Diferencia entre revisiones de «Neuroleptic malignant syndrome»

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==Background==
==Background==
*Life threatening neurologic emergency associated with the use of neuroleptic agents<ref>Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013</ref><ref>Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92</ref>
[[File:NMS clinical features.jpg|thumb|Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.]]
**Can occur with single dose, increasing dose, or same dose as usual <ref>Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109</ref>
*Life-threatening neurologic emergency associated with dopamine receptor blockade<ref>Su YP, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. ''Acta Psychiatr Scand''. 2014;130(1):52-60. PMID 24256459</ref>
**May also occur with withdrawal of anti-Parkinson medication or use of antiemetics
*Can occur with single dose, dose increase, or stable chronic dosing
*Develops over 1-3 days
*Onset typically 1-3 days after exposure (but can occur weeks later)
*Majority of deaths occur from complications of muscle rigidity
*Causative agents:
**"Typical" high-potency antipsychotics: haloperidol (most common), chlorpromazine, fluphenazine
**"Atypical" antipsychotics: risperidone, olanzapine, quetiapine, aripiprazole<ref>Trollor JN, et al. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. ''CNS Drugs''. 2009;23(6):477-92. PMID 19480467</ref>
**Antiemetics: metoclopramide, promethazine, droperidol
**Withdrawal of dopaminergic agents (levodopa, bromocriptine) in Parkinson's disease
*Mortality: 5-20%<ref>Shalev A. Mortality from neuroleptic malignant syndrome. ''J Clin Psychiatry''. 1989;50(1):18-25. PMID 2562951</ref>
*Most deaths from '''complications of severe muscle rigidity''' (rhabdomyolysis → renal failure, respiratory failure)


==Clinical Features==
==Clinical Features==
*Tetrad of:<ref>Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013</ref>
*Develops over 1-3 days (distinguishes from serotonin syndrome which is more acute)
*[[Altered mental status]]
*Classic tetrad<ref>Gurrera RJ, et al. A validation study of the international consensus diagnostic criteria for NMS. ''J Clin Psychopharmacol''. 2013;33(6):747-54. PMID 24100788</ref>:
**Agitated delirium progressing to stupor/coma
 
*Muscular Rigidity
===1. Altered Mental Status===
**Generalized, "lead pipe" rigidity
*Agitated delirium progressing to stupor and coma
*[[Hyperthermia]]
*May be earliest feature
**>38C (87%)
 
**>40C (40%)
===2. Muscle Rigidity===
*Autonomic Instability
*Generalized "lead-pipe" rigidity (distinguishing feature from serotonin syndrome)
**Tachycardia
*May cause chest wall rigidity → respiratory failure
**Hypertension
 
**Diaphoresis
===3. Hyperthermia===
*>38°C in 87% of cases; >40°C in 40%
*Can exceed 42°C
 
===4. Autonomic Instability===
*Tachycardia, labile blood pressure, diaphoresis
*Sialorrhea (drooling), urinary incontinence
 
===Complications===
*[[Rhabdomyolysis]] → [[acute kidney injury]] (major cause of morbidity)
*Dysrhythmias, [[ACS]]
*Respiratory failure (chest wall rigidity, aspiration)
*[[DIC]], [[seizures]], hepatic failure, [[sepsis]]


==Differential Diagnosis==
==Differential Diagnosis==
*[[Serotonin Syndrome]]
{| class="wikitable"
**More likely to have hyperreflexia, myoclonus, ataxis, nausea and vomiting, diarrhea
|-
**Rigidity and hyperthermia, if present, is less severe than in NMS
! Feature !! '''NMS''' !! '''[[Serotonin syndrome]]''' !! '''[[Malignant hyperthermia]]''' !! '''Anticholinergic toxicity'''
*[[Malignant Hyperthermia]]
|-
**Distinguish by clinical setting (use of inhalational anesthetics or sux)
| Onset || Days || Hours || Minutes (OR) || Hours
**Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
|-
*[[Anticholinergic Toxicity]]
| Rigidity || Lead-pipe || Clonus/hyperreflexia || Generalized || Absent
**Diaphoresis, rigidity, elevated CK are absent
|-
**Flushing, mydriasis, bladder distension are common
| Skin || Diaphoresis || Diaphoresis || Mottled/diaphoresis || Dry, flushed
*[[Sympathomimetics]]
|-
**Rigidity is not seen
| CK || >1000 || Mildly elevated || Markedly elevated || Normal
*[[Meningitis]]/[[encephalitis]]
|-
*[[Alcohol_Withdrawal*Delirium_Tremens|Delirium Tremens]]
| Pupils || Normal || '''Mydriasis''' || Normal || '''Mydriasis'''
*[[Heat Stroke]]
|-
| Bowel sounds || Normal/decreased || '''Hyperactive''' || Normal || '''Absent'''
|}


{{AMS and fever DDX}}
{{Altered mental status and fever DDX}}


==Diagnosis==
==Evaluation==
===Workup===
*CK: typically >1000 IU/L; correlates with degree of rigidity; may exceed 100,000
*Total CK
*CBC: leukocytosis (WBC >10K typical, may exceed 40K)
**Typically >1000
*BMP: hypocalcemia, hypomagnesemia, [[hyperkalemia]], metabolic acidosis
**Correlates with degree of rigidity
*LFTs: transaminitis common
*CBC
*Serum iron: low iron level supports NMS diagnosis (distinguishes from serotonin syndrome)
**WBC >10K is typical
*Urinalysis: myoglobinuria from [[rhabdomyolysis]]
*Chemistry
*Coagulation studies: DIC screening
**May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
*Blood cultures: rule out [[sepsis]]
*UA
*CT head/LP: rule out CNS infection; CSF may show mildly elevated protein
**Myoglobinuria (from rhabdo)
*LFT
**Transaminitis
*CT/[[LP]]
**CSF may have mildly elevated protein


{{Serotonin syndrome vs neuroleptic malignant syndrome}}
===NMS vs Serotonin Syndrome===
*History of neuroleptic drug → NMS; serotonergic drug → serotonin syndrome
*NMS: lead-pipe rigidity, slow onset (days), elevated CK, low iron
*SS: clonus/hyperreflexia, rapid onset (hours), hyperactive bowel sounds, diarrhea


==Management==
==Management==
*The causative agent should be stopped
===Immediate===
*If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient
*'''Stop all dopamine-blocking agents immediately'''
===Supportive Care===
*If precipitated by withdrawal of dopaminergic therapy (levodopa): restart at lower dose
*Agitation should be controlled with [[Benzodiazepines]]  
*Aggressive IV fluid resuscitation (goal UOP >1-2 mL/kg/hr for rhabdomyolysis)
*[[Fluid resuscitation]]
*Active cooling measures for hyperthermia >40°C
*Cooling measures
 
===Agitation and Rigidity===
*Benzodiazepines first-line:
**Lorazepam 2 mg IV q5min until agitation and muscle rigidity resolve
*For severe cases with respiratory failure or chest wall rigidity:
**'''Intubation with NON-DEPOLARIZING paralytic''' (rocuronium, vecuronium)
**AVOID succinylcholine (risk of [[hyperkalemia]] from rhabdomyolysis)
 
===Directed Medical Therapy===
*Efficacy controversial — limited to case reports/series<ref>Addonizio G, et al. Neuroleptic malignant syndrome: review and analysis of 115 cases. ''Biol Psychiatry''. 1987;22(8):1004-20. PMID 3620091</ref>
*Dantrolene (skeletal muscle relaxant):
**Consider for severe rigidity with hyperthermia >40°C
**0.25-2 mg/kg IV q6-12h (max 10 mg/kg/day)
**Monitor LFTs (hepatotoxicity risk)
*Bromocriptine (dopamine agonist):
**2.5 mg PO/NGT q6-8h (max 40 mg/day)
**Continue for 10 days after NMS resolves to prevent relapse
*Amantadine (alternative to bromocriptine):
**100 mg PO initially; titrate to 200 mg q12h
 
===Electroconvulsive Therapy===
*Consider for refractory NMS unresponsive to pharmacotherapy<ref>Morcos N et al. Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. ''J ECT''. 2019;35(4):225-230. PMID 31651674</ref>
 
===Monitoring===
*Serial CK, renal function, electrolytes
*Continuous cardiac monitoring
*Treat [[hyperkalemia]] aggressively if present


===Directed Medical therapy<ref>Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20 </ref>===
==Disposition==
*Controversial with unclear and disputed efficacy
*Admit to ICU for all suspected cases
*Dantrolene
*Symptoms typically resolve over 7-10 days (longer with depot antipsychotics — up to 2-4 weeks)
**Skeletal muscle relaxant; may cause hepatotoxicity in patients with liver disease
*After recovery, cautious rechallenge with a different, low-potency antipsychotic may be attempted after 2 weeks
**Consider only in patients with severe rigidity
*Psychiatric consultation for medication management
**Give 0.25-2mg/kg IV q6-12hr
*Bromocriptine
**Dopamine agonist
**Give 2.5mg NG q6-8hr
*Amantadine
**Alternative to bromocriptine
**Give 100mg PO/NG initially; titrate up as needed to max dose 200mg q12hr


==Complications==
==See Also==
*Dehydration
*[[Serotonin syndrome]]
*[[Electrolyte imbalance]]
*[[Malignant hyperthermia]]
*[[Acute renal failure]] ([[rhabdo]])
*[[Rhabdomyolysis]]
*[[Dysrhythmias ]]
*[[Anticholinergic toxicity]]
*[[ACS]]
*[[Heat stroke]]
*[[Respiratory failure]]
**Chest wall rigidity, aspiration [[PNA]], [[PE]]
*[[DIC]]
*[[Seizure]] ([[hyperthermia]], [[electrolyte derangements]])
*[[Hepatic failure]]
*[[Sepsis]]


==References==
==References==
<references/>
<references/>
*Strawn JR, et al. Neuroleptic malignant syndrome. ''Am J Psychiatry''. 2007;164(6):870-876. PMID 17541044
*Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. ''Neurohospitalist''. 2011;1(1):41-47. PMID 23983836


[[Category:Psychiatry]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Toxicology]]

Revisión actual - 09:30 22 mar 2026

Background

File:NMS clinical features.jpg
Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.
  • Life-threatening neurologic emergency associated with dopamine receptor blockade[1]
  • Can occur with single dose, dose increase, or stable chronic dosing
  • Onset typically 1-3 days after exposure (but can occur weeks later)
  • Causative agents:
    • "Typical" high-potency antipsychotics: haloperidol (most common), chlorpromazine, fluphenazine
    • "Atypical" antipsychotics: risperidone, olanzapine, quetiapine, aripiprazole[2]
    • Antiemetics: metoclopramide, promethazine, droperidol
    • Withdrawal of dopaminergic agents (levodopa, bromocriptine) in Parkinson's disease
  • Mortality: 5-20%[3]
  • Most deaths from complications of severe muscle rigidity (rhabdomyolysis → renal failure, respiratory failure)

Clinical Features

  • Develops over 1-3 days (distinguishes from serotonin syndrome which is more acute)
  • Classic tetrad[4]:

1. Altered Mental Status

  • Agitated delirium progressing to stupor and coma
  • May be earliest feature

2. Muscle Rigidity

  • Generalized "lead-pipe" rigidity (distinguishing feature from serotonin syndrome)
  • May cause chest wall rigidity → respiratory failure

3. Hyperthermia

  • >38°C in 87% of cases; >40°C in 40%
  • Can exceed 42°C

4. Autonomic Instability

  • Tachycardia, labile blood pressure, diaphoresis
  • Sialorrhea (drooling), urinary incontinence

Complications

Differential Diagnosis

Feature NMS Serotonin syndrome Malignant hyperthermia Anticholinergic toxicity
Onset Days Hours Minutes (OR) Hours
Rigidity Lead-pipe Clonus/hyperreflexia Generalized Absent
Skin Diaphoresis Diaphoresis Mottled/diaphoresis Dry, flushed
CK >1000 Mildly elevated Markedly elevated Normal
Pupils Normal Mydriasis Normal Mydriasis
Bowel sounds Normal/decreased Hyperactive Normal Absent

Template:Altered mental status and fever DDX

Evaluation

  • CK: typically >1000 IU/L; correlates with degree of rigidity; may exceed 100,000
  • CBC: leukocytosis (WBC >10K typical, may exceed 40K)
  • BMP: hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
  • LFTs: transaminitis common
  • Serum iron: low iron level supports NMS diagnosis (distinguishes from serotonin syndrome)
  • Urinalysis: myoglobinuria from rhabdomyolysis
  • Coagulation studies: DIC screening
  • Blood cultures: rule out sepsis
  • CT head/LP: rule out CNS infection; CSF may show mildly elevated protein

NMS vs Serotonin Syndrome

  • History of neuroleptic drug → NMS; serotonergic drug → serotonin syndrome
  • NMS: lead-pipe rigidity, slow onset (days), elevated CK, low iron
  • SS: clonus/hyperreflexia, rapid onset (hours), hyperactive bowel sounds, diarrhea

Management

Immediate

  • Stop all dopamine-blocking agents immediately
  • If precipitated by withdrawal of dopaminergic therapy (levodopa): restart at lower dose
  • Aggressive IV fluid resuscitation (goal UOP >1-2 mL/kg/hr for rhabdomyolysis)
  • Active cooling measures for hyperthermia >40°C

Agitation and Rigidity

  • Benzodiazepines first-line:
    • Lorazepam 2 mg IV q5min until agitation and muscle rigidity resolve
  • For severe cases with respiratory failure or chest wall rigidity:
    • Intubation with NON-DEPOLARIZING paralytic (rocuronium, vecuronium)
    • AVOID succinylcholine (risk of hyperkalemia from rhabdomyolysis)

Directed Medical Therapy

  • Efficacy controversial — limited to case reports/series[5]
  • Dantrolene (skeletal muscle relaxant):
    • Consider for severe rigidity with hyperthermia >40°C
    • 0.25-2 mg/kg IV q6-12h (max 10 mg/kg/day)
    • Monitor LFTs (hepatotoxicity risk)
  • Bromocriptine (dopamine agonist):
    • 2.5 mg PO/NGT q6-8h (max 40 mg/day)
    • Continue for 10 days after NMS resolves to prevent relapse
  • Amantadine (alternative to bromocriptine):
    • 100 mg PO initially; titrate to 200 mg q12h

Electroconvulsive Therapy

  • Consider for refractory NMS unresponsive to pharmacotherapy[6]

Monitoring

  • Serial CK, renal function, electrolytes
  • Continuous cardiac monitoring
  • Treat hyperkalemia aggressively if present

Disposition

  • Admit to ICU for all suspected cases
  • Symptoms typically resolve over 7-10 days (longer with depot antipsychotics — up to 2-4 weeks)
  • After recovery, cautious rechallenge with a different, low-potency antipsychotic may be attempted after 2 weeks
  • Psychiatric consultation for medication management

See Also

References

  1. ↑ Su YP, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. 2014;130(1):52-60. PMID 24256459
  2. ↑ Trollor JN, et al. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92. PMID 19480467
  3. ↑ Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25. PMID 2562951
  4. ↑ Gurrera RJ, et al. A validation study of the international consensus diagnostic criteria for NMS. J Clin Psychopharmacol. 2013;33(6):747-54. PMID 24100788
  5. ↑ Addonizio G, et al. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. 1987;22(8):1004-20. PMID 3620091
  6. ↑ Morcos N et al. Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019;35(4):225-230. PMID 31651674
  • Strawn JR, et al. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164(6):870-876. PMID 17541044
  • Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41-47. PMID 23983836
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