hyperthermic toxidromes

feature	serotonin syndrome	neuroleptic malignant syndrome (nms)	malignant hyperthermia	heat stroke
Pathophysiology	Excess Serotonin (5-HT).	Dopamine Depletion.	Genetic (RYR1) $C{a}^{2+}$ dysregulation.	Environmental thermoregulatory failure.
Inciting Agents	SSRIs/SNRIs, TCAs, MAOIs. Linezolid, Tramadol, Fentanyl, Meperidine. MDMA/Cocaine, St. John’s Wort.	Antipsychotics (All classes). Antiemetics (Metoclopramide). Abrupt L-Dopa withdrawal (Parkinson’s).	Volatile Anaesthetics. Succinylcholine.	Environmental: High ambient temp. Risk Factors: Diuretics, Anticholinergics.
Onset	Rapid: Hours (< 24h).	Slow: Days to Weeks.	Immediate: Minutes to hours (Intra-op).	Variable (Exertional vs Non-exertional).
Vital Signs	Hyperthermia, Tachycardia, Labile BP.	Hyperthermia (often > 40°C), Autonomic instability.	Extreme Hyperthermia (> 42°C), Rising $EtC{O}_2$.	Temp > 40°C, Tachycardia, hypotension.
Neuromuscular	Hyperreflexia, Clonus (Lower > Upper). Tremor, Myoclonus.	”Lead Pipe” Rigidity. Hyporeflexia (No clonus).	Severe Rigidity. Hyporeflexia.	Weakness, ataxia. +/- Rhabdomyolysis.
Mental Status	Agitated, Restless, Delirium.	Agitated delirium $\to$ Catatonia $\to$ Coma.	Coma (under anaesthesia).	Confusion, Agitation, Coma, Seizures.
Treatment	Stop Agent. Benzodiazepines. Cyproheptadine (5-HT antagonist).	Stop Agent. Benzodiazepines. Bromocriptine (DA agonist). Dantrolene (rarely).	Stop Agent. Hyperventilate. Dantrolene.	Rapid Cooling (Target 38°C). Supportive (Fluids). NO Dantrolene.

serotonin vs nms

• Clonus / Hyperreflexia = Serotonin Syndrome.
• Rigidity / Hyporeflexia = NMS.
• NMS Tetrad “FARM”: Fever, Autonomic instability, Rigidity, Mental status change.

hunter criteria (serotonin syndrome)

• Serotonergic Agent + one of:
  1. Spontaneous Clonus.
  2. Inducible Clonus + Agitation.
  3. Ocular Clonus + Agitation.
  4. Tremor + Hyperreflexia.
  5. Hypertonia + Temp > 38°C + Ocular Clonus.