Orthostatic hypotension is the most common adverse effect associated with the use of MAOIs (Box 96-1). Octopamine, a false neurotransmitter, is formed by the β-hydroxylation of tyramine in the sympathetic nerve terminal and is stored within the presynaptic storage vesicle, displacing norepinephrine. Neural impulses that normally would stimulate the release of norepinephrine from these storage vesicles now release less norepinephrine along with some octopamine, which has very little α- and β-receptor activity. When an individual taking MAOIs assumes an upright position, the presence of this false neurotransmitter manifests itself by causing less vasoconstriction than normally would occur, resulting in hypotension.

Patients should avoid consuming foods that contain tyramine (aged cheese, liver, fava beans, avocados, and Chianti wine) while they are taking MAOIs and for 2 weeks after discontinuation of MAOIs. Ingested tyramine is normally metabolized prior to entering the systemic circulation by MAO in the intestinal mucosa and liver. If a patient on an MAOI ingests a tyramine-rich food, the tyramine that is absorbed in the intestine escapes intestinal and hepatic metabolism. The delivery of large amounts of tyramine, a monoamine with indirect-acting sympathomimetic activity to the nerve terminal, results in the release of a supranormal amount of norepinephrine into the synaptic cleft. Profound hypertension may develop and, in some patients, may cause a myocardial infarction or cerebrovascular accident.

Anesthetic management

Because of the covalent bond that the MAOI forms with the enzyme, the inhibition of MAO persists even after the MAOIs are no longer detectable in plasma. The resumption of MAO activity depends upon de novo synthesis of the enzyme, a process that takes approximately 8 to 12 days to restore 50% of pretreatment activity. Therefore, if an MAOI is going to be stopped prior to surgery, it should be discontinued for at least 2 weeks prior to a surgical procedure to allow for resumption of normal enzyme activity.

However, it is debatable whether MAOIs should be discontinued prior to elective operations. If the patient’s clinical condition will deteriorate upon halting therapy, the MAOI should probably be continued. If the MAOI must be continued or the operation is an emergency, the anesthetic should be tailored to avoid adverse drug interactions.

Regional anesthesia and general anesthesia are acceptable anesthetic modalities in these patients. One benefit of a regional technique is the decreased postoperative opioid requirement. If a regional technique is utilized, the local anesthetic solution should not contain epinephrine.

Intraoperative fluctuations in blood pressure are common in patients taking MAOIs. Orthostatic hypotension is common for the reasons described previously. A direct-acting sympathomimetic may be used to maintain mean arterial pressure in hypotensive patients. The dose should be titrated to effect in small increments because patients can have an exaggerated response to treatment. Indirect-acting sympathomimetics may induce a severe hypertensive response, and their use should be avoided. Ketamine and pancuronium are not used because they enhance sympathetic activity.

MAOIs also decrease plasma cholinesterase activity. If succinylcholine is chosen for neuromuscular blockade, its duration of action may be prolonged. The use of opioids should be limited and, when used, the patient should be closely monitored for adverse effects. If an opioid is required, morphine is the preferred agent because its use has not been associated with the serotonergic syndrome in patients taking MAOIs.

Caution must be exercised when administering medications that are metabolized by the liver because MAOIs inhibit hepatic microsomal enzymes. Prolonged or exaggerated depressant effects may be seen with the use of drugs such as benzodiazepines or barbiturates in combination with an MAOI. Rarely, patients taking MAOIs develop liver failure.