Cynthia A. Lien, M.D.
Associate Professor of Anesthesiology, Cornell University
New York Presbyterian Hospital
calien@mail.med.cornell.edu
Aging affects the neuromuscular junction in many ways. The
distance between the junctional axon and the motor end-plate
is increased; the folds of the motor end-plate are flattened;
the concentration of acetylcholine receptors at the motor end-plate
is decreased; the amount of acetylcholine in the junctional
vesicles is decreased; and the amount of acetylcholine released
is also decreased. In spite of all of these changes in the neuromuscular
junction, alterations in the pharmacodynamics of nondepolarizing
neuromuscular blocking agents in the elderly are largely due
to alterations in the pharmacokinetics of these agents. Sensitivity
of the acetylcholine receptor to neuromuscular blocking agents
is not affected by advanced age. Altered pharmacokinetics are
the result of decreases in hepatic and renal blood flow and
function that occur with advanced age as well as altered volumes
of distribution of relaxants in geriatric patients.
Clearance is decreased in the elderly for those nondepolarizing
muscle relaxants that depend primarily on either the kidney
or the liver for their elimination from the plasma. The long-acting
agents metocurine, pancuronium and d-tubocurarine have all been
found to have a prolonged duration of action in the elderly.
Surprisingly, the newer long-acting relaxants, doxacurium and
pipecuronium, which still depend on renal mechanisms for elimination
from the body, seem to have pharmacodynamics that are unaffected
by advanced age. Of the intermediate-acting relaxants, vecuronium
and rocuronium, both of which depend on end-organ elimination
from the body, have prolonged durations of action. Atracurium
and cisatracurium, which depend on the kidney only as a secondary
means of elimination from the body, do not have a prolonged
duration of action in the elderly. They are eliminated primarily
by Hofmann elimination, which is a temperature and base catalyzed
process of spontaneous degradation. The process is not affected
by advanced age. Mivacuriumâs duration of action in the elderly
is prolonged because of the decreases in plasma cholinesterase
activity that accompany aging.
In choosing a nondepolarizing neuromuscular blocking agent
to provide relaxation during an anesthetic, the use of the intermediate-acting
agents is prudent as the duration of action of even a single
dose of a long-acting agent may be too prolonged for the planned
surgery. Mivacuriumâs only potential advantage as a muscle relaxant
with a short duration of action may be lost in the elderly as
it may behave pharmacokinetically as an intermediate-acting
relaxant. In general, when maintaining neuromuscular blockade
with nondepolarizing relaxants one can expect that the dosing
interval will be increased and that fewer doses of relaxant
will be required to maintain the desired depth of neuromuscular
block. Atracurium and cisatracurium may be the only exceptions
to this.
The choice of nondepolarizing neuromuscular blocking agent
and monitoring of the depth of blockade are exceptionally important
in this patient population as recovery of neuromuscular function
is generally delayed in the elderly. Inadequate or incomplete
recovery of neuromuscular function is associated with a greater
incidence of perioperative pulmonary complications.
Bibliography:
- Frolkis VV, Martynenko OA, Zamostyan VP. Aging of the neuromuscular
apparatus. Gerontology. 1976; 22(4):244-279.Matteo
RS, Backus WW, McDaniel DD, et al.
- Pharmacokinetics and pharmacodynamics of d-tubocurarine
and metocurine in the elderly. Anesth Analg. 1985;
64(1):23-29.
- Berg H, Roed J, Viby-Mogensen J, et al. Residual neuromuscular
block is a risk factor for postoperative pulmonary complications.
A prospective, randomised, and blinded study of postoperative
pulmonary complications after atracurium, vecuronium and pancuronium.
Acta Anaesthesiol Scand. 1997; 41(9):1095-1103.