Bupivacaine 0.01% and/or epinephrine 0.5 microg/ml improve epidural fentanyl analgesia after cesarean section.

BACKGROUND: The authors studied the addition of bupivacaine and epinephrine, separately and together, to epidural fentanyl to determine whether this improved postcesarean analgesia and reduced the incidence of side effects. METHODS: After elective cesarean section, 100 parturient patients who received fentanyl (3 microg/ml) epidurally for 48 h were allocated randomly in a double-blinded manner to four groups to receive, in addition to the study solution, 0.01% bupivacaine, 0.5 microg/ml epinephrine, both, or neither. A neurologic assessment of breast-fed neonates was made at 2 and 48 h of life. Plasma fentanyl concentrations were determined in a subset of patients at intervals after treatment. RESULTS: Patients receiving fentanyl alone made more attempts at patient-controlled analgesia (P < 0.01), required a greater total dose of fentanyl (P < 0.01), reported more pain (P < 0.003) and less satisfaction (P < 0.003), and had more nausea and urinary retention (P < 0.05) than all other groups. Patients who received bupivacaine with or without epinephrine had better overall satisfaction scores than those who did not receive bupivacaine (P < 0.001), and they required less fentanyl (P < 0.02) than patients who received fentanyl with only epinephrine. Motor blockade or orthostatic hypotension did not develop in any patient, and all patients could ambulate without difficulty. Neurobehavioral scores, which were similar among all neonates, were within the normal range. Plasma concentrations of fentanyl increased after epinephrine-containing solutions were discontinued. CONCLUSIONS: During the conditions of this study, the addition of epinephrine and bupivacaine to a 3-microg/ml epidural fentanyl solution for postcesarean section pain relief provided superior analgesia compared with fentanyl alone or fentanyl with epinephrine. Whether increasing the concentration of fentanyl alone might improve the efficacy of fentanyl remains unclear.

Epidural analgesia for labour and delivery: fentanyl or sufentanil?

PURPOSE: The highly lipid soluble opioids, fentanyl and sufentanil, are used in combination with local anaesthetics with/without epinephrine to provide epidural analgesia during labour and delivery. Our aim was to determine whether wither opioid was superior when used with low dose local anaesthetic. METHODS: In a double-blind study patients were randomized to two epidural infusion groups: Group I (n = 50) fentanyl 2 micrograms.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1, Group II(n = 50) sufentanil 1 microgram.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1. Following a 20 ml bolus of the study solution an infusion was started at 10 ml.h-1. To achieve analgesia patients could receive two boluses of 5 ml of the study solution and if analgesia was still inadequate, a further 5 ml bupivacaine 0.25% was used. Pain and overall satisfaction were assessed with a 10-point visual scale. Plasma samples obtained from the mother at the time the infusion was discontinued and from the umbilical cord vein at delivery were assayed to determine opioid concentration. RESULTS: Pain scores were greater for Group I than for Group II patients throughout the first and second stages of labour (P = 0.002). More patients in Group I (42%) requested a dose of bupivacaine 0.25% than in Group II (6%) (P < 0.001) and the total dose of bupivacaine given to Group I patients was greater than that of Group II, 26.0 +/- 22.0 mg vs. 13.4 +/- 12.6 mg, P = 0.005. There were no differences with respect to first or second stage duration, incidence of side effects, infusion duration, outcome of labour or neonatal Apgar scores. There was no opioid accumulation in either maternal or foetal blood. CONCLUSION: Epidural opioid infusion with very low dose bupivacaine (0.015%) achieved an overall high level of patient satisfaction in both groups without serious maternal or neonatal side effects. At the fentanyl-to-sufentanil ratio used here patients receiving sufentanil had lower pain scores and substantially fewer patients required bupivacaine rescue.

Decreased incidence of headache after accidental dural puncture in caesarean delivery patients receiving continuous postoperative intrathecal analgesia.

To examine the effects of prolonged (> 24 h) intrathecal catheterization with the use of postoperative analgesia on the incidence of post-dural puncture headache (PDPH), charts of 45 obstetric patients who had accidental dural puncture following attempts at epidural block were reviewed retrospectively. Three groups were identified: Group I (n = 15) patients had a dural puncture on the first attempt at epidural block, but successful epidural block on a repeated attempt; Group II (n = 17) patients had a dural puncture with immediate conversion to continuous spinal anaesthesia with catheterization lasting only for the duration of caesarean delivery; Group III (n = 13) patients had an immediate conversion to spinal anaesthesia and received post-caesarean section continuous intrathecal patient-controlled analgesia consisting of fentanyl 5 micrograms.ml-1 with bupivacaine 0.25 mg.ml-1 and epinephrine 2 micrograms.ml-1 with catheterization lasting > 24 h. No parturient in group III developed a PDPH. This was substantially lower (P < 0.009) than the 33% incidence for group I and the 47% incidence for group II. The incidence of a PDPH did not differ between group I and II. Similarly, there was no difference between group I and II with regard to requests for a blood patch. Patients receiving continuous intrathecal analgesia had excellent pain relief, could easily ambulate and none complained of pruritus, nausea, vomiting, sensory loss or weakness. In conclusion, indwelling spinal catheterization > 24 h with continuous intrathecal analgesia following accidental dural puncture in parturients may for some patients be a suitable method for providing PDPH prophylaxis and postoperative analgesia.

Plasma cholinesterase: gene and variations.

The traditional tests that have been used for the past 30 yr to determine plasma cholinesterase phenotype--measurement of esterase activity with a variety of substrates, dibucaine inhibition, fluoride inhibition, and Ro2-0683 inhibition--are inadequate for identifying some variants of this enzyme and leave many cases of prolonged response to succinylcholine unexplained. The application of the techniques of molecular genetics has permitted precise identification of plasma cholinesterase variants and has resulted in the discovery of previously unrecognized variants. It is now possible, in cases of prolonged response to succinylcholine resulting from genetically determined alterations in plasma cholinesterase, to ascertain the nature of the mutations in the alleles, and from them to deduce the structural changes in the enzymes responsible for the impairment in drug metabolism.

Postcesarean delivery epidural patient-controlled analgesia. Fentanyl or sufentanil?

BACKGROUND: The highly lipid-soluble opioids, fentanyl and sufentanil, frequently are used in combination with local anesthetic agents and/or epinephrine to provide postoperative epidural analgesia. The authors compared the incidence of side effects and patient satisfaction during prolonged epidural patient-controlled analgesia (PCA) infusions of these opioids in combination with bupivacaine and epinephrine. METHODS: Using a double-blind study design, 250 patients scheduled for elective cesarean delivery were, on arrival in the postanesthesia care unit, randomized into two epidural PCA infusion groups: group I (n = 125) received fentanyl 2 micrograms/ml with bupivacaine 0.01% and epinephrine 0.5 micrograms/ml and group II (n = 125) received sufentanil 0.8 micrograms/ml with bupivacaine 0.01% and epinephrine 0.5 microgram/ml. The initial infusion rate was 16 ml/h with self-administered 3-ml boluses every 15 min by PCA as desired. At intervals after discontinuation of the infusion, plasma samples were obtained to determine opioid concentrations. RESULTS: The median overall satisfaction scores were 9.0 for group I and 10.0 for group II (difference not significant). Pain relief was satisfactory and comparable in both groups, and all patients could ambulate easily. The total number of times PCA requests were made was greater (P < 0.05, by Wilcoxon rank-sum test) for group I than for group II (106.7 +/- 312 vs. 70.8 +/- 138). There were no differences between the groups with respect to incidence of pruritus, sedation, and nausea; however, vomiting occurred more frequently with sufentanil than with fentanyl (12% vs. 4.8%, respectively; P < 0.05). At approximately 1-2 h after discontinuation of the infusion, 1 patient receiving fentanyl and 42 patients receiving sufentanil complained of lightheadedness and dizziness (P < 0.0001). CONCLUSIONS: Epidural PCA in both groups had no serious side effects and achieved a high level of patient satisfaction. Those receiving sufentanil made fewer PCA requests but had a significantly greater incidence of vomiting during the infusion and dizziness after the termination of the infusion. Epidural sufentanil offered no advantages over epidural fentanyl.

Effect of ginseng on plasma levels of ethanol in the rat.

The effect of red ginseng extract on the disposition of ethanol was studied in male Fischer 344 rats. Blood was drawn from the tail vein before and at 0.5, 1, 2, 3, 4, and 5 hours after dosing rats orally with aqueous ginseng (200 mg/kg), or an equivalent volume of water, followed immediately by 50% ethanol orally (3.2 g/kg) or intraperitoneally (1.5 g/kg). When the ethanol was administered orally, the mean area under the plasma concentration-time curve (0-->5 h) of ethanol was 21.0% less in the ginseng-treated rats than in the control rats. When the ethanol was administered intraperitoneally, there was no significant difference between ginseng-treated and control rats in area under the plasma concentration-time curve. The results show that plasma levels of ethanol are lower when the ethanol is administered orally with ginseng than when it is administered alone, but that orally administered ginseng has no effect on plasma levels of ethanol administered intraperitoneally.

Adverse effects of epidural 0.03% bupivacaine during analgesia after cesarean section.

To develop a regimen that would provide good analgesia after cesarean section with minimal side effects in the setting of prolonged (> 24 h) epidural infusion, buprenorphine or fentanyl was combined with 0.03% bupivacaine in a double-blind study of 23 parturients. Patients were randomly assigned to two groups: group I (n = 12), patient-controlled analgesia by epidural infusion of buprenorphine (3 micrograms/mL) with 0.03% bupivacaine; group II (n = 11), patient-controlled analgesia by epidural infusion of fentanyl (2 micrograms/mL) with 0.03% bupivacaine. Plasma for determination of opioid concentrations was obtained at intermittent intervals. Pain relief was similar and satisfactory in both groups. The median overall satisfaction score was higher (10.0 vs 7.5; P < 0.03) for group II. Pruritus was mild in most patients. Nausea and vomiting, which were most disturbing to the patients, were seen only with buprenorphine. No patient had a respiratory rate of < 12 breaths/min. Mean plasma opioid concentrations did not exceed 1 ng/mL during the study. However, four patients (33%) in group I and six patients (55%) in group II experienced sensory loss in the lower extremities, which made ambulation difficult. One patient in each group developed extensive pressure blisters on both heels. These complications led us to terminate the study. We conclude that 0.03% bupivacaine used in combination with an opioid in prolonged epidural infusions produces a high incidence of sensory loss in the lower extremities and is unsuitable for situations in which early ambulation is desired.

Epidural patient-controlled analgesia after cesarean section: buprenorphine-0.015% bupivacaine with epinephrine versus fentanyl-0.015% bupivacaine with and without epinephrine.

We compared the analgesia, side effects, and plasma concentrations of buprenorphine and fentanyl in a double-blind study of 78 parturients receiving one of these drugs by patient-controlled epidural infusion after elective cesarean section with epidural anesthesia. Patients were randomized to three epidural infusion groups: group 1 (n = 26), 3 micrograms/mL buprenorphine with 0.015% bupivacaine and 1 microgram/mL epinephrine; group 2 (n = 26), 3 micrograms/mL fentanyl with 0.015% bupivacaine and 1 microgram/mL epinephrine; and group 3 (n = 26), 3 micrograms/mL fentanyl with 0.015% bupivacaine. Plasma for determination of opioid concentrations was obtained in some subjects in each group at intervals up to 48 h during the infusion and in some subjects from each group at intervals after the infusion was stopped. Pain relief was similar and satisfactory in all three groups. The median overall satisfaction scores were high for all three groups. Pruritus was more common in the fentanyl groups (P less than 0.05). However, vomiting was more disturbing to the patients and seen only with buprenorphine. No patient had a respiratory rate less than 12 breaths/min. Epinephrine use was associated with a slower infusion rate (P less than 0.05, group 2 vs 3). All patients were able to ambulate without difficulty. Mean opioid plasma concentrations did not exceed 1.5 ng/mL. Thus, epidural patient-controlled analgesia in all three groups provided excellent analgesia, permitted ambulation, and was without serious side effects. Epidural buprenorphine offered no advantages over epidural fentanyl.

Metabolism of desflurane and isoflurane to fluoride ion in surgical patients.

The metabolism of isoflurane and the investigational volatile anaesthetic desflurane to fluoride ion was examined in 25 surgical patients. The patients were randomly assigned to four groups, to receive isoflurane or desflurane at either 0.65 MAC or 1.25 MAC. Anaesthesia was induced in all patients with thiopentone and midazolam and included nitrous oxide 60% in addition to the volatile agent. Blood was drawn before induction and at the end of the operation for determination of serum fluoride ion concentration. Plasma fluoride ion concentrations increased (+ 1.36 +/- 0.93 microM, P less than 0.01) in patients receiving isoflurane but were unchanged (-0.13 +/- 0.50 microM) in patients receiving desflurane. Metabolic release of fluoride ion is less with desflurane than with isoflurane during administration of the anaesthetics to surgical patients, and is unlikely to be of clinical significance.

Effects of protein and carbohydrate content of diet on drug conjugation.

Eight healthy subjects were fed a high-protein-low-carbohydrate diet and, after a 3-day washout period, an isocaloric low-protein-high-carbohydrate diet. They received acetaminophen and oxazepam, drugs metabolized primarily by conjugation, on days 11 and 13, respectively, of each diet. Changing the diets of subjects from the high-protein-low-carbohydrate diet to the low-protein-high-carbohydrate diet resulted in a 14% increase in urinary recovery of acetaminophen glucuronide and a 32% increase in urinary recovery of oxazepam glucuronide (p less than 0.05). The increases in glucuronidation were at the expense of other pathways of metabolism, and there were no significant changes in the metabolic clearance rates of acetaminophen and oxazepam. Mean renal clearances of acetaminophen glucuronide, acetaminophen sulfate, and oxazepam glucuronide decreased 45%, 32%, and 54%, respectively (p less than 0.05), when the subjects were switched to the low-protein-high-carbohydrate diet.

Regulation of hepatic microsomal cytochrome P450IIE1 level by dietary lipids and carbohydrates in rats.

The present work tests the hypothesis that high fat/low carbohydrate diets elevate the level of liver microsomal cytochrome P450IIE1. Male Sprague-Dawley rats were fed liquid diets containing varied ratios of corn oil/carbohydrate for 4 d. Rats fed diets with higher fat/carbohydrate ratios produced higher serum acetone levels and higher hepatic microsomal P450IIE1 content and N-nitrosodimethylamine demethylase activity than those fed diets with lower fat/carbohydrate ratios. This dietary fat/carbohydrate effect on P450IIE1 also was observed with modified semipurified AIN-76A diets. In addition, both the quantity and the extent of unsaturation of dietary lipids affected P450IIE1 regulation. At moderate fat levels (5 and 20% diet), rats fed corn oil and menhaden oil diets produced higher P450IIE1 activity than those fed lard and olive oil diets. Rats fed a diet containing 20% corn oil or an amount of linoleic acid equivalent to the 20% corn oil diet showed twofold to threefold increases in the level of P450IIE1 over those fed a fat-free diet. Rats fed a 25% corn oil diet showed twofold higher enflurane metabolism in vivo than those fed a 0.5% corn oil diet. The present results suggest that the constitutive P450 enzyme level is regulated by dietary fat/carbohydrate ratios.

Desflurane and isoflurane in surgical patients: comparison of emergence time.

In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro-2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was designed to compare time of emergence from anesthesia in patients undergoing elective surgery under desflurane anesthesia to that of patients under isoflurane anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1 received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane 1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147 +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences between groups. The times from discontinuation of anesthetic gases until patients opened their eyes and squeezed the investigator's hand in response to a command were averaged and recorded as "emergence time." Emergence time was significantly less with desflurane than with isoflurane given at the same MAC. Patients receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane 1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min (P less than 0.05). Our results confirm that emergence from desflurane anesthesia is more rapid than from isoflurane.

Effects of parenteral amino acid nutritional regimens on oxidative and conjugative drug metabolism.

Our goals were to determine the time-course of the increase in oxidative drug metabolism that occurs when parenteral nutrition is changed from dextrose to amino acids (23% branched-chain), whether the composition of the amino acid regimen influences this effect, and whether drug conjugation is similarly altered. We examined in healthy volunteers the effects of changing isocalorically from intravenous dextrose 440 kcal/day to amino acids, on one occasion 23% branched-chain and on another 85%. The change to the 23% regimen produced a significant increase in metabolic clearance of antipyrine, a model for oxidation (mean +/- SE 3.0 +/- 0.3 to 3.7 +/- 0.4 L/h, N = 6, P less than 0.003), but the change to the 85% regimen did not, indicating that the composition of an amino acid infusion can influence its effect on oxidative metabolism. Analysis of the concentration-time curve for antipyrine after simultaneous dosing and start of the 23% regimen suggests that the increase in metabolic capacity occurred within a few hours. Metabolic clearance of acetaminophen, a model for conjugation, was not altered by changing to either amino acid regimen.

Effects of cyclosporine on anesthetic action.

The effects of a single dose of cyclosporine on anesthetic actions of pentobarbital and fentanyl were studied in mice. Mice given pentobarbital 2 hr after receiving cyclosporine, 60 mg/kg, slept a statistically significant 2.3 times longer than did controls. In a second study, each of two dose levels of cyclosporine was given before each of four dose levels of fentanyl. The analgesic effect of fentanyl, measured with the abdominal constriction test, was dose-dependent. Cyclosporine significantly increased the analgesia produced by fentanyl and did so in a dose-dependent manner. Cyclosporine by itself did not produce analgesia. Plasma levels of fentanyl and binding of fentanyl by plasma proteins were unchanged by cyclosporine treatment. The results show that a single dose of cyclosporine can increase pentobarbital hypnosis and fentanyl analgesia in mice but do not establish the mechanism of these interactions.

Antipyrine metabolism not influenced by level of carbohydrate intake.

The effects on antipyrine metabolism of two levels of carbohydrate, fed intravenously as the sole source of nutrition, were compared. After a 36-hour baseline period during which they received 5% dextrose, 440 kcal per day, intravenously, 8 healthy men were administered 2 sequential intravenous nutritional regimens for 3 days each. One regimen consisted of dextrose 8.1 kcal per kg per day and the other 30.7 kcal per kg per day. The order of the 2 regimens was randomized. Antipyrine metabolism was studied on the last day of each nutritional regimen. Antipyrine kinetics were not influenced by level of carbohydrate intake. Our study indicates that in humans carbohydrate does not by itself have an effect on oxidative drug-metabolizing capacity.

Effect of streptozotocin-induced diabetes in the rat on the metabolism of fluorinated volatile anesthetics.

Three weeks after dosing male Fischer 344 rats with streptozotocin to induce diabetes, enflurane was administered ip, and 1 h later, fluoride levels were measured in plasma and livers were removed. Hepatic microsomes were prepared, and the oxidative defluorination of enflurane, isoflurane, and methoxyflurane and the reductive defluorination of halothane were measured in vitro. In diabetic rats the defluorination of enflurane was increased 3.4-fold over control levels in vivo and 2.7-fold in vitro. Insulin treatment prevented these effects. In vitro metabolism of isoflurane by livers from diabetic rats was 2.5-fold greater than by livers from control rats, but defluorination of methoxyflurane and of halothane was not altered. The results show that streptozotocin-induced diabetes in rats enhances the defluorination of enflurane and of isoflurane but not of methoxyflurane or halothane.

Stimulation of oxidative drug metabolism by parenteral refeeding of nutritionally depleted patients.

To determine whether intravenous nutritional repletion can influence oxidative drug metabolizing capacity, antipyrine metabolism was studied in 6 malnourished patients on the second day of a 2-day baseline period and on the last day of two sequential, 8-day intravenous nutritional repletion periods. During the baseline period they received 5% dextrose, 440 kcal per day, intravenously. During the repletion periods they received 20 mg of nitrogen per kilocalorie of baseline resting energy expenditure and, in random order, dextrose to provide a total caloric intake of either 0.95 or 1.75 times baseline resting energy expenditure. There were no statistically significant differences between the high- and low-dextrose repletion regimens in their effects on antipyrine metabolism. Seven days of nutritional repletion resulted in a 42% decrease in mean half-life (range 12%-52%) and an 87% increase in mean metabolic clearance rate (range 29%-155%) for antipyrine. An additional 8 days of nutritional repletion resulted in no further change in these pharmacokinetic parameters.

Inhibition and stimulation of enflurane metabolism in the rat following a single dose or chronic administration of ethanol.

The effects of a single oral dose or chronic ingestion of ethanol on in vivo and in vitro metabolism of enflurane were studied in Fischer 344 rats. At various intervals after ethanol treatment, enflurane was administered ip and 1 h after enflurane administration fluoride and ethanol levels were measured in plasma and hepatic microsomes were prepared. The concentration of ethanol in plasma (+/- SE) was 0.138 +/- 0.035% at 9 h after the single dose of ethanol and decreased almost to control levels by 17 h. The hepatic microsomal defluorination of enflurane was enhanced 3.5-fold and 6.3-fold at 9 and 25 h after the ethanol dose and returned to the control level by 33 h. In vivo defluorination was inhibited almost completely at 8 h after the ethanol dose, increased to 3.4 times the control level at 24 h, and decreased to the control level by 32 h. At 1 h after the end of chronic ethanol treatment, the concentration of ethanol in plasma was 0.254 +/- 0.018%, and it decreased to the control level by 9 h. Hepatic microsomal enflurane defluorinating activity was increased 10.5-fold at 1 h after the end of chronic treatment and decreased to the control level by 13 h. Immediately following chronic treatment, enflurane defluorination in vivo was almost totally inhibited. It increased to 9.3 times the control level at 4 h after chronic treatment was stopped and then decreased to nearly the control level at 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)