Pharmacokinetic mass of fentanyl for postoperative analgesia in lean and obese patients.

BACKGROUND: We previously proposed dosing weights for fentanyl, termed 'pharmacokinetic mass', that span the total body weight (TBW) range from 40 to 210 kg. In this study, we examined the relationships among fentanyl doses needed to achieve postoperative analgesia, corresponding plasma fentanyl concentrations, and pharmacokinetic mass in lean and obese patients undergoing abdominal surgery. METHODS: A total of 69 patients were studied, with TBW ranging from 48 to 181 kg. Fentanyl infusion was used during surgery. After surgery, fentanyl infusion rates were titrated to achieve analgesia without significant respiratory depression. Plasma fentanyl concentrations were measured when an apparent steady analgesic state was obtained. Comparisons were made for dosing requirements and effective plasma concentrations for 37 lean patients (body mass index < 30, TBW < 85 kg) and 33 obese patients (body mass index > 30, TBW > or = 85 kg). RESULTS: The average fentanyl dose (microg h(-1)) required to achieve and maintain analgesia over the 4 h postoperative period had a non-linear relationship to TBW; in comparison, fentanyl dose had a strong linear relationship to pharmacokinetic mass: dose (microg h(-1)) = 1.22 x pharmacokinetic mass - 7.5; r = 0.741, P < 0.001. Based on results from our earlier study, the corresponding values of TBW and pharmacokinetic mass are: 52 kg--52 kg; 70 kg--65 kg; 100 kg--83 kg; 120 kg--93 kg; 140 kg--99 kg; 160 kg--104 kg; 180 kg--107 kg; 200 kg--109 kg. In the group comparisons, there was no statistically significant difference in the postoperative fentanyl dose per unit of pharmacokinetic mass between lean and obese patients. The plasma concentration of fentanyl required for analgesia was approximately 1.5 ng ml(-1), and was similar in the two groups. CONCLUSION: The relationship between dose and pharmacokinetic mass, compared with that of dose vs TBW, may provide confidence for the use of pharmacokinetic mass as a dosing approximation for fentanyl. Fentanyl dose based on TBW may cause overdosing in obese patients.

Enhancement of bupivacaine sensory blockade of rat sciatic nerve by combination with phenol.

We sought to determine whether the addition of phenol would enhance a bupivacaine nerve block. The effects on nerve conduction of bupivacaine (0.125%) and phenol (0.5%), singly and combined, were evaluated in vivo on the rat sciatic nerve. Three groups of 10 animals each were used. The left sciatic nerve was infiltrated with 0.125% bupivacaine, 0.5% phenol, or a solution that contained 0.125% bupivacaine and 0.5% phenol. The right limb served as control (saline injected). Motor deficits (visual assessment) and sensory blockade (hot-plate assay) were evaluated at 30-min intervals after injection. Phenol injected alone produced no motor blockade. The incidence of motor blockade at 30 min for 0.125% bupivacaine was 70% (P = 0.003), and for the combination treatment, 80% (P = 0.001). The analgesia score derived from the hot-plate test was more and persisted longer for the combination treatment than for either 0.125% bupivacaine or 0.5% phenol given singly; e.g., the average sensory block score after 150 min for the combination treatment was 1.0 compared with 0.1 for either bupivacaine or phenol given alone (P = 0.003). Analysis of the areas under the sensory score-time curves also demonstrated enhanced blockade from the combination treatment, which would be consistent with a synergism of the separate Na(+)-channel blocking effects of charged and uncharged local anesthetics. These findings may suggest other candidates for clinically useful combinations of amine and neutral local anesthetics.

Plasma levels and renal removal of gastrin after acute hepatic ischemia in dogs.

Plasma levels and renal uptake of gastrin were determined in ten dogs submitted to complete liver devascularization in order to induce an acute liver failure. Renal function was evaluated by renal plasma flow (RPF) and glomerular filtration rate (GFR) determinations. Liver devascularization was obtained by end-to-side porto-caval shunt (PCS) followed by temporary clamping of the hepatic artery. PCS alone did not affect renal function and renal ability to remove gastrin; after hepatic ischemia, both RPF, GFR and renal extraction of gastrin showed an abrupt decrease. At the end of the period of hepatic ischemia 5 dogs were submitted to glucose infusion, in consideration that: i) glucagon is able both to affect gastrin release and renal hemodynamics, and ii) hypoglycemia that develops after liver failure releases elevated amounts of glucagon. The renal handling of gastrin was not related to glucagon plasma levels, though the higher gastrin levels occurred at the lower glucagon concentrations. These data suggest that in acute liver failure there is a striking decrease of the renal clearance of gastrin associated with the impairment of kidney function. Furthermore, in this pathological condition plasma gastrin levels are affected by blood glucose concentrations through its effect on plasma glucagon levels.