Halothane development

A child who underwent induction of anesthesia with halothane developed hiccups associated with pulmonary edema (17). 

An isomer of enflurane named isoflurane (l-chloro-2,2,2-tnfluoroethyl difluoromethyl ether) does not produce uncontrolled movements, is nonflammable, and IS metabolized to an even lesser extent than enflurane [7] As of this wntmg, isoflurane is the fastest growing anesthebc m more economically developed coun tries, but because of cost, it has not overtaken halothane in the rest of the world... 

Contraction is a general term that refers to the mechanically activated state of myofibrils which is usually caused by action potentials). Contracture means muscle shortening or tension development, which is not triggered by action potentials), e.g. K+ contracture, and caffeine or halothane contracture. The word is also used for deformity or distortion of fingers, hand or limb, such as Dupuytren s or Volkmann s contracture. 

In a joint halothane-caffeine contracture test, both caffeine and halothane are used. A positive test is defined as the development of 1 g contracture after exposure of viable muscle fibers to a concentration of 1 mM or less caffeine in the presence of 1% halothane. 

Weissenburger, J., Nesterenko, V.V. and Antzelevitch, C. (2000) Transmural heterogeneity of ventricular repolarization under baseline and long QTconditions in the canine heart in vivo torsades de pointes develops with halothane but not pentobarbital anesthesia. Journal of Cardiovascular Electrophysiology, 11, 290-304. 

Hepatitis occasionally occurs in patients after clinical anesthesia. Typically, 2-5 days after anesthesia, a fever develops, accompanied by anorexia, nausea, and vomiting. There may be a progression to hepatic failure, and death occurs in about 50% of these patients. The incidence of the syndrome is 1 in 10,000 anesthetic administrations, and it is seen most often after repeated administration of halothane over a short period of time. 

The arrhythmias associated with halothane or cyclopropane anesthesia have been attributed to the interaction of the anesthetic with catecholamines, and they have been suppressed by IV administration of 1 to 3 mg propranolol. An increase in circulating catecholamines also has been observed in patients with acute myocardial infarction and has been correlated with the development of arrhythmias. 

Although both metabolic and immune factors may be involved in the aetiology of severe hepatitis after halothane the aetiology of postanaesthetic/postsurgical hepatitis is far from clear. A recent study revealed that paediatric anaesthesiologists had high titres of serum autoantibodies which react with specific hepatic proteins. Since the vast majority of these individuals have not developed hepatitis the pathological role of autoantibodies in volatile anaesthetic-induced hepatitis remains questionable (Njoku and co-workers 2002). 

Halothane, isoflurane, and enflurane have similar depressant effects on the EEG up to doses of 1-1.5 MAC. At higher doses, the cerebral irritant effects of enflurane may lead to development of a spike-and-wave pattern and mild generalized muscle twitching (ie, myoclonic activity). However, this seizure-like activity has not been found to have any adverse clinical consequences. Seizure-like EEG activity has also been described after sevoflurane, but not desflurane. Although nitrous oxide has a much lower anesthetic potency than the volatile agents, it does possess both analgesic and amnesic properties when used alone or in combination with other agents as part of a balanced anesthesia technique. 

Postoperative hepatic dysfunction is typically associated with factors such as blood transfusions, hypovolemic shock, and other surgical stresses rather than volatile anesthetic toxicity. However, a small subset of individuals who have been previously exposed to halothane may develop potentially life-threatening hepatitis. The incidence of severe hepatotoxicity following exposure to halothane is in the range of one in 20,000-35,000. Obese patients who have had more than one exposure to halothane during a short time interval may be the most susceptible. There is no specific treatment for halothane hepatitis, and therefore liver transplantation may ultimately be required in the most severe cases. 

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. 

For almost 30 years, from its introduction in 1956, halothane was the standard of comparison for inhaled anesthetics. However, the onset of its anesthetic action is slow compared with many intravenous agents, and the rate of recovery from its anesthetic effects is not rapid. In addition, its hepatic metabolism to a reactive compound may lead to development of halothane-associated hepatitis. 

Halothane was the first halogenated agent to be used widely, but in the developed world it has been largely superseded by isoflurane and sevoflurane. We provide a detailed description of isoflurane, and of the others in so far as they differ. The MAC of some volatile agents is ... 

About 20% of halothane is metabolised and it induces hepatic enzymes, including those of anaesthetists and operating theatre staff. Hepatic damage occurs in a small proportion of exposed patients. Typically fever develops 2 or 3 days after anaesthesia accompanied by anorexia, nausea and vomiting. In more severe cases this is followed by transient jaundice or, very rarely, fatal hepatic necrosis. Severe hepatitis is a complication of repeatedly administered halothane anaesthesia and has an incidence of 1 50000. It follows immime sensitisation to an oxidative metabolite of halothane in susceptible individuals. This serious complication, along with the other disadvantages of halothane and the popularity of sevoflurane for inhalational induction, has almost eliminated its use in the developed world. It remains in common use other parts of the world because it is comparatively inexpensive. 

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