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Topic: Thyroidectomy - postop agitation and rigidity; serotonin syndrome
A 50-year-old 90-kg female with a multinodular goiter and history of hyperthyroidism is scheduled for a subtotal thyroidectomy. She is euthyroid on propylthiouracil. She underwent a lung resection 3 months ago with no known complications. She has COPD and takes Prednisone and Levalbuterol. She is induced with propofol and relaxed with succinylcholine. Maintenance is with sevoflurane/air/oxygen. She is given 50 cc 1% methylene blue iv to identify the parathyroid glands. The 4-hour anesthetic (0800 – 1200) is uneventful.
In the PACU, the patient became progressively agitated, tachycardic and diaphoretic. SpO2 was 88% on 6 l/min. O2 by face mask. Methemoglobin level was < 0.3%. While muscle tone in the arms was normal, she had severe lower extremity rigidity. The patient is reintubated following propofol and 10 mg vecuronium. The lower extremity rigidity completely resolves.
1) The complete resolution of muscle rigidity following full relaxation with vecuronium excludes MH as the cause of rigidity?
A) True
B) False
The patient was also taking Zoloft (sertraline) and Buspar (buspirone). Metoclopramide had been ordered but had not been given. An MRI performed excluded an acute intracranial lesion. Her temperature is 101° F.
2) Which of the following are possible diagnoses? (May have more than one correct choice)
A) Thyroid storm
B) Acute hypocalcemia
C) Neuroleptic Malignant Syndrome
D) Serotonin Syndrome
E) Central Anticholinergic Syndrome
The serum calcium level is 8 mg/dL. The patient is sedated with propofol and lorazepam and muscle relaxation is maintained with vecuronium overnight. The patient is successfully weaned and extubated on the afternoon of post-operative day 1, with no neurologic sequelae.
3) The most likely diagnosis explaining this patient’s postoperative agitation, rigidity, and hyperthermia is:
A) Neuroleptic Malignant Syndrome
B) Malignant Hyperthermia
C) Thyroid Storm
D) Serotonin Syndrome
4) Methylene blue is an oxidizing agent?
A) True
B) False
Answers:
1. A
2. B & D
3. D
4. A
Narrative:
This patient exhibited postoperative agitation, tachycardia, diaphoresis, and lower extremity rigidity. The anesthesiologist who called the hotline was evaluating the patient in the recovery room and had not taken care of her in the OR. The patient was reintubated because of hypercarbia, hypoxemia, and agitation. The striking finding of severe lower extremity rigidity rapidly resolved following complete relaxation with vecuronium. In MH, muscle rigidity will persist despite full relaxation with a non-depolarizing muscle relaxant; the pathology is within the myocyte (i.e., distal to the neuromuscular junction).
Acute hypocalcemia results in increased nerve excitability. Tremor, agitation, paresthesia, fasciculation, muscle spasm, or seizures may occur. This patient’s serum calcium, while decreased, was not low enough to account for the clinical findings. With acute hypocalcemia, one also would not expect increased muscle tone to be limited to the lower extremities.
Thyroid storm may cause hyperthermia, agitation, and diaphoresis but it is not associated with muscle rigidity.
Central anticholinergic syndrome is associated with absence of sweating and dry mucous membranes.
Neuroleptic Malignant Syndrome (NMS) is characterized by altered mental status (lethargy), autonomic instability, “lead-pipe” rigidity, extrapyramidal side effects, rhabdomyolysis. The onset is typically (but not always) gradual. Mortality is substantial (> 10%). NMS is an idiosyncratic response to CNS dopamine antagonists (e.g., droperidol, phenothiazines, or metoclopramide); it is sometimes seen during withdrawal from therapy for Parkinson’s disease. In addition to supportive measures, dantrolene is often given to treat the muscle rigidity and prevent further muscle injury. Bromocriptine is given to correct the underlying CNS pathophysiology. Dantrolene and bromocriptine are often continued as combination therapy for at least 1 week after initial control of NMS to prevent recrudescence. ECT has been used for treatment of refractory cases.
Serotonin Syndrome is characterized by altered mental status (agitation, confusion), myoclonus, clonus, hyperreflexia, tremor, trismus, shivering, autonomic instability, pupillary dilatation, and diarrhea. Severe cases may develop hyperthermia, rigidity (first in lower extremities), and rhabdomyolysis. The onset is typically faster (e.g. minutes to hours) than seen in neuroleptic malignant syndrome.
Serotonin syndrome is associated with:
· Combination Demerol, tramadol (Ultram) or dextromethorphan (cough
suppressant) +MAOI
· Combination SSRI, SNRI [serotonin + norepinephrine reuptake inhibitor (e.g.
Effexor)], serotonin (5-HT2A) agonists (e.g., LSD or mescaline), lithium, or
tricyclic antidepressant (clomipramine or imipramine) + MAOI
· Serotonin releasers - Ecstasy (MDMA), other amphetamines, cocaine,
fenfluramine
· Occasionally with monotherapy: overdose SSRI
Treatment is generally supportive (discontinuing the offending medications and hydration) but severe episodes may be fatal without aggressive treatment. Some patients will require sedation (benzodiazepines), ventilatory support, muscle relaxation, hydration and cooling measures. Chlorpromazine (12.5 – 25 mg IV initial dose), a 5-HT2A antagonist, is recommended by Gillman for use in life-threatening serotonin syndrome. Chlorpromazine may cause hypotension, though patients with severe serotonin syndrome are usually hypertensive and not ambulating. Bromocriptine, which is beneficial for treatment of NMS, may worsen serotonin syndrome.
The hotline consultant suggested the diagnosis of serotonin syndrome because the patient was taking an SSRI (Zoloft) preoperatively and postoperatively rapidly manifested agitation, lower extremity rigidity, hyperthermia, tachycardia and diaphoresis. No neuroleptic had been given. The question arises why the patient, who was not taking an MAO inhibitor or thought to have taken an overdose of Zoloft, developed serotonin syndrome. Review of the literature revealed a remarkably similar case of a female taking fluoxetine (Prozac) who received 7.5 mg/kg methylene blue during general anesthesia for a parathyroidectomy and had early postoperative agitation, ocular clonus, myoclonus, increased muscle tone, and diaphoresis. In addition, the acute injection of methylene blue in the presence of an SSRI has been shown to increase CNS levels of serotonin by more than 2-fold in rats. In 1986, Naylor, using po methylene blue 300 mg/day, reported a reduction in the duration and severity of depression in patients with bipolar affective disorder. The hotline consultant speculated that methylene blue caused an abrupt increase in CNS serotonin level in this patient chronically taking Zoloft.
Methylene blue is an oxidizing agent. In the treatment of methemoglobinemia, methylene blue is reduced (by NADPH) to leukomethylene blue, which then reduces methemoglobin to deoxy-hemoglobin.
Suggested references
Serotonin Syndrome:
1) Isbister GK, Buckley NA. Clin Neuropharmacol 2005; 28: 205-214
2) Gillman PK. Br J Anaesth 2005; 95: 434-441
3) Boyer EW, Shannon M. N Eng J Med 2005; 352: 1112-20
4) Gillman’s website: www.psychotropical.com
Methylene blue, depression, serotonin and serotonin syndrome:
1) Martindale SJ, Stedeford JC. Anaesthesia 2003; 58: 1041-2
2) Deam R, Francis DM. Anaesthesia 2004; 59: 826
3) Wegener G, Volke V, Rosenberg R. Br J Pharmacol 2000; 130: 575-80
4) Eroglu L, Caglayan B. Pharmacol Res 1997; 36: 381-5
5) Naylor GJ, Martin B, Hopwood SE, et al. Biol Psychiatry 1986; 21: 915-
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_____________________________________________
MH Hotline Consultant
Professor of Anesthesiology
UCLA School of Medicine
Los Angeles CA 90095-1778
