Introduction

Serotonin syndrome (SS) is the result of excess serotonergic activity in the CNS. It can occur with therapeutic use of multiple serotonergic medications or from supratherapeutic dosing of a single serotonergic medication. Classic manifestations include altered mental status, autonomic hyperactivity, and clonus. Like Neuroleptic Malignant Syndrome (NMS), SS exists on a continuum and not all above mentioned manifestations need be present for a diagnosis. Onset is typically rapid occurring over the course of minutes up to about 24 h.

Symptoms

Agitation

Disorientation

Restlessness

Delirium

Signs

Clonus (typically more pronounced in the lower extremities)

Hyperreflexia

Muscular hyperactivity

Diarrhea

Akathisia

Rigidity

Hypertension

Tachycardia

Diaphoresis

Hyperthermia

Mydriasis

Seizures

Life-Threatening Symptoms /Signs

Serotonin Syndrome is a medical emergency and should be treated as such. Life-threatening manifestations include rhabdomyolysis with resultant renal failure. Hyperthermia can lead to multi-organ system failure, cardiopulmonary collapse, and death. Episodes of disseminated intravascular coagulation have also been reported.

Differential

Antimuscarinic poisoning

Dystonic reaction

Encephalitis

Excited catatonia

Heat-stroke

Malignant hyperthermia

Meningitis

Nonconvulsive status epilepticus

Pheochromocytoma

Porphyria

Rabies

Serotonin syndrome

Strychnine poisoning

Sympathomimetic intoxication, cocaine, methamphetamine, PCP

Tetanus

Thyroid storm

Baclofen Withdrawal

Testing

  • Diagnosis is based on history, clinical findings, and exclusion of other diagnoses.

  • The Hunter Criteria (see below) are a set of decision rules used to diagnose SS. They are internally validated and found to have good agreement with the diagnosis by a clinical toxicologist.

  • Basic labs including a BMP, CBC, and UA

  • A CPK should be checked to assess for muscle breakdown

  • A liver panel, ammonia, TSH, CT head, LP, CXR, Vitamin B12 and Thiamine levels, HIV, RPR, and VDRL should be considered in the clinical context

Treatment

  • Largely supportive, stabilize ABCs.

  • IV fluid resuscitation

  • Liberal use of benzodiazepines is a mainstay of treatment

  • Aggressive cooling measures

  • Patients with resistant hyperthermia can be intubated and paralyzed to prevent heat production from muscles

  • Discontinuation of all serotonergic medications

  • Cyproheptadine, an early anti-histamine with anti-serotonergic activity, can also be used. It is only available as an oral preparation complicating administration in critically ill patients. No evidenced based dosing recommendations exist. A starting dose of 8 mg repeated as necessary is reasonable based on case reports.

Tool

Tool 1: Hunter Criteria

If any of the following, may diagnose SS:

Spontaneous clonus

Inducible clonus + agitation OR diaphoresis

Ocular clonus + agitation OR diaphoresis

Tremor + hyperreflexia

Hypertonia + temp above 38 + ocular clonus OR inducible clonus

  1. Sensitivity 84%, specificity 97%

  • How to induce clonus: Clonus refers to a persistent reflex contraction of a muscle after an initial stimulus. Clonus can often be best appreciated with regard to the Achilles reflex. To check for clonus, forcefully dorsiflex the foot at the ankle and maintain slight dorsal pressure on the foot.

Tool 2

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