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PubMed1979

A prospective study of liver enzyme and other changes following repeat administration of halothane and enflurane.

A prospective study of liver enzymes and other measurements following repeat administrations of halothane or enflurane was carried out in patients undergoing minor urological operations. The patient populations were similar with respect to frequency of factors which might influence liver function, social habits, drug therapy and time intervals between administrations. Sixty-three received two or more administrations of halothane and 66 received two or more administrations of enflurane, both drugs given with nitrous oxide in oxygen. There was a greater frequency of increased enzymatic activity following repeat administrations of halothane than following enflurane and the average alanine aminotransferase and gamma glutamyl transpeptidase concentrations were increased to a greater degree following halothane than enflurane. There was no change in the eosinophil count and no significant postoperative morbidity. Change in alanine aminotransferase, lactate dehydrogenase and gamma glutamyl transpeptidase occured more frequently in obese patients receiving halothane.

Aged↗
PubMed1980

Changes in the respiratory pattern induced by halothane in the cat.

The effect of halothane on the respiratory pattern was investigated in lightly anaesthetized cats. Following the administration of 2.0% halothane there was a transient increase in respiratory frequency because of a decrease in the duration of expiration, followed by a progressive decrease in respiratory frequency as a result of prolongation of inspiration; both events could be demonstrated before and after vagotomy. During the steady state obtained following the administration of 0.5, 1.0 and 1.5% halothane and after vagotomy there was a decrease in the duration of expiration and a progressive increase in the duration of inspiration. Tidal phrenic output decreased progressively as the concentration of halothane was increased. These results suggest that changes in respiratory pattern seen during halothane anaesthesia might involve some excitatory central mechanisms other than the bulbopontine system.

Animals↗
PubMed1980

Halothane anaesthesia can block insulin stimulation of pyruvate dehydrogenase activity in mammary glands of 24-hour starved lactating rats.

The effect of halothane anaesthesia on the activity of the mitochondrial enzyme pyruvate dehydrogenase was studied in starved lactating rats. Extracts of freeze-clamped mammary gland and liver were assayed for pyruvate dehydrogenase activity. The fraction of the enzyme in the phosphorylated inactive form was increased greatly by starvation or by streptozotocin diabetes, and halothane anaesthesia did not disturb this effect. In starved animals not exposed to halothane, injection of insulin led to a rapid increase in the active fraction of the enzyme in mammary gland but not in liver. In animals under halothane anaesthesia this effect of insulin was largely abolished. The combination of starvation and halothane anaesthesia may impair mitochondrial accumulation of calcium which may be involved in the stimulation of pyruvate dehydrogenase by insulin.

Anesthesia, Inhalation↗
PubMed1980

Effect of low concentrations of halothane on the oxygen electrode.

The effect of low concentrations of halothane dissolved in saline (equivalent to 0.34% halothane) on the oxygen electrode was examined using a multi-wire Clark type electrode, consisting of eight platinum wires, each of 15 microns tip diameter. On the first exposure of the day to saline equilibrated with halothane in 10% oxygen or air, the output of the oxygen electrode increased by 40% over 56 min. On the second and subsequent exposures the increase in output was much less, but was still 10% greater than the correct values. After immersing the electrode overnight in saline without halothane the high sensitivity to halothane was present again next morning, even if neither membrane nor electrolyte was changed.

Blood Gas Analysis↗
PubMed1983

Drug metabolizing enzymes in the rat after inhalation of halothane and enflurane. Different pattern of response in liver, kidney and lung and possible implications for toxicity.

Male Sprague-Dawley rats were exposed in inhalation chambers to halothane and enflurane in concentrations from 50 to 1000 p.p.m. (0.0025 MAC-0.05 MAC) 6 h a day for 3-11 days. No signs of general toxicity were found. There was a normal increase in weight, and normal food consumption, organ to body weight ratios and normal histological findings in liver, kidney and lung. Exposure to 500 p.p.m. (0.05 MAC) of halothane induced the activity of NADPH-cytochrome-c-reductase in the liver, decreased the concentration of cytochrome P-450 in the kidney and decreased all the enzyme concentrations measured in lung microsomes. Exposure to halothane 50 p.p.m. (0.005 MAC) and enflurane produced only minor changes. It is concluded that the inhalation of halothane, in contrast to enflurane, may affect drug metabolism and thereby drug kinetics and toxicity. Halothane may increase its own toxicity by increasing the activity of NADPH-cytochrome-c-reductase in liver. An organ differentiation in enzymatic response was observed.

Animals↗
PubMed1983

Separate effects of halothane and carbon dioxide on respiratory duration in vagotomized cats.

The independent effects of halothane and carbon dioxide on central mechanisms regulating respiratory frequency were investigated in 12 vagotomized, artificially ventilated cats. Changes in respiratory pattern analysed from the phrenic neurogram revealed that increasing PaCO2 at a constant depth of halothane anaesthesia caused a progressive increase in TE with various changes in TI, whereas increasing the depth of halothane anaesthesia at a constant PaCO2 caused a progressive decrease in TE with various changes in TI. These results suggest that the effect of carbon dioxide on central mechanisms regulating respiratory duration is exactly the opposite of that produced by halothane and that respiratory frequency is modified by both the depth of halothane anaesthesia and PaCO2.

Animals↗
PubMed1984

Effect of nitrous oxide on halothane-induced hepatotoxicity in hypoxic, enzyme-induced rats.

The degree of hepatotoxicity induced by halothane in hypoxic (14% inspired oxygen), enzyme-induced (phenobarbitone treatment for 10 days), male Sprague-Dawley rats was assessed by histological examination and analysis of serum aspartate aminotransferase (Asp. AT) concentrations. There was a significant direct, linear relationship between dose of halothane and histology score (P = 2.96 X 10(-5), and Asp. AT concentration (P = 4.8 X 10(-5) ). The effect of administration of nitrous oxide before (70%) and during (86%) hypoxia was tested for in the presence and absence of 0.75% halothane. Nitrous oxide was found to produce no effect in the absence of halothane, but to potentiate the hepatotoxicity of 0.75% halothane (P = 0.0003 for Asp. AT and 0.0016 for histology scores). The possible mechanisms of this effect are discussed.

Animals↗
PubMed1985

Effect of halothane on spinal somatosensory evoked potentials in sheep.

The effects of increasing concentrations of halothane on the morphology of spinal somatosensory evoked potentials (SEP) were studied in seven anaesthetized sheep. Anaesthesia was induced with thiopentone and maintained with nitrous oxide in oxygen. Ventilation was controlled throughout. Arterial pressure, temperature and end-tidal carbon dioxide tension were monitored. A lumbar laminectomy was performed, the sciatic nerve exposed and a baseline spinal SEP was recorded from the surface of the lumbar spinal cord. Halothane was introduced in incremental steps of 1% up to 3% and further SEP were recorded. These recordings revealed that the spinal SEP peak latencies and general waveform configuration were stable under halothane anaesthesia. Baseline SEP amplitude was similar to that obtained with 1% halothane; however, at concentrations of 2% halothane or greater, there was a significant (P less than 0.005) attenuation of all components of the spinal SEP. These findings have important anaesthetic implications for patients undergoing spinal cord monitoring using SEP, although interspecies differences may occur.

Animals↗
PubMed1986

Effect of halothane and nitrous oxide anaesthesia on natural killer lymphocytes from patients with benign and malignant breast disease.

The effect of halothane and nitrous oxide on the capacity of natural killer (NK) lymphocytes from female patients with benign and malignant breast disease to kill the tumour cell line K562, was studied in vitro. There was no depression of activity of NK lymphocytes when exposed to 2% halothane and 66% nitrous oxide either alone or in combination. However, NK lymphocyte activity was depressed at higher concentrations of halothane and the decrease in activity was significant (P less than 0.01) when 4% halothane was used. These findings suggest that exposure to clinically-used concentrations of halothane and nitrous oxide does not interfere with the NK lymphocyte response of the host.

Adult↗
PubMed1986

Control of end-tidal halothane concentration. Part B: Verification in dogs.

Conventional anaesthetic techniques do not allow for the automatic control of end-tidal halothane concentration and, therefore, brain concentration cannot be predicted. In this study, eight dogs were ventilated with halothane in oxygen using a new closed-loop anaesthetic breathing system which provided a constant end-tidal concentration. During the first 60 min the end-tidal concentration was maintained at 0.87 vol% (1 MAC). Then followed 60 min of halothane wash-out and a further 120-min period of halothane at 1.74 vol% (2 MAC). Halothane concentrations were measured in the inspired and expired air, and in the arterial, cerebral venous and mixed venous blood. Haemodynamic and respiratory variables were measured. The system reached 95% of the target end-tidal concentration within 6 min without over-shooting. After 2 h of wash-in, significant gradients still persisted between end-tidal, arterial and cerebral venous blood concentrations. Measured uptake differed from theoretically calculated uptake by 18.3-57.6%, depending on the model used. Measured arterial and cerebral venous concentrations differed from theoretically calculated values by 7% and 17.5%, respectively. It was shown that the required end-tidal concentrations can be obtained rapidly and accurately, and that brain tissue concentrations can be predicted within certain limits.

Anesthesia, Inhalation↗
PubMed1988

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 received halothane, enflurane or isoflurane anaesthesia for elective minor surgery. The GST concentrations increased significantly at 3 h after anaesthesia in patients who received halothane or enflurane, but not in patients who were given isoflurane. A secondary increase in GST concentration, at 24 h, was seen in a small number of individuals who received halothane or enflurane. Abnormal GST concentrations were found in 50% of patients following halothane anaesthesia, 20% following enflurane and 11% after isoflurane. The small but significant increases in GST concentrations in patients receiving halothane or enflurane suggests an impairment of hepatocellular integrity following the administration of these anaesthetics. In contrast, isoflurane anaesthesia did not appear to be associated with this effect.

Adult↗
PubMed1988

Decontamination of halothane from anaesthetic machines achieved by continuous flushing with oxygen.

The contamination of four types of anaesthetic machine with halothane was sequentially sampled by mass spectrometry while the machines were continuously flushed with oxygen 8 litre min-1 for up to 24 h. Contamination decreased in an exponential manner. Machines fitted with Selectatec vaporizer mounting systems and with the vaporizer removed showed contamination less than 0.02 parts per million (p.p.m.) of halothane after 12 h flushing. Machines with cage-mounted vaporizers or with vaporizers left connected to the Selectatec block demonstrated persisting contamination. The Fluotec Mk.4 vaporizer showed an improvement on earlier designs in this respect. Background contamination concentrations of greater than 0.05 p.p.m. were measured in a patient-free recovery area of an operating theatre suite. Concentrations increased to 1 p.p.m. when patients were admitted following halothane anaesthesia. Decontamination of anaesthetic machines to concentrations of halothane below those detected as background contamination within recovery areas may allow such machines to be used safely to anaesthetize patients at risk from halothane.

Anesthesia, Inhalation↗
PubMed1989

Effects of halothane on somatosensory evoked potentials recorded in the extradural space.

We studied the effects of supplementing anaesthesia with halothane (up to 1.5%, inspired) on the somatosensory evoked potential recorded in the extradural space of six patients before corrective surgery for idiopathic adolescent scoliosis. A further six patients in whom anaesthesia was supplemented with thiopentone acted as a control group. Halothane 1.5% resulted in a significant decrease in overall amplitude (P less than 0.05) from the left leg only. Halothane had no significant effect on overall amplitude, first peak amplitude, second peak amplitude and first peak latency. We conclude that halothane is unlikely to alter the interpretation of somatosensory evoked potentials recorded extradurally during scoliosis surgery. A possible unilateral effect of halothane on the concave side in idiopathic adolescent scoliosis needs further investigation.

Adolescent↗
PubMed1989

Incidence of arrhythmias in dental anaesthesia: a cross-over comparison of halothane and isoflurane.

Fifty patients received halothane anaesthesia during the surgical removal of 3rd molars from one side of the mouth and isoflurane during extractions on the other. Degree of surgical difficulty was matched, and end-tidal PCO2 did not differ significantly between sides. A significantly higher incidence of arrhythmias occurred during halothane, compared with isoflurane, anaesthesia. This difference occurred primarily when halothane was given for the first operated side. A clinically important feature of the stability of cardiac rhythm during isoflurane anaesthesia was demonstrated--when frequent ectopic beats occur during halothane anaesthesia, a significant decrease in the rate of premature contractions occurs within 3 min of discontinuing halothane and introducing isoflurane.

Adult↗
PubMed1992

Indocyanine green clearance and hepatic function during and after prolonged anaesthesia: comparison of halothane with isoflurane.

Specific biochemical and physiological tests of liver function were used to assess 20 consecutive patients undergoing prolonged head and neck surgery with halothane or isoflurane anaesthesia. Hepatic function was assessed by measurement of serum concentrations of total bilirubin and albumin, and plasma activity of pseudocholinesterase, gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alkaline phosphatase (ALP) and hepatic glutathione S-transferase. Plasma clearance of indocyanine green was used as an estimate of hepatic blood flow. No major differences were observed in serum concentrations of GGT, ALP, bilirubin, albumin or pseudocholinesterase. Serum AST activity in those patients receiving halothane was increased at 24 h and at 48 h compared with those who received isoflurane (not statistically significant). Glutathione S-transferase activity was increased significantly in the halothane group throughout the period of study, compared with those who received isoflurane. Similarly, there was a significant difference between the two groups as measured by plasma clearance of indocyanine green: in the halothane group there was a slower disappearance rate of the dye from plasma at specific times than in the patients who received isoflurane. Our data support the use of isoflurane rather than halothane for prolonged anaesthesia.

Adult↗
PubMed1992

Anaesthetic modification of regional myocardial functional adjustments during myocardial ischaemia: halothane vs fentanyl.

During myocardial ischaemia, functional compensation occurs by non-ischaemic regions of the left ventricle (LV). Anaesthetics may affect compensation by altering contractility, metabolism and perfusion. This was studied in dogs anaesthetized with fentanyl (150 micrograms kg-1 loading dose and 100 micrograms kg-1 h-1) or 0.75% and 1.5% halothane and subjected to left anterior descending artery (LAD) occlusion. After 15 min of anterior wall ischaemia, cardiac output, mean arterial pressure and LV maximum dP/dt were diminished in the 1.5% halothane but not in the 0.75% halothane or fentanyl groups. In all groups, stroke volume decreased, LV end-diastolic pressure increased and anterior wall function deteriorated (measured as systolic shortening, peak systolic intramyocardial pressure (IMP), regional wall stroke work (RSW) and slope of preload recruitable stroke work curve (Mw)) with ischaemia. Functional changes in the lateral (non-ischaemic) wall were different between groups. Regional function during occlusion in this area improved with fentanyl (mean (SEM) IMP, RSW and Mw increased by 23 (2)%, 37 (3)% and 69 (7)%, respectively), was relatively well maintained with 0.75% halothane and diminished with 1.5% halothane.

Anesthesia, Inhalation↗
PubMed1992

Interaction between halothane and mu, delta and kappa opioid agonists on the isolated right atria of the rat.

We have examined the interaction between halothane and specific opioid agonists at mu (morphine and [D-ala2 N-mephe4, gly-ol5]-enkephalin (DAGO)), delta ([D-pen2,5]-enkephalin (DPDPE)) and kappa (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrroliknyl)cyclohexyl]- bencetamide methane sulphonate (U-50,488H)) receptors on the isolated right atria of the rat. All the opioid agonists tested decreased atrial rate. The maximal effects obtained with U-50,488H (75 (SE 3.3)%) were significantly (P < 0.001) greater than those obtained with morphine (12 (2.7)%), DAGO (8 (0.6)%) or DPDPE (11 (1.8)%). Halothane 1.5 v/v% did not modify the inhibitory effects induced by morphine, DAGO or DPDPE. However, U-50,488H had a potentiating effect in the presence of halothane 1.5 v/v% (P < 0.001). Naloxone 5 x 10(-7) and 1 x 10(-6) mol litre-1 antagonized the inhibitory effects of U-50,488H in the presence of halothane. We conclude that halothane increased the potency of a kappa agonist on isolated right atria and suggest that this effect was mediated by opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Effects of isoflurane-nitrous oxide and halothane-nitrous oxide anaesthesia on myocardial contractility assessed by transoesophageal echocardiography.

In order to evaluate the direct effect of isoflurane-nitrous oxide and halothane-nitrous oxide anaesthesia on cardiac contractility in 20 adults, we have used a method based on left ventricular end-systolic wall stress (LVESWS) vs velocity of circumferential fibre shortening with corrected heart rate (Vcfc), obtained by transoesophageal echocardiography. We found that LVESWS (index of afterload) decreased significantly with isoflurane-nitrous oxide (n = 10) in concentrations of 1.5-1.95 MAC, but there were no significant changes in LVESWS with halothane-nitrous oxide (n = 10). Vcfc decreased significantly with halothane-nitrous oxide in concentrations of 1.5-1.95 MAC, but this index did not change significantly with isoflurane-nitrous oxide. However, there was no significant difference between the two groups in LVESWS or Vcfc. In the analysis of the LVESWS-Vcfc relationship, myocardial contractility associated with isoflurane-nitrous oxide anaesthesia did not differ significantly from that associated with halothane-nitrous oxide anaesthesia at equiMAC concentrations. The results suggest that halothane-nitrous oxide anaesthesia, at 1.5-1.95 MAC, maintained myocardial contractility in similar anaesthetic concentrations to isoflurane-nitrous oxide.

Adult↗