Interact CardioVasc Thorac Surg 2008;7:656-657. doi:10.1510/icvts.2007.173104
© 2008 European Association of Cardio-Thoracic Surgery
Negative results - Cardiac general |
Serotonin syndrome following cardiac surgery
Ganesh Shanmugama,*,
Blaine Kentb,
Turki Alsaiwadic and
Roger Basketta
a Department of Cardiac Surgery, QEII Health Sciences Centre, Halifax Infirmary, 1796 Summer Street, Halifax, Nova Scotia B3L 4P7, Canada
b Department of Anaesthesiology, QEII Health Sciences Centre, Halifax Infirmary, 1796 Summer Street, Halifax, Nova Scotia B3L 4P7, Canada
c Department of Internal Medicine, QEII Health Sciences Centre, Halifax Infirmary, 1796 Summer Street, Halifax, Nova Scotia B3L 4P7, Canada
Received 4 December 2007;
received in revised form 16 February 2008;
accepted 19 February 2008
*Corresponding author. Tel.: +1 902 473 3808; fax: +1 902 473 4448.
E-mail address: sgunpat{at}hotmail.com (G. Shanmugam).
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Abstract
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Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression. We report a case of serotonin syndrome following cardiac surgery. This syndrome is rare in the cardiac literature. The clinical features, diagnosis and management of this unusual syndrome are described. In patients with polypharmacy, it is important to take cognisance of serotonergic antidepressants and anticipate their potential interactions with drugs used peri-operatively. Early recognition and treatment is important as this condition is potentially fatal.
Key Words: Serotonin syndrome; Mitral valve replacement; Paroxetine
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1. Case report
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A 49-year-old lady presented with rheumatic mitral disease, cardiac failure and pulmonary hypertension. Co-morbidities included hypertension, anxiety and depression. Pre-operative medication included clonazepam 0.5 mg daily, seroquel 25 mg twice daily, and paroxetine 40 mg daily for anxiety and depression.
She underwent mitral valve replacement using a 29 carbomedics mechanical valve. Premedication included diazepam 10 mg sixty minutes preoperatively. Anesthetic medication included fentanyl (5 µg/kg), midazolam (0.3 µg/kg), and propofol (9 mg/kg) for induction, rocuronium (1 mg/kg) for muscle relaxation, and sevoflurane (0.5–1.0%) for maintenance during bypass. A target mean arterial pressure >50 mmHg on CPB was initially managed with intermittent boluses of phenylepherine and vasopressin. Resistant hypotension was managed with a norepinepherine (0.03 µg/kg/min) infusion and methylene Blue (1 mg/kgx2 doses). Fentanyl was given by intermittent bolus to a total dose of 13 µg/kg. Propofol (25 µg/kg/min) was commenced upon rewarming and continued into the intensive care unit.
Postoperatively, she woke up confused and agitated. Her temperature was 40 °C. Neurologic examination revealed myoclonic jerks, fine tremors of the extremities, dilated pupils, shivering, hyperactive reflexes, and hypertonicity. Muscle rigidity was greater in the lower than upper limbs. The neck was supple. Vital signs included a heart rate of 110/min, blood pressure of 170/100 mmHg, and a central venous pressure of 15 mmHg.
Laboratory tests revealed a peak white cell count of 23.2x10–9/l, a peak creatinine of 225 µmol/l, and a peak potassium of 7.1 mmol/l. LDH peaked at 5494 U/l, CPK at 6734 U/l, ALT at 3594 U/l, amylase at 514 U/l, troponin at 2.13 µg/l, and urine myoglobin at 5640 U/l. Blood cultures were negative. Brain CT-scan and MRI revealed no acute pathology. EEG demonstrated disturbances of electrocerebral function, consistent with a toxic encephalopathy, with no evidence of epilepsy.
Based on her preoperative medication, clinical findings and laboratory results, a diagnosis of serotonin syndrome was made. The patient was sedated with propofol, ventilated and paralysed for 24 h. The fentanyl infusion was discontinued. She was treated with a loading dose of 12 mg of cyproheptadine, followed by 2 mg every second hour, for 48 h. Her neurological manifestations and laboratory parameters gradually improved over the next week, and the core temperature reduced. She was extubated one week later, and was transferred to the ward, where recovery of strength and mobility was slow but complete. A psychiatric evaluation was obtained. Quetiapine (50 mg daily) was commenced instead of paroxetine, which is known to potentiate serotonin toxicity. She was discharged home with no neurological deficit, and arrangements for neurological and psychiatric follow-up.
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2. Discussion
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Serotonin syndrome is a potentially lethal pharmacodynamic interaction in patients on combinations of serotonergic drugs, acting by different mechanisms that raise intra-synaptic serotonin to threatening levels. The commonest drug combination involves the monoaminooxidase inhibitors (MAOI), SSRIs, and tricyclic antidepressants. Noble and Baker suggested that MAOIs should be discontinued before surgery especially when catecholamines are needed [1].
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3. Mechanism
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Serotonin syndrome is the result of overstimulation of 5-HT1A and 5-HT2 receptors [2, 3] in central grey nuclei, the midline raphe nuclei and the medulla.
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4. Clinical features
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The symptoms of serotonin syndrome are described as a triad of abnormalities [4]:- Cognitive effects: confusion, hallucinations, agitation, coma.
- Autonomic effects: shivering, sweating, fever, hypertension, tachycardia
- Somatic effects: myoclonus, hyperreflexia, tremor.
Complications include metabolic acidosis, rhabdomyolysis, seizures, renal failure, and disseminated intravascular coagulation [2]. Mortality associated with this condition is estimated to be 11% [5].
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5. Drug interactions
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Drug classes include those that increase serotonin synthesis, inhibit catabolism or uptake (fluoxetine, paroxetine, sertraline, and meperidine), antidepressants (SSRIs, paroxetine), opioids and analgesics (fentanyl, meperidine) [6].
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6. Diagnosis
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To diagnose serotonin syndrome, a history of use of serotonergic agents, recognised clinical features, and exclusion of other conditions are required. A review of the preoperative medication and a detailed neurological examination is important. The diagnosis is made on the presence of at least three of Sternbach's 10 criteria [6] – Agitation, ataxia, diaphoresis, diarrhea, hyperreflexia, fever, confusion, and myoclonus, coincident with the addition of or increase in a known serotonergic agent. The Hunter Serotonin Toxicity Criteria [7] use a smaller, more specific diagnostic set. Clonus is the most important diagnostic criterion, but may be masked by rigidity. There is no specific test for serotonin syndrome. Besides routine blood investigations, renal and hepatic function, and indices of haemolysis should be monitored. Other investigations include a toxicology screen, microbiological samples to exclude sepsis, CT-scan of head and lumbar puncture. Abdominal imaging for serotonin secreting tumours, and electronmicroscopy and immunohistochemistry of the explanted valve could exclude unrecognised serotonin producing microtumours. In our patient, echocardiogram and histopathology of the excised valve did not reveal tumours on the valves.
The principal differential diagnosis is neuroleptic malignant syndrome, where patients usually have higher fevers, pronounced extrapyramidal signs, and raised WBC and CK [8].
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7. Management
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Management includes cessation of serotonergic agents, haemodynamic stabilisation, sedation, temperature control, and hydration. In severe cases, ventilation and paralysis with non-depolarising agents such as vecuronium provides airway control, ensures oxygenation, controls muscle rigidity and hyperthermia and prevents rhabdomyolysis. Myoclonus is treated with benzodiazepines and muscle relaxants. Cyproheptadine and chlorpromazine have been used, with variable efficacy [9]. Our patient had been on escalating doses of paroxetine (SSRI). Perioperatively, she received fentanyl which is known to interact with paroxetine and predispose to serotonin syndrome. Methylene Blue is a potent reversible inhibitor of MAO, leading to perturbations of 5-hydroxytryptamine metabolism and causing serotonin toxicity in patients on SSRI treatment [10]. Clinical examination revealed several of the features described in the Sternbach's criteria. Hence a diagnosis of serotonin syndrome was made. Patients with atypical neurological features postoperatively warrant a detailed neurologic exam and neurology/psychiatric consults. Clinicians should be aware of the potential for lethal pharmaco-dynamic interactions between SSRIs and peri-operative drugs and their impact on clinical outcome. Aggressive management is warranted to ensure a favourable outcome.
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References
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- Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth 1992;39:1061–1066.[Medline]
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112–1120.[Free Full Text]
- Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100–109.[Abstract/Free Full Text]
- Martin T. Serotonin syndrome. Ann Emerg Med 1996;28:520–526.[CrossRef][Medline]
- Mills KC. Serotonin syndrome. Am Fam Physician 1995;52:1475–1482.[Medline]
- Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705–713.[Abstract/Free Full Text]
- Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635–642.[Abstract/Free Full Text]
- Carbone JR. The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am 2000;18:317–325.[CrossRef][Medline]
- Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998;16:615–619.[CrossRef][Medline]
- Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol 2007;152:946–951.[CrossRef][Medline]
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Abstract
1. Case report