Theophylline toxicity: Difference between revisions

No edit summary
 
(24 intermediate revisions by 6 users not shown)
Line 1: Line 1:
''See [[theophylline]] for general drug information.''
==Background==
==Background==
#Still used in patients with debilitating brochospastic disease
*Primarily used as a bronchodilator, however rarely used now due to better available options
#Studied for treatment of [[Acute Mountain Sickness]] and [[Contrast-Induced Nephropathy]]
*Also studied for treatment of [[Acute Mountain Sickness]] and [[Contrast-Induced Nephropathy]]
#PO in elixir, extended release, or controlled release forms but absorption erratic
*PO available as elixer and capsule (12 or 24-hour extended release)
#IV as aminophylline
*IV as aminophylline (shorter acting than PO)
#Adenosine antagonism, Increase catecholamines, and Phosphodiesterase inhibition
*Mechanism of action<ref name="Fisher">Fisher, J., & Graudins, A. (2015). Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(3), 359-63.</ref>:
**Release of endogenous catecholamines → β2 agonism → bronchodilation
**PDE inhibition → increases cAMP
**Adenosine antagonist


==Clinical Features==
==Clinical Features==
#Neurologic
*Cardiovascular
##Tremor
**[[Sinus Tachycardia]]
##Agitation
**Atrial/Ventricular [[arrhythmias]]
##[[Seizure]]
**[[Hypotension]] (due to β2-mediated vasodilation)
#Cardiovascular
*Metabolic
##[[Sinus Tachycardia]]
**[[Hypokalemia]]
##Atrial/Ventricular [[arrhythmias]]
**[[Metabolic Acidosis]]
##[[Hypotension]]
**[[Hyperthermia]]
#Metabolic
**[[Hyperglycemia]]
##[[Hypokalemia]]
*Neurologic
##[[Metabolic Acidosis]]
**Tremor
##[[Hyperthermia]]
**Agitation
##[[Rhabdomyolysis]]
**[[Seizure]]
##[[Hyperglycemia]]
*GI
#GI
**[[Nausea/Vomiting]]
##[[Nausea/Vomiting]]


==Workup==
==Differential Diagnosis==
#[[EKG]]
*[[Beta-2 agonist]] toxicity
#Chem
*[[Sympathomimetic toxicity]]
#CK
*[[Iron toxicity]]
#Theophylline level
*[[Salicylate toxicity]]
 
==Evaluation==
*Theophylline level<ref name="Aggelopoulou">Aggelopoulou, E., Tzortzis, S., Tsiourantani, F., Agrios, I., & Lazaridis, K. (2018). Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 27(4), 387-391.</ref>
**10–20 μg/mL - Therapeutic
**20-80 μg/mL - Toxic level
**80-100 μg/mL - Severe toxicity or death
*[[ECG]]
*Metabolic panel
*Lactic acid level
*CK
*Evaluate for co-ingestion


==Management==
==Management==
#GI decontamination ([[Multidose Activated Charcoal]], [[Whole Bowel Irrigation]])
*Supportive care is the mainstay of treatment
##Considered in life-threatening overdose
*Cardiovascular
###contraindications: unsecured airway, nausea, vomiting, [[ileus]], [[Bowel Obstruction]], or need for emergent endoscopy
**Norepinephrine (alpha-agonist) for hypotension resistant to IVF
#[[Seizures]]
**Refractory hypotension may respond to non-selective beta-blockers<ref name="Fisher" />
##[[Lorazepam]] (Ativan) 1st line
**Beta-blockers (esmolol preferred due to short half-life) for tachydysrhythmias
##Phenobarbital if [[lorazepam]] ineffective
*GI decontamination ([[Multidose Activated Charcoal]], [[Whole Bowel Irrigation]])
##[[Dilatin]] contraindicated as increases seizure in animal studies
**Consider in recent severe overdose
#Cardiovascular
**Contraindications: unsecured airway, [[nausea]]/[[vomiting]], ileus, [[Bowel Obstruction]], or need for emergent endoscopy
##[[IV Fluids]] for [[hypotension]]
*[[Seizures]]
##Beta blockers for [[tachyarrhymias]]
**[[Lorazepam]] (Ativan) 1st line
###Controversial, involve a toxicologist
**Phenobarbital if [[lorazepam]] ineffective
#Dialysis
**Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
##Indicated in [[seizures]], severe [[arrhythmias]]
*Dialysis or plasmapheresis
##Theophylline level >90mcg/ml in acute ingestion
**Indicated in [[seizures]], severe [[arrhythmias]], hypotension, serum level >90 μg/mL (>40 μg/mL in chronic ingestion)
##Theophylline level >40mcg/ml in chronic ingestion
#Supportive care
##Cardiac monitoring
##Zofran for antiemetic
##EEG for sedated and paralyzed patients


==Disposition==
==Disposition==
#Immediate release-Home after 6 hours if nontoxic, asymptomatic, and normal vital sign
*Almost all patients will require admission
#Sustained release-Home after 12 hours if nontoxic, asymptomatic, and normal vital sign
*Can consider discharge with close followup (in conjunction with toxicology) if unintentional overdose, asymptomatic, and normal vital signs
 
==See Also==
*[[Toxicology (main)]]
 
==External Links==
 
 
==References==
<references/>


==Sources==
[[Category:Toxicology]]
Tintinalli

Latest revision as of 23:51, 15 November 2018

See theophylline for general drug information.

Background

  • Primarily used as a bronchodilator, however rarely used now due to better available options
  • Also studied for treatment of Acute Mountain Sickness and Contrast-Induced Nephropathy
  • PO available as elixer and capsule (12 or 24-hour extended release)
  • IV as aminophylline (shorter acting than PO)
  • Mechanism of action[1]:
    • Release of endogenous catecholamines → β2 agonism → bronchodilation
    • PDE inhibition → increases cAMP
    • Adenosine antagonist

Clinical Features

Differential Diagnosis

Evaluation

  • Theophylline level[2]
    • 10–20 μg/mL - Therapeutic
    • 20-80 μg/mL - Toxic level
    • 80-100 μg/mL - Severe toxicity or death
  • ECG
  • Metabolic panel
  • Lactic acid level
  • CK
  • Evaluate for co-ingestion

Management

  • Supportive care is the mainstay of treatment
  • Cardiovascular
    • Norepinephrine (alpha-agonist) for hypotension resistant to IVF
    • Refractory hypotension may respond to non-selective beta-blockers[1]
    • Beta-blockers (esmolol preferred due to short half-life) for tachydysrhythmias
  • GI decontamination (Multidose Activated Charcoal, Whole Bowel Irrigation)
  • Seizures
    • Lorazepam (Ativan) 1st line
    • Phenobarbital if lorazepam ineffective
    • Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
  • Dialysis or plasmapheresis
    • Indicated in seizures, severe arrhythmias, hypotension, serum level >90 μg/mL (>40 μg/mL in chronic ingestion)

Disposition

  • Almost all patients will require admission
  • Can consider discharge with close followup (in conjunction with toxicology) if unintentional overdose, asymptomatic, and normal vital signs

See Also

External Links

References

  1. 1.0 1.1 Fisher, J., & Graudins, A. (2015). Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(3), 359-63.
  2. Aggelopoulou, E., Tzortzis, S., Tsiourantani, F., Agrios, I., & Lazaridis, K. (2018). Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 27(4), 387-391.