Editorial Monoamine Oxidase Inhibitors: Are We Condemned to Relive History, or Is History No Longer Relevant? Michael F. Roizen, MD* I)epartment of Anesthesia (Chicago, IL.
*Professor Anesthesia Medicine
and Chairman, Department and Critical Care: Professor
of of’
Address reprint requests to Dr. Roizen at the Department of‘ Anesthesia and Critical Care, University of’ Chicago, 5841 S. Maryland Avenue, Box 428, Chicago, IL 60637, USA. Received fk publication April 9, 1990; revised article accepted for publication April IO, 1990. 0 1990 Butterworth-Heinemann
and Critical
Care,
University
of‘ Chicago,
In his article “Ketamine Induction and Monoamine Oxidase Inhibitors”’ in this issue of Journal of Clinical Anesthesia, Doyle describes a case with good results in which monoamine oxidase (MAO) inhibitors were not discontinued preoperatively. The major problem with continuing MAO inhibitors preoperatively is not the hemodynamic fluctuations that might occur intraoperatively because of abnormal intraneuronal levels of amine neuronal transmitters, but rather the rare instance of hyperpyrexic coma following narcotic administration to the patient being treated with an MAO inhibitor. While there are reports of continuing MAO inhibitors with patients undergoing electroconvulsive therapy or of giGng anesthetic for specific treatments without discontinuing an MAO inhibitor, whether we should or should not discontinue MAO inhibitors before anesthesia is not clear to me at this time. With respect to MAO inhibitors, Santayana’s observation that “those who don’t know history are condemned to repeat it” seems appropriate and has been illustrated to me many times. It is apparent that with certain patients, if you do not know their anesthetic history, you are condemned to relive-or at least participate in solving-some of their problems (e.g., the patient with the surprisingly difficult airway). Sometimes, however, history is no longer relevant. For instance, in the early 1960s, we discontinued antihypertensive medication three weeks in advance of an operation to prevent intraoperative bradycardia and hypotension. Today, not only do we advocate the preoperative use of antihypertensive drugs, including sympatholytics, but we also debate the risk/benefit ratio of perioperative sympathectomy for those who are sickest. Which of these two situations applies to the discontinuance of MAO inhibitors before anesthesia is not clear to me yet. MAO inhibitors irreversibly bind to the enzyme MAO and thereby increase intraneuronal levels of amine neurotransmitters (serotonin, nor-
J. Clin.
Anesth.,
vol. 2, September/October
1990
293
epinephrine. dopamine, epinephrine, and octopamint’). ‘I‘his ilic rt’ast is associated with an antidepressant, an antihypertensive, anti ;III ;tntill;lrcoleptic effect: an increase in liver enzymes; ant1 a delay irl the onset of Parkinson’s disease.’ Since there are two fimm of the en/vmca. MAC )-A and MAO-B, which are selective in vitro fbr substrate (MAO-A is selrc1ive f’or serotonin, dopamine, and norepinephrine; MAO-B is selective fi)r tyramine and phenylethylamine), presumably MAO inhibitors that are selective for MAO-A or MAO-B would have different effects. s Such has not been proven, however, since cleprenyl, an MAO-B selective drug, improves a dopamine-deficient state, Parkinson’s disease. ‘l‘here are no reported experiences of interaction between narcotics and del~renyl, so the judgment that discontinuing MAO inhibitors is or is not worth the risk of worsening Parkinson’s disease has no basis in data. Interaction between MAO inhibitors and a variety of foods and drugs containing substances that act indirectly as sympathomimetics, such as ephedrine or tyramine (found especially in red wine and blue cheese), can occur for as long as 2 weeks after the last dose of’ an MAO inhibitor is gi\,en. ‘l’he most serious effects of this interaction are convulsions and hyperpyrexic For this reason, anesthetic management coma, especially after narcotics. fbra patient given an MAO inhibitor cm be chaotic, and it has been a widely accepted practice to discontinue MAO inhibitors at least 2 to 3 weeks before any planned operation. ‘L”’ Another point of view has been expressed for treating severely psychotic patients or when emergency surgery is needecl. ‘.:‘,I’Clearly, in such cases, the risk of discontinuing MAOs must be weighed against the advantage. As Doyle points out, emergency surgery on patients given MAO inhibitors can be punctuated by hemodynamic instability. Kegional block can be attempted as treatment for postoperative pain to avoid having to give narcotics. Case reports of’ hyperpyrexic coma in humans following administration of most narcotics exist, and animal studies document a 10% to SO% rate of hyperpyrexic coma in animals pretreated wirh MAO inhibitors and then given a variety of narcotics. ‘F’~” Are we condemned to relive the history of MAO drugs with narcotic administration, or has the practice of anesthesia and the types of narcotics we use changed enough so that this history is no longer relevant? I don’t know, but I worry that if we forget that a patient is taking an MAO inhibitor, we may be forced to relive problematic situations that might have been avoided. When the day comes that each anesthesia machine and patient bedside is equipped with a computer that alerts IIS to the interactions between the drugs the patient is taking and warns us about the dangers of using, for instance, meperidine or morphine to provide pain relief for such a patient, perhaps then we will not have to deal with the consequences of our lack of perfection. But more than 60% of’anesthesiologists practicing now were not in practice during the era when the combination of MAO inhibitors and narcotics caused hyperpyrexic coma. My concern is that we anesthesiologists may not remember the prohibition vividly enough to avoid reliving this interaction.
References 1. Doyle DJ: Ketamine
induction and Monoamine Oxidase inhibitors. ,/ Clin Atmlh 1990;2:324-325. 2. The Parkinson Study Group: Effect of deprenyl on the progression of disability in early Parkinson’s disease. N En,@ J Med 1989;32 1: 1364-7 1.
294
,I. Clin. Anesth.,
vol. 2, September/October
1990
MAO inhibitors: Roizen
3. Michaels I, Serrins M, Shier NQ, Barash PG: Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors. An&h Annlg 1984;63: 1041-4. 4. Evans-Prosser CDG: The use of pethidine and morphine in the presence of monoamine oxidase inhibitors. HrJ Anaesth 1968;40:279-82. 5. Campbell GD: Dangers of monoamine oxidase inhibitors. Hr MedJ 1963; 35:750-Y. 6. Rogers KJ, Thornton JA: The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice. BrJ Pharmacol 1969;36:470-80. 7. Sjoqvist F: Psychotropic drugs. Part 2: Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proc R Sot Mrd 1965;58:9677x. Mrd Lett Drugs Ther 1989;31: 1 l-2. 8. Foods interacting with MAO inhibitors. 9. Drugs for psychiatric disorders. Med Lett Drug.s Ther 1989;3 1: 13-20. 10. El-Ganzouri AR, lvankovich AD, Braverman B, McCarthy R: Monoamine Anesth Analg oxidase inhibitors: should they be discontinued preoperatively? 1985;64:592-6. 11. Schwartz AJ, Wollman H: Anesthetic considerations for patients on chronic drug therapy: I.-dopa monoamine oxidase inhibitors, tricyclic antidepressants, and propranolol. In: Hershey SG, ed. ASA Refresher Couvws in Anesthesiology. Vol 4. Philadelphia: ,JB Lippincott, 1976;99.
J. Clin. Anesth.,
vol. 2, September/October
1990
295
*Professor Anesthesia Medicine
and Chairman, Department and Critical Care: Professor
of of’
Address reprint requests to Dr. Roizen at the Department of‘ Anesthesia and Critical Care, University of’ Chicago, 5841 S. Maryland Avenue, Box 428, Chicago, IL 60637, USA. Received fk publication April 9, 1990; revised article accepted for publication April IO, 1990. 0 1990 Butterworth-Heinemann
and Critical
Care,
University
of‘ Chicago,
In his article “Ketamine Induction and Monoamine Oxidase Inhibitors”’ in this issue of Journal of Clinical Anesthesia, Doyle describes a case with good results in which monoamine oxidase (MAO) inhibitors were not discontinued preoperatively. The major problem with continuing MAO inhibitors preoperatively is not the hemodynamic fluctuations that might occur intraoperatively because of abnormal intraneuronal levels of amine neuronal transmitters, but rather the rare instance of hyperpyrexic coma following narcotic administration to the patient being treated with an MAO inhibitor. While there are reports of continuing MAO inhibitors with patients undergoing electroconvulsive therapy or of giGng anesthetic for specific treatments without discontinuing an MAO inhibitor, whether we should or should not discontinue MAO inhibitors before anesthesia is not clear to me at this time. With respect to MAO inhibitors, Santayana’s observation that “those who don’t know history are condemned to repeat it” seems appropriate and has been illustrated to me many times. It is apparent that with certain patients, if you do not know their anesthetic history, you are condemned to relive-or at least participate in solving-some of their problems (e.g., the patient with the surprisingly difficult airway). Sometimes, however, history is no longer relevant. For instance, in the early 1960s, we discontinued antihypertensive medication three weeks in advance of an operation to prevent intraoperative bradycardia and hypotension. Today, not only do we advocate the preoperative use of antihypertensive drugs, including sympatholytics, but we also debate the risk/benefit ratio of perioperative sympathectomy for those who are sickest. Which of these two situations applies to the discontinuance of MAO inhibitors before anesthesia is not clear to me yet. MAO inhibitors irreversibly bind to the enzyme MAO and thereby increase intraneuronal levels of amine neurotransmitters (serotonin, nor-
J. Clin.
Anesth.,
vol. 2, September/October
1990
293
epinephrine. dopamine, epinephrine, and octopamint’). ‘I‘his ilic rt’ast is associated with an antidepressant, an antihypertensive, anti ;III ;tntill;lrcoleptic effect: an increase in liver enzymes; ant1 a delay irl the onset of Parkinson’s disease.’ Since there are two fimm of the en/vmca. MAC )-A and MAO-B, which are selective in vitro fbr substrate (MAO-A is selrc1ive f’or serotonin, dopamine, and norepinephrine; MAO-B is selective fi)r tyramine and phenylethylamine), presumably MAO inhibitors that are selective for MAO-A or MAO-B would have different effects. s Such has not been proven, however, since cleprenyl, an MAO-B selective drug, improves a dopamine-deficient state, Parkinson’s disease. ‘l‘here are no reported experiences of interaction between narcotics and del~renyl, so the judgment that discontinuing MAO inhibitors is or is not worth the risk of worsening Parkinson’s disease has no basis in data. Interaction between MAO inhibitors and a variety of foods and drugs containing substances that act indirectly as sympathomimetics, such as ephedrine or tyramine (found especially in red wine and blue cheese), can occur for as long as 2 weeks after the last dose of’ an MAO inhibitor is gi\,en. ‘l’he most serious effects of this interaction are convulsions and hyperpyrexic For this reason, anesthetic management coma, especially after narcotics. fbra patient given an MAO inhibitor cm be chaotic, and it has been a widely accepted practice to discontinue MAO inhibitors at least 2 to 3 weeks before any planned operation. ‘L”’ Another point of view has been expressed for treating severely psychotic patients or when emergency surgery is needecl. ‘.:‘,I’Clearly, in such cases, the risk of discontinuing MAOs must be weighed against the advantage. As Doyle points out, emergency surgery on patients given MAO inhibitors can be punctuated by hemodynamic instability. Kegional block can be attempted as treatment for postoperative pain to avoid having to give narcotics. Case reports of’ hyperpyrexic coma in humans following administration of most narcotics exist, and animal studies document a 10% to SO% rate of hyperpyrexic coma in animals pretreated wirh MAO inhibitors and then given a variety of narcotics. ‘F’~” Are we condemned to relive the history of MAO drugs with narcotic administration, or has the practice of anesthesia and the types of narcotics we use changed enough so that this history is no longer relevant? I don’t know, but I worry that if we forget that a patient is taking an MAO inhibitor, we may be forced to relive problematic situations that might have been avoided. When the day comes that each anesthesia machine and patient bedside is equipped with a computer that alerts IIS to the interactions between the drugs the patient is taking and warns us about the dangers of using, for instance, meperidine or morphine to provide pain relief for such a patient, perhaps then we will not have to deal with the consequences of our lack of perfection. But more than 60% of’anesthesiologists practicing now were not in practice during the era when the combination of MAO inhibitors and narcotics caused hyperpyrexic coma. My concern is that we anesthesiologists may not remember the prohibition vividly enough to avoid reliving this interaction.
References 1. Doyle DJ: Ketamine
induction and Monoamine Oxidase inhibitors. ,/ Clin Atmlh 1990;2:324-325. 2. The Parkinson Study Group: Effect of deprenyl on the progression of disability in early Parkinson’s disease. N En,@ J Med 1989;32 1: 1364-7 1.
294
,I. Clin. Anesth.,
vol. 2, September/October
1990
MAO inhibitors: Roizen
3. Michaels I, Serrins M, Shier NQ, Barash PG: Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors. An&h Annlg 1984;63: 1041-4. 4. Evans-Prosser CDG: The use of pethidine and morphine in the presence of monoamine oxidase inhibitors. HrJ Anaesth 1968;40:279-82. 5. Campbell GD: Dangers of monoamine oxidase inhibitors. Hr MedJ 1963; 35:750-Y. 6. Rogers KJ, Thornton JA: The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice. BrJ Pharmacol 1969;36:470-80. 7. Sjoqvist F: Psychotropic drugs. Part 2: Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proc R Sot Mrd 1965;58:9677x. Mrd Lett Drugs Ther 1989;31: 1 l-2. 8. Foods interacting with MAO inhibitors. 9. Drugs for psychiatric disorders. Med Lett Drug.s Ther 1989;3 1: 13-20. 10. El-Ganzouri AR, lvankovich AD, Braverman B, McCarthy R: Monoamine Anesth Analg oxidase inhibitors: should they be discontinued preoperatively? 1985;64:592-6. 11. Schwartz AJ, Wollman H: Anesthetic considerations for patients on chronic drug therapy: I.-dopa monoamine oxidase inhibitors, tricyclic antidepressants, and propranolol. In: Hershey SG, ed. ASA Refresher Couvws in Anesthesiology. Vol 4. Philadelphia: ,JB Lippincott, 1976;99.
J. Clin. Anesth.,
vol. 2, September/October
1990
295
