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Vein pretreatment with magnesium sulfate to prevent pain on injection of propofol is not justified.

PURPOSE: Propofol produces anesthesia with rapid recovery. However, it causes pain or discomfort on injection. A number of techniques have been tried for minimizing propofol-induced pain with variable results. We have compared the efficacy of magnesium and lidocaine for the prevention of propofol induced pain. METHODS: Three hundred ASA I and II adults undergoing elective surgery were randomly assigned into three groups of 100 each. Group I received magnesium sulfate 1 g, Group II received lidocaine 2% (40 mg) and Group III received normal saline, all in a volume of 2 mL and accompanied by venous occlusion for one minute. Induction with propofol 2.5 mg.kg(-1) was accomplished following the release of venous occlusion. Pain was assessed on a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain at the time of pretreatment and propofol injection. Results were analyzed by 'Z' test. A P value of < 0.05 was considered as significant. RESULTS: Pain during i.v. pretreatment with magnesium was 31% as compared to 2% for both the lidocaine and control groups (P < 0.05). Seventy-six percent of patients in the control group had pain during i.v. propofol as compared to 32% and 42% in the magnesium and the lidocaine groups respectively (P < 0.05). Lidocaine and magnesium pretreatment were equally effective in attenuating pain during the propofol injection (P > 0.05). CONCLUSIONS: Intravenous magnesium and lidocaine pretreatment are equally effective in attenuating propofol-induced pain. However, magnesium pretreatment itself causes pain. Therefore, there is no justification in the use of magnesium pretreatment for attenuating pain associated with i.v. propofol.

Adolescent↗

Propofol inhibits renal cytochrome P450 activity and enflurane defluorination in vitro in hamsters.

PURPOSE: To determine the effect of propofol on renal cytochrome P450 activity and defluorination of enflurane. METHODS: Renal microsomes were prepared by homogenization and differential centrifugation from pooled hamster kidneys. Defluorination of enflurane was assessed by measuring free fluoride metabolites after reacting enflurane with renal microsomes incubated with various concentrations, 0.05 - 1.0 mmol x L(-1) propofol in the NADPH-generating system. Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were evaluated within microsomes preincubated with propofol and reacted with the specific marker substrates, aniline, benzo(a)pyrene, erythromycin and pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively. RESULTS: Renal defluorination of enflurane was inhibited by clinical concentrations, 0.05 mmol x L(-1) of propofol (P < 0.05). Dose-dependent inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within kidney microsomes was related to propofol concentration. Propofol demonstrated a profound inhibition of renal pentoxyresorufin dealkylase activity even at low concentrations, 0.05 mmol x L(-1) (P < 0.01). Propofol did not exhibit inhibition of erythromycin N-demethylation of kidney microsomes except at high concentration, 1.0 mmol x L(-1). Spectral analyses of key coenzymes of renal cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase, demonstrated an inhibition when incubated with high concentrations of propofol (P < 0.05). CONCLUSION: In an in vitro study in an NADPH-generating system of hamster kidney microsomes, propofol, in clinical concentrations, exhibited a broad-spectrum of inhibition to renal monooxygenase activities and enflurane defluorination.

Anesthetics, Inhalation↗

Hypnotic and cardiovascular effects of proprietary and generic propofol formulations do not differ.

PURPOSE: The aim of the study was to compare the potency of two different propofol formulations: proprietary and generic propofol using the bispectral index (BIS) monitoring. METHODS: Forty female patients undergoing breast surgery received propofol 3 mg x kg(-1) followed by propofol infusion adjusted to maintain a 40% BIS value, supplemented by 50% nitrous oxide. Proprietary or generic propofol was administered in a randomized double-blind manner. RESULTS: The propofol mg/BIS% ratio obtained after the bolus dose, the cumulative infused propofol mg/BIS% ratio at the end of each five-minute interval and the total dose of propofol administered as bolus + infusion were similar between the two groups. The two groups did not differ with regard to systolic and diastolic blood pressure, heart rate, end-tidal carbon dioxide and arterial oxygen saturation. CONCLUSION: The two propofol formulations are equipotent when hypnotic effect is assessed by BIS monitoring.

Adult↗

Propofol-containing sedatives increase levels of parathyroid hormone.

OBJECTIVE: To evaluate the effects of propofol and propofol containing disodium edetate (ethylenediaminetetraacetic acid [EDTA]) on the parathyroid-calcium axis in normal subjects. DESIGN: Randomised, double-blind, age-stratified, crossover trial. SETTING: Single centre. PATIENTS: A total of 50 healthy subjects. INTERVENTIONS: Each subject was randomised to receive propofol or propofol containing EDTA on day 1 and the alternate treatment between days 15 and 29, with a 2-week wash-out period in between. On the day of treatment, subjects received a bolus of trial medication (1 or 2 mg/kg) followed by a 60-minute observation period. At the end of 60 minutes, subjects received trial medication infused for 60 minutes at 1 of 4 randomised infusion rates (25, 50, 100, or 200 microg/kg per min). Subjects were monitored for an additional 60 minutes following the infusion. MEASUREMENTS AND RESULTS: Blood pressure, heart rate, respiratory rate, oxygen saturation, blood ionised calcium concentration, serum total magnesium concentration, serum intact parathyroid hormone (PTH) level, and plasma EDTA level were assessed at periodic intervals during and following the bolus and continuous infusion of trial medication. Mean arterial pressure significantly decreased (p < 0.05) following the bolus injection of both trial medications and returned to baseline at 60 minutes; it significantly decreased again during the continuous infusion and returned to baseline during recovery. Heart rate and respiratory rate fluctuated in both groups with significant increases and decreases throughout the study period following the bolus injection; both returned to baseline during the recovery period in each group. Ionised calcium and total magnesium concentrations remained within normal limits and were unchanged in response to both study medications. PTH levels significantly increased following the bolus injection of both study drugs. The increase in PTH levels was greater with higher doses of study medication during the infusion period. There was no difference in the response of blood pressure, heart rate, respiratory rate, or PTH levels between propofol and propofol with EDTA. EDTA levels increased significantly during the infusion of propofol with EDTA, reaching mean levels of 240 ng/mL. CONCLUSIONS: The results of this study indicate that propofol increases PTH levels in normal subjects; however, propofol with EDTA does not alter ionised calcium or total magnesium concentrations.

Adult↗

[Incidence and quality of dreaming during anesthesia with propofol in comparison with enflurane].

UNLABELLED: Since the introduction of propofol into clinical practice, dreaming during general anaesthesia has been frequently reported with this drug. We investigated the incidence and character of these dreams with regard to distinction from intraoperative awareness and in comparison with habitual dreams or dreams during general anaesthesia with enflurane. METHOD: A total of 230 patients (ASA I-II) undergoing minor elective surgery were randomly assigned to one of two groups. Both groups received the same premedication (1 mg flunitrazepam) the previous evening. After induction using etomidate 2 mg/kg, anaesthesia in group I was maintained using 0.8%-1.5% enflurane supplemented in the sense of "balanced anaesthesia" with fentanyl, vecuronium, and nitrous oxide. Anaesthesia in group II was induced with propofol 2 mg/kg. After a saturation phase of approximately 10 mg/kg.h, 5-6 mg/kg.h was administered for maintenance supplemented by fentanyl, Vecuronium, and N2O as in group I. Interviews were conducted preoperatively, just after recovery from anaesthesia, and 24 h later. We inquired about preoperative fears or concerns, sensory perceptions, and the incidence and character (pleasant, unpleasant, indifferent) of habitual dreams. After recovery the patients were asked if they had had any conscious perceptions, whether they believe them to be dreams or reality, and repeated the preoperative questions as to common feelings and the character of sensory perceptions. RESULTS: The two groups were not entirely comparable due to the distribution of sex and age, but we did not find any differences in preoperative grades of fear and incidence of dreams. Of the propofol patients, 60% dreamed intraoperatively versus 11% in the enflurane group. No evidence of any intraoperative awareness was found. Because of the low incidence of dreams in the enflurane group, a comparison of detailed information between the groups could not be provided. Except for 1, all patients in the propofol group had very pleasant dreams compared to their habitual dreams (4.5% in the enflurane group). One day after surgery 37% of all patients in the propofol group remembered having dreamed intraoperatively. We did not found any correlation to the incidence of habitual dreaming, preoperative fear, age, sex, duration of anaesthesia, or total dose of propofol. Furthermore, intraoperative dreams differed from habitual dreams in character and content. CONCLUSIONS: We conclude that sensory experiences during propofol anaesthesia are not stimulus-related perceptions or awareness, but dreams similar to normal ones. In view of the absence of clear signs of stimulus-related response, we presume that dreaming is a specific side effect of propofol. Because of the absence of difficulties, dreaming during propofol anaesthesia appears not to be a disadvantage with regard to the quality of anaesthesia.

Adult↗

[Interaction of nimodipine and propofol in dogs. Hemodynamics and cardiodynamics].

UNLABELLED: Nimodipine is frequently used for treatment of cerebral vasospasm in patients undergoing intracerebral vascular surgery and during intensive care therapy of patients with subarachnoid haemorrhage. Propofol is being increasingly used as a hypnotic drug in neuroanaesthesia and for sedation in critically ill patients. There is evidence of a propofol effect on voltage-dependent calcium channels; hence, the administration of propofol may interact with the haemodynamic effects of nimodipine. We investigated the haemodynamic interactions of both compounds in chronically instrumented dogs. METHODS: Five mongrel dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic (ABP), and left ventricular pressure (LVP), LV dP/dt, cardiac output (CO), systemic vascular resistance (SVR), coronary blood flow velocity (CBFV), and myocardial wall-thickening fraction (WTF). After complete recovery from surgery and assessment of normal resting blood gas values and temperature, all animals received on separate days either propofol 30 mg/kg.h (P), nimodipine in two maintenance doses in the awake state (N), or the combination of nimodipine and propofol (N+P). The maintenance doses of nimodipine in N and N+P were 1 and 2 micrograms/kg.min for 40 min each after a bolus of either 10 or 20 micrograms/kg min over 2 min. Measurements were performed as controls, in the middle (20 min), and at the end (40 min) of each maintenance infusion of nimodipine or at equivalent points in time in group P (Fig. 1). Animals receiving propofol were mechanically ventilated after endotracheal intubation. Blood gas values were kept within the normal range. All data were analysed with repeated measures of ANOVA followed by student's t-test with Bonferroni correction. RESULTS: There was no statistically significant difference for any of the measured parameters between N and N+P or between the two maintenance doses of nimodipine (Table 1). HR was significantly higher with both doses of nimodipine in the awake state compared to the control values (123 +/- 7.1 and 146 +/- 6.4 vs 78 +/- 2.4/min). The administration of nimodipine with and without propofol led to a significant increase in CBFV (Fig. 2). However, there was no difference in CBFV between nimodipine in the awake state and in combination with propofol (Fig. 2). CONCLUSIONS: We conclude that administration of propofol does not alter the systemic haemodynamic and regional myocardial effects of a nimodipine infusion in a dose of 1 or 2 micrograms/kg.min in chronically instrumented dogs.

Anesthetics, Intravenous↗

The effect of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under propofol anaesthesia in an ovine model.

OBJECTIVE: To compare the effects of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under steady-state propofol anaesthesia with the awake state. DESIGN: Prospective, randomised, interventional animal study. SETTING: University laboratory. SUBJECTS: Six studies in two cohorts of adult ewes: awake and steady-state propofol anaesthesia (15 mg/min). INTERVENTIONS: In random order, each animal received ramped infusions of adrenaline, noradrenaline (0-40 microg/min) and dopamine (0-40 microg/kg per min). MEASUREMENTS AND RESULTS: Cerebral blood flow (CBF) was measured continuously from changes in Doppler velocities in the sagittal sinus and normalised to a PaCO(2) 35 mmHg. Propofol decreased CBF by 55% relative to pre-anaesthesia values (p=0.0001). All three catecholamines significantly and equivalently increased mean arterial pressure (MAP) from baseline in a dose-dependent manner in both awake and propofol cohorts. Adrenaline significantly increased CBF from baseline in both awake sheep (p<0.01) and during propofol anaesthesia (p<0.001); noradrenaline and dopamine did not statistically increase CBF. When comparing the effects of individual catecholamines with each other within each cohort, no statistically significant difference between the catecholamines was demonstrated. (p>0.05). Using linear regression analysis, normalised CBF was correlated against associated changes in MAP. No significant differences were demonstrated between the slopes of regression lines for adrenaline, noradrenaline and dopamine in either cohort (ANCOVA). There was a statistically significant difference between the intercepts of the awake and propofol cohorts (p<0.0001), but no difference between the slopes (p=0.69). CONCLUSIONS: Over a specific dose range, catecholamine-induced hypertension caused increased CBF during steady-state propofol anaesthesia. This effect was offset by an associated reduction in CBF caused by propofol. The concomitant administration of propofol and catecholamines was not associated with altered autoregulatory function compared to the awake state.

Anesthesia, Intravenous↗

Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase.

Nitric oxide is an active oxidant that contributes to the physiology and pathophysiology of macrophages. Propofol has been widely used in intravenous anesthesia. It possess antioxidant and immunomodulating effects. This study aimed to evaluate the effects of propofol on nitric oxide production in lipopolysaccharide-activated macrophages. Exposure of macrophages to propofol (25, 50 and 75 micro M), to lipopolysaccharide (0.5, 1, 1.5 and 2 ng/ml) or to a combination of propofol and lipopolysaccharide did not affect cell viability. However, propofol at 100 micro M led to significant cell death ( P<0.05). The levels of nitrite, an oxidative product of nitric oxide, were increased in lipopolysaccharide-treated macrophages in a concentration-dependent manner ( P<0.01), while propofol could concentration-dependently decrease the lipopolysaccharide-enhanced nitrite levels ( P<0.01). Immunoblotting analysis revealed that lipopolysaccharide increased the protein level of inducible nitric oxide synthase (iNOS). The co-treatment of propofol and lipopolysaccharide significantly reduced this lipopolysaccharide-induced iNOS protein (357+/-49 x 10(3) versus 92+/-6 x 10(3) arbitrary units, P<0.01). Analysis by reverse transcriptase-polymerase chain reaction showed that lipopolysaccharide induced mRNA of iNOS, but that the inductive effect was inhibited by propofol (95+/-7 x 10(2) versus 30+/-4 x 10(2) arbitrary units, P<0.01). This study has demonstrated that propofol, at therapeutic concentrations, could suppress nitric oxide biosynthesis by inhibiting iNOS expression in lipopolysaccharide-activated macrophages. The mechanism of suppression was at a pretranslational level.

Animals↗

Propofol does not modify the hemodynamic status of children with intracardiac shunts undergoing cardiac catheterization.

Immobility and cardiovascular stability are required for cardiac catheterization. Pediatric patients need a type of sedation that also allows spontaneous ventilation without supplemental oxygen. Propofol has been adequate in hemodynamically stable patients with congenital heart disease undergoing cardiac catheterization. However, mild systemic hypotension caused by propofol may increase a preexisting right-to-left shunt. The aim of this study is to evaluate, in pediatric patients scheduled for cardiac catheterization, the effects of propofol on systemic and pulmonic circulations. Fifteen patients aged 18 months to 9 years were studied. After a fast of 4-6 hours for solid food, the patient arrived at the cardiac catheterization suite, where an IV catheter was placed. Usual monitoring was used. For sedation, without supplemental oxygen, patients received 1 mg/kg of fentanyl followed by propofol (1-2 mg/kg) titrated to immobility during preparation of the groin. A continuous infusion of propofol (100 mg/kg/min) was also started to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations, and pressures, were recorded; Qp and Qs were calculated. The same set of data was re-corded 4 minutes after discontinuation of propofol and when the patient was responding to tactile stimuli. Despite lower pressures during propofol infusion, as compared with those pressures measured after discontinuation of propofol, the extent of the intracardiac shunt remained unchanged. Propofol seems to be an adequate sedative agent for pediatric patients undergoing cardiac catheterization, including those with intracardiac shunts.

Anesthetics, Intravenous↗

Propofol in status epilepticus: little evidence, many dangers?

INTRODUCTION: Several guidelines recommend the use of propofol for the treatment of refractory status epilepticus. An increased mortality rate in high dose, long-term treatment with propofol in adult patients was published recently. This prompted us to assess the literature on the scientific evidence for the efficacy and safety of propofol in the treatment of refractory status epilepticus. METHODS: Medline was searched and the three authors independently reviewed all Medline abstracts for selection of papers. RESULTS: We included 22 articles with original data on the use of propofol in refractory status epilepticus. Randomised clinical trials were lacking. Two non-randomised studies compared propofol with barbiturates and midazolam respectively. Both studies reported a higher risk of mortality for propofol. In addition, case reports and case series on the use of propofol as anaesthetic or sedative in children and adults reported several lethal cases. CONCLUSIONS: Serious doubts may be raised on the safety of propofol in the treatment of refractory status epilepticus. The two non-randomised studies and several case reports show an increased risk of mortality. Guidelines should not recommend the use of propofol as a routine treatment in refractory status epilepticus before a proper randomised trial has been performed.

Anticonvulsants↗

The effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion system.

The purpose of this study was to assess the effect of gynecologic laparoscopy on propofol concentrations administered by the target-controlled infusion (TCI) system. Thirteen patients undergoing gynecologic laparoscopy (intraabdominal pressure of 10 mmHg) were enrolled in this study. Anesthesia was induced with vecuronium 0.1 mg.kg(-1) and propofol, then maintained by 60% nitrous oxide and sevoflurane in oxygen and a constant infusion of propofol. Propofol was administered to all subjects by means of a target-controlled infusion to achieve propofol plasma concentration at 6.0 microg.ml(-1) at intubation and 2.0 microg.ml(-1) after intubation. Before and during laparoscopy, plasma propofol concentration was determined using high-performance liquid chromatograhy. Cardiac output (CO) and effective liver blood flow (LBF) were also measured using indocyanine green as an indicator. Before and during pneumoperitoneum, there were no significant differences in propofol concentrations between each point. Propofol concentrations were well achieved to predicted concentrations administered by the TCI system during gynecologic laparoscopy under propofol and sevoflurane anesthesia.

Adult↗

Nitrous oxide can enhance the hypnotic effect, but not the suppression of spinal motor neuron excitability by propofol in humans.

PURPOSE: We investigated whether nitrous oxide can enhance the suppressive effect of propofol on spinal motor neuron excitability in humans. METHODS: Sixteen adult patients were prospectively randomly assigned to be given either propofol alone (group P; n = 8) or a supplement of 66% nitrous oxide with propofol (group PN; n = 8) for intraoperative sedation. Propofol was administered by a target-controlled infusion system to maintain sequentially increasing plasma propofol concentrations (Cpt) of 0.5, 0.8, 1.0, 1.3, 1.5 and 1.8 microg x ml(-1) in all patients. Assessment of the patient's level of sedation in both groups was performed with the Wilson Sedation Scale (WSS). F-wave analysis on the left abductor pollicis brevis muscle was carried out for the assessment of spinal motor neuron excitability at each plasma propofol concentration. RESULTS: Significant differences in the WSS scores between group P and group PN were observed at 0.8, 1.0, 1.3, and 1.5 microg x ml(-1) of Cpt (group P < group PN; P < 0.01). Cpt greater than 1.0 microg x ml(-1) significantly reduced F-wave persistence in a concentration-dependent manner, and the ICpt 50 and ICpt 95 values for plasma propofol concentration (plasma propofol concentrations that produced 50% and 95% inhibition of the baseline, respectively) were 1.05 and 1.95 microg x ml(-1) in group P, and 1.07 and 2.14 microg x ml(-1) in group PN, respectively. CONCLUSION: These results suggest that nitrous oxide can enhance the hypnotic effect, but not the suppression of spinal motoneuron excitability by propofol in humans at clinical levels of Cpt.

Adult↗

Biochemical evaluations of the effects of loreclezole and propofol on the GABAA receptor in rat brain.

The effects of loreclezole on the function of the gamma-aminobutyric acid type A (GABAA) receptor complex in rat cerebral cortical membrane preparations were compared with those of propofol and diazepam. Loreclezole and propofol modulated [3H]muscimol binding and t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to washed and unwashed membranes with potencies and efficacies greater than those of diazepam. Loreclezole and propofol enhanced [3H]flunitrazepam binding to washed membranes with efficacies lower than those of GABA and muscimol. Both loreclezole and propofol showed biphasic effects on [35S]TBPS binding to washed membranes: at low concentrations (5 to 10 microM), both drugs, with different efficacies, enhanced [35S]TBPS binding whereas, at higher concentrations (30 to 100 microM), they inhibited this biochemical parameter. In contrast, diazepam enhanced [35S]TBPS binding to washed membranes at all concentrations tested. The combination of loreclezole with GABA, at a concentration (0.3 microM) that only slightly increased [35S]TBPS binding to washed membranes, reversed the increase in binding elicited by loreclezole (5 to 10 microM) and significantly potentiated the inhibitory effect exerted by higher concentrations (30 to 100 microM) of this drug. Similar effects were observed with the combination of GABA and propofol. However, GABA had no effect on the enhancement of [35S]TBPS binding induced by diazepam. The ability of GABA to reverse and potentiate the effects of loreclezole and propofol on [35S]TBPS binding to washed membranes was shared by pentobarbital (200 microM) and alphaxalone (3 microM). These anesthetics showed greater efficacies in combination with pentobarbital (200 microM) and alphaxalone (3 microM). These anesthetics showed greater efficacies in combination with propofol than with loreclezole. These results suggest that, unlike diazepam, loreclezole and propofol may activate the receptor-associated Cl- channel in the absence of GABA. Furthermore, the difference in the pharmacological profiles of loreclezole and propofol may result from their different effectiveness in activating the receptor Cl- channel directly.

Anesthetics↗

Effects of propofol, pentobarbital and alphaxalone on t-[35S]butylbicyclophosphorothionate binding in rat cerebral cortex.

The effects of propofol, pentobarbital, alphaxalone, etomidate and diazepam on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to membrane preparations from rat cerebral cortex were studied in the absence of gamma-aminobutyric acid (GABA). Addition of low concentrations (3-10 microM) of propofol to washed membrane preparations (devoid of GABA) markedly enhanced [35S]TBPS binding (maximal enhancement, 85%), whereas higher concentrations (50-100 microM) inhibited this parameter. Diazepam also enhanced [35S]TBPS binding in this preparation (maximal enhancement, 38%). In contrast, pentobarbital, alphaxalone and etomidate decreased [35S]TBPS binding in a concentration-dependent manner. The propofol-induced increase in [35S]TBPS binding in washed membranes was completely reversed by the addition of GABA at a concentration (0.3 microM) that alone did not modify [35S]TBPS binding (78% increase with 10 microM propofol alone, 33% decrease in the additional presence of GABA). The ability of GABA to reverse the effect of propofol on [35S]TBPS binding in washed membranes was shared by pentobarbital (200 microM) and alphaxalone (3 microM); etomidate (20 microM) only partially antagonized the effect of propofol. Diazepam at a concentration (30 microM) that alone had no effect on [35S]TBPS binding failed to modify the propofol-induced increase in [35S]TBPS binding, whereas at a concentration (3 microM) that alone increased [35S]TBPS binding the effect of diazepam was additive with that of propofol. The addition of bicuculline to washed membranes failed to abolish the increase in [35S]TBPS binding induced by propofol or diazepam, but completely antagonized the effects of pentobarbital, alphaxalone and etomidate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

Propofol versus thiamylal-enflurane anesthesia for outpatient laparoscopy.

STUDY OBJECTIVE: To determine whether propofol anesthesia differs from thiamylal-enflurane anesthesia in induction characteristics, intraoperative hemodynamics, postoperative side effects, and postoperative psychomotor function recovery. DESIGN: A randomized, double-blind, two-group study. SETTING: A large university hospital with gynecologic outpatient operations performed in an integrated operating room suite. PATIENTS: Sixty adult women (ASA physical status I or II) undergoing an outpatient gynecologic laparoscopic operation with an anesthesia time of approximately 60 minutes. INTERVENTIONS: No pharmacologic premedication. Pretreatment with intravenous droperidol 0.6 mg and sufentanil 0.2 micrograms/kg before induction of anesthesia. Anesthesia was induced with either thiamylal 4 mg/kg (Group 1) or propofol 2.5 mg/kg (Group 2). Anesthesia was maintained with either nitrous oxide (N2O) and enflurane, 2-0.5% inspired concentrations; (Group 1) or with a continuous infusion of propofol 200-100 micrograms/kg/min and N2O (Group 2). MEASUREMENTS AND MAIN RESULTS: In psychomotor function tests (Trieger dot test and p-deletion test) administered preoperatively and postoperatively, no difference was found between the groups. No difference was found in induction time, although significantly more patients reported pain after the propofol injection, or in intraoperative hemodynamics (mean arterial pressure and heart rate). Immediate recovery time (emergence from anesthesia) and intermediate recovery time (ambulation, oral intake, and discharge time) were significantly shorter after propofol anesthesia. Fewer postoperative side effects, such as nausea and vomiting, were reported after propofol anesthesia. CONCLUSIONS: Induction and maintenance of anesthesia with propofol were comparable to those with thiamylal-enflurane, except patients experienced more pain on injection after propofol. Both immediate and intermediate recovery were more rapid after propofol anesthesia compared with enflurane-based anesthesia.

Adult↗

Patient-controlled drug administration during local anesthesia: a comparison of midazolam, propofol, and alfentanil.

STUDY OBJECTIVE: To evaluate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia. DESIGN: Randomized, single-blind comparative study. SETTING: Outpatient surgery center at a university teaching hospital. PATIENTS: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups. INTERVENTIONS: After premedication with midazolam 1 mg intravenously (IV) and fentanyl 50 micrograms IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 micrograms/ml, midazolam 0.4 mg/ml, or propofol 10 mg/ml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 ml/hr. MEASUREMENTS AND MAIN RESULTS: The total intraoperative dosages of alfentanil, midazolam, and propofol were 2.7 +/- 1.1 mg, 4.7 +/- 2.7 mg, and 114 +/- 42 mg, respectively, for procedures lasting 48 +/- 28 minutes to 51 +/- 19 minutes (means +/- SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil (28%) than with midazolam (3%) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was significantly decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients. CONCLUSIONS: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperative complications than was alfentanil.

Adult↗

Propofol-nitrous oxide versus thiopental sodium-isoflurane-nitrous oxide for strabismus surgery in children.

STUDY OBJECTIVES: To assess the quality of anesthesia and recovery and the frequency of postanesthetic retching and vomiting with propofol anesthesia for pediatric strabismus surgery. DESIGN: Randomized, open, prospective study. SETTING: University hospital. PATIENTS: Forty children scheduled for strabismus surgery. INTERVENTIONS: The 40 patients were all premedicated with oral midazolam and received intraoperative opioids. They were divided into two groups: Twenty children received propofol at induction, followed by maintenance of anesthesia with propofol infusion and an oxygen-nitrous oxide (O2-N2O) mixture. The other 20 children received thiopental sodium at induction, followed by isoflurane in an O2-N2O mixture. MEASUREMENTS AND MAIN RESULTS: At induction, pain and spontaneous movements were seen significantly more with propofol (11 of 20 vs. 0 of 20 for pain and 13 of 20 vs. 0 of 20 for spontaneous movements; p < 0.001), whereas thoracic rigidity was observed only with thiopental sodium (4 of 20). During maintenance of anesthesia, significantly more oculocardiac reflexes were seen with propofol (10 of 20 vs. 3 of 20; p < 0.02). The interval between termination of anesthesia and extubation was significantly shorter with propofol (13 minutes vs. 16 minutes; p < 0.02). For the first 24 hours after surgery, significantly less retching and vomiting were observed in the propofol group (4 of 20 vs. 11 of 20; p = 0.02). CONCLUSIONS: Propofol induction and maintenance of anesthesia for strabismus surgery in children significantly lowers the frequency of postanesthetic retching and vomiting, but propofol is associated with pain and spontaneous movements at induction and a high frequency of oculocardiac reflexes during maintenance infusion.

Anesthesia Recovery Period↗

Clinical pharmacokinetics of propofol given as a constant-rate infusion and in combination with epidural blockade.

STUDY OBJECTIVES: To investigate the pharmacokinetics of propofol in combination with epidural anesthesia or with intravenous (i.v.) alfentanil infusion, and to investigate the clinical feasibility of this anesthetic technique in lower abdominal surgery. DESIGN: Randomized, open clinical study. SETTING: Operating theaters and postanesthesia recovery unit at the department of gynecology of a university medical center. PATIENTS: 20 healthy, consenting ASA physical status I and II adult female patients undergoing lower abdominal surgery. INTERVENTIONS: A total i.v. anesthetic technique was used in all patients. In Group 1, a continuous infusion of propofol was combined with an epidural block with bupivacaine. Group 2 patients received a combination of propofol and alfentanil infusions. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of propofol are best fitted to a two-compartment open model and were similar in both patient groups. Propofol blood clearance was 29.8 +/- 6.51 ml/min/kg, and volume of distribution was 3.60 +/- 1.34 L/kg, resulting in a blood elimination half-life of 144 +/- 46 minutes. The entire period of anesthesia was stable in the alfentanil group. In the epidural group, the initial period of anesthesia was too light as judged by the autonomic response to tracheal intubation, which also correlated in time to a lower propofol blood concentration than was seen in the alfentanil group. No evidence was found that an epidural block induced a change in propofol kinetics, apart from the lower blood concentration during the initial period of anesthesia. CONCLUSIONS: We could not show any statistically significant influence of an epidural blockade on the pharmacokinetic parameters of propofol. Nevertheless, the concentration-time profile changed during infusion, rendering the described infusion regimen, in combination with epidural anesthesia, unsatisfactory for adequate hypnosis. The propofol infusion regimen combined with alfentanil provided immediate and stable blood concentrations that were adequate for surgery.

Adult↗