DEPRESSION OF HYPOXIC VENTILATORY RESPONSE BY HALOTHANE, ENFLURANE AND ISOFLURANE IN DOGS

The ventilatory responses to isocapnic hypoxia and hypercapniawere studied in six dogs each with a tracheostomy, awake andduring anaesthesia with halothane, enflurane and isoflurane(1–2.5 MAC). Isocapnic hypoxic ventilatory response (HVR)was expressed as the parameter A, such that the greater thevalue of A, the greater the hypoxic response. In the anaesthetizeddogs HVR (A) was reduced significantly from the awake valueof 2010±172 (mean+SEM) to 630±173 by 1 MAC halothane,495± 105 by 1 MAC enflurane and 952±157 by 1 MACisoflurane (P<0.05). All three anaesthetic agents producedsignificant depression of HVR at 1 MAC, but enflurane was moredepressant than isoflurane. At 1.5 MAC all three anaestheticsproduced equal and significant depression of HVR at equianalgesicconcentrations. Further increases in anaesthetic concentrationcaused no increase in depression. Hypercapnic drive, as measuredby the slope of the VE/PA_co2 response curve, was reduced significantlyfrom 9.75 litre min^–1 kPa^–1 ± 2.4 in awakedogs to 0.83 ± 0.56 after 1 MAC halothane, 0.68 ±0.53after 1 MAC enflurane and 1.58 ±0.75 after 1 MAC isoflurane.In addition, hypercapnia-induced augmentation of the hypoxicdrive was abolished by 1 MAC halothane or enflurane and diminishedmarkedly by 1 MAC isoflurane. It may be clinically significantthat hypoxia and hypercapnia during anaesthesia with these agentsdid not produce optimal stimulation of ventilation.     

POTENTIATION OF THE NEUROMUSCULAR BLOCKADE PRODUCED BY ALCURONIUM WITH HALOTHANE, ENFLURANE AND ISOFLURANE

The potentiation of alcuronium by halothane, enflurane and isofluranewas investigated using electromyography. In the first study,cumulative dose-response curves were constructed in four groupsof 10 patients anaesthetized with one of the inhalation agentsand nitrous oxide, or with fentanyl and droperidol (control).All three agents reduced the ED₅₀ of alcuronium; the effectwas marked with isoflurane (P < 0.005) but less so with halothane(P < 0.05) and enflurane (ns). In the second part of theinvestigation, designed primarily to test the duration of actionof alcuronium with each agent, a single bolus dose of alcuronium0.2 mg kg^–1 was given to four similar groups (n = 5).The duration of action was significantly prolonged by enflurane(P < 0.01) and isoflurane (P < 0.05), but not by halothane.The possible reasons for this are discussed.     

EFFECTS OF HALOTHANE, ISOFLURANE AND ENFLURANE ON VENTILATION IN CHILDREN

The ventilatory effects of halothane in eight children werecompared with those of isoflurane in eight children and enfluranein six children. All studies were completed before surgery commenced,and the children received no preopera-tive medication. The depressionof ventilation produced by the three agents increased in a dose-relatedfashion as the alveolar concentrations were increased, and thedepression of ventilation that they produced in oxygen was greaterthan that produced by equipotent concentrations in nitrous oxide.While the increase in ventilatory frequency and the decreasein T_E associated with increasing concentrations of halothanewere statistically significant (P < 0.05), the increase infrequency associated with isoflurane was not, although it wassufficient to maintain the end-tidal and arterial-ized venousPco, in the isoflurane group at a value which did not differsignificantly from that in the halothane group. Profound depressionof ventilation was produced in the children by enflurane, clearlybecause no increase in ventilatory frequency was associatedwith its use. It was evident that the ventilatory effects ofthe three volatile agents in unstimulated children are verysimilar to those described elsewhere in the adult. There wasno difference of any clinical significance between the degreeof depression of ventilation produced by halothane and isofluranein children.     

EFFECTS OF HALOTHANE, ENFLURANE AND ISOFLURANE ANAESTHESIA ON RENAL PLASMA FLOW

Effective renal plasma flow (ERPF) and linear cardiac output(aortic blood velocity) were measured in 15 patients who receivedhalothane, enflurane or isoflurane in oxygen. All three agentscaused a significant reduction in ERPF (P < 0.05) and theeffect was greater at 1.25 MAC than at 0.75 MAC. No significantdifference was demonstrated between the agents. Linear cardiacoutput did not change significantly during the study, suggestingthat the observed reduction in ERPF was not caused by cardiovasculardepression.     

EFFECT OF HALOTHANE, ENFLURANE AND ISOFLURANE ON BODY TEMPERATURE DURING AND AFTER SURGERY

The superficial and deep body temperatures of 40 healthy femalesundergoing total abdominal hysterectomy were measured duringsurgery and for 4 h afterwards. The patients were allocatedrandomly to one of five groups and anaesthetized to producean end-tidal concentration of 1% halothane, 1% enflurane, 2%enflurane, 1% isoflurane or 2% isoflurane. The patients receivedalso 70% nitrous oxide in oxygen and neuromuscular blockade.The theatre temperature was maintained at 22.0°C. Therewere significant body temperature changes during operation inall groups. The mean (SD) decrease in core temperature over85 min was approximately 1.1 (0.3) °C in the 1% halothane,2% enflurane and 2% isoflurane groups, and 0.6 (0.4) °Cin the 1% enflurane and 1% isoflurane groups (P<0.05). Duringthe recovery period the 1% halothane, 2% enflurane and 2% isofluranegroups took 2 h to rewarm to preoperative temperatures, andthe rate of rewarming during this time was similar for all groups.     

EFFECT OF HALOTHANE, ENFLURANE AND ISOFLURANE ON BRONCHOMOTOR TONE IN ANAESTHETIZED PONIES

The effects of halothane, enflurane and isoflurane on bronchialcalibre were investigated in five anaesthetized ponies usinga computer-aided forced airflow oscillation technique to derivespecific lower airways conductance (s.G_law) and expiratory reservevolume (ERV). All the agents tended to increase s.G_law (indicatingbronchodilatation), but ERV was reduced by halothane and enflurane,and increased by isoflurane. It was concluded that the effectsof these agents on bronchomotor tone were similar to those whichoccur in man. However, the reasons for the differences in theireffects on ERV compared with those found in man remain to bedetermined.     

EFFECTS OF CHRONIC INHALATION OF HALOTHANE, ENFLURANE OR ISOFLURANE IN RATS

Male Fischer 344 rats were exposed to halothane, enflurane orisoflurane vapour 20 p.p.m., or air, for up to 30 weeks. Noneof the anaesthetic agents led to hepatocellular necrosis. Exposureto halothane resulted in slight increases in serum alanine aminotransferaseactivity, an increase in the size of the liver, an increasein hepatic microsomal cytochrome P-450 content and a minimalamount of fatty change in the liver. None of these effects wereobserved during exposure to enflurane or isoflurane. Urinaryfluoride excretion was increased during exposure to either enfluraneor isoflurane. Using this increase as an index of anaestheticbiotransformation, we found that the extent of bsiotransformationof isoflurane was only slightly lower than that of enflurane. ^*Histopathology, Flinders Medical Centre, Bedford Park, SouthAustralia 5042     

MORBIDITY IN MINOR GYNAECOLOGICAL SURGERY: A COMPARISON OF HALOTHANE, ENFLURANE AND ISOFLURANE

A comparison was made between halothane, enflurane and isofluranewith regard to their suitability for minor gynaecological proceduresin patients who would be leaving the hospital within 24 h ofthe anaesthetic. Seventy-five healthy patients were randomlyallotted to one of three groups which received one of theteanaesthetics. In respect of patient acceptance and postoperativemorbidity there were no significant differences between halothaneand enflurane, but after isoflurane there was a significantlygreater frequency of minor sequelae (headache, nausea, dizzinessand coughing) and its pungent odour made it unacceptable tosome patients.     

BIODEGRADATION OF HALOTHANE, ENFLURANE AND METHOXYFLURANE

The biodegradation of halothane, enflurane and methoxyfluranewas studied in 22 patients undergoing abdoninal surgery, bymeasuring the uptake and elimination of each agent and the fluorideexcretion in urine. Six control patients were anaesthetizedwith nitrous oxide in oxygen together with neuromuscular blockingdrugs, five patients with nitrous oxide in oxygen and 0.93%halothane, five with nitrous oxide in oxygen and 1.30% enflurane,and six with nitrous oxide in oxygen and 0.31% methoxyflurane.The ratio of the fluoride excretion in urine to the total amountof fluoride contained in the amount of each anaesthetic agentabsorbed during anaesthesia was estimated to be 17.7% for halothane,2.3% for enflurane and 46.3% for methoxyflurane. The serum fluorideconcentration increased to a maximum of 15.8±3.8 µmollitre^–1 (mean±SD) at 6 h after anaesthesia withmethoxyflurane, while it did not exceed 8 µmol litre^–1with the other anaesthetic agents.     

EFFECT OF HALOTHANE, ENFLURANE AND ISOFLURANE ON CAROTID BODY CHEMORECEPTOR ACTIVITY IN THE RABBIT AND THE CAT

The response of the carotid body chemoreceptors to administrationof halothane, enflurane and isoflurane was tested in the rabbitand cat. In the steady-state all three volatile anaesthetics,in doses up to 1%, were mildly chemodepressant. The oxygen responsecurves were shifted down-wards, but hypoxic stimuli below 5.3kPa over-came this chemodepression. Two-point carbon dioxideresponse curves were also shifted downwards, but with no changein slope. Possible mechanisms involved in the chemoreceptorresponse to transient and steady-state anaesthetic administrationare discussed.     

TRANSCRANIAL DOPPLER SONOGRAPHY: EFFECTS OF HALOTHANE, ENFLURANE AND ISOFLURANE ON BLOOD FLOW VELOCITY IN THE MIDDLE CEREBRAL ARTERY

Systolic, diastolic, and mean blood flow velocity in the middlecerebral artery (Vs,mca; Vd,mca; Wm,mca) and pulsatility (Vs- Vd)/Vm of the waveform obtained were recorded in 51 patientsbefore, during and after general anaesthesia. Transcranial Doppler(TCD) sonographic variables were measured in the awake patientand after induction of anaesthesia with thiopentone 5–6mg kg^–1. After tracheal intubation, 17 patients received0.8% halothane and 66% nitrous oxide in oxygen for 30 min (15minnormoventilation; 15min hyper-ventilation). The inspired halothaneconcentration was then increased to 1.6% for 45min (15min normoventilation;15 min hyperventilation; 15 min normoventilation with nitrousoxide replaced by oxygen). Enflurane (1.7% for 30 min and 3.4%for 45 min) was given to another 17 patients; 17 other patientsreceived isoflurane (1.2% and 2.4%). Mean arterial pressure(MAP), nasopharyngeal temperature, end-tidal carbon dioxideconcentration, inspired and end-tidal anaesthetic agent concentrations,haemoglobin concentration, PVC and TCD variables were measuredat the end of each 15 min period. After recovery from anaesthesia,TCD variables were measured again. There were no intergroupdifferences in changes in MAP, nasopharyngeal temperature, haemoglobinconcentration and PCV. Halothane, enflurane and isoflurane atlow doses and normoventilation had little influence on TCD variablescompared with awake values. In large concentrations with nitrousoxide in oxygen and normoventilation, there were differencesbetween the volatile agents. Halothane increased blood flowvelocities, but enflurane and isoflurane caused little change.Hyperventilation always decreased blood flow velocities andincreased pulsatility. Six of 17 patients undergoing hyperventilationwith 2.4% isoflurane and nitrous oxide in oxygen showed zerodiastolic flow. This phenomenon was not observed in any patientreceiving halothane or enflurane. With high doses of the volatileagents and normoventilation, blood flow velocities decreasedin all groups after discontinuation of nitrous oxide. Our TCDresults are compatible with the known effects of halothane,enflurane and isoflurane on cerebral blood flow (CBF). However,the relative changes in blood flow velocity and CBF may notbe proportional with large doses of volatile agents, as a constantdiameter of basal cerebral arteries may not be assumed underthese conditions.     

COMPARISON OF RESPIRATORY CHARACTERISTICS DURING ENFLURANE AND HALOTHANE ANAESTHESIA

The effects of enflurane on certain respiratory characteristicswere compared with those of halothane in 70 patients duringanaesthesia with spontaneous breathing using a specially designedcircuit. The rate of respiration with enflurane (mean 22 b.p.m.)was slower than with halothane (mean 31 b.p.m.; P<0.001)and the tidal volume greater (enflurane mean 240ml, halothane180ml; P<0.05). There was no statistically significant differencein the minute volume of ventilation or end-tidal carbon dioxideconcentration between the two agents. The effects of a narcoticpremedication were observed in 16 patients in the study. Themain effect was to produce slowing of respiratory rate (enfluranemean 16 b.p.m.; halothane 18 b.p.m.). The value of the respiratorypattern compared with the measurement of heart rate and arterialpressure as a clinical guide during anaesthesia is discussed.     

DISPLACEMENT OF SOME BASIC DRUGS FROM HUMAN SERUM PROTEINS BY ENFLURANE, HALOTHANE AND THEIR MAJOR METABOLITES

The influence of volatile anaesthetics (halothane, enflurane)on the serum protein binding of three highly bound basic drugshas been studied in vitro by equilibrium dialysis. Radioactivelabelled isotopes were used for the determination of drug concentrations.Enflurane, halothane and the halothane metabolite trifluoroaceticacid (TFA) inhibited the binding of diazepam to serum and toits main binding protein, albumin. The binding of diazepam toalbumin was inhibited in a competitive manner and was not relatedto the anaesthetic potency of the vapours. Thus the observeddisplacement of diazepam should be regarded as a side-effectof the volatile anaesthetics. The binding of propranolol andprazosin in serum was not significantly influenced by the investigatedanaesthetics. At clinically relevant concentrations of the anaesthetics,diazepam was displaced significantly only by enflurane withan increase in free fraction of 60% in serum. TFA in concentrationsseen after operation significantly increased te free fractionof diazepam up to 90%. We conclude that enflurane anaesthesiamay temporarily potentiate the pharmacological effect of diazepamand that, in the postoperuative period following halothane anaesthesia,a more rapid elimination of diazepam could be expected.     

COMPARISON OF ISOFLURANE AND HALOTHANE IN OUTPATIENT PAEDIATRIC DENTAL ANAESTHESIA

Isoflurane was compared with halothane as the sole supplementto anaesthesia with nitrous oxide and oxygen for outpatientdental extractions in 80 children. Induction and maintenanceof anaesthesia were satisfactory with both agents, althoughthere was a higher incidence of coughing, salivation and laryngospasmin the group receiving isoflurane. However, in contrast to predictionsfrom the physical properties of isoflurane and halothane, immediaterecovery was significantly slower in patients who had receivedisoflurane. Recovery was complicated by coughing in a significantnumber of patients in the isoflurane group. The incidence ofreported complications during later recovery was similar withboth agents, apart from the complaint of non-specific postoperativeaches in a significant number of patients to whom isofluranewas administered.     

COMPARISON OF HALOTHANE AND ENFLURANE ANAESTHESIA FOR OTOLARYNGOLOGICAL SURGERY IN CHILDREN

Halothane and enflurane were compared in 132 children undergoingadenoidectomy with or without tonsillectomy. Anaesthesia foradenoidectomy was induced with thiopentone or Althesin and fortonsillectomy with thiopentone. The response to surgery wasminimal (0–5%) during both inhalation anaesthetics. Duringimmediate recovery, respiratory depression was more profoundafter enflurane than after halothane. Both the i.v. and theinhalation anaesthetics had an influence on recovery. The totalrecovery scores (0–10) based on activity, respiration,heart rate, consciousness and colour improved most rapidly afterAlthesin + enflurane and most slowly after thiopentone + halothanein the adenoidectomy groups. In the tonsillectomy groups, therecovery scores were better after enflurane than after halothane.After both inhalation anaesthetics, the frequency of shiveringranged from 0 to 17%.     

ELECTROENCEPHALOGRAPHIC AND BEHAVIOURAL EFFECTS OF ENFLURANE AND HALOTHANE ANAESTHESIA IN THE CAT

The effects of enflurane and halothane on the electroencephalogram(e.e.g ) were studied in 10 cats. Animals underwent at least2 MAC-hours of anaesthesia with either agent, and the e.e.g.was monitored continuously Arterial blood-gas tensions weremaintain within normal limits. In addition, e.e.g. and behaviourwere monitored during the period following anaesthesia, at fixedintervals, for 4 weeks. Despite the production of the centralstimulatory effects of enflurane during anaesthesia, no animaldemonstrated any central nervous system sequelae on any occasionfollowing the anaesthetic.     

INTRA-OCULAR PRESSURE CHANGES DURING HALOTHANE AND ENFLURANE ANAESTHESIA

We have measured intra-ocular pressure (i.o.p.) in 20 patientsanaesthetized with halothane or enflurane (0.6 MAC in oxygen)for repair of trauma to the eye. The changes in i.o.p. withhalothane 0.5% were unpredictable, whereas enflurane 1% reducedintra-ocular tension consistently in all the patients studied.Enflurane is recommended as a possible alternative anaestheticfor surgery on the open eye.     

PLASMA GLUTATHIONE S-TRANSFERASE CONCENTRATION AS A MEASURE OF HEPATOCELLULAR INTEGRITY FOLLOWING A SINGLE GENERAL ANAESTHETIC WITH HALOTHANE, ENFLURANE OR ISOFLURANE

The plasma concentration of hepatic glutathione S-transferase(GST) was measured in matched groups of patients who receivedhalothane, enflurane or isoflurane anaesthesia for electiveminor surgery. The GST concentrations increased significantlyat 3 h after anaesthesia in patients who received halothaneor enflurane, but not in patients who were given isoflurane.A secondary increase in GST concentration, at 24 h, was seenin a small number of individuals who received halothane or enflurane.Abnormal GST concentrations were found in 50% of patients followinghalothane anaesthesia, 20% following enflurane and 11% afterisoflurane. The small but significant increases in GST concentrationsin patients receiving halthane or enflurane suggests an impairmentof hepatocellular integrity following the administration ofthese anaesthetics. In contrast, isoflurane anaesthesia didnot apear to be associated with this effect.     

CARDIOVASCULAR EFFECTS OF ISOFLURANE AND HALOTHANE IN YOUNG AND ELDERLY ADULT PATIENTS

We have studied the cardiovascular effects of 1 MAC end-tidalconcentrations of halothane and isoflurane in young (n = 40)and elderly (n = 40) adult patients using non-invasive techniques.Cardiac output was measured by Doppler ultrasonography. Halothanereduced heart rate, systolic, mean and diastolic arterial pressuresand cardiac index in both age groups (P < 0.05). lsofluranereduced systolic, mean and diastolic arterial pressures also,but reduced cardiac index and heart rate only in the older patients(P < 0.05). Halothane depressed cardiovascular state significantlymore than isoflurane in the younger adults (P < 0.05), butcardiovascular depression was similar for the two agents inthe older age group. The decreases in systolic and diastolicpressures in the older patients were significantly greater withisoflurane compared with halothane (P < 0.05). (Br. J. Anaesth.1993; 71: 696–701)     

ARTERIAL WASHIN OF HALOTHANE AND ISOFLURANE IN YOUNG AND ELDERLY ADULT PATIENTS

We have studied the effect of age on washin of isoflurane andhalothane by comparing end - tidal (PE') and arterial (Pa) partialpressures of the agents in young (18–32 yr) and elderly(63–82 yr) healthy patients for 20 min after introductionof the agents, before surgery. PE' was measured by infra - redanalysis and Pa by gas chromatography. Washin of isofluraneoccurred at the same rate in the young and elderly, with nosignificant difference between young and elderly in PE' or Paas proportions of the inspired partial pressure (PI). After20 min of isoflurane administration, mean Pa/Pl in the youngwas 0.57 (95% confidence limit (CL) 0.53–0.62) and 0.55in the elderly (95% CL 0.51–0.59). Washin of halothanewas slower in the elderly than in the young, with Pa/Pl significantlyless in the elderly from 10 min after introduction of halothane.The difference between age groups, however, was small: meanPa/Pl after 20 min of halothane administration 0.45 (95% CL0.41–0.49) in the young and 0.38 (95% CL 0.35–0.41)in the elderly. Washin of isoflurane was significantly fasterthan that of halothane in both young and elderly subjects. Forisoflurane, the PE'-Pa gradient was small relative to Pa anddid not differ significantly between young and elderly. Forhalothane, PE'-Pa in the young did not differ significantlyfrom that for isoflurane. In the elderly, PE'-Pa for halothanewas significantly greater than in the young and than PE'-Pafor isoflurane.