Serotonin Syndrome

Serotonin Syndrome from Sun YaiCheng

The Serotonin Syndrome
N Engl J Med 2005;352:1112-20.

Clinical triad of the serotonin syndrome:

1. Mental-status changes
   

   agitation and delirium

2. Autonomic hyperactivity
   

   tachycardia, mydriasis, diaphoresis, the presence of bowel sounds and diarrhea

3. Neuromuscular abnormalities
   

   Hyperreflexia, inducible clonus, myoclonus, ocular clonus, spontaneous clonus, peripheral hypertonicity, and shivering

Diagnosis

• The presence of tremor, clonus, or akathisia without additional EPS should consider the diagnosis. 

• Physical examination should include a focused assessment of DTR, clonus, and muscle rigidity, in addition to an evaluation of the size and reactivity of the pupils, the dryness of the oral mucosa, the intensity of bowel sounds, skin color, and the presence or absence of diaphoresis.

Hunter Serotonin Toxicity Criteria
QJM 2003;96:635-42

Differential Diagnosis

Condition	Serotonin syndrome	Anticholinergic “toxidrome”	NMS	Malignant hyperthermia
Medication History	Proserotonergic drug	Anticholinergic agent	Dopamine antagonist	Inhalational anesthesia
Onset	<12 hr	<12 hr	1–3 days	30 min to 24 hr
Vital Signs	Hypertension, tachycardia, tachypnea, Hyperthermia (>41.1°C)	Hypertension (mild), tachycardia, tachypnea, hyperthermia (typically < 38.8°C)	Hypertension, tachycardia, tachypnea, hyperthermia (>41.1°C)	Hypertension, tachycardia, tachypnea, hyperthermia (can be as high as (46.0°C)
Pupils	Mydriasis	Mydriasis	Normal	Normal
Mucosa	Sialorrhea	Dry	Sialorrhea	Normal
Skin	Diaphoresis	Erythema, hot and dry	Pallor, diaphoresis	Mottled, diaphoresis
Bowel Sounds	Hyperactive	Decreased or absent	Normal or decreased	Decreased
Neuromuscular Tone	Increased, predominantly in lower extremities	Normal	“Lead-pipe” rigidity present in all muscle groups	Rigor mortis–like rigidity
Reflexes	Hyperreflexia, clonus	Normal	Bradyreflexia	Hyporeflexia
Mental Status	Agitation, coma	Agitated delirium	Stupor, alert Mutism, coma	Agitation

Management

1. Removal of the precipitating drugs 

2. Provision of supportive care 

3. Control of agitation

Control of agitation with benzodiazepines is essential in the management of the serotonin syndrome, regardless of its severity. 

Physical restraints are ill-advised and may contribute to mortality by enforcing isometric muscle contractions that are associated with severe lactic acidosis and hyperthermia.

4. Administration of 5-HT2a antagonists

Cyproheptadine

Initial dose: po 12 mg and then 2 mg q2h if symptoms continue
Maintenance dose: po 8 mg q6h

Olanzapine, sublingual 10 mg

Chlorpromazine, intramuscular 50-100 mg

5. Control of autonomic instability

Hypotension should be treated with low doses of direct-acting sympathomimetic amines (e.g., norepinephrine, phenylephrine, and epinephrine).

Hypertension and tachycardia should be treated with short-acting agents such as nitroprusside and esmolol.

6. Control of hyperthermia

In severely ill patients with hyperthermia (temperature >41.1°C), immediate paralysis should be induced with non-depolarizing agents such as vecuronium, followed by orotracheal intubation and ventilation.

There is no role for antipyretic agents in the management of the serotonin syndrome.

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