Serotonin syndrome - NYSORA

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Serotonin syndrome

Learning objectives

  • Describe the wide variety of signs and symptoms of serotonin syndrome (SS)
  • Management of a patient with SS

Definition and mechanisms

  • The serotonin syndrome (SS) is a potentially life-threatening drug interaction caused by excessive serotoninergic activity in the CNS
  • Can arise from therapeutic drug use, drug interactions, or intentional overdose of medications that affect the serotonergic system, use the mnemonic MAD HOT:
    • Myoclonus
    • Autonomic instability
    • Delirium, Diarrhea
    • Hot (fever)
  • CNS: seizure, altered LOC
  • CVS: tachycardia & HTN, autonomic instability, arrhythmia
  • MSK: rigidity, rhabdomyolysis, hyperkalemia & renal failure
  • Hyperthermia
  • Disseminated intravascular coagulation
  • Onset of SS typically occurs all of a sudden within 24-48h of exposure to the triggering agents and usually resolves quickly after the triggering agent is discontinued
  • Note that the washout period after discontinuation is highly variable between psychotropic drugs 

Signs and symptoms

MildSweating
Fever
Agitation
Confusion
Anxiety
Tachycardia
Diarrhea
Tremors
Poor coordination
Full-blownHyperthermia
Shivering
Diaphoresis
Hypomania
Hypervigilance
Hypertension
Hyperreflexia
Clonus
Myoclonus
SevereHyperthermia > 40°C
Seizures
Coma
Rigidity

Differential diagnosis

Disease Medication exposureShared clinical featuresDistinguishing clinical features
Serotonin SyndromeSerotonergic medicationsHypertensionClonus
Hyperreflexia
Hyperactive bowel sounds
Neuroleptic malignant syndromeDopamine antagonists TachycardiaNo clonus or hyperreflexia
Bradykinesia
Anticholinergic toxicity Acetylcholine antagonistHyperthermiaNo clonus or hyperreflexia
Dry skin
Absent bowel sounds
Malignant hyperthermiaHalogenated anesthetics
Succinylcholine
Altered mental statusNo clonus or hyperreflexia
Extreme muscular rigidity

Management

Serotonin syndrome (SS), cyproheptadine, benzodiazepines, noradrenaline, epinephrine, dopamine, MOAIs, esmolol, glyceryl trinitrate, paracetamol, topic cooling, suxamethonium, hyperkalemia, bromocriptine

Suggested reading

  • Bartakke, A., Corredor, C., Van Rensburg, A., 2020. Serotonin syndrome in the perioperative period. BJA Education 20, 10–17.
  • Francescangeli, J., Karamchandani, K., Powell, M., Bonavia, A., 2019. The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice. International Journal of Molecular Sciences 20, 2288.
  • Chinniah, S., French, J.L.H., Levy, D.M., 2008. Serotonin and anaesthesia. Continuing Education in Anaesthesia Critical Care & Pain 8, 43–45.

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