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KEY CONCEPTS
It is important to realize that muscle relaxation does not ensure unconsciousness, amnesia, or analgesia.
Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists, whereas nondepolarizing muscle relaxants function as competitive antagonists.
Because depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by another enzyme, pseudocholinesterase (nonspecific cholinesterase, plasma cholinesterase, or butyrylcholinesterase).
Muscle relaxants owe their paralytic properties to mimicry of ACh. For example, succinylcholine consists of two joined ACh molecules.
In contrast to patients with low enzyme levels or heterozygous atypical enzyme in whom blockade duration is doubled or tripled, patients with homozygous atypical enzyme will have a very long blockade (eg, 4–8 h) following succinylcholine administration.
Succinylcholine is considered relatively contraindicated in the routine management of children and adolescents because of the risk of hyperkalemia, rhabdomyolysis, and cardiac arrest in children with undiagnosed myopathies.
Normal muscle releases enough potassium during succinylcholine-induced depolarization to raise serum potassium by 0.5 mEq/L. Although this is usually insignificant in patients with normal baseline potassium levels, a life-threatening potassium elevation is possible in patients with burn injury, massive trauma, neurological disorders, and several other conditions.
Pancuronium and vecuronium are partially excreted by the kidneys, and their action is prolonged in patients with kidney failure.
Cirrhotic liver disease and chronic kidney failure often result in an increased volume of distribution and a lower plasma concentration for a given dose of water-soluble drugs, such as muscle relaxants. On the other hand, drugs dependent on hepatic or renal excretion may demonstrate prolonged clearance. Thus, depending on the drug, a greater initial dose—but smaller maintenance doses—might be required in these diseases.
Atracurium and cisatracurium undergo degradation in plasma at physiological pH and temperature by organ-independent Hofmann elimination. The resulting metabolites (a monoquaternary acrylate and laudanosine) have no intrinsic neuromuscular blocking effects.
Hypertension and tachycardia may occur in patients given pancuronium. These cardiovascular effects are caused by the combination of vagal blockade and catecholamine release from adrenergic nerve endings.
After long-term administration of vecuronium to patients in intensive care units, prolonged neuromuscular blockade (up to several days), may be present after drug discontinuation, possibly from accumulation of its active 3-hydroxy metabolite, changing drug clearance, or the development of a polyneuropathy.
Rocuronium (0.9–1.2 mg/kg) has an onset of action that approaches succinylcholine (60–90 s), making it a suitable alternative for rapid-sequence inductions, but at the cost of a much longer duration of action. The new reversal agent, sugammadex, permits rapid reversal of rocuronium-induced neuromuscular blockade.
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Skeletal muscle relaxation can be produced by deep inhalational anesthesia, regional nerve block, or neuromuscular blocking agents (commonly called muscle relaxants). In 1942, Harold Griffith published the results of a study using an extract of curare (a South American arrow poison) during anesthesia. Following the introduction of succinylcholine as a “new approach to muscular relaxation,” these agents rapidly became a routine part of the ...