Theophylline is a methylxanthine of the same class of agents as caffeine and is typically used to treat treatent-refractory asthma and COPD. It happens to be dirt-cheap (as it has been in the market for 80 years). It is an anti-inflammatory and a bronchodiltaor; it remains a third-line agent mainly because we have better anti-inflammatory drugs (steroids) and we have better bronchodilators (β-agonists).
Question 29 from the first paper of 2017 was the one and only time theophylline overdose had ever come up in the CICM Part II exam. The overdose was masquerading behind some lactic acidosis and because of its highly nonspecific nature "several candidates failed to recognise theophylline overdose". Given the rarity of this hideously toxic drug in modern management of COPD and asthma, it is hardly surprising that nobody knew how to deal with it, leaving the examiners to complain that "management of theophylline toxicity was discussed poorly". The trainees can be forgiven for mistaking this for some sort of sympathomimetic toxidrome (much more common in light of our apparently crippling meth epidemic).
As far as literature goes, for raw untreated pharmacology one cannot go past the excellent 2013 article by Peter J. Barnes. Realistically, that would be all you need. Unless otherwise stated the rest of this summary is basicaly derived from Barnes' work.
Some unique pharmacokinetic features:
Some ...undesirable pharmacodynamic features:
Because of the PDE inhibition, methylxanthines at toxic doses begin to act as "inodilators", with peripheral vasodilation and increased inotropy. Hence the widened pulse pressure. Also, the electrolyte derangement is precisely what you might expect with a β-agonist overdose (see Hall et al, 1984). Particularly hypercalcemia is mentioned in the college paper, and is thought to be some sort of β-adrenergic effect (McPherson et al, 1986)
Levels tend to correlate with toxicity:
A - the patient will likely need intubation at some stage
B - ventilate them with a slightly higher rate to maintain the compensation for metabolic acidosis
C - they will likely be hypotensive with a large overdose; noradrenaline will be required.
They will also have arrhythmias. The college answer helpfully suggests esmolol or amiodarone. Esmolol has been used successfully (Seneff et al, 1990) and may paradoxically improve blood pressure by acting as a β2-antagonist, as well as slowing the rate and improving diastolic filling.
D - Sedation with benzodiazepines seems like a sensible move.
Likely, the patient will need them anyway for seziure control.
Other antiepileptics are apparently ineffective.
E - Correct all their electrolyte disturbances
F - Consider dialysis; high efficiency dialysis may even remove some theophylline
G - Regular antiemetics and/or NGT (given how much you are relying on multi-dose charcoal )
Barnes, Peter J. "Theophylline." American journal of respiratory and critical care medicine 188.8 (2013): 901-906.
Hendeles, Leslie, et al. "Food-induced “dose-dumping” from a once-a-day theophylline product as a cause of theophylline toxicity." Chest 87.6 (1985): 758-765.
Ehlers, Sally M., Darwin E. Zaske, and Ronald J. Sawchuk. "Massive theophylline overdose: Rapid elimination by charcoal hemoperfusion." Jama240.5 (1978): 474-475.
Hall, Kevin W., et al. "Metabolic abnormalities associated with intentional theophylline overdose." Annals of internal medicine 101.4 (1984): 457-462.
Seneff, Michael, et al. "Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability." Annals of emergency medicine 19.6 (1990): 671-673.
MILTON, L. McPHERSON, et al. "Theophylline-lnduced Hypercalcemia."Annals of internal medicine 105 (1986): 52-54.