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PubMed2006

Dopamine induces postischemic cardiomyocyte apoptosis in vivo: an effect ameliorated by propofol.

BACKGROUND: Dopamine is commonly used to improve postischemic myocardial contractile function. However, there is evidence that dopamine augments apoptosis after ischemia through increased intracellular calcium and opening of the mitochondrial permeability transition pore. Propofol (2,6-diisopropylphenol) is an anesthetic that has been shown to prevent mitochondrial permeability transition pore opening. We evaluated the effects of propofol given during reperfusion on dopamine-mediated apoptosis. METHODS: Hearts from 8-week-old inbred New Zealand White rabbit siblings were subjected to 2 hours of cold cardioplegic ischemia and 6 hours of reperfusion in a heterotopic transplant model. Controls consisted of the recipient rabbit's nonischemic heart. The ischemia-reperfusion (IR) group consisted of postischemic hearts reperfused with no drugs; the IR plus dopamine (IR+D) group received dopamine (20 microg x kg(-1) x min(-1)) continuously; the IR+D plus propofol (IR+D+P) group received dopamine (20 microg x kg(-1) x min(-1)) plus propofol (500 to 600 microg x kg(-1) x min(-1)); and the IR plus propofol (IR+P) group received propofol only (500 to 600 microg x kg(-1) x min(-1)) throughout reperfusion (n = 7 to 9 in each group). Myocardial function was measured using a left ventricular balloon; terminal nick-end labeling (TUNEL) staining, DNA electrophoresis, and immunoblotting for caspase-3 cleavage were performed at the end of reperfusion. RESULTS: Dopamine increased the number of TUNEL-positive nuclei significantly (14.0 +/- 2.0/1,000 for IR+D versus 6.7 +/- 2.0/1,000 for IR, p = 0.01). Propofol (IR+D+P) reduced the total number of apoptotic cells in hearts receiving dopamine (7.1 +/- 1.8/1,000, p = 0.01 versus IR+D) to the extent seen in IR alone. DNA laddering and caspase-3 cleavage were observed at greater frequency in the IR+D group compared with the IR and IR+D+P groups. Propofol had no effect on dopamine-mediated increased systolic function, but improved diastolic function after ischemia. CONCLUSIONS: Dopamine infusion has a positive inotropic effect on the postischemic heart at the expense of increased cardiomyocyte apoptosis. The addition of propofol prevents dopamine-induced apoptosis after ischemia while maintaining positive inotropy.

Anesthetics, Intravenous↗
PubMed2005

Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients.

BACKGROUND: Pain on injection is still a major problem with propofol used for general anesthesia. A number of techniques for reducing propofol-induced pain on injection have been tried, with variable results. Flurbiprofen axetil, a prodrug of the nonsteroidal anti-inflammatory drug flurbiprofen, has been used for postoperative pain management but has not been studied for managing pain on injection of propofol when preceded with venous occlusion. OBJECTIVE: The present study was undertaken to examine the efficacy of flurbiprofen axetil for reducing pain on propofol injection in Japanese adult surgical patients. METHODS: This prospective, randomized, double-blind, vehicle-controlled, dose-finding study was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Japanese patients aged 18 to 65 years scheduled to undergo elective surgery were eligible. Patients were randomized to receive flurbiprofen axetil IV at 1 of 3 doses (25, 50, or 75 mg), or vehicle (control group), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by administration of 25% of the total calculated dose of propofol (2 mg/kg), injected into the largest vein of the hand through a 20-gauge IV cannula. During propofol injection, a researcher who was blinded to treatment assignment asked each patient about his or her pain at the injection site. Responses were scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe). Median pain intensity scores in each group were determined. Adverse effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were monitored for up to 24 hours after surgery. RESULTS: A total of 120 patients (62 men, 58 women; mean [SD] age, 41 [12] years, mean [SD] height, 162 [8] cm; mean [SD] body weight, 58 [10] kg) were enrolled. Each treatment group comprised 30 patients. No significant between-group differences in demographic characteristics were found. A significantly higher proportion of patients in the control group (77%) experienced pain compared with the flurbiprofen axetil 50- and 75-mg groups (47% and 43%, respectively; both, P < 0.01). The median pain intensity scores were significantly lower in the flurbiprofen axetil 50- and 75-mg groups (both, 0 [no pain]) compared with controls (2 [moderate]; both, P < 0.01). The incidence and intensity of propofol-induced pain were statistically similar between the flurbiprofen axetil 25-mg and control groups. The incidence and intensity of pain associated with the injection of propofol were significantly lower in the flurbiprofen axetil 50- and 75-mg groups compared with the 25-mg group (incidence, 70% [both, P < 0.05]; median pain intensity score, 1 [mild] [both, P < 0.01]). No AEs were observed. CONCLUSION: In this study of Japanese adult surgical patients, flurbiprofen axetil at doses of 50 and 75 mg, preceded by venous occlusion for 2 minutes, was found to be effective in reducing propofol-induced pain on injection.

Adult↗
PubMed2006

Influence of age on flurbiprofen axetil requirements for preventing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study.

BACKGROUND: Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Preceded by venous occlusion, flurbiprofen axetil, a prodrug of the NSAID flurbiprofen, has been associated with a reduction in pain induced by propofol injection. A review of the literature determined that no published data were available on the influence of age on the requirements for flurbiprofen axetil dose. OBJECTIVE: This study was undertaken to examine the influence of age on flurbiprofen axetil requirements for the treatment of propofol-induced pain on injection in Japanese adult surgical patients. METHODS: This prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Young (age 20-40 years) and older (age 60-80 years) Japanese patients scheduled for various types of surgery (eg, cholecystectomy) were eligible. Patients were randomized to receive flurbiprofen axetil at 1 of 2 doses (25 or 50 mg, regardless of body weight) or inactive vehicle (saline), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by the infusion of the first 25% of calculated propofol dose (0.5 mg/kg at room temperature, 23 degrees C) into the largest dorsal vein of the hand through a 20-G IV cannula (without local anesthesia), followed by the release of the occlusion and delivery of propofol 2 mg/kg. An investigator blinded to treatment questioned each patient about pain intensity during propofol injection which was assessed using a verbal rating scale: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The overall prevalence of pain was calculated in each group. AEs at the injection site (pain, edema, wheal, inflammation) were assessed by the study investigator for 24 hours after surgery using spontaneous reporting and patient interview. RESULTS: A total of 150 patients, 75 young adults (38 men, 37 women; mean [SD] age, 31 [5] years; mean [SD] height, 163 [7] cm; mean [SD] body weight, 58 [9] kg) and 75 older adults (38 men, 37 women; mean [SD] age, 70 [6] years; mean [SD] height, 154 [8] cm; mean [SD] body weight, 53 [10] kg), were enrolled. Each treatment group comprised 25 patients. No differences in demographic characteristics were observed among the 3 study groups. In young patients, the overall prevalence of propofol-induced pain was significantly lower in patients who received flurbiprofen axetil 50 mg (12 [48%]) compared with that in patients who received flurbiprofen axetil 25 mg (20 [80%]) or vehicle (22 [88%]) (P < 0.05 and P < 0.01, respectively). The median pain intensity score was significantly lower in patients who received flurbiprofen axetil 50 mg (0) compared with that in patients who received flurbiprofen axetil 25 mg (1) or vehicle (2) (P < 0.05 and P < 0.01, respectively). In older patients, the overall prevalences of pain on propofol injection were 9 (36%) in the flurbiprofen axetil 50-mg group and 11 (44%) in the flurbiprofen axetil 25-mg group compared with 21 (84%) in the vehicle group (both, P < 0.01). The median pain score was significantly lower in patients who received flurbiprofen 50 mg (0) or 25 mg (0) than in those who received vehicle (1) (both, P < 0.01). All treatments were well tolerated. CONCLUSIONS: In this small clinical trial in Japanese surgical patients undergoing general anesthesia, flurbiprofen axetil requirements for the reduction of pain during injection of propofol were found to be 50 mg in young adults (age 20-40 years) and 25 or 50 mg in older adults (age 60-80 years), regardless of weight, preceded by venous occlusion for 2 minutes.

Adult↗
PubMed2005

Effect of continuous infusion of propofol on its concentration in blood with and without the liver in pigs.

In living donor liver transplantation, propofol, an intravenous anesthetic drug, has recently been used in both donors and recipients. Propofol is known to have intra- and extrahepatic metabolic pathways, but the effect of its continuous infusion during a long-term anhepatic state is yet to be determined. Recently, we successfully established a simplified pig model of the complete anhepatic state. In this state, we first evaluated hemodynamic parameters relating to the pharmacokinetics of continuously infused propofol (6 mg.kg(-1) x h(-1)). No significant changes in the concentration of hemoglobin or in hemodynamic parameters other than the heart rate were observed during the anhepatic phase when porpofol was continuously infused at the rate that maintains the state. Blood propofol concentrations in the mixed vein, artery, and portal vein were stable during the anhepatic phase. Finally, we confirmed the pharmacokinetics of continuously infused propofol using orthotropic liver transplantation in miniature pigs. The propofol concentration did not change markedly during the transplant procedure. In conclusion, the pharmacokinetics of continuously infused propofol was almost stable with and without the liver in pigs. Extrahepatic metabolism of propofol might help prevent changes in propofol concentrations.

Anesthetics, Intravenous↗
PubMed2003

Effects of propofol on GABAA channel conductance in rat-cultured hippocampal neurons.

Channels were activated, in ripped-off patches from rat-cultured hippocampal neurons, by propofol alone, propofol plus 0.5 microM GABA (gamma-aminobutyric acid) or GABA alone. The propofol-activated currents were chloride-selective, showed outward-rectification and were enhanced by 1 microM diazepam. The maximum propofol-activated channel conductance increased with propofol concentration from less than 15 pS (10 microM) to about 60 pS (500 microM) but decreased to 40 pS in 1 mM propofol. Fitting the data from 10 to 500 microM propofol with a Hill-type equation gave a maximum conductance of 64 pS, an EC50 value of 32 microM and a Hill coefficient of 1.1. Addition of 0.5 microM GABA shifted the propofol EC50 value to 10 microM and increased the maximum channel conductance to about 100 pS. The Hill coefficient was 0.8. The maximum channel conductance did not increase further when 1 microM diazepam was added together with a saturating propofol concentration and GABA. The results are compared to effects other drugs have on GABAA channels conductance.

Anesthetics, Intravenous↗
PubMed1996

Propofol and flurazepam act synergistically to potentiate GABAA receptor activation in human recombinant receptors.

The intravenous general anaesthetic propofol (2,6-di-isopropylphenol) is frequently combined with a benzodiazepine. There are clinical reports of synergism between these two agents for induction of general anaesthesia. To investigate a possible mechanism of this synergistic interaction between propofol and benzodiazepines, the effect of propofol and flurazepam on GABAA receptor function was examined in Xenopus oocytes expressing recombinant alpha 1 beta 2 gamma 2L and alpha 2 beta 2 gamma 2L receptor constructs. Potentiation of GABA receptor-activated current by low (1-10 microM) concentrations of propofol together with flurazepam (0.25-0.5 microM) was significantly greater than predicted by an additive response. Isobolographic analysis indicated a strong synergistic interaction between propofol and flurazepam at either of the receptor constructs examined. In contrast, the cyclopyrrolone derivative zopiclone, which produced a similar facilitation of GABA receptor-activated current compared to flurazepam, produced a less than additive potentiation when combined with propofol. Flurazepam significantly decreased the EC50 concentration of propofol for potentiation of GABA responses. Thus, flurazepam, in addition to facilitating GABA receptor activity on its own, also increases on its own, also increases the apparent affinity of the GABAA receptor complex to propofol, resulting in a greater than expected potentiation by the combination of propofol plus flurazepam.

Anesthetics, Intravenous↗
PubMed1999

Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study.

BACKGROUND: Adequate patient sedation is mandatory for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The short-acting anesthetic propofol offers certain potential advantages for endoscopic procedures, but controlled studies proving its superiority over benzodiazepines for ERCP are lacking. METHODS: During a 6-month period 198 consecutive patients undergoing routine ERCP randomly received either midazolam (n = 98) or propofol (n = 99) for sedation. Vital signs (heart rate, blood pressure, oxygen saturation) were continuously monitored and procedure-related parameters, the recovery time and quality (recovery score) as well as the patient's cooperation and tolerance of the procedure (visual analog scales) were prospectively assessed. RESULTS: Patients receiving propofol or midazolam were well matched with respect to demographic and clinical data, ERCP findings, and the performance of associated procedures. Propofol caused a more rapid onset of sedation than midazolam (p < 0.01). Clinically relevant changes in vital signs were observed at comparable frequencies with temporary oxygen desaturation occurring (< 85 %) in 6 patients in the propofol group and 4 patients receiving midazolam (not significant). However, an episode of apnea had to be managed by mask ventilation via an ambu bag (lasting 8 minutes) in one of the patients receiving propofol sedation. Mean recovery times as well as the recovery scores were significantly shorter with propofol (p < 0. 01). Propofol provided significantly better patient cooperation than midazolam ( p < 0.01), but procedure tolerability was rated the same by both groups of patients (not significant). CONCLUSIONS: Intravenous sedation with propofol for ERCP is (1) more effective than sedation with midazolam, (2) safe under adequate patient monitoring, and (3) associated with a faster postprocedure recovery.

Adult↗
PubMedDate not supplied

The role of the GABA(A) receptor alpha1 subunit N-terminal extracellular domain in propofol potentiation of chloride current.

Propofol (2,6-diisopropylphenol), an intravenous general anesthetic in active clinical use today, potentiates the action of gamma-aminobutyric acid (GABA) at the type-A receptor and also directly induces current in the absence of GABA. We expressed different combinations of murine GABA(A) receptor alpha1, beta3 and gamma2 subunits in Xenopus oocytes to investigate the subunit dependence of propofol potentiation of pentobarbital-induced current. Pentobarbital induces current in all beta3-subunit-containing receptors, whereas current gating by GABA requires the presence of both alpha1 and beta3 subunits. Therefore, pentobarbital rather than GABA was used to induce current in order to separate the subunit dependence of current gating from the subunit dependence of potentiating action of propofol. alpha1beta3gamma2, alpha1beta3, beta3gamma2, or beta3 subunit combinations all responded to pentobarbital in a dose-dependent manner. True potentiation was defined as the current magnitude to simultaneous application of pentobarbital and propofol exceeding the additive responses to individual drug applications. A dose-dependent propofol potentiation of pentobarbital-induced current was observed in oocytes injected with alpha1beta3 or alpha1beta3gamma2 but not in beta3gamma2 or beta3 subunits, suggesting that the alpha1 subunit was necessary for this modulatory action of propofol. Further examination of the propofol potentiation in chimeras between the alpha1 and beta3 subunits showed that the extracellular amino-terminal half of the alpha1 subunit was sufficient to support propofol potentiation. The different requirements of the receptor structure for the agonistic (gating) and the potentiating actions suggest that these two actions of propofol are distinct processes mediated through its action at distinct sites.

Anesthetics, Intravenous↗
PubMed1996

Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum.

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg-1 intravenously (group 1) or with a mixture of propofol at 3 mg kg-1 and ketamine at 1 mg kg-1 intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64.8 (3.1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56.6 (13.1) minutes in group 1 and 50.3 (21.4) minutes in group 2; the mean volume of distribution at steady state was 1.037 (0.480) litre kg-1 in group 1 and 1.515 (0.939) litre kg-1 in group 2; the mean body clearance was 85.4 (28.0) ml kg-1 min-1 in group 1 and 128.0 (35.0) ml kg-1 min-1 in group 2; the mean residence time corrected for a bolus injection was 12.1 (4.2) minutes in group 1 and 11.9 (6.6) minutes in group 2; for the infusion, the mean residence time was 72.1 (4.2) minutes in group 1 and 69.9 (7.9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2.8 (0.4), 6.3 (1.2) and 10.9 (1.6) minutes from the end of the infusion, and the times for group 2 were 5.3 (0.9), 11.2 (1.7) and 15.1 (2.2) minutes.

Acepromazine↗
PubMed1987

[Hemodynamic effects of propofol].

The new form of propofol gives the same haemodynamic effects as the old one (propofol diluted in cremophor EL). There are few experimental studies concerning the haemodynamic effects of propofol. In the dwarf pig, Glen and Turner found a fall in arterial blood pressure and peripheral resistances, whilst the heart rate and cardiac output rose. In man, studies have shown that propofol gives haemodynamic effects similar to the other intravenous anaesthetic drugs, and especially thiopentone. In subjects with a healthy heart, and for doses included between 1.5 and 2.5 mg X kg-1, propofol gave a 25 to 30% fall in arterial blood pressure. There are also a 20% fall in peripheral resistances and a small fall (10%) in cardiac output. Blood pressure returned to its initial level 3 to 5 min after the injection. The heart rate was not much changed, and rather slowed, perhaps because of central vagotonia. When propofol was used to maintain anaesthesia, either by repeat injections, or by infusion, with the patient breathing spontaneously and not undergoing painful stimuli, blood pressure and heart rate remained steady within 55 to 65% of their initial values. Propofol appeared to avoid to some extent the increase in blood pressure and heart rate seen during intubation. When propofol and fentanyl were used together, the cardiovascular effects were more pronounced than when they were used alone. Moreover, propofol appeared to limit to a large extent the hypertension due to intubation and sternotomy in patients undergoing aorto-coronary arterial graft surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1987

[Ambulatory anesthesia and induced abortion. Comparative study of propofol-alfentanyl and ketamine-midazolam combinations].

The use of propofol alone or with alfentanil in the day-case anaesthesia for abortion was compared with that of ketamine with midazolam. Two hundred young women were assigned to two successive series of two groups each. The four groups were: group 1 (2 mg . kg-1 propofol only); group II (0.5 mg . kg-1 ketamine with 0.25 mg . kg-1 midazolam); group III (2 mg . kg-1 propofol with 4 micrograms . kg-1 alfentanil); group IV (1 mg . kg-1 ketamine with 0.1 mg . kg-1 midazolam). All the patients were premedicated one hour before anaesthesia with 0.25 mg . kg-1 midazolam orally. All the patients were asleep at the end of the propofol injection (60 s), and 10 to 15 s later for the ketamine-midazolam groups. The haemodynamic parameters did not vary much during induction with ketamine-midazolam. In the propofol groups, the heart rate remained steady, with an 8 to 12% fall in blood pressure. A fall of the mandible was seen in 40 and 84% of the patients in the propofol groups, with a short apnoea in 32 and 48% of these same patients. Clinical recovery was very quick, less than 12 min for all groups. The four psychomotor and sensory tests were carried out at the 30th min by 95% of the patients in the propofol groups, whereas only 50% of those in the ketamine-midazolam groups did so. Speed and quality were significantly better in the propofol groups. The most frequent adverse effect of propofol was pain during injection in 32 and 14% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1996

Propofol inhibits epileptiform activity in rat hippocampal slices.

Propofol (2,6 di-isopropylphenol) is an intravenous general anesthetic used widely in neuroanesthesia, as a sedative in intensive care units, and has successfully aborted refractory status epilepticus. We investigated the effects of propofol on epileptiform activity in rat hippocampal slices. Interictal epileptiform activity was produced by bath applying one of the following: picrotoxin (PTX; 10 and 50 microM), bicucculine methiodide (BMI; 10 and 50 microM), 4-aminopyridine (4-AP; 50 microM), 8.5 mM [K+]o or 0 [Mg2+]o artificial cerebrospinal fluid. Propofol was then added in increasing concentrations and the effect on the rate of extracellular field epileptiform discharges was measured. Ictal-like discharges (> 2 Hz for > 2 s) were produced by 7.5 mM [K+]o and pilocarpine (10 microM). Propofol (30 micrograms/ml, 168 microM) completely abolished discharges induced by 8.5 mM [K+]o and at 60 micrograms/ml (337 mM) completely suppressed discharges induced by 4-AP and 0 [Mg2+]o. Propofol was less effective in reducing discharges produced by GABAA/Cl- receptor complex antagonists. Propofol at a concentration of 300 micrograms/ml (1.7 mM) was needed to reduce BMI-induced (50 microM) discharges by 77% and only reduced PTX-induced (50 microM) discharges by 20%. Ictal-like discharges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 micrograms/ml, 16.9-56.2 microM) and the duration of the ictal-like discharge period was significantly reduced. We found that propofol has significant in vitro antiepileptic effects. Additionally, propofol was less effective against GABAA antagonists suggesting that the GABAA receptor complex is the site of its action.

Analysis of Variance↗
PubMed2003

The interaction between fentanyl and propofol during emergence from anesthesia: monitoring with the EEG-Bispectral index.

STUDY OBJECTIVE: To investigate the effect of different plasma levels of fentanyl on the concentration of propofol and the Bispectral Index (BIS) required for patients to regain consciousness and orientation following surgery. DESIGN: Prospective, open-label study. SETTING: Operating room of a university hospital. PATIENTS: 28 patients, aging 20 to 50 years, scheduled for elective, 1- to 4-hour surgeries under general anesthesia. INTERVENTIONS: BIS was continuously monitored from bifrontal montage (At1-Fpz and At2-Fpz) using an Aspect A-1,050 EEG system (Aspect, Natick, MA). Anesthesia was induced with bolus injections of fentanyl 2 microg/kg and propofol 2 mg/kg, and maintained with intermittent injections of fentanyl and constant infusion of propofol. Propofol infusion was stopped at the end of surgery. MEASUREMENTS: Consciousness and orientation were assessed as clinical endpoints once every 2 minutes following the end of the surgery. Blood samples were extracted for plasma propofol and fentanyl concentrations (PCp and FCp, respectively), and BIS values were recorded when patients regained consciousness and orientation. Patients were allocated to one of three groups depending on FCp on awakening: Group 1, FCp > 1 microg/L (n = 8); Group 2, FCp < 1 microg/L and >0.45 microg/L (n = 9); and Group 3, FCp < 0.45 microg/L (n = 11). PCp, BIS, recovery time, and other data were compared between the three groups. MAIN RESULTS: Demographic values, duration of surgery, and consumption of propofol and fentanyl were not different between the three groups. Group 3 patients regained consciousness with significantly higher propofol concentration (mean PCp = 3.2 mg/L) compared with those in Groups 1 and 2 (p < 0.05). However, the BIS values at both recovery endpoints were not different among the three groups. CONCLUSIONS: The plasma levels of fentanyl affect the concentrations of propofol required for patients to regain consciousness. The BIS values for wakefulness are unaltered at the different combinations of propofol and fentanyl concentrations. Thus, the BIS appears to be a useful and consistent indicator for level of consciousness during emergence from propofol/fentanyl intravenous anesthesia.

Adult↗
PubMed1997

Propofol decreases ocular pressure in outpatients undergoing trabeculectomy.

STUDY OBJECTIVE: To examine the effect of a continuous low-dose intravenous (i.v.) infusion of propofol on ocular pressure in outpatients undergoing trabeculectomy. DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 40 unpremedicated outpatients with history of primary open angle glaucoma undergoing trabeculectomy. INTERVENTIONS: In the operating room, an infusion of 5% dextrose into a peripheral vein was started. The propofol group (n = 20) received 0.5 mg/kg i.v. propofol bolus followed immediately by a continuous 0.5 mg/kg/hr infusion. The control group (n = 20) received only the dextrose solution. A peribulbar block was performed with bupivacaine with added adrenaline, plus lidocaine. The ocular pressure (tonometer) on the eye undergoing trabeculectomy and the other eye, blood pressure (BP), and heart rate (HR) were measured at the following times: (1) preoperatively; (2) 2 minutes; (3) 5 minutes; (4) 10 minutes; (5) 15 minutes after propofol bolus administration for the propofol group (approximately 4 minutes after the peribulbar blockade on the eye undergoing surgery for the propofol and control groups). MEASUREMENTS AND MAIN RESULTS: Ocular pressure decreased 2 minutes after propofol infusion (p < 0.0001) and remained significantly lower than in the control group throughout the study period. All patients remained awake and cooperative during all procedures. Mean BP and HR were kept constant throughout the study. CONCLUSION: Low-dose propofol sedation resulted in a decrease in ocular pressure, was quick in onset, and was unrelated to BP and HR. The decrease in ocular pressure may be due to relaxation of extraocular muscles by propofol.

Adult↗
PubMed1997

The effect of a propofol-based sedation technique on cumulative embryo scores, clinical pregnancy rates, and implantation rates in patients undergoing embryo transfers with donor oocytes.

STUDY OBJECTIVE: To determine the effect, if any, of a propofol-based sedation technique on the reproductive outcomes of patients undergoing embryo transfers with donor oocytes. These ova recipients form a unique subgroup, whose clinical outcomes are unrelated to direct anesthetic effects on their reproductive tracts. DESIGN: Retrospective chart review. SETTING: A 1200-bed university medical center. PATIENTS: 117 patients who received fresh embryo transfer cycles between January 1991 and December 1995. MEASUREMENTS AND MAIN RESULTS: The anesthesia records of 106 women who donated ova were reviewed for propofol usage during the transvaginal needle aspiration of the ova. The medical records of the 117 patients who received these donated embryos were reviewed for cumulative embryo scores, clinical pregnancy rates, and implantation rates. Fourteen patients received ova from women who were sedated with fentanyl and midazolam during ovum retrievals, while 103 patients received ova from women who had been given fentanyl, midazolam, and propofol in doses of 1.87 mg/kg to 8 mg/kg. The pregnancy rate among all patients who received ova from women who received propofol (44 of 103 = 42.7%) was 14.1% greater than those whose ovum donors did not receive propofol (4 of 14 = 28.6). 78.6% of both propofol and non propofol-exposed groups had cumulative embryo scores of greater than 50. Among patients who became pregnant, 52.3% of propofol-exposed and 50% of nonpropofol-exposed cases had greater than 20% implantation rates. CONCLUSION: There is no evidence from our data that the administration of propofol during the aspiration of ovarian follicles for oocyte donation had a negative impact on the oocytes as measured by cumulative embryo scores, probability of a clinical pregnancy, or implantation rate.

Anesthetics, Intravenous↗
PubMed1998

Effect of propofol on perception of pain in mice: mechanisms of action.

The latencies of pain threshold to different subhypnotic doses (12.5, 25 and 50 mg kg-1) of propofol, an anaesthetic, administered intraperitoneally (i.p.) into male mice were measured using a hot plate method. The possible mechanism of pain control by propofol was also investigated through blocking beta-endorphin receptors and measuring serum level of beta-endorphin. Morphine (1.5 mg kg-1; i.p.) was used as a reference of reduction of pain sensation. The results showed that propofol in doses of 25 and 50 mg kg-1 significantly (P < 0.01) increased the latency of pain threshold but a lower dose (12.5 mg kg-1) failed to produce any significant change. This indicates that propofol reduced pain and this effect is dose-dependent. Propofol prevents hyperalgesia produced by prostaglandin PGE2, (0.5 mg kg-1, i.p.; P < 0.01). Pretreatment with naloxone (1.0 mg kg-1, i.p.) abolished significantly (P < 0.01) the antinociceptive action of propofol. Furthermore, serum level of beta-endorphin was increased (P < 0.01) after propofol injection particularly at the peak time of propofol action. The serum level of corticosterone was also increased (P < 0.01) at the time of beta-endorphin release. It was concluded that propofol can control pain and this action may be centrally modulated through the opioid system rather than at the level of the spinal cord.

Analgesics↗
PubMed2002

Propofol in rats: testing for nonlinear pharmacokinetics and modelling acute tolerance to EEG effects.

BACKGROUND AND OBJECTIVE: Pharmacokinetics of propofol in rats have usually been described using linear models. Furthermore, there are only a few investigations for a pharmacodynamic model of the electroencephalographic effects of propofol in rats. We investigated pharmacokinetics and pharmacodynamics of propofol in rats with special regard to linearity in pharmacokinetics and development of tolerance. METHODS: Twelve adult male Sprague-Dawley rats received propofol in three successive infusion periods of 30 min each with infusion rates of 0.5, 1 and 0.5 mg kg(-1) min(-1). Propofol plasma concentrations were determined from arterial blood samples. Pharmacokinetics were tested for linearity using the ratio of the concentrations at the end of the first and second infusion interval as a model independent criterion. Several linear and nonlinear models were investigated with population pharmacokinetic analysis. Pharmacodynamics were analysed using the median frequency of the electroencephalographic power spectrum as a quantitative measure of the hypnotic effect. RESULTS: Pharmacokinetics were found to be nonlinear and were best described by a two-compartment model with Michaelis-Menten elimination (Vm = 2.17 microg mL(-1) min(-1), Km = 2.65 microg mL(-1), k12 = 0.30 min(-1), k21 0.063 min(-1), Vc = 0.13 L). Acute tolerance to the electroencephalographic effect of propofol was observed. The hypnotic effect was best described by a sigmoid Emax model (E0 = 17.8 Hz, Emax = 17.7 Hz, EC50 = 4.1 microg mL(-1), gamma = 2.3, ke0 = 0.36 min(-1)) with competitive antagonism of propofol and a hypothetical drug in an additional tolerance compartment. CONCLUSIONS: For the applied infusion scheme, propofol pharmacokinetics in rats were nonlinear and a development of tolerance to the electroencephalographic effect of propofol was observed during an infusion time of 90 min.

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PubMed2002

Conditions for insertion of the laryngeal mask airway: comparisons between sevoflurane and propofol using fentanyl as a co-induction agent. A pilot study.

BACKGROUND AND OBJECTIVE: To compare the conditions for insertion of the laryngeal mask airway using sevoflurane or propofol plus fentanyl. We evaluated the haemodynamic changes and cost of induction of anaesthesia in both groups. METHODS: Sixty patients were equally and randomly divided into two groups. Both groups received fentanyl 1 microg kg(-1). Patients in the sevoflurane group were induced with 8% sevoflurane and those in the propofol group with propofol 2.5 mg kg(-1). Conditions for insertion were graded on a three-point scale using six variables. Overall, conditions were assessed as excellent, satisfactory or poor based on the total score in each group. Systolic and diastolic arterial pressure and heart rate were recorded for 6 min after mask insertion. The financial cost of induction in both groups was calculated. RESULTS: The mean (+/- SD) time taken from induction to successful laryngeal mask insertion was significantly shorter with propofol (68.70 +/- 22.60 s) compared with sevoflurane (149.83 +/- 55.25 s). Excellent or satisfactory conditions were observed in 30 (100%) patients in the propofol group and in 29 (96.66%) in the sevoflurane group. Systolic and diastolic arterial pressures were significantly lower in the propofol group. The cost of sevoflurane used was 3.95 euros +/- 1.48 (Rs 216.23 +/- 64.66) (P < 0.05) compared with that of propofol, which was 3.23 euros +/- 0.65 (Rs 141.00 +/- 28.20). CONCLUSIONS: Although there was a faster induction with propofol-fentanyl, conditions for insertion of the laryngeal mask airway were similar in both groups. Haemodynamic stability was better with sevoflurane-fentanyl. The propofol-fentanyl combination was more cost-effective.

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