patient died from multiple organ failure as a result of multiple trauma. Four patients simultaneously received infusion of propofol and muscle relaxant. CONCLUSIONS: We concluded that propofol infusion given at a rate of 0.71 +/- 0.31 mg/kg/h and a plasma concentration level of less than 1 microgram/ml would be sufficient to produce a sedation with RSS value between 2 and 3.

Adult↗
PubMed1999

Cardiac effects of propofol and its interaction with autonomic nervous system in isolated, cross-circulated canine atria.

PURPOSE: The effects of propofol on sinoatrial pacemaker activity and myocardial contractility and its interaction with the autonomic nervous system were investigated in isolated, cross-circulated right atrial canine preparations. METHODS: An isolated right atrial preparation was perfused with heparinized arterial blood from an anesthetized support dog and changes in atrial rate and atrial contractile force were recorded. RESULTS: Propofol (30-1000 microg) and thiopental (30-1000 microg), injected into the sinus node artery of the isolated atrium, induced dose-dependent decreases in atrial rate and contractile force. The negative chronotropic and inotropic effects of propofol were greater than those of thiopental. The propofol-induced negative chronotropic and inotropic responses were not inhibited by atropine. Propofol had no effects on the cardiac responses to acetylcholine, norepinephrine, and the intracardiac parasympathetic nerve stimulation which activates ganglionic nicotinic acetylcholine receptors. CONCLUSION: These results indicate that: (a) propofol directly depresses sinoatrial pacemaker activity and myocardial contractility, (b) the negative chronotropic and inotropic effects of propofol do not involve activation of muscarinic receptors, and (c) propofol has little interaction with the autonomic nervous system at the effector site.

Journal Article↗
PubMed2002

Flumazenil reduces the hypnotic dose of propofol in male patients under spinal anesthesia.

PURPOSE: Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia. METHODS: After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 microg.kg(-1), followed by the administration of saline or midazolam, 10 microg.kg(-1). Then, 250 microg.kg(-1).min(-1) of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration. RESULTS: Flumazenil significantly decreased the dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 +/- 10 [mean +/- SD] vs 71 +/- 14 mg and 212 +/- 42 vs 268 +/- 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 +/- 0.5 and 2.5 +/- 0.6 microg.ml(-1), respectively; P < 0.05). CONCLUSION: These results suggested that flumazenil may potentiate the hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced hypnotic activity of propofol induced by the coadministration of midazolam.

Journal Article↗
PubMed1997

The use of propofol for induction of anaesthesia in dogs premedicated with acepromazine, butorphanol and acepromazine-butorphanol.

Cardiovascular, pulmonary and anaesthetic-analgesic responses were evaluated in 18 male and female dogs to determine the effect of the injectable anaesthetic propofol used in conjuction with acepromazine and butorphanol. The dogs were randomly divided into three groups. Dogs in Group A were premeditated with 0.1 mg/kg of intramuscular acepromazine followed by an induction dose of 4.4 mg/kg of intravenous propofol; Group B received 0.2 mg/kg of intramuscular butorphanol and 4.4 mg/kg of intravenous propofol; dogs in Group AB were administered a premeditation combination of 0.1 mg/kg of intramuscular acepromazine and 0.2 mg/kg of intramuscular butorphanol, followed by induction with 3.3 mg/kg of intravenous propofol. The induction dose of propofol was given over a period of 30-60 seconds to determine responses and duration of anaesthesia. Observations recorded in the dogs included heart and respiratory rates, indirect arterial blood pressures (systolic, diastolic and mean), cardiac rhythm, end-tidal CO, tension, oxygen saturation, induction time, duration of anaesthesia, recovery time and adverse reactions. The depth of anaesthesia was assessed by the response to mechanical noxious stimuli (tail clamping), the degree of muscle relaxation and the strength of reflexes. Significant respiratory depression was seen after propofol induction in both groups receiving butorphanol with or without acepromazine. The incidence of apnea was 4/6 dogs in Group B, and 5/6 dogs in Group AB. The incidence of apnea was also correlated to the rate of propofol administration. Propofol-mediated decreases in arterial blood pressure were observed in all three groups. Moderate bradycardia (minimum value > 55 beats/min) was observed in both Groups B and AB. There were no cardiac dysrhythmias noted in any of the 18 dogs. The anaesthetic duration and recovery times were longer in dogs premeditated with acepromazine/butorphanol.

Journal Article↗