Sympathomimetic Drugs (also see
Chapter 16
)
Many antiasthmatic drugs (bronchodilators) such as terbutaline,
aminophylline, and theophylline are sympathomimetic drugs that can interact with
volatile anesthetics to cause cardiac arrhythmias. Halothane (and to some degree
most other volatile anesthetics) sensitizes the myocardium to exogenous catecholamines.
[990]
[991]
[992]
[993]
Sensitization means that the minimum dose
of exogenous epinephrine administered intravenously that is needed to produce PVCs
would be lower in patients anesthetized with halothane than in awake patients.
How much epinephrine is safe to give when halothane is the anesthetic?
Katz and Bigger[990]
reported that the administration
of 0.15 mL/kg of a 1:100,000 epinephrine solution per 10-minute period (not to exceed
0.45 mL/kg of a 1:100,000 solution per hour) was safe. Several studies have shown
that lidocaine given with epinephrine affords extra protection and that enflurane
and isoflurane are less sensitizing than halothane.[991]
[992]
[993]
Because
halothane is a potent bronchodilator,[994]
it may
be the best choice for anesthetizing patients with asthma.[995]
However, such may not be the case; many asthmatic patients are already taking exogenous
catecholamines such as xanthines as chronic bronchodilator therapy.
Xanthines are effective bronchodilators because they produce β-adrenergic
stimulation in two ways: they cause release of norepinephrine[996]
[997]
and also inhibit the breakdown of cAMP,[998]
the mediator of many of the actions of β-adrenergic receptor agonists.[545]
Phosphodiesterase catalyzes the breakdown of cAMP. Thus, inhibition of phosphodiesterase
by theophylline increases the concentration of cAMP. Marcus and associates[996]
and Westfall and Flemming[997]
showed that at least
40% of the inotropic effects of aminophylline are due to its ability to release norepinephrine
directly. Experimentally, aminophylline decreases the threshold for ventricular
fibrillation.[999]
Plasma theophylline levels of 5 mg/L are needed to reduce abnormally
high airway resistance. No further beneficial effects are obtained when levels exceed
20 mg/L; instead, toxic effects appear.[1000]
Theophylline (aminophylline is a combination of 85% theophylline and 15% ethylenediamine)
is metabolized largely by the liver, with less than 10% being excreted unchanged
in urine. The average half-life is 4.4 ± 1.15 hours
in adults, and clearance is 1.2 mL/min/kg.[1000]
Significant liver disease or pulmonary edema can decrease clearance of the drug
by half and by a third, respectively.[1001]
Cigarette
smokers clear aminophylline more rapidly than nonsmokers do.[1002]
An interaction between aminophylline and halothane appears to
be a frequent, predictable occurrence: of 16 dogs anesthetized with 1% halothane
and given highdose bolus injections of aminophylline, 12 had ventricular arrhythmias
and 8 had ventricular tachycardia or fibrillation.[1003]
[1004]
[1005]
Thus, it is advisable to wait three drug half-lives after the last dose of aminophylline
is given (i.e., approximately 13 hours in normal individuals) before using halothane
to anesthetize an asthmatic patient. Using another anesthetic that is a bronchodilator
[994]
but is less likely to predispose the patient
to catecholamine-induced arrhythmias[991]
[992]
[993]
(e.g., enflurane or isoflurane or sevoflurane)
or using inhaled or systemic steroids started several days in advance might be alternatives
in patients requiring aminophylline or other exogenous sympathomimetic drugs before
or during surgery.[1006]
