Pharmacokinetics of human cerebral opioid extraction: a comparative study on sufentanil, fentanyl, and alfentanil in a patient after severe head injury.
(9/224)
BACKGROUND: The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans. METHODS: After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia. RESULTS: Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90. CONCLUSIONS: The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes. (+info)
Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison.
(10/224)
BACKGROUND: This study compared the administration of 0.1% ropivacaine and 0.5 microg/ml sufentanil with that of 0.1% bupivacaine and 0.5 microg/ml sufentanil via patient-controlled epidural analgesia route during labor. METHODS: Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 microg/ml sufentanil or 0.1% bupivacaine and 0.5 microg/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery. RESULTS: No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively; P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD]; P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm; P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses; P < 0.05). CONCLUSIONS: Delivered as patient-controlled epidural analgesia, 0.1% ropivacaine and 0.5 microg/ml sufentanil produce less motor block but are clinically less potent than 0.1% bupivacaine and 0.5 microg/ml sufentanil. (+info)
Interaction of p-fluorofentanyl on cloned human opioid receptors and exploration of the role of Trp-318 and His-319 in mu-opioid receptor selectivity.
(11/224)
In this study, we investigated the interactions of p-fluorofentanyl, an opioid designer drug, fentanyl, sufentanyl, and morphine on cloned human mu-, kappa-, and delta-opioid receptors coexpressed with heteromultimeric G protein-coupled inwardly rectifying K(+) channels (GIRK1/GIRK2) and a regulator of G protein signaling (RGS4) in Xenopus oocytes. We demonstrate that p-fluorofentanyl more potently activates GIRK1/GIRK2 channels through opioid receptors than fentanyl and that the p-fluoro substitution also changes the potency profile from mu > kappa > delta (fentanyl) to mu > delta > or = kappa (p-fluorofentanyl). A comparison of ligand efficacy revealed that morphine, fentanyl, and its analogs less efficiently activate GIRK1/GIRK2 channels through human mu-opioid receptor than [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. Using site-directed mutagenesis, we investigated whether mutating residues Trp-318 and His-319 to their corresponding residues in kappa- and delta-opioid receptors provides the molecular basis for mu/delta selectivity and mu/kappa selectivity. Changes in EC(50) values for the W318L and W318Y/H319Y mu-opioid receptors show a partial contribution of these residues to the decreased GIRK1/GIRK2 channel activation by fentanyl analogs through kappa- and delta-opioid receptors. The most pronounced effect was observed for p-fluorofentanyl, suggesting that an interaction between the 4-fluorophenylpropanamide moiety of the drug and residues Trp-318 and His-319 is important for the resulting enhanced GIRK1/GIRK2 channel activation through the mu-opioid receptor. Finally, we demonstrate that mutation of W318L confers delta-like potency for morphine on the mutant mu-opioid receptor. (+info)
Predictive accuracy of target-controlled propofol and sufentanil coinfusion in long-lasting surgery.
(12/224)
BACKGROUND: The predictive accuracy of target concentration infusions of propofol has been documented only for less than 4 h, and no prospective study of sufentanil target controlled infusion is available. The authors investigated the predictive accuracy of pharmacokinetic models for propofol and sufentanil coadministered during long-lasting surgery. METHODS: Ten patients, American Society of Anesthesiologists physical status I and II, were studied during extended cervicofacial surgery. Target controlled infusion of propofol and sufentanil was administered during surgery using decisional algorithms, taking into consideration pain assessment, hemodynamic changes, and peroperative blood losses. Intrasubject data analysis included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble. RESULTS: The range of plasma target concentrations was 2-5 microgram/ml for propofol and 0.2-1 ng/ml for sufentanil. Median performance error was -12.1% for propofol and -10% for sufentanil. The wobble values were 11.6% and 22.3% for propofol and sufentanil, respectively. The pharmacokinetic sets used slightly overpredicted the concentrations, with negative values of divergence of 2.92% and 0.22% units/h for propofol and sufentanil, for a mean infusion period of 762 min. CONCLUSIONS: This prospective study demonstrates the predictive accuracy of the pharmacokinetic model for sufentanil infusion and confirms that for propofol during long-lasting surgery using standardized rules for the management of target controlled infusion and blood loss replacement. (+info)
Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery.
(13/224)
We have studied the pharmacokinetics and pharmacodynamics of alfentanil, fentanyl and sufentanil together with propofol in patients undergoing coronary artery bypass graft surgery (CABG). Sixty patients (age 40-73 yr, 56 male) were assigned randomly to receive alfentanil, fentanyl or sufentanil and propofol. Plasma concentrations of these drugs and times for the plasma concentration to decrease by 50% (t50) and 80% (t80) after cessation of the infusion were determined. Times were recorded to awakening and tracheal extubation. Total dose and plasma concentrations of propofol were similar in all groups. Mean total doses of alfentanil, fentanyl and sufentanil were 443, 45 and 4.4 micrograms kg-1, respectively. Time to awakening did not differ significantly. In patients receiving fentanyl, the trachea was extubated on average 2 h later than in those receiving sufentanil and 3 h later than in those receiving alfentanil (P < 0.05). The t80 of fentanyl was longer (P < 0.05) than that of alfentanil or sufentanil, and there was a linear correlation between the t80 of the opioid and the time to tracheal extubation (r = 0.51; P < 0.01). However, the t50 values for these opioids were similar and did not correlate with recovery time. In conclusion, patients undergoing CABG and who were anaesthetized with fentanyl and propofol needed mechanical ventilatory support for a significantly longer time than those receiving alfentanil or sufentanil and propofol. On the basis of the interindividual variation observed, the time to tracheal extubation was most predictable in patients receiving alfentanil and most variable in patients receiving fentanyl, a finding which may be important if the patients are transferred to a step-down unit on the evening of the operation. (+info)
Fentanyl versus sufentanil: plasma concentrations during continuous epidural postoperative infusion in children.
(14/224)
No pharmacokinetic data are available with respect to the plasma concentrations and fentanyl or sufentanil during epidural administration in children. This double-blind randomized study included 12 children (5-12 yr). Patients in group F were given an epidural loading dose of fentanyl 1.5 micrograms kg-1 and in group S sufentanil 0.6 microgram kg-1. Both groups then received a continuous epidural infusion of bupivacaine 5 mg kg-1 day-1 with either fentanyl 5 micrograms kg-1 day-1 or sufentanil 2 micrograms kg-1 day-1. An epidural PCA system was also given to the children (bolus: bupivacaine 0.2 mg kg-1 and fentanyl 0.2 microgram kg-1 or sufentanil 0.08 microgram kg-1). Maximal median concentrations of plasma (0.117-0.247 ng ml-1 for fentanyl and 0.027-0.074 ng ml-1 for sufentanil) were reached approximately 30 and 20 min respectively after the loading doses. These values were similar to those measured after 48 h. (+info)
Subarachnoid sufentanil for early postoperative pain management in orthopedic patients: a placebo-controlled, double-blind study using spinal microcatheters.
(15/224)
BACKGROUND: Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative. METHODS: Eighty patients randomly received a subarachnoid injection of 10 microg sufentanil, 5 mg bupivacaine, 2.5 microg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 microg sufentanil over 24 h. RESULTS: All drugs provided excellent pain relief within 15 min after injection, lasting 128 +/- 61 min with sufentanil, 146 +/- 74 min with bupivacaine, and 167 +/- 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100-115 min) than after the first injection (198 +/- 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 +/- 167 ng/ml) but were at the level of detection in the plasma. CONCLUSIONS: Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting. (+info)
Minimum analgesic dose of epidural sufentanil for first-stage labor analgesia: a comparison between spontaneous and prostaglandin-induced labors in nulliparous women.
(16/224)
BACKGROUND: The aim of this prospective, double-blind, sequential allocation study was to compare the effects of spontaneous and prostaglandin-induced labor on the minimum analgesic dose of epidural sufentanil in the first stage of labor. METHODS: Seventy healthy, nulliparous women, at more than 37 weeks' gestation with cervical dilatation from 2 to 4 cm, requesting epidural pain relief in labor were enrolled. The subjects were assigned to two different groups according to whether labor was spontaneous or induced with dinoprostone 0.5 mg. Parturients received 10 ml of the study solution through a lumbar epidural catheter. The initial dose was sufentanil 25 microg, and subsequent doses were determined by the response of the previous patient in the same group using up-down sequential allocation. The analgesic effectiveness was assessed using 100-mm visual analog pain scores. The up-down sequences were analyzed using the method of independent paired reversals and probit regression. RESULTS: The minimum analgesic dose of sufentanil in spontaneous labor was 22.2 microg (95% CI: 19.6, 22.8) and 27.3 microg (95% CI: 23.8, 30.9) in induced labor. The minimum analgesic dose of sufentanil in induced labor was significantly greater (P = 0.0014) than that in spontaneous labor (95% CI difference: 2.9, 9.3) by a factor of 1.3 (95% CI: 1.1, 1.5). CONCLUSION: Prostaglandin induction of labor produces a significantly greater analgesic requirement than does spontaneous labor. (+info)