Other Factors That May Interfere with Antagonism
It is not advisable to administer further anticholinesterase if
maximal doses of edrophonium (1.5 mg/kg), neostigmine (70 µg/kg), or pyridostigmine
(350 µg/kg) fail to antagonize residual blockade.[590]
[592]
These doses inhibit acetylcholinesterase
completely,
and if they fail to fully antagonize residual blockade, another likely cause of the
inadequate antagonism should be sought. Some of these additional potential causes
of inadequate antagonism of neuromuscular blockade are described in the following
sections.
Acid-Base State
Both metabolic and respiratory acidosis may augment a nondepolarizing
neuromuscular blockade, but only respiratory acidosis prevents adequate antagonism.
[588]
[618]
[619]
The probability of achieving adequate antagonism of nondepolarizing neuromuscular
blockade in the presence of significant respiratory acidosis (PaCO2
greater than 50 mm Hg) is low. Therefore, if a patient hypoventilates, attempts
to antagonize a residual block may fail. Administration of narcotics to relieve
pain may, by producing hypoventilation, increase the likelihood of this adverse event.
Although metabolic acidosis might also be predicted to prevent
antagonism by neostigmine, this theory has not been substantiated.[588]
[618]
[619]
Metabolic
alkalosis, but not metabolic acidosis, prevents neostigmine antagonism of dTc and
pancuronium.[588]
[618]
[620]
These results suggest that
the extracellular hydrogen ion concentration (pH) may not be as important as changes
in electrolytes and intracellular pH.
Electrolyte Imbalance
Although it has been the subject of review articles,[621]
few data are available on the effect of electrolyte imbalance on antagonism of nondepolarizing
neuromuscular blockade by neostigmine. Low extracellular concentrations of potassium
enhance the blockade from nondepolarizing neuromuscular blockers and diminish the
ability of neostigmine to antagonize the blockade. This effect is based on the increase
in end-plate transmembrane potential that results from a higher ratio of intracellular
to extracellular potassium. Thus, a decrease in extracellular potassium causes hyperpolarization
and produces resistance to depolarization. Patients with an imbalance in potassium
may have other diseases or injuries that alter their response to neuromuscular blockers
(e.g., patients with burns). Cohen[622]
and Feldman
[621]
speculated that in chronic diseases, both
intracellular
and extracellular potassium is depleted with little net effect on transmembrane potential.
Therefore, the response to neuromuscular blockers and their antagonists should be
normal. However, muscle transmembrane potentials are changed in patients who are
severely ill or bedridden for a few days.[623]
In addition, severe dehydration will concentrate the neuromuscular blocker present
in plasma, in effect decreasing the volume of distribution and increasing muscle
relaxant activity. In an animal model of chronic hypokalemia, cats were given a
diuretic without potassium supplementation for 15 days. Less pancuronium was required
for neuromuscular blockade and more neostigmine for antagonism.[624]
Even though the differences were small, the blockade was always antagonized completely.
Assuming that this animal model approximates the clinical situation, changes in
potassium appear to be of relatively minor consequence with respect to the clinical
question of adequacy of reversal.
Other Factors
The calcium channel blocker verapamil will potentiate nondepolarizing
neuromuscular blocking drugs and may make it difficult to achieve adequate reversal
of blockade.[625]
[626]
When attempting reversal of neuromuscular blockade in patients receiving verapamil,
edrophonium may be more effective than neostigmine.[625]
[626]
Other factors that may interfere with antagonism
are hypothermia and the administration of antibiotics, particularly the aminoglycoside
or polypeptide classes (see "Drug Interactions").[467]
[468]
[469]
[470]
[471]
[472]
[473]
[474]
In the case of antibiotics, administration
of an anticholinesterase may in fact deepen the blockade. Monitoring with a nerve
stimulator, if aminoglycosides have been administered,[627]
may give misleading results.
