ANESTH ANALG 1041
Anesthesia for Cardiac Surgery in Patients Receiving Monoamine
Ira Michaels, MD, PhD, Martin Serrins, MD, Nicte-ha Q. Shier, MD, and Paul G. Barash, MD
Affective disorders in association with the psycho- the coronary care unit. He was continued on the pre-
logic aspects of cardiac disease may require phar- viously mentioned medications, and in addition, in-
macologic treatment for severe depression. A small travenous nitroglycerin (3 pgkg '.min - *) was added
number of these patients continues to be treated with to control the angina. Of importance was a 3-month
monoamine oxidase inhibitors (MAOI). It is likely that use of the MA0 inhibitor phenelzine (Nardil, 45
there will be an increase in the number of patients mg/day) for treatment of severe depression after the
being treated with MAOI. Patients may routinely re- death of his son. Phenelzine was discontinued at the
ceive MA01 for postelectroconvulsive maintenance time of admission.
therapy. In addition, elderly patients who do not re- The day after admission, the patient underwent a
spond to tricyclic antidepressants may respond to cardiac catheterization, complicated by several epi-
MAOI. Phenelzine (60 mg/day) has been shown to be sodes of angina that resolved spontaneously. Angi-
as effective as 150 mg of amitriptyline (1).Phenelzine ography revealed severe diffuse coronary artery dis-
has also been shown to be superior to imipramine in ease, with 1 + mitral regurgitation and a mildly
patients with atypical depression (1).Studies indicate enlarged left ventricle showing both dyskinesis and
that MA01 may also be useful as therapy for regu- hypokinesis. Hemodynamic measurements included
lation of weight and appetite, posttraumatic stress pulmonary capillary wedge pressure (PCWP) of 8 mm
disorders, and endogenous depression (1).When these Hg, and a cardiac output of 4.2 L/min. After cathe-
patients present for emergency cardiac surgery, the terization, the patient continued to have persistent
anesthesiologist is confronted with a clinical dilemma, angina despite maximal medical treatment. All labo-
because the normal practice of discontinuing this class ratory data were within normal limits. Due to the
of drugs two to three weeks before operation is pre- nature of his disease and lack of pharmacologic con-
cluded (2). We report two patients who underwent trol of his symptoms, it was felt that the patient was
cardiac operation in whom this period of withdrawal at a very high risk for myocardial infarction. Discus-
of MA01 therapy was not feasible. sion centered around his recent MA0 inhibitor ex-
posure and the fact that the phenelzine had been
discontinued for only 36 hr. Despite the potential risk
Case I associated with MA01 exposure, the decision to pro-
A 46 yr-old, 100-kg man, with substernal chest pain ceed with emergency coronary artery bypass opera-
at rest was admitted for emergency cardiac catheter- tion was felt to be a better alternative than continued
ization and a coronary artery bypass operation. Two medical therapy for control of ischemic heart disease.
months before admission, despite treatment with pro- After intramuscular premedication with morphine
pranolol (240 mg/day) and nifedipine (60 mg/day) sulfate (10 mg) and scopolamine (0.4mg), intravenous
therapy, the patient had an increased frequency of catheters, a radial arterial cannula, and a pulmonary
angina. Eight months before admission, he sustained artery catheter were inserted percutaneously. Prein-
an inferior wall myocardial infarction, and during that duction hemodynamics revealed a blood pressure of
admission had a positive stress test. Severe substernal 140190 mm Hg, a heart rate of 90 beatsimin, m P of
chest pain at rest resulted in his current admission to 8 mm Hg and cardiac output of 5 L/min. With the
patient breathing 100% oxygen, an infusion of fen-
Received from the Department of Anesthesiology, Yale Uni- tanyl (75 @kg) and an infusion of 200 mg of succi-
versity School of Medicine, New Haven, Connecticut. Accepted nylcholine (0.2%) were started. After a hemodynam-
for publication July 27, 1984.
Address correspondence to Dr. Michaels, Department of Car-
ically uneventful laryngoscopy and intubation, the
diothoracic Anesthesia, St. Francis Hospital, Roslyn, NY 11576. patient was then given pancuronium (0.1 mgikg) for
0 1984 by the International Anesthesia Research Society
1042 ANESTH ANALG CLINICAL REPORTS
maintenance of muscle relaxation. Approximately 10 150/70 mm Hg, a heart rate of 100 beatdmin (atrial
min later, prior to surgical incision, PCWP had in- fibrillation), pulmonary artery diastolic pressure of 30
creased to 20 mm Hg and an intravenous nitroglycerin mm Hg and cardiac output of 3 L/min. With the pa-
infusion (2 pgkg-'.rnin-') was started. The PCWP tient breathing 100% oxygen, an infusion of fentanyl
returned to 12 mm Hg with maintenance of the cardiac (75 pgkg) was begun. The patient also received pan-
output. Cardiopulmonary bypass and hypothermia curonium (0.1 mg/kg) for relaxation. The patient's vi-
(26°C) was then instituted. A five-vessel coronary ar- tal signs continued to be stable with the addition of
tery bypass graft operation was performed. The aortic enflurane and sodium nitroprusside for control of blood
cross clamp time was 59 min. After CPB, the patient pressure. Cardiopulmonary bypass and hypothermia
required sodium nitroprusside for vasodilatation. He (26°C)was instituted. The aortic cross clamp time was
required no inotropic or vasopressor support and had 59 min. The mitral valve was replaced with a Car-
an uneventful operative course. He was extubated on pentier-Edwards valve and she was hemodynami-
the second postoperative day (24 hr postoperatively) cally stable after CPB. She was extubated on the sec-
and was discharged on the eighth postoperative day. ond postoperative day (30 hr postoperatively) and
Phenelzine was not required postoperatively. was discharged from the intensive care unit 24 hr
later. On the seventh postoperative day, phenelzine
(45 mg) was reinstituted due to a recurrence of her
Case I1 depression. She was discharged on the thirteenth
A 51-yr-old, 65-kg woman was scheduled for elective postoperative day and continued to have an unevent-
mitral valve replacement secondary to increasing ful postoperative course.
symptoms of shortness of breath, orthopnea, and par-
oxysmal nocturnal dyspnea. She had a history of
rheumatic fever as a child. Twelve years before ad- Discussion
mission she underwent a mitral valve commissuro- Monoamine oxidase, an intraneural enzyme, is in-
tomy. Five months before admission, cardiac cathe- volved in the degradation of sympathetic amines. In-
terization revealed moderate mitral stenosis, 1 mitral hibition of M A 0 is thought to be effective in the treat-
regurgitation, and a pulmonary artery pressure of 44/20 ment of endogenous depression by increasing central
mm Hg. PCWP at that time was 18 mm Hg and cardiac nervous system catecholamine content. Due to dif-
output was 3.9 L/min. The patient was found to have ferences of substrate preference, two forms of the
normal coronary arteries and a ventriculogram showed enzyme have been defined: MAO-A and MAO-B.
anterior apical and left ventricular akinesia. The pa- Nonselective drugs inhibit both the A and B forms
tient's medication upon admission included digoxin (Table 1). Selective MA01 inhibit either the A or the
(0.25mgiday), furosemide (60 mg/day), coumadin (2.5 B forms. Type A selectively deaminates serotonin,
mglday), and perphenazine (8 mglday). In addition, norepinephrine, and dopamine (Fig. 1) (3). Inhibition
she was receiving phenelzine (45 mglday), which was of MAO-A is clinically relevant, since serotonin and
discontinued 5 days before admission. She had re- norepinephrine are important neurotransmitters in
ceived this MA01 for approximately 2.5 yr for severe affective disorders. Type B preferentially deaminates
depression. phenethylamine and tyramine. Theoretically, a selec-
On the basis of the severity of her depression, the tive type B MA01 could spare the patient from a hy-
psychiatric consultant felt that alternative pharma- pertensive reaction mediated by tyramine's norepi-
cologic therapy could not be effectively substituted nephrine releasing effect, since metabolism of
within 7-14 days. The day before operation (4 days norepinephrine will still continue via the MAO-A en-
after admission), all laboratory values were within zyme. However, the monoamine oxidase inhibitors
normal limits. Her electrocardiogram, however, currently used in the US are nonselective. Two classes
showed atrial fibrillation with a ventricular rate of 80 of nonselective MA01 are available: hydrazine and
beatslmin. nonhydrazine drugs.
Ninety minutes before entering the operating room, A further consideration is the potential reversibility
the patient was premedicated with intramuscular of M A 0 inhibition. At least 80% of MAO-enzyme
morphine sulfate (4 mg) and scopolamine (0.3 mg). must be inhibited before observing an adequate ther-
Intravenous catheters, a radial artery cannula and a apeutic effect (4). The nonhydrazine derivatives such
pulmonary arterial catheter were inserted percuta- as pargyline and tranylcypromine are reversible
neously under local anesthesia. Preinduction hemo- blockers and when discontinued will have no phar-
dynamics at this time revealed a blood pressure of macologic effects after 24 hr. In contrast, the hydra-
CLINICAL REPORTS ANESTH ANALC 1043
Table 1. D r u g Selectivity for M A 0 Enzymes SEROTONIN DOPAMINE NOR- TYRAMINE PHENETHYL-
(5-HT) I EPINEPHRINE AMINE
MAO-A MAO-B I
Clorgyline + f f f f
5-HYOROXY INDOLE HOMOVANILIC VANILMANDELIC 4-HYDROXY PHENYLACETIC
Deprenyl ? ACETIC ACID ACID ACID PHENYLACETIC ACID
(5-UIAA) (UVAI (VMA) ACID
Figure 1. Substrate selectivity of monoamine oxidase enzyme
zine class, such as phenelzine, irreversibly blocks M A 0
and its effects persist for at least 14-21 days after operative intubation was not prolonged. At our in-
cessation of therapy (1). stitution, weaning from respiratory support com-
MA01 have the ability to interact with sympatho- mences 12-18 hr after surgery. In a study investigating
mimetic agents causing hypertensive crises. This has the effect of fentanyl on dogs who received MAOI,
been reported with tyramine (5), ephedrine (6), met- no difference was found in awakening time nor were
araminol (7), and others (8,9). If vasopressors are re- untoward cardiovascular effects seen (19).
quired during surgery, it is recommended that small Of further clinical importance for surgery involving
doses of direct acting agents be used (10) and if hy- large blood loss is the observation that MA01 may
pertensive crises occur, P-blockers or sodium nitro- adversely affect platelet function (20,21). Lieb et al.
prusside can be added (11). Wong et al., using a par- have suggested that platelet M A 0 inhibition may be
gyline-pretreated canine model, suggested that an important method of monitoring the degree of MA0
avoidance of reflex or indirect stimulation of the sym- inhibition (20).
pathetic nervous system can minimize cardiovascular In conclusion, an increase in the number of patients
lability (12). receiving MAOI is likely to be seen in the clinical
MAOI also interact with narcotic analgesics. A nar- practice of anesthesiology. This report suggests that
cotic-based anesthetic technique is thought to be "in- patients receiving MA01 may be safely anesthetized
advisable" (2,lO). A study in mice has shown that for major surgical procedures. Appropriate monitor-
pretreatment with MA01 increased the mortality rate ing and preparation may obviate the need for with-
with meperidine, morphine, pentazocine,and phen- drawal of MA01 prior to surgery.
azocine (13). Several authors postulate that the mech-
anism is due to an increase in serotonin (14). Meper- References
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hypertension, convulsions, and hyperpyrexia (15). timore: Ayd Medical Communications, 1983:41-55.
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dose of narcotics be used for patients who must re- 1976;7:381-6.
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to the perioperative period in a hemodynamically and and metaraminol. Br Med J 1965;2:460-1.
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1044 ANESTH ANALG CLINICAL REPORTS
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Couto da Silva JM, Tubino PJ, Vieira ZEG, and Saraiva RA. Closed circuit anes-
thesia in infants and children. Volume 63, Number 8, August 1984.
Page 765, right column, the equation should be changed to read as follows:
2(065 MAC x A B/G x Q)
Volume of liquid anesthetic = 2
Vapor o 1 ml of the used anesthetic .
Also, on page 768, Table 4, footnote a should read as follows:
“According to Brody’s equation (lO-kg’/’).