Halogenated Anaesthetics

Halothane was the first halogenated agent to be used widely, but in the developed world it has been largely superseded by isoflurane and sevoflurane.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:

Isoflurane

Isoflurane is a volatile colourless liquid, which is not flammable at normal anaesthetic concentrations. It is relatively insoluble, and has a lower blood/gas coefficient than halothane or enflurane, which allows rapid adjustment of the depth of anaesthesia. It has a pungent odour and can cause bronchial irritation, which makes inhalational induction unpleasant. Isoflurane is minimally metabolised (0.2%), and none of the breakdown products has been related to anaesthetic toxicity.

Respiratory effects. Isoflurane causes respiratory depression: the respiratory rate increases, tidal volume decreases, and the minute volume is reduced. The ventilatory response to carbon dioxide is diminished. Although it irritates the upper airway it is a bronchodilator.

Cardiovascular effects. Anaesthetic concentrations of isoflurane, i.e. 1-1.5 MAC, cause only a slight impairment of myocardial contractility and stroke volume and cardiac output is usually maintained by a reflex increase in heart rate. Isoflurane causes peripheral vasodilatation and reduces blood pressure. It does not affect atrioventricular conduction and does not sensitise the heart to catecholamines. Low concentrations of isoflurane (< 1 MAC) do not increase cerebral blood flow or intracranial pressure, and cerebral autoregulation is maintained. Isoflurane is a potent coronary vasodilator and in the presence of a coronary artery stenosis it may cause redistribution of blood away from an area of inadequate perfusion to one of normal perfusion. This phenomenon of 'coronary steal' may cause regional myocardial ischaemia.

Other effects. Isoflurane relaxes voluntary muscles and potentiates the effects of nondepolarising muscle relaxants. Isoflurane depresses cortical EEG activity and does not induce abnormal electrical activity or convulsions.

Sevoflurane is a chemical analogue of isoflurane. It is less chemically stable than the other volatile anaesthetics in current use. About 3% is metabolised in the body and it is degraded by contact with carbon dioxide absorbents, such as soda lime. The reaction with soda lime causes the formation of a vinyl ether (Compound A), which may be nephrotoxic. Sevoflurane is less soluble than isoflurane and is very pleasant to breathe, which makes it an excellent choice for inhalational induction of anaesthesia, particularly in children. The respiratory and cardiovascular effects of sevoflurane are very similar to isoflurane.

Enflurane is a structural isomer of isoflurane. It is more soluble than isoflurane. It causes more respiratory depression than the other volatile anaesthetics and hypercapnia is almost inevitable in patients breathing spontaneously. It causes more cardiovascular depression than isoflurane and is occasionally associated with cardiac arrythmias. Two percent of enflurane is metabolised and prolonged administration or use in enzyme-induced patients generates sufficient free inorganic fluoride from the drug molecule to cause polyuric renal failure. There have been a few cases of jaundice and heptatoxicity associated with enflurane but the incidence of about one in 1-2 million anaesthetics is lower than with halothane.

Desflurane has the lowest blood / gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised; this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and cannot be administered with conventional vaporisers. It has a very pungent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia.

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe and is second choice to sevoflurane for inhalational induction of anaesthesia. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia; arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 363).

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 immune 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.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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