This document provides guidelines for managing intoxication from theophylline, a bronchodilator. Key points include: 1. Theophylline has a narrow therapeutic index and toxicity can occur even at low doses, presenting with nausea, vomiting, tachycardia, seizures and coma. 2. Initial treatment focuses on stabilizing vital signs and eliminating the drug through induction of vomiting, gastric lavage or activated charcoal. Hemodialysis may be needed for severe cases. 3. Patients with seizures, coma, cardiac issues or high initial blood levels require ICU admission for close monitoring and management of arrhythmias or acidosis. Serial blood levels guide further treatment.

1. Management protocol for
intoxication
By
Kerolus Ekram Gad Shehata
• PGY-III IM resident, Ain Shams University
• ECFMG certified

2. General Hints
 Frequency: Very common
 Mode: Accidental & Suicidal
 Preparations: Epicophylline, Aminophylline,
Theo SR, Quibron SR…etc. “Anti-asthmatics”
 Presentation: Acute or acute on top of chronic
toxicity.
 Characteristic shape of the tablet: rectangular,
dividable.

3. Characteristic tablet description

4. Presentation
• Generally: Any patient with severe intractable
vomiting + Tachycardia in the PCC ER unit =
Theophylline toxicity till proved otherwise.
• GIT: nausea, severe up to intractable vomiting +/-
upper GI bleeding, diarrhea and abdominal pain.
• CVS: palpitation and hypotension
• CNS: Tremors, agitation, restlessness, seizures and
coma in late severe stages.
• Respiratory: Tachypnea

5. Take Care!!
• Theophylline has narrow TI.
• Some preparations may form concretions in the
stomach especially with the sustained release
preparations.
• Theophylline undergoes significant entero-
hepatic circulation…MDAC
• Toxicity can occur in low doses in patients taking
theophylline chronically.

6. How to proceed?
• Vitals are Vital.
• Pulse: Tachycardic +/- irregularity
• B.P.: Hypotension.
• R.R.: Tachypneic.
• N.B. once symptomatic = Admission
• Stabilizing the patient’s condition is our first
priority before inquiring about the detailed
history.
• Seizing patient should be treated promptly with
BZP and we may use phenobarbital or Thiopental
if needed.

7. How to proceed...Cont’d
• GI elimination is of utmost importance.
• Ipecac is not preferred as the patient may
already have intractable vomiting.
• We can just give plenty amount of water to
induce vomiting unless it is contraindicated e.g.
comatosed patient, severely shocked patient,
history of upper GI bleeding.
• Elimination should never be skipped even if the
presentation is delayed esp. with SR tablets.

8. How to proceed...Cont’d
• Gastric lavage can be done in uncooperative
patients or in patients with DCL.
• Activated charcoal is a cornerstone in our
management plan and should be given in multiple
doses as a GI dialysis.
• In severe intractable vomiting: Metoclopramide up
to Ondansetron.
• N.B. Never to use phenothiazines as antiemetics as
they decrease threshold of seizures.
• Hypotension: Crystalloids, colloids or even
vasopressors e.g. NEp.

9. Severe cases
• N.B. Severely agitated patients, seizing patients
or those with history of seizures, comatosed
patients: That indicate severe toxicity and we can
resort to hemodialysis immediately after initial
stabilization of the patients even before
admission.
• N.B. Extremes of age, patients chronically treated
with theophylline and those with other premorbid
conditions are more susceptible to severe toxicity.

10. Investigations
• Routine lab: Glucose, Na, K
• Glucose: Hyperglycemia (usually well tolerated)
• Potassium: HYPOkalemia due to many causes
(catecholamine release, severe vomiting,
respiratory alkalosis). So, it is actually
PESUDOhypokalemia that shouldn’t be treated
aggressively as it will be spontaneously corrected
(redistribution process).
• ABG: Metabolic acidosis (correlate with the
severity of the condition) + Respiratory alkalosis.

11. Investigations…Cont’d
• ECG on admission and repeated thereafter:
Tachyarrhythmias are common (atrial and
ventricular)
• Continuous cardiac monitoring is needed in
severely intoxicated patients and those with
premorbid cardiac conditions.
• Theophylline blood level: we should have a
baseline value on admission and repeated later on
to follow up case progression.
• CPK: if you suspect rhabdomyolysis (repeatedly
seizing patient)

12. What is next?
• Serial follow up of the patient’s vital data,
clinical progression and laboratory studies is of a
great significance to determine if further
therapeutic protocol is needed.
• N.B. Severely intoxicated patients may present
with severe agitation that can be easily mistaken
by the inexperienced ER physicians as a psychic
patients in the mean time that she needs
immediate hemodialysis.

13. What is next?
• Management strategies for theophylline intoxication
include supportive care, administration of multiple-
dose activated charcoal, and, in severe cases,
hemodialysis.
• N.B. The major life-threatening events of theophylline
intoxication are seizures and cardiac arrhythmias.
• Management of Metabolic acidosis: NaHCO3 + serial
ABG monitoring.
• For hyperthermia: Cold fomentations +/- BZP to calm
the patient down

14. Indications of ICU ADMISSION
1. Unstable vital data despite initial ER management.
2. Severe agitation +/- Seizures.
3. History of convulsions.
4. Comatosed patients.
5. Severe metabolic acidosis.
6. Premorbid condition e.g. cardiac patients
7. ECG shows potentially dangerous arrhythmias e.g.
multiple PVCs.
8. Initial blood level > 35 microgram/dl.

15. Special Notes
• For atrial Tachyarrhythmias: we can use
propranolol (unless there is bronchospasm),
esmolol or verapamil.
• For Ventricular arrhythmias : use lidocaine.
• Phenytoin is ineffective in theophylline induced
seizures and actually been shown to decrease
the seizure threshold and lower the lethal dose
(Enzyme inhibitor just like Macrolides)
• Never use phenothiazines as antiemetics as
they may induce seizures in these patients.

16. Questions & Comments