Atracurium

Atracurium is an intermediate acting relaxant, is virtually devoid of side-effects, and is suitable for administration by continuous infusion. It releases histamine only at higher doses and this does not appear to be a problem in ICU patients. Its novel mode of metabolism makes it popular for use in the ICU. In the normal healthy individual, about 60 per cent is metabolized by esterases in the liver, while the remainder undergoes spontaneous degradation in the plasma by the Hofmann elimination reaction. Because the Hofmann reaction is completely independent of all organ systems, minimal prolongation of action is seen in the presence of liver and/or renal impairment. Recovery is predictable and it can be reliably expected that the effect will have worn off about 1 h after an infusion is terminated.

The metabolic products of atracurium include laudanosine and acrylates. Although acrylates are potentially hepatotoxic, they are produced in insignificant amounts. More interest has centered around laudanosine, a drug which produces cerebral excitation in certain laboratory animals. Laudanosine accumulates in patients who have received a prolonged infusion of atracurium, particularly in the presence of impaired renal function. It is not known whether laudanosine is toxic in humans and, if so, the plasma concentration at which this might occur. It appears unlikely, on present evidence, that laudanosine is of clinical relevance.

An interesting phenomenon has been observed when atracurium is administered by continuous infusion for several days. After a delay of about 2 to 4 days, resistance to its action begins to develop and an increased infusion rate is required in order to maintain a constant degree of paralysis. This is not observed in every patient and the mechanism is unclear.

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