Asian Cardiovasc Thorac Ann 2002;10:365-366
© 2002 Asia Publishing EXchange Pte Ltd
Neuroleptic Malignant Syndrome: Uncommon Postoperative Diagnostic Dilemma
Suraj Bhan, MD,
Vinay Kulkarni, MD,
Yatin Mehta, MD,
Krishan Kant Sharma, MD,
Naresh Trehan, MD,
Madan Lal Suri, MD
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Department of Anaesthesia Escorts Heart Institute Research Centre New Delhi, India
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For reprint information contact: Vinay Kulkarni, MD Tel: 91 11 682 5000 Fax: 91 11 682 5013 Department of Anaesthesia, Escorts Heart Institute and Research Centre, Okhla Road, New Delhi 110025, India.
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ABSTRACT
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Neuroleptic malignant syndrome occurred in a 71-year-old man on haloperidol therapy for mild depressive dementia. After coronary artery bypass grafting, he developed hyperthermia, elevated creatine kinase without a corresponding rise in the MB-isoenzyme, leukocytosis, raised liver enzymes, urea, and creatinine. His condition responded to bromocriptine therapy.
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INTRODUCTION
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Neuroleptic malignant syndrome (NMS) is a rare hyperthermic condition associated with antipsychotic medications, which can pose a diagnostic problem postoperatively. Recognition is crucial as early therapy can be lifesaving.
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CASE REPORT
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A 71-year-old man with recent myocardial infarction and double-vessel coronary disease, was scheduled for coronary artery bypass grafting. His medications included metoprolol, ramipril, aspirin, isosorbide dinitrate, atorvastatin, and haloperidol (for mild depressive dementia). Echocardiography revealed a left ventricular ejection fraction of 35%, hypokinesia of the distal interventricular septum, lateral and anterior walls, and trivial mitral and aortic regurgitation. Physical examination and routine laboratory tests were normal. Oral ranitidine 150 mg, lorazepam 2 mg, and intramuscular morphine sulphate 6 mg were administered one hour before surgery. Radial arterial and right internal jugular venous cannulation and pulmonary artery catheter insertion were accomplished under local anesthesia. General anesthesia was induced with midazolam 3 mg, fentanyl citrate 300 µg, and thiopentone sodium 250 mg. Orotracheal intubation was facilitated with vecuronium bromide 8 mg. Anesthesia was maintained with isoflurane in an air-oxygen mixture, intravenous fentanyl, midazolam, and vecuronium, with intermittent positive-pressure ventilation. Following heparinization (2 mg.kg-1), the left internal mammary artery was anastomosed to the diagonal branch of the left anterior descending artery using a suction stabilizer on the beating heart. During positioning for distal anastomosis of the right coronary artery, the patient became hemodynamically unstable, and cardiopulmonary bypass was established. A saphenous vein graft was anastomosed to the left anterior descending artery. High-dose inotropic support was required on discontinuation of bypass. By 4 hours postoperatively, the patient’s neurological status could be assessed and he was sedated for ventilation because of hemodynamic instability. His temperature started rising at 8 hours, reaching 39.6°C by 12 hours postoperatively despite cooling measures. Plasma creatine kinase (CK) increased from 273 to 6,542 IU.L-1 on day 2, without a corresponding rise in the MB-isoenzyme (172 IU.L-1). This was accompanied by leukocytosis (19,000/mm3) and slight increases in liver enzymes, urea, and serum creatinine. Thyroid function tests were normal. There were several episodes of hypotension. Hyperthermia persisted despite antipyretics, adequate antibiotic coverage, and negative bacterial cultures in blood, urine, and tracheal secretions. In view of his age, laboratory findings, and haloperidol intake preoperatively, NMS was diagnosed and bromocriptine 2.5 mg was administered 2 hourly through a gastric feeding tube. Temperature returned to normal (36.5°C) 15 hours after starting bromocriptine. Bromocriptine 2.5 mg 12 hourly was continued until day 5, laboratory findings normalized, and ventilatory support was discontinued. The patient had another 5 days of intensive care, and was discharged on the 15th postoperative day with no neurological deficit. Haloperidol therapy was discontinued.
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DISCUSSION
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Neuroleptic agents are widely used for psychoses, Alzheimer’s disease, organic mental syndrome, schizophrenia, paraphrenia, depression, and bipolar disorder.1 They are also used for nausea and vomiting, in cough medications, and as adjuvants to sedation for diagnostic procedures. NMS is characterized by hyperthermia, altered mental state, autonomic dysfunction, lead-pipe muscle rigidity, dyspnea, rhabdomyolysis, leukocytosis, and elevated CK. These manifestations are related to dopamine depletion in the central nervous system (CNS) due to neuroleptic or dopamine antagonistic therapy. Although common in young patients, many cases have been reported in those over 60 years old, not only because of the frequency of neuroleptic therapy in the elderly but also because of potential underlying CNS impairment.1 The incidence varies from 0.2%-2.4%. Drugs associated with NMS include phenothiazine, butyrophenones, thioxanthenes, lithium carbonate, anticholinergics, benzodiazepines, beta-adrenergic antagonists, and benzamide derivatives such as metoclopramide, which deplete dopamine in the CNS.2 Impaired heat regulation in NMS is due to dopamine receptor blockade in the basal ganglia, raising heat generation (muscle rigidity), and in the hypothalamus, impairing heat dissipation.3 Abnormal laboratory tests include leukocytosis, elevated CK and liver enzymes. Fever and elevated CK are considered the major diagnostic criteria, while tachycardia, hypertension, diaphoresis, altered sensorium, and leukocytosis are minor criteria for definitive diagnosis.4
Urinary myoglobin was negative in our patient, and muscle rigidity could not be demonstrated as he was on mechanical ventilation and receiving sedatives and muscle relaxants; NMS without muscle rigidity has been reported.5 Complications of NMS include renal and respiratory failure and disseminated intravascular coagulation. Differential diagnosis includes malignant hyperthermia (MH), drug-induced acute dystonic/idiosyncratic reactions, and septicemia. Although MH can occur perioperatively, the lack of a rise in end-tidal or arterial carbon dioxide tension despite constant minute ventilation, tachycardia, arrhythmia, respiratory and metabolic acidosis, myoglobinuria, muscle rigidity, or any triggering agent in this patient was incompatible with MH. Isoflurane was used intraoperatively and there are reports of isoflurane triggering MH.6 Septicemia was unlikely in view of adequate antibiotic therapy and negative bacterial cultures. Hyperthyroidism can also manifest in this fashion, but thyroid function tests were normal.
As NMS is primarily related to the CNS, a centrally acting dopaminergic agonist such as bromocriptine is the drug of choice.7 Alternatives include levodopa-carbidopa, amantadine, anticholinergic agents, and calcium channel blockers. Treatment of NMS includes withdrawal of the causative agent, rehydration, measures to reduce temperature, and management of respiratory, cardiovascular, and renal complications. A swift response to bromocriptine therapy supports the diagnosis of NMS. Haloperidol is not indicated immediately postoperatively but for psychosis developing after prolonged intensive care stay.8 Its use should be monitored closely as QT-interval prolongation, dysrhythmias, and sudden death may occur. It is necessary to recognize and treat NMS which has a mortality of 10%-50%, and a high index of suspicion should be maintained perioperatively in patients presenting with hyperpyrexia, raised CK without a corresponding rise in CK-MB, leukocytosis, and neuroleptic therapy, even if other risk factors for NMS are absent.
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REFERENCES
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- Addonizio G. Neurological malignant syndrome in elderly patients. J Am Geriatr Soc
1987;35:1011–2.[Medline]
- Kellam AMP. The (frequently) neuroleptic (potentially) malignant syndrome. Br J Psychiatry
1990;157:169–71.
- Hom E, Lach B, Lapierre Y, Hrdina P. Hypothalamic pathology in the neuroleptic malignant syndrome. Am J Psychiatry
1988;145:617–20.[Abstract/Free Full Text]
- Levinson DF, Simpson GM. Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the "neuroleptic malignant syndrome." Arch Gen Psychiatry
1986;43:439–48.
- Wong MM. Neuroleptic malignant syndrome. Two cases without muscle rigidity. Aust NZ J Psychiatry
1996;30:415–8.[Medline]
- Thomas DW, Dev VJ, Whitehead MJ. Malignant hyperpyrexia and isoflurane. A case report. Br J Anaesth
1987;59:1196–8.[Abstract/Free Full Text]
- Lieberman A, Pasternack P, Colvin S. The neuroleptic malignant syndrome after open heart surgery: successful treatment with bromocriptine. N Y State J Med
1987;87:362–3.[Medline]
- Michael JM, Torres NE. Critical care medicine for the cardiac patient. In: Kaplan JA, editor. Cardiac anesthesia
, 4th ed. Philadelphia: Saunders, 1999:1292–3.
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ABSTRACT
INTRODUCTION
