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PubMed2002

Oral clonidine premedication reduces the awakening concentration of propofol.

UNLABELLED: To investigate the effects of oral clonidine premedication on emergence from propofol/fentanyl anesthesia, we studied 72 healthy male patients who were undergoing elective orthopedic surgery: the Control group, the 2.5 microg/kg Clonidine group, and the 5.0 microg/kg Clonidine group (n = 24 each). Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was orally administered 90 min before the induction of anesthesia in the Clonidine groups. Patients were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with the three groups receiving the same concentrations of propofol (3 microg/mL) and fentanyl (1 ng/mL) starting 20 to 30 min before the end of surgery. Propofol infusion was then abruptly discontinued at the end of surgery in all patients. After propofol was discontinued, the response to verbal commands was evaluated every 30 s, and arterial blood samples for propofol and clonidine concentrations were taken when the patients opened their eyes. The time required to respond to a verbal command was 14.9 plus/minus 8.3 min for the 5.0 microg/kg Clonidine group, and this was significantly longer than the Control (8.2 plus/minus 5.0 min) and the 2.5 microg/kg Clonidine (9.0 plus/minus 3.7 min) groups (P < 0.01). Serum propofol concentration at awakening in the 5.0 microg/kg Clonidine group was 1.0 plus/minus 0.4 microg/mL, which was significantly smaller than the Control (1.6 plus/minus 0.4 microg/mL) and the 2.5 microg/kg Clonidine (1.4 plus/minus 0.3 microg/mL) groups (P < 0.01). The blood clonidine concentration was associated with a decrease in the awakening propofol concentration. In conclusion, 5 microg/kg oral clonidine premedication decreases the awakening propofol concentration and delays arousal from propofol/fentanyl anesthesia. IMPLICATIONS: Preanesthetic medication with 5 microg/kg oral clonidine, but not 2.5 microg/kg clonidine, is associated with prolonged recovery from propofol/fentanyl anesthesia.

Administration, Oral↗
PubMed2002

The interaction between propofol and clonidine for loss of consciousness.

UNLABELLED: Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics. Clonidine also reduces the induction dose of IV anesthetics. There is no information, however, regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness, and the interaction between propofol and clonidine. We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5. 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients: Control (n = 35), 2.5 microg/kg Clonidine (n = 36), and 5.0 microg/kg Clonidine (n = 36) groups. Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was administered orally 90 min before the induction of anesthesia in the Clonidine groups. After equilibration between the blood and effect-site for 15 min, a verbal command to open their eyes was given two times to the patients. Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given. Measured serum propofol concentrations in equilibrium with the effect-site at which 50% of the patients did not respond to verbal commands (EC50 for loss of consciousness) were determined by logistic regression. The EC50 +/- SE values in the Control, 2.5 microg/kg Clonidine, and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18, 1.31 +/- 0.12, and 0.91 +/- 0.13 microg/mL, respectively. The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group (P < 0.001). The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness. These results indicate that propofol and clonidine act additively for loss of consciousness. IMPLICATIONS: Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness.

Administration, Oral↗
PubMed2002

Mild core hypothermia and anesthetic requirement for loss of responsiveness during propofol anesthesia for craniotomy.

UNLABELLED: Mild hypothermia may be induced during neurosurgery for brain protection. However, its effect on propofol requirement has not been defined. Accordingly, we tested the hypothesis that 3 degrees C of core hypothermia decreases the propofol blood concentration at which patients respond to command (CP50-awake) in neurosurgical patients. Forty patients were anesthetized with alfentanil 50 microg/kg i.v., nitrous oxide, propofol target-controlled infusion, and rocuronium. The bispectral index (version 3.12) was monitored continuously. Patients were randomized to a core temperature of 34 degrees C or 37 degrees C. At the end of surgery, neuromuscular blockade was reversed, nitrous oxide was ceased, and propofol was infused to achieve a blood target determined by the previous patient's response. Responsiveness to command was assessed 15 min later. Results were analyzed with logistic regression models; P < 0.05 was considered statistically significant. The CP50-awake of propofol was 3.05 microg/mL (95% confidence interval, 2.34-3.66). Propofol concentration, but not core temperature, predicted loss of response to command (odds ratio, 11.76; 95% confidence interval, 2.40-57.63; P < 0.01). Core temperature did not alter the relationship between bispectral index and response to command. Propofol infusion regimens may not require adjustment during mild hypothermia. IMPLICATIONS: Neurosurgical patients may be allowed to become mildly hypothermic during anesthesia in an effort to provide brain protection. Propofol maintenance infusion doses may not require adjustment in these patients.

Adult↗
PubMed1991

Peripheral vascular effects of thiopental and propofol in humans with artificial hearts.

The peripheral vascular effects of thiopental 5 mg/kg and propofol 2.5 mg/kg were compared in five patients whose lungs were being ventilated and in whom a Jarvik-7 artificial heart had been implanted. The patients were monitored, using catheters that had been surgically inserted into the radial artery, the right and left atria, and the pulmonary artery. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient received both drugs, with the interval between each drug ranging from 16 to 28 h. Hemodynamic parameters and catecholamine and atrial natriuretic peptide plasma concentrations were measured before drug administration and 5, 10, 15, 30, and 45 min later. Both drugs significantly decreased arterial pressure, systemic vascular resistance index, pulmonary arterial pressure (PAP), and right and left atrial pressures (RAP and LAP, respectively). However, propofol 2.5 mg/kg induced a significantly greater and more prolonged decrease in arterial pressure, systemic vascular resistance index, and RAP than that after administration of thiopental 5 mg/kg (P less than 0.05). Five minutes after drug injection, mean arterial pressure decreased by 21% after thiopental and by 39% after propofol (P less than 0.01); systemic vascular resistance index decreased by 21% after thiopental and by 44% after propofol (P less than 0.05); RAP decreased by 20% after thiopental and by 50% after propofol (P less than 0.05); mean PAP decreased by 18% after thiopental and by 32% after propofol (P less than 0.09); and LAP decreased by 40% after thiopental and by 46% after propofol (P less than 0.2). With both drugs, atrial natriuretic peptide, norepinephrine, and epinephrine plasma concentrations remained stable throughout the study period. Because cardiac output was maintained constant throughout the study, these results suggest that propofol 2.5 mg/kg is a more potent vasodilator of venous and arterial beds than is thiopental 5 mg/kg.

Adult↗
PubMed1992

Subhypnotic doses of propofol relieve pruritus induced by epidural and intrathecal morphine.

We investigated the efficacy of subhypnotic doses of propofol for spinal morphine-induced pruritus in a prospective, randomized, double-blind, placebo-controlled study. Fifty patients, ASA physical status 1-3, with spinal morphine-induced pruritus were allocated to receive either 1 ml propofol (10 mg) or 1 ml placebo (Intralipid) intravenously after gynecologic, orthopedic, thoracic, or gastrointestinal surgery. In the absence of a positive response, a second drug treatment was given 5 min later. The persistence of pruritus 5 min after the second treatment dose was considered a treatment failure. All failures then received, in an open fashion, a supplementary dose of propofol (10 mg) and were reevaluated 5 min later. Both groups were well matched. The success rate was significantly greater in the propofol group (84%) than in the placebo (16%) group (P less than 0.05). Ninety percent of the treatment failures in the placebo group were successfully treated by a supplementary dose of 10 mg propofol. Eight percent of the patients (4% in each group) were resistant to all treatments, including naloxone 0.08 mg intravenously. Three patients had a slight increase in sedation in the propofol group versus none in control (not significant). The beneficial effect of treatment was longer than 60 min in 85% of patients in the propofol group and in 100% of the controls (not significant). These results suggest that propofol in a subhypnotic dose is an efficient drug treatment for spinal morphine-induced pruritus. At the dose administered (10 mg), side effects were rare and minor.

Adult↗
PubMed1992

The general anesthetic potency of propofol and its dependence on hydrostatic pressure.

Although plasma concentrations of propofol during anesthesia are well known, the free concentration remains unknown because of uncertainties regarding plasma protein binding, interaction with other protein-bound substances, the level of binding to its lipid carrier, and the use of adjuvants. At elevated surrounding pressure, all general anesthetics require higher concentrations to reach adequate levels of anesthesia. To determine the anesthetic potency of propofol at equilibrium conditions and to study the effects of pressure on propofol-induced anesthesia, Rana pipiens tadpoles were exposed to different concentrations of pure, not emulsified, propofol in aqueous solution. Anesthesia was defined as loss of the righting reflex. Ten animals per concentration were used, and each experiment was conducted twice. Pressure experiments were performed with nonanesthetized tadpoles and urethane-anesthetized tadpoles as control groups. Propofol concentrations were measured spectrophotometrically. At 1 atmosphere absolute (atm abs), a semilogarithmic sigmoidal concentration-response curve was obtained with a half-maximal effect of propofol at 2.2 +/- 0.22 microM (EC50; mean +/- SE). Increased pressure shifted the concentration-response curve to the right. The EC50 increased linearly with increasing pressure up to 121 atm abs (EC50 at 121 atm abs = 4.1 +/- 0.41 microM). For pressure greater than 121 atm abs, an increased excitability of the tadpoles made it difficult to distinguish the righting reflex from involuntary movements. The saturated solubility of propofol in aqueous solution was found to be 1.0 +/- 0.02 mM (mean +/- SD), and the octanol/water partition coefficient was 4,300 +/- 280. Propofol adhered to the correlation between anesthetic potency and octanol/water partition coefficient exhibited by other general anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1993

Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study.

BACKGROUND: The pharmacokinetic and pharmacodynamic properties of propofol indicate that this may be an appropriate agent for induction and maintenance of anesthesia in obese patients. This study was designed to assess the rates of recovery and the pharmacokinetics of propofol infusions in morbidly obese patients. METHODS: Anesthesia was induced and maintained using a stepwise infusion regimen of propofol in eight morbidly obese patients. The patients' lungs were ventilated with nitrous oxide:oxygen (66:34%). Pharmacokinetic parameters were calculated from iterative blood sampling during the propofol infusion and during 8 h after its completion. RESULTS: Results were compared with those from a concurrent study of propofol pharmacokinetics in nonobese adults. The initial volume of distribution of propofol was not modified in obese patients. Total body clearance increase was correlated to body weight (R = 0.76, 25.4 +/- 6.5 ml.kg-1.min-1, mean +/- SD). Volume of distribution at steady state was also correlated to body weight (R = 0.61, 1.63 +/- 0.54 l.kg-1, mean +/- SD). Propofol concentration at the time of eye opening in response to verbal command was 0.94 +/- 0.26 mg.l-1. CONCLUSIONS: Results from this study confirm the absence of propofol accumulation in morbidly obese patients when the current dosing scheme is used. Dosing schemes expressed in mg.kg-1 are the same as those in normal patients.

Adult↗
PubMed1993

Effect of propofol infusion on splanchnic hemodynamics and liver oxygen consumption in the rat. A dose-response study.

BACKGROUND: Propofol has been used for the maintenance of anesthesia. The effects of propofol infusion on splanchnic hemodynamics and liver oxygen consumption, however, have not been reported. In the current investigation, the authors studied the effects of a continuous infusion of propofol on systemic and splanchnic hemodynamics using a new method to measure liver oxygen consumption in awake control and anesthetized rats. METHODS: Cannulas were inserted into the left ventricle, femoral artery, portal vein, and hepatic vein during ether anesthesia, and the rats were allowed to awaken and recover for 3-4 h before study. Animals were infused for 30 min with either saline (controls) or propofol at a rate of 300, 600, 900, or 1,200 micrograms.kg-1 x min-1. Cardiac output and organ blood flows were measured using radiolabelled microspheres, and blood samples from the femoral artery, portal vein, and hepatic vein were used to determine liver oxygen consumption. RESULTS: Mean arterial pressure decreased in a dose-dependent manner with a 25% reduction at the highest infusion rate. Systemic vascular resistance similarly decreased, whereas cardiac output remained unchanged at all the infusion rates. Hepatic arterial blood flow increased in a dose-dependent fashion over the dose range studied, to a maximum increase of 120%. Portal tributary blood flow increased by 30% at the highest infusion rate. Total liver blood flow increased in a dose-dependent manner to a maximum of 38%. Total oxygen delivery to the liver by the hepatic artery and portal vein increased in a dose-dependent fashion. Liver oxygen consumption increased in a dose-dependent fashion to a maximum increase of 51% at an infusion rate of 1,200 micrograms.kg-1 x min-1. The percent of oxygen extracted by the liver was not altered by propofol infusion, and hepatic venous oxygen saturation did not decrease at any dose studied. Coronary and renal blood flows were not altered. Arterial PaCO2, increased from 31 +/- 2 mmHg in awake control rats to 41 +/- 2 mmHg in spontaneously breathing rats infused with 1,200 micrograms.kg-1 x min-1 propofol. CONCLUSIONS: The maintenance of anesthesia using an infusion of propofol resulted in an increase in liver oxygen consumption that was fully compensated for by an increase in oxygen delivery to the liver. Splanchnic hemodynamics and liver oxygenation are not adversely affected during maintenance of anesthesia with propofol in the normal rat.

Animals↗
PubMed1994

Relative potency of eltanolone, propofol, and thiopental for induction of anesthesia.

BACKGROUND: The primary purpose of this investigation was to determine the relative potency of eltanolone, a new steroid hypnotic, and propofol and thiopental when used for induction of general anesthesia. In addition, the induction characteristics of propofol and eltanolone were compared. METHODS: One hundred seventy-five patients, premedicated with lorazepam 1 mg orally, randomly received one of six different doses of either eltanolone or propofol. The probability of successful induction (defined as not responsive to verbal commands within 2 min) was related to the logarithm of the dose for each drug by means of logistic regression analysis. Estimates of ED50 and ED95 for each drug were obtained. The incidence of side effects was compared for eltanolone and propofol. The potency of thiopental was determined in a parallel study, using an identical methodology in 105 patients receiving one of seven different doses of the barbiturate. RESULTS: The relative potency of eltanolone was 3.2 times (95% confidence interval 2.7-3.8) greater than propofol and 6.0 times (5.3-6.9) greater than thiopental. ED50 and ED95 values for eltanolone were 0.46 (0.40-0.52) and 0.82 (0.68-1.28) mg.kg-1, respectively. Compared to propofol, induction of anesthesia with eltanolone is characterized by a lower incidence of injection pain (3.5% vs. 58%) and apnea (1.2% vs. 11.2%). CONCLUSIONS: Eltanolone appeared to be an effective induction agent that is 3.2 times more potent than propofol and 6 times more potent than thiopental. Its use was associated with less pain on injection than was propofol.

Adolescent↗
PubMed1994

The pharmacokinetics of propofol in children using three different data analysis approaches.

BACKGROUND: Accurate dosing of propofol in children requires accurate knowledge of propofol pharmacokinetics in this population. Improvement in pharmacokinetic accuracy may depend on the incorporation of individual patient factors into the pharmacokinetic model or the use of population approaches to estimating the pharmacokinetic parameters. We investigated whether incorporating individual subject covariates (e.g., age, weight, and gender) into the pharmacokinetic model improved the accuracy. We also investigated whether the use of a mixed-effects population model (e.g., the computer program NONMEM) improved the accuracy of the pharmacokinetic model beyond the accuracy obtained with models estimated using two simple approaches. METHODS: We studied 53 healthy, unpremedicated children (28 boys and 25 girls) ranging from 3 to 11 yr of age. Twenty children only received an initial loading dose of 3 mg/kg intravenous propofol. In the remaining 33 children, an initial intravenous propofol dose of 3.5 mg/kg was followed by a propofol maintenance infusion. Six hundred fifty-eight venous plasma samples were gathered and assayed for propofol concentrations. Three different regression techniques were used to analyze the pharmacokinetics: the "standard two-stage" approach, the "naive pooled-data" approach, and the nonlinear mixed-effects modeling approach (as implemented in NONMEM). In both the pooled-data and mixed-effects approaches, individual covariates (age, weight, height, body surface area, and gender) were added to the model to examine whether they improved the quality of the fit. Accuracy of the model was measured by the ability of the model to describe the observed concentrations. RESULTS: The pharmacokinetics of propofol in children were best described by a three-compartment pharmacokinetic model. There were no appreciable differences among the pharmacokinetics estimated using the two-stage, pooled-data, and mixed-effects approaches. Weight was a significant covariate, and the weight-proportional model was supported by all three regression approaches. The pharmacokinetic parameters of the weight-proportional pharmacokinetic model (pooled-data approach) were: central compartment (V1) = 0.52 1 x kg-1; rapid-distribution compartment (V2) = 1.01 x kg-1; slow-distribution compartment (V3) = 8.2 1 x kg-1; metabolic clearance (Cl1) = 34 ml.kg-1 x min-1; rapid-distribution clearance (Cl2) = 58 ml.kg-1 x min-1; and slow-distribution clearance (Cl3) = 26 ml.kg-1 x min-1. The inclusion of age as an additional covariate of V2 statistically improved the model, but the actual improvement in the fit was small. CONCLUSIONS: The pharmacokinetics of propofol in children are well described by a standard three-compartment pharmacokinetic model. Weight-adjusting the volumes and clearances significantly improved the accuracy of the pharmacokinetics. Adjusting the pharmacokinetics for inclusion of additional patient covariates or using a mixed-effects model did not further improve the ability of the pharmacokinetic parameters to describe the observations.

Child↗
PubMed1995

Propofol modulates the effects of chemoconvulsants acting at GABAergic, glycinergic, and glutamate receptor subtypes.

BACKGROUND: Propofol has been used to treat status epilepticus, but its use in patients with seizure disorders remains controversial, because of concerns that it produces paroxysmal motor phenomenon. Chemoconvulsants act by known discrete mechanisms and neurotransmitters, and therefore, they are useful tools for screening anticonvulsant activity. The main objective of this study was to characterize the effect of propofol pretreatment on convulsions induced by picrotoxin, bicuculline, and strychnine, all which decrease inhibitory neurotransmission, and by N-methyl-D-aspartic acid, kainic acid, and quisqualic acid, which enhance excitatory neurotransmission. METHODS: Groups of male Swiss Webster mice (n > or = 10/group) were given either vehicle (intralipid, 10 ml.kg-1, control groups) or propofol (50 mg.kg-1, test groups) injected intraperitoneally. Five min after injection, convulsions were induced with either bicuculline (1.36-5.44 nmoles), picrotoxin (0.21-1 nmol), N-methyl-D-aspartic acid (0.51-2 nmol), quisqualic acid (1-10 nmol), kainic acid (0.252-2 mole), or strychnine (1.35-10.78 nmol) injected intracerebroventricularly. The number of animals with convulsions after each dose was recorded. Analysis of statistical significance was based on the log-probit lines of the quantal dose-response for the respective control and test groups, calculated 50% effective doses (ED50), the potency ratios (ED50higher/ED50lower) and their 95% confidence limits. RESULTS: Propofol pretreatment decreased the potency ratio of both bicuculline (0.47, 95% confidence interval = 0.23-0.94) and picrotoxin (0.61, 0.47-0.79), signifying an anticonvulsant effect. Conversely, propofol pretreatment significantly enhanced the convulsive potency of kainic acid (potency ratio and 95% confidence interval = 1.66, 1.21-2.29), quisqualic acid (3.17, 1.98-5.09), and strychnine (1.76, 0.79-3.89). CONCLUSIONS: Current results suggest that propofol augments the paroxysmal motor phenomenon induced by kainic acid, quisqualic acid, and strychnine. This action may be, at least partly, responsible for the motor manifestations reported after propofol administration. These in vivo results on modulation of gamma-aminobutyric acid, glycine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptor-mediated transmission may be of significance in understanding the mechanism of propofol action at the excitatory and inhibitory amino acid receptors.

Anesthetics, Intravenous↗
PubMed1996

Pharmacokinetics of propofol after a single dose in children aged 1-3 years with minor burns. Comparison of three data analysis approaches.

BACKGROUND: No complete pharmacokinetic profile of propofol is yet available in children younger than 3 yr, whereas clinical studies have demonstrated that both induction and maintenance doses of propofol are increased with respect to body weight in this age group compared to older children and adults. This study was therefore undertaken to determine the pharmacokinetics of propofol after administration of a single dose in aged children 1-3 yr requiring anesthesia for dressing change. METHODS: This study was performed in 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 12% of total body surface area. Exclusion criteria were: unstable hemodynamic condition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg.kg(-1))plus fentanyl (2.5 microg.kg(-1)) was administered while the children were bathed and the burn area cleaned during which the children breathed spontaneously a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 microl were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4, 8, and 12 thereafter injection; an earlier sample was obtained from 8 of 12 children. The blood concentration curves obtained for individual children were analyzed by three different methods: noncompartmental analysis, mixed effects population model, and standard two-stage analysis. RESULTS: Using noncompartmental analysis, total clearance of propofol (+/-SD) was 0.053+/-0.013l.kg(-1).min(-1), volume of distribution at steady state9.5 +/- 3.7l.kg(-1),and residence time 188 +/- 85 min. Propofol pharmacokinetics were best described by a weight-proportional three-compartmental model in both population and two-stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of population versus two-stage analysis are as follow: systemic clearance 0.049 versus 0.048 l.kg(-).min(-1), volume of central compartment 1.03 versus 0.95 l.kg(-1), volume of steady state 8.09 versus 8.17 l.kg(-1). CONCLUSIONS: The volume of the central compartment and the systemic clearance were both greater than all values reported in older children and adults. This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children 1-3 yr. (Key words: Anesthesia: pediatric. Pharmacokinetics: propofol.)

Age Factors↗
PubMed1996

Multicenter study of target-controlled infusion of propofol-sufentanil or sufentanil-midazolam for coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The use of target-controlled infusions of anesthetics for coronary artery bypass graft surgery has not been studied in detail. The effects of target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were evaluated and compared. METHODS: At 14 clinical sites, 329 patients were given a target-controlled infusion of propofol (n = 165) to produce effect-site concentration (Ce) of > or = 3-micrograms/ml or a target-controlled infusion of sufentanil (n = 164). Sufentanil or midazolam, respectively, also were infused. Systolic hypertension, hypotension, tachycardia, and bradycardia were assessed by measuring heart rate and blood pressure every minute during operation. Myocardial ischemia was assessed perioperatively by monitoring ST segment deviation via continuous three-lead Holter electrocardiography, and it was evaluated during operation by monitoring left ventricular wall motion abnormality via transesophageal echocardiography. RESULTS: The measured cardiovascular parameters were satisfactory and usually similar for the patients receiving propofol-sufentanil or sufentanil-midazolam. The primary endpoint of the percentage of patients with intraoperative ST segment deviation (23 +/- 6% vs. 24 +/- 6%, P = 0.86) did not differ significantly between the two groups. The incidence of left ventricular wall motion abnormality shown on transesophageal echocardiography before (19 +/- 4% vs. 26 +/- 4%, P = 0.25) and after (23 +/- 4% vs. 31 +/- 5%, P = 0.32) cardiopulmonary bypass also did not differ significantly for the two groups. Changes in intraoperative target concentration were more frequent with propofol-sufentanil anesthetic than with sufentanil-midazolam (11.7 +/- 7.1 vs. 7.3 +/- 3.6, P < 0.001). The incidence of intraoperative hypotension (77% vs. 55%, P < 0.001), the use of inotropic/vasopressor medications (93% vs. 84%, P = 0.01), and the administration of crystalloids (2.8 +/- 1.4 L vs. 2.4 +/- 1.2 L, P < 0.001) were significantly greater in the propofol-sufentanil group. Conversely, the incidence of intraoperative hypertension (43% vs. 54%, P = 0.05) and the use of antihypertensive/vasodilator medications (70% vs. 90%, P < 0.001) were significantly less in the propofol-sufentanil group. CONCLUSIONS: Target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were suitable to provide anesthesia for coronary artery bypass graft surgery. Continuous monitoring revealed a high prevalence of hemodynamic abnormalities. Despite greater hypotension in the propofol-sufentanil group and greater hypertension in the sufentanil-midazolam group, episodes of myocardial ischemia were similar for both groups and were not temporally related to episodes of hemodynamic abnormalities.

Aged↗
PubMed1996

Double-blind, randomized comparison of ondansetron and intraoperative propofol to prevent postoperative nausea and vomiting.

BACKGROUND: Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens. METHODS: Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide-oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Group PIP received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Thirty minutes before expected skin closure, isoflurane was discontinued and 50 to 150 micrograms.kg-1.min-1 propofol was given intravenously to maintain anesthesia. Group PP received propofol for induction and maintenance of anesthesia, nitrous oxide-oxygen, and fentanyl. Postoperative pain relief was provided with morphine administered by a patient-controlled analgesia pump. The incidence of nausea and vomiting, requests for rescue antiemetic and sedation, pain scores, and hemodynamic data were recorded for 24 h. RESULTS: Within 6 h of surgery, groups O and PP had a lower incidence of nausea compared with groups PI and PIP (P < 0.05). Fewer patients in group PP (19%) vomited during the 24-h period compared with groups O (48%), PI (64%), and PIP (52%) (P < 0.05). The incidence of antiemetic use was also less in group PP (P < 0.05). Patients in group PP had lower sedation scores at 30 min and at 1 h (P < 0.05). There were no differences among the groups in pain scores, blood pressure, heart rate, respiratory rate, and incidence of pruritus. CONCLUSIONS: Propofol administered to induce and maintain anesthesia is more effective than ondansetron (with thiopental-isoflurane anesthesia) in preventing postoperative vomiting and is associated with fewer requests for rescue antiemetic and sedation in the early phase of recovery. It is equally effective in preventing postoperative nausea as ondansetron in the first 6 h after operation. Propofol used only as an induction agent or for induction and at the end of surgery were not as protective against postoperative nausea and vomiting.

Adult↗
PubMed1998

The effect of propofol on isolated human pregnant uterine muscle.

BACKGROUND: Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation. METHODS: Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 microg/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined. RESULTS: Propofol concentrations of 2.7 x 10(-6) M (0.5 microg/ml) and 1.1 x 10(-5) M (2 microg/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10(-5) M (10 microg/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension. CONCLUSIONS: These results imply that the decline in the active tension of muscle contraction was most likely caused by propofol and not by the fat emulsion. However, the propofol concentrations needed to produce a significant reduction in the uterine muscle tension appear to be much greater than the free propofol concentrations reported by others during cesarean section.

Adult↗
PubMed1998

Nefiracetam prevents propofol-induced anterograde and retrograde amnesia in the rodent without compromising quality of anesthesia.

BACKGROUND: Propofol is a short-acting intravenous anesthetic agent. However, cognitive function remains depressed for several hours thereafter. We have evaluated the ability of nefiracetam, a novel cognition-enhancing agent, to alleviate propofol-induced amnesia in a rodent model of learning. METHODS: Rats were trained in a one-trial, step-through, light-dark passive avoidance paradigm. Propofol (10 and 75 mg/kg) was administered by the intraperitoneal route at 15 min before training and separately at increasing times in the immediate 0-6 h post-training period (100 and 150 mg/kg). Nefiracetam, 9 mg/kg, was administered by the intraperitoneal route 1 h before training. Animals were tested for recall at the 12 h post-training time, and after their killing, immunocytochemistry was used to determine the increase in hippocampal neuronal polysialylation, an event associated with memory consolidation. Induction and duration of anesthesia induced by propofol was determined using tail pinch and pedal withdrawal reflexes. RESULTS: Propofol-induced anterograde amnesia occurred in a dose-dependent manner. Induction of retrograde amnesia required a higher dose of propofol, which anesthetized the animals and was effective only in the immediate 3-h post-training period. In the absence of any evident effect on the onset or duration of anesthesia, nefiracetam prevented both forms of propofol-induced amnesia and preserved the learning-associated changes of neuronal polysialylation state. CONCLUSIONS: The ability of nefiracetam to prevent propofol-induced anterograde and retrograde amnesia is proposed to be indirect and to result from modulation of gene transcription in a manner that initiates a cascade of events involving protein synthesis leading to synaptic growth associated with the formation of the long-term memory trace.

Amnesia↗
PubMed1999

Effect of nonsedative doses of propofol on an innate anxiogenic situation in rats.

BACKGROUND: The effect of propofol on anxiety has not been well studied. In humans, such investigations are confused by the fact that sedation often coexists with anxiolysis. Therefore, the authors evaluated the effects of minimal sedation with propofol in rats placed in an innate anxiogenic situation, the elevated plus-shaped maze. METHODS: In experiment 1, spontaneous locomotor activity was determined in rats as a measure of sedative effect induced by propofol (0-9 mg/kg administered intraperitoneally). In experiment 2, groups of rats received propofol (0-9 mg/kg) or diazepam (0-2 mg/kg) and then were placed on a plus-shaped maze elevated above the ground that was composed of two opposite closed arms and two opposite open arms. On an initial exposure to the maze, undrugged rats avoid the open arms, with the number of entries into and time spent within the open arms constituting approximately 20% of their total activity. This reflects normal anxiety in a rodent for any elevated open platform. RESULTS: In experiment 1, 0-9 mg/kg propofol did not alter spontaneous activity in rats. In experiment 2, propofol and diazepam significantly increased the number of entries into and the time spent within the open arms. Propofol at a dose of 9 mg/kg significantly increased the rats' level of exploration of the open arms to about 50% of all exploratory activity, and a similar observation was made with 2 mg/kg diazepam. CONCLUSIONS: In a standard animal model, propofol has anxiolytic properties at doses that do not produce sedation.

Animals↗
PubMed1999

Propofol prevents peroxide-induced inhibition of glutamate transport in cultured astrocytes.

BACKGROUND: Glutamate transporters located in the plasma membrane of cerebral astrocytes take up excitatory neurotransmitters from the synaptic cleft. In diseases characterized by oxidative stress, the extracellular glutamate concentration increases and contributes to neuronal death. The authors wanted to determine whether propofol defends brain cells against oxidant-induced changes in their transport of glutamate. METHODS: Primary cultures of rat cerebral astrocytes were exposed to tert-butyl hydroperoxide (1 mM) to serve as an in vitro model of oxidative stress. Astrocytes were incubated with propofol for 2 h and tert-butyl hydroperoxide was added for the final hour. Alternatively, astrocytes were incubated with tert-butyl hydroperoxide for 30 min and then with propofol for another 30 min. Control cells received drug vehicle rather than propofol. The rate of uptake of glutamate, the efflux of the nonmetabolizable analog D-aspartate, and the intracellular concentration of the endogenous antioxidant glutathione were measured. RESULTS: Tert-butyl hydroperoxide decreased the glutathione concentration and inhibited glutamate uptake but had a negligible effect on D-aspartate efflux. At clinically relevant concentrations, propofol did not affect the glutathione concentration but did prevent the effect of tert-butyl hydroperoxide on glutamate transport. Furthermore, the addition of propofol after tert-butyl hydroperoxide reversed the inhibition of glutamate uptake. CONCLUSIONS: Propofol prevents and reverses the inhibition of excitatory amino acid uptake in astrocytes exposed to tert-butyl hydroperoxide. The ability of propofol to defend against peroxide-induced inhibition of glutamate clearance may prevent the pathologic increase in extracellular glutamate at synapses, and thus delay or prevent the onset of excitotoxic neuronal death.

Anesthetics, Intravenous↗