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PubMed2005

Impact of patient age on propofol consumption during propofol-remifentanil anaesthesia.

BACKGROUND: This study was designed to investigate the impact of patient age on propofol consumption and recovery time using a propofol-remifentanil anaesthetic standardized with Narcotrend EEG monitoring. The Narcotrend is a monitor for measuring the depth of anaesthesia based upon a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. METHODS: In 200 patients scheduled for minor orthopaedic surgery Narcotrend EEG electrodes were positioned on the patient's forehead as recommended by the manufacturer. Anaesthesia was induced with remifentanil 0.4 microg kg(-1) min(-1) and 2 mg kg(-1) propofol. Immediately after intubation remifentanil was reduced to a constant rate of 0.2 microg kg(-1) min(-1) whereas a propofol infusion was now started at 3 mg kg(-1) h(-1) and then adjusted accordingly to achieve a target Narcotrend stages of D(0-2) indicating general anaesthesia. At the end of surgery the propofol and remifentanil infusions were stopped without tapering, the time to unstimulated opening of eyes was determined, and the propofol consumption (given as mg kg(-1) h(-1)) was calculated from the total amount of infused propofol but without the induction bolus, from the actual body weight and the duration of propofol infusion. Furthermore, a linear regression analysis was applied for propofol consumption vs. age. RESULTS: The ages of the patients studied ranged from 16 to 83 yr old and patients were classified as ASA I-III. Propofol consumption significantly decreased with the patients' age: 30 yr of age or below the propofol consumption was calculated as 5.9 +/- 1.7 mg kg(-1) h(-1), for 31-50 yr as 5.4 +/- 1.8 mg kg(-1) h(-1), for 51-70 yr as 4.5 +/- 1.7 mg kg(-1) h(-1) and above 70 yr as 3.5 +/- 1.4 mg kg(-1) h(-1). Linear regression analysis revealed propofol (mg kg(-1) h(-1)) = 9.136 - (0.0597 x age (yr)); R = 0.53. Concomitantly, the recovery time to opening of eyes increased with the patients' age: < or = 30 yr, 7.4 +/- 3.7 min; 31-50 yr, 9.5 +/- 4.0 min; 51-70 yr, 9.8 +/- 4.1 min; and > or = 71 yr, 14.9 +/- 12.1 min. CONCLUSIONS: We conclude that with Narcotrend guidance, mean propofol consumption and recovery times are age dependent. However, as a result of large inter-individual variability, age per se does not allow a prediction of individual propofol need or recovery time.

Adolescent↗
PubMed2002

Propofol metabolites in man following propofol induction and maintenance.

BACKGROUND: The pharmacokinetics of propofol in man is characterized by a rapid metabolic clearance linked to glucuronidation of the parent drug to form the propofol-glucuronide (PG) and sulfo- and glucuro-conjugation of hydroxylated metabolite via cytochrome P450 to produce three other conjugates. The purpose of this study was to assess the urine metabolite profile of propofol following i.v. propofol anaesthesia in a Caucasian population. METHODS: The extent of phase I and phase II metabolism of propofol was studied in 18 female and 17 male patients after an anaesthesia induced and maintained for at least 4 h with propofol. The infusion rates (mg kg(-1) h(-1)) of propofol were (mean (SD)) 4.1 (1.0) and 4.5 (1.3) for males and females, respectively. Urine was collected from each patient for the periods 0-4, 4-8, 8-12, and 12-24 h after the start of propofol administration. In a preliminary study, the three main glucuro-conjugated metabolites were isolated from urine and characterized by magnetic resonance spectroscopy. The quantification of these metabolites for the different collection periods was then performed by a HPLC-UV assay. RESULTS: Total recovery of propofol in the metabolites studied amounts to 38%, of which 62% was via the PG metabolite and 38% via cytochrome P-450. This percentage is significantly higher than that previously reported from patients after a bolus dose of propofol. Extreme values for PG (0-24 h period) were included from 73 to 49%. There was no significant difference between female and male patients in the metabolite ratio. CONCLUSIONS: We conclude that the extent of hydroxylation in propofol metabolism was higher than in previous findings after administration of anaesthetic doses of propofol. Moreover, the ratio between hydroxylation and glucuronidation of propofol is subject to an inter-patient variability but this does not correlate with the dose of propofol. However, the variation of the metabolite profile observed in the present report does not seem to indicate an extended role of metabolism in pharmacokinetic variability.

Adult↗
PubMed2006

Rat cytochrome P450 2C11 in liver microsomes involved in oxidation of anesthetic agent propofol and deactivated by prior treatment with propofol.

Propofol (2,6-diisopropylphenol) is a widely-used anesthetic agent attributable to its rapid biotransformation. Liver microsomal cytochrome P450 (P450) isoforms involved in the biotransformation of propofol in rats and the effects of propofol in vivo on P450 levels in rats were investigated. Of six cDNA-expressed rat P450 isoforms tested, CYP2B1 and CYP2C11 had high catalytic activities from 5 microM and 20 microM propofol concentrations, respectively. Rates of propofol metabolism, at a substrate concentration of 20 microM based on the reported human blood concentration, were decreased by intraperitoneal treatment of propofol with male rats, in contrast to a strong induction by phenobarbital. Single intravenously administered propofol (10 mg/kg) caused the decrease of total P450 and CYP2C contents and activities of testosterone 16alpha-hydroxylation and propofol metabolism in liver microsomes from male rats. The suppressive effects were caused by administered propofol (10 mg/kg) twice every 4 h on CYP2B activities such as testosterone 16beta-hydroxylation or pentoxyresorufin O-depentylation, in addition to the strong suppression of CYP2C function by the single propofol treatment. These results suggest that CYP2C11, presumably deactivated by propofol, has an important role in propofol metabolism in rat liver microsomes. Repeated administration of propofol could markedly decrease the biotransformation of propofol via P450 deactivation.

Anesthetics, Intravenous↗
PubMed2003

The effect of mixing lidocaine with propofol on the dose of propofol required for induction of anesthesia.

UNLABELLED: Lidocaine is used to reduce pain associated with propofol injection, either mixed with propofol or preceding it as a separate injection. The addition of lidocaine to propofol causes destabilization of the emulsion and reduces anesthetic potency in rats and humans. We conducted a randomized double-blinded study on 67 patients to assess the effect of mixing lidocaine with propofol on the dose of propofol required for the induction of anesthesia. Patients in Group S (n = 32) received IV lidocaine 0.2 mg/kg followed by an infusion of propofol whereas those in Group M (n = 35) received IV normal saline (placebo) followed by an infusion of a freshly prepared mixture of propofol 1%/lidocaine 1% in 10:1 volume ratio. The infusion was stopped when the subjects lost consciousness, as detected by the syringe-drop method. There was no statistically significant difference between the two groups in the mean (95% confidence interval) doses of propofol required for loss of consciousness: 2.0 (1.8-2.2) mg/kg for Group S versus 1.9 (1.7-2.0) mg/kg for Group M (P = 0.206). Mixing 20 mg of lidocaine with 200 mg of propofol is unlikely to affect the dose of propofol required for the induction of anesthesia. IMPLICATIONS: Adding lidocaine to propofol destabilizes the propofol emulsion. A randomized double-blinded trial found no statistically significant difference in the doses of propofol required for the induction of anesthesia whether administered as a freshly prepared propofol 1%/lidocaine 1% 10:1 mixture or as a separate injection after a dose of lidocaine.

Adolescent↗
PubMed2000

Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery.

OBJECTIVE: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). METHODS: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery. RESULTS: The average pharmacokinetic parameter estimates of clearance (Cl), volume of distribution at steady state (Vd,ss), elimination half-life (t1/2,beta) and distribution half-life (t1/2,alpha) observed in the three groups were 28 +/- 1.1 ml/kg/min, 1.8 +/- 0.12 l/kg, 94 +/- 4.1 min and 3.1 +/- 0.26 min, respectively (mean +/- SEM, n = 24) and no significant differences were noted between the three formulations (P > 0.05). In one patient receiving propofol 6% SAZN, in two patients receiving propofol 1% SAZN and in three patients receiving Diprivan-10, the level of sedation was inadequate and additional sedative medication had to be given. In all other 18 patients, the level of sedation was adequate. The mean propofol concentration in these six inadequately sedated patients was lower than the adequately sedated patients (P = 0.015). The serum triglyceride concentrations were not significantly different between the groups studied. No adverse events occurred in any of the patients. CONCLUSIONS: The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN are in good agreement with those of the 1% formulations. Propofol 6% SAZN therefore provides a useful alternative to the commercially available 1% formulation for short-term sedation in the intensive care unit. Expected advantages in long-term sedation of the 6% over 1% formulation are the subject of an ongoing study.

Adult↗
PubMed1997

Outpatient general anesthesia: a comparison of a combination of midazolam plus propofol and propofol alone.

STUDY OBJECTIVE: To compare the hemodynamics, efficacy, safety, and postoperative recovery of patients following the use of either midazolam plus propofol or placebo plus propofol for induction and maintenance of general anesthesia for outpatient surgical procedures of less than two hours' duration. DESIGN: Prospective, parallel, randomized, double-blind, placebo-controlled, multicenter study. SETTING: Ten outpatient surgery centers. PATIENTS: 203 ASA physical status I, II, and III patients undergoing various outpatient surgical procedures. INTERVENTIONS: Patients were randomly assigned to one of the two treatment groups. For induction of anesthesia, Group 1 received midazolam (0.077 +/- 0.0021 mg/kg) via slow intravenous (IV) push plus continuous infusion propofol (provided in a concentration of 5 mg/ml), and Group 2 received placebo plus full-concentration (10 mg/ml) propofol. Thereafter, Group 1 received half-concentration propofol and Group 2 received full-concentration propofol via continuous infusion for maintenance of anesthesia. Investigators administered doses of study medication in a blinded fashion as required to achieve the desired clinical effect. Drugs used to maintain anesthesia were restricted to study drug, short-acting opioids, and nitrous oxide. Succinylcholine chloride or vecuronium were used to facilitate intubation of study patients. MEASUREMENTS AND MAIN RESULTS: There were no statistically significant differences between the midazolam/propofol and placebo/propofol groups with respect to the mean (SE) decrease in mean arterial pressure from pre-dose to time of intubation or from time of intubation to initiation of surgery; the mean (SE) time required from initiation of study medication to completion of intubation [6.7 (0.23) minutes vs. 7.0 (0.26) minutes, respectively]; or the mean (SE) amount of propofol required to induce and maintain anesthesia [6.03 (0.329) mg/kg vs. 9.71 (0.489) mg/kg, respectively]. There was no significant difference between the two treatment groups in the time to recovery following the completion of surgery (as assessed by Aldrete Post Anesthesia Recovery Score). Most patients (approximately 79%) in both groups rated the quality of the anesthetic regimen as excellent; however, as assessed by patient questionnaires, fewer patients in the midazolam/ propofol group were able to recall the events surrounding their surgical procedure as compared with patients in the placebo/ propofol group (89.2% vs. 77.9%; p = 0.022). There were no differences between the two groups with respect to the frequency or severity of adverse events. CONCLUSIONS: Concomitantly administered midazolam and reduction-concentration propofol did not exacerbate the well-described hypotensive effects of full-strength propofol during induction of anesthesia. The time to intubation was equivalent with the combination of midazolam/propofol as compared with propofol alone. Recovery from the two regimens was not significantly different. However, reduced recall of perioperative events was observed more often in the midazolam/propofol regimen compared with propofol alone.

Adolescent↗
PubMed1999

Growth of Escherichia coli in propofol, lidocaine, and mixtures of propofol and lidocaine.

BACKGROUND: Microorganisms grow rapidly in propofol. Extrinsic contamination of propofol is thought to be a source of postoperative sepsis and wound infection. We studied growth of a strain of Escherichia coli in thiopental, propofol, lidocaine, and mixtures of propofol and lidocaine. METHODS: The pathogen was exposed to 2.5% thiopental; 1.0% propofol; 1.0%, 2.0% and 4.0% preservative-free lidocaine; and propofol solutions containing 0.25%, 0.5%, 1.0%, 2.0%, or 4.0% lidocaine for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 h at room temperature, respectively. The inocula from these suspensions were cultured for 48 h at 37 degrees C after the antimicrobial activity of the local anesthetics in the inocula was inactivated by a 1:1000 dilution with distilled water. RESULTS: No organisms grew after exposure to 2.5% thiopental. The exposure of E. coli to propofol increased the colony count to approximately 90 times the control count. The colony counts of E. coli after exposure to 1.0%, 2.0% and 4.0% lidocaine and 0.25%, 0.5%, 1.0%, 2.0% and 4.0% lidocaine in 1.0% propofol were lower than the counts after exposure to 1.0% propofol (P = 0.0048, 0.0027, 0.0003, 0.0503, 0.0188, 0.0080, 0.0044, and 0.0001, respectively). The growth rate of the microorganism was significantly higher in cultures exposed to 1.0% propofol than that in cultures exposed to lidocaine alone or lidocaine-propofol mixtures (P < 0.0001, respectively). CONCLUSION: Lidocaine possesses bacteriostatic activity against E. coli. Addition of lidocaine to propofol confers its bacteriostatic activity to the mixture and may decrease the hazard of infection associated with the extrinsic contamination of propofol.

Anesthetics, Intravenous↗
PubMed2000

Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: a prospective, randomized study.

AIM: Adequate patient sedation is mandatory for most interventional endoscopic procedures. Recent anaesthesiologic studies indicates that propofol and midazolam act synergistically in combination and therefore may be superior to sedation with propofol alone in terms of sedation efficacy, recovery and costs (due to a presumed lower total dose of propofol needed). METHODS: A total of 239 consecutive patients undergoing therapeutic EGD or ERCP (EGD/ERCP-ratio, 1:1) randomly received either propofol alone (n=120, group A, loading dose 40-60 mg intravenously, followed by repeated doses of 20 mg) or propofol plus midazolam (n=119, group B, initial midazolam dose of 2. 5-3.5 mg intravenously, followed by repeated doses of 20 mg of propofol) for sedation. Vital signs (heart rate, blood pressure, oxygen saturation, electrocardiogram) were continuously monitored. Procedure-related parameters, the recovery time and quality (post-anaesthesia recovery score) as well as the patient's co-operation and tolerance to the procedure (visual analogue scale) were prospectively assessed. RESULTS: Patients of group A and B were well matched with respect to demographic and clinical data, endoscopic findings, and the type of associated procedures. In group A, a mean dose of 0.25 +/- 0.13 mg.min/kg propofol was used compared to 0.20 +/- 0.09 mg.min/kg of propofol in group B (P < 0.01, plus additional 2.9 +/- 0.5 mg of midazolam). Clinically relevant changes in vital signs were observed at comparable frequencies with a lowering of the systolic blood pressure < 90 mmHg in six out of 119 patients in group B and one out of 120 patients in group A (P=0.07). The sedation efficacy was rated similarly in both groups, whereas the mean recovery time (group A, 19 +/- 7 min vs. group B, 25 +/- 8 min, P < 0.05) as well as the recovery score (post-anaesthesia recovery score group A, 8.0 +/- 1.1 vs. post-anaesthesia recovery score group B, 7.3 +/- 1.2, P < 0.001) were significantly better with propofol alone than with propofol plus midazolam. CONCLUSION: During therapeutic endoscopy, sedation with propofol and midazolam requires a lower total dose of propofol, but otherwise has no superior sedation efficacy and is associated with a slower post-procedure recovery than sedation with propofol alone.

Adult↗
PubMed2005

Comparative study between propofol in a long-chain triglyceride and propofol in a medium/long-chain triglyceride during sedation with target-controlled infusion.

This study was performed to compare the pharmacological characteristics of propofol in an emulsion of both medium- and long-chain triglycerides (MCT/LCT) with those of propofol in an LCT emulsion, by measuring the sedative level and the plasma concentration of propofol during sedation using a target-controlled infusion (TCI) technique. Forty ASA 1 or 2 adult patients who required spinal anaesthesia for surgery were enrolled in this study. The patients were divided into two groups: a propofol LCT group (n = 20) and a propofol MCT/LCT group (n = 20). Propofol was injected intravenously at target blood concentrations of 2.0, 3.0 and 4.0 microg x ml(-1). The bispectral (BIS) index was recorded, and arterial blood was drawn to measure the actual plasma concentrations of propofol at each predicted concentration. Propofol was assayed by high-performance liquid chromatography. Propofol MCT/LCT was associated with significantly less pain than propofol LCT (P < 0.05). There were no significant differences between the two groups in BIS index or in plasma concentration of propofol at each predicted concentration. Computer-generated TCI of propofol MCT/LCT during sedation is comparable with that of propofol LCT with respect to pharmacokinetics and pharmacodynamics. The formulation of MCT/LCT has a beneficial effect with respect to less pain on injection.

Adult↗
PubMed2005

Recovery after anesthesia for short pediatric oncology procedures: propofol and remifentanil compared with propofol, nitrous oxide, and sevoflurane.

Anesthesia techniques in children undergoing short painful oncology procedures should allow rapid recovery without side effects. We compared the recovery characteristics of two anesthetic techniques: propofol with sevoflurane and nitrous oxide and a total IV technique using propofol and remifentanil. Twenty-one children, undergoing two similar painful procedures within 2 wk were studied in a single-blind manner within patient comparison. The order of the techniques was randomized. Propofol and remifentanil involved bolus doses of both propofol 3-5 mg/kg and remifentanil 1-4 microg/kg. Propofol with sevoflurane and nitrous oxide involved propofol 3-5 mg/kg with 2%-8% sevoflurane and 70% nitrous oxide. The primary outcome variable was the time taken to achieve recovery discharge criteria; other recovery characteristics were also noted. The mean age of the children was 6.5 yr (range, 2.5-9.8 yr). Nineteen had lymphoblastic leukemia and two had lymphoma. All children had intrathecal chemotherapy and one had bone marrow aspiration. Most procedures lasted <4 min. The mean time to achieve recovery discharge criteria was appreciably shorter after propofol and remifentanil than propofol with sevoflurane and nitrous oxide by nearly 19 min (P = 0.001). All other time comparisons had similar trends and statistical differences. Seven parents expressed a preference for the propofol and remifentanil technique compared with one preferring propofol with sevoflurane and nitrous oxide. Children are apneic during the procedure and require respiratory support from an anesthesiologist. Discharge readiness from the recovery ward was achieved on average 19 min earlier after propofol with remifentanil compared with the combination of propofol, sevoflurane and nitrous oxide. Parents more often preferred propofol with remifentanil.

Anesthesia Recovery Period↗
PubMed2004

A comparison of anesthetic quality in propofol-spinal anesthesia and propofol-fentanyl anesthesia for total knee arthroplasty in elderly patients.

STUDY OBJECTIVE: To compare propofol plus spinal anesthesia during spontaneous ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia during mechanical ventilation with an endotracheal tube on quality of recovery after anesthesia. DESIGN: Prospective, randomized study. SETTING: Hirosaki National Hospital. PATIENTS: 150 patients (aged > 70 years) undergoing total knee arthroplasty. INTERVENTIONS: Patients were divided randomly into two groups, to receive spontaneous ventilation with a Laryngeal Mask Airway during propofol-spinal anesthesia, or to receive propofol-fentanyl anesthesia with mechanical ventilation via endotracheal tube. MEASUREMENTS: Quality of anesthesia recovery such as nausea, vomiting, headache, pain throat, hoarse voice, back pain, dizziness, feeling comfortable, dreaming, recovery times in recovery of anesthesia, recovery times, postoperative pain, confusion, was assessed. MAIN RESULTS: The frequency of postoperative pain throat, hoarse voice, and nausea was significantly lower in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The time to extubation, emergence, response to commands, and orientation were significantly faster (p < 0.001) in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The frequency of postoperative confusion occurring in the propofol-spinal anesthesia group during the first 24 hours was significantly lower than that of the propofol-fentanyl anesthesia group (p = 0.03). CONCLUSIONS: Propofol-spinal anesthesia provided better and faster recovery than did propofol-fentanyl anesthesia for elderly patients undergoing total knee arthroplasty.

Aged↗
PubMed2004

Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion.

BACKGROUND: GPI 15715 is a new water-soluble prodrug that is hydrolyzed to release propofol. The objectives of this crossover study in volunteers were to investigate the pharmacokinetics and pharmacodynamics of GPI 15715 in comparison with propofol emulsion. METHODS: In two separate sessions, nine healthy male volunteers (19-35 yr, 70-86 kg) received GPI 15715 and propofol emulsion as a target controlled infusion over 60 min. In the first 20 min, the propofol target concentration increased linearly to 5 microg/ml. Subsequently, the targets were reduced to 3 microg/ml and 1.5 microg/ml for 20 min each. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h and pharmacokinetics were analyzed. The pharmacodynamic effect was measured by the median frequency of the power spectrum of the electroencephalogram, and a sigmoid model with effect compartment was fitted to the data. RESULTS: Compared with propofol emulsion, propofol from GPI 15715 showed a different disposition function and especially larger volumes of distribution. The propofol effect site concentration for half maximum effect was 2.0 +/- 0.5 microg/ml for GPI 15715 and 3.0 +/- 0.7 microg/ml for propofol emulsion (P < 0.05). Propofol from GPI 15715 did not show a hysteresis between plasma concentration and effect. CONCLUSIONS: Compared with propofol emulsion, propofol from GPI 15715 showed different pharmacokinetics and pharmacodynamics, particularly a higher potency with respect to concentration. These differences may indicate an influence of the formulation.

Adult↗
PubMed2002

Propofol and midazolam versus propofol alone for sedation following coronary artery bypass grafting: a randomized, placebo-controlled trial.

The aim was to compare the efficacy and side-effects of propofol combined with a constant, low dose of midazolam versus propofol alone for sedation. In a prospective, randomized and double-blinded study, 60 male patients scheduled for elective coronary bypass grafting were enrolled. Postoperatively, patients were stratified to receive either a continuous intravenous infusion of midazolam 1 mg/h or placebo. Target Ramsay sedation score was 3 to 5 corresponding to conscious sedation. An intention-to-treat design for propofol was performed to reach target sedation. Efficacy of sedation was statistically significantly higher in the group midazolam + intention-to-treat with propofol compared with the group placebo + intention-to-treat with propofol (91% vs 79%; P=0.0005). Nine of 27 patients in the midazolam group (33.4%) and nine of 26 patients in the placebo group (34.6%) needed no supplementary propofol. Weaning time from mechanical ventilation was longer in the midazolam group whether or not they required supplemental propofol when compared with placebo group (all: 432 +/- 218 min vs 319 +/- 223 min; P=0.04; supplementary propofol: 424 +/- 234 min vs 265 +/- 175 min; P=0.03). The cumulative number of patients remaining intubated was significantly higher in the group midazolam + propofol compared with the group placebo + propofol (P=0.03). In conclusion, target sedation is reached slightly more often by the co-administration of propofol and a low dose of midazolam, but weaning time from mechanical ventilation is prolonged by the co-administration of propofol and a low dose of midazolam.

Aged↗
PubMed2004

Preventing pain on injection of propofol: a comparison between lignocaine pre-treatment and lignocaine added to propofol.

A randomized double-blind study compared two methods of preventing the pain from injection of propofol, lignocaine pre-treatment followed by propofol and lignocaine added to propofol. One hundred patients received a 4 ml solution intravenously with a venous tourniquet for 1 minute, followed by propofol mixed with 2 ml of solution. Patients were divided into two treatment groups of 50 patients each: 4 ml 1% lignocaine pre-treatment followed by propofol and 2 ml saline, or 4 ml saline followed by propofol and 2 ml 2% lignocaine. Pain was assessed with a 100 mm visual analogue scale after induction and in recovery. The incidence of injection pain was 8% in the propofol mixed with lignocaine group, and 28% in the lignocaine pre-treatment group. This difference is statistically significant (P=0.017). For those patients who had pain, the mean pain score was 26.5 on induction for the propofol with lignocaine group (n =4), while the mean score was 44.4 for the pre-treatment group (n=13). The difference was not statistically significant (P=0.25). None of the propofol mixed with lignocaine group recalled pain, while 13 of the pre-treatment group did so. Lignocaine pre-treatment does not improve the immediate or the recalled comfort of patients during propofol induction when compared to lignocaine added to propofol. It is recommended that lignocaine should be added to propofol for induction rather than given before induction.

Anesthetics, Intravenous↗
PubMed2005

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells.

INTRODUCTION: Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 microg/ml). Clinically relevant concentrations of propofol (3 to 8 microg/ml; 20 to 50 microM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA). METHODS: The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells. RESULTS: At low concentrations (25 microM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells. CONCLUSION: These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.

Antineoplastic Agents↗
PubMed2005

A comparison of sevoflurane-propofol versus sevoflurane or propofol for laryngeal mask airway insertion in adults.

In a prospective, randomized study, we investigated the incidence of successful insertion of laryngeal mask airway (LMA) at the first attempt and the incidence of side effects after LMA insertion using the combination of sevoflurane and propofol as compared with either sevoflurane or propofol alone for induction of anesthesia. Eighty-three unpremedicated ASA physical status I-II patients were anesthetized with a single vital capacity breath (VCB) of sevoflurane 8% supplemented with IV propofol 1.5 mg/kg, a single VCB of sevoflurane 8%, or IV propofol 3 mg/kg. The coinduction technique was associated with the most frequent incidence of successful LMA insertion at the first attempt (93.5%) than either sevoflurane alone (46%) or propofol alone (61.5%) (P < 0.001). Propofol-induced induction of anesthesia allowed the fastest insertion of LMA and was associated with the least frequent incidence of postoperative nausea and vomiting. However, this advantage of propofol was offset by a frequent incidence of pain on injection (69%) and the occurrence of movements during insertion of the LMA (50% in the propofol group versus 19% and 26% in the sevoflurane and sevoflurane-propofol groups, respectively; P < 0.05), as well as a more frequent incidence of apnea (84% in the propofol group versus 7% and 16% in the sevoflurane and sevoflurane-propofol groups, respectively; P < 0.001). The report shows that induction of anesthesia with sevoflurane-propofol combined provides a frequent incidence of successful LMA insertion at the first attempt that is associated with an infrequent incidence of apnea.

Adolescent↗
PubMed1992

A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits.

We evaluated and compared the effects of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine-midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam-propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits.

Anesthesia, General↗
PubMed2006

Early postoperative cognitive recovery after remifentanil-propofol or sufentanil-propofol anaesthesia for supratentorial craniotomy: a randomized trial.

BACKGROUND AND OBJECTIVE: This study was designed to evaluate early postoperative cognitive recovery after total intravenous anaesthesia with remifentanil-propofol or sufentanil-propofol in patients undergoing craniotomy for supratentorial expanding lesions. METHODS: Sixty patients were consecutively enrolled, and randomly assigned to one of two study groups: remifentanil-propofol or sufentanil-propofol anaesthesia. To evaluate cognitive function the Short Orientation Memory Concentration Test (SOMCT) and Rancho Los Amigos Scale (RLAS) were administered to all patients in a double-blind procedure before surgery at 15, 45 min and 3 h after extubation. RESULTS: Mean extubation time was similar in the two groups (13 +/- 5 min vs. 19 +/- 6 min). A significantly larger number of patients in the remifentanil-propofol group than in the sufentanil-propofol group required antihypertensive medication postoperatively to maintain mean arterial pressure within 20% of baseline (18/30 vs. 4/29; P = 0.0004). Intergroup analysis showed no differences in baseline SOMCT scores (28 +/- 1 vs. 28 +/- 1) whereas mean SOMCT scores at 15, 45 min and 3 h after extubation were significantly higher in the remifentanil-propofol group (30 patients) than in the sufentanil-propofol group (29 patients) (22 +/- 3 vs. 16 +/- 3; P < 0.0001 and 27 +/- 1 vs. 22 +/- 3; P < 0.0001; 28 +/- 1 vs. 26 +/- 2; P = 0.0126). CONCLUSIONS: In conclusion, propofol-remifentanil and propofol-sufentanil are both suitable for fast-track neuroanaesthesia and provide similar intraoperative haemodynamics, awakening and extubation times. Despite a higher risk of treatable postoperative hypertension propofol-remifentanil allows earlier cognitive recovery.

Analysis of Variance↗