Neuroleptic malignant syndrome: Difference between revisions

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==Pathogenesis==
==Background==
 
 
Related to Dopamine Blockade in:
Related to Dopamine Blockade in:
#Anterior Hypothalamus --> Hyperthermia
#Frontal Lobe --> AMS
#Nigrostriatal Pathways --> Rigidity
#Sympathetic Nervous System --> Autonomic Instability


Anterior Hypothalamus --> Hyperthermia
===Potential Pitfalls===
 
#Overlooking the AMS in a “psych pt”
Frontal Lobe --> AMS
#Delay in obtaining rectal temp
 
#Use of physical restraints
Nigrostriatal Pathways --> Rigidity
#Isometric contractions leads increased metabolism, worsening rhabdo and hyperthermia
 
#Use of high potency antipsychotics in the ER
Sympathetic Nervous System --> Autonomic Instability
 
== ==
 


==Diagnosis==
==Diagnosis==
Mortality of 10-20%
Classic Tetrad of Symptoms:
Classic Tetrad of Symptoms:
# Altered Mental Status
# Muscular Rigidity
# Fever
# Autonomic Instability


1) Altered Mental Status
===Clinical History===
 
2) Muscular Rigidity
 
3) Fever
 
4) Autonomic Instability
 
 
Clinical History
 
Drug Exposure:
Drug Exposure:
#Typical high potency antipsychotics (haloperidol)
#Atypical neuroleptics (risperidone, olanzapine, clozapine)
#Antiemetics (metochlopromide, promethazine)
#Withdrawal of anti-Parkinson medication


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


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


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):
Laboratory Examination (non-specific):
#Total CK > 1000
#WBC > 10K
#Mildly elevated LDH, LFTs
#Renal Insufficiency
#CSF with mildly elevated Protein
#Low Serum Iron


Total CK > 1000
WBC > 10K
Mildly elevated LDH, LFTs
Renal Insufficiency
CSF with mildly elevated Protein
Low Serum Iron


Diagnostic Criteria:
Diagnostic Criteria:


DSM-IV:
DSM-IV:
#Recent administration of antipsychotic
#Elevated Temp (> 40C)
#Muscle Rigidity
#Atleast 2 other signs/symptoms or lab findings c/w NMS


Recent administration of antipsychotic
==DDx==
 
#Delirium tremens
Elevated Temp (> 40C)
#Heat Stroke (altered CNS, temp >40)
 
#Meningitis
Muscle Rigidity
#Malignant Hyperthermia (genetic d/o; 1h post general anesthetic; hyperthermia up to 45deg C, rigidity, tachy, skin cyanosis with mottling)
 
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==
==Treatment==
 
#ABCs
 
#Stop the Offending Agent
ABCs
#Aggressive Cooling Measures
 
#Fluid Resuscitation
Stop the Offending Agent
#Supportive Care
 
#Benzos: for agitation
Aggressive Cooling Measures
#Dantrolene:
 
##direct skeletal muscle relaxant
Fluid Resuscitation
##(Showed improvement in 80% cases)
 
##Dosage: 10mg/kg per day
Supportive Care
##Relative Contraindication in pts on CCB (can lead to cardiovascular collapse)
 
#Bromocriptine:
Benzos: for agitation
##dopamine agonist to counteract central blockade
 
##Max: 40mg/day
#Amantadine:
 
##dopamine agonist and anticholinergic agent
Dantrolene:
##Max 400mg/day
 
#Consider ECT
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)
Retrospective analysis: suggests pts on dantrolene +/- bromocriptine have a faster recovery (9days vs 12Days)


==Woodbury Stages==
 
Woodbury Stages
 
Incorporates severity of disease with treatment
Incorporates severity of disease with treatment


(I-III: supportive care +/- benzos)
#(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
Stage IV (Moderate NMS): All four features present
##TX: benzos, dantrolene, bromocriptine, consider ECT
 
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
arrhthmias, renal failure, seizures, pneumonia, DIC, death


===Prognosis===
 
Prognosis==
 
 
Most resolve within 2 weeks, without long term sequelae
Most resolve within 2 weeks, without long term sequelae


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


Mortality of 10-20%
 
==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==
==Source==
Pani 6/2009 based on Rosen's  
Pani 6/2009 based on Rosen's  


[[Category:Neuro]]
[[Category:Neuro]]

Revision as of 07:44, 28 March 2011

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. Atleast 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