Hyperthermia Syndromes

Hyperthermia Syndromes in the ICU — Comparative Guide

This quick-reference table compares the major non-infectious hyperthermia syndromes encountered in critical care, highlighting typical triggers, timing, clinical features, laboratory clues, and first-line treatments.

Syndrome	Typical Trigger(s)	Onset Tempo	Key Neuromuscular Findings	Autonomic / Systemic Features	Lab Clues	First-Line Treatment(s)
Malignant Hyperthermia (MH)	Volatile anesthetics, succinylcholine (RYR1 / CACNA1S variants)	Minutes during anesthesia; may recur post-op	Generalized or masseter rigidity	Rapid ETCO2 rise, tachycardia, late hyperthermia	CK > 10 000, hyper-K+, acidosis, ↑ lactate	IV dantrolene 2.5 mg/kg bolus (repeat to 10 mg/kg), aggressive cooling, treat K+/acidosis
Neuroleptic Malignant Syndrome (NMS)	D2 antagonists (e.g., haloperidol) or dopamine-agonist withdrawal	Days (gradual)	“Lead-pipe” rigidity, bradyreflexia, mutism	Fever, autonomic storms, altered mental status	CK > 1 000, leukocytosis, acidosis	Stop culprit; dantrolene 1–2 mg/kg q6 h or bromocriptine 2.5–10 mg q6-8 h + support
Serotonin Syndrome (SS)	Serotonergic agent(s) / interaction (e.g., SSRI + MAOI)	Hours (< 24 h)	Hyperreflexia, inducible/sustained clonus, myoclonus, tremor	Fever, diaphoresis, mydriasis, hypertension, agitation	Mild CK rise, ± acidosis	Stop serotonergic drugs; cyproheptadine 12 mg load then 2 mg q2 h (max 32 mg/24 h), benzodiazepines, cooling
Thyroid Storm	Stress in hyperthyroid pt (surgery, sepsis, trauma)	Hours – days	Tremor, agitation ± weakness	High fever, tachyarrhythmias, heart failure, GI symptoms	↓ TSH, ↑ free T4/T3	PTU or methimazole, β-blocker, iodide (≥ 1 h post-thionamide), hydrocortisone, cooling
Heat Stroke (Exertional / Classic)	Environmental heat ± exertion, impaired heat dissipation	Acute collapse (mins–hrs)	Ataxia, seizures, possible rhabdo	Core T ≥ 40 °C, CNS dysfunction, DIC	CK↑, ↑ AST/ALT, coagulopathy, ↑ creatinine	Rapid whole-body cooling (ice bath preferred); airway/BP support; dantrolene if shivering refractory

Clonus — Clinical Significance

Clonus is a rhythmic, involuntary, self-sustaining muscle contraction triggered by sudden passive stretch (classically at the ankle). In serotonin syndrome, inducible or sustained (≥ 5-beat) clonus is a key diagnostic clue and correlates with severity. Clonus is typically absent in MH and NMS, where rigidity is “lead-pipe” or generalized.

Selected References

1. Chiew AL et al. Management of serotonin syndrome. Br J Clin Pharmacol. 2025.
2. StatPearls. Neuroleptic Malignant Syndrome. 2024.
3. UpToDate. Serotonin syndrome (serotonin toxicity). 2024.
4. Critical Care Medicine. Malignant Hyperthermia Review. 2024.
5. NCBI Bookshelf. Malignant Hyperthermia. 2024.

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