- 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).
- With the exception of mivacurium, nondepolarizing
agents are not significantly metabolized by either acetylcholinesterase
or pseudocholinesterase. Reversal of their blockade depends on redistribution,
gradual metabolism, and excretion of the relaxant by the body, or
administration of specific reversal agents (eg, cholinesterase inhibitors)
that inhibit acetylcholinesterase enzyme activity.
- Muscle relaxants owe their paralytic properties
to mimicry of ACh. For example, succinylcholine consists of two
joined ACh molecules.
- Compared with 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, 4–6 h) following succinylcholine
- Succinylcholine is considered 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.
- As a general rule, the more potent the nondepolarizing
muscle relaxant the longer its speed of onset.
- Doxacurium, pancuronium, vecuronium, and pipecuronium
are partially excreted by the kidneys, and their action is prolonged
in patients with renal failure.
- Cirrhotic liver disease and chronic renal 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.
- Mivacurium, like succinylcholine, is metabolized
by pseudocholinesterase. It is only minimally metabolized by true
- 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
- Long-term administration of vecuronium to patients
in intensive care units has resulted in prolonged neuromuscular
blockade (up to several days), 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.
Skeletal muscle relaxation can be produced by deep
inhalational anesthesia, regional ...