The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte:plasma partition, and heptane:water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes. It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.
The perioperative pharmacokinetics of transdermally-delivered fentanyl were compared in 10 young adult (mean [range] age 32.7, [25-38] yr) and eight elderly (mean [range] age 73.7 [64-82] yr) patients following abdominal surgery. Transdermal fentanyl patches designed to release 50 micrograms h-1 were applied 2 h preoperatively and left in place for 72 h. Plasma fentanyl concentrations were measured by radioimmunoassay during patch application and for 30 h after patch removal. The mean half-time (time for plasma concentrations to double after patch application) was 4.2 h in the younger group and 11.1 h in the elderly group (P < 0.005). Mean maximum plasma concentrations were 1.9 ng ml-1 and 1.5 ng ml-1 in the younger and elderly groups respectively (ns). There were no differences in the time at which maximum plasma concentrations occurred (tmax), elimination half-life after patch removal, or AUC(0-infinity).
We administered combined femoral 3 in 1 and sciatic nerve blocks to provide postoperative pain relief in 22 consecutive patients undergoing elective knee replacement surgery under spinal anaesthesia. The patients were allocated randomly to two groups. In group A (n = 11) the blocks were performed with 0.5% bupivacaine (with adrenaline) 3 mg/kg body weight and in group B (n = 11) 0.5% plain bupivacaine in the same dose was used. Serial plasma concentrations of bupivacaine were measured for up to 2 h and the duration of postoperative analgesia was measured in both groups. No significant differences were found between the two groups. There were no clinical signs or symptoms of bupivacaine toxicity in each group. This study demonstrated that, after combined sciatic and 3 in 1 femoral block, concentrations of bupivacaine associated with toxicity were not reached, even though the dose of bupivacaine administered exceeded the manufacturer's recommended dose by 50%.
Peripheral administration of opioids has been suggested as a means of improving regional block. We studied 60 patients receiving axillary brachial plexus anaesthesia, allocated randomly to receive either normal saline 10 ml or normal saline 10 ml with alfentanil 10 micrograms/kg body weight through an axillary cannula. All patients received 1.5% lignocaine at a dose of 7 mg/kg body weight with adrenaline 1 in 200,000. The incidence of satisfactory block was similar in both groups. Although the percentage of patients with complete anaesthesia in the median nerve distribution was greater in the alfentanil group, there was no significant difference in any other distribution. The time to return of sensation and motor function was prolonged significantly in the alfentanil group (P < 0.05). After return of normal sensation, there was no significant difference between groups in postoperative analgesia. In a second part of the study, there was no significant increase in plasma concentrations of alfentanil in 10 patients given lignocaine and alfentanil, as outlined above. These observations suggest that alfentanil may have a peripheral local anaesthetic action.
Hyperlipoproteinaemic patients with raised pre beta-, or pre beta- and beta-lipoprotein fractions showed a significant (P less than 0.001) increase in binding of fentanyl to whole plasma, compared with normal subjects. The presence of chylomicra had no significant effect on binding. In patients with chronic renal failure, a correlation of probability P less than 0.07 was found between percent binding and concentrations of pre beta-lipoprotein (P = 0.001), serum albumin (P = 0.0101), total protein minus albumin (P = 0.0576) and beta-lipoprotein (P = 0.0625). There was no significant correlation of binding with elevation of alpha- or gamma-globulins, with urea or creatinine concentrations, or with age or sex (P greater than 0.223). The magnitude of changes in the free fraction found in these patients should not produce a clinical effect as the total distribution volume of fentanyl exceeds 200 litres.
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