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Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome
- Neuroleptic Malignant Syndrome (NMS) is a rare but life-threatening reaction to dopamine-blocking agents
- Key features: Hyperthermia, muscle rigidity, altered mental status, autonomic dysfunction
- Incidence: 0.1% to 3.2% in patients on neuroleptics
- Early recognition and treatment are essential to reduce morbidity and mortality
Case Presentation
- 45-year-old female with schizophrenia treated with haloperidol and lorazepam
- Developed fever, rigidity, altered consciousness, autonomic instability
- Laboratory findings:
- Leukocytosis (14,000/mm³)
- Elevated CPK (5919 IU/L) – sign of muscle breakdown
- Acute kidney injury (Creatinine 1.6 mg/dL)
- Diagnosis: Neuroleptic Malignant Syndrome
Management and Outcome
- Immediate discontinuation of neuroleptics
- Supportive care: Fluids, cooling, oxygen therapy
- Pharmacologic treatment:
- Bromocriptine (dopamine agonist)
- Benzodiazepines (for agitation and muscle rigidity)
- Recovery: Neurological improvement by Day 5, discharged from ICU on Day 9
Pathophysiology & Risk Factors
- Cause: Dopamine blockade → impaired thermoregulation, muscle rigidity, and autonomic dysfunction
- High-risk medications:
- Typical antipsychotics (haloperidol, fluphenazine)
- Atypical antipsychotics (olanzapine, risperidone)
- Other dopamine antagonists (metoclopramide, TCAs)
- Risk factors:
- High-dose or rapid escalation of antipsychotics
- Parenteral administration
- Dehydration
- Underlying psychiatric illness
Clinical Presentation
- Onset: Within 24 hours to 1 week of exposure
- Cardinal Symptoms:
- Hyperthermia (above 38°C)
- Lead-pipe rigidity
- Altered mental status
- Autonomic instability (tachycardia, diaphoresis)
- Lab findings:
- Elevated CPK (above 1000 IU/L) → Rhabdomyolysis
- Leukocytosis, AKI
Differential Diagnosis
- Serotonin Syndrome – Hyperreflexia, clonus, mydriasis
- Malignant Hyperthermia – Post-anesthetic exposure
- Malignant Catatonia – Psychiatric disorder-related
- Toxic/Metabolic Encephalopathy
- CNS infections
Treatment Approaches
1. Stop offending agent immediately
2. Supportive care
- IV hydration, electrolyte correction
- Cooling measures
- Oxygen therapy
3. Pharmacologic therapy (if severe):
- Dopamine agonists (Bromocriptine 2.5 mg TID, max 45 mg/day)
- Muscle relaxants (Dantrolene 1-2.5 mg/kg IV, max 10 mg/kg/day)
- Benzodiazepines
Prognosis and Prevention
- Mortality reduced from 40% to 10-20% with ICU management
- High recurrence risk if reintroducing neuroleptics
- Prevention:
- Use low-dose, gradual titration if restarting neuroleptics
- Avoid high-potency agents if possible
Conclusion
- NMS is a medical emergency requiring rapid recognition and ICU management
- Dopaminergic blockade is the core mechanism
- Early discontinuation of neuroleptics & supportive care are crucial
- Emergency physicians must stay vigilant, especially with IM haloperidol