Effects of Combining Propofol and Alfentanil on Ventilation, Analgesia, Sedation, and Emesis in Human Volunteers

Background: Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea.

Methods: Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm).

Results: During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (Delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment.     

Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers

BACKGROUND: The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil. METHODS: The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed. RESULTS: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model. CONCLUSIONS: Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.     

Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers

Background: The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil.

Methods: The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 [mu]g/kg intravenous alfentanil was given in 2 min, followed by 25 [mu]g [middle dot] kg-1 [middle dot] h-1 for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 [mu]g/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed.

Results: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil. Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model.     

Psychophysical and electrophysiological responses to experimental pain may be influenced by sedation: comparison of the effects of a hypnotic (propofol) and an analgesic (alfentanil)

Sedation may influence the responses of some experimental pain models used to test analgesic efficacy. In this study we compared the effects of a sedative (propofol) and analgesic (alfentanil) on: nociceptive reflex to single and repeated electrical stimulations; mechanical pressure pain; and evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation. We studied 12 healthy volunteers with two subanaesthetic concentrations of propofol and two analgesic concentrations of alfentanil. Both propofol and alfentanil increased the threshold for nociceptive reflex to single electrical stimulations, but only alfentanil increased the threshold for nociceptive reflex to repeated electrical stimulations. The pressure pain tolerance thresholds were increased significantly by alfentanil, whereas propofol significantly decreased the thresholds (hyperalgesia). Propofol and alfentanil induced similar reductions in the amplitudes of the evoked potentials elicited by nociceptive (electrical and laser) and non-nociceptive (acoustical) stimulation, whereas only alfentanil reduced the perceived pain to nociceptive stimulations. We have shown that sedation can influence both the psychophysical and electrophysiological responses of some experimental pain tests used to measure analgesic efficacy, and that propofol in subhypnotic doses, has no analgesic effect on painful electrical and heat stimulations, but has a hyperalgesic effect on mechanical pressure pain.      

Mixed-effects modeling of the influence of alfentanil on propofol pharmacokinetics

BACKGROUND: The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol. METHODS: The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg.kg(-1).h(-1) for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed. RESULTS: A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model. CONCLUSIONS: Alfentanil alters the pharmacokinetics of propofol. Cardiac output and heart rate have an important influence on the pharmacokinetics of propofol.     

Mixed-effects Modeling of the Influence of Alfentanil on Propofol Pharmacokinetics

Background: The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol.

Methods: The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg [middle dot] kg-1 [middle dot] h-1 for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed.

Results: A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model.     

Alfentanil co-induction for laryngeal mask insertion

We assessed the effect of two different doses of alfentanil (5 and 10 micrograms.kg-1) on the conditions for laryngeal mask airway insertion in ASA 1 and 2 patients who received propofol for induction of anaesthesia. One hundred and fifty unpremedicated patients were randomly allocated to receive either propofol 2.5 mg.kg-1 only (Group P), alfentanil 5 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A5), or alfentanil 10 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A10). The addition of alfentanil to propofol resulted in a greater ease of insertion and a better quality of airway patency. Pretreatment with alfentanil also resulted in a significantly higher success rate during the first attempt at inserting the laryngeal mask airway compared with Group P (Group P 58%, Group A5 96%, Group A10 94%). Patients in Group P were apnoeic for a mean (+/- SD) time of 3.3(+/- 1.9) min, 4.71 (+/- 2.2) min in Group A5, and 7.32(+/- 4.3) min in Group A10. The use of alfentanil 10 micrograms.kg-1 with propofol, however, led to a significant decrease in mean arterial pressure and heart rate. We concluded that pretreatment with intravenous alfentanil 5 micrograms.kg-1 prior to propofol provides excellent conditions for insertion of laryngeal mask with minimal adverse haemodynamic changes.     

Optimal Propofol-Alfentanil Combinations for Supplementing Nitrous Oxide for Outpatient Surgery

Background: The combination of propofol and alfentanil with nitrous oxide provides balanced anesthesia with rapid recovery and minimal emetic side effects. The object of this study was to compare recovery parameters at varying proportions of propofol and alfentanil, and to determine the dosing rate and plasma concentration of propofol necessary to supplement nitrous oxide in the presence of varying concentrations of alfentanil.

Methods: Forty-eight patients were anesthetized with nitrous oxide, targeted manual infusions of alfentanil (target plasma concentrations of 0, 50, 100, and 150 ng/ml), and propofol at rates that were varied up or down by 25% depending on the response (movement/no movement) of the preceding patient (at the same alfentanil target concentrations) to ulnar-nerve stimulation. The minimum concentrations of propofol and alfentanil required to prevent movement in 50% of patients (EC50) was determined by logistic regression. Speed of emergence and recovery of cognitive function, time of discharge, and incidence of side effects were compared for four different combinations of propofol and alfentanil with nitrous oxide.

Results: The EC50 for propofol alone with nitrous oxide was 6.1 [micro sign]g/ml. Alfentanil, at concentrations of 41 +/- 17 (SD), 113 +/- 54, and 130 +/- 61 ng/ml, reduced the EC50 of propofol to 3.3, 2.3, and 2.2 [micro sign]g/ml, respectively, and decreased emergence time (eye opening) to 8.1, 4.9, and 3.4 min, compared with 24.3 min for propofol alone. Side effects did not differ between groups.     

Propofol and alfentanil total intravenous anaesthesia: a comparison of techniques for major thoracic surgery

Background : Previous work has highlighted the disadvantages of propofol as a sole agent for total intravenous anaesthesia (TIVA). This randomised study investigated three combinations of propofol and alfentanil as TIVA for major thoracic surgery.
Methods : In 73 patients undergoing elective thoracic surgery, anaesthesia was conducted either with sodium thiopentone induction and inhalational maintenance (incorporating isoflurane) or with TIVA using propofol with alfentanil (by infusion at one of two rates or in incremental doses). Vital signs and recovery characteristics were recorded.
Results : There were no significant differences in heart rate or blood pressure between groups during either induction or maintenance. Depth of anaesthesia was controlled satisfactorily in all groups. Recovery characteristics were similar between treatment groups, although there was a trend towards earlier orientation
Conclusion : Continuous infusions of propofol and alfentanil provide safe and reliable TIVA for major thoracic surgery. TIVA was found to be a satisfactory technique in more elderly patients than previously described. The higher of the two alfentanil infusion rates may result in a better combination of propofol and alfentanil with respect to recovery times than the lower.     

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 μg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 μg/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.     

Effect of the association propofol-alfentanil on bronchial resistances in asthmatic patients

The bronchial resistances in 17 patients scheduled for ENT surgery were studied during general anaesthesia carried out with propofol and alfentanil. There were nine controls, all free from any allergic pathology. The other eight had bronchial hyperreactivity, with clinical asthma (one or two crises a month) treated with bronchodilators. Two had a complete Fernand-Widal syndrome, and the remaining six documented allergic asthma. All the patients were premedicated with hydroxyzine 2 mg.kg-1 orally on the eve of surgery, and two hours beforehand. Those patients who were on bronchodilators were given their drugs as usual with the premedication. Because bronchial resistances were measured with the patient breathing spontaneously (forced oscillation technique), induction was carried out in two steps, first with propofol 1.5 mg.kg-1, followed, two minutes later, by alfentanil 7 micrograms.kg-1. Once the bronchial resistances had been assessed the patient was given a further 2 mg.kg-1 dose of propofol, and alfentanil 40 micrograms.kg-1. The patient was then intubated, and anaesthesia maintained with propofol 9 mg.kg-1.h-1, and alfentanil 15 micrograms.kg-1 every fifteen minutes. In all, bronchial resistances were measured on the day before surgery, after premedication but before the patient had been given any anaesthetic drug, two minutes after the first injection of propofol, two minutes after the first injection of alfentanil, and after extubation. There were no significant differences between the two groups. Despite the small number of patients included in this study, it would seem that hydroxyzine, propofol and alfentanil may be used safely in patients with hyperreactive bronchi.     

Alfentanil-mediated analgesia during propofol injection: no evidence for a peripheral action

We have investigated if alfentanil acts via peripheral opioid receptors to relieve the pain which occurs on injection of propofol. Thirty seconds before induction of anaesthesia and immediately after a tourniquet at 50 mm Hg greater than systolic pressure was inflated on the upper arm, patients were given either placebo (n = 22), alfentanil 1 mg (n = 22) or lignocaine 40 mg (n = 22) via an i.v. cannula in the dorsum of the hand. Pain during injection of propofol was assessed using a three-point verbal rating scale, recorded at 8-s intervals. We found a significant reduction in pain after lignocaine compared with the two other groups (P < 0.001), but there was no difference between the placebo and alfentanil groups. We conclude that alfentanil does not relieve pain on injection with propofol via an action on peripheral opioid receptors when alfentanil is limited to the forearm for 30 s before induction of anaesthesia.      

The effects of alfentanil or remifentanil pretreatment on propofol injection pain

STUDY OBJECTIVE: To compare the efficacy of alfentanil, remifentanil, and saline in minimizing the propofol injection pain. DESIGN: Randomized, double-blind study. SETTING: University hospital. PATIENTS: 175 ASA physical status I and II, adult female patients undergoing minor gynecological procedures with general anesthesia. INTERVENTIONS: Unpremedicated patients were randomly allocated to one of four groups. Patients received 2 mL (1 mg) of alfentanil (n=43), 2 mL of remifentanil 0.01 mg (n = 43), 2 mL of remifentanil 0.02 mg (n=45), or 2 mL of saline (n=44) 30 seconds prior to administration 5 mL of propofol 1%. MEASUREMENTS: Patients were asked whether they had pain due to propofol injection. Their pain scores were evaluated with a Visual Analogue Scale. In the Postanesthesia Care Unit, frequency of postoperative nausea, vomiting, hypotension, and flushing were all determined. MAIN RESULT: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group (p <0.05). When the alfentanil group was compared with the remifentanil groups, significant differences in pain relief associated with injection of propofol (p <0.001) were noted. Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p <0.001). CONCLUSIONS: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group. Remifentanil was effective in preventing propofol injection pain, and should be used at a dose of at least 0.02 mg for this purpose. Remifentanil may be an alternative drug for prevention of propofol injection pain.     

Testing and modelling the interaction of alfentanil and propofol on the EEG

BACKGROUND AND OBJECTIVE: For total intravenous anaesthesia an opioid is often combined with a hypnotic. A supra-additive interaction has been reported for clinical signs such as loss of consciousness or loss of the eyelash reflex. This study investigated the type of interaction of alfentanil and propofol on the electroencephalogram. METHODS: Twenty patients scheduled for abdominal surgery were enrolled in the study. Anaesthesia was induced and maintained with alfentanil and propofol. Each patient received a target-controlled infusion of alfentanil. Three target concentrations of 150, 225 and 300 ng mL(-1) were applied to each patient in random order. Propofol was added to the alfentanil infusion by a feedback system. The set point was the range of 1.5-2.5 Hz median frequency of the electroencephalogram. Four arterial blood samples were taken within the last 20 min of each period. The mean drug concentrations were used to determine the type of interaction and an isobole was estimated by fitting Bernstein spline functions to the data. RESULTS: In 17 patients, all three alfentanil target concentrations could be administered. The test for supra-additivity as well as the isobole construction resulted in an additive type of interaction. The line of additivity cA/cA0 + cP/cP0 = 1 was best fitted for the values (standard deviation) cA0 = 1240 (51)ng mL(-1) and cP0 = 5.21 (0.36) microg mL(-1). CONCLUSIONS: The type of interaction between alfentanil and propofol on the electroencephalogram in the investigated dose range is additive. This gives the freedom and need to select the appropriate dosing ratio of alfentanil and propofol by other considerations.     

Effect of methohexitone and propofol with or without alfentanil on seizure duration and recovery in electroconvulsive therapy

We have studied the effects of methohexitone and propofol with and without alfentanil on seizure duration and recovery in this observer- blinded, prospective, randomized, crossover study involving 24 patients undergoing electroconvulsive therapy (ECT). Each patient had four treatment sessions, and received the following four i.v. regimens in random order: methohexitone 0.75 mg kg-1, methohexitone 0.50 mg kg-1 and alfentanil 10 micrograms kg-1, propofol 0.75 mg kg-1, propofol 0.50 mg kg-1 and alfentanil 10 micrograms kg-1. Additional methohexitone or propofol was given as needed in 10-20-mg increments until loss of consciousness. Suxamethonium 1.0 mg kg-1 i.v. was given for muscular paralysis. Mean motor and EEG seizure durations were longer with methohexitone-alfentanil (44.7 (SD 15.0) and 70.5 (29.7) s) than with methohexitone (37.6 (12.6) and 52.6 (15.3) s) and similarly, seizures were longer with propofol-alfentanil (36.8 (15.2) and 54.5 (20.9) s) than with propofol alone (27.2 (11.9) and 39.2 (3.9) s). Seizures were longest with methohexitone-alfentanil and shortest with propofol. Recovery time was statistically shorter in patients receiving propofol compared with methohexitone-alfentanil and methohexitone alone. Alfentanil with a reduced dose of methohexitone or propofol provided unconsciousness and increased seizure duration in patients undergoing ECT. We conclude that the combination of methohexitone with alfentanil is a good regimen for ECT, especially for patients with short seizure duration.      

Tracheal intubating conditions after induction with sevoflurane 8% in children. A comparison with two intravenous techniques

We studied tracheal intubating conditions in 120 healthy children, aged 3-12 years, in a blinded, randomised clinical trial. Children were randomly allocated to one of three groups: group PS, propofol 3 mg.kg-1 and succinylcholine 1 mg.kg-1 (n = 40); group PA, propofol 3 mg.kg-1 and alfentanil 10 microg.kg-1 (n = 40); group SF, sevoflurane 8% in 60% nitrous oxide in oxygen for 3 min (n = 40). Tracheal intubating conditions were graded according to ease of laryngoscopy, position of vocal cords, coughing, jaw relaxation and movement of limbs. Overall intubating conditions were acceptable in 39 of 40 children in the propofol/succinylcholine group, 21 of 40 children in the propofol/alfentanil group and 35 of 40 children in the sevoflurane group. Children receiving propofol and succinylcholine or sevoflurane had better intubating conditions overall than those given propofol and alfentanil (p < 0.01). In conclusion, anaesthetic induction and tracheal intubation using sevoflurane 8% for 3 min is a satisfactory alternative to propofol with succinylcholine in children.     

Comparison of propofol/alfentanil anaesthesia with isoflurane/N2O/fentanyl anaesthesia for renal transplantation

Total intavenous anaesthesia (TIVA) with propofol and alfentanil was compared with balanced anaesthesia (BA) in 30 uraemic patients undergoing renal transplantation. TIVA (n=15) was induced with propofol and alfentanil and maintained with propofol and alfentanil infusions, which were started immediately after induction. Thereafter the infusion rates were adjusted as needed. Ventilation was with oxygen in air. BA (n= 15) was induced with thiopentone and fentanyl and maintained with isoflurane/N20/fentanyl. Vecuronium was used for muscle relaxation in both groups. Mean infusion rates for propofol and alfentanil were 10 1.8 mg kg^-1 h^-1 and 70 9 μg kg^-1 h^-1, respectively. To control hypertension during TIVA, larger amounts of propofol and alfentanil were needed and slower recovery was observed than in previous studies in ASA 1–2 patients. Also, significantly more vecuronium was needed during TIVA than during BA ( P < 0.05). The recovery parameters were similar in both groups, except for the occurrence of nausea, which was less after TIVA. In conclusion, TIVA had no clinical advantages over BA.     

Esmolol promotes electroencephalographic burst suppression during propofol/alfentanil anesthesia.

This study examined the effects of an esmolol infusion on the electroencephalogram during propofol/alfentanil IV anesthesia. After informed consent, 20 patients were randomly assigned into four groups on the basis of two target alfentanil concentrations (alfentanil 50 or 150 ng/mL) and of a saline or esmolol infusion. Bispectral index (BIS), burst suppression ratio (SR), and physiologic variables were continuously monitored. A 30-min blinded infusion of saline or esmolol was started after establishing a stable baseline and followed by a washout period. The electroencephalogram was significantly suppressed by esmolol (BIS, 37 +/- 6 to 22 +/- 6, 40% decrease [mean +/- SD]; SR, 5 +/- 7 to 67 +/- 23, 13.4-fold increase) compared with baseline in the small-dose alfentanil groups. Discontinuation of esmolol reversed the response. BIS and SR were unaffected by placebo infusion. Twelve-minute to 16-min hysteresis between esmolol administration and the onset of half-maximal cortical suppression was observed. Physiologic variables and serum propofol and alfentanil concentrations were not significantly altered by esmolol. Although the mechanism remains unclear, significant cortical depression and the onset of burst suppression during a stable, computer-controlled propofol/alfentanil anesthetic was associated with esmolol infusion. IMPLICATIONS: This study demonstrated the suppression of cerebral cortical electrical activity after blinded esmolol infusion during propofol/alfentanil anesthesia. A significant lag was noted between infusion and half-maximal effect (12-16 min). Whether esmolol, a metabolite, or a secondary process was responsible for this cortical suppression remains unknown and requires further study.     

Propofol and alfentanil for sedation during placement of retrobulbar block for cataract surgery

Study Objective: To determine if the addition of alfentanil to propofol is more effective than propofol alone to provide adequate conditions for placement of a retrobulbar block prior to cataract surgery.Design: Randomized, double-blinded study.Setting: Outpatients at a university hospital.Patients: 40 adult ASA physical status I, II, and III outpatients scheduled for elective cataract surgery.Interventions: Patients were randomly assigned to receive one of four drug combinations prior to the placement of a retrobulbar block: Group 1, propofol alone; Group 2, alfentanil 5 μg/kg plus propofol; Group 3, alfentanil 10 μg/kg plus propofol; Group 4, alfentanil 15 μg/kg plus propofol. All patients were preoxygenated by face mask for two minutes prior to drug administration. The quality of conditions for block placement were determined by: (1) assessing the amount of movement by the patients while the block needle was in place, (2) cooperativeness of the patients during the operation, (3) hemodynamic side effects, (4) incidence and severity of respiratory depression, (5) incidence of nausea and vomiting, (6) recall of placement of the block, and (7) time to discharge from the hospital.Measurements and Main Results: The addition of alfentanil to propofol for sedation prior to placement of the retrobulbar block resulted in a dose-dependent reduction in movement by the patients. However, the highest dose of alfentanil (15 μg/kg) resulted in the greatest frequency (40% of the patients in this group) of respiratory depression (SpO₂ < 90%). All patients were cooperative during the operation and responsive to verbal command within 5 minutes of placement of the block. In addition, all of the patients denied being nauseated, having vomited, or recalling block placement in the recovery room or the next day.Conclusions: The combination of alfentanil and propofol may be used to sedate patients in order to limit movement and provide a cooperative, alert patient with stable hemodynamics and limited respiratory depression during placement of retrobulbar block prior to ophthalmic surgery. However, excessive dosage of these drugs may result in hazardous respiratory depression in this patient population.     

Cost comparison between three different general anaesthetic techniques for elective arthroscopy of the knee

INTRODUCTION: We compared three anaesthetic techniques for elective knee arthroscopy with special reference to cost-effectiveness. METHOD: Seventy-five ASA I-II patients having elective arthroscopy of the knee joint were randomised to receive an anaesthetic technique based on propofol, fentanyl for induction followed by sevoflurane in oxygen:nitrous oxide (1:2 l/min) for maintenance of one of two intravenous techniques: propofol alfentanil or propofol-remifentanil infusions in combination with oxygen in air. RESULTS: All patients had an uncomplicated course. No differences were seen with regard to emergence, postoperative pain or emesis or time to discharge. The anaesthetic technique based on sevoflurane was associated with the lowest cost US$ 14.7 as compared to US$ 18 for the propfol/alfentanil and US$ 19.9 for the propofol/remifentanil technique, including both cost for wastage as well as premedication and other fixed drug costs. Looking only at the anaesthetic drugs consumed, the cost per minute was US$ 0.56 for sevoflurane/nitrous oxide as compared to US$ 0.68 and 0.63 per minute for the propofol/alfentanil and proprofol/remifentanil, respectively. When the cost for wastage was taken into account, the difference in mean anaesthetic drug cost was more pronounced: the sevoflurane anaesthetic technique US$ 0.58, the propofol/alfentanil US$ 0.74 and the propofol/remifentanil US$ 0.84 per minute respectively. CONCLUSION: From a cost-minimisation point of view, anaesthesia based on sevoflurane in oxygen:nitrous oxide is the technique of choice.