Management protocol for theophylline intoxication

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