Elderly Patients (also see Chapter
62
)
The pharmacodynamics of neuromuscular blockers is altered in elderly
patients. A number of physiologic changes accompany the aging process, including
decreases in total-body water, increases in total-body fat, decreases in hepatic
and renal blood flow, and decreases in cardiac reserve, which account for the altered
responses of the elderly to neuromuscular blockers. A number of physiologic and
anatomic changes at the neuromuscular junction also occur with aging. These changes
include an increase in the distance between the junctional axon and the motor end
plate, flattening of the folds of the motor end plate, a decreased concentration
of acetylcholine receptors at the motor end plate, a decrease in the amount of acetylcholine
in each vesicle in the prejunctional axon, and decreased release of acetylcholine
from the preterminal axon in response to a neural impulse.[687]
As shown by Matteo and coworkers,[688]
despite
these age-related changes, acetylcholine receptor sensitivity to nondepolarizing
neuromuscular blockers is not altered by advancing age ( Fig.
13-34
). That is, the elderly and young adults have similar degrees of
neuromuscular blockade at the same plasma concentration of a neuromuscular blocker.
Rather, it appears that in the elderly, decreased splanchnic and renal blood flow,
decreased glomerular filtration rate, and decreased hepatic function are responsible
for the prolonged duration of action of most neuromuscular blockers. The greater
depth of blockade with a given dose of relaxant in elderly patients versus young
patients may also be due in part to altered volumes of distribution. The impact
of aging alone, versus disease states often associated with the aging process, may
be difficult to distinguish when identifying mechanisms of altered neuromuscular
blocker action in the elderly.
Pancuronium,[688]
[690]
metocurine,[688]
dTc,[688]
vecuronium,[569]
[665]
[691]
and rocuronium[354]
all show altered pharmacodynamics and pharmacokinetics in the elderly patient population.
Decreased clearance of each of these drugs from plasma explains the prolonged duration
of action in these patients. These neuromuscular blockers depend on the kidney or
the liver (or both) for their metabolism and elimination.
Figure 13-34
Correlation of plasma metocurine concentration versus
percent paralysis (twitch depression) in young and elderly patients (open
and closed circles). Differences are not significant. (Redrawn
from Matteo RS, Backus WW, McDaniel DD, et al: Pharmacokinetics and pharmacodynamics
of d-tubocurarine and metocurine in the elderly.
Anesth Analg 64:23–29, 1985.)
Surprisingly, the pharmacokinetics and pharmacodynamics of the
long-acting neuromuscular blockers doxacurium[692]
and pipecuronium,[693]
which rely almost exclusively
on the kidney for elimination, do not seem to be significantly different in the elderly.
The duration of neuromuscular blockade induced by doxacurium has been found to be
more variable in the elderly than in younger patients and tends to be longer. However,
clearance and elimination half-lives are the same in the two patient groups. Similarly,
recovery from pipecuronium-induced neuromuscular blockade, the volume of distribution,
clearance, and the elimination half-life of the drug are the same in young and old
patients. Further studies in the elderly with doxacurium and pipecuronium may be
needed to better define this issue.
In the case of drugs whose elimination is independent of hepatic
or renal blood flow, their pharmacokinetics and pharmacodynamics should be unaffected
by age. This is true of atracurium, which depends on Hofmann degradation for its
clearance.[242]
[694]
Cisatracurium, which also undergoes Hofmann elimination, has a delayed onset of
effect in elderly patients.[343]
[359]
The duration of action of the relaxant, however, appears to not be influenced by
advanced age. The prolonged elimination half-life of the drug in the elderly is
due to an increased volume of distribution. Clearance is not decreased with advanced
age.
Butyrylcholinesterase activity in the elderly, though still in
the normal range, is decreased by approximately 26% when compared with that in young
adults.[695]
Because mivacurium is metabolized
by butyrylcholinesterase, its clearance is likely to be slightly reduced in the elderly;
as a result, the duration of action is 20% to 25% longer,[696]
and the infusion requirement to maintain a stable depth of blockade is decreased.
[697]
In general, when maintaining a neuromuscular blockade with nondepolarizing
neuromuscular blockers in elderly patients, one can expect that with the exception
of atracurium and cisatracurium, the dosing interval will be increased and fewer
doses of neuromuscular blocker will be required to maintain the desired depth of
neuromuscular blockade. The choice of agent and the use of monitoring of the depth
of blockade are exceptionally important in this population because recovery of neuromuscular
function is generally delayed in the elderly. Inadequate or incomplete recovery
of muscle strength after the use of pancuronium is associated with an increased incidence
of perioperative pulmonary complications in this patient population.[60]
