Behavioral and physiological effects of remifentanil and alfentanil in healthy volunteers.
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BACKGROUND: The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug. METHODS: Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test. RESULTS: Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects. CONCLUSIONS: The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued. (+info)
Balanced pre-emptive analgesia: does it work? A double-blind, controlled study in bilaterally symmetrical oral surgery.
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We studied 32 patients undergoing bilateral symmetrical lower third molar surgery under general anaesthesia to determine if the combined effects of pre-emptive local anaesthetic block using 0.5% bupivacaine, together with i.v. tenoxicam and alfentanil had any benefits over postoperative administration. Patients acted as their own controls and were allocated randomly to have surgery start on one side, the second side always being the pre-emptive side. Difference in pain intensity between the two sides was determined using visual analogue scales completed by each individual at 6 h, and at 1, 3 and 6 days after operation. A long-form McGill pain questionnaire was also used to assess difference in pain intensity between the two sides on the morning after surgery. There was no significant difference in pain intensity at any time after surgery. Our findings indicate that the combined use of pre-emptive analgesia from 0.5% bupivacaine, tenoxicam and alfentanil did not reduce postoperative pain intensity in patients undergoing molar exodontia. (+info)
Recirculatory and compartmental pharmacokinetic modeling of alfentanil in pigs: the influence of cardiac output.
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BACKGROUND: Cardiac output (CO) is likely to influence the pharmacokinetics of anesthetic drugs and should be accounted for in pharmacokinetic models. The influence of CO on the pharmacokinetic parameters of alfentanil in pigs was evaluated using compartmental and recirculatory models. METHODS: Twenty-four premedicated pigs were evaluated during halothane (0.6-2%) anesthesia. They were assigned randomly to one of three groups. One group served as control. In the other groups, the baseline CO was decreased or increased by 40% by pharmacologic intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and indocyanine green (25 mg) were injected into the right atrium. Blood samples were taken for 150 min from the right atrium and aortic root. Arterial concentration-time curves of indocyanine green and alfentanil were analyzed using compartmental models (two-stage and mixed-effects approach) and a recirculatory model, which can describe lung uptake and early distribution. RESULTS: The CO of individual pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2 = 0.54), fast peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 = 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO. CONCLUSIONS: Cardiac output markedly influences the pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the predictive value of pharmacokinetic models of alfentanil. (+info)
Recovery after halothane anaesthesia induced with thiopental, propofol-alfentanil or halothane for day-case adenoidectomy in small children.
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We studied recovery from halothane anaesthesia in 93 children, aged 1-3 yr, undergoing day-case adenoidectomy. Children were allocated randomly to receive thiopental 5 mg kg-1 (group TH), alfentanil 10 micrograms kg-1 and propofol 3 mg kg-1 (group PAH) or 5% halothane (group HH) for induction of anaesthesia. In group TH, tracheal intubation was facilitated with succinylcholine (suxamethonium) 1.5 mg kg-1. In groups PAH and HH, tracheal intubation was performed without neuromuscular block, and succinylcholine was used only if required. Anaesthesia was maintained with 1-3% halothane during spontaneous respiration. Times to achieving predetermined recovery end-points were recorded. Quality of recovery was assessed using a score of 1-9 (best to worst) for sedation, crying, restlessness and agitation. A postoperative questionnaire was used to determine the well-being of the child at home, 24 h after operation. Emergence from anaesthesia (response to non-painful stimuli) occurred earlier in group HH (mean 9 (SD 6) min) than in groups PAH (13 (6) min, P < 0.01) and TH (18 (14) min, P < 0.01). Sitting up, walking and home readiness were achieved earlier in groups PAH and HH than in group TH (P < 0.05 for each variable). Children in group TH were more sedated during the first 30 min after anaesthesia than those in the two other groups (P < 0.05) while emergence-related delirium was more common in group HH than in group TH (P < 0.01). Well-being at home was similar in all groups. We conclude that induction of halothane anaesthesia with propofol-alfentanil or halothane provided more rapid recovery and earlier discharge than that with thiopental. (+info)
Haemodynamic stability and ketamine-alfentanil anaesthetic induction.
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We have determined if alfentanil could obtund the haemodynamic instability commonly seen at induction of anaesthesia with ketamine. Five groups of ASA I and II patients received ketamine 1 mg kg-1 i.v., preceded by saline (group 1) or alfentanil 10, 20, 30 or 40 micrograms kg-1 (groups 2-5, respectively). Heart rate (HR), mean arterial pressure (AP), postoperative patient complaints and dysphoria were noted. All groups showed increases (P < 0.05) in both HR and AP after administration of ketamine, which were progressively smaller as the dose of alfentanil increased. After tracheal intubation, all groups showed further increases in HR and AP, with groups 3-5 (alfentanil 20-40 micrograms kg-1) showing significant obtundation (P < 0.05) of these increases compared with group 1. No patient in any group reported postoperative dysphoria or dissatisfaction with their anaesthetic. Ketamine 1 mg kg-1 with alfentanil 20-40 micrograms kg-1 provided statistically significant obtundation of the haemodynamic instability that is common with ketamine alone. (+info)
Women emerge from general anesthesia with propofol/alfentanil/nitrous oxide faster than men.
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BACKGROUND: Recovery from general anesthesia is governed by pharmacodynamic and pharmacokinetic factors. Gender has not previously been recognized as a factor influencing the time to emergence from general anesthesia. METHODS: This multicenter study was originally designed to measure the effects of the bispectral index on intraoperative anesthetic management and patient recovery. We compared the wake-up and recovery times of 274 adults after propofol/alfentanil/nitrous oxide anesthesia. Patients were randomly assigned to have the titration of propofol performed with or without the use of bispectral index monitoring. Specific guidelines were given for the titration of drugs. The aim in all cases was to provide a safe anesthetic with the fastest possible recovery. RESULTS: There was a significant reduction in propofol dose, time to eye opening, and response to verbal command when the anesthetic was titrated using the bispectral index. Unexpectedly, gender proved to be a highly significant independent predictor for recovery time. Women woke significantly faster than men: the time from end of anesthesia to eye opening was 7.05 versus 11.22 min, P < 0.05, and response to verbal command was 8.12 versus 11.67 min, P < 0.05. These differences were significant at all four study sites and in each treatment group. Men consistently had prolonged recovery times compared to women, P < 0.001. There was no difference in the dose of anesthetic used between gender. CONCLUSIONS: Gender appears to be an important variable in recovery from general anesthesia. These findings may explain the increased reported incidence of awareness in women (three times more frequent) and support the need to include gender as a variable in pharmacokinetic and pharmacodynamic studies of anesthetic drugs. (+info)
Bone marrow harvesting using EMLA (eutectic mixture of local anaesthetics) cream, local anaesthesia and patient-controlled analgesia with alfentanil.
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Bone marrow harvesting (BMH) was performed on 40 consecutive allogeneic or autologous donors using EMLA (eutectic mixture of local anaesthetics), local anaesthesia (LA) and patient-controlled analgesia with alfentanil (PCA-A). The effect of alkalinizing the LA solution on reducing pain during LA infiltration in the presence of EMLA was also investigated. EMLA 10 g with occlusive dressing was applied to the harvest sites at least 60 min before BMH. The PCA device was programmed to deliver an intravenous loading dose of 15 microg/kg alfentanil, followed by a background alfentanil infusion of 0.05 microg/kg/min. Demand dose was 4 microg/kg and lockout time was 3 min. Donors were randomized to receive either alkalinized (n = 19) or non-alkalinized (n=21) LA solution (lignocaine 1% with 1:100000 adrenaline). While post-operative nausea and vomiting were the only side-effects, all donors in both groups reported satisfactory pain scores during LA infiltration and satisfactory overall intra-operative comfort scores. They completed BMH using either regimen successfully, found this technique acceptable and would recommend this form of anaesthesia to others. Alkalinizing the LA solution did not significantly improve the pain scores during LA infiltration in the presence of EMLA. In conclusion, BMH can be performed safely using EMLA, LA and PCA-A without major complications. (+info)
Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect.
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BACKGROUND: Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil. METHODS: Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined. RESULTS: Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC50 for alfentanil was 49.4 (32.4-66.5) ng/ml. CONCLUSION: Based on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids. (+info)