A 48-year-old man with schizophrenia is admitted to the psychiatric ward on haloperidol 15 mg daily. On day 4 of admission, nursing staff report he is rigid, febrile (39.2°C), diaphoretic, and has not passed urine in 8 hours. Serum CK is 2400 U/L (normal <200), and creatinine is 1.8 mg/dL (baseline 0.9). What is the most appropriate immediate next step?

Explanation

## Clinical Diagnosis: Neuroleptic Malignant Syndrome (NMS) **Key Point:** This patient meets **all four diagnostic criteria for NMS**: 1. **Exposure to antipsychotic** (haloperidol, a typical/first-generation agent) 2. **Fever** (39.2°C, core temperature > 38.5°C) 3. **Muscle rigidity** (reported by nursing) 4. **Elevated CK** (2400 U/L, indicating rhabdomyolysis) + **acute kidney injury** (creatinine 1.8, baseline 0.9) **High-Yield:** NMS is a **rare but life-threatening idiosyncratic reaction** to antipsychotics. Unlike serotonin syndrome (hours to days), NMS typically develops over **24–72 hours** after antipsychotic initiation or dose increase. ## Comparison: NMS vs Serotonin Syndrome | Feature | NMS | Serotonin Syndrome | |---------|-----|--------------------| | **Onset** | 24–72 hrs (days) | Hours to 24 hrs | | **Causative drugs** | Antipsychotics (esp. typical) | SSRIs, SNRIs, tramadol, MAOIs | | **Clonus** | Absent/rare | Present (specific sign) | | **GI symptoms** | Rare | Common (diarrhea) | | **Recovery time** | 7–10 days (even after drug stop) | 24–72 hrs after drug stop | | **Dantrolene** | Indicated in severe cases | Not indicated | | **Bromocriptine** | May accelerate recovery | Not used | ## Management Algorithm ```mermaid flowchart TD A[Suspected NMS:<br/>Antipsychotic + Fever + Rigidity + High CK]:::outcome --> B{Severity?}:::decision B -->|Mild| C[Stop antipsychotic<br/>Supportive care<br/>Monitor CK/Renal]:::action B -->|Moderate-Severe<br/>CK > 1000 or AKI| D[STOP antipsychotic immediately]:::urgent D --> E[Aggressive IV hydration<br/>Target UOP > 200 mL/hr]:::action D --> F[Active cooling if T > 39.5°C]:::action D --> G[Consider dantrolene<br/>2.5 mg/kg IV Q4-6H]:::action D --> H[ICU monitoring<br/>Daily CK, creatinine, K+]:::action H --> I[Bromocriptine 2.5 mg TDS<br/>if no improvement in 24-48 hrs]:::action ``` ## Immediate Management Steps 1. **Stop haloperidol immediately** — do not continue or reduce; complete cessation is mandatory 2. **Aggressive IV hydration** — target urine output > 200 mL/hr to prevent myoglobinuria-induced acute tubular necrosis 3. **Monitor vital signs, CK, creatinine, potassium, urine myoglobin** — daily or more frequently 4. **Active cooling** if core temperature > 39.5°C 5. **ICU admission** — given elevated CK (rhabdomyolysis) and rising creatinine (AKI) 6. **Dantrolene sodium** — consider if: - CK rapidly rising (> 5000 U/L) - Severe hyperthermia (> 40°C) - No improvement with hydration/cooling in 24 hrs - Dose: 2.5 mg/kg IV bolus, repeat Q4–6H (max 10 mg/kg/day) 7. **Bromocriptine** (dopamine agonist) — if NMS persists despite drug cessation and supportive care (2.5 mg TDS, increase gradually) **Clinical Pearl:** The presence of **acute kidney injury** (rising creatinine) in the setting of elevated CK indicates **myoglobinuria**. This is a medical emergency requiring ICU-level care and aggressive hydration to prevent progression to irreversible renal failure. **Warning:** Do NOT continue or reduce the antipsychotic dose — this is a common error. NMS does not improve with dose reduction; the drug must be stopped entirely. Rechallenge with the same or similar antipsychotic is contraindicated unless absolutely necessary and only after full recovery (weeks to months). [cite:Harrison 21e Ch 397; Adityanjee et al. (2005) CNS Drug Reviews]