EFFECT OF ALFENTANIL ANAESTHESIA ON THE ADRENOCORTICAL AND HYPERGLYCAEMIC RESPONSE TO ABDOMINAL SURGERY

Plasma concentrations of cortisol and glucose were measuredfrom before to 9 h after skin incision in 24 patients undergoingabdominal hysterectomy. The patients were randomly allocatedto receive either high-dose alfentanil anaesthesia (150 µgkg^–1 initially, followed by continuous infusion at a rateof 3 µg kg^–1 min^–1) or neurolept anaesthesia(droperidol 0.25 mg kg^–1 plus fentanyl 5 µg kg^–1initially, followed by intermittent incremental doses of fentanyl50 µg). The intraoperative and initial postoperative increasesin plasma cortisol and glucose concentrations were inhibited(P < 0.05) by alfentanil but, later in the postoperativeperiod, both groups showed identical increases in cortisol andglucose concentrations. Mean arterial pressure and heart ratewere more stable in the alfentanil group. The concept of "stress-free"anaesthesia during highdose opiate administration seems to bevalid during operation and for the initial 1–3 h intothe postoperative period.     

USE OF SIMPLE TESTS TO DETERMINE THE RESIDUAL EFFECTS OF THE ANALGESIC COMPONENT OF BALANCED ANAESTHESIA

In order to evaluate simple means of determining the rate ofrecovery after general anaesthesia, the usefulness of the criticalflicker fusion threshold test, the Maddox wing apparatus andthe visual analogue scale were compared. The postanaestheticrecovery score was used as a reference. Two patient groups (n= 15 in each) received, in a randomized double-blind study,a similar balanced anaesthesia for Caesarean section, exceptthat the analgesic component was either fentanyl 2.5µgkg^–1 i.v. or buprenorphine 7.5 µg kg^–1 i.v.Maddox wing apparatus and visual analogue scale were sensitiveenough to differentiate between the postanaesthetic residualeffects of the two opioids, but critical flicker fusion thresholdand, especially, postanaesthetic recovery score were insensitivein this respect. There was no difference between the two patientgroups in mean arterial pressure and heart rate. Our resultsshow that the residual effects of different kinds of opioidsas an analgesic component of balanced anaesthesia can be differentiatedusing simple means like Maddox wing apparatus and visual analoguescales.     

EFFECTS OF PROPOFOL AND OF THIOPENTONE ANAESTHESIA ON THE RENAL CLEARANCE OF CEFOXITIN IN THE SHEEP

We have examined the renal extraction ratios and clearancesof cefoxitin in three groups of adult merino ewes. One group(n = 3) was studied for 12 h without perturbation; these weredesignated control studies. The other two groups (n = 4 each)were studied before (baseline values), during and after theinduction and 70-min maintenance of anaesthesia with propofolor thiopentone. In the control studies, mean renal extractionratio and clearance for cefoxitin were, respectively, 0.67–0.92and 0.66–0.91 litre min^–1 and were consistent throughoutthe entire study period in individual animals. Comparable valueswere obtained as baseline values in the anaesthesia groups.Compared with individual baseline values, blood concentrationsof cefoxitin doubled during anaesthesia with each agent. Atthe same time, renal extraction ratio and clearance for cefoxitineach decreased significantly to about 50–60% of theircontrol values. Recovery to control values of arterial bloodconcentrations and renal extraction ratio of cefoxitin tookat least 5 h, but recovery of renal clearance was more rapid.The results indicate that renal elimination of an organic anionsuch as cefoxitin may be affected by changes in renal bloodflow and in renal function produced by propofol and thiopentone;these effects may last for several hours after recovery of renalblood flow. ^*Present address: Department of Anaesthesia and Intensive Care,Royal Adelaide Hospital, The University of Adelaide, AdelaideSA 5000, Australia.     

USE OF AN EMULSION OF ICI 35868 (PROPOFOL) FOR THE INDUCTION AND MAINTENANCE OF ANAESTHESIA

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol)has been used to supplement 67% nitrous oxide in oxygen anaesthesiain 20 patients premedicated with morphine 0.15 mg kg^-1and atropine0.6 mg, and undergoing body surface surgery. Following an inductiondose of propofol 2.5 mg kg^-1, the mean maintenance dose was73.4µg kg^-1min^-1. When compared with 10 patients receivingAlthesin to supplement nitrous oxide in oxygen in a similarmanner, recovery was considerably faster following propofol.The only major side-effect associated with the use of propofolwas pain on injection in nine out of 20 patients. When the patientsreceiving propofol were compared with a second control group(n = 11) in whom anaesthesia was induced with thiopentone 4mg kg^-1and maintained with 1 % halothane and nitrous oxide inoxygen, the former group showed a significant (P<0.01) decreasein the plasma cortisol concentration 30 min after the inductionof anaesthesia. However, by 3 h after induction, the cortisolconcentration in both groups was not significantly differentfrom the baseline (pre-induction) value. The mechanism of thisdecrease is not known. In vestigation of the influence of thefat emulsion on blood coagulation andfibrinolysis revealed nodifferences when compared with patients receiving Althesin.     

EFFECTS OF PROPOFOL AND OF THIOPENTONE ANAESTHESIA ON THE REGIONAL KINETICS OF PETHIDINE IN THE SHEEP

We have examined the extraction ratios, net fluxes and clearancesof pethidine by the liver, kidneys and hindquarters in sheepbefore, during and after continuous anaesthesia (70 min) withpropofol or thiopentone. Before anaesthesia, the overall meanrespective regional pethidine extraction ratios were 0.98 (SD0.01), 0.20 (0.06) and 0.44 (0.13), the corresponding net fluxeswere 47 (7), 5 (2) and 20 (10)% dose min^–1 and the clearances1.44 (0.22), 0.17 (0.07) and 0.80 (0.39) litre min^–1.During propofol anaesthesia, arterial blood concentrations ofpethidine approximately doubled (P < 0.05), mean pethidinehepatic extraction ratio was unchanged, flux was increased to145 (20)% and clearance decreased to 79 (10)% (P < 0.05)of baseline values; mean pethidine renal extraction ratio, fluxand clearance were 73 (34), 112 (43) and 69 (31)% of baselinevalues; mean hindquarter pethidine extraction ratio decreasedto 65 (25)% (P < 0.05) of baseline values. During thiopentoneanaesthesia, arterial blood concentrations of pethidine approximatelydoubled (P < 0.01), mean pethidine hepatic extraction ratiowas 97 (2)% of baseline values and flux and clearance were unchanged,mean pethidine renal extraction ratios, flux and clerance decreasedto 37 (21), 54 (18) and 27 (19)% (all P < 0.05) of baselinevalues and mean pethidine hindquarter extraction ratio was 81(20)% of baseline values. In spite of only modest changes inhepatic and renal blood flow during anaesthesia, blood concentrationsof pethidine doubled and pethidine kinetics were disturbed forseveral hours after anaesthesia. Overall, however, the changeswere of smaller magnitude and shorter duration than those thathave been described for anaesthesia with the volatile anaestheticagents. ^*Present address: Department of Anaesthesia and Intensive Care,Royal Adelaide Hospital, The University of Adelaide, AdelaideSA 5000, Australia.     

EFFECTS OF TRIMETAPHAN ON THE CARDIOVASCULAR RESPONSE TO TRACHEAL INTUBATION

In three groups of 10 patients, we have studied the effect onthe cardiovascular responses to laryngoscopy and intubationof bolus doses of saline or trimetaphan 0.05 mg kg^–1 or0.1 mg kg^–1 given 1.75 min before the start of laryngoscopy.Anaesthesia was induced with thiopentone 5 mg kg^–1 i.v.and tracheal intubation was facilitated with vecuronium 0.2mg kg^–1. During anaesthesia, ventilation was assistedor controlled with 1% enflurane and 50% nitrous oxide in oxygen.Patients receiving saline showed a significant increase in meanarterial pressure and rate-pressure product associated withtracheal intubation. These increases following tracheal intubationwere less in trimetaphan-treated patients compared with thoseof the control group (P<0.05). There was no significant differencein heart rate following tracheal intubation between the threegroups. These data suggest that trimetaphan may be used as asupplement during induction, to attenuate the hypertensive responseassociated with laryngoscopy and tracheal intubation.     

POSTGANGLIONIC SYMPATHETIC DISCHARGE AND THE EFFECT OF INHALATION ANAESTHETICS

Postganglionic cardiac, carotid, and hypogastric sympatheticactivity was recorded before and during administration of inhalationanaesthetics, in rabbits ventilated with oxygen and given gallamine.During control periods, when light anaesthesia was maintainedwith pentobarbitone, changes in postganglionic sympathetic dischargepreceded, or responded to, alterations in arterial pressure.Postganglionic activity was increased by cyclopropane, whichraised arterial pressure; by ether, which produced more variablecirculatory changes; and usually by halothane, which loweredarterial pressure. Occasional sympathetic units, identifiedon film, showed partial inhibition during halothane anaesthesia. ^*Addenbrooke's Hospital, Cambridge. Present address: Dept. of Physiology, Australian National University,Canberra.     

EFFECTS OF INHALATION ANAESTHETICS ON FILTRATION OF VENOUS GAS EMBOLI BY THE PULMONARY VASCULATURE

Venous gas emboli are prevented from reaching the systemic circulationby filtration in the pulmonary vasculature. This filtrationcan be overwhelmed by exceeding certain critical rates of venousair infusion. To characterize further these filtration phenomena,the effects of pentobarbitone, isoflurane and halothane anaesthesiaon the incidence of spillover of venous bubbles into the arterieswere studied in groups of nine dogs. Venous air was infusedat rates of 0.25, 0.30, and 0.35 ml kg^–1 min^–1.Spillover of venous bubbles into the arteries was detected witha Doppler ultrasonic probe located over the suprarenal aorta.At the lowest venous air dose (0.25 ml kg^–1 min^–1),no bubbles were detected in the systemic circulation in thepentobarbitoneor halothane-anaesthetized dogs, while arterialbubbles were detected in two with isoflurane anaesthesia. At0.30 ml kg^–1 min^–1 air, one, four and two dogs hadarterial bubbles detected with pentobarbitone, halothane orisoflurane anaesthesia, respectively, while at 0.35 ml kg^–1min^–1 spillover of bubbles occurred in four, five andthree, respectively. The spillover of venous bubbles into thearteries was dose-related for the pentobarbitone- and halothane-anaesthetizeddogs.     

ARTERIAL OXYGEN SATURATION BEFORE INTUBATION OF THE TRACHEA: An assessment of oxygenation techniques

Arterial oxygenation in patients was measured with an ear oximeterto assess factors that were associated with hypoxaemia at theinduction of anaesthesia. Twenty patients breathed air duringthe induction of anaesthesia with thiopentone and followingneuromuscular blockade with suxamethonium. Mean Sa_O2 decreasedfrom 95.7% before induction to 85.5% 1 min after induction.The Sa_O2 1 min was less in those patients whose weight was morethan expected (Sa_O2 80.5%), than in those patients whose weightwas as expected or less than expected (Sa_O2 88.8%). Other factorssuch as haemoglobin concentration, FEV₁, FVC, age, or smokinghabits, were not related to the degree of arterial desaturarion.To assess the efficacy of different methods of oxygen administration,four groups of 10 patients, were given oxygen in different waysusing a Magill anaesthetic system with a supply of 10 litremin^–1. Measurements were made for up to 3min after theinduction of anaesthesia and maintenance of apnoea. Group Ibreathed normally from the system for 1 min before anaesthesiawas induced. Group II were treated similarly, but the mask hada standardized "leak", a 9.5-mm diameter hole. Group III tookthree vital capacity breaths from the system before anaesthesia,and group IV breathed air before anaesthesia, but their lungswere given three maximal manual inflations after the inductionof anaesthesia. Mean Sa_O2 values after 3 min apnoea were: 96.8%(group I), 93.6%(group II), and 98.0% (group III). In groupIV, measurements were stopped at 2 min when mean Sa_O2 was 92.9%.These values are significantly different (P<0.05) and suggestthat three vital capacity breaths from a non-rebreathing anaesthesiasystem is an adequate and acceptable method of pre-oxygenation ^*Present address: Department of Anaesthetics, Addenbrookes Hospital,Hills Road, Cambridge CB2 2QQ     

COMPARISON OF THE EFFECTS OF ISOFLURANE OR FENTANYL-NITROUS OXIDE ANAESTHESIA ON PROPRANOLOL DISPOSITION IN DOGS

The disposition of propranolol was studied, using dual-routeadministration, in two groups of six dogs. Each dog was studiedon three consecutive days: day 1 awake, day 2 during anaesthesia,and day 3, 24 h after anaesthesia. Anaesthesia was with isoflurane2.0 MAC (in oxygen) in one group and with a fentanyl—nitrousoxide—atracurium regimen in the other group. In the groupreceiving fentanyl, anaesthesia caused a significant decrease(63%) in intrinsic clearance from the day 1 value (P < 0.05)and a 45% decrease in systemic clearance (P < 0.05). Hepaticplasma flow decreased by 27% (ns). A similar pattern was foundwith isoflurane: intrinsic clearance decreased by 53% (P <0.05) and systemic clearance by 40% (P< 0.05). Hepatic plasmaflow decreased by 40% (ns). In both groups, the values 24 hafter anaesthesia were not significantly different from thoseobtained on day 1. Anaesthesia with either fentanyl—nitrousoxide—atracurium or isoflurane has a marked, but short-lastingeffect on the disposition of propranolol, in part as a resultof a decrease in intrinsic clearance. ^* Present address: Department of Anaesthetics, University ofSheffield, Sheffield     

EFFECT OF SALBUTAMOL AND SUXAMETHONIUM ON THE PLASMA POTASSIUM CONCENTRATION

In a double-blind randomized study, patients received premedicationwith Iorazepam 0.04 mg kg–^–1 and salbutamol 0.1mg kg–^–1 or lorazepam 0.04 mg kg–^–1and placebo given orally 2.5–3 h before anaesthesia. Theplasma potassium concentration was measured at the time of premedication,before the induction of anaesthesia and at selected intervalsafter suxa-methonium 1 mg kg–^–1 i. v. The plasmapotassium concentration was lower in those patients who receivedsalbutamol than in those given placebo, and remained lower atall the subsequent sample times. Oral salbutamol did not appearto affect the incidence of suxamethonium related muscle pain.     

PREVENTION OF HISTAMINE-INDUCED CARDIOVASCULAR REACTIONS DURING THE INDUCTION OF ANESTHESIA FOLLOWING PREMEDICATION WITH H1- + H2-ANTAGONISTS I. M.

In a prospective controlled double-blind study, 60 electivesurgical patients were randomly assigned to three premedicationgroups. Twenty patients received promethazine 0. 5 mg kg^–1i.m. 45 min before induction of anaesthesia; a further 20 patientsreceived an additional i. m. injection of cimetidine 400 mg120 min before induction. The third group (n = 20) served asthe control group. Following vecuronium 0.02 mg kg^–1,anaesthesia was induced with fentanyl, and etomidate. All patientsthen received suxamethonium 1.5 mg kg^–1 i. v. The combinedadministration of H₁- + H₂-antagonists as premedication ledto a significant reduction in the increase in heart rate whencompared with the effects in the other groups.     

COMPARISON OF PROPOFOL WITH METHOHEXITONE IN THE PROVISION OF ANAESTHESIA FOR SURGERY UNDER REGIONAL BLOCKADE

Propofol was compared with methohexitone for provision of lightgeneral anaesthesia in patients undergoing surgery under spinalanalgesia. Intermittent bolus administration of both agentsproved a feasible way of maintaining anaesthesia, a mean infusionrate of 0.13 mg kg^–1 min^–1 being required for propofoland 0.089 mg kg^–1 min^–1 for methohexitone. Propofolproduced smoother anaesthesia with significantly fewer excitatoryside effects and less pain on injection, but cardiovascularand respiratory depression occurred commonly. Recovery was rapidwith both agents, but minor postoperative sequelae occurredmore frequently after methohexitone.     

THE SENSITIVITY OF THE RESPIRATORY TRACT DURING ANAESTHESIA IN THE CAT

In cats the sensitivity of the respiratory tract to stimulationwith diethyl ether was studied during nitrous oxide, cyclopropane,halothane and trichloroethylene anaesthesia. Nitrous oxide causedlittle change in sensitivity; halothane and trichloroethylenecaused a gradually decreasing sensitivity; and cyclopropanedepressed the response only in deep anaesthesia. In addition,following stimulation, the severity of breath-holding was markedwith cyclopropane but not with the other agents. ^*At present at the Department of Anaesthetics, Welsh NationalSchool of Medicine, Cardiff, Wales. At present at Stobhill Hospital, Glasgow, Scotland.     

COMPARISON OF I.V. GLYCOPYRROLATE AND ATROPINE IN THE PREVENTION OF BRADYCARDIA AND ARRHYTHMIAS FOLLOWING REPEATED DOSES OF SUXAMETHONIUM IN CHILDREN

The effectiveness of administration of grycopyrrolate 5 and10 µg kg^–1 and atropine 10 and 20 µg kg^–1i.v. immediately before the induction of anaesthesia, to preventarrhythmia and bradycardia following repeated doses of suxamethoniumin children, was studied. A control group was included for comparisonwith the lower dose range of grycopyrrolate and atropine. Afrequency of bradycardia of 50% was noted in the control group,but this was not significantly different from the frequencywith the active drugs. Bradycardia (defined as a decrease inheart rate to less than 50 beat min^–1) was prevented whenthe larger dose of either active drug was used. It is recommendedthat either glycopyrrolate 10 mg kg^–1 or atropine 20 µgkg^–1 i.v. should immediately precede induction of anaesthesia,in children, if the repeated administration of suzamethoniumis anticipated     

ULTRASOUND ASSESSMENT OF THE POSITION OF THE TONGUE DURING INDUCTION OF ANAESTHESIA

Tongue position was assessed in 15 female patients at inductionof anaesthesia with either thiopentone or propofol. A videorecording of a midline sagittal section of the tongue was madeusing an ultrasound transducer placed below the chin, and representativefigures analysed by an observer who was not aware of the patient'sstate. In 11 satisfactory recordings, the tongue movement wasinconsistent in direction and not more than 8 mm in the anteriortongue and 6 mm in the posterior tongue. The movements detecteddid not suggest that the tongue is likely to be an importantcause of airway obstruction on induction of anaesthesia. This paper was presented at the Anaesthetic Research Societymeeting at the University of Warwick on April 7, 1989.     

THE USE OF DIFFERENT DOSES OF VECURONIUM IN PATIENTS WITH LIVER DYSFUNCTION

The clinical neuromuscular effects of two doses of vecuronium(0.15 mg kg^-1 and 0.2 mg kg^-1) were investigated in 20 healthypatients and 20 patients with cirrhosis, and compared with previouswork in which vecuronium 0.1 mg kg^-1 was given under identicalconditions of anaesthesia and monitoring. Ten healthy patientsreceived vecuronium 0.15 mg kg^-1 and 10 received 0.2 mg kg^-1.Similarly, 10 patients with cirrhosis received vecuronium 0.15mg kg^-1 and 10 received 0.2 mg kg^-1. Vecuronium 0.1 mg kg^-1has previously been shown to have a somewhat shorter durationof action in cirrhotic as opposed to healthy patients. In thisstudy, vecuronium 0.15 mg kg^-1 was found to have a similar durationof action in both groups, and vecuronium 0.2 mg kg^-1 had a significantlylonger action in the cirrhotic group. It is suggested that vecuroniumshould be used with caution in patients with hepatic dysfunctionand that, in such patients, monitoring of neuromuscular functionis desirable.     

PHARMACOKINETICS OF FENTANYL DURING CONSTANT RATE I.V. INFUSION FOR THE RELIEF OF PAIN AFTER SURGERY

Forty-five patients in four groups undergoing orthopaedic, upperabdominal, prolonged or cardiac surgery received a constantrate i.v. infusion of fentanyl 100 µg h^–1 for 24h starting 2 h before surgery. A single bolus dose was giveni.v. at the induction of anaesthesia. Plasma fentanyl concentrations,measured by radio-immunoassay were between 1 and 3 ng ml^–1until the infusions were discontinued. Clearance of fentanylwas decreased in the cardiac surgery group only. The eliminationhalf-life was 7.3–9.7 This simple regimen produced effectiveanalgesia.     

MEASUREMENT OF THE RATES OF NITROUS OXIDE UPTAKE AND NITROGEN EXCRETION IN MAN

Using a completely closed anaesthetic circuit, nitrous oxideuptake and nitrogen excretion were measured simultaneously inpatients undergoing nitrous oxide in oxygen anaesthesia forabdominal surgery. The results have been compared with standardmodels of uptake and excretion. Mean nitrous oxide uptake wasmeasured and did not exceed 400 ml min^–1 (normalized to70-kg man) and was not less than 60 ml min at 100 min^–1after the start of nitrous oxide in oxygen anaesthesia. Nitrogenexcretion did not exceed 100 ml min^–1 and was measurable(8ml min^–1) at 100 min. The persistence of nitrogen excretioncontrasts with other published data obtained with intact volunteersand this suggests that exposure at surgery of abdominal tissues,including fat, affect substantially the rates of excretion anduptake after 70 min.     

EFFECTS OF DIFFERENT DOSES OF THIOPENTONE ON THE INCREASE IN SERUM MYOGLOBIN INDUCED BY SUXAMETHONIUM IN CHILDREN

We have studied the effects of different doses of thiopentoneon the increase in serum myoglobin after administration of suxamethoniumduring inhalation induction of anaesthesia in children. Forty-threechildren were anaesthetized with halothane and nitrous oxidein oxygen and allocated to four groups. group S received suxamethonium1 mg kg^–1 to facilitate intubation; group ST2 receivedthiopentone 2 mg kg^–1 and group ST4 received thiopentone4 mg kg^–1 before administration of suxamethonium 1 mgkg^–1; group N did not receive thiopentone or suxamethonium.Serum myoglobin and creatine kinase (CK) concentrations weremeasured until 60 min after the injection of suxamethonium.Both myoglobin and CK concentrations increased in the threegroups receiving suxamethonium. There were no significant differencesbetween groups S and ST2, but the myo globin concentration wasless in group ST4 than in groups S and ST2. A significant differencein CK concentration was found only between groups ST2 and ST4at 60min. In group N, both values remained reasonably constant.Thiopentone 4mg kg^–1, but not 2 mg kg^–1, attenuatedthe increase. The results indicate that to prevent a markedelevation in serum myoglobin after administration of suxamethonium,thiopentone 4 mg kg^–1 should be administered. Presented in part at the Annual Meeting of the American Societyof Anesthesiology, October 1989 (Anesthesiology 1989; 71: A1046).