Side Effects of Anticholinesterases
Cardiovascular Effects
Because only the nicotinic effects of edrophonium, neostigmine,
and pyridostigmine are desired, the muscarinic effects must be blocked by atropine
or glycopyrrolate.[27]
Atropine induces its vagolytic
effect much more rapidly than glycopyrrolate does. To minimize cardiovascular changes,
atropine is better suited for administration with the rapid-acting edrophonium,[27]
and glycopyrrolate is better suited for administration with the slower-acting neostigmine
and pyridostigmine.[628]
In general, 7 to 10 µg/kg
of atropine should be given with 0.5 to 1.0 mg/kg of edrophonium.[585]
Atropine administration 30 seconds before edrophonium will decrease the ventricular
ectopy associated with this anticholinesterase.[629]
Glycopyrrolate (7 to 15 µg/kg) should be given with neostigmine (40 to 70
µg/kg). Administration of atropine with pyridostigmine will induce an initial
tachycardia,[630]
and giving glycopyrrolate with
edrophonium may result in an initial bradycardia unless it is administered at least
1 minute earlier.[631]
Dysrhythmias can occur,
[631]
[632]
[633]
[634]
[635]
and
anticholinesterases
should be used with caution in patients with autonomic neuropathy.[632]
When cardiac dysrhythmias are a concern, glycopyrrolate may be preferable to atropine,
[635]
and the anticholinesterases and anticholinergics
should be administered over a longer period (e.g., 2 to 5 minutes) to reduce the
incidence and severity of the disorders of rhythm.
Nausea and Vomiting
Reports on the effect of anticholinesterase administration on
postoperative nausea and vomiting are conflicting. Neostigmine administration has
been implicated as a cause of postoperative nausea and vomiting.[636]
[637]
It has also been described as having antiemetic
properties[638]
and as having no impact on postoperative
nausea and vomiting.[639]
A meta-analysis by Tramer
and Fuchs-Bader[640]
looked at the results of anticholinesterase
administration in over 1100 patients. They found a dose-response relationship for
the incidence of nausea and vomiting after the administration of neostigmine. The
highest incidence of emesis after the administration of 1.5 mg neostigmine was lower
than the lowest incidence of emesis after the administration of 2.5 mg neostigmine.
Discrepancies in the other studies may have been at least in part attributable to
different dosing regimens. Although emesis will develop in one in three to six patients
after the administration of neostigmine, the authors did not recommend letting all
patients recover spontaneously because this practice introduced the risk of patients
having postoperative residual paralysis. A more recent study demonstrated the hazards
of not antagonizing residual neuromuscular blockade at least 2 hours after the administration
of two times the ED95
of vecuronium, rocuronium, or atracurium.[55]
Two hours after administration of these agents, 10% of 526 patients had TOF ratios
less than 0.7 and 37% had TOF ratios less than 0.9.
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