Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Propofol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1998

The significance of lipoproteins in serum binding variations of propofol.

UNLABELLED: The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) and in serum samples from the following subjects: healthy normolipemic volunteers (n = 16), hyperlipidemic subjects diagnosed with familiar polygenic hypercholesterolemia (n = 26) showing high levels of cholesterol, and elderly subjects (n = 15). Protein binding was determined by using ultrafiltration, and the concentration of unbound propofol was measured by using liquid chromatography. Levels of total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alpha1-acid glycoprotein were also measured. Propofol was extensively bound to the three lipoprotein fractions (88%+/-2% to VLDL, 93%+/-1% to LDL, and 91%+/-4% to HDL). The percentage of unbound propofol was significantly decreased (P < 0.0001) in hyperlipidemic (0.88%+/-0.20%) individuals whose levels of cholesterol and triglycerides were increased versus healthy subjects (1.26%+/-0.22%), whereas no significant difference was found in the elderly group (1.12%+/-0.23%). A positive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subjects, showed that changes in the levels of total cholesterol and triglycerides explained approximately 62% of the variability in the serum protein binding of propofol. These results stress the importance of triglycerides and cholesterol in the serum protein binding of propofol. We therefore suggest that these variations in lipid levels, and consequently in protein binding, may influence anesthetic practice with propofol. IMPLICATIONS: We investigated the effect of serum lipids in the protein binding of propofol. We found that propofol binds extensively to all lipoprotein fractions. Propofol binding showed a significant relationship with the serum levels of cholesterol and triglycerides.

Adult↗
PubMed2000

The effect of propofol on angiotensin II-induced Ca(2+) mobilization in aortic smooth muscle cells from normotensive and hypertensive rats.

UNLABELLED: We studied the effect of propofol (5.6-560 micromol/L; 1-100 microg/mL) on the mechanisms involved in Ca(2+) mobilization elicited by angiotensin II (AngII) in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We studied the variations in intracellular Ca(2+) ([Ca(2+)](i)) concentrations in cultured aortic vascular smooth muscle cells (VSMCs) isolated from 6-wk-old WKY and SHR rats loaded with the Ca(2+)-sensitive fluorescent dye, Fura-2, using fluorescent imaging microscopy. In the absence of external Ca(2+), AngII (1 micromol/L) induced a transient [Ca(2+)](i) mobilization from internal stores that was larger in SHR than in WKY rats. Ca(2+) influx was assessed after external Ca(2+) (1 mmol/L) reintroduction. Propofol (1-100 microg/mL) added 5 min before the experiments did not alter AngII-induced Ca(2+) release from internal stores in either strain. By contrast, Ca(2+) influx elicited by AngII was significantly decreased by propofol. This effect occurred at a smaller concentration of propofol in the SHR than in the WKY rats. When Ca(2+) stores were depleted by exposure of cells to thapsigargin, an inhibitor of the sarcoendoplasmic reticulum Ca(2+)-ATPase, reintroduction of Ca(2+) to the medium induced a capacitative Ca(2+) influx of similar magnitude than that elicited by AngII. This influx was also significantly decreased by propofol at 100 microg/mL ( WKY: 27 +/- 3% of control values, n = 107; SHR: 16 +/- 3%, n = 47; P < 0.001). In conclusion, propofol decreased AngII-induced Ca(2+) influx through voltage-independent channels, without altering Ca(2+) release from internal stores in aortic VSMCs. The hypertensive rats were found to be more sensitive to the effect of propofol than the normotensive rats. This suggests that the response of VSMCs to AngII may be altered by propofol. IMPLICATIONS: In rat aortic vascular smooth muscle cells, propofol reduced angiotensin II-elicited Ca(2+) entry through capacitative Ca(2+) channels without altering Ca(2+) release from intracellular stores. Spontaneously hypertensive rats were more sensitive to these effects of propofol than normotensive rats. The response of vascular smooth muscle cells to angiotensin II may be altered by propofol.

Anesthetics, Intravenous↗
PubMed2001

The effects of propofol in the area postrema of rats.

UNLABELLED: Propofol has an antiemetic effect that may be mediated by gamma-aminobutyric acid (GABA) influences on the serotonin system, the mechanism of which is not known. We used three techniques, immunohistochemistry, High Performance Liquid Chromatography, and electrophysiology, to define propofol's effects on the rat's brainstem. Paired male Wistar rats received propofol, 20 mg/kg/hr, or Intralipid for 6 h. The brains were then subjected to immunohistochemical analysis of serotonin. In a separate experiment after a propofol or Intralipid infusion, cerebrospinal fluid (CSF) was extracted from the fourth ventricle and analyzed for the amount of serotonin and 5-hydroxyindoleacetic acid. Electrophysiological neuronal recordings were made in the area postrema (AP) in response to propofol with and without a GABA or serotonin antagonist. Results showed that immunohistochemical staining for serotonin in the propofol rats was significantly increased (28 +/- 12%) in the dorsal raphe and decreased in the AP (17 +/- 6%) compared with control. There were no significant changes in the isoflurane-anesthetized animals. Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth ventricle at the level of the AP were significantly reduced by 63% and 36%, respectively. Both propofol and pentobarbital injections reduce AP neuronal activity, but only the propofol response was blocked by bicuculline, a GABA antagonist. We conclude that the reduced levels of serotonin in the AP and the CSF may explain the antiemetic property of propofol. Propofol may also directly act on AP neurons via a GABA(A) receptor to reduce their activity. IMPLICATIONS: Propofol may produce its antiemetic effect by depleting the area postrema of serotonin as well as by a direct gamma-aminobutyric acid-mediated inhibition.

Anesthetics, Intravenous↗
PubMed2002

Propofol in a medium- and long-chain triglyceride emulsion: pharmacological characteristics and potential beneficial effects.

UNLABELLED: Hypertriglyceridemia is a possible unwanted effect during long-term propofol sedation while using a formulation containing long-chain triglycerides (LCT) from soybean oil. The use of propofol formulated in a solvent consisting of medium-chain triglycerides (MCT) and LCT might reduce the risk. Because a new solvent may affect the pharmacological profile of propofol, in this prospective, randomized, controlled, and double-blinded study we compared the pharmacodynamic and kinetic characteristics of propofol diluted in MCT/LCT fat solution with those of propofol formulated in LCT fat emulsion. In addition, serum triglyceride levels were measured during and after the administration of both drugs. Thirty patients likely to require mechanical ventilation over at least 48 h were randomized to receive either propofol 2% MCT/LCT (Group 1) or propofol 2% LCT (Group 2). Infusion rates of propofol (2.34 +/- 0.83 mg. kg(-1). h(-1) in Group 1 versus 2.31 +/- 0.6 mg. kg(-1). h(-1) in Group 2), the plasma propofol concentrations during infusion (0.95 +/- 0.53 versus 0.98 +/- 0.32 micro g/mL), and the concentrations and arousal behavior after discontinuation of the drug did not show significant differences. Plasma triglyceride concentrations during sedation did not differ between the groups, whereas there was a tendency toward a more rapid triglyceride elimination in Group 1 after termination of the propofol administration. IMPLICATIONS: Propofol diluted in an emulsion of medium- and long chain-triglycerides shows equivalent pharmacological properties during long-term sedation compared with its hitherto well known formulation containing long-chain triglycerides only. In addition, potential favorable effects on the plasma triglyceride profile could be found.

Adult↗
PubMed1988

Pharmacokinetics and protein binding of propofol in patients with cirrhosis.

The pharmacokinetics and protein binding of propofol were studied in ten patients with cirrhosis and in ten control patients undergoing elective surgery. All patients received 2.5 mg.kg-1 propofol as an intravenous bolus injection for the induction of anesthesia. Whole blood propofol concentrations were measured at intervals up to 12 h, using a high-performance liquid chromatography (HPLC) technique. Propofol protein binding was estimated by equilibrium dialysis 10 min after injection of propofol. Individual propofol profiles for all patients were best described by a three-compartment open mammillary model. Rapid and slow propofol distribution half-times were observed, followed by an elimination phase with a half-time of 4-5 h. Propofol total body clearance was reduced (1.99 +/- 0.68 l.min-1) in the patients with cirrhosis but did not differ significantly from that in the control patients (2.30 +/- 0.61 l.min-1). The apparent volume of distribution at steady state (Vdss) was similar in the two groups. No significant difference in elimination half-life was observed between the two groups. Propofol was extensively bound (mean: 97-98%) to the plasma protein of both cirrhotic and control groups. This study shows that propofol pharmacokinetics and protein binding of propofol following a single intravenous bolus dose were not markedly affected by uncomplicated cirrhosis of the liver.

Adult↗
PubMed1991

Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain.

The influence of propofol, a new intravenous anesthetic agent, on brain gamma-aminobutyric acid (GABA)-ergic transmission has been investigated both in vitro and in vivo. In vitro, propofol, like benzodiazepines, 1) markedly enhanced 3H-GABA binding in cortical membrane preparations; 2) potentiated muscimol-induced stimulation of 36Cl- uptake in membrane vesicle preparations (the propofol potentiating effect was antagonized by bicuculline); and 3) inhibited 35S-TBPS binding to unwashed membrane preparations from rat cerebral cortex. Finally, propofol failed to displace 3H-flunitrazepam from its binding site, indicating that its site of action in brain is different from that of benzodiazepines. In vivo, the effect of propofol was studied using single-unit recording of the electrical activity of both nondopaminergic neurons in the pars reticulata of the substantia nigra (PR neurons) and of dopaminergic neurons in the pars compacta of the substantia nigra (DA neurons). PR neurons are known to be inhibited by GABA-mimetic drugs and benzodiazepines, whereas DA neurons are tonically inhibited by PR neurons. The intravenous administration of propofol, in a fat emulsion formulation, produced a brief dose-dependent inhibition of the firing rate of PR neurons. The dose producing 50% inhibition of the firing rate was calculated to be 1.2 +/- 0.1 mg/kg. The inhibitory effect lasted less than 5 min. Repeated injections of propofol reproduced the same inhibitory response, whereas continuous infusion (0.5 mg.kg-1.min-1) produced a persistent inhibition of neuronal firing. The inhibitory effect of propofol on PR neurons was potentiated by diazepam and reversed by picrotoxin and bicuculline but was not influenced by the benzodiazepine antagonist Ro 15-1788. These findings suggest that propofol exerts a GABA-mimetic action on PR neurons by acting on a site distinct from the benzodiazepine recognition site. Unlike benzodiazepines, propofol inhibited the firing rate of DA neurons with a potency proportional to its inhibitory effect on PR neurons. The inhibition of DA neurons was reversed by bicuculline and picrotoxin. The results suggest that propofol enhances the inhibitory control over DA neurons by strionigral GABAergic neurons.

Animals↗
PubMed1991

Enhancement by propofol of epinephrine-induced arrhythmias in dogs.

Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine-induced arrhythmias in a dose-dependent manner in dogs.

Anesthesia↗
PubMed1992

Subjective and psychomotor effects of subanesthetic doses of propofol in healthy volunteers.

Propofol is increasingly being used in medical and surgical procedures in which conscious sedation of the patient is desired. The mood-altering and psychomotor effects of subanesthetic concentrations of propofol have not been well characterized. Therefore, we examined the effects of intravenous infusions of different subanesthetic doses of propofol on mood and psychomotor/cognitive performance in healthy volunteers (n = 10). A prospective, randomized, placebo-controlled, double-blind, crossover design was used in which subjects first were administered an intravenous loading dose of propofol or placebo (Intralipid) and then were infused over a 20-min period with a given dose of propofol or placebo. Each subject received placebo (Intralipid loading dose and infusion), low-dose propofol (0.08 mg/kg loading dose and 0.5 mg.kg-1.h-1 infusion), moderate-dose propofol (0.16 mg/kg loading dose and 1.0 mg.kg-1.h-1 infusion), and high-dose propofol (0.32 mg/kg loading dose and 2.0 mg.kg-1.h-1 infusion) in four sessions spaced approximately 1 week apart. Propofol induced changes in mood in a dose-related fashion. Some of these mood-altering effects lingered for as long as 30 min after termination of the infusion, but, in general mood had returned to baseline levels 1 h after termination of the infusion. Intralipid induced no changes in mood during the infusion period. Psychomotor functioning was impaired during, and anterograde amnesia was present after, the high-dose propofol infusion. These results suggest that propofol as a sedative has a spectrum of effects that are well-suited for ambulatory surgery (e.g., sedation, amnesia, and rapid and complete recovery).

Adult↗
PubMed1992

Life-threatening anaphylactoid reactions to propofol (Diprivan)

Fourteen patients who had had a life-threatening reaction within a few minutes after receiving propofol (Diprivan) were investigated for anaphylaxis 4-6 weeks after the incident. Three kinds of immunologic tests were carried out: skin tests (prick tests and intradermal tests with the drugs used and Intralipid, the solvent for propofol), a leukocyte histamine release test, and a radioimmunoassay (RIA) of immunoglobulin E (IgE) against propofol and muscle relaxants, when they had been given with propofol. It had been previously shown that these were always negative in patients anesthetized with propofol without any complications. Thirteen of the 14 patients had at least one positive test supporting hypersensitivity to propofol; 2 patients had three tests positive; 4 had two tests positive; and 7 had one test positive. The skin tests with Intralipid were negative in 4 patients whose tests with propofol were positive. Two patients who had been given muscle relaxants at the same time as the propofol had positive IgE-RIA to both drugs. In one patient, results of all the tests remained negative, and the mechanism involved in the reaction remained unidentified. It is note-worthy that 9 patients of 14 had allergic histories that were known before the anesthetic (atopy; allergy to antibiotics, muscle relaxants, lidocaine, colloids) and that none of the patients had ever received propofol or Intralipid before. It is possible that the IgE that linked abnormally with the propofol had specific binding sites for the phenyl nucleus and the isopropyl groups, which are present in propofol and many other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Vasodilation and mechanism of action of propofol in porcine coronary artery.

BACKGROUND: A decrease in myocardial perfusion pressure may reduce myocardial blood flow. However, it may not significantly affect myocardial perfusion when in presence of a concurrent coronary artery vasodilation. However, the effects of propofol in coronary arteries are not well determined. In this study, the effects of propofol on porcine coronary artery responses to vasoactive agents that operate through voltage- and receptor-mediated calcium mechanisms were investigated. METHODS: Hearts of adult pigs (n = 103) were obtained from a slaughter house, and the left anterior descending coronary arteries were dissected. The arteries were cut into vessel rings and prepared with and without the endothelium organ chambers filled with buffered salt solution. The effect of propofol (10(-7), 10(-6), 10(-5), and 10(-4) M) on vascular smooth muscle contraction caused by intracellular Ca(2+)-influx through voltage- and receptor-mediated mechanism also was studied at a cellular level. RESULTS: Propofol relaxed coronary rings that were contracted by KCl, norepinephrine (NE), serotonin (5-HT), or carbachol (CCh). The minimal concentrations of propofol that produced significant vasorelaxation ranged from 3.16 x 10(-7) M to 3.16 x 10(-6) M. Vasodilation was more pronounced in rings contracted by NE, 5-HT, and CCh than by KCl. Propofol (10(-5) M) attenuated coronary vasoconstriction in response to cumulative concentrations of KCl, NE, 5-HT, and acetylcholine. Maximal contractions produced by NE and 5-HT were inhibited to a greater degree than contractions produced by KCl. Propofol at concentrations of 10(-5) M and higher attenuated a contraction in response to CaCl2 in vascular rings depolarized by KCl, but concentrations of 10-M did not attenuate contractions. Vasoconstriction in response to calcium entry in the presence of NE (and nifedipine 10(-6) M) was attenuated by propofol at concentrations of 10(-6) M and higher. Caffeine-induced contraction, caused by intracellular calcium release, was attenuated only at 10(-4) M of propofol. CONCLUSIONS: Propofol possesses vasodilator effect and attenuates the effects of vasoconstrictor agents in porcine coronary artery. Further, an antagonism of calcium channels may be responsible for these effects of propofol.

Animals↗
PubMed1995

Additive interactions between propofol and ketamine when used for anesthesia induction in female patients.

BACKGROUND: Propofol and ketamine may be paired for anesthesia induction and for total intravenous anesthesia. The nature of any sedative interactions occurring between propofol and ketamine are unknown. The combination when used for anesthesia induction in female patients was studied. METHODS: Quantal dose-response curves were determined in 180 female patients to whom the drugs were administered individually and in combination. Two minutes after administering the drugs, two endpoints were assessed. First, loss of response to verbal command (hypnosis) and then, in those who failed to respond to this endpoint, loss of response to a 5-s transcutaneous tetanus (anesthesia). Interactions were analyzed by fitting the data to a mathematical model in which response was analyzed in terms of the doses of the two drugs and an additional term included to describe nonadditive interactions. The incidences of apnea, arterial pressure, and heart rate changes during the first 5 min were recorded. RESULTS: At the hypnotic endpoint, the ED50s were 1.10 mg/kg propofol (95% CIs 0.93-1.27), 0.39 mg/kg ketamine (95% CIs 0.27-0.46), and the combination of 0.63 mg/kg propofol and 0.21 mg/kg ketamine (95% CIs 0.53/0.18-0.73/0.24). At the anesthetic endpoint, the ED50s were 1.85 mg/kg propofol (95% CIs 1.58-2.36) 0.66 mg/kg ketamine (95% CIs 0.58-0.77), and the combination of 1.05 mg/kg propofol and 0.35 mg/kg ketamine (95% CIs 0.88/0.29-1.27/0.42). The effects were additive at both endpoints; there was no evidence of an interaction. The ED50s for apnea were 1.61 mg/kg propofol (95% CIs 1.39-1.94), greater than 0.85 mg/kg ketamine and for the combination 1.50 mg/kg propofol and 0.50 mg/kg ketamine (95% CIs 1.15/0.38-3.09/1.03). The addition of ketamine did not significantly alter the ED50 for apnea of propofol. There was a significant difference in the arterial pressures among the three groups (P < 0.001). Using the combination, the cardiostimulant effects of ketamine balanced the cardiodepressant effects of propofol. There was no change in arterial pressure or heart rate after the noxious stimulus. CONCLUSIONS: When using the combination, doses were additive at hypnotic and anesthetic endpoints. Ketamine had no influence on the incidence of apnea after propofol, and the net hemodynamic effects were minimal.

Adult↗
PubMed1995

Frequency-dependent effects of propofol on atrioventricular nodal conduction in guinea pig isolated heart. Mechanism and potential antidysrhythmic properties.

BACKGROUND: The use of propofol has been associated with episodes of bradycardias. The mechanism(s) underlying these phenomena are not well defined. Therefore we investigated (1) the chronotropic and dromotropic effects of propofol, (2) the frequency-dependent effects of propofol on the atrioventricular (AV) node, and (3) the physiologic mechanism(s) underlying propofol's effects on AV nodal conduction. METHODS: Guinea pig isolated, perfused hearts were instrumented for measurement of atrial rate and AV nodal conduction time in spontaneously beating hearts, or stimulus-to-His bundle (S-H) intervals in atrially paced hearts. In addition, the Wenckebach cycle length, effective refractory period and S-H interval prolongation to an abrupt increase in pacing rate were measured to further define propofol's dromotropic effects and frequency-dependent behavior. RESULTS: Propofol, in a concentration-dependent manner, (1) slowed atrial rate and AV nodal conduction time in spontaneously beating hearts, (2) prolonged the S-H interval in atrially paced hearts, and (3) prolonged Wenckebach cycle length and effective refractory period. The negative dromotropic effect of propofol was greater during atrial pacing than in spontaneously beating hearts. Furthermore, this effect was enhanced at faster pacing rates, indicating frequency-dependent behavior. Atropine significantly antagonized propofol-induced S-H interval prolongation. The results of competition binding studies also supported a M2-muscarinic receptor-mediated mechanism. CONCLUSIONS: We conclude that in the isolated guinea pig heart, propofol slows atrial rate and depresses AV nodal conduction in a concentration-dependent manner. The negative dromotropic effect of propofol shows frequency dependence and is predominantly mediated by M2-muscarinic receptors. Given the marked rate dependence of propofol's AV nodal actions, this anesthetic agent may impart antidysrhythmic protection to those patients susceptible to supraventricular tachycardias.

Animals↗
PubMed1996

Effects of combining propofol and alfentanil on ventilation, analgesia, sedation, and emesis in human volunteers.

BACKGROUND: Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea. METHODS: Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm). RESULTS: During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment. CONCLUSIONS: The combination of propofol and alfentanil produced greater sedation and analgesia than that with either drug alone. Propofol offset the emetic effects of alfentanil. Equivalent depression of the carbon dioxide response curve, and elevation of end-tidal carbon dioxide occurred with propofol/alfentanil combined and alfentanil.

Adult↗
PubMed1996

Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia.

BACKGROUND: Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 unpremedicated ASA physical status 1 patients aged 20-55 yr. METHODS: Patients were randomly divided into four groups to receive a computer- controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer- controlled infusion of propofol, with an initial target concentration of 0.5-1 microgram/ml, that was increased every 12 min by 0.5-1 microgram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested an an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-alfentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression. RESULTS: The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC(50) of propofol decreased from 2.07 to 0.83 microgram/ml for loss of eyelash reflex and from 3.62 to 1.55 microgram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 microgram/ml and from 2.36 to 0.04 microgram/ml, respectively. CONCLUSIONS: Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness. In addition, alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate. Hemodynamic stability, therefore, does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia.

Adult↗
PubMed1996

Cardiovascular responses during sedation after coronary revascularization. Incidence of myocardial ischemia and hemodynamic episodes with propofol versus midazolam. Institutions of the McSPI Research Group.

BACKGROUND: Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient, but concern for adverse hemodynamic effects potentially limits its use in these patients. The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization. METHODS: Three hundred fifty-one patients undergoing coronary revascularization were anesthetized using a standardized sufentanil/midazolam regimen, and assigned randomly to 12 h of sedation with either propofol or midazolam while tracheally intubated. The incidence and characteristics of hemodynamic episodes, defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg, were determined using data electronically recorded at 1-min intervals. The presence of myocardial ischemia was determined using continuous three-channel Holter electrocardiography (ECG) and of myocardial infarctions (MI) using 12-lead ECG (Q wave MI, Minnesota Code) or creatine kinase isoenzymes (CK-MB) analysis (non-Q wave MI, peak CK-MB > 70 ng/ml, or CK-MB > 70 IU/I). RESULTS: Ninety-three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation. Propofol sedation resulted in a 17% lower incidence of tachycardia (58% vs. 70%, propofol vs. midazolam; P = 0.04), a 28% lower incidence of hypertension (39% vs. 54%; P = 0.02), and a greater incidence of hypotension (68% vs. 51%; P = 0.01). Despite these hemodynamic effects, the incidence of myocardial ischemia did not differ between treatment groups (12% propofol vs. 13% midazolam; P = 0.66), nor did its severity, as measured by ischemic minutes per hour monitored (8.7 +/- 5.8 vs. 6.2 +/- 4.6 min/h, propofol vs. midazolam; P = 0.19) or ischemic area under the curve (6.8 +/- 4.0 vs. 5.3 +/- 4.2; P = 0.37). The incidence of cardiac death (one per group), Q wave MI (propofol, n = 7; midazolam, n = 3; P = 0.27), or non Q wave MI (propofol, n = 16; midazolam, n = 18; P = 0.81) did not differ between treatment groups. CONCLUSIONS: Hemodynamic episodes occur frequently in the first 12 h after coronary revascularization. Compared with a standard sedation regimen (midazolam), propofol sedation appears to modulate postoperative hemodynamic responses by reducing the incidence and severity of tachycardia and hypertension and increasing the incidence of hypotension. Both sedation regimens appear similarly safe with respect to myocardial ischemia. These findings indicate that propofol infusion provides effective sedation without deleterious hemodynamic effects in patients recovering from cardiac surgery.

Adult↗
PubMed1998

Identification of a genetic region in mice that specifies sensitivity to propofol.

BACKGROUND: Long-sleep (LS) and short-sleep (SS) mice, initially selected for differential sensitivity to ethanol, also exhibit differential sensitivity to propofol. By interbreeding LS and SS mice to obtain progeny whose chromosomes are a patchwork of the LS and SS chromosomes, the authors determined whether differential propofol sensitivity cosegregates with any particular chromosomal region(s). Such cosegregation is the essence of genetic linkage mapping and a first step toward isolating a gene that can modulate propofol sensitivity in mammals. A gene underlying a quantitative trait such as anesthetic sensitivity is commonly called a quantitative trait locus (QTL). METHODS: The propofol dose was 20 mg/kg injected retroorbitally. Sensitivity was measured as the duration of the loss of righting reflex (LORR). The LORR and propofol brain levels at awakening were determined for 24 LSXSS recombinant-inbred (RI) strains, derived by intercrossing LS and SS for two generations followed by >20 generations of inbreeding. A genetic linkage between LORR and an albino mutation on chromosome 7 was investigated further using 164 second-generation progeny (F2s) from intercrossing inbred LS and inbred SS mice, similar to the LSXSS RIs except F2s are not inbred. The linkage between propofol sensitivity and the albino locus also was investigated using additional genetic markers on chromosome 7. Statistical significance was assessed by interval mapping using a regression method for RIs and Mapmaker/QTL (Whitehead Institute, Cambridge, MA) for F2s. RESULTS: Genetic mapping in the LSXSS RIs revealed a QTL tightly linked to the Tyr (albino) locus that accounts for nearly all of the genetic difference in propofol sensitivity between LS and SS mice. Analysis of propofol brain levels at awakening indicated that this QTL results from differential neurosensitivity. Mapping in F2s confirmed the genetic linkage to Tyr. Mice (ISS c/c x C57BL/6 c2j/C) that differed only by an albino mutation at Tyr were not differentially sensitive to propofol. CONCLUSIONS: A single QTL, called Lorp1, underlies most of the genetic difference in propofol neurosensitivity between LS and SS mice. Although this QTL is tightly linked to Tyr, propofol sensitivity is not modulated by albinism. For mapping this QTL, the LSXSS RIs proved to be an especially powerful resource, localizing the candidate-gene region to a 99% confidence interval of only 2.5 centimorgans.

Anesthetics, Intravenous↗
PubMed1998

Effect of propofol on norepinephrine-induced increases in [Ca2+]i and force in smooth muscle of the rabbit mesenteric resistance artery.

BACKGROUND: Propofol (2,6-diisopropylphenol) possesses vasodilating activity in vivo and in vitro. The propofol-induced relaxation of agonist-induced contractions in small resistance arteries has not been clarified. METHODS: The effect of propofol was examined on the contractions induced by norepinephrine and high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and isometric force in ryanodine-treated strips. RESULTS: Propofol attenuated the contractions induced by high K+ and norepinephrine, the effect being greater on the high K+-induced contraction than on the norepinephrine-induced contraction. In Ca2+-free solution, norepinephrine produced a transient contraction resulting from the release of Ca2+ from storage sites that propofol attenuated. In ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In the presence of nicardipine, propofol had no inhibitory action on the residual norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased resting [Ca2+]i, as in the absence of nicardipine. CONCLUSIONS: In smooth muscle of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine-induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly as a result of an inhibition of [Ca2+]i removal mechanisms. These results may explain in part the variety of actions seen with propofol in various types of vascular smooth muscle.

Anesthetics, Intravenous↗
PubMed1999

Optimal propofol-alfentanil combinations for supplementing nitrous oxide for outpatient surgery.

BACKGROUND: The combination of propofol and alfentanil with nitrous oxide provides balanced anesthesia with rapid recovery and minimal emetic side effects. The object of this study was to compare recovery parameters at varying proportions of propofol and alfentanil, and to determine the dosing rate and plasma concentration of propofol necessary to supplement nitrous oxide in the presence of varying concentrations of alfentanil METHODS: Forty-eight patients were anesthetized with nitrous oxide, targeted manual infusions of alfentanil (target plasma concentrations of 0, 50, 100, and 150 ng/ml), and propofol at rates that were varied up or down by 25% depending on the response (movement/no movement) of the preceding patient (at the same alfentanil target concentrations) to ulnar-nerve stimulation. The minimum concentrations of propofol and alfentanil required to prevent movement in 50% of patients (EC50) was determined by logistic regression. Speed of emergence and recovery of cognitive function, time to discharge, and incidence of side effects were compared for four different combinations of propofol and alfentanil with nitrous oxide. RESULTS: The EC50 for propofol alone with nitrous oxide was 6.1 microg/ml. AlfentaniL at concentrations of 41+/-17 (SD), 113+/-54, and 130+/-61 ng/mL reduced the EC50 of propofol to 3.3, 2.3, and 2.2 microg/ml, respectively, and decreased emergence time (eye opening) to 8.1, 4.9, and 3.4 min, compared with 24.3 min for propofol alone. Side effects did not differ between groups. CONCLUSIONS: The authors conclude that there is a synergistic effect between propofol and alfentanil, and that combining alfentanil with propofol is associated with faster early recovery.

Adolescent↗