Halothane anesthesia

Baboons were surgically prepared with chronically indwelling silastic catheters implanted in either femoral or jugular veins under pentobarbital or halothane anesthesia using methods described in detail by Lukas et al. 

Wollmer P, Schainer W, Bos JA, Bakker W, Krenning EP, Lachmann B (1990) Pulmonary clearance of "mTC-DTPA during halothane anesthesia. Acta Anaes-thesiol Scand 34 572-575. 

Halothane (boiling point BP] 50 °C), enfhirane (BP 56 °C), isoflurane (BP 48 °C), and the obsolete methoxyflu-rane (BP 104 °C) have to be vaporized by special devices. Part of the administered halothane is converted into hepatotoxic metabolites (B). Liver damage may result from halothane anesthesia. With a single exposure, the risk involved is unpredictable however, there is a correlation with the frequency of exposure and the shortness of the interval between successive exposures. 

Anon Summary of the National Halothane Study. Possible association between halothane anesthesia and postoperative hepatic necrosis. JAMA 197 775-788, 1966... 

Pulmonary macrophage mobilization in cigarette smoke-exposed mice after halothane anesthesia. Anesth Analg 1986 65(1) 37-45. 

Inhaled anesthetics that are relatively insoluble in blood (low blood gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, which leads to a more rapid recovery from their anesthetic effects compared to halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane anesthesia is predictably less rapid. The duration of exposure to the anesthetic can also have a marked effect on the time of recovery, especially in the case of more soluble anesthetics. Accumulation of anesthetics in tissues, including muscle, skin, and fat, increases with continuous inhalation (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is gradually eliminated from these tissues. Thus, if exposure to the anesthetic is short, recovery may be rapid even with the more soluble agents. However, after prolonged anesthesia, recovery may be delayed even with anesthetics of moderate solubility such as isoflurane. 

Of the inhaled anesthetics, nitrous oxide increases cerebral blood flow the least. However, when 60% nitrous oxide is added to halothane anesthesia, cerebral blood flow usually increases more than with halothane alone. At low doses, all of the halogenated agents have similar effects on cerebral blood flow. At larger doses, enflurane and isoflurane increase cerebral blood flow less than halothane. If the patient is hyperventilated before the anesthetic is given (reducing PaCCU), the increase in intracranial pressure from inhaled anesthetics can be minimized. 

The mechanisms underlying hepatotoxicity from halothane remain unclear, but studies in animals have implicated the formation of reactive metabolites that either cause direct hepatocellular damage (eg, free radical intermediates) or initiate immune-mediated responses. With regard to the latter mechanism, serum from patients with halothane hepatitis contains a variety of autoantibodies against hepatic proteins, many of which are in a trifluoroacetylated form. These trifluoroacetylated proteins could be formed in the hepatocyte during the biotransformation of halothane by liver drug-metabolizing enzymes. However, TFA proteins have also been identified in the sera of patients who did not develop hepatitis after halothane anesthesia. 

Neuromuscular blockade from tubocurarine during isofiurane and halothane anesthesia in patients. Note that at equivalent levels of anesthesia, isofiurane augments the block far more than does halothane. 

Ten years ago, it was observed in a model of 5-min global ischemia in gerbils that the expected severe hippocampal neuronal loss could be markedly attenuated by prolonging the period of halothane anesthesia, which blunted the mild postischemic hyperthermia (approx 1,5°C) that would otherwise occur (55). This effect was not specific to halothane but rather could be duplicated by warming the head by a similar amount in its absence. This study established the marked sensitivity of the postischemic brain to even mild hyperthermia. 

DM Fisher. Neuromuscular effects of vecuronium (ORG NC45) in infants and pediatric patients during N20 halothane anesthesia. Anesthesiology 58 519, 1983. 

Halothane is a volatile general anesthetic that was introduced into the practice of clinical anesthesia in 1956. Shortly after its introduction two forms of hepatic injury were noted to occur in patients who received halothane anesthesia. A subclinical increase in blood concentration of transaminase enzymes is observed in 20% of patients and has been attributed to lipid peroxidation caused by the free radical formed by reductive metabolism of halothane as shown in Figure 16.7 (39/ 40). The second form of toxicity is a potentially fatal hepatitis-like reaction that is characterized by severe hepatocellular necrosis and is thought to be initiated by the oxidative formation of trifluoroacetyl chloride (Figure 16.7). Fatal hepatic necrosis occurs in only 1 of 35/000 patients exposed to halothane/ but the risk of this adverse event is greater in females and is increased with repeat exposure/ obesity/ and advancing age (40). Because the onset of halothane hepatitis is delayed but is more frequent and occurs more rapidly following multiple exposures/ and because these patients usually are febrile and demonstrate eosinophilia/ this reaction is suspected... 

Plotz J, Schreiber W. Vergleichende Untersuchung von Atracurium und Alcuronium zur Intubation alterer Patienten in Halothannarkose. [Comparative study of atracurium and alcuronium for the intubation of older patients in halothane anesthesia.] Anaesthesist 1984 33(11) 548-51. 

Stirt JA, Murray AL, Katz RL, Schehl DL, Lee C. Atracurium during halothane anesthesia in humans. Anesth Analg 1983 62(2) 207-10. 

In the nucleus accumbens of rats the dopamine concentration was increased by both cyclopropane and halothane anesthesia cyclopropane, but not halothane, also increased the dopamine concentration in the caudate nucleus halothane, but not cyclopropane, significantly reduced the dopamine concentration in the ventral nucleus of the thalamus (4). It has been suggested that potentiation of the actions of dopamine could occur with cyclopropane or halogenated hydrocarbon anesthetics, but there is no direct evidence that this interaction occurs in humans. 

Mazze RI, Calverley RK, Smith NT. Inorganic fluoride nephrotoxicity prolonged enflurane and halothane anesthesia in volunteers. Anesthesiology 1977 46(4) 265-71. 

The importance of multiple anesthetics should not be overlooked. For example, patients in whom halothane anesthesia is given twice, at an interval of less than 6 weeks, are at major risk of developing jaundice. Some anesthetists avoid any second exposure to this agent. However, there are several reasons why single agents are often insufficient in anesthesia different problems require separate treatments the severity of the adverse effects of indi-vidual drugs can sometimes be reduced by... 

Rubiano R, Chang JL, Carroll J, Sonbolian N, Larson CE. Acute rhabdomyolysis following halothane anesthesia without succinylcholine. Anesthesiology 1987 67(5) 856-7. 

Bundle branch block and aberrant conduction were noted in children during halothane anesthesia (8). 

In a double-blind, randomized, controlled study of 77 children undergoing halothane anesthesia for adenoidect-omy, the effects of atropine 0.02 mg/kg, glycopyrrolate 0.04 mg/kg, and physiological saline were compared (9). There was no difference in the incidence of ventricular dysrhythmias. Atropine prevented bradycardia but was associated with sinus tachycardia in most patients. The bradycardias that occurred in the groups that received glycopyrrolate or placebo were short-lived and resolved spontaneously. 

Pulsus altemans in association with hjrpercapnia occurred in a study of 120 patients who breathed spontaneously during halothane anesthesia (10). End-tidal... 

Preterm infants can become apneic during the immediate postoperative period, even if the ventilatory response to CO2 is not depressed after halothane anesthesia (12). In a prospective study in 167 preterm infants after inguinal herniorrhaphy with halothane/nitrous oxide anesthesia, only one had an episode of apnea up to 2 days postoperatively however, the authors recommended careful monitoring until complete recovery from anesthesia has occurred (13). 

Postoperative nausea and vomiting can occur after halothane anesthesia (24). In one series, postoperative vomiting occurred in 13 of 29 patients who had received halothane for induction, but when dyxirazine was added during anesthesia the incidence of postoperative vomiting was significantly reduced (three of 29 patients) (25). 

Bruchiel KJ, Stockard JJ, Calverley RK, Smith NT, Scholl ML, Mazze Rl. Electroencephalographic abnormalities following halothane anesthesia. Anesth Analg 1978 57(2) 244-51. 

Sessler DI, Olofsson Cl, Rubinstein EH, Beebe JJ. The thermoregulatory threshold in humans during halothane anesthesia. Anesthesiology 1988 68(6) 836-42. 

The potentiation of D-tubocurarine block produced by enflurane slowly continues to increase with time, even after the usual equilibration period has passed (SEDA-5, 132) (128). This does not occur with halothane, and the discrepancy is said to mean that more D-tubocurarine will be required in the first hour of enflurane anesthesia than during equipotent halothane anesthesia, but that thereafter less will be required during enflurane anesthesia. It has been suggested that enflurane, unhke halothane, may produce an effect on muscle that takes time to develop. This may also be part of the mechanism, in addition to the... 

Rupp SM, Miller RD, Gencarelli PJ. Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans. Anesthesiology 1984 60(2) 102-5. 

Halothane anesthesia increases the risks of tachydys-rhythmias when pancuronium is used (47). 

Phenol is cardiotoxic, and varions cardiac dysrhythmias have been noted after apphcation to the skin, or less commonly when it has been nsed for nenrolysis. Ventricular extra beats occurred during topical apphcation of phenol and croton oil in hexachlorophene soap and water for chemical peehng of a giant hairy nevus (12). Three of sixteen children treated with motor point blocks for cerebral palsy with a phenohc solution under halothane anesthesia developed cardiac dysrhythmias (13). Severe cardiac dysrhythmias followed by circulatory arrest occurred in an elderly patient with pancreatic cancer, injected with a phenohc solution to produce splanchnic neurolysis (14). The authors recommended that ethanol should replace phenol for this purpose. 

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