Intraoperative ketorolac has an opioid-sparing effect in women after diagnostic laparoscopy but not after laparoscopic tubal ligation.

Ketorolac tromethamine (Toradol) is a parenteral, nonsteroidal antiinflammatory drug that is being extensively used to provide postoperative analgesia. This study evaluated whether intraoperative ketorolac would act synergistically with fentanyl to decrease postoperative analgesic requirements in outpatients undergoing gynecologic procedures. The patients studied were adult ASA physical status I or II females scheduled for diagnostic laparoscopy (DL) (n = 80) or laparoscopic tubal ligation (TL) (n = 46). Each patient received fentanyl 2 micrograms/kg intravenously (i.v.) before induction, followed by a standardized propofol anesthetic and 2 mL of saline or ketorolac 60 mg i.v. in a randomized double-blind fashion 30 min before the anticipated end of the operative procedure. Patients were assessed for postoperative pain via a 10-cm visual analog scale (VAS) (0 = no pain; 10 = severe pain) before analgesic treatment in the postanesthesia care unit (PACU). Severe postoperative pain (VAS or 5 or more) was treated with incremental doses of fentanyl, 25-50 micrograms i.v. by a blinded PACU nurse. Ibuprofen or acetaminophen with codeine was administered for pain control once the patient tolerated oral medications. This study showed that intraoperative ketorolac (60 mg i.v.) with fentanyl (2 micrograms/kg i.v.) administered at the induction of anesthesia resulted in significant opioid sparing and a diminution in pain in the DL sample but not in the TL sample. The analgesic regimen was also associated with a lower incidence of nausea and vomiting and resulted in earlier discharge, which was not seen after TL. These results demonstrate that pain after TL is far greater than that after DL, which suggests that these procedures should be considered separately when designing analgesic regimens.

Somatostatin inhibits bombesin-stimulated Gi-protein via its own receptor in rabbit colonic smooth muscle cells.

The effect of somatostatin on Bombesin-induced contraction of isolated rabbit colonic smooth muscle cells was examined. Preincubation of muscle cells with somatostatin 10(-6) M inhibited bombesin-induced contraction. To characterize somatostatin receptors, muscle cells (10(5) cells/tube) were incubated at 24 degrees C with 125I-Tyr0-SS-28. Binding reached a plateau at 60 sec and was reversible by addition of excess synthetic SS-28. Scatchard analysis revealed high and low affinity bindings sites (Ka = 0.48 +/- 0.01 and 40 +/- 13 (nM +/- S.E.), 1830 +/- 433 and 65820 +/- 13183 receptors/cell +/- S.E.). Inhibition of 125I-Tyr0-SS-28 binding was possible with biologically active analogs of somatostatin, indicating the specificity of the receptors to somatostatin. Binding of 125I-Tyr0-SS-28 was inhibited by GTP gamma s, a nonhydrolysable analog of guanosine 5'-triphosphate, whereas adenosine 5'-triphosphate at a high concentration (100 microM) slightly inhibited the binding. Further, pretreatment of muscle cells with pertussis toxin at 37 degrees C abolished binding of 125I-Tyr0-SS-28, although pretreatment of cells with cholera toxin had no effect. Inasmuch as Gi protein is postulated as a signal protein, muscle cells were labeled with 3H-methionine, before stimulation with Bombesin (10(-6) M), in the presence and absence of somatostatin (10(-6) M). The cells were then lysed and Gi was precipitated by a Gi specific antibody. Gi synthesis was stimulated by bombesin at 60 sec and somatostatin inhibited it (6114 +/- 986 vs. 2998 +/- 841 cpm +/- S.E., P < .05). These data suggest that colonic smooth muscle cells contain specific receptor for somatostatin-28 and that somatostatin reverses bombesin-induced contraction regulated by Gi-type G protein.

Desflurane versus propofol anesthesia: a comparative analysis in outpatients.

This study compares the induction, hemodynamic, and recovery characteristics of a general anesthetic with desflurane to one with propofol. Sixty outpatients presenting for orthopedic surgery received either a propofol induction of anesthesia followed by desflurane and nitrous oxide (Group 1), a propofol induction followed by propofol infusion and nitrous oxide (Group 2), a desflurane and nitrous oxide induction and maintenance (Group 3), or a desflurane induction and maintenance (Group 4). The quality of induction was inferior in Groups 3 and 4 with more breath-holding and excitation than in Groups 1 and 2. However, there was a more rapid emergence in Group 4 patients than any of the other groups. Group 4 patients were able to say their names (5.6 +/- 2.0 min vs 10.3 +/- 3.3 min, 8.6 +/- 3.1 min, and 9.3 +/- 1.5 min for Groups 1, 2, and 3, respectively) sooner after the discontinuation of anesthesia. Nonetheless, intermediate recovery was similar in Groups 2 and 4 being numerically but not statistically more rapid than in Groups 1 and 3. This pattern of intermediate recovery was also demonstrated by psychomotor function test results. Although there was no difference between the groups in postoperative narcotic requirement, more patients in Group 3 vomited (50%) than in either Group 2 (0%) or Group 4 (12.5%). Hemodynamically, the anesthetics were very similar. Although desflurane was a difficult drug to use for induction of anesthesia, this study demonstrates that desflurane is a suitable maintenance anesthetic for ambulatory surgery because it provides a rapid awakening and an intermediate recovery similar to propofol.

Propofol versus thiamylal-enflurane anesthesia for outpatient laparoscopy.

STUDY OBJECTIVE: To determine whether propofol anesthesia differs from thiamylal-enflurane anesthesia in induction characteristics, intraoperative hemodynamics, postoperative side effects, and postoperative psychomotor function recovery. DESIGN: A randomized, double-blind, two-group study. SETTING: A large university hospital with gynecologic outpatient operations performed in an integrated operating room suite. PATIENTS: Sixty adult women (ASA physical status I or II) undergoing an outpatient gynecologic laparoscopic operation with an anesthesia time of approximately 60 minutes. INTERVENTIONS: No pharmacologic premedication. Pretreatment with intravenous droperidol 0.6 mg and sufentanil 0.2 micrograms/kg before induction of anesthesia. Anesthesia was induced with either thiamylal 4 mg/kg (Group 1) or propofol 2.5 mg/kg (Group 2). Anesthesia was maintained with either nitrous oxide (N2O) and enflurane, 2-0.5% inspired concentrations; (Group 1) or with a continuous infusion of propofol 200-100 micrograms/kg/min and N2O (Group 2). MEASUREMENTS AND MAIN RESULTS: In psychomotor function tests (Trieger dot test and p-deletion test) administered preoperatively and postoperatively, no difference was found between the groups. No difference was found in induction time, although significantly more patients reported pain after the propofol injection, or in intraoperative hemodynamics (mean arterial pressure and heart rate). Immediate recovery time (emergence from anesthesia) and intermediate recovery time (ambulation, oral intake, and discharge time) were significantly shorter after propofol anesthesia. Fewer postoperative side effects, such as nausea and vomiting, were reported after propofol anesthesia. CONCLUSIONS: Induction and maintenance of anesthesia with propofol were comparable to those with thiamylal-enflurane, except patients experienced more pain on injection after propofol. Both immediate and intermediate recovery were more rapid after propofol anesthesia compared with enflurane-based anesthesia.

Intravenous narcotics for premedication in outpatient anaesthesia.

One hundred adult female patients scheduled for outpatient laparoscopic procedures were studied. Each patient received intravenous premedication about 30 min before induction of anaesthesia. The premedications were given in a double-blind random order and were either a placebo, morphine (0.04 mg/kg), meperidine (0.35 mg/kg), fentanyl (0.75 microgram/kg) or sufentanil (0.15 microgram/kg). All patients received a standard anaesthetic regimen. Transient light-headedness was common following narcotic injections. Overall, sufentanil was superior to the placebo and to other narcotics in its ability to reduce preoperative anxiety and to provide more satisfactory induction, maintenance and recovery from anaesthesia. The incidence of postoperative nausea, vomiting and other side effects was not higher and discharge times were not longer after sufentanil compared to the placebo group. Complete recovery as assessed by telephone interview 24-48 h after the operation revealed no difference between the sufentanil and the other groups. The results of this study indicate that intravenous short-acting narcotics like fentanyl or sufentanil should be considered as an alternative premedicant for anxious patients who are scheduled for outpatient surgery.

Comparison of fentanyl and butorphanol for outpatient anaesthesia.

Equianalgesic doses of butorphanol (40 micrograms X kg-1) and fentanyl (2.0 micrograms X kg-1) were compared as supplements to balanced general anaesthesia for outpatient laparoscopic procedures. Thirty-six adult female patients (ASA physical status I or II) participated in the study. The study drugs (butorphanol or fentanyl) were given just prior to induction of anaesthesia in a double-blind fashion. Following induction with a standard dose of thiopentone and tracheal intubation using succinylcholine, nitrous oxide in oxygen and a succinylcholine infusion were used for maintenance of anaesthesia. Seventeen of the 18 patients in the butorphanol group and 14 of the 18 patients in the fentanyl group showed signs of light anaesthesia and required supplementation with isoflurane. Induction, maintenance and recovery characteristics were not different in the two groups except that the post-intubation arterial pressure and heart rate in the fentanyl group were significantly higher than the base line values and the patients receiving butorphanol were more drowsy and also more pain-free in the postoperative period. The incidence of nausea and vomiting was high in both groups. Overall, butorphanol (40 micrograms X kg-1) used as part of a standard balanced general anaesthetic for a standard outpatient procedure was not superior to fentanyl (2 micrograms X kg-1) used in the same fashion.

Premedication with cimetidine and metoclopramide. Effect on the risk factors of acid aspiration.

A randomised, double-blind, placebo-controlled parallel study was conducted in adult females to evaluate the efficacy and safety of a combination of cimetidine 300 mg orally and metoclopramide 10 or 20 mg intravenously in reducing pre-operative residual gastric volume and raising gastric pH. The effect of preoperative metoclopramide on postoperative nausea and vomiting was also investigated. Oral cimetidine was given approximately 2-2.5 hours before, and intravenous metoclopramide either 15 or 30 minutes prior to induction of anaesthesia. The study showed that placebo-treated patients undergoing outpatient operations have an increased risk of acid aspiration because of high residual gastric volume and low pH and increased risk of serious pulmonary injury should acid aspiration occur. Metoclopramide 10 or 20 mg intravenously prior to induction of anaesthesia was effective in reducing the residual gastric volume significantly, but not in raising pH. The combination of cimetidine and metoclopramide, as well as cimetidine alone, reduced the risk factors of acid aspiration by raising gastric pH and reducing residual volume. No anti-emetic effect of metoclopramide was observed. Higher doses of metoclopramide (20 mg) produced significant side effects (flushing, dizziness, extrapyramidal side effects), but were only marginally more effective than 10 mg doses in reducing residual gastric volume.

Intravenous dezocine for postoperative pain: a double-blind, placebo-controlled comparison with morphine.

Dezocine, a new mixed agonist-antagonist opioid analgesic, and morphine were compared in a double-blind study in 206 patients with postoperative pain. The analgesic efficacy of single intravenous injections of dezocine (2.5, 5.0, and 10.0 mg), morphine (5.0 mg), and placebo was assessed by verbal and visual scales at regular intervals for six hours after administration. All active treatments provided greater pain relief than placebo. Pain relief with dezocine 5 and 10 mg was significantly greater (P less than .05) than with placebo for up to four and five hours, respectively, and with morphine up to one hour. Pain relief scores were significantly higher (P less than .05) with morphine than with placebo at all observations except that of the fifth hour, and higher with dezocine 2.5 mg than with placebo for the first 30 minutes. Doses of 5 and 10 mg of dezocine produced approximately the same peak analgesic effect, with the larger dose having a longer duration of effect. All active treatments produced mild to moderate sedation. Side effects were few and mild or moderate with all of the treatments. The physician's and the patients' evaluations favored dezocine in a dose-dependent order, with morphine 5 mg rated lower than dezocine 5 mg and higher than dezocine 2.5 mg.

Double-blind placebo-controlled comparison of dezocine and morphine for post-operative pain relief.

Dezocine, a new mixed agonist-antagonist-type opioid analgesic, was compared in a double-blind trial with placebo and 10 mg of morphine in 190 patients with acute postoperative pain. The medications were given intramuscularly. Dezocine was administered at three dose levels (5, 10, and 15 mg). Pain relief scores, sedation, and side effects were recorded at 15, 30, 60, 120 and 240 min after injection. Significantly higher pain relief scores (p less than 0.05) were reported for the groups receiving dezocine 10 and 15 mg than the placebo group at all observation times, except for dezocine 15 mg at four hours. Morphine produced significantly better pain relief than placebo only between the second and fourth hour after administration. Significantly better pain relief was obtained with dezocine (10 and 15 mg) than with morphine during the first hour. The mean four-hour cumulative pain relief scores (TOTPAR) were significantly (p less than 0.05) higher than placebo for all active treatment groups. Side effects were few with no significant differences between the treatment groups. Seventy-nine per cent of the patients in the dezocine 15 mg group, and 73, 68, 58 and 50 per cent respectively, of the patients in the dezocine 10 mg, dezocine 5 mg, morphine 10 mg and placebo group had a satisfactory clinical response. Significantly (p less than 0.05) more patients in the groups receiving dezocine 10 and 15 mg than in the placebo group had a satisfactory clinical response; the difference was not significant for the dezocine 5 mg and morphine 10 mg groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind comparison of orally administered ciramadol and codeine for relief of postoperative pain.

Ciramadol, a new analgesic with mixed narcotic agonist-antagonist actions, was compared with codeine and placebo in a double-blind study in 343 patients with postoperative pain. The patients received a single oral dose of either 30 or 60 mg of ciramadol, 60 mg of codeine, or placebo. As indicated by three efficacy measures (verbal and visual analog pain scores and pain relief scores), the three active treatments were superior to placebo in relieving pain, and 30 and 60 mg of ciramadol generally were equivalent and superior, respectively, to 60 mg of codeine. The group who took 60 mg of ciramadol had a significantly (P less than .05) lower cumulative remedication frequency than that for the other three groups and the highest proportion of satisfactory evaluations by patients and physicians. There was no statistically significant difference in the incidence of side effects (4% to 11%) among the treatment groups. Demonstrated safety and efficacy suggest a role for ciramadol in the treatment of postoperative pain.

Effect of halogenated anaesthetics on heart rate changes during reversal of neuromuscular block with glycopyrrolate and neostigmine.

The effect of halothane and enflurane on changes in heart rate during reversal of neuromuscular blockade was compared in 48 patients. Premedication and anaesthetic technique was standardized. Either halothane or enflurane was used as the primary anaesthetic. Neuromuscular block was reversed by injection of glycopyrrolate and neostigmine, given either separately or simultaneously. Heart rate changes were significantly different between the halothane and enflurane subgroups. Patients anaesthetized with enflurane showed less fluctuations in heart rate. Simultaneous injection of glycopyrrolate and neostigmine minimized the tachycardia in the halothane subgroups only.

Physostigmine fails to reverse clinical, psychomotor, or EEG effects of lorazepam.

Physostigmine salicylate (2.0 mg) or 0.9% NaCl (2.0 ml) was administered intravenously in a double-blind fashion to adult volunteers in an attempt to reverse the effects of a 0.05-mg/kg dose of lorazepam given intravenously 30 min earlier. No other medication affecting the central nervous system was given. No differences were observed between the two groups with regard to the frequency of amnesia, psychomotor impairment, or EEG changes during a period of 4 h. The only significant difference in the level of sedation between the two groups was observed 60 min into the study. This difference is attributed to the high incidence of nausea and vomiting that occurred at that time exclusively in one group. Time to complete recovery was the same in both groups. However, physostigmine, not saline, was associated with a high incidence of muscarinic and sympathetic stimulating effects. The results obtained indicate that at the dose used, physostigmine is of no clinical value in treating sedation induced by lorazepam.

Modification by halogenated anaesthetics of chronotropic response during reversal of neuromuscular blockade.

The effect of halothane and enflurane on changes in heart rate during reversal of neuromuscular block was compared in 48 adult patients. Premedication and anaesthetic technique were standardized. Either halothane or enflurane was the primary anaesthetic while pancuronium was used in all patients to achieve muscle relaxation. Ventilation was mechanically controlled and PaCO2 was between 30-40 mmHg. The neuromuscular block was reversed by an intravenous injection of atropine 1.2 mg and neostigmine 2.5 mg, given either separately or simultaneously, in different patient subgroups. Heart rate changes were significantly different between the halothane and enflurane groups. In general, reversal of neuromuscular block was accompanied by less fluctuations in heart rate after enflurane as compared to halothane anaesthesia. Simultaneous injection of atropine and neostigmine modified the tachycardiac response in the halothane sub-group only. Our observations suggest that use of enflurane offers an advantage over halothane in those patients in whom rapid fluctuations in heart rate during reversal of neuromuscular block may be dangerous.

Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay.

Ketamine and two of its metabolites were determined up to 24 hours by a sensitive and specific gas chromatographic mass fragmentographic (GCMF) assay in the plasma of seven premedicated surgical patients. Each patient received ketamine in a dose between 2.0 and 2.2 mg/kg given intravenously over a 30-second period. Plasma levels of ketamine varied from 9,000 to 25,800 ng/ml 1 minute after injection to approximately 1,000 ng/ml when the patients began to recover consciousness. Within the next 24 hours, the patients had a complex logarithmic decline after injection. The data suggest rather complex pharmacokinetics with multiple compartments. Ketamine metabolites I and II were also found in the plasma over comparable periods of time. Ketamine metabolite I levels ranged from a high of 245 to 668 ng/ml within 30 minutes after ketamine administration to as low as 15 ng/ml 24 hours later. Ketamine metabolite II levels were lower with a peak of 515 ng/ml in approximately 60 minutes to 13 to 27 ng/ml 24 hours later. Recovery from anesthesia was related to the first two phases of rapid redistribution of ketamine. The plasma levels of the two ketamine metabolites were first detectable approximately 5 minutes after ketamine injection. Their relatively low levels throughout ketamine anesthesia and postanesthesia do not correlate with recovery from anesthesia. CSTRIP and NONLIN analysis indicated that a three-exponential equation best approximated the data obtained. It is concluded that a three-compartment open model best approximates ketamine pharmacokinetics in these patients.

Time course of antirecall effect of diazepam and lorazepam following oral administration.

The time course of antirecall effect and grades of sedation after the oral administration of diazepam and lorazepam were determined in 120 patients. Three standard doses of each drug were employed. Grades of sedation following oral diazepam were dose related, with a latency of 30-60 min and duration of 120-150 min. All three doses of lorazepam produced significantly more sedation with a similar latency (30-60 min) but longer duration (more than 240 min). Peak frequencies of the antirecall effects of diazepam 10, 15, and 20 mg were 5, 20, and 30 per cent, respectively. The duration was about two hours. Peak frequencies of the antirecall effect after lorazepam 2, 3, and 4 mg were 30, 45, and 72 per cent, respectively. Latency of peak action was about 60-90 min for all the doses, but the duration, especially with 3 and 4 mg doses, was long (4 h).

Improved method for the identification of the fluoride-resistant plasmacholinesterase genotypes.

This investigation was prompted by the findings that (1) dibucaine-resistant homozygotes and heterozygotes for plasmacholinesterase also exhibit resistance to fluoride inhibition, (2) the differentiation of dibucaine-resistant from the fluoride-resistant genotypes is ambiguous with the method of Harris and Whittaker, (3) the plasmacholinesterase inhibition by Na fluoride (FN) is markedly influenced by the temperature. Therefore, we modified their method by increasing (1) the temperature of the reaction from 25C to 37C and (2) the concentration of Na fluoride from 5.0 x 10(-5) M to 2.5 x 10(-4) M. With this method, gentically normal individuals have a mean FN + or - SD equals 43.0 + or - 10.0 and atypical dibucaine-resistant heterozygotes 67.0 + or - 5.37. Since a linear correlation was observed between DN and FN by our new method, a fluoride number 2 SD lower than the predicted FN from the DN can distinctly identify the fluoride-resistant plasmacholinesterase genotype Ef.

Lack of cardiovascular stimulation during endotracheal intubation in cardiac surgical patients anesthetized with diazepam-ketamine-pancuronium.

Anesthesia was induced with diazepam-ketamine-pancuronium in 12 adult patients scheduled for cardiac surgery. Intubation caused no significant changes in arterial blood pressure, heart rate, or plasma levels of norepinephrine and epinephrine. Circulatory stability was an advantage in critically ill patients.