Rosen & Barkin's 5-Minute Emergency Medicine Consult (485 page)

DIAGNOSIS

• Acute overdose:
  
  • Symptom onset within 6 hr, 9 hr with aripiprazole, up to 24 hr with extended-release formulations (paliperidone)
    
  • Can be delayed if anticholinergic symptoms predominate
    
  • CNS:
    
    • Ranges from mild sedation to coma
      
    • Anticholinergic delirium possible
      
    • Extrapyramidal symptoms (dystonia, akathisia)
      
    • Seizures
      
  • Cardiovascular:
    
    • Tachycardia (anticholinergic)
      
    • Hypotension (antiadrenergic)
      
    • QT prolongation
      
    • Torsade de pointes (rare)
      
  • Respiratory:
    
    • Respiratory depression
      
    • Loss of airway reflexes
      
  • GI:
    
    • Constipation
      
    • Dry mouth
      
  • Genitourinary:
    
    • Urinary retention
      
• Dystonic reactions:
  
  • Involuntary muscle spasms of face, neck, back, and limbs
    
  • Dramatic appearance is frightening to patient and family
    
  • Laryngeal dystonia is a rare form that may cause stridor and dyspnea.
    
• NMS:
  
  • Occurs in <1% of patients, 30% mortality
    
  • Severe hyperthermia
    
  • Skeletal muscle rigidity
    
  • Altered mental status
    
  • Autonomic dysfunction
    
  • Electrolyte disturbance
    
  • Rhabdomyolysis
    
• Agranulocytosis:
  
  • Seen with clozapine and olanzapine
    
  • Occurs with chronic treatment
    
• Diabetes:
  
  • Hyperglycemia, new-onset diabetes, and DKA have all been reported with initiation of neuroleptics.
    

• Monitor vital signs with significant ingestions.
  
• Cardiac monitor
  
• Pulse oximetry
  
• Core body temperature for hyperthermia
  

• Electrolytes, BUN, creatinine, glucose, LFTs
  
• CBC for clozapine overdose, WBC can be elevated in NMS
  
• Creatine phosphokinase (CPK) levels if NMS suspected, agitation, or prolonged immobilization
  
• Serum drug screen with drug levels for possible coingestions based on history:
  
  • Aspirin
    
  • Acetaminophen
    
  • Lithium
    
  • Valproate
    
  • Phenytoin
    
  • Phenobarbital
    
• Urine toxicologic screens are rarely helpful
  
  • False-negatives and false-positives can be misleading
    
• Quantitative levels are rarely available and not helpful in acute management
  

• ECG:
  
  • QT prolongation
    
  • QRS prolongation (rare)
    
• Head CT:
  
  • Indicated for significant mental status change
    

• Serotonin syndrome
  
• Malignant hyperthermia (if recent anesthesia)
  
• Antidepressant overdose
  
• Anticholinergic crisis
  
• Sympathomimetic overdose
  
• Opioid overdose
  
• Occult head injury
  
• Endocrine disorder
  
• Sepsis
  
• Heat stroke
  

TREATMENT

Bring medication bottles when transporting patient to hospital.

Airway, breathing, and circulation management (ABCs):

• Administer supplemental oxygen.
  
• Consider naloxone, thiamine, D
  ₅₀
  (or check blood glucose) for altered mental status
  
• Intubate if respiratory depression
  

• Supportive care is the mainstay of treatment
  
• Decontamination:
  
  • Administer single dose of activated charcoal if ingestion within 1 hr
    
  • Do not give charcoal to patient with unprotected airway
    
  • Use NG tube for charcoal only if pt is intubated
    
  • Consider whole bowel irrigation if large amounts of extended-release formulation ingested (paliperidone)
    
  • Hemodialysis unlikely to be helpful due to high degree of protein binding
    
  • Consider lipid emulsion therapy for cardiovascular collapse
    
• Hypotension:
  
  • 0.9% normal saline (NS) IV fluid bolus
    
  • Treat resistant hypotension with norepinephrine or phenylephrine
    
  • Dopamine may be ineffective
    
• Ventricular dysrhythmias:
  
  • Class IA, IB, and III antidysrhythmics can potentiate cardiotoxicity. Lidocaine can be used in refractory cases
    
  • Magnesium for prolonged QT
    
  • Cardioversion if hemodynamically unstable
    
  • Consider intralipid (20% lipid emulsion) for cardiovascular collapse
    
  • For asymptomatic QTc prolongation, replete potassium, calcium, and magnesium to normal levels
    
  • QRS prolongation (>120 msec) should be treated with sodium bicarbonate therapy
    
• Dystonic reactions:
  
  • Administer diphenhydramine or benztropine mesylate.
    
  • Treatment should be continued for 3 days to prevent recurrence.
    
• NMS:
  
  • Recognition and cessation of neuroleptics is critical.
    
  • Active cooling for hyperthermia
    
  • Aggressive benzodiazepines for agitation
    
  • Severe cases may require bromocriptine (dopamine agonist) or dantrolene (a direct-acting muscle relaxant)
    
  • Consider intubation and neuromuscular blockade
    
• Seizures:
  
  • Treat initially with diazepam or lorazepam.
    
  • Phenobarbital for persistent seizures
    
  • There is no role for phenytoin in toxin-induced seizures
    
• Anticholinergic delirium:
  
  • Benzodiazepines are 1st-line agents
    
  • Physostigmine can be used with caution
    
    • Physostigmine is contraindicated in a patient with dysrhythmias, heart block, or interval prolongation on EKG
      

• Activated charcoal: 1–2 g/kg PO
  
• Benztropine mesylate: 1–2 mg IV or PO
  
• Bromocriptine: 2.5–10 mg q8h PO
  
• Dantrolene: 2–3 mg/kg/d as continuous infusion (10 mg/kg max.)
  
• Diazepam: 5–10 mg IV q10–15min
  
• Diphenhydramine: 25–50 mg IV (1 mg/kg)
  
• Lidocaine 1–2 mg/kg followed by infusion
  
• Lipid emulsion (20%) 1.5 mL/kg bolus followed by 0.25 mL/kg/min infusion for 30–60 min, may repeat bolus for persistent hemodynamic compromise
  
• Lorazepam: 2–4 mg (peds: 0.03–0.05 mg/kg) IV q10–15min
  
• Magnesium sulfate: 1–2 g IV over 5–15 min
  
• Norepinephrine: 1–2 μg/kg/min IV titrate to BP
  
• Phenobarbital: 10–20 mg/kg IV (loading dose); monitor for respiratory depression
  
• Physostigmine 0.5 mg IV q3–5min
  

FOLLOW-UP

• Overdose with CNS sedation, agitation, dysrhythmias, or vital sign abnormalities to monitored bed or ICU
  
• NMS require ICU care
  
• New-onset diabetes (secondary to neuroleptic use) with severe hyperglycemia and/or ketoacidosis.
  

• Asymptomatic after 6 hr of observation
  
• Longer observation required for aripiprazole and paliperidone ingestion as well as ingestion of extended release formulations
  

• Patients with unintentional (accidental) poisoning require poison prevention counseling.
  
• Patients with intentional (e.g., suicide) poisoning require psychiatric evaluation.
  
• New-onset diabetes requires primary care/endocrine follow-up.
  

• Psychiatric referral for intentional overdoses
  
• Primary care follow-up for accidental ingestions or medication side effect follow-up
  

• Neuroleptics represent a group of drugs with diverse indications and a wide range of toxicity.
  
• Most overdoses are mild, and CNS depression predominates.
  
• Dystonic reactions are the most common side effect of neuroleptics. These reactions are dramatic in appearance but easily treatable.
  
• NMS is a potentially fatal reaction that can be seen in acute or chronic usage of neuroleptics.
  
• Newer antipsychotics can have delayed onset up to 24 hr.
  
• Contact the poison control center for further guidance
  

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• Lipscombe LL, Lévesque L, Gruneir A, et al. Antipsychotic drugs and hyperglycemia in older patients with diabetes.
  Arch Intern Med
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• Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotics.
  J Emerg Med
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• Ngo A, Ciranni M, Olson KR. Acute quetiapine overdose in adults: A 5-year retrospective case series.
  Ann Emerg Med
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• Reulbach U, Dütsch C, Biermann T, et al. Managing an effective treatment for neuroleptic malignant syndrome.
  Crit Care
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• Wittler MA. Antipsychotics. In: Marx, ed.
  Rosen’s Emergency Medicine
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• www.lipidrescue.org
  .
  

CODES