Pharmacology

Since the introduction of the muscle relaxants in 1942 many potential relaxants have been synthesized, although only a few have become established in clinical practice. Although every agent has been administered to intensive care unit (ICU) patients at some time, we only need to consider five in any detail: succinylcholine (suxamethonium), pancuronium, atracurium, vecuronium, and cisatracurium. The other agents currently available possess a number of undesirable properties which severely limit their use.

The principal differences between the available drugs are speed of onset, duration of action, route of elimination, and side-effects. A rapid onset is of importance when tracheal intubation must be secured without delay, a situation which does not often pertain in the ICU. An intermediate duration of action is convenient because it offers better control than a long-acting drug. The rate of consumption of a short-acting drug would be excessive. Impairment of renal and/or hepatic function are common in the critically ill patient, and ideally any drug should rely as little as possible on either of these systems for elimination. Finally, many critically ill patients have significant cardiovascular instability and drugs should possess minimal side-effects.

A number of pathophysiological changes which may modify the action of a relaxant commonly occur in the critically ill patient. Acidosis (respiratory or metabolic), hypothermia, hypokalemia, hypocalcemia, hypernatremia, and hypermagnesemia may all potentiate a block. Pre-existing muscular or neuromuscular disorders (e.g. myasthenia gravis, myotonias, and muscular dystrophies) prolong a block. Many other drugs may modify the action of muscle relaxants. Important interactions include potentiation of succinylcholine by neostigmine, ecothiopate, alkylating agents, and trimetaphan, and potentiation of the non-depolarizing agents by calcium-channel blockers, aminoglycoside antibiotics, immunosuppressants, furosemide (frusemide), local analgesics, and lithium.

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