Psychiatry · Year 3 · from Psychiatry

Case 3: Neuroleptic Malignant Syndrome

Patient Demographics

• Age: 28 years old
• Sex: Male
• Occupation: Unemployed

Chief Complaint

Per group home staff: "He's confused, stiff, and has a high fever. His medication was just increased."

History of Present Illness

The patient is a 28-year-old man with schizophrenia who was recently discharged from inpatient psychiatry 5 days ago. During hospitalization, his haloperidol was increased from 10 mg to 20 mg daily due to persistent psychosis. He was also started on haloperidol decanoate 100 mg IM at discharge for maintenance.

Group home staff report that over the past 2 days, he has become increasingly confused and "not himself." Today, he was found in his room, rigid, barely responsive, and soaking wet with sweat. They took his temperature and found it to be 104.2°F.

Medication History

• Haloperidol 20 mg daily (increased 7 days ago)
• Haloperidol decanoate 100 mg IM (5 days ago)
• Benztropine 2 mg BID

Physical Examination

Vital Signs:

• Temperature: 104.8°F (40.4°C)
• Heart rate: 124 bpm
• Blood pressure: 168/110 mmHg (fluctuating, was 92/58 earlier)
• Respiratory rate: 24
• O2 saturation: 94% on room air

General: Diaphoretic, ill-appearing, minimal responsiveness

HEENT: Drooling, dry mucous membranes

Cardiovascular: Tachycardia, regular rhythm

Pulmonary: Clear, tachypneic

Neurological:

• Level of consciousness: Obtunded, responds minimally to voice, withdraws to pain
• Motor: Severe generalized "lead-pipe" rigidity throughout all extremities
• Tremor: Coarse tremor superimposed on rigidity
• Reflexes: Increased throughout
• Other: Mutism

Laboratory Studies

STAT Labs:

• WBC: 18,400 (elevated)
• Creatine kinase (CK): 12,840 IU/L (massively elevated; normal <200)
• BUN: 42 (elevated)
• Creatinine: 2.1 (elevated from baseline 0.9)
• AST: 186, ALT: 124 (elevated)
• Sodium: 148 (elevated)
• Myoglobin: Elevated
• Lactate: 3.8 (elevated)
• UA: Brown, positive for blood (no RBCs) - myoglobinuria

ECG: Sinus tachycardia, QTc 460 ms

Diagnosis

Neuroleptic Malignant Syndrome (NMS) (G21.0)

Cardinal Features - All Present:

1. Hyperthermia: 104.8°F
2. Severe muscular rigidity: Lead-pipe rigidity
3. Autonomic instability: Tachycardia, labile BP, diaphoresis
4. Altered mental status: Obtundation, confusion

Supporting Features:

• Recent antipsychotic dose increase
• Elevated CK (rhabdomyolysis)
• Leukocytosis
• Acute kidney injury (from rhabdomyolysis)
• Elevated liver enzymes

Precipitating Factors:

• Recent haloperidol dose increase
• High-potency antipsychotic
• IM depot formulation (prolongs exposure)
• Rapid dose titration

Differential Diagnosis

Must Rule Out:

• Serotonin syndrome (different features - clonus, hyperreflexia, GI symptoms; different med history)
• Malignant hyperthermia (occurs with anesthetics)
• Lethal catatonia (may be difficult to distinguish)
• CNS infection (meningitis/encephalitis)
• Heatstroke
• Sepsis

Distinguishing NMS from Serotonin Syndrome:

Emergency Management

1. STOP ALL ANTIPSYCHOTICS IMMEDIATELY:

• Discontinue haloperidol (cannot reverse depot, but stop oral)
• Stop benztropine (anticholinergic may worsen)
• Alert: Long-acting injectable will continue to release drug for weeks

2. Supportive Care - ICU Admission:

• Aggressive IV fluid resuscitation (protect kidneys from myoglobin)
• Target urine output >200 mL/hour
• Cooling measures: Cooling blankets, ice packs, cooled IV fluids
• Continuous monitoring: Temperature, cardiac, BP
• Intubation if respiratory compromise

3. Specific Treatments:

Dantrolene:

• Skeletal muscle relaxant (blocks calcium release from sarcoplasmic reticulum)
• Dose: 1-2.5 mg/kg IV, may repeat to max 10 mg/kg/day
• Indicated for severe hyperthermia and rigidity
• Started in this patient: Dantrolene 2 mg/kg IV

Bromocriptine:

• Dopamine agonist (counteracts dopamine blockade)
• Dose: 2.5-5 mg PO/NG TID
• Started in this patient: Bromocriptine 2.5 mg via NG tube TID

Benzodiazepines:

• For muscle relaxation and agitation
• Lorazepam 1-2 mg IV q6h

4. Monitoring:

• CK every 6 hours (trending for rhabdomyolysis)
• Renal function daily (AKI risk)
• Temperature every 1 hour
• Continuous cardiac monitoring
• Watch for compartment syndrome (from rigidity)
• Watch for DIC

Hospital Course

Day 1-2:

• Temperature slowly decreasing with dantrolene and cooling
• CK peaked at 24,000, then began trending down
• Required 8L IV fluids to maintain urine output
• Creatinine peaked at 2.8, then improved

Day 3:

• Temperature normalized
• Rigidity improving
• More alert, following commands
• CK 4,200 and trending down

Day 7:

• Mental status at baseline
• CK normalized
• Renal function normalized
• Dantrolene and bromocriptine tapered

Discharge Planning

Antipsychotic Rechallenge Considerations:

• Wait at least 2 weeks after NMS resolution
• Choose low-potency or second-generation agent
• Start at low dose, titrate slowly
• Clozapine has lowest NMS risk
• Close monitoring
• 30% recurrence risk with rechallenge

Documentation:

• NMS documented in medical record as adverse reaction
• Alert in electronic system
• Patient and family education about symptoms of NMS
• Medical alert bracelet recommended

Image Attribution

Image: Clinical flowchart for psychiatric emergency assessment including suicide risk stratification, agitation management algorithm, and NMS diagnostic criteria. Source: Wikimedia Commons. Used for educational purposes under Creative Commons license.

All cases for this lecture as Markdown