Neuroleptic malignant syndrome
Pathogenesis
Related to Dopamine Blockade in:
Anterior Hypothalamus --> Hyperthermia
Frontal Lobe --> AMS
Nigrostriatal Pathways --> Rigidity
Sympathetic Nervous System --> Autonomic Instability
Diagnosis
Mortality of 10-20%
Classic Tetrad of Symptoms:
1) Altered Mental Status
2) Muscular Rigidity
3) Fever
4) Autonomic Instability
Clinical History
Drug Exposure:
Typical high potency antipsychotics (haloperidol)
Atypical neuroleptics (risperidone, olanzapine, clozapine)
Antiemetics (metochlopromide, promethazine)
Withdrawal of anti-Parkinson medication
Timing:
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):
Total CK > 1000
WBC > 10K
Mildly elevated LDH, LFTs
Renal Insufficiency
CSF with mildly elevated Protein
Low Serum Iron
Diagnostic Criteria:
DSM-IV:
Recent administration of antipsychotic
Elevated Temp (> 40C)
Muscle Rigidity
Atleast 2 other signs/symptoms or lab findings c/w NMS
DDx
Delirium tremens
Heat Stroke (altered CNS, temp >40)
Meningitis
Malignant Hyperthermia (genetic d/o; 1h post general anesthetic; hyperthermia up to 45deg C, rigidity, tachy, skin cyanosis with mottling)
Treatment
ABCs
Stop the Offending Agent
Aggressive Cooling Measures
Fluid Resuscitation
Supportive Care
Benzos: for agitation
Dantrolene:
direct skeletal muscle relaxant
(Showed improvement in 80% cases)
Dosage: 10mg/kg per day
Relative Contraindication in pts on CCB (can lead to cardiovascular collapse)
Bromocriptine:
dopamine agonist to counteract central blockade
Max: 40mg/day
Amantadine:
dopamine agonist and anticholinergic agent
Max 400mg/day
Consider ECT
Retrospective analysis: suggests pts on dantrolene +/- bromocriptine have a faster recovery (9days vs 12Days)
Woodbury Stages
Incorporates severity of disease with treatment
(I-III: supportive care +/- benzos)
Stage IV (Moderate NMS): All four features present
TX: benzos, bromocriptine
Stage V (Severe NMS) Tetrad with more severe hyperthermia
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
Potential Pitfalls
Overlooking the AMS in a “psych pt”
Delay in obtaining rectal temp
Use of physical restraints
Isometric contractions leads increased metabolism, worsening rhabdo and hyperthermia
Use of high potency antipsychotics in the ER
Source
Pani 6/2009 based on Rosen's