Neuroleptic malignant syndrome: Difference between revisions
No edit summary
Line 1: Line 1:
==Background==
==Background==
Related to Dopamine Blockade in:
*Life threatening neurologic emergency associated with the use of neuroleptic agents
#Anterior Hypothalamus --> Hyperthermia
**Can occur with single dose, increasing dose, or same dose as usual
#Frontal Lobe --> AMS
**May also occur with withdrawal of anti-Parkinson medication or use of antiemetics
#Nigrostriatal Pathways --> Rigidity
*Develops over 1-3 days
#Sympathetic Nervous System --> Autonomic Instability
*Majority of deaths occur from complications of muscle rigidity


===Potential Pitfalls===
==Clinical Features==
#Overlooking the AMS in a “psych pt”
*Tetrad of:
#Delay in obtaining rectal temp
#Altered Mental Status
#Use of physical restraints
##Agitated delirium progressing to stupor/coma
#Isometric contractions leads increased metabolism, worsening rhabdo and hyperthermia
#Muscular Rigidity
#Use of high potency antipsychotics in the ER
##Generalized, "lead pipe" rigidity
#Hyperthermia
##>38C (87%)
##>40C (40%)
#Autonomic Instability
##Tachycardia
##Hypertension
##Diaphoresis


==Diagnosis==
==DDX==
Classic Tetrad of Symptoms:
#[[Serotonin Syndrome]]
# Altered Mental Status
##More likely to have hyperreflexia, myoclonus, ataxis, N/V, diarrhea
# Muscular Rigidity
##Rigidity and hyperthermia, if present, is less severe than in NMS
# Fever
#[[Malignant Hyperthermia]]
# Autonomic Instability
##Distinguish by clinical setting (use of inhalational anesthetics or sux)
##Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
#Anticholinergic Toxidrome
##Diaphoresis, rigidity, elevated CK are absent
##Flushing, mydriasis, bladder distension are common
#Sympathomimetics
##Rigidity is not seen
#Meningitis/encephalitis
#Delirium Tremens
#Heat Stroke


===Clinical History===
==Work-Up==
Drug Exposure:
#Total CK
#Typical high potency antipsychotics (haloperidol)
##Typically >1000
#Atypical neuroleptics (risperidone, olanzapine, clozapine)
##Correlates with degree of rigidity
#Antiemetics (metochlopromide, promethazine)
#CBC
#Withdrawal of anti-Parkinson medication
##WBC >10K is typical
 
#Chemistry
 
##May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
Timing:
#UA
#Symptoms typically occur within 4-14d following initiation of med or an increase in dosing; can occur years after initiating therapy
##Myoglobinuria (from rhabdo)
 
#LFT
 
##Transaminitis
Laboratory Examination (non-specific):
#CT/LP
#Total CK > 1000
##CSF may have mildly elevated protein
#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
#At least 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==
==Treatment==
#ABCs
#Stop causative agent
#Stop the Offending Agent
##If precipitant is discontinuation of dopaminergic therapy, it should be restarted
#Aggressive Cooling Measures
#Fluid Resuscitation
#Supportive Care
#Supportive Care
#Benzos: for agitation
##Fluid resuscitation
#Dantrolene:
##Cooling measures
##direct skeletal muscle relaxant
###Consider paralysis with nondepolarizing agents
##(Showed improvement in 80% cases)
##Agitation control with benzos
##Dosage: 10mg/kg per day
##Blood pressure control with clonidine or nitroprusside
##Relative Contraindication in pts on CCB (can lead to cardiovascular collapse)
#Medical therapy
#Bromocriptine:
##Controversial; efficacy is unclear and disputed
##dopamine agonist to counteract central blockade
###Dantrolene
##Max: 40mg/day
####Skeletal muscle relaxant; may cause hepatotoxicity in pts w/ liver disease
#Amantadine:
####Consider only in pts with severe rigidity
##dopamine agonist and anticholinergic agent
####Give 0.25-2mg/kg IV q6-12hr
##Max 400mg/day
###Bromocriptine
#Consider ECT
####Dopamine agonist
 
####Give 2.5mg NG q6-8hr
Retrospective analysis: suggests pts on dantrolene +/- bromocriptine have a faster recovery (9days vs 12Days)
###Amantadine
 
####Alternative to bromocriptine
==Woodbury Stages==
####Give 100mg PO/NG initially; titrate up as needed to max dose 200mg q12hr
Incorporates severity of disease with treatment
###ECT
 
#(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==
==Complications==
arrhthmias, renal failure, seizures, pneumonia, DIC, death
#Dehydration
 
#Electrolyte imbalance
===Prognosis===
#ARF (rhabdo)
Most resolve within 2 weeks, without long term sequelae
#Dysrhythmias
 
#ACS
Poorer prognosis in those with high peak and/or long duration of hyperthermia
#Respiratory failure
 
##Chest wall rigidity, aspiration PNA, PE
Mortality of 10-20%
#DIC
#Seizure (hyperthermia, electrolyte derangements)
#Hepatic failure
#Sepsis


==Source==
==Source==
Pani 6/2009 based on Rosen's
*Tintinalli
*UpToDate


[[Category:Airway/Resus]]
[[Category:Psych]]
[[Category:Neuro]]
[[Category:Tox]]

Revision as of 21:15, 1 January 2012

Background

  • Life threatening neurologic emergency associated with the use of neuroleptic agents
    • Can occur with single dose, increasing dose, or same dose as usual
    • May also occur with withdrawal of anti-Parkinson medication or use of antiemetics
  • Develops over 1-3 days
  • Majority of deaths occur from complications of muscle rigidity

Clinical Features

  • Tetrad of:
  1. Altered Mental Status
    1. Agitated delirium progressing to stupor/coma
  2. Muscular Rigidity
    1. Generalized, "lead pipe" rigidity
  3. Hyperthermia
    1. >38C (87%)
    2. >40C (40%)
  4. Autonomic Instability
    1. Tachycardia
    2. Hypertension
    3. Diaphoresis

DDX

  1. Serotonin Syndrome
    1. More likely to have hyperreflexia, myoclonus, ataxis, N/V, diarrhea
    2. Rigidity and hyperthermia, if present, is less severe than in NMS
  2. Malignant Hyperthermia
    1. Distinguish by clinical setting (use of inhalational anesthetics or sux)
    2. Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
  3. Anticholinergic Toxidrome
    1. Diaphoresis, rigidity, elevated CK are absent
    2. Flushing, mydriasis, bladder distension are common
  4. Sympathomimetics
    1. Rigidity is not seen
  5. Meningitis/encephalitis
  6. Delirium Tremens
  7. Heat Stroke

Work-Up

  1. Total CK
    1. Typically >1000
    2. Correlates with degree of rigidity
  2. CBC
    1. WBC >10K is typical
  3. Chemistry
    1. May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
  4. UA
    1. Myoglobinuria (from rhabdo)
  5. LFT
    1. Transaminitis
  6. CT/LP
    1. CSF may have mildly elevated protein

Treatment

  1. Stop causative agent
    1. If precipitant is discontinuation of dopaminergic therapy, it should be restarted
  2. Supportive Care
    1. Fluid resuscitation
    2. Cooling measures
      1. Consider paralysis with nondepolarizing agents
    3. Agitation control with benzos
    4. Blood pressure control with clonidine or nitroprusside
  3. Medical therapy
    1. Controversial; efficacy is unclear and disputed
      1. Dantrolene
        1. Skeletal muscle relaxant; may cause hepatotoxicity in pts w/ liver disease
        2. Consider only in pts with severe rigidity
        3. Give 0.25-2mg/kg IV q6-12hr
      2. Bromocriptine
        1. Dopamine agonist
        2. Give 2.5mg NG q6-8hr
      3. Amantadine
        1. Alternative to bromocriptine
        2. Give 100mg PO/NG initially; titrate up as needed to max dose 200mg q12hr
      4. ECT

Complications

  1. Dehydration
  2. Electrolyte imbalance
  3. ARF (rhabdo)
  4. Dysrhythmias
  5. ACS
  6. Respiratory failure
    1. Chest wall rigidity, aspiration PNA, PE
  7. DIC
  8. Seizure (hyperthermia, electrolyte derangements)
  9. Hepatic failure
  10. Sepsis

Source

  • Tintinalli
  • UpToDate
Retrieved from "https://www.wikem.org/w/index.php?title=Neuroleptic_malignant_syndrome&oldid=7349"