Rosen & Barkin's 5-Minute Emergency Medicine Consult (707 page)

DIAGNOSIS

• Cardiovascular:
  
  • Sinus, atrial, and ventricular tachycardias:
    
    • Multifocal atrial tachycardia
      
    • Atrial fibrillation
      
    • Premature ventricular contractions
      
    • Ventricular tachycardia
      
    • Due to β
      ₁
      -receptor stimulation and adenosine antagonism
      
  • Hypotension:
    
    • Associated with theophylline >100 μg/mL (acute ingestion)
      
    • Due to vasodilatation induced by β
      ₂
      -receptor stimulation
      
    • May be refractory to fluids, positioning, and conventional vasopressors
      
• CNS:
  
  • Tremor
    
  • Mental status changes
    
  • Seizures:
    
    • 14% of chronic intoxications
      
    • 5% of acute intoxications
      
• GI:
  
  • Nausea, vomiting:
    
    • Protracted and may be refractory to antiemetics at usual doses
      
    • 75% of acute intoxications
      
    • 30% of chronic intoxications
      
  • Abdominal pain
    
  • Pharmacobezoar:
    
    • From sustained-release preparations in acute ingestions
      
    • Delays peak concentrations
      
• Metabolic:
  
  • Hypokalemia:
    
    • Typically decreases approximately to 3 mEq/L
      
    • Due to β-receptor stimulation
      
  • Hyperglycemia
    
  • Leukocytosis
    
  • Hypophosphatemia and hypomagnesemia
    
  • Metabolic acidosis with increased serum lactate levels
    

• Serum theophylline concentration:
  
  • Finding of ≥20 μg/mL confirms diagnosis.
    
• ECG and cardiac monitoring
  
• Detailed history to differentiate acute from acute-on-chronic from chronic intoxication
  

• Serum theophylline level:
  
  • Repeat every 2 hr until decreasing to confirm immediate absorption is complete and peak value has occurred.
    
  • Serious morbidity in acute overdose if ≥100 μg/mL
    
• CBC
  
• Electrolytes
  

• KUB (kidneys, ureters, bladder):
  
  • Undissolved sustained-release tablets or pharmacobezoars may appear as radiopacities.
    
  • Bead-filled capsules may appear as radiolucencies.
    
• US of stomach may detect intact sustained-release dosage forms.
  

• Caffeine/β-agonist bronchodilator overdose
  
• Amphetamines
  
• Sympathomimetics
  
• Anticholinergic agents
  
• Drug withdrawal syndromes
  
• Pheochromocytoma
  
• Thyrotoxicosis
  

TREATMENT

Bring pill bottles/pill samples in suspected overdose.

• ABCs:
  
  • Cardiac monitor
    
  • Isotonic crystalloids as needed for hypotension
    
• Naloxone, thiamine, and dextrose (D
  ₅₀
  W) as indicated for altered mental status
  
• Cardiovascular:
  
  • Initiate β-blockers or calcium channel blockers for rate control with supraventricular tachyarrhythmias (SVT).
    
  • Adenosine is antagonized by theophylline and may not be effective to treat SVT.
    
  • Administer isotonic crystalloid IV fluid resuscitation for hypotension:
    
    • With treatment failure, consider β-blocker to reverse theophylline-induced β
      ₂
      -receptor–stimulated vasodilation.
      
    • If vasopressors are needed, choose vasopressor that is not a β-agonist, such as phenylephrine.
      
  • Treat ventricular dysrhythmias conventionally.
    
• Seizures:
  
  • Administer benzodiazepines.
    
  • Phenytoin is contraindicated; it is usually ineffective and may paradoxically worsen seizures in theophylline intoxications.
    

• Administer activated charcoal
  
• Multidose activated charcoal:
  
  • Especially with sustained-release products
    
  • Binds theophylline, which back-diffuses in to the small intestine
    
  • For mild to moderate toxicity
    
  • 25 g q2h until theophylline level ≤20 μg/mL
    
• Initiate whole-bowel irrigation with sustained-release products:
  
  • Administer 1–2 L/hr of polyethylene glycol until a clear, colorless rectal effluent or theophylline level ≤20 μg/mL
    
• Treat protracted vomiting with metoclopramide or 5-HT3-receptor antagonists.
  
• Avoid syrup of ipecac.
  

• Treat hypokalemia in acute ingestions cautiously:
  
  • Relative hypokalemia owing to β-receptor–mediated intracellular shift of extracellular potassium.
    
  • Aggressive correction leads to potentially serious hyperkalemia as theophylline concentrations decrease.
    
• Most electrolyte imbalances respond to β-blocker therapy:
  
  • Generally not indicated; however, because of absence of associated morbidity and potential for β-blocker–induced bronchospasm in pulmonary patients
    

Initiate hemodialysis or hemoperfusion if theophylline level:

• ≥90 μg/mL and symptomatic in acute ingestions
  
• ≥40 μg/mL and:
  
  • Seizures or
    
  • HTN unresponsive to IV fluid or
    
  • Ventricular dysrhythmias
    

• Activated charcoal: 1 g/kg PO, if dose ingested is known, 10 g/1 g theophylline ingested, max. dose 100 g
  
  • Multidose-activated charcoal 25 g q2h until theophylline level ≤20 μg/mL
    
• Diazepam: 0.1 mg/kg IV q5–10min until seizures controlled, up to 30 mg
  
• Diltiazem: 0.25 mg/kg IV bolus; may repeat after 15 min, then 5–15 mg/h infusion for control of heart rate in patients with contraindication to β-blockade
  
• Esmolol: 500 μg/kg IV bolus, followed by 50 μg/kg/min infusion; increase by 50 μg/kg/min increments to max. of 200 μg/kg/min
  
• Metoclopramide: 10 mg IV bolus; may repeat to max. of 1 mg/kg
  
• Ondansetron: 0.15 mg/kg IV bolus up to max. of 16 mg total
  
• Polyethylene glycol (high molecular weight): 1–2 L/h via nasogastric tube
  

FOLLOW-UP

ICU:

• Acute overdoses with serum theophylline concentrations ≥100 μg/mL
  
• Acute-on-chronic or chronic theophylline with either serum concentration ≥60 μg/mL or patient >60 yr old
  
• Seizures or hypotension refractory to fluids and vasopressors in a patient with serum theophylline concentration ≥40 μg/mL
  

• 2 consecutive (≥2 hr apart) decreasing serum theophylline concentrations with most recent concentration <30 μg/mL
  
• Mildly symptomatic or asymptomatic patient meeting above criterion and no evidence of suicidal intention
  

• Follow up with medical toxicologist or primary care doctor
  
• If patient is on chronic theophylline, dosing regimen may have to be adjusted.
  

• Seizures are a major complication.
  
• Tachydysrhythmias are common in overdose.
  
• Multi-dose activated charcoal is beneficial in theophylline overdose.
  

A special thanks to Dr. Harry Karydes who contributed to the previous edition.

• Henderson A, Wright DM, Pond SM. Management of theophylline overdose patients in the intensive care unit.
  Anaesth Intensive Care
  . 1992;20:56–62.
  
• Hoffman RJ. Methylxanthines and selective β2-adrenergic agonists. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, et al., eds.
  Goldfranks’s Toxicologic Emergencies.
  9th ed. New York, NY: McGraw-Hill Medical; 2011.
  
• Shannon M. Life-threatening events after theophylline overdose: A 10-year prospective analysis.
  Arch Intern Med
  . 1999;159:989–994.
  
• Shannon MW. Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication.
  Acad Emerg Med
  . 1997;4:674–678.
  

CODES

975.7 Poisoning by antiasthmatics

BASICS