TIME COURSE OF NEUROMUSCULAR EFFECTS AND PHARMACOKINETICS OF ROCURONIUM BROMIDE (ORG 9426) DURING ISOFLURANE ANAESTHESIA IN PATIENTS WITH AND WITHOUT RENAL FAILURE

We have studied the onset and duration of action and pharmacokineticsof rocuronium bromide (Org 9426) during anaesthesia with nitrousoxide, fentanyl and isoflurane after a single bolus dose ofrocuronium 0.6 mg kg^–1 in nine patients with chronic renalfailure requiring regular haemodialysis, and in nine healthycontrol patients. Blood samples were collected over 390 minand concentrations of rocuronium and its putative metabolitesmeasured using HPL C. Onset time for maximum block, durationof clinical relaxation (T1₂₅) and recovery index, were 61 (SD25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and28 (12.3) min and 19 (8.8) min, respectively, for patients withand without renal failure. The time for TOF ratio to returnspontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively,in the two groups. None of these differences was significant.The pharmacokinetic data were best described by a three-exponentialequation. There were significant differences between patientswith and without renal failure in the rates of clearance (2.5(1.1) ml kg^–1 min^–1 and 3.7(1.4) ml kg^–1 min^–1respectively) and the mean residence times (97.1 (48.7) minand 58.3(9.6) min) (P<0.05). The differences in other kineticparameters were not significant. We conclude that the effectsof rocuronium may be prolonged in patients with renal disease,because of a decreased clearance of the drug.     

ANTAGONISM OF THE MUSCARINIC EFFECTS OF EDROPHONIUM WITH ATROPINE OR GLYCOPYRROLATE: A Comparative Study R.

The efficacy of atropine or glycopyrrolate in doses of 10 or20 µg kg^–1 and 5 or 10 µgkg^–l, respectively,has been compared when administered to block the muscariniceffects of edrophonium 0.5 µg kg^–1 administeredfor the reversal of neuromuscular blockade. Both doses of atropineand the higher dose of glycopyrrolate prevented any edrophonium-induceddecreases in heart rate; glycopyrrolate at this dose was associatedwith tachycardia. Atropine and edrophonium could be safely administeredtogether in a mixture. The control of oropharyngeal secretionswas adequate even with the lower doses of both anticholinergicagents. Atropine 10 µg kg^–1 appears to be a betteranticholinergic agent for use with edrophonium.     

PROBABLE HISTAMINE LIBERATION WITH ATRACURIUM: A Case Report

An histaminoid reaction after the administration of thiopentoneand atracurium is described. Serial blood sampling showed noevidence of complement activation. Intradermal testing 6 weekslater yielded a positive result with atracurium (1 in 1000),but not with thiopentone. The clinical course of the reactionand the subsequent investigations suggest a direct pharmacologicalliberation of histamine.     

STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA XVII: ANTICHOLINERGIC PREMEDICANTS

The effects of premedication with the anticholinergic drugsatropine, hyoscine and glycopyrronium when administered by oraland i.m. routes have been evaluated in patients undergoing minorsurgery and compared with a placebo-using a double-dummy double-blindtechnique. Although the mouths of those patients who receivedadequate doses of anticholinergic drugs were dry, subjectivelyand observed, as compared with those who received a placebo,the overall course of anaesthesia did not appear to be different.Of the three drugs atropine seemed to be absorbed best followingoral administration. Equally effective oral and i.m. doses ofatropine were considered to be 2.0 and 1.0 mg respectively;of hyoscine 1.0 and 0.25–0.5 mg. The appropriate doseof glycopyrronium was 0.2 mg i.m. The routine use of anticholinergicdrugs in preanaesthetic medication in minor surgery appearsto be unnecessary.     

Premedication with cimetidine and metoclopramide

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.     

POTENCY ESTIMATION OF MIVACURIUM: COMPARISON OF TWO DIFFERENT MODES OF NERVE STIMULATION

We have assessed the potency of mivacurium, a new non-depolarizingneuromuscular blocker, using two different modes of nerve stimulationin patients anaesthetized with thiopentone, fentanyl and nitrousoxide in oxygen. The force of contraction of adductor polliciswas measured after single twitch stimulation at 0.1 Hz or train-of-fourstimulation (TOF) at 2 Hz every 70s. Dose-response curves wereconstructed using a single -dose method for each mode of stimulation.The ED50 and ED95 were 43 fig kg^-1 and 83kgkg^-1, respectively,for the single twitch responses and 34 ng kg^-1 and 66 fig kg^-1,respectively, for the first response of the TOF stimulation.The difference between the ED95 doses was not significant (?= 0.051), but the difference between the ED50 doses was significant(? = 0.03), suggesting greater sensitivity of the neuromuscularjunction using TOF stimulation. The results show that the informationobtained using single twitch stimulation at 0.1 Hz is not thesame as that obtained from the first response of the TOF stimulation.(Br. J. Anaesth. 1993; 70: 694–695)     

A comparison of the forces exerted during laryngoscopy

The forces exerted at laryngoscopy with the McCoy and Macintosh blades have been compared in 40 patients. The variables measured were the duration of laryngoscopy, the three maximally-applied forces and the mean force. The mean (SD) forces recorded were 18.9 (7.82) and 10.1 (5.33) N, respectively, with the Macintosh and the McCoy blades (p < 0.001) with a similar duration of laryngoscopy. There was a significant positive correlation between the mean force and patients' weight, height and body mass index for the Macintosh blade but only for weight and height for the McCoy blade. It is concluded that the use of the McCoy blade results in significantly less force being applied during laryngoscopy. This may be the reason for the reduction in the stress response reported previously with the use of the McCoy blade.     

Effect of four i.v. induction agents on T-lymphocyte proliferations to PHA in vitro

Anaesthetic agents are believed to have an adverse effect onhuman immunity. We have studied the effects of four i.v. inductionagents, thiopentone, methohexitone, etomidate and propofol,on T-lymphocyte proliferations to phytohaemagglutinin in vitro.We found that at plasma concentrations similar to those obtainedafter induction doses, all drugs, with the exception of propofol,caused depression of T-lymphocyte function.