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PubMed1988

Cerebral blood flow and oxygen consumption during isoflurane and halothane anesthesia in man.

In 13 patients, the effects on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of isoflurane and halothane administered in a clinically relevant situation were studied. Measurements were performed during fentanyl/nitrous oxide (65%) anesthesia together with moderate hyperventilation (PaCO2 approx 4.5 kPa), and repeated after addition of 0.65 MAC of isoflurane (n = 6) or halothane (n = 7). CBF was measured after intravenous administration of 133xenon and CMRO2 was calculated from the arterial venous differences of oxygen content (AVDO2) determined in arterial and jugular venous bulb blood. CBF and CMRO2 (means +/- s.e. mean) determined prior to administration of volatile agents were 28 +/- 5 ml x 100(-1) x min-1 and 2.0 +/- 0.3 ml x 100 g-1 x min-1, respectively, in the isoflurane group. In the halothane group, CBF was 25 +/- 0.4 ml x 100 g-1 x min-1 and CMRO2 was 2.0 +/- 0.4 ml x 100 g-1 x ml-1. There were no significant intergroup differences. Isoflurane did not change CBF, whereas halothane produced an increase of 36% (P less than 0.05) compared to values obtained during fentanyl/N2O anesthesia. In addition, isoflurane caused a further decrease in CMRO2 of 12% (P less than 0.01) as compared to a 20% increase (P less than 0.05) with halothane. The cerebral metabolic depression caused by the short-acting anesthetic induction agents would be expected to decrease with time, and could partly explain the observed increase in CMRO2 produced by halothane. The study suggests that the cerebrovascular and metabolic properties of isoflurane differ from those of halothane, also in man.

Adult↗
PubMed1988

The cardiovascular effects of anticholinergic agents administered during halothane anaesthesia in children.

The cardiovascular effects of anticholinergic agents administered during halothane anaesthesia were studied in 31 children aged 1-12 years undergoing peripheral orthopaedic surgery. Either normal saline, glycopyrrolate (10 micrograms.kg-1) or atropine (20 micrograms.kg-1) was administered in randomized double-blind fashion during the induction of anaesthesia with halothane while the electrocardiogram was continuously recorded. After induction, the children were paralyzed with atracurium, intubated, and ventilated. Anaesthesia was maintained with N2O/O2 and halothane (up to 2.5% inspired). The concentrations of expired CO2 and halothane were measured continuously using mass spectrometry. Sixty-one percent (19/31) of the children developed one or more dysrhythmias. Junctional rhythm occurred in 74% (14/19) of the children with dysrhythmias, developed early during induction (mean +/- s.d. time = 2.29 +/- 2.0 min after commencement of induction), and usually resolved before the administration of the study drug (8/14). All dysrhythmias initially occurred before or during induction and none developed during intubation, during incision, during the maintenance of anaesthesia, or after the administration of anticholinergic agents. The data suggest that: 1) a combination of factors present during halothane induction is highly dysrhythmogenic especially for junctional rhythm; 2) junctional rhythm will resolve spontaneously; 3) the administration of an anticholinergic agent during halothane induction is safe but may be unnecessary in children greater than 1 year of age; and 4) the dysrhythmogenic factors present during induction are attenuated during the maintenance of halothane anaesthesia.

Anesthesia, Inhalation↗
PubMed1991

Minimum alveolar concentration of halothane-diethyl-ether azeotrope.

The azeotropic mixture of halothane and diethyl ether (HE) may be a valuable alternative to other anaesthetic agents under circumstances such as war, civil disaster, and primitive conditions. In the present study the minimum alveolar concentrations (MACs) for HE in man (n = 25) and in pigs (n = 6) were determined. For comparison with results of other studies, the MAC for halothane in man (n = 14) was also determined. A Normac gas analyser and a Varian 3700 gas chromatograph were calibrated against known standards of HE. The performance of two vaporizers (Fluotec Mark III, Servo vaporizer for halothane) was studied. The Fluotec Mark III vaporizer and the Servo halothane vaporizer filled with HE gave a linear performance with increasing dial settings. The Normac gas analyser set for methoxyflurane was linearly sensitive to the ether component of the azeotrope. The MAC for HE in man was 0.71 vol.% +/- 0.03 (s.e.mean) (ether 0.21 vol.%, halothane 0.50 vol.%) in the age group 19-42 years. MAC for halothane in man was 0.65 +/- 0.03 in the age group 19-32 years. The MAC for HE in pigs between 20-24 kg was 0.99 vol.% +/- 0.07. The ether component seems to act synergistically with halothane in the azeotropic mixture. The present study provides an opportunity to compare HE with other volatile anaesthetic agents.

Adult↗
PubMed1992

Myocardial circulatory and metabolic effects of halothane when used to control intraoperative hypertension in patients with coronary artery disease.

The effect of halothane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anaesthesia, to treat intraoperative hypertension was investigated. Fifteen patients with two- or three-vessel coronary artery disease with an ejection-fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary haemodynamics, global (coronary sinus, CSF) and regional (great cardiac vein, GCVF) myocardial blood flow were measured. Measurements were made: 1) after induction of anaesthesia but prior to skin incision, 2) during sternotomy, and 3) during halothane administration after its use to reduce arterial pressure to the pre-sternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance index (SVRI), and was accompanied by an increase in pulmonary capillary wedge pressure (PCWP), regional myocardial oxygen consumption and extraction, GCFV and CSF. Halothane reduced arterial blood pressure to pre-sternotomy levels within 7.1 +/- 0.6 min at an end-tidal concentration of 0.96 +/- 0.11%. Halothane caused a decrease in SVRI, total coronary vascular resistance, regional myocardial oxygen consumption and extraction, while cardiac index, heart rate and GCVF/CSF ratio remained unchanged. Mean regional myocardial lactate extraction was not affected by sternotomy or halothane. During halothane administration one patient developed regional myocardial lactate production which was not present during sternotomy. However, another two patients, who had regional myocardial lactate production during sternotomy, did not produce lactate or had less negative value of regional myocardial lactate extraction during halothane administration.

Aged↗
PubMed1996

MAC for halothane and isoflurane during normothermia and hypothermia in the newborn piglet.

BACKGROUND: Halothane and isoflurane are frequently used in studies of perinatal hypoxia and ischemia. Little information exists on the minimum alveolar concentration (MAC) necessary to prevent movement to a painful stimulus in newborn pigs and no information on the effects of hypothermia on MAC in pigs. Hypothermia is currently investigated as a posthypoxic neuroprotective intervention. METHODS: The MAC of halothane and isoflurane necessary to prevent movement when a 25 cm hemostatic clamp was applied to the tail were determined in six 20-48-hour-old piglets, and when the same stimulus was applied to the hoof. MAC for halothane was first determined at 39 degrees C, then at 35 degrees C, whereafter halothane was discontinued and MAC for isoflurane determined first at 35 degrees C and then at 39 degrees C. RESULTS: In all six piglets MAC was lower at 35 degrees C than at 39 degrees C for both anesthetics with both tail and hoof determination, lower for halothane than isoflurane for both stimuli at both temperatures, and lower for tail than hoof determination for both anesthetics at both temperatures. For halothane at 39 degrees C, mean (SD) MAC hoof was 0.82 (0.05)% vs tail 0.60 (0.12)%, and at 35 degrees C, hoof 0.65 (0.06)% vs tail 0.42 (0.10)%. For isoflurane at 39 degrees C, MAC hoof was 2.47 (0.28)% vs tail 1.83 (0.28)%, and at 35 degrees C, hoof was 1.83 (0.18)% vs tail 0.85 (0.25)%. CONCLUSION: In the newborn piglet, MAC should be determined by hoof clamp, MAC of isoflurane is approximately three times that of halothane, and both are reduced during hypothermia.

Anesthetics, Inhalation↗
PubMed1997

Effect of temperature variation (22 degrees C-44 degrees C) on halothane and caffeine contracture testing in normal humans.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is diagnosed using halothane-caffeine contracture testing of a muscle sample maintained at 37 degrees C. However, there has not been a systematic study that examines the effect of different temperatures on the response of normal muscle to halothane and caffeine. We hypothesized that altering bath temperature would modify the contracture responses. METHODS: We obtained muscle samples from 20 patients undergoing surgical procedures of the lower extremities. The samples were dissected into 245 bundles and the bundles were exposed to halothane 3% or incremental caffeine, according to the North American MH group protocol. Several bundles from each patient were simultaneously studied at four different temperatures (22 degrees C, 30 degrees C, 37 degrees C and 44 degrees C). Each bundle was studied at only one temperature, the muscle samples of 3 patients were simultaneously studied at all four temperatures for halothane and caffeine. RESULTS: Maximum contracture to caffeine (32 mM) was highest at 37 degrees C; however, at lower caffeine concentrations (2-4 mM), there was no consistent effect of temperature on contracture response. Likewise, temperature did not alter contracture responses to halothane. The extremes of temperature (22 degrees C and 44 degrees C) were associated with lack of twitch in response to electrical stimulation. For the bundles exposed to halothane at 22 degrees C, the absence of a twitch was associated with the presence of a contracture, although these were never above the diagnostic threshold. CONCLUSIONS: We conclude that temperature has little effect on responses of normal muscle to halothane and caffeine.

Aged↗
PubMed1997

The effect of halothane on mivacurium infusion requirements in adult surgical patients.

BACKGROUND: The extent of interaction between volatile anaesthetics and neuromuscular blocking agents depends both on the inhalational anaesthetic and the muscle relaxant. Halothane has the weakest potentiating effect on neuromuscular blocking drugs and previous studies of the interaction between halothane and mivacurium have been contradictory. We were interested in determining the effect of different levels of halothane-nitrous oxide anaesthesia on infusion requirements of mivacurium. METHODS: Sixty adult surgical patients were studied. Anaesthesia was induced with thiopentone and fentanyl and intubation facilitated with mivacurium 0.15 mg.kg-1. The patients were randomly assigned to one of four study groups. The control group received nitrous oxide in oxygen (2:1) supplemented with fentanyl, while in the other groups halothane was administered at different end-tidal concentrations: 0.19% (group 2), 0.37% (group 3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane. Neuromuscular block was kept at 95% with a closed-loop feedback infusion of mivacurium and monitored with electromyography. Plasma cholinesterase concentrations and dibucaine numbers were determined. RESULTS: Mivacurium infusion requirements (mean +/- SD) were 7.5 +/- 3.1 micrograms.kg-1.min-1 with nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC of halothane the steady-state infusion rates of mivacurium were reduced to 6.3 +/- 2.8, 5.6 +/- 1.4 and 5.7 +/- 2.5 micrograms.kg-1.min-1 (P < 0.05), respectively. There was a linear relationship between mivacurium infusion requirements and plasma cholinesterase activity. CONCLUSIONS: Halothane anaesthesia reduces mivacurium infusion requirements by 15-25% compared to nitrous oxide-fentanyl anaesthesia. Interindividual differences in the extent of this interaction are great.

Adult↗
PubMed1997

In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal microcirculation.

BACKGROUND: It has been proposed that halogenated anaesthetics interfere with the endothelium-dependent circulatory control by attenuating the effects of endothelium-derived relaxing factor (EDRF/NO). This study was designed to determine whether or not volatile anaesthetics in vivo influence the microvascular tone in hepatic sinusoids. METHODS: Using epifluorescence videomicroscopy, we compared the effects of the volatile anaesthetics halothane, enflurane, and isoflurane on hepatic microcirculation halothane, enflurane, and Animals were initially anaesthetized with pentobarbitone (50 mg.kg-1 i.p.) to allow instrumentation and laparotomy and were randomly allocated to one of 4 groups (n = 5-6 each) to receive either a supplementary dose of i.v. pentobarbitone (25 mg.kg-1; control group) or 0.75 MAC halothane, enflurane or isoflurane (1.5 MAC.h). RESULTS: Halothane decreased significantly the volumetric blood flow as compared with isoflurane (P < 0.05) or pentobarbitone controls (P < 0.05). The decrease in sinusoidal blood flow caused by halothane was largely attributable to a decrease in sinusoidal diameter (P < 0.05), while red blood cells velocity remained unchanged. Isoflurane led to a significant decrease in sinusoidal width compared with controls (P < 0.05) but an increase in red cell velocity offset the effect of sinusoidal narrowing of volumetric blood flow, while enflurane had no significant effect on any of the measured parameters. CONCLUSION: This study provides the first direct evidence that the volatile anaesthetics halothane and isoflurane in vivo shift the hepatic microvascular tone toward a more constricted state; however, flow velocity is enhanced with isoflurane, offsetting this effect. As a result the volumetric flow is at least affected by isoflurane, then enflurane and most significantly by halothane. Furthermore, our data are consistent with the concept that volatile anaesthetics in clinically relevant concentrations may influence the balance between endothelium-derived vasoactive factors which control microvascular tone.

Anesthetics, Inhalation↗
PubMed1998

Vomiting, retching, headache and restlessness after halothane-, isoflurane- and enflurane-based anaesthesia. An analysis of pooled data following ear, nose, throat and eye surgery.

BACKGROUND: Isoflurane has exceeded halothane and enflurane in usage. A literature search, however, revealed no data comparing the effects on emesis, headache and restlessness of these three agents. METHODS: With hospital ethics committee approval and patient consent, a prospective, randomised, double-blind study of 556 patients undergoing ENT and eye surgery was undertaken to evaluate the effects of halothane, isoflurane and enflurane on vomiting, retching, headache and restlessness until 24 h after anaesthesia. Balanced general anaesthesia was administered comprising benzodiazepine premedication, induction with thiopentone-atracurium-morphine (ENT patients) or fentanyl (eye patients), controlled ventilation and maintenance with either halothane 0.4-0.6 vol% (n = 186), isoflurane 0.6-0.8 vol% (n = 184) or enflurane 0.8-1 vol% (n = 186) in nitrous oxide 67% and oxygen. RESULTS: The three study groups were comparable, and comprised comparable subgroups having ear, nose, throat, intraocular and non-intraocular surgery. During early recovery from anaesthesia, the respective requirements for halothane, isoflurane and enflurane for analgesia (7%, 9% and 10%), frequency of emesis (6%, 8% and 8%), antiemetic requirements (1%, 1% and 2%), restlessness-pain scores and time spent in the recovery ward (27 SD 10, 31 SD 12 and 26 SD 9 min) were similar. During the ensuing 24-h postoperative period, patients who had isoflurane experienced emesis less often than those who had halothane (36% vs 46%, P < 0.025) but did so with similar frequency to those who had enflurane (46% vs 41%). Antiemetic requirements were least in those given isoflurane (isoflurane 12%, halothane and enflurane 23% each, P < 0.005), but headache and analgesic requirements were similar. CONCLUSION: Isoflurane induces less postoperative emesis than halothane, but headache is similarly frequent after anaesthesia with any of these agents.

Adult↗
PubMed1992

The kidney as a novel target tissue for protein adduct formation associated with metabolism of halothane and the candidate chlorofluorocarbon replacement 2,2-dichloro-1,1,1-trifluoroethane.

Hydrochlorofluorocarbons (HCFCs) have been identified as chemical replacements of the widely used chlorofluorocarbons (CFCs) that are implicated in stratospheric ozone depletion. Many HCFCs are structural analogues of the anesthetic agent halothane and may follow a common pathway of biotransformation and formation of adducts to protein-centered and other cellular nucleophiles. Exposure of rats to a single dose of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) or of the candidate CFC substitute HCFC 123 (2,2-dichloro-1,1,1-trifluoroethane) led to the formation of trifluoroacetylated protein adducts (CF3CO-proteins) not only in the liver, but also in the kidney as a novel target tissue for protein trifluoroacetylation. CF3CO-proteins in the kidney amounted to about 5% of those formed in the liver of the same animal. The amount of CF3CO-proteins formed within the kidney was roughly reflected by the capacity of metabolism of halothane or HCFC 123 by rat kidney microsomes in vitro which amounted to about 10% of that observed with liver microsomes. By immunohistochemistry, CF3CO-proteins in the kidney were mainly localized in the tubular segments of the cortex. In the liver, the density of CF3CO-proteins decreased from the central vein towards the portal triad. In vitro incubation of rat liver microsomes with halothane or HCFC 123 resulted in extensive formation of CF3CO-proteins and reproduced faithfully the pattern of liver CF3CO-proteins obtained in vivo. CF3CO-proteins generated in vitro were immunochemically not discernible from those generated in vivo. Glutathione (5 mM) and cysteine (5 mM) virtually abolished CF3CO-protein formation; the release of Br- from halothane and Cl- from HCFC 123 was reduced to much lesser a degree. S-Methyl-glutathione, N-acetyl-cysteine, methionine, and N-acetyl-methionine only slightly affected the formation of CF3CO-proteins or metabolism of either substrate. The data suggest that metabolism and concomitant CF3CO-protein formation of halothane or of candidate CFC replacements like HCFC 123 is not restricted to the liver but also takes place in the kidney. Furthermore, an in vitro system for CF3CO-protein formation has been developed and used to show that protein-centered and glutathione-centered nucleophilic sites compete for intermediates of metabolism of halothane or of HCFC 123.

Animals↗
PubMed1994

Evaluation of halothane as an anaesthetic in camels (Camelus dromedarius).

Halothane as an anaesthetic was evaluated in 12 adult camels, thiopentone being used as an induction agent. In six camels, clinical signs and haematological and blood biochemical changes were investigated while in other six haemodynamic, acid base and blood gas changes were monitored. The dose of thiopentone required to ensure intubation for halothane anaesthesia was 7.25 +/- 0.33 mg/kg. A modified technique of tracheal intubation was found to be safe and quick. During halothane administration all anaesthetic effects were predictable. Complete recovery occurred in 39.5 +/- 9.8 min after discontinuation of halothane administration. Halothane moderated the thiopentone-induced tachycardia. The mean arterial pressure decreased significantly. There was an increase in the arterial carbon dioxide and venous oxygen tension during halothane anaesthesia and development of hypoxaemia after its discontinuation. The alanine aminotransferase values increased during recovery, while plasma sodium, potassium and calcium decreased. Halothane appears to be safe for camels. However, to avoid hypoxaemia in the immediate post-anaesthetic period, oxygen administration should be continued.

Anesthesia, Inhalation↗
PubMed2003

Hepatic effects of halothane, isoflurane or sevoflurane anaesthesia in dogs.

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty-one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between 13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre-anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12-14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre-medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.

Alkaline Phosphatase↗
PubMed1970

Influence of halothane and catecholamines on heart rate and rhythm in the horse.

1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anaesthesia appeared to protect the heart against adrenaline-induced arrhythmias.3. From a comparison of the arrhythmogenic, chronotropic and pressor actions of adrenaline, noradrenaline and isoprenaline during halothane anaesthesia, it was concluded that sensitization to the arrhythmogenic actions of catecholamines resulted primarily from the action of halothane on the ventricle. The results also indicated that the pressor responses to catecholamines during halothane anaesthesia probably played some part in the genesis of arrhythmias.4. No "spontaneous" ventricular arrhythmias were recorded in twenty-four horses anaesthetized with halothane or in sixteen animals under ether anaesthesia.5. The available evidence indicates that a moderate to fairly severe degree of hypercapnia produced little increase in sympathetic control of the myocardium during halothane anaesthesia; the absence of irregularities in ventricular rhythm during halothane anaesthesia were attributed to this factor.

Anesthesia, Inhalation↗
PubMedDate not supplied

Electroencephalography of detomidine-ketamine-halothane and detomidine-ketamine-isoflurane anesthetized horses during orthopedic surgery. A comparison.

This study was done to compare the electroencephalographic (EEG) response evoked by orthopedic surgery in halothane- and isoflurane-anesthetized horses. Eight horses scheduled for bilateral arthroscopic surgery of the stifle were premedicated with detomidine (20 micrograms/kg) intravenously and five minutes later induced to anesthesia with ketamine (2.2 mg/kg) intravenously. Anesthesia was maintained with either halothane or isoflurane. Assignment of inhalation anesthetic was done randomly. The multiple of minimal alveolar concentration (MAC) of halothane required for anesthesia was significantly higher than the multiple of MAC of isoflurane (p < .05) required. Total amplitude of the EEG with halothane was smaller than with isoflurane (p < .05), but 13.0 to 32.0 Hz high frequency/0.0 to 3.9 Hz low frequency (beta/delta) ratio was greater for halothane (p < .05). Arterial partial pressure of oxygen (PaO2) was significantly (p < .05) higher with isoflurane than with halothane. The differences in EEG frequency shift observed suggest that isoflurane provided better analgesia than halothane for this group of horses.

Anesthesia, Inhalation↗
PubMed1983

Influence of dithiocarb, (+)-catechin and silybine on halothane hepatotoxicity in the hypoxic rat model.

In phenobarbital (phenemalum NFN)-pretreated male rats exposed to 1% halothane for 2 hrs under hypoxic conditions (10% O2), significant increases in serum enzyme activities of alanine aminotransferase and sorbitol dehydrogenase were observed 24 and 48 hrs later indicating liver damage. In this known model of halothane hepatotoxicity, pretreatment with (+)-catechin (200 mg/kg orally) or silybine (150 mg/kg orally) protected against halothane-induced liver injury, whereas diethyldithiocarbamate (200 mg/kg orally) failed to be effective. Halothane decreased the concentration of reduced glutathione in liver only under hypoxic conditions indicating that glutathione might be involved in the non-oxidative metabolic pathways of halothane. Free fluoride in plasma was used as a measure of non-oxidative defluorination of halothane. Higher plasma fluoride levels were observed under conditions which led to hepatotoxicity but did not correlate with the protective effects of the antidotes. This further supports the assumption that 2-chloro-1,1,1-trifluoroethane might be the radical intermediate responsible for halothane hepatotoxicity.

Animals↗
PubMed1990

Halothane increases Ca2+ efflux via Ca2+ channels of sarcoplasmic reticulum in chemically skinned rat myocardium.

1. A method has been developed to study Ca2+ fluxes across the sarcoplasmic reticulum (SR) of chemically (saponin) skinned myocardium without interference from the SR Ca2+ pump. 2. Exposure of rat cardiac trabeculae to a solution containing 50 micrograms/ml saponin for 10 min or longer caused an SR Ca2+ efflux which was not blocked by Ruthenium Red (RRed) and did not require the presence of nucleotides. 3. Exposure of the saponin-treated cardiac preparation to 11 mM-AMP, when the SR Ca2+ pump was not active, enhanced Ca2+ release from the SR by a mechanism which was blocked by 10 microM-RRed. 4. The amount of Ca2+ loaded by the 10 min saponin-treated trabeculae was maintained constant for at least 3 min when the preparations were transferred to low [Ca2+] solutions (0.1 mM-EGTA; pCa greater than 7.5) containing ATP. This indicated that the Ca2+ pump can efficiently recycle Ca2+ lost from the SR under these conditions. 5. Halothane (0.47 and 1.89 mM) reversibly increased the rate of Ca2+ release from the SR regardless of whether or not the SR Ca2+ pump was active. This effect was more marked at 1.89 mM than at 0.47 mM. RRed (10 microM) completely blocked the Ca2+ release induced by both concentrations of halothane. 6. The presence of nucleotide (11 mM-AMP) did not affect the halothane-induced Ca2+ release when the Ca2+ pump was inactive. 7. Exposure of cardiac preparations to solutions containing more than 5 mM-halothane irreversibly damaged the ability of the SR to load Ca2+. 8. The results suggest that at lower doses (0.47 and 1.89 mM) halothane specifically and reversibly stimulates Ca2+ efflux via the RRed-sensitive SR Ca2(+)-release channel by a mechanism which does not require the presence of nucleotides or relatively high [Ca2+]. The results also suggest that AMP and halothane act independently and non-synergistically to increase Ca2+ efflux through the same SR Ca2(+)-release channel. At higher doses (greater than 5 mM) halothane irreversibly damages the SR membrane, presumably by disrupting the lipid bilayer.

Adenosine Monophosphate↗
PubMed2003

Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons.

General anesthetics are thought to act on both excitatory and inhibitory neuronal pathways at both post- and presynaptic sites. However, the literature in these regards is somewhat controversial. The aim of the present study was to reassess the relative importance of the various anesthetic actions using a common preparation. Rat cortical neurons in primary culture were used to record spontaneous miniature postsynaptic currents by the whole-cell patch-clamp technique. Halothane at clinically relevant concentrations prolonged the decay phase of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in the presence of tetrodotoxin and at higher concentrations decreased the frequency of mIPSCs. The mIPSC amplitudes underwent little change. Spontaneous action potential-dependent IPSCs recorded in the absence of tetrodotoxin were similarly affected by halothane. Halothane also decreased the frequency of spontaneous miniature non-N-methyl-D-aspartate (NMDA) excitatory postsynaptic currents (mEPSCs) as well as spontaneous action potential-dependent NMDA EPSCs and non-NMDA EPSCs without affecting their decay phase. The halothane effect on mIPSC and mEPSC frequency was dependent on the external calcium concentration. In contrast to halothane, the only effect of propofol was the prolongation of the decay phase of mIPSCs and IPSCs. The prolongation of mIPSCs and IPSCs by halothane and propofol coupled with the ineffectiveness on mEPSCs and EPSCs suggests a selective postsynaptic modulation of GABA(A) receptors. The additional calcium-dependent inhibition of mIPSC and mEPSC frequency by halothane (but not propofol) suggests a more general mechanism by this anesthetic on presynaptic transmitter release.

Anesthetics, Inhalation↗
PubMed1976

Unexplained hepatitis following halothane.

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.

Adolescent↗