ISOBUTENE FORMATION DURING HALOTHANE ANAESTHESIA IN MAN

The concentrations of volatile hydrocarbons were studied inbreath samples from patients before and after anaesthesia. Inpatients to whom halothane was administered, there was a significantincrease in the concentration of isobutene (from 0.43±0.09to 4.66±2.22 nmol litre^–1). There was no changein the concentration of isobutene in six patients anaesthetizedwith ketamine and diazepam. The concentrations of ethane andpentane were not altered significantly in either group.     

RAPID INDUCTION OF HALOTHANE ANAESTHESIA IN MAN

The cardiopulmonary and anaesthetic responses of nine healthyvolunteers, breathing concentrations of 1-4% halothane in oxygen,were studied. Supine fasting subjects breathing room air exhaledto residual volume and then inhaled a vital capacity breathof 1, 2, 3 or 4% halothane in oxygen. After a breath-hold of30–90 s they exhaled and then breathed spontaneously thesame anaesthetic mixture for up to 2 min. The electrocardiogram,arterial pressure, heart sounds and arterial oxygen saturation,were monitored, and respiratory gases were analysed by massspectrometry. The maximum effect was seen after breathing 4%halothane. All volunteers were amnesic after the first breathand unresponsive to command after 2 min. Little or no excitementoccurred. A maximum decrease of 12 mm Hg in systolic pressurewas seen while breathing 4% halothane. Bradycardia, hypoxiaand clinically important hypercarbia did not occur. At all inspiredconcentrations of halothane, the end-tidal halothane concentrationincreased rapidly and was 30% of the inspired value after 1min. No volunteer found this technique to be unpleasant. Rapidinduction of general anaesthesia with 2–4 % halothanein oxygen is effective, safe and well accepted by healthy youngadults.     

RIB CAGE MOVEMENT DURING HALOTHANE ANAESTHESIA IN MAN

Chest wall movement, partitioned into rib cage and abdomen/diaphragmcontributions, was measured using four mercury-in-rubber straingauges and an analog computer. The relative volume contributionof the rib cage and the abdomen/diaphragm to tidal volume wasmeasured in 13 subjects before and during anaesthesia with thiopentoneand halothane. In awake subjects, movement of the abdomen/diaphragmcontributed more than 70% of the tidal volume, the smaller ribcage contribution ranged from 5 to 30%. Manual ventilation duringinduction of anaesthesia showed that the rib cage was less compliantthan the abdomen/diaphragm, but when suxameth-onium was giventhere was a disproportionate increase in rib cage compliance.In nine out of 12 subjects, halothane anaesthesia resulted ina large decrease in the fractional contribution of the rib cage.In two of these subjects there was paradoxical breathing, therib cage and the abdomen/ diaphragm movement being 180°out of phase. This effect was produced easily in three othersubjects by inserting a resistance (1 kPa litre^–1 s) intothe anaesthetic circuit. The technique also produced informationabout changes in volume of the trunk induced by anaesthesia.Eleven subjects showed an increase in end-expiratory abdominalvolume (mean increase 120 ml) during halothane anaesthesia whilethere was a mean reduction in end-expiratory rib cage volumeof 29 ml. We concluded that halothane depressed both phasicand tonic postural reflex activity, which affected predominantlythe rib cage musculature. This reduced the amplitude of phasicrib cage movement, impaired stability of the rib cage and predisposedto paradoxical ventilation. The results also suggested thatthe reduction in lung volume during anaesthesia may result froma loss of postural control of the chest wall and a central shiftof blood volume. ^*Present address: R.A.F. Institute of Aviation Medicine, Farnborough,Hants     

CEREBRAL BLOOD FLOW AND METABOLISM DURING ETOMIDATE ANAESTHESIA IN MAN

The effects of etomidate on regional cerebral blood flow (rc.b.f.)and cerebral metabolic rate for oxygen (CMRo₂) were studiedin seven patients undergoing diagnostic carotid angiography.Following determination of baseline rc.b.f. while awake, thepatients were anaesthetized with a single dose of etomidate15 mg. Thereafter an infusion of etomidate (2 or 3 mg min–¹)was administered. Etomidate decreased both rc.b.f.₁₀ (mean decrease34%) and CMRo₂ (mean decrease 45%). It was concluded that etomidateis a potent cerebral metabolic depressant. Furthermore, thecerebrovascular reactivity to carbon dioxide was maintainedunder etomidate anaesthesia.     

THE INFLUENCE ON RENAL FUNCTION OF CHLOROFORM AND HALOTHANE ANAESTHESIA IN MAN

Sixty healthy adult patients undergoing uncomplicated surgeryof intermediate duration were randomly allocated to anaesthesiawith chloroform or halothane. For 48 hours postoperatively renalfunction was measured using the renal excretory index of Lindsayand others (1965). A significant difference between chloroformand halothane patients was found in the first 24 hours. ^* Present address: Department of Anaesthesia, The Universityof Leeds.     

EFFECT OF PROPRANOLOL ON ARTERIAL HYPOTENSION INDUCED BY HALOTHANE IN THE DOG UNDER NITROUS OXIDE ANAESTHESIA

The effect of propranolol hydrochloride on arterial hypotensionproduced by halothane has been investigated in atropinized dogsduring nitrous oxide-oxygen anaesthesia. Propranolol alone produceda slight transient fall in blood pressure, but greatly enhancedthe hypotensive action of halothane. Following the applicationof electric shock to the heart to terminate adrenaline-inducedventricular fibrillation during halothane-nitrous oxide anaesthesia,propranolol produced a profound fall in arterial pressure. Ashock-like state associated with marked bradycardia resulted.Therapy with adrenaline and mephentermine produced slow recovery,and the pressor response was not associated with any increasein heart rate. The outcome of pressor therapy was related tothe number of electric shocks applied to the heart. Two dogsin which electric shock was applied thrice failed to recoverin spite of vigorous pressor therapy. It is suggested that cautionshould be exercised when injecting propranolol during halothaneanaesthesia in humans. The use of this drug following the applicationof electric shock to the heart to terminate ventricular fibrillationmay be hazardous and should be avoided.     

CEREBRAL BLOOD FLOW DURING HALOTHANE ANAESTHESIA

Cerebral blood flow has been measured in dogs using the methodof Lassen and Ingvar (1961), and Ingvar and Lassen (1962), whichinvolves measurement of the rate of clearance of krypton 85from an area of exposed cerebral cortex after injection intothe internal carotid artery. In every measurement during halothaneanaesthesia there was a considerable reduction in cerebral bloodflow compared with the flows obtained with nitrous oxide andoxygen. The average reduction in flow was 46 per cent and thiswas accompanied by an average increase in cerebrovascular resistanceof 50 per cent. Measurements were also made of the cerebraloxygen uptake (CMRO2) and halothane produced an average decreasein uptake of 49 per cent. Possible mechanisms for the observedresults are discussed.     

EFFECT OF TRIMETAPHAN ON HAEMODYNAMICS AND OXYGEN CONSUMPTION DURING HALOTHANE ANAESTHESIA IN MAN

Haemodynamic and metabolic observations have been carried outbefore, during, and after the administration of trimetaphanin six unpremedicated, paralyzed, hyperventilated patients duringvaricose vein operations and halothane anaesthesia. With trimetaphan,arterial pressure and stroke volume fell, cardiac output changedlittle, and oxygen uptake fell slightly. In the majority ofcases, an increased pulse rate compensated for the reduced strokevolume. Myocardial contractility or distensibility, or both,were apparently altered since right atrial pressure was unchanged.Both calculated (mixed venous) and observed (right atrial) centralvenous oxygen saturations were fairly normal with little changeduring the trimetaphan infusion. The theoretical and clinicalimplications of these and comparable observations during anaesthesiawith ether are discussed. ^*This investigation was supported in part by Research GrantH-4881 from the National Institutes of Health, Public HealthService.     

EFFECT OF PROPRANOLOL ON THE VENTRICULAR ARRHYTHMIAS INDUCED BY HYPERCARBIA DURING HALOTHANE ANAESTHESIA IN MAN

The effects of propranolol on arterial blood pressure, heartrate, and cardiac rhythm during ventricular arrhythmias initiatedby hypercarbia were investigated in thirteen subjects during1 per cent halothane anaesthesia. Propranolol was consistentlyeffective in the treatment of ventricular arrhythmia inducedby hypercarbia in all subjects. The successful use of propranololsuggests that the mechanism for ventricular arrhythmia producedby respiratory acidosis during halothane anaesthesia was relatedto beta adrenergic receptors. Blockade of these receptors bybeta adrenergic agents decreased markedly the sensitizationof myocardium to sympathetic stimulation.     

EFFECTS OF HYPOTENSION INDUCED BY HALOTHANE, ON THE CEREBRAL CIRCULATION IN BABOONS WITH EXPERIMENTAL RENOVASCULAR HYPERTENSION

The effect of graded, progressive hypotension on the autoregulationof cerebral blood flow was studied in anaesthetized baboonswith experimental renovascular hypertension. Graded hypotensionwas induced over a period of 5–6 h by the administrationof increasing concentrations of halothane. In these chronicallyhypertensive animals cerebral blood flow remained constant untilthe mean arterial pressure had decreased to approximately 90mm Hg. At mean arterial pressures of less than this value cerebralblood flow was pressure passive. At the completion of the investigationthe brains were fixed by perfusion and submitted to neuropathologicalexamination. Evidence of chronic hypertension and of ischaemicbrain damage was found in every animal. ^* Present address: Cardiac Department, The Radcliffe Infirmary,Oxford.     

CARDIOVASCULAR EFFECTS OF BETA-RECEPTOR BLOCKING DRUGS DURING HALOTHANE ANAESTHESIA IN MAN

Fifteen patients anaesthetized with halothane were given a beta-adrenergic receptor blocking substance intravenously, either propranolol or l-alprenolol.
The drugs usually induced an insignificant drop in blood pressure, a slight bradycardia, and a small reduction in cardiac output in patients not subjected to concomitant surgery. In one patient, the reaction was more pronounced. The immediate administration of atropine seemed to restore the circulatory state.
Nine patients were subjected to surgery during the administration of the beta-blocking agents. Pronounced hypotension resulted in seven of them. This effect was observed both after propranolol and l-alprenolol. Again, atropine reversed the hypotension.
These observations suggest that the administration of beta-adrenergic receptor blocking agents during anaesthesia should be limited by very strict indications, and be used under carefully controlled conditions.

ZUSAMMENFASSUNG

15 mit Halothan narkotisierte Patienten erhielten i.v. einen Beta-Rezep-torenblocker, und zwar entweder Propanolol oder 1-Alprenolol.
Diese Mittel fiihrten in der Regel zu einem nicht-signifikanten Blutdruck-abfall, zu einer geringgradigen Bradykardie und einer leichten Verminderung des Herzminutenvolumens bei Patienten, die nicht gleichzeitig operiert wurden. Bei einem Patienten war die Reaktion dramatischer. Die sofortige Gabe von Atropin schien den Kreislaufzustand wieder zu normalisieren.
Neun Patienten erhielten Betablocker wahrend einer Operation. Bei sieben von ihnen kam es zu ausgepragten Blutdruckabfall. Diese Wirkung wurde sowohl nach Propranolol als auch nach 1-Alprenolol beobachtet.
Diese Beobachtungen geben Grund zur Empfehlung, Betarezeptoren-blocker wahrend der Narkose nur bei strengster Indikation zu verabreichen und sie nur unter sorgfaltig kontrollierten Bedingungen anzuwenden.     

HALOTHANE ANAESTHESIA IN TURKEYS

An anaesthetic technique employing halothane in oxygen for usein adult turkeys is described. The mixture was administeredusing a Magill attachment and a Hall cat mask. Induction wasrapid and excitement-free. Anaesthesia was maintained for varyingperiods of time up to a maximum of 80 minutes. Recovery wasrapid. In a total of twenty-five turkeys no deaths occurredwhich were attributable to the anaesthetic.     

E.E.G. ACTIVITY DURING HALOTHANE ANAESTHESIA IN MAN

The effects of i.v. administration of suxamethonium and noxiousstimulation induced by skin incision on the e.e.g. were studiedduring halothane anaesthesia in man. These stimuli induced activationof the e.e.g. which was represented by either low-voltage fastwaves or high-voltage slow waves. The low-voltage fast waveresponse was observed in adult patients while the high-voltageslow wave response was the predominant response in infants andchildren aged less than 8 yr. Suxamethonium induced the high-voltageslow wave response in 77% of cases; skin incision in 88%. Thee.e.g. of four infants aged less than 60 days did not show activationwith either stimulus. Both types of e.e.g. activation were associatedwith an increase in heart rate, increase in arterial pressureand pupillary dilatation. The possible mechanisms involved inthe production of activation of e.e.g. by i.v. administrationof suxamethonium are discussed.     

EFFECT OF HALOTHANE ANAESTHESIA ON SURVIVAL OF DOGS SUBJECTED TO CONTROLLED POSTHAEMORRHAGIC HYPOTENSION FOLLOWED BY RETRANSFUSION

The results of our previous investigations (Vajs, Reberniacand Pantelic, 1965) suggest that halothane anaesthesia may adverselyaffect the survival of severely bled dogs. In order to examinefurther this effect of halothane fifteen dogs were subjectedto controlled posthaemorrhagic hypotension at a level of 40mm Hg for 2 hours and then retransfused. Halothane anaesthesiastarted at the 15th minute after initial haemorrhage and wasdiscontinued at the 15th minute after the end of retransfusion.Only four dogs died. In the control group of experiments withoutanaesthesia, six out of fifteen dogs died. It is concluded thathalothane anaesthesia probably does not influence the survivalof dogs subjected to controlled posthaemorrhagic hypotensionfollowed by retransfusion.     

RELATIONSHIP BETWEEN LOWER OESOPHAGEAL CONTRACTILITY, CLINICAL SIGNS AND HALOTHANE CONCENTRATION DURING GENERAL ANAESTHESIA AND SURGERY IN MAN

The effects of a range of concentrations of halothane upon loweroesophageal contractility (LOC) and on defined clinical signshas been studied in patients undergoing surgery. Changes inclinical signs were assigned a numerical value by means of ascoring system. One hundred and eighty-one sets of measurementswere made in 46 patients exposed to concentrations of halothanebetween 2.0 and 0.5 minimum alveolar concentration (MAC). Theresults were examined to identify relationships between (i)the clinical signs and alveolar halothane concentration, (ii)the clinical signs and LOC and (iii) the changes in LOC andalveolar concentration; significant correlations were foundbetween these variables. Decreasing alveolar halothane concentrationwas associated with an increase in LOC and these increases inLOC were also associated with increases in the clinical score.     

CEREBRAL RESPONSES TO THE ADDITION OF NITROUS OXIDE TO HALOTHANE IN MAN

Cerebral responses to the substitution of 60% nitrous oxidefor nitrogen during halothane anaesthesia (0.84%, end-tidal)were studied in four patients during surgery. The mean (±SEM)cerebral blood flow equivalent and internal jugular venous oxygentension during halothane anaesthesia, 27±3 ml blood/mloxygen and 41±2 mm Hg respectively, increased significantlyto 45±3ml blood/ml oxygen and 54±3 mm Hg followingthe introduction of nitrous oxide. On the withdrawal of nitrousoxide, the mean cerebral blood flow equivalent and internaljugular venous oxygen tension returned gradually to the controlvalues. Cerebral perfusion pressure and blood-gas values, otherthan the internal jugular venous oxygen tension, did not changesignificantly. Marked slowing of the e.e.g. was observed followingthe addition of nitrous oxide to halothane. Upon the withdrawalof nitrous oxide the e.e.g. returned to the control pattern.These results indicate that cerebral blood flow was in excessof oxygen demand during nitrous oxide/halothane anaesthesiain man. This work was performed at the Department of Anaesthesiology,Yamaguchi University Hospital.     

EFFECTS OF GENERAL ANAESTHESIA WITH HALOTHANE ON ANTRODUODENAL MOTILITY, pH AND GASTRIC EMPTYING RATE IN MAN

Antroduodenal motility, pH and gastric emptying rate were measuredin 11 patients undergoing orthopaedic or plastic surgery withgeneral anaesthesia. Motility was measured by manometry andgastric emptying rate by the rate of paracetamol absorption.During anaesthesia, gastric emptying was delayed in eight patients.General anaesthesia with halothane reduced the duration of theinterdigestive motility complex (P < 0.01), mainly by a shorteningof phase II (P < 0.01) which correlated with the inhaledconcentrations of halothane (P < 0.01). Anaesthesia impededthe occurrence of antral contractions during phase II (P <0.01); the frequency of contractions was unchanged during anaesthesia,but decreased during the recovery period (P < 0.01). Theamplitudes of antral contractions diminished with anaesthesia(P < 0.01), but increased after operation. The frequencyof contractions in the duodenum was unchanged during phase IIand reduced during phase III (P < 0.01). Gastric pH increasedduring and after operation (P < 0.01). General anaesthesiawith halothane affects gastroduodenal motility especially duringphase II, increases gastric pH and delays gastric emptying rate. ^*Address for correspondence: Rosenvangsalle 30, DK-8260 VibyJ, Denmark.     

ISOFLURANE AND HALOTHANE FOR OUTPATIENT DENTAL ANAESTHESIA IN CHILDREN

A trial was undertaken in children to compare the use of halothaneand isoflurance in outpatient dental anaesthesia. A wholly inhalationtechnique was chosen and nitrous oxide in oxygen was deliveredfrom a Boyle‘s machine via a coaxial (Bain) breathingsystem and was supplemented with either halothane or isoflurane.Isoflurance produced significantly fewer arrhythmias than halothanebut the induction of anaesthesia took longer and proved moredifficult.     

BRADYCARDIA AND HYPOTENSION DURING CYCLOPROPANE ANAESTHESIA CAUSED BY HYOSCINE AS PREMEDICATION

In a series of 613 patients, most of whom were undergoing abdominaloperations under anaesthesia with cyclopropane and tubocurarine,the incidence of fall in pulse rate and arterial pressure was38 per cent following morphine-hyoscine premedication, 20 percent with morphine as premedication and 10 per cent when morphine-hyoscinewas supplemented with atropine 0.6 mg intravenously. Electrocardiographictracings revealed a high incidence of arrhythmia, includingtwo instances of multifocal ventricular extrasystoles, whenatropine was administered during cyclopropane anaesthesia. Itis concluded that hyoscine is the cause of these changes dueto its central vagal stimulating effect. Atropine injectionduring cyclopropane anaesthesia appears to lead to a high incidenceof arrhythmia, with a risk of ventricular fibrillation and shouldbe avoided. It is advised that atropine be given intravenously(0.6 mg in adults) before induction of anaesthesia with cyclopropanewhen hyoscine has been used for premedication.