Updated: 9/16/2020

Neuroleptic Malignant Syndrome

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Snapshot
  • A 32-year-old woman is brought to the psychiatric emergency department by emergency medical service for a suicidal attempt. The patient expressed to the hospital staff that she wishes to end her life due to concerns someone is attempting to kidnap her. She has a medical history of schizophrenia and has not been adherent to her aripiprazole. The patient attempted to attack 1 of the security guards due to the belief that he is involved in her kidnapping. She was given multiple doses of intramuscular haloperidol. Approximately 2 days later, the patient's temperature is 102°F (38.9°C), blood pressure is 163/95 mmHg, pulse is 115/min, and respirations are 26/min. On physical examination, the patient is diffusely rigid and is profusely diaphoretic.
Introduction
  • Overview
    • life-threatening neurologic and psychiatric emergency associated with neuroleptic (antipsychotic) medication use
    • classic clinical syndrome tetrad
      • altered mental status
      • fever
      • rigidity
      • autonomic instability
  • Epidemiology
    • demographics
      • typically seen in young adults
        • can occur at any age
    • risk factors
      • antipsychotic use
        • first- and second-generation
      • antiemetic use
        • e.g., metoclopramide and prochlorperazine
      • antiparkinson medication withdrawal
        • also called neuroleptic malignant-like syndrome or parkinsonism hyperpyrexia syndrome
  • Pathophysiology
    • unknown but dopamine receptor blockade in the central nervous system is believed to be involved
  • Associated conditions
    • psychiatric disorders that require high or frequent doses of antipsychotic medications
  • Prognosis
    • natural history of disease
      • most cases resolve within 2 weeks
    • survival with treatment
      • improved
Presentation
  • History
    • tetrad usually occurs over the course of 1-3 days after neuroleptic use
  • Physical exam
    • altered mental status
      • agitated delirium
      • confusion
      • catatonia
      • mutism
    • fever
      • ≥ 38°C
    • rigidity
      • typically diffuse
      • can be described as a "lead-pipe rigidity"
      • patients may also have a tremor (45-92% of cases)
    • autonomic instability
      • tachycardia
        • patients may develop dysrhythmias
      • hypertension or labile blood pressure
      • tachypnea
      • diaphoresis
    • hyporeflexia
Studies
  • Labs
    • ↑ creatine kinase
      • usually > 1000 U/L
    • basic metabolic panel
      • hypo- or hypernatremia
      • hyperkalemia
      • hypomagnesemia
      • hypocalcemia
      • metabolic acidosis
      • acute renal failure
        • may occure if myoglobinuria
    •  iron concentration
      • sensitive but not specific
Tested Differential
  • Serotonin syndrome
    • key distinguishing factors
      • acute onset
      • myoclonus
      • hyperreflexia
      • mydriasis (large pupils)
  • Malignant hyperthermia
    • key distinguishing factorss
      • offending agents are
        • halogenated inhalational anesthetics
        • succinylcholine
Prevention
  • Conservative use of antipsychotics
  • Gradual titration of antopsychotics
Treatment
  • Lifestyle
    • supportive care
      • indication
        • first-line in preventing further complications
          • intravenous fluids to prevent dehydration and acute kidney injury from myglobinuria
          • electrolyte repletion to prevent cardiac arrythmias and seizures
  • Pharmacologic
    • discontinue the offending agent
      • indication
        • first-line to prevent further progression of neuroleptic malignant syndrome
    • benzodiazepines 
      • indication
        • usually initially used along with dantrolene in moderate or severe cases
      • medication
        • lorazepam
        • diazepam
    • dantrolene
      • indication
        • usually given with benzodiazepines in moderate or severe cases
          • effective in relaxing skeletal muscles
    • bromocriptine
      • indication
        • administered after benzodiazepines and dantrolene is administered in order to restore dopaminergic tone
      • alternative agent
        • amantadine
Complications
  • Seizure
  • Cardiac dysrhythmia
  • Myocardial infarction
  • Respiratory failure
  • Hepatic failure
  • Acute renal failure
  • Deep venous thrombosis
  • Disseminated intravascular coagulation

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