Diferencia entre revisiones de «Neuroleptic malignant syndrome»

(Major update: NMS vs SS comparison table, iron level evaluation, avoid succinylcholine, bromocriptine duration, rechallenge guidance, depot antipsychotic timeline, added references with PMIDs)
(Strip excess bold)
 
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[[File:NMS clinical features.jpg|thumb|Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.]]
[[File:NMS clinical features.jpg|thumb|Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.]]
*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>
*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>
*Can occur with '''single dose, dose increase, or stable chronic dosing'''
*Can occur with single dose, dose increase, or stable chronic dosing
*Onset typically '''1-3 days''' after exposure (but can occur weeks later)
*Onset typically 1-3 days after exposure (but can occur weeks later)
*Causative agents:
*Causative agents:
**'''"Typical" high-potency antipsychotics''': '''haloperidol''' (most common), chlorpromazine, fluphenazine
**"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>
**"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
**Antiemetics: metoclopramide, promethazine, droperidol
**'''Withdrawal of dopaminergic agents''' (levodopa, bromocriptine) in Parkinson's disease
**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>
*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)
*Most deaths from '''complications of severe muscle rigidity''' (rhabdomyolysis → renal failure, respiratory failure)


==Clinical Features==
==Clinical Features==
*Develops over '''1-3 days''' (distinguishes from serotonin syndrome which is more acute)
*Develops over 1-3 days (distinguishes from serotonin syndrome which is more acute)
*'''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>:
*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>:


===1. Altered Mental Status===
===1. Altered Mental Status===
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===2. Muscle Rigidity===
===2. Muscle Rigidity===
*Generalized '''"lead-pipe" rigidity''' (distinguishing feature from serotonin syndrome)
*Generalized "lead-pipe" rigidity (distinguishing feature from serotonin syndrome)
*May cause '''chest wall rigidity''' → respiratory failure
*May cause chest wall rigidity → respiratory failure


===3. Hyperthermia===
===3. Hyperthermia===
*'''>38°C in 87%''' of cases; '''>40°C in 40%'''
*>38°C in 87% of cases; >40°C in 40%
*Can exceed 42°C
*Can exceed 42°C


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===Complications===
===Complications===
*'''[[Rhabdomyolysis]]''' → [[acute kidney injury]] (major cause of morbidity)
*[[Rhabdomyolysis]] → [[acute kidney injury]] (major cause of morbidity)
*Dysrhythmias, [[ACS]]
*Dysrhythmias, [[ACS]]
*Respiratory failure (chest wall rigidity, aspiration)
*Respiratory failure (chest wall rigidity, aspiration)
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==Evaluation==
==Evaluation==
*'''CK''': typically '''>1000 IU/L'''; correlates with degree of rigidity; may exceed 100,000
*CK: typically >1000 IU/L; correlates with degree of rigidity; may exceed 100,000
*'''CBC''': leukocytosis (WBC >10K typical, may exceed 40K)
*CBC: leukocytosis (WBC >10K typical, may exceed 40K)
*'''BMP''': hypocalcemia, hypomagnesemia, [[hyperkalemia]], metabolic acidosis
*BMP: hypocalcemia, hypomagnesemia, [[hyperkalemia]], metabolic acidosis
*'''LFTs''': transaminitis common
*LFTs: transaminitis common
*'''Serum iron''': '''low iron level''' supports NMS diagnosis (distinguishes from serotonin syndrome)
*Serum iron: low iron level supports NMS diagnosis (distinguishes from serotonin syndrome)
*'''Urinalysis''': myoglobinuria from [[rhabdomyolysis]]
*Urinalysis: myoglobinuria from [[rhabdomyolysis]]
*'''Coagulation studies''': DIC screening
*Coagulation studies: DIC screening
*'''Blood cultures''': rule out [[sepsis]]
*Blood cultures: rule out [[sepsis]]
*'''CT head/LP''': rule out CNS infection; CSF may show mildly elevated protein
*CT head/LP: rule out CNS infection; CSF may show mildly elevated protein


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


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


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


===Directed Medical Therapy===
===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>
*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):
*Dantrolene (skeletal muscle relaxant):
**Consider for '''severe rigidity with hyperthermia >40°C'''
**Consider for severe rigidity with hyperthermia >40°C
**'''0.25-2 mg/kg IV q6-12h''' (max 10 mg/kg/day)
**0.25-2 mg/kg IV q6-12h (max 10 mg/kg/day)
**Monitor LFTs (hepatotoxicity risk)
**Monitor LFTs (hepatotoxicity risk)
*'''Bromocriptine''' (dopamine agonist):
*Bromocriptine (dopamine agonist):
**'''2.5 mg PO/NGT q6-8h''' (max 40 mg/day)
**2.5 mg PO/NGT q6-8h (max 40 mg/day)
**Continue for '''10 days''' after NMS resolves to prevent relapse
**Continue for 10 days after NMS resolves to prevent relapse
*'''Amantadine''' (alternative to bromocriptine):
*Amantadine (alternative to bromocriptine):
**100 mg PO initially; titrate to 200 mg q12h
**100 mg PO initially; titrate to 200 mg q12h


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


==See Also==
==See Also==

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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