A 42-year-old man from Mumbai with a history of type 2 diabetes presents to the emergency department with acute onset severe hyperthermia (core temperature 40.8°C), profuse diaphoresis, muscle rigidity, and altered mental status. His wife reports he started taking a newly prescribed medication 3 days ago for depression. Serum creatine kinase is 3200 U/L (normal <200), and urine myoglobin is positive. Vital signs: HR 118/min, BP 168/95 mmHg, RR 24/min. What is the most appropriate immediate next step in management?

Explanation

## Clinical Diagnosis: Neuroleptic Malignant Syndrome (NMS) This patient presents with the classic tetrad of NMS: 1. **Hyperthermia** (40.8°C) 2. **Muscle rigidity** ("lead-pipe" rigidity) 3. **Altered mental status** (confusion) 4. **Autonomic instability** (tachycardia, hypertension, diaphoresis) Plus **rhabdomyolysis** (elevated CK, myoglobinuria), a life-threatening complication. ## Why Dantrolene Sodium? **Key Point:** Dantrolene is the specific pharmacological treatment for NMS and malignant hyperthermia. It acts as a skeletal muscle relaxant by inhibiting calcium release from the sarcoplasmic reticulum, reducing muscle contractility and heat generation. **High-Yield:** NMS is a medical emergency with mortality 5–20% if untreated. Dantrolene is the only drug that directly addresses the underlying pathophysiology. ### Mechanism of Dantrolene in NMS ```mermaid flowchart TD A[Antipsychotic exposure]:::outcome --> B[Dopamine D2 receptor blockade in hypothalamus]:::outcome B --> C[Loss of thermoregulation + muscle hypertonicity]:::outcome C --> D[Uncontrolled muscle contraction & heat generation]:::urgent D --> E[Hyperthermia + Rhabdomyolysis]:::urgent E --> F{Dantrolene administered?}:::decision F -->|Yes| G[Inhibit Ca2+ release from SR]:::action F -->|No| H[Progressive organ failure, death]:::urgent G --> I[Reduced muscle contractility & heat]:::action I --> J[Temperature normalization]:::outcome ``` ## Management Algorithm for NMS | Step | Action | Rationale | |------|--------|----------| | **Immediate** | Discontinue antipsychotic | Remove trigger | | **Immediate** | Dantrolene 2.5 mg/kg IV bolus (max 10 mg/kg/day) | Specific muscle relaxant; reduces heat & CK | | **Concurrent** | Aggressive cooling (ice packs, cold IV fluids, cooling blanket) | Reduce core temperature | | **Concurrent** | IV fluid resuscitation (target UOP >200 mL/hr) | Prevent acute kidney injury from myoglobin precipitation | | **Concurrent** | Continuous cardiac monitoring & ICU admission | Monitor for arrhythmias, organ failure | | **Supportive** | Treat hyperkalemia if present (calcium gluconate, insulin-glucose, furosemide) | Prevent cardiac arrhythmias from rhabdomyolysis | **Clinical Pearl:** Dantrolene must be given **immediately**—every hour of delay increases mortality. Do NOT wait for diagnostic confirmation or ICU bed availability. **Mnemonic: DANTROLENE in NMS** — **D**opamine blockade → **A**ntipsychotic stop + **N**euromuscular **T**reatment (dantrolene) → **R**apid **O**xygen/cooling + **L**arge IV fluids → **E**lectrolyte monitoring → **N**ormalization of temp → **E**arly ICU discharge. [cite:Harrison 21e Ch 395]