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Pathophysiology

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(Medicine 2000;79:201; N Engl J Med 2005;352:1112)

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  • Central & peripheral serotonin (5-HT) receptors responsible for SS → excess stimulation caused by excess serotonin precursors or agonists, ↑ serotonin release, ↓ serotonin reuptake, ↓ serotonin metabolism
  • Pharmacologic treatment → control signs/symptoms & ↓ 5-HT receptor activation if symptoms are severe
  • ∼60% of SS cases occur ≤6h after change in dose or addition of medication (The ICU book. 3rd ed. 2007; N Engl J Med 2005;352:1112) 25% of cases present after 24h (Med Clin North Am 2005;89:1277); just as likely to develop with therapeutic doses as with overdoses (Crit Care Clin 1997;13:763)
  • Left untreated → seizures, coma, rhabdomyolysis, metabolic acidosis, renal failure, cardiac failure, DIC; ↑ death in environments with ↑ ambient temp (Med Clin North Am 2005;89:1277)
  • Most cases resolve within 24h after appropriate management (supportive care, stop serotonergic meds) (The ICU book. 3rd ed. 2007; N Engl J Med 2005;352:1112)

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Clinical Pearl 44-1

Bupropion (Wellbutrin®) is the only antidepressant without significant serotonergic activity; may exhibit some at 10× the recommended dose

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Clinical Pearl 44-2

The effects of fluoxetine & MAOIs can last more than a week, so monitor for persistent symptoms of SS

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Clinical Pearl 44-3

What about linezolid? FDA warning (7/26/11) indicates linezolid should not be combined with serotonergic medications due to its MAOI-A inhibition. Serotonergic medications must be stopped 2wk before starting linezolid (5wk for fluoxetine). Serotonergic medications may be restarted 24h after last dose of linezolid.

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Figure 44-1.
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Serotonin syndrome pathogenesis. (Data from Rusyniak DE, Sprague JE: Toxin-induced hyperthermic syndromes, Med Clin North Am 2005: Nov;89(6):1277.)

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Table 44-1 Medications Associated with SS
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Diagnosis & Evaluation

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Signs & Symptoms

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(N Engl J Med 2005;352:1112; Med Clin North Am 2005;89:1277)

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  • Neurologic changes: AMS, agitation, confusion, ataxia, akathisia; neuromuscular abnormalities (greater in lower extremities): tremor, muscle rigidity, hyperreflexia, clonus (most sensitive physical finding; most obvious in patellar deep tendon ...

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