Inhalational General Anesthetics


Halothane, a halogenated hydrocarbon, was first synthesized in 1951. It was introduced into clinical practice in 1956 in the United Kingdom and in 1958 in the United States. It quickly replaced the other volatile agents because


it was nonflammable, easy to administer, and relatively safe. Halothane, enflurane, isoflurane, and sevoflurane depress cerebral metabolism, with isoflurane having the greatest effect.y Electrical activity of the cerebral cortex recorded by a fronto-occipital electroencephalogram (EEG) shows progressive replacement of fast, low-voltage activity by slow, high-amplitude waves as anesthesia gets deeper. y Since cerebral blood flow generally increases during halothane anesthesia, cerebrospinal fluid (CSF) pressure increases. After several hours of anesthesia with halothane, the changes in cerebral blood flow and metabolism return to normal. Recovery of mental function after anesthesia with halothane is not complete for several hours. y

Tonic-clonic activity and spike and wave EEG complexes have been reported with enflurane anesthesia. Deepening anesthesia and hyperventilation may exacerbate these phenomena. This excitatory action of enflurane does not appear to be associated with aggravation of seizures in epileptic patients; nevertheless, enflurane is best avoided in such patients. y , y

Rarely, the induction of anesthesia with halothane or any of the other halogenated inhalational anesthetics triggers an uncontrolled hypermetabolic reaction in the skeletal muscle of susceptible patients. There is defective uptake of Ca 2+ by the sarcoplasmic reticulum resulting in elevation of intracellular free Ca 2+ levels. The resultant syndrome of malignant hyperthermia has an incidence of 1 in 12,000 and a mortality rate of 24 percent. y It is more common in men and children, in association with various myopathies, and in genetically susceptible individuals. The order in which available agents cause malignant hyperthermia is halothane, which is greater than enflurane, which, in turn, is greater than isoflurane. The concomitant use of suxamethonium and gallamine, neuroleptics, infection, stress, heat, and alcohol tend to increase the risk of malignant hyperthermia. Larach and colleagues demonstrated that generalized muscle rigidity that occurs as a result of an anesthetic is a valuable, but not absolute, predictor of a patient's susceptibility to malignant hyperthermia, its presence being associated with an 18-fold increase in risk of being susceptible, as determined by subsequent muscle biopsy testing. y

Clinically, there is a rapid rise in body temperature, generalized muscular rigidity, high metabolic rate with increased oxygen consumption and carbon dioxide production, tachycardia, tachyarrythmias, metabolic acidosis, and hyperkalemia. The most reliable method of diagnosis is by muscle biopsy and in vitro contracture tests with halothane and caffeine.'d Treatment consists of cessation of known triggering agents, supportive measures, and the administration of dantrolene.


Nitrous oxide (N2 O), or so-called laughing gas, was first used as a dental anesthetic. Although when it is used by itself it produces a light level of anesthesia, when it is used to supplement more potent anesthetics, it reduces the dose requirements for those other agents. However, its euphorogenic properties, ready availability, and low cost have contributed to its popularity as a recreational gas. Human nitrous oxide toxicity is associated with its occupational, iatrogenic, and recreational use.

Nitrous oxide toxicity is due to inactivation of methionine synthase, a vitamin B 12 -dependent enzyme, resulting in defective biosynthesis of DNA and myelin in nervous tissue. Monkeys exposed to 15 percent nitrous oxide develop the biochemical changes and neurological signs of vitamin B 12 deficiency very rapidly. Morphologically, their spinal cords show degeneration of both the myelin sheaths and axis cylinders in the posterior columns and in the lateral and anterior corticospinal and spinocerebellar tracts. y

Nitrous oxide is more likely to produce megaloblastosis or subacute combined degeneration-like clinical presentation when it is used repetitively or for periods longer than 3 hours or in individuals with vitamin B12 deficiency. Occupational exposure of medical and dental personnel during its use as an analgesic is not likely to produce adverse neurological effects except in vitamin B12 -deficient individuals or in those routinely exposed to high nitrous oxide levels. '15' An epidemiological survey of over 30,000 dental personnel occupationally exposed to nitrous oxide found an incidence of neurological complaints of less than 2 percent in the population at risk.'14' In the elderly, in whom subclinical vitamin B12 deficiency reportedly ranges from 7.3 to 21 percent, the frequency of neuropathic symptoms after anesthesia due to nitrous oxide may be underrecognized.y

Clinically, nitrous oxide neuropathy presents with numbness, paresthesias, ataxia, and clumsiness in the extremities. Many but not all of the symptoms resolve with time if exposure is discontinued. With further exposure, weakness, gait disturbance, impotence, and loss of sphincter control can occur. y Administration of folinic acid or methionine have been shown to protect against megaloblastosis and neurotoxicity occurring following nitrous oxide administration. y

Tension pneumoencephalus can follow any intracranial neurosurgical procedure if nitrous oxide has been used. Following dural closure, the increase in volume due to nitrous oxide can result in pressure changes that may lead to seizures, brain stem herniation, and death. Discontinuing nitrous oxide at the time of dural closure can prevent tension pneumoencephalus. Nitrous oxide can expand air emboli in the blood stream. In patients undergoing posterior fossae exploration in the sitting position, nitrous oxide increases the risk of air emboli and should be avoided. '14

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