Neuroleptic malignant syndrome

Background

Related to Dopamine Blockade in:

1. Anterior Hypothalamus --> Hyperthermia
2. Frontal Lobe --> AMS
3. Nigrostriatal Pathways --> Rigidity
4. Sympathetic Nervous System --> Autonomic Instability

Potential Pitfalls

1. Overlooking the AMS in a “psych pt”
2. Delay in obtaining rectal temp
3. Use of physical restraints
4. Isometric contractions leads increased metabolism, worsening rhabdo and hyperthermia
5. Use of high potency antipsychotics in the ER

Diagnosis

Classic Tetrad of Symptoms:

1. Altered Mental Status
2. Muscular Rigidity
3. Fever
4. Autonomic Instability

Clinical History

Drug Exposure:

1. Typical high potency antipsychotics (haloperidol)
2. Atypical neuroleptics (risperidone, olanzapine, clozapine)
3. Antiemetics (metochlopromide, promethazine)
4. Withdrawal of anti-Parkinson medication

Timing:

1. Symptoms typically occur within 4-14d following initiation of med or an increase in dosing; can occur years after initiating therapy

Laboratory Examination (non-specific):

1. Total CK > 1000
2. WBC > 10K
3. Mildly elevated LDH, LFTs
4. Renal Insufficiency
5. CSF with mildly elevated Protein
6. Low Serum Iron

Diagnostic Criteria

DSM-IV:

1. Recent administration of antipsychotic
2. Elevated Temp (> 40C)
3. Muscle Rigidity
4. At least 2 other signs/symptoms or lab findings c/w NMS

DDx

1. Delirium tremens
2. Heat Stroke (altered CNS, temp >40)
3. Meningitis
4. Malignant Hyperthermia (genetic d/o; 1h post general anesthetic; hyperthermia up to 45deg C, rigidity, tachy, skin cyanosis with mottling)

Treatment

1. ABCs
2. Stop the Offending Agent
3. Aggressive Cooling Measures
4. Fluid Resuscitation
5. Supportive Care
6. Benzos: for agitation
7. Dantrolene:
   1. direct skeletal muscle relaxant
   2. (Showed improvement in 80% cases)
   3. Dosage: 10mg/kg per day
   4. Relative Contraindication in pts on CCB (can lead to cardiovascular collapse)
8. Bromocriptine:
   1. dopamine agonist to counteract central blockade
   2. Max: 40mg/day
9. Amantadine:
   1. dopamine agonist and anticholinergic agent
   2. Max 400mg/day
10. Consider ECT

Retrospective analysis: suggests pts on dantrolene +/- bromocriptine have a faster recovery (9days vs 12Days)

Woodbury Stages

Incorporates severity of disease with treatment

1. (I-III: supportive care +/- benzos)
2. Stage IV (Moderate NMS): All four features present
   1. TX: benzos, bromocriptine
3. Stage V (Severe NMS) Tetrad with more severe hyperthermia
   1. TX: benzos, dantrolene, bromocriptine, consider ECT

Complications

arrhthmias, renal failure, seizures, pneumonia, DIC, death

Prognosis

Most resolve within 2 weeks, without long term sequelae

Poorer prognosis in those with high peak and/or long duration of hyperthermia

Mortality of 10-20%

Source

Pani 6/2009 based on Rosen's