Prolonged analgesia after epidural injection of a poorly soluble salt of fentanyl.

Epidurally administered fentanyl is commonly used in postoperative pain management. The onset of action is rapid, but the duration of analgesia is short. In this study we examined the hypothesis that a poorly soluble salt of fentanyl (fentanyl pamoate) would create a depot of the drug in the epidural space and thus provide prolonged analgesia. The dose-response relationship and duration of analgesic action of epidural fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in white male Sprague-Dawley rats. Somatic and visceral nociceptive stimulation (tail flick and colorectal distension, respectively) were used to test the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31 micrograms toward somatic and 33 micrograms toward visceral noxious stimulation, and for FC it was 3 micrograms toward both stimulations. The antinociceptive effects were similar, with 31 micrograms of FP and 3 micrograms of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5 micrograms of FC or 50 micrograms of FP) were used, but with doses expected to produce 100% MPE, differences between the study drugs were not observed in the duration of analgesia. We conclude that the duration of antinociceptive effect of fentanyl can be prolonged when administered as a poorly soluble salt.

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.

Does epidural fentanyl decrease the efficacy of epidural morphine after cesarean delivery?

Earlier studies have suggested that epidural fentanyl improves intraoperative analgesia during cesarean section, but others have suggested that it worsens postoperative analgesia from epidural morphine. The purpose of this study was to determine whether epidural fentanyl given before epidural morphine improves the quality of intraoperative epidural anesthesia without worsening postoperative analgesia provided by epidural morphine. Sixty patients having epidural anesthesia for cesarean delivery were studied. Epidural anesthesia was established using 2% lidocaine with epinephrine 5 micrograms/mL. After delivery, either fentanyl 100 micrograms/10 mL or normal saline-control 10 mL was injected through the epidural catheter in a randomized, double-blind manner. All patients received 3.5 mg of morphine epidurally after uterine repair. After administration of the epidural study drug, there were no significant differences in the pain responses during surgery between the two groups. Patients in the fentanyl group experienced significantly less nausea and vomiting between delivery and the end of surgery than did patients in the normal saline-control group (P = 0.013). Postoperatively, visual analogue scale scores for pain, pruritus, nausea, and sedation were similar at 1, 2, 4, and 8 h in the two groups. We conclude that fentanyl 100 micrograms administered epidurally during cesarean delivery did not improve intraoperative analgesia, but significantly reduced intraoperative nausea and vomiting without diminishing the efficacy of postoperative analgesia provided by epidural morphine.

Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam.

A placebo-controlled, double-blind, crossover trial in 11 healthy male volunteers compared clinical sedation and psychomotor function after intravenous injection of midazolam (0.05, 0.1, or 0.15 mg/kg), diazepam (0.15 or 0.3 mg/kg), or placebo (saline). The depth of sedation was estimated at 5-10-min intervals during the first hour after injection. A comprehensive battery of psychomotor tests was used to collect objective data of psychomotor performance before drug injection and 1, 3, 5, and 7 h after injection. Midazolam (0.15 mg/kg) produced the highest scores of sedation and most impairment of psychomotor performance. In most tests, the maximal psychomotor effects seen after 0.3 mg/kg of diazepam did not reach those of 0.1 mg/kg of midazolam. Although the strongest psychomotor effects were induced by midazolam, these effects disappeared sooner than those of diazepam. By 5 h after injection, 0.3 mg/kg of diazepam showed the highest scores of psychomotor impairment. The authors conclude that at least four times as much diazepam as midazolam is needed to produce equally severe psychomotor impairment. That the residual effects of midazolam terminate sooner than those of diazepam probably accounts for the occasional underestimation of the potency of midazolam in clinical practice.

Is the antiemetic effect of the emulsion formulation of propofol due to the lipid emulsion?

The hypothesis that the lipid emulsion of the emulsion formulation of propofol is responsible for the low frequency of nausea, retching, and vomiting after propofol anesthesia was tested. A randomized, prospective, and comparative study was performed to evaluate the antiemetic effect of 10% lipid solution in 60 women, ASA physical status I and II, scheduled for ambulatory laparoscopic procedures. Two groups of patients were studied. Induction of anesthesia (thiopental) and maintenance of anesthesia (enflurane, nitrous oxide) were similar in both groups. At induction the study group received 10% Intralipid (3 mL/min for 20 min). The control group received 5% dextrose in lactated Ringer's solution at the same rate. Other drugs administered during or after anesthesia were similar among the groups. The groups were similar with respect to duration of anesthesia, characteristics of early and intermediate recovery, as well as pain scores in the postanesthesia care unit. There were no differences in the amount of antiemetic medications administered or postoperative nausea, retching, or vomiting when the patients were evaluated objectively by a blinded observer or subjectively by patient self-evaluation. It is concluded that 10% Intralipid, the lipid in the emulsion formulation of propofol, does not possess significant antiemetic effects.

Circulatory collapse during laparoscopy.

This case report details the intraoperative course of a patient, in her early pregnancy, who had a cardiac arrest during transvaginal insufflation of carbon dioxide (CO2) for laparoscopic tubal ligation. Modern monitoring methods and their ability to detect gas embolism and aid in the diagnosis and treatment of this rare but life-threatening complication are discussed.

Randomized comparison of outcome after propofol-nitrous oxide or enflurane-nitrous oxide anaesthesia in operations of long duration.

A randomized, prospective, comparative study was performed to evaluate induction characteristics, haemodynamic changes and recovery in 60 ASA I-II patients undergoing mainly gynaecological laparotomies with either propofol or thiopentone-enflurane anaesthesia. The propofol group (n = 30) received 2 mg.kg-1 propofol for induction of anaesthesia followed by propofol infusion. The thiopentone-enflurane group (n = 30) received thiopentone 4 mg.kg-1 for induction followed by enflurane (0.5-2 per cent). All patients received nitrous oxide (66 per cent] in oxygen begun one minute after tracheal intubation, and fentanyl (1.5 micrograms.kg-1) four minutes prior to induction. Other drugs administered during or after anaesthesia were similar among the groups. Haemodynamic measurements were similar between propofol and enflurane groups except after tracheal intubation when the mean arterial pressure was lower in the propofol group (P less than 0.05). The propofol group had significantly less (P less than 0.01) emesis in the recovery room than the enflurane group. The propofol group experienced significantly less (P less than 0.05) dizziness, depression/sadness and hunger than the enflurane group in the postoperative period as assessed with a visual analogue questionnaire. We conclude that propofol provided better outcome than enflurane in terms of these nonvital but annoying outcome measures after relatively long intra-abdominal operations.

Metoclopramide versus droperidol for prevention of nausea and vomiting during epidural anesthesia for cesarean section.

In a randomized, double-blind study, we compared the efficacy of metoclopramide hydrochloride with that of low-dose droperidol for prevention of nausea and vomiting during and after elective cesarean section with epidural anesthesia. Immediately after the umbilical cord was clamped, each patient received fentanyl (50 micrograms) and the study drug intravenously over 30 to 60 seconds. In one study group, 40 women received metoclopramide (15 mg); in the other group, 41 women received droperidol (0.5 mg). Twelve women (30%) in the metoclopramide group, versus eight (20%) in the droperidol group, had intraoperative, postdelivery nausea (P = NS). One woman (3%) in the metoclopramide group, versus two women (5%) in the droperidol group, had intraoperative, postdelivery vomiting (P = NS). During the first four postoperative hours, five women (12%) in each group complained of nausea. Three women (7%) in each group had postoperative vomiting. We conclude that metoclopramide (15 mg) and droperidol (0.5 mg) were similarly effective.

Transplacental passage and hemodynamic effects of esmolol in the gravid ewe.

Using a chronic maternal-fetal sheep preparation, the authors determined the transplacental passage and the hemodynamic changes consequent to maternal administration of esmolol. Fifteen experiments were performed in six chronically instrumented pregnant ewes near term. Each animal received esmolol iv, 500 micrograms.kg-1.min-1, for 4 min and then 300 micrograms.kg-1.min-1 for 6 min. Maternal and fetal blood esmolol concentrations (mean +/- SEM) were 1.2 +/- 0.28 and 0.1 +/- 0.03 micrograms/ml, respectively, at the completion of the infusion, and 0.03 +/- 0.01 microgram/ml in the mother and not detectable in the fetus 10 min after stopping the infusion. Despite the relatively low blood esmolol concentration in the fetus compared to the mother, the hemodynamic effects in the fetus were similar to those in the mother. The maximal decrease of maternal mean arterial pressure (MAP) and heart rate (HR) were 7 +/- 2 and 14 +/- 3% (mean +/- SEM), respectively (P less than .05). The maximal decrease of fetal MAP and HR were 7 +/- 2 and 12 +/- 3%, respectively (P less than .05). No changes were seen in maternal or fetal acid-base variables, and intra-amniotic pressure was not affected. The authors conclude that esmolol has a rapid but relatively small transplacental passage, and it is eliminated rapidly from both maternal and fetal plasma.