Malignant Hyperthermia vs. Neuroleptic Malignant Syndrome: Key Differences
Malignant hyperthermia (MH) and neuroleptic malignant syndrome (NMS) are distinct hypermetabolic disorders that differ fundamentally in their triggers, patient populations, and treatments—MH is triggered exclusively by volatile anesthetics and succinylcholine during general anesthesia, while NMS is caused by antipsychotic medications or abrupt withdrawal of dopaminergic agents. 1, 2, 3
Triggers and Context
Malignant Hyperthermia
- Triggered exclusively by: All volatile inhalational anesthetic agents (sevoflurane, desflurane, isoflurane, halothane) and succinylcholine during general anesthesia 1, 2, 4
- Occurs: During or shortly after anesthetic exposure in the operating room setting 1
- Can occur: Even in patients who have had multiple uneventful previous anesthetics with triggering agents 1, 5
Neuroleptic Malignant Syndrome
- Triggered by: Antipsychotic medications (neuroleptics), thymoleptics (antidepressants), metoclopramide, or abrupt withdrawal of dopaminergic agents like levodopa 2, 3
- Occurs: In psychiatric or medical settings during treatment with these medications, not related to anesthesia 3, 6
- Risk factors include: Dehydration, agitation, exhaustion, rapid dose titration, high doses of neuroleptics, or abrupt discontinuation of antiparkinsonism agents 3, 6
Patient Population
Malignant Hyperthermia
- Any patient can develop MH during anesthesia with trigger agents—this is a pharmacogenetic disorder with autosomal-dominant inheritance 1
- Prevalence: Estimated up to 1:3000 in the general population 1
- Genetic predisposition: Related to abnormalities in calcium-induced calcium release (CICR) in skeletal muscle 7
Neuroleptic Malignant Syndrome
- Patients receiving antipsychotic medications for psychiatric conditions or antiemetics like metoclopramide 3, 6
- Higher risk in: Patients with organic brain syndrome, dehydration, exhaustion, or those on high-dose or long-acting neuroleptics 3
Clinical Presentation Differences
Malignant Hyperthermia
- Earliest sign: Unexplained increase in end-tidal CO₂ despite increased minute ventilation, often before temperature elevation 2
- Muscle rigidity: Masseter spasm (if succinylcholine used) or generalized muscle rigidity 1, 4
- Rapid onset: Develops during or immediately after anesthetic exposure 1
- Hypermetabolic crisis: Tachycardia, tachypnea, hyperthermia, hypercarbia, acidosis 1
Neuroleptic Malignant Syndrome
- Initial manifestations: Mental status changes or "lead pipe" skeletal muscle rigidity, followed by hyperthermia and autonomic dysfunction 2, 3
- Slower onset: Typically develops over days to weeks after starting or increasing antipsychotic medication 3, 6
- Characteristic features: Altered consciousness, autonomic instability, leukocytosis, elevated creatine phosphokinase 3, 8
Treatment Differences
Malignant Hyperthermia Treatment
Immediate actions:
- Stop all trigger agents immediately (volatile anesthetics and succinylcholine) 1
- Hyperventilate with 100% oxygen at 2-3 times normal minute volume 1
- Administer dantrolene 2 mg/kg IV immediately, repeating until cardiac and respiratory systems stabilize (may exceed 10 mg/kg maximum) 1, 2
- Change to non-trigger anesthesia (total intravenous anesthesia) 1
- Active cooling: Chilled IV saline (4°C), surface cooling with ice packs, stop cooling once temperature <38.5°C 1
- Treat hyperkalemia: Dextrose 50% with insulin, calcium chloride, dialysis if needed 1
- Monitor for minimum 24 hours in ICU/HDU setting 1, 2
Neuroleptic Malignant Syndrome Treatment
Immediate actions:
- Immediately discontinue all antipsychotic medications 2, 3, 6
- Aggressive supportive care: Benzodiazepines for agitation, external cooling for hyperthermia 2, 6
- Dantrolene IV infusion (same dosing as MH) 3, 8
- Bromocriptine orally (dopamine agonist) to restore dopaminergic function 9, 3, 8
- Alternative regimen: Dantrolene plus levodopa-carbidopa combination 3
- Anticholinergic drugs (benztropine) may enhance bromocriptine effectiveness 3
- Electroconvulsive therapy if psychotic symptoms persist despite medical management 3
Critical Pitfalls to Avoid
Diagnostic Confusion
- Do not assume NMS in the operating room setting—if volatile anesthetics or succinylcholine were used, MH must be ruled out first even if the patient is on antipsychotics 10, 7
- Recognize that patients on chronic antipsychotics can still develop MH during anesthesia with triggering agents—the two conditions can coexist 7
- Do not delay dantrolene administration while attempting to differentiate between MH and NMS—both respond to dantrolene, and early treatment is critical for survival 1, 2, 3
Treatment Errors
- In MH, stopping trigger agents is mandatory—dantrolene alone without removing the triggering anesthetic will not resolve the crisis 1
- In NMS, bromocriptine (dopamine agonist) is beneficial, but this is not used in MH treatment 9, 3
- Avoid calcium channel blockers in suspected MH as they may interfere with dantrolene treatment 10
- Do not rechallenge with antipsychotics for at least 2 weeks following NMS resolution 6
Mortality and Prognosis
Malignant Hyperthermia
- Survival is highly dependent on early recognition and prompt dantrolene administration 1, 2
- Mortality has decreased significantly with availability of dantrolene and increased awareness 1
Neuroleptic Malignant Syndrome
- Mortality has decreased from 76% in the 1960s to <10-15% with prompt management and early recognition 2
- Requires active rather than passive treatment to avert fatalities 3
Pathophysiology Distinction
Malignant Hyperthermia
- Intrinsic abnormality of skeletal muscle tissue with abnormal calcium-induced calcium release from sarcoplasmic reticulum 11, 7
- Triggering agents produce elevated myoplasmic calcium, activating acute cellular catabolic processes 11