CEREBRAL BLOOD FLOW DURING ANAESTHESIA: INFLUENCE OF PRETREATMENT WITH METOPROLOL OR CAPTOPRIL

We have studied the influence of a beta adrenergic blockingagent and an angiotensin converting enzyme (ACE)-inhibitor oncerebral blood flow (CBF) during general anaesthesia beforesurgery. Nine patients served as controls and received no specialpretreatment. Two other groups were allocated randomly to receiveeither metoprolol 0.07 mg kg^–1 i.v. (nine patients) atthe time of induction or captopril 1 mg kg^–1 by mouth(11 patients) 1.5 h before induction. There was no significantdifference in CBF or CBF values corrected for changes in Pa_co2(CBF_corr.) between the metoprolol group and controls. In thegroup pretreated with captopril, CBF_corr. values were significantlylower compared with the metoprolol group. Low CBF_corr. in associationwith low mean arterial pressure was observed in two patientstreated with captopril. These findings suggest that treatmentwith ACE-inhibitors should be discontinued before anaesthesia.     

INFLUENCE OF PREOPERATIVE GASTRIC ASPIRATION ON THE VOLUME AND pH OF GASTRIC CONTENTS IN OBSTETRIC PATIENTS UNDERGOING CAESAREAN SECTION

Aspiration of gastric contents, the most common anaestheticcause of maternal mortality, is decreased by emptying of thestomach and the use of antacids and H₂-receptor antagonists.One hundred and eighty-three mothers presenting for emergencyCaesaren section were allocated to three groups. In group 1,the stomach was emptied before operation via an orogastric tubeand thereafter 30 ml of sodium citrate 0.3 mol litre^–1was ingested 5–15 min before induction of general anaesthesia(our usual practice). Group 2 received only 30 ml of sodiumcitrate 0.3 mol litre^–1. Group 3 received ranitidine 50mg i.v. before operation, 5–15 min before induction ofanaesthesia, in addition to sodium citrate. Our results showthat preoperative gastric emptying with an orogastric tube followedby sodium citrate is preferred if anaesthesia should be induced15–20 min later. However, the use of ranitidine and sodiumcitrate is preferred at subsequent times. Although our datashow that preoperative gastric emptying decreased the mean intragastricvolumes before Caesarean section, the number of patients atrisk of acid aspiration was not reduced. In view of these findingsand the unpleasantness of orogastric intubation, we suggestthat routine preoperative gastric aspiration via an orogastrictube is not justified, although the manoeuvre should still beused following a recent meal.     

Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation

Background. Lung resistance increases after induction of anaesthesia.We hypothesized that prophylactic bronchodilation with i.v.carperitide before tracheal intubation would decrease airwayresistance and increase lung compliance after placement of thetracheal tube in both smokers and nonsmokers. Methods. Ninety-seven adults aged between 24 and 59 yr wererandomized to receive i.v. normal saline (0.9% saline) (control)or carperitide, 0.2 µg kg^–1 min^–1 throughoutthe study. The 97 patients included smokers and nonsmokers.Thus the patients were allocated to one of the four groups:smokers who received normal saline (n=21), nonsmokers who receivednormal saline (n=27), smokers who received carperitide (n=19)or nonsmokers who received carperitide (n=30). Thirty minutesafter starting normal saline or carperitide infusion, we administeredthiamylal 5 mg kg^–1 and fentanyl 5 µg kg^–1to induce general anaesthesia and vecuronium 0.3 mg kg^–1for muscle relaxation. Continuous infusion of thiamylal 15 mgkg^–1 h^–1 followed anaesthetic induction. Mean airwayresistance (R_awm), expiratory airway resistance (R_awe) and dynamiclung compliance (C_dyn) were determined 4, 8, 12 and 16 min aftertracheal intubation and compared between the four groups. Results. At 4 min after intubation, R_awm and R_awe were higherand C_dyn lower in smokers than in nonsmokers in the controlgroup. R_awm and R_awe were lower and C_dyn higher in smokers inthe carperitide group than in smokers in the control group.R_awm and R_awe were lower in nonsmokers in the carperitide groupthan in nonsmokers in the control group. Conclusions. Marked bronchoconstriction occurred in the controlgroups (smokers and nonsmokers) 4 min after tracheal intubation.Prophylactic treatment with carperitide before induction ofanaesthesia and tracheal intubation was advantageous, particularlyin smokers.     

EFFECTS OF ATRACURIUM ON INTRAOCULAR PRESSURE

The effects of attacurium on intraocular pressure (IOP) werecompared with those of pancuronium in 20 patients less than45 years-of-age requiring surgery for trauma of one eye. Aftera standard premedication and the application of topical analgesiato the upper airway, anaesthesia was induced with thiopentonei.v. and the trachea was intubated without the use of neuromuscularblockade. Following 20min of steady state anaesthesia duringwhich measurements of IOP, arterial pressure, heart rate, F_IO2,F_E'CO2 and CVP were recorded, one group of patients receivedatracurium 0.45 mg kg^–1 and the other pancuronium 0.1mg kg^–1. The observations were repeated for a further15 min before surgery commenced. Neither atracurium nor pancuroniumproduced any change in IOP. Atracurium was associated with greatercardiovascular stability than pancuronium.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: I: Patients Premedicated with Morphine Sulphate

The study was performed to determine the ED₅₀ and ED₉₅ of acontinuous infusion of the emulsion formulation of propofolduring 67% nitrous oxide anaestheisa in 57 patients premed-icatedwith morphine sulphate 0.15 mg kg^–1. Anaesthesia was inducedwith propofol 2 mg kg^–1, and maintained before incisionwith a fixed-rate infusion of propofol to supplement nitrousoxide. The response to the first surgical incision, made atleast 30 min after induction of anaesthesia, was observed. TheED₅₀; was 53.5 µg kg^–1 min^–1 and the ED₉₅was 112.2 µg kg^–1 min^–1. At the time of thefirst surgical incision, the venous whole blood concentrationsof propofol at the ED₅₀ and ED₉₅ infusion rates (EC₅₀and EC₉₅were 1.66 µg ml^–1 and 3.39 fig ml^–1 respectively.The satisfactory maintenance of anaesthesia provided by nitrousoxide supplemented with propofol was associated with stabilityand rapid, uncomplicated recovery.     

EFFECT OF NALOXONE ON THE LOSS OF CONSCIOUSNESS INDUCED BY I.V. ANAESTHETIC AGENTS IN MAN

The effect of a specific opioid antagonist, naloxone, was studiedin two comparable groups of patients who received i.v. the doseof an anaesthetic agent required to produce loss of consciousnessin 50% of subjects. The first group received naloxone 0.006mg kg^–1 5 min before induction of anaesthesia; the secondgroup received a similar volume of saline solution. Thiopentone,Althesin, diazepam, ketamine and propanidid were studied. Thedifferences in percentage of unconscious patients between thenaloxone-treated group and the control group were statisticallysignificant for diazepam, ketamine and propanidid. Naloxonedid not modify the induction of anaesthesia with thiopentoneor Althesin     

CARDIAC EFFECTS OF ATROPINE AND GALLAMINE IN PATIENTS RECEIVING SUXAMETHONIUM

Eighty healthy patients were randomly allocated to four groups.Atropine 0.01 mg kg^–1 i.v. (group I), gallamine 0.3 mgkg^–1 i.v. (group II), atropine 0.01 mg kg^–1 i.m.and gallamine 0.3 mg kg^–1 i.v. (group III), or atropine0.01 mg kg^–1 i.v. and gallamine 0.3 mg Lrg^–1 i.v.(group IV) were given before operation. After induction of anaesthesiawith thiopentone, suxamethonium 1 mg kg^–1 was given i.v.The lungs were ventilated with halothane in nitrus oxide inoxygen. Five minutes later the same dose of suxamrthonium wasrepeated. E.c.g. was monitored continuously. No serious bradycardiawas observed following a second injection of suxamethonium inany group. The results suggest that thiopentone protects againstsuxamethonium-induced bradycardia during halothane anaesthesia.     

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     

NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF MIVACURIUM CHLORIDE (BWB1090U) DURING NITROUS OXIDE-FENTANYL-THIOPENTONE AND NITROUS OXIDE-HALOTHANE ANAESTHESIA

Seventy-two adult surgical patients were studied to compareneuromuscular and cardiovascular effects of mivacurium chlorideduring nitrous oxide-fentanyl-thiopentone (BAL group) or nitrousoxide-halothane (HAL group) anaesthesia. Eighteen patients inthe BAL group received an initial bolus of mivacurium, eitherthe ED₂₅ (n = 9) or the ED50 (n = 9) (0.03 and 0.05 mg kg^–1).These doses were based on the assumption that the slope of thedose-response curve during nitrous oxide-opioid anaesthesiawould be approximately the same as the slope of the neuromuscularresponse from the first human studies with mivacurium. Twenty-sevenadditional patients were allocated to subgroups of nine patientsto receive mivacurium 0.04. 0.08 or 0.15 mg kg^–1. Twenty-sevenpatients in the HAL group were allocated also to subgroups ofnine patients to receive mivacurium 0.03, 0.04 or 0.15 mg kg^–1.During stable anaesthesia, mean endtidal halothane concentrationswere maintained at 0.49±0.01%. The estimated ED₅₀, ED₇₅and ED₉₅ for BAL and HAL groups were 0.039, 0.05 and 0.073 mgkg^–1 and 0.040, 0.053 and 0.081 mg kg^–1, respectively.Halothane did not potentiate maximum block or time to maximumblock. Halothane did affect spontaneous recovery. With the 0.15-mgkg^–1 dose, time to 95% recovery was prolonged significantlyin the HAL group (30.0 (SEM 1.4) min) compared with the BALgroup (24.1 (1.5) min). Recovery index from 25% to 75% recoverywas also prolonged significantly in the HAL group (7.0 (0.4)min) compared with the BAL group (5.4 (0.4) min). There wereno significant haemodynamic changes in groups given mivacuriumdoses up to and including 2 x ED₉₅ by bolus i.v. administration ^*Department of Anesthesia, University of Iowa Hospitals andClinics, Iowa City, Iowa 52242, U.S.A.     

DEXMEDETOMIDINE ATTENUATES SYMPATHOADRENAL RESPONSES TO TRACHEAL INTUBATION AND REDUCES THE NEED FOR THIOPENTONE AND PEROPERATIVE FENTANYL

The effects of the new, highly selective alpha₂-adrenergic agonist,dexmedetomidine, were studied in a randomized, placebo-controlled,double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6µg kg^–1 or saline was given i.v. 10 min before inductionof anaesthesia. The required dose of thiopentone was significantly(P < 0.001) smaller in the dexmedetomidine group (mean 4.4(SD 0.9) mg kg^–1) than in the control group (6.9 (1.6)mg kg^–1), and the drug attenuated the cardiovascular responsesto laryngoscopy and tracheal intubation. The concentration ofnoradrenaline in mixed venous plasma was smaller in the dexmedetomidinegroup during all phases of induction (P < 0.01). During surgery,fentanyl was required in a dose of 0.5 (0.6) mg kg^–1 and2.8(2.6) mg kg^–1 in the dexmedetomidine and control groups,respectively (P < 0.001). During 2h postoperative follow-up,oxycodone 0.06 (0.06) mg kg^–1 and 0.16 (0.1) mg kg^–1(P < 0.05) was given to the two groups respectively.     

I.V. PRACTOLOL DURING MICROLARYNGOSCOPY. EFFECT ON ARTERIAL PRESSURE, HEART RATE, BLOOD GLUCOSE AND LIPOLYSIS

Twenty-five patients undergoing microlaryngoscopy were anaesthetizedwith thiopentone and nitrous oxide with suxamethonium as a musclerelaxant. Thirteen received practolol 0.4 mg kg^–1 andatropine 1.5mg i.v. shortly before anaesthesia. During anaesthesiapractolol 0.2 mg kg^–1 was given. Twelve (control) receivedatropine 0.5 mg before anaesthesia. Practolol reduced the frequencyof tachycardia and arrhythmia. The treatment group had a greaterreduction in systolic arterial pressure during induction. Thehypertensive response to laryngoscopy was not significantlyattenuated by practolol. A weak hyperglycaemic response to microlaryngoscopywas not affected, nor was the plasma concentration of glycerol.     

THIOPENTONE-NITROUS OXIDE-HALOTHANE ANAESTHESIA AND SUXAMETHONIUM: PRETREATMENT WITH PANCURONIUM AND GALLAMINE

Eighty healthy adult patients randomly allocated to four groupsreceived pancuronium 0.01, 0.015, 0.02 mg kg^–1 or gallamine0.3 mg kg^–1 i.v. 3 min before induction. Just before inductionof anaesthesia, the patients were examined for signs and symptomsof neuromuscular blockade. After induction of anaesthesia withthiopentone, suxamethonium 1.5 mg kg^–1 was administeredi.v. Five minutes later the second dose was injected. No seriousarrhythmia was seen in any of the four groups following therepeated dose of suxamethonium. However, the highest dose ofpancuronium (0.02 mg kg^–1) caused an unacceptably highfrequency of partial neuromuscular blockade.     

PHARMACOKINETICS OF ATRACURIUM BESYLATE IN HEALTHY PATIENTS (AFTER A SINGLE I.V. BOLUS DOSE)

The plasma decay of atracurium besylate was examined in twogroups of six patients. Group I received atracurium 0.6 mg kg^–1and group II 0.3 mg kg^–1 as a single bolus dose i.v. Theplasma concentrations were measured by high performance liquidchromatography. An individual two-compartment pharmacokineticmodel was used for interpretation. The results from the twogroups were not significantly different, giving overall meanvalues of 2 min (±0.2 SEM) for the distribution half-life(T_t), 19.9 min (±0.6) for the elimination half-hie (T_t^ß),5.5 ml min^–1 kg^–1 (±0.2) for total clearance(CI) and 157 mlkg^–1 (±7) for total distributionvolume (V _ares).     

PROPOFOL FOR INDUCTION AND MAINTENANCE OF ANAESTHESIA: COMPARISON BETWEEN YOUNGER AND OLDER PATIENTS

The propofol requirements for the induction and maintenanceof anaesthesia were compared in groups of younger and olderpatients. Side effects, influence on the cardiovascular systemand recovery times were compared between 20 unpremedicated ASAI–III, 25–40-yr-old patients and 20 65–80-yr-oldpatients all scheduled to undergo elective surgery. After inductionwith propofol, anaesthesia was maintained with a continuousinfusion of the drug. Vecuronium and fentanyl were administeredas required. In the young group propofol 2.2 mg kg^–1 andin the elderly 1.7 mg kg^–1 were needed for induction (P< 0.05). The maintenance doses were 10.0 mg kg^–1 h^–1and 8.6 mg kg^–1 h^–1, respectively (P < 0.01).Side effects were more pronounced in the younger patients. Influenceson the cardiovascular system were definite, but mild. The youngerpatients awoke sooner: 7.8 v. 14.3 min (P < 0.01) after thediscontinuation of the infusion of propofol.     

PRELIMINARY STUDY OF A PREGNANOLONE EMULSION (KABI 2213) FOR I.V. INDUCTION OF GENERAL ANAESTHESIA

Pregnanolone emulsion was administered i.v. to 13 healthy malevolunteers to assess its potential as an agent for i.v. inductionof general anaesthesia and to establish a pharmacokinetic profileat two doses. Each subject received 0.5mg kg^–1 0.75mgkg^–1 and 1.0 mg kg^–1 on successive occasions, therate of administration being constant for each dose. Pregnanoloneemulsion was found to produce smooth and reliable inductionof general anaesthesia with cardiorespiratory effects comparableto those of other i. v. induction agents.     

PREMEDICATION DETERMINES THE CIRCULATORY RESPONSES TO RAPID SEQUENCE INDUCTION WITH SUFENTANIL FOR CARDIAC SURGERY

Thirty-three patients undergoing elective aortocoronary bypasswere allocated randomly to receive morphine 0.1 mg kg^–1i.m. and either lorazepam 50 µg kg^–1 by mouth orhyoscine 6 µg kg^–1 i.m. before rapid sequence inductionof anaesthesia with sufentanil 5 µg kg^–1 i.v. andsuxamethonium 1 mg kg^–1 i.v. Following induction and trachealintubation, patients premedicated with hyoscine had a significantlyhigher mean heart rate, mean arterial pressure, cardiac indexand left ventricular stroke-work index than patients premedicatedwith lorazepam. The incidence of new myocardial ischaemia waslow in both groups.     

Oral clonidine premedication attenuates the hypertensive response to ketamine

Clonidine diminishes sympathetic nervous system activity viaa central action. To test if the haemodynamic responses to ketamine,a centrally acting sympathomimetic drug, are attenuated by clonidine,we studied arterial pressure (AP) and heart rate (HR) changesafter ketamine 1 mg kg^–1 in 40 normotensive patients undergoinggeneral anaesthesia. They were allocated randomly to receiveclonidine 5 µg kg^–1 and famotidine 20 mg (n = 20)or to a control group (n = 20) which received only famotidine20 mg orally 90 mm before induction of anaesthesia. After administrationof ketamine 1 mg kg^–1 and vecuronium 0.2 mg kg^–1ventilation of the lungs was controlled with 67% nitrous oxidein oxygen to maintain end-tidal carbondioxide at 4–4.7kPa. AP and HR were measured non-invasively at 1-min intervalsfor 10 min after ketamine. After induction of anaesthesia, APwas increased significantly from resting values in the controlgroup, but remained unchanged in the clonidine group (P <0.05). Maximum changes in mean AP were also significantly greaterin the control group compared with the clonidine group (29.2(12.8) vs 19.5 (13.1) mm Hg, P = 0.02). However, no change inHR was noted throughout the 10-min study.     

PHARMACOKINETICS OF I. V. AND RECTAL METHOHEXITONE IN CHILDREN

The pharmacokinetics of methohexitone were investigated in 15healthy children undergoing minor surgery under inhalation anaesthesia.Six received 1% methohexitone 1–2 mg kg^–1 i.v. andnine received 10% methohexitone 20–25 mg kg^–1 perrectum. On i. v. administration, three-compartment pharmacokineticsgenerally applied. The mean elimination half-life of methohexitonewas 193 ± 75 min; that is, considerably longer than previouslyreported for children, but in good agreement with findings inadults. The mean clearance was 17.9 ± 8.3 ml min^–1kg^–1, the volume of distribution at steady state was 2.1± 0.24 litre kg^–1 and the mean residence time was134 ± 47 min. The pharmacokinetic model used for thei.v. data was easily modified to suit the plasma concentrationcurves obntained on rectal administration. The mean bioavailabilityof methohexitone administered per rectum was 17% with a six-foldvariation between individuals.     

INDUCTION DOSE-RESPONSE STUDIES WITH PROPOFOL AND THIOPENTONE

The relative potencies of propofol and thiopentone were assessedusing different indicators of induction of anaesthesia: abolitionof the response to verbal commands and eyelash stimulation.Log-probit dose-response curves for these end-points were determined30, 60 and 90 s after induction in 96 unpremedicated ASA groupI patients. For propofol, ED₅₀ values for abolition of the responseto verbal commands and eye/ash stimulation at different timeintervals were in the ranges 1.76–1.42 and 1.23–1.72mg kg^–1, respectively; corresponding ED₉₅ values were2.18–2.67 and 2.42–3.27 mg kg^–1, respectively.For thiopentone, the calculated ED₅₀ values for verbal commandsand eyelash stimulation at the same time intervals were 1.81–2.23and 3.55–3.40 mg kg^–1; corresponding ED₉₅ valueswere 5.11–6.29 and 6.41–6.70 mg kg^–1, respectively.The potency ratio of propofol to thiopentone observed in thisstudy varied from 1:1.27 to 1:2.88. It is concluded that a dose-responsecurve reflecting one end-point of anaesthesia cannot be usedto define another end-point of anaesthesia.     

COMPARISON OF DEXMEDETOMIDINE, AN ALPHA2-ADRENOCEPTOR AGONIST, AND MIDAZOLAM AS I.M. PREMEDICATION FOR MINOR GYNAECOLOGICAL SURGERY

The effects of i.m. dexmedetomidine 1.0 ng kg^–1, a new<t2-adrenoceptor agonist, were compared with those of i.m.midazolam 0.08 mg kg^–1 and placebo on vigilance, anaestheticrequirements, haemodynamic state and plasma catecholamine concentrationsin a double-blind placebo-controlled study in 107 healthy (ASAphysical status l-ll) women undergoing cervical dilatation anduterine curettage. The premedicants were administered i.m. 60min before induction of anaesthesia with thiopentone. Nitrousoxide 70% in oxygen and thiopentone were used for maintenance.Both premedicants were tolerated well and no serious haemodynamicor other adverse events occurred. Dexmedetomidine caused moderatereductions in arterial pressure (maximally by 20%) and heartrate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia < 45 beat min^–1.Both premedicants decreased the plasma concentrations of nor-adrenalineby about 50%, but only dexmedetomidine attenuated the catecholamineresponse to anaesthesia and surgery. The thiopentone requirementswere decreased significantly (P =0.003) by both dexmedetomidine(17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2)min after midazolam, 8.5 (5.2) min after dexmedetomidine and5.6 (11.4) min after placebo (? =0.006 between midazolam andplacebo groups, other differences ns).