Rosen & Barkin's 5-Minute Emergency Medicine Consult (484 page)

DIAGNOSIS

• Life-threatening condition
  
• Hallmarks of the disease:
  
  • Hyperthermia (temperature may be as high as 106–107°F, 41°C)
    
  • Altered level of consciousness—stupor
    
  • Significant skeletal muscle rigidity—”lead-pipe rigidity.”
    
  • Autonomic instability
    
    • Tachycardia
      
    • Labile BP
      
    • Tachypnea
      
    • Profuse sweating
      
    • Dysrhythmias
      

• Neuroleptic use
  
• Discontinuation of antiparkinsonian drugs
  
• Change in mental status
  

• Fever
  
• Tachycardia, labile BP
  
• Delirium
  
• Muscle rigidity
  
• Diaphoresis
  

• An accurate history (especially current medications) and physical exam confirm the diagnosis.
  
• Creatine phosphokinase, WBC determination, liver function tests, and iron level
  

• Electrolytes, glucose
  
• BUN, creatinine
  
• PT/PTT, urinalysis, and urine myoglobin
  
• Creatine kinase
  
• LFTs (lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, etc.)
  
• Venous blood gas (VBG)
  

CT scan, EEG if the cause of altered level of consciousness is unclear

Lumbar puncture to rule out other causes of fever or altered mental status

Related disorders

• Malignant hyperthermia
  
• Serotonin syndrome
  
• Anticholinergic poisoning
  
• Sympathomimetic poisoning (cocaine, methamphetamine)
  
• Drug intoxication toxicity (PCP, ecstasy MDMA)
  
• Withdrawal from intrathecal baclofen therapy
  

Unrelated disorders

• CNS infection (meningitis, encephalitis)
  
• Tetanus
  
• Heat stroke
  
• Acute dystonia
  
• Strychnine poisoning
  
• Vascular CNS event
  
• Thyrotoxicosis
  
• Rabies
  
• Alcohol withdrawal
  
• Seizures
  
• Pheochromocytoma
  
• Acute porphyria
  
• Acute hydrocephalus
  
• Acute spinal cord injury
  
• Systemic infections (e.g., pneumonia, sepsis)
  

TREATMENT

• Ventilation may be difficult because of chest wall rigidity
  
• Cool the patient and treat seizures if they occur
  
• Check fingerstick glucose
  

• Airway intervention and circulatory support as needed
  
• IV, supplemental O
  ₂
  , cardiac monitor
  
• Immediate IV benzodiazepines (diazepam, lorazepam, midazolam):
  
  • May require repeated large doses
    
• If symptoms are not controlled within a few minutes, rapid sequence intubation (RSI) and neuromuscular blockade are necessary:
  
  • Nondepolarizing neuromuscular blockers (vecuronium, rocuronium, pancuronium) are preferable to succinylcholine.
    
• Measures to control hyperthermia:
  
  • Ice packs
    
  • Mist and fan
    
  • Cooling blankets
    
  • Ice water gastric lavage
    
• Aggressive IV fluid therapy with lactated Ringer solution or normal saline
  

• Relief of muscle rigidity
  
• Benzodiazepines are the drug of choice
  
• Bromocriptine is a dopamine agonist that may play a role in longer-term management
  
• Dantrolene is a direct skeletal muscle relaxant that may play a role in longer-term management
  
• Neither bromocriptine nor dantrolene has a rapid onset and neither has been shown to alter outcome
  
• Amantadine has dopaminergic and anticholinergic effects and can be used as an alternative to bromocriptine
  
• Discontinue neuroleptics
  
• Recognize complications (rhabdomyolysis, respiratory failure, acute renal failure)
  

• Diazepam: 5 mg IV q5min
  
• Lorazepam: 1 mg IV q5min
  
• Midazolam 1 mg IV q5min
  
• Rocuronium: 600–1,200 μg/kg IV × 1 for RSI
  
• Pancuronium: 60–100 μg/kg IV × 1 for intubation
  

• Bromocriptine: 5–10 mg PO TID–QID (start 2.5 mg)
  
• Dantrolene: 1 mg/kg IV q4–6h × 24–48 hr
  
• Amantadine: 100 mg PO BID
  

FOLLOW-UP

• Patients with NMS should be admitted
  
• Patients will often require intensive care
  

Patients and families must be counseled on the future use of any drug that may trigger NMS

• Maintain high clinical suspicion for NMS in patients on neuroleptics with mental status changes, rigidity, fever, or dysautonomia
  
• Must rule out other causes of fever and altered mental status (i.e., meningitis, encephalitis)
  
• Medication history is essential when considering NMS
  
• Discontinuing causative agent is the key step in treatment
  
• Aggressive supportive care is essential
  

• Bellamy CJ, Kane-Gill SL, Falcione BA, et al. Neuroleptic malignant syndrome in traumatic brain injury patients treated with haloperidol.
  J Trauma
  . 2009;66:954–958.
  
• Marx JA, Hockberger RS, Walls RM, et al.
  Rosen’s Emergency Medicine: Concepts and Clinical Practice
  . 7th ed. St. Louis, MO: Mosby; 2009.
  
• Seitz DP, Gill SS. Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: Case reports and a review of the literature.
  Psychosomatics
  . 2009;50:8–15.
  
• Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome.
  Ann Pharmacother
  . 2008;42:1290–1297.
  
• Wijdicks EFM. Neuroleptic malignant syndrome. In: Aminoff MJ, ed.
  UpToDate
  . Waltham, MA: 2012.
  

CODES

333.92 Neuroleptic malignant syndrome

BASICS

• Neuroleptics (antipsychotics) used for management of:
  
  • Psychotic disorders
    
  • Agitation
    
  • Dementia in the elderly
    
  • Autism and behavioral problems in children
    
  • Eating disorders
    
  • Antiemetic
    
  • Migraine headaches
    
• Acute overdose:
  
  • Symptoms usually mild to moderate
    
  • CNS and cardiovascular symptoms predominate
    
  • CNS depression, seizure, and coma possible
    
• Dystonic reactions (dystonia):
  
  • Most common adverse effect
    
  • Can occur at any time, often within 48 hr of starting medication
    
• Akathisia:
  
  • Patient has motor restlessness and feels a need to pace or move constantly
    
  • Occurs within hours to weeks of starting medication
    
• Neuroleptic malignant syndrome (NMS):
  
  • Idiosyncratic, life-threatening event
    
  • Can occur at any time but most commonly in overdose, dose increase, and during the 1st wk of usage
    
• Tardive dyskinesia:
  
  • Movement disorder usually affecting patients after years of taking neuroleptics
    
  • Treated by decreasing, discontinuing, or changing the drug
    

• Typical neuroleptics (phenothiazines, butyrophenones) strongly antagonize dopaminergic receptors, these include:
  
  • Haloperidol (Haldol)
    
  • Chlorpromazine (Thorazine)
    
  • Prochlorperazine (Compazine)
    
  • Thioridazine (Mellaril)
    
  • Fluphenazine (Prolixin)
    
  • Promethazine (Phenergan)
    
  • Droperidol (Inapsine)
    
  • Hydroxyzine (Atarax)
    
• Typical neuroleptics also have varying degrees of antagonism for histamine, muscarinic, and α-adrenergic receptors.
  
• Atypical neuroleptics have weaker dopaminergic antagonism and moderate serotonergic antagonism, these include:
  
  • Asenapine (Saphris)
    
  • Aripiprazole (Abilify)
    
  • Clozapine (Clozaril)
    
  • Paliperidone (Invega)
    
  • Risperidone (Risperdal)
    
  • Olanzapine (Zyprexa)
    
  • Quetiapine (Seroquel)
    
  • Ziprasidone (Geodon)