A 52-year-old man with schizophrenia on haloperidol 10 mg daily presents with a 3-day history of high fever (40.2°C), severe muscle rigidity, altered mental status, and dark urine. On examination, he has marked lead-pipe rigidity, bradykinesia, and is diaphoretic. Laboratory investigations show: CK 8500 U/L, creatinine 2.1 mg/dL (baseline 0.9), potassium 5.8 mEq/L, and myoglobin in urine. Which of the following is the most appropriate immediate management?

Explanation

## Neuroleptic Malignant Syndrome (NMS): Acute Management ### Clinical Diagnosis This patient presents with the **classic tetrad of NMS**: 1. **Fever** — 40.2°C (high-grade) 2. **Muscle rigidity** — severe lead-pipe rigidity 3. **Altered mental status** — confusion/delirium 4. **Autonomic instability** — tachycardia, diaphoresis, hypertension (implied by severe presentation) ### Diagnostic Confirmation **Key Point:** The markedly elevated CK (8500 U/L), myoglobinuria, acute kidney injury (Cr 2.1), and hyperkalemia (5.8) confirm **rhabdomyolysis** secondary to NMS. ### Pathophysiology Antipsychotics (especially typical/first-generation agents like haloperidol) block dopamine in the hypothalamus and basal ganglia, causing: - Loss of thermoregulation → fever - Increased muscle tone → rigidity and rhabdomyolysis - Autonomic dysregulation **Mnemonic: FEVER** — (F)irst-generation antipsychotics, (E)levated CK, (V)ery high fever, (E)xtrapyramidal rigidity, (R)habdomyolysis ### Immediate Management Algorithm ```mermaid flowchart TD A[Suspected NMS]:::outcome --> B[Discontinue antipsychotic immediately]:::action B --> C[Aggressive IV hydration<br/>1-2 L/hr normal saline]:::action C --> D[Monitor urine output & color]:::action D --> E{Myoglobinuria present?}:::decision E -->|Yes| F[Alkalinize urine<br/>Target pH > 6.5]:::action E -->|No| G[Continue hydration<br/>& monitoring]:::action F --> H[Check CK, Cr, K+ Q4-6H]:::action G --> H H --> I{CK declining<br/>& Cr stable?}:::decision I -->|Yes| J[Continue supportive care]:::action I -->|No| K[Consider ICU admission<br/>for dialysis]:::urgent K --> L[Dantrolene if severe/refractory]:::action ``` ### Step-by-Step Acute Management **High-Yield:** The FIRST and MOST CRITICAL step is **immediate discontinuation of the antipsychotic**. This is non-negotiable. 1. **Discontinue haloperidol immediately** — do not continue or reduce dose 2. **Aggressive IV hydration** — 1–2 L/hr normal saline to maintain urine output > 200 mL/hr 3. **Urine alkalinization** — sodium bicarbonate to target urine pH > 6.5 (prevents myoglobin precipitation in renal tubules) 4. **Frequent monitoring** — CK, creatinine, potassium, urine myoglobin Q4–6H 5. **Electrolyte correction** — treat hyperkalemia (calcium gluconate, insulin + dextrose, loop diuretics) 6. **Cooling measures** — ice packs, cooling blankets if fever > 39.5°C 7. **Dantrolene** — reserved for severe/refractory cases (inhibits calcium release from sarcoplasmic reticulum); dose 1 mg/kg IV Q5–10 min up to 10 mg/kg ### Why Dantrolene Is NOT First-Line Here **Clinical Pearl:** Dantrolene is used in **severe, refractory NMS** or when rhabdomyolysis is life-threatening despite supportive care. In this case, aggressive hydration and discontinuation of the antipsychotic are the cornerstones. Dantrolene is expensive, has significant side effects (hepatotoxicity), and is not indicated as first-line therapy. ### Prognosis & Recovery **Key Point:** With prompt discontinuation and supportive care, most patients recover within 5–7 days. Mortality is 5–20% if untreated; < 5% with appropriate management. ### Prevention of Recurrence - Avoid all antipsychotics (especially typical agents) in future - If antipsychotic is absolutely necessary, use atypical agents (risperidone, olanzapine) at lowest effective dose - Ensure adequate hydration and monitoring