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PubMed2005

Blood concentration of propofol in a patient with delayed emergence from propofol-nitrous oxide anesthesia.

We measured the blood concentration of propofol in a patient with delayed emergence from propofol-nitrous oxide anesthesia. A 78-year-old man underwent subtotal gastrectomy under both epidural and propofol-nitrous oxide anesthesia and did not regain consciousness soon after termination of propofol infusion. Preoperative laboratory examination revealed anemia and a low blood total protein concentration, but there was no evidence of impaired liver function. While the anesthesiologists were waiting for the patient to regain consciousness, a surgeon mentioned that the common hepatic artery might have been occluded during surgical manipulation. Arterial blood samples were obtained 50 and 80 minutes after termination of propofol infusion, and the blood concentration of propofol was measured. We considered that clearance of propofol through the hepatic route may have been impaired; however, the actual blood concentrations of propofol were not significantly increased compared with the respective blood concentrations obtained in the simulation. Therefore, the acute liver damage did not significantly impair elimination of propofol. Because most propofol molecules in the blood bind to proteins and erythrocytes, it is suspected that the anemia and low blood total protein concentration led to an increase in the free fraction of propofol in the blood, thereby delaying emergence from anesthesia.

Aged↗

PubMed1999

Effects of propofol (intravenous propofol emulsion) on cell membranes measured by electrofusion and electroporation.

The influence of propofol (CAS 2078-54-8 (intravenous propofol emulsion) on cell membrane properties was investigated in vitro with techniques of cell electrofusion and cell electroporation. Human lymphoma cells and plant protoplasts were chosen as a model system. Propofol (intravenous propofol emulsion) decreased the electrofusion yield of the cells and their membrane permeability. A 50% decrease in relative electrofusion was observed in human lymphoma cells in the presence of about 0.05 mmol/l propofol (intravenous propofol emulsion) and in plant protoplasts in the presence of about 0.1 mmol/l. The fusion of human lymphoma cells was inhibited to 100% at concentrations higher than 0.2 mmol/l propofol and 0.4 mmol/l intravenous propofol emulsion. The membrane permeability of human lymphoma cells decreased by the factor of two with increasing propofol concentrations up to about 0.1 mmol/l. The effects of electroporation were highly reversible. Propofol (intravenous propofol emulsion) was more effective than tetracaine. These sensitive techniques are suitable for the investigation of interactions between anesthetic drugs and the cell membrane.

Anesthetics, Intravenous↗

PubMed2005

Comparison on pain on injection of a small particle size-lipid emulsion of propofol and standard propofol with or without lidocaine.

Pain on injection, reported in 28-90% of patients, is one of the most described side effects of the intravenous application of propofol. Many different approaches have been used in attempts to minimize propofol induced pain, with varied results. Using a randomized, double-blind protocol design, the author-section pain following the administration of two different particle size formulations of propofol with or without lidocaine in 388 nonpremedicated ASA I-II adult patients scheduled for elective surgery under general anesthesia. Patients were allocated randomly to receive either a small particle size lipid emulsion of propofol (Anepol: average particle size 140.5 nm), or standard propofol (Propofol: average particle size 193.3 nm), by dividing into 4 groups. Group 1 received 2 ml NaCl 0.9% and Propofol, group 11 received 2 ml lidocaine 2% and Propofol, group III received 2 ml NaCl 0.9% and Anepol and group IV received 2 ml lidocaine 2% and Anepol into a dorsal vein of the hand. Pain during propofol injection was evaluated over 5-10 seconds, until loss of conscious, using a four point scale. Sixty-seven patients (69.1%) complained of pain in group 1, as compared with 50%, 41.2% and 39.2% in group II, III and IV (p < 0.05). The reported severity of injection pain was not significantly different between the groups. The authors conclude that small particle size propofol causes less pain on injection than standard propofol.

Adult↗

PubMed2005

Comparison of propofol-alfentanil and propofol-remifentanil anaesthesia in percutaneous nephrolithotripsy.

BACKGROUND AND OBJECTIVE: Percutaneous nephrolithotripsy (PCNL) is used for the fragmentation and removal of stones from the renal pelvis and renal calyceal systems. We compared the effects of propofol-alfentanil or propofol-remifentanil anaesthesia on haemodynamics, recovery characteristics and postoperative analgesic requirements during percutaneous nephrolithotripsy. METHODS: Thirty non-premedicated patients were randomly allocated to receive either propofol-alfentanil (Group A) or propofol-remifentanil (Group R). The loading dose of the study drug was administered over 60 s (alfentanil 10 microg kg(-1) or remifentanil 1 microg kg(-1)) followed by a continuous infusion (alfentanil 15 microg kg(-1) h(-1) or remifentanil 0.15 microg kg(-1) min(-1)). Propofol was administered until loss of consciousness and maintained with a continuous infusion of 75 microg kg(-1) min(-1) in both groups. Atracurium was given for endotracheal intubation at a dose of 0.5 mg kg(-1) and maintained with a continuous infusion of 0.4 mg kg(-1) h(-1). Mean arterial pressure heart rate, the total amount of propofol, time of recovery of spontaneous ventilation, extubation and eye opening in response to verbal stimulus and analgesic requirement were recorded. RESULTS: In Group A, mean arterial pressure was higher at the first minute in the prone position, and during skin incision and lithotripsy, and heart rate was higher during skin incision and lithotripsy when compared with Group R (P < 0.05). The total amount of propofol did not differ between groups. Time of recovery of spontaneous ventilation, extubation and eye opening were significantly shorter in Group R than Group A (P < 0.05). CONCLUSIONS: Both propofol-remifentanil and propofol-alfentanil anaesthesia provided stable haemodynamics during percutaneous nephrolithotripsy, whereas propofol-remifentanil allowed earlier extubation.

Adult↗

PubMed2002

The influence of induction technique on intubating conditions 1 min after rocuronium administration: a comparison of a propofol-ephedrine combination and propofol.

We conducted a double blind, prospective, controlled trial comparing intubating conditions after induction with a propofol-ephedrine combination or propofol alone, followed by rocuronium. One hundred adult patients were randomly assigned to receive either propofol 2.5 mg x kg(-1) and ephedrine 15 mg in combination or propofol 2.5 mg x kg(-1) given over 30 s, followed by rocuronium 0.6 mg x kg(-1) given over 5 s. Tracheal intubation was performed 1 min later. Jaw relaxation, vocal cord position and diaphragmatic response were used to assess intubation conditions. Tracheal intubation was successful and acceptable in all patients. There was a significantly higher proportion of intubating conditions graded as 'excellent' in the propofol-ephedrine group (84%) than in the propofol group (32%) (p < 0.0001). Vocal cord position and response to intubation were significantly better in the propofol-ephedrine group, although jaw relaxation was similar. Mean arterial pressure was maintained at pre-induction levels in the propofol-ephedrine group. In conclusion, induction with propofol and ephedrine in combination provided significantly better intubating conditions than propofol alone, when followed by rocuronium.

Adult↗

PubMed1999

Effects of propofol, propofol-nitrous oxide and midazolam on cortical somatosensory evoked potentials during sufentanil anaesthesia for major spinal surgery.

Recording of cortical somatosensory evoked potentials (CSEP) enables monitoring of spinal cord function. We studied the effects of propofol, propofol-nitrous oxide or midazolam during sufentanil anaesthesia on CSEP monitoring during major spinal surgery. Thirty patients with normal preoperative CSEP were allocated randomly to one of the following anaesthesia regimens: propofol (2.5 mg kg-1 followed by 10-6 mg kg-1 h-1) with or without nitrous oxide, or midazolam (0.3 mg kg-1 followed by 0.15 mg kg-1 h-1) combined with sufentanil 0.5 microgram kg-1 h-1 in the propofol and midazolam groups, or 0.25 microgram kg-1 h-1 in the propofol-nitrous oxide group. CSEP were elicited by alternate right and left tibial posterior nerve stimulation and recorded before and after induction (15 min, 1, 2 and 3 h), and during skin closure. CSEP latencies were not significantly modified in the three groups. CSEP amplitude decreased significantly in the propofol-nitrous oxide group (from mean 2.0 (SEM 0.3) to 0.6 (0.1) microV; P < 0.05) but not in the propofol (from 1.8 (0.6) to 2.2 (0.3) microV) or midazolam (1.7 (0.5) to 1.6 (0.5) microV) groups. The time to the first postoperative voluntary motor response (recovery) delay was significantly greater in the midazolam group (115 (19) min) compared with the propofol and propofol-nitrous oxide groups (43 (8) and 41 (3) min, respectively). Consequently, the use of propofol without nitrous oxide can be recommended during spinal surgery when CSEP monitoring is required.

Adult↗

PubMed2002

Propofol phosphate, a water-soluble propofol prodrug: in vivo evaluation.

UNLABELLED: After a single IV injection of the water-soluble propofol prodrug propofol phosphate (PP) in mice, rats, rabbits, and pigs, propofol was produced rapidly (1-15 min), inducing dose-dependent sedative effects. In mice, the hypnotic dose (HD(50)), lethal dose (LD(50)), and safety index (defined as a ratio: LD(50)/HD(50)) were 165.4 mg/kg, 600.6 mg/kg, and 3.6, respectively. Propofol was produced with half-lives of 5.3 +/- 0.6 min in rats, 2.1 +/- 0.6 min in rabbits, and 4.4 +/- 2.4 min in pigs. The maximal concentration was dose and species dependent. The elimination half-life was 24 +/- 12 min in rats, 21 +/- 16 min in rabbits, and 225 +/- 56 min in pigs. Propofol generated from PP produced pharmacological effects similar to those described in the literature. We found a correlation between PP dose and duration of sedation with propofol concentrations larger than 1.0 microg/mL, which produced somnolence and sedation in rats and pigs. Adequate sedation and, at large enough doses, anesthetic-level sedation were produced after the administration of PP. Overall, PP, the water-soluble prodrug of propofol, seems to be a viable development candidate for sedative and anesthetic applications. IMPLICATIONS: Propofol phosphate, a water-soluble prodrug of the widely used IV anesthetic propofol, was developed and evaluated in mice, rats, rabbits, and pigs after IV injection. The results of the study clearly demonstrate the feasibility of the prodrug approach to achieve sedative and anesthetic levels of propofol in laboratory animals; this warrants further evaluation in humans.

Anesthetics, Intravenous↗

PubMed1998

Awakening propofol concentration with and without blood-effect site equilibration after short-term and long-term administration of propofol and fentanyl anesthesia.

BACKGROUND: The propofol awakening concentration can vary. However, the effect site awakening propofol concentration will be a fixed value. The purpose of this study was to determine the awakening propofol concentrations obtained from infusion Schede using abrupt discontinuation of propofol (half-maximal effective concentration [EC50]) or a descending decrease in concentration to allow blood-effect site equilibration (EC50eq). METHODS: Patients undergoing short-term (group 1) and long-term (group 2) elective surgery were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with both groups receiving the same propofol (3 microg/ml) and fentanyl (1 ng/ml) concentrations 20-30 min before the end of surgery until the end. Then both groups were further divided into two subgroups: subgroup A abrupt discontinuation, and subgroup B descending concentrations of propofol (15-min duration per concentration). In the A subgroups, the response to verbal command was evaluated every 30 s. In the B subgroups, the blood propofol concentrations just permitting and just preventing response to command were averaged individually. The EC50 and EC50eq values were determined by probit analysis. RESULTS: The EC50 of group 1A was 1 microg/ml, which was significantly less than the 1.6 microg/ml of group 2A (P < 0.05). The awakening time of group 1A was 5.2 +/- 1.8 min, which was significantly shorter than the 9.3 +/- 3.5 min of group 2A (means +/- SD). The EC50eq of both groups 1B and 2B was 2.2 microg/ml. CONCLUSIONS: The EC50eq was independent of propofol infusion length, compared with the EC50. Thus the potential for hysteresis during emergence from propofol anesthesia was confirmed.

Adult↗

PubMed2001

Respiratory sites of action of propofol: absence of depression of peripheral chemoreflex loop by low-dose propofol.

BACKGROUND: Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol. METHODS: In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 microg/ml (P(low)), and two studies at a target propofol concentration of 1.5 microg/ml (P(high)) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD. RESULTS: Plasma propofol concentrations were approximately 0.5 microg/ml for P(low) and approximately 1.3 mg/ml for P(high), Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (P(low); P < 0.01 vs. control) and 0.9 +/- 0.1 l x min(-1) x mmHg(-1) (P(high); P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; P(low), 0.5 +/- 0.2; P(high), 0.5 +/- 0.2 l x min(-1) x mmHg(-1)). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (P(low); P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (P(high); P < 0.01 vs. control). CONCLUSIONS: Sedative concentrations of propofol have an important effect on the control of breathing, showing depression of the ventilatory response to hypercapnia. The depression is attributed to an exclusive effect within the central chemoreflex loop at the central chemoreceptors. In contrast to low-dose inhalational anesthetics, the peripheral chemoreflex loop, when stimulated with carbon dioxide, remains unaffected by propofol.

Adolescent↗

PubMed2003

Propofol reduces perioperative remifentanil requirements in a synergistic manner: response surface modeling of perioperative remifentanil-propofol interactions.

BACKGROUND: Remifentanil is often combined with propofol for induction and maintenance of total intravenous anesthesia. The authors studied the effect of propofol on remifentanil requirements for suppression of responses to clinically relevant stimuli and evaluated this in relation to previously published data on propofol and alfentanil. METHODS: With ethics committee approval and informed consent, 30 unpremedicated female patients with American Society of Anesthesiologists physical status class I or II, aged 18-65 yr, scheduled to undergo lower abdominal surgery, were randomly assigned to receive a target-controlled infusion of propofol with constant target concentrations of 2, 4, or 6 microg/ml. The target concentration of remifentanil was changed in response to signs of inadequate anesthesia. Arterial blood samples for the determination of remifentanil and propofol concentrations were collected after blood-effect site equilibration. The presence or absence of responses to various perioperative stimuli were related to the propofol and remifentanil concentrations by response surface modeling or logistic regression, followed by regression analysis. Both additive and nonadditive interaction models were explored. RESULTS: With blood propofol concentrations increasing from 2 to 7.3 microg/ml, the C(50) of remifentanil decreased from 3.8 ng/ml to 0 ng/ml for laryngoscopy, from 4.4 ng/ml to 1.2 ng/ml for intubation, and from 6.3 ng/ml to 0.4 ng/ml for intraabdominal surgery. With blood remifentanil concentrations increasing from 0 to 7 ng/ml, the C(50) of propofol for the return to consciousness decreased from 3.5 microg/ml to 0.6 microg/ml. CONCLUSIONS: Propofol reduces remifentanil requirements for suppression of responses to laryngoscopy, intubation, and intraabdominal surgical stimulation in a synergistic manner. In addition, remifentanil decreases propofol concentrations associated with the return of consciousness in a synergistic manner.

Adult↗

PubMed2006

The performance of a target-controlled infusion of propofol in combination with remifentanil: a clinical investigation with two propofol formulations.

Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery lasting longer than 1 h received a combined TCI of propofol (Marsh parameter set; propofol randomly either dissolved with long- or middle-/long-chain triglycerides) and remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived electroencephalogram variables were determined at various stages before, during, and after surgery. Measured propofol plasma concentrations exceeded the predicted values by 59%, and 48% when recalculated with the Schnider parameter set. Pharmacokinetic population analysis showed a small central volume of distribution (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were the only variables that had a significant influence on propofol pharmacokinetics. In a second step, a new pharmacokinetic variable set for propofol was determined in the first 27 patients. Post hoc performance analysis of the remaining 27 patients showed improved accuracy using the new variable set. Our results show that when remifentanil and propofol are combined, the Marsh and Schnider parameter sets systematically underestimate propofol plasma concentrations. Presented, in part, at the Annual Meeting of the European Society of Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12, 1999.

Anesthetics, Combined↗

PubMedDate not supplied

Propofol 1% and propofol 2% are equally effective and well tolerated during anaesthesia of patients undergoing elective craniotomy for neurosurgical procedures.

BACKGROUND: The 2% formulation of the intravenous anaesthetic agent, propofol (Diprivan), delivers half the amount of lipid compared with the original 1% formulation. This may provide an acceptable alternative for patients who have an impaired ability to metabolise lipids. METHODS: This study was a multicentre, randomised, open comparison of parallel groups. Seventy-three adult patients undergoing elective craniotomy in neurosurgery were randomised to receive either propofol 1% (10 mg/ml) or propofol 2% (20 mg/ml) for induction and maintenance of anaesthesia. RESULTS: Analysis of induction time (199 s, 1%; 202 s, 2%; p > 0.05) and induction dose (1.13 mg/kg, 1.12 mg/kg; p > 0.05) shows that propofol 1% and propofol 2% are pharmacodynamically equivalent. Both formulations were similar regarding overall administration rates, recovery times, haemodynamic variables and tolerability. Plasma triglyceride levels, were lower in the propofol 2% group compared with the propofol 1% group, and significantly lower (p < 0.05) from 1 to 4 hours after induction. CONCLUSIONS: We conclude that propofol 2% is as effective and as well-tolerated as propofol 1% for anaesthesia and is an acceptable alternative to propofol 1% in patients undergoing elective craniotomy in neurosurgery. The lower lipid load suggests it may be of particular benefit to patients with disorders of lipid metabolism.

Adult↗

PubMed2002

[Bispectral index monitoring is useful to reduce total amount of propofol and to obtain immediate recovery after propofol anesthesia].

Bispectral index (BIS) is a processed EEG parameter for assessment of hypnotic effects of anesthetics. We studied whether BIS monitoring can improve recovery from propofol anesthesia and decrease the total amount of propofol needed. Forty-six patients without hypertension and obesity were studied. In the BIS group (n = 20), propofol infusion rate was adjusted to achieve a target BIS value between 40-60, increasing to 65 during the final 10 min of the surgical procedure. In the control group (n = 19), propofol infusion rate was adjusted based only on standard clinical signs. Compared with the control group, patients in the BIS group required lower propofol infusion rates(4.3 +/- 1.1 vs 4.9 +/- 0.8 mg.kg-1.h-1; P < 0.05), and the total amount of propofol decreased significantly (709 +/- 210 vs 914 +/- 326 mg; P < 0.05). BIS monitoring led to immediate recovery after propofol anesthesia. There were no significant differences in the incidence of intraoperative responses between the two groups. BIS monitoring decreased the total amount of propofol and led to immediate recovery after propofol anesthesia. These findings indicate that the use of BIS monitoring may be useful in controlling the infusion rate of propofol during surgery.

Adult↗

PubMed2005

[Comparison of propofol LCT and propofol MCT/LCT regarding the injection pain at different sites and the memory].

BACKGROUND: Incidence and intensity of pain on intravenous injection of propofol LCT were compared with those of propofol MCT/LCT. METHODS: Eighty adult patients scheduled to receive general anesthesia were divided into two groups, propofol LCT (Group L, AstraZeneca) and propofol MCT/LCT (Group M, Maruishi Pharmaceutical). The peripheral vein was inserted with an 18 gauge intravenous catheter at the dorsal hand, the wrist, or the anterior brachial region. Propofol 2.0 mg x kg(-1) was injected at the speed of 5 mg x sec(-1). Noninvasive arterial blood pressure, heart rate, a BIS value and a degree of pain were measured. We used chi2 analysis and Wilcoxon t-test for statistical evaluation. RESULTS: There was a significantly larger incidence of injection pain in the Group L than the Group M (70% vs. 30%). The pain at the brachial region was significantly less as compared with the wrist or the dorsal hand in both groups. The ratio of patients having the memory of pain on the next day to those complaing the injection pain was 50% in the Group L and 36% in the Group M. There were no significant differences between the two groups in changes in BIS values and doses of propofol necessary for the loss of consciousness. CONCLUSIONS: The results suggest that propofol MCT/LCT elicits less pain on injection than propofol LCT. The injection pain is less at the brachial region than the wrist or the hand. Amnesia of pain may be obtained both with propofol MCT/ LCT and propofol LCT.

Anesthesia, General↗

PubMed1998

[Treatment of the hypertensive response during coronary surgery: comparison of high-dose propofol to propofol with nitroprusside].

OBJECTIVE: To determine the efficacy of high doses of propofol for controlling hypertension during coronary surgery and to compared cardiovascular stability with propofol to that observed under lower doses of propofol with nitroprusside. PATIENTS AND METHODS: Forty patients were studied prospectively. The patients had good ventricular function and were scheduled for coronary surgery, randomized to two groups. Group P (n = 20) received 0.3 mg/kg propofol plus a 10 mg/kg/h perfusion. Hypertensive responses were treated with boluses of 0.3 mg/kg of propofol and progressive increases in the perfusion dose of 2.5 mg/kg/h at intervals of 2 minutes (maximum 15 mg/kg/h). If hypertension persisted it was treated with nitroprusside. Group N (n = 20) received propofol in perfusion at a dose of 8 mg/kg/h and hypertension was controlled directly with nitroprusside. During extracorporeal circulation, the propofol dose was reduced to 3 mg/kg/h in both groups and was adjusted in response to changes in arterial pressure, with nitroprusside added as needed. We recorded the number of patients becoming hypertensive during sternotomy and mediastinal dissection, the maximum doses of propofol and nitroprusside and the time taken to achieve control of hypertension. Arterial pressure and heart rate were recorded at intervals of one minute throughout the operation. RESULTS: Eight patients in group P and eleven in group N suffered hypertension (NS). Increasing the dose of propofol in group P controlled arterial hypertension in one patient. We found no significant differences between groups in amount of nitroprusside needed or time taken to bring episodes under control. Differences between the two groups in rates of intraoperative hypertension (65% in group P and 85% in group N) and hypotension (75% in group P and 55% in group N) and in duration of episodes were not statistically significant. CONCLUSIONS: Using high doses of propofol rather than moderate doses in combination with nitroprusside in coronary surgery does not improve control of either hypertension or hemodynamic stability.

Aged↗

PubMed2001

Epinephrine, norepinephrine and dopamine infusions decrease propofol concentrations during continuous propofol infusion in an ovine model.

OBJECTIVE: To determine the effects of exogenous ramped infusions of epinephrine, norepinephrine and dopamine on arterial and effluent brain blood concentrations of propofol under steady state intravenous anesthesia. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Five adult female merino sheep. INTERVENTIONS: Induction (5 mg/kg) and continuous infusion of propofol (15 mg/min) with controlled mechanical ventilation to maintain PaCO2 40 mmHg. After 1 h of continuous anesthesia, each animal randomly received ramped infusions of epinephrine, norepinephrine (10, 20, 40 microg/min) and dopamine (10, 20, 40 microg x kg x min) in 3 x 5 min intervals followed by a 30-min washout period. MEASUREMENTS: Arterial and sagittal sinus whole blood for determination of propofol concentrations using high-pressure liquid chromatography. Cardiac output using a thermodilution method. Level of consciousness using an observational scale. MAIN RESULTS: All three drugs significantly and transiently increased cardiac output in a dose-dependent fashion to a maximum of 146-169% of baseline. Baseline arterial and sagittal sinus propofol concentrations were not statistically different prior to catecholamine infusions. All three drugs significantly reduced mean arterial propofol concentrations (95 % CI, p < 0.05): epinephrine to 41.8% of baseline (11.4-72), norepinephrine to 63 % (27-99) and dopamine to 52.9 % (18.5-87.3). There were parallel reductions of concentrations in sagittal sinus blood leaving the brain. The lowest blood concentrations were associated with emergence from anesthesia. Arterial concentrations were inversely related to the simultaneously determined cardiac output (r2 = 0.74, p < 0.0001). Comparison of the data with the predictions of a previously developed recirculatory model of propofol disposition in sheep showed the data were consistent with a mechanism based on increased first pass dilution and clearance of propofol secondary to the increased cardiac output. CONCLUSIONS: Catecholamines produced circulatory changes that reversed propofol anesthesia. These observations have potential clinical implications for the use of propofol in hyperdynamic circulatory conditions, either induced by exogenous catecholamine infusions or pathological states.

Anesthetics, Intravenous↗

PubMed1995

Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat.

We evaluated the pharmacokinetics and regional distribution of propofol in the brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using high-performance liquid chromatographic determination of propofol concentration in brain, whole blood and plasma. We found that the concentration of propofol in the brain increased and decreased expeditiously during and after a 15-min and 30-min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol. Furthermore, propofol was evenly distributed in the brain and spinal cord during infusion, with a significant inter-individual variation. Upon the establishment of anesthesia 15 and 30 min following intravenous infusion of propofol, the concentration of propofol in the brain, whole blood and plasma was respectively 15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6 or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest that propofol manifests a pharmacokinetic profile that is different from at least thiopental.

Anesthesia↗

PubMed2003

Propofol 1% versus propofol 2% in children undergoing minor ENT surgery.

BACKGROUND: The induction characteristics of propofol 1% and 2% were compared in children undergoing ENT surgery, in a prospective, randomized, double-blind study. METHODS: One hundred and eight children received propofol 1% (n=55) or 2% (n=53) for induction and maintenance of anaesthesia. For induction, propofol 4 mg kg(-1) was injected at a constant rate (1200 ml h(-1)), supplemented with alfentanil. Intubating conditions without the use of a neuromuscular blocking agent were scored. RESULTS: Pain on injection occurred in 9% and 21% of patients after propofol 1% and 2%, respectively (P=0.09). Loss of consciousness was more rapid with propofol 2% compared with propofol 1% (47 s vs 54 s; P=0.02). Spontaneous movements during induction occurred in 22% and 34% (P=0.18), and intubating conditions were satisfactory in 87% and 96% (P=0.19) of children receiving propofol 1% or 2%, respectively. There were no differences between the two groups in respect of haemodynamic changes or adverse events. CONCLUSIONS: For the end-points tested, propofol 1% and propofol 2% are similar for induction of anaesthesia in children undergoing minor ENT surgery.

Adenoidectomy↗