Question 29

College answer

a)

• Acute Theophylline Poisoning. The clinical findings of vomiting, seizures, hypotension, 
Atrial Flutter combined with metabolic abnormalities strongly suggests theophylline 
poisoning
• Above biochemical abnormalities may suggest β-agonist toxicity; but cardiac arrhythmias 
and seizures are rare features of β-agonist toxicity
• Biochemical findings and ECG abnormalities do not favour tricyclic anti-depressant or
SSRI overdose

b)
• Check serum theophylline
• Repeated doses of activate charcoal, as means of decontamination. Theophylline is also 
more rapidly cleared from the blood in patients receiving activated charcoal
• Extracorporeal removal such as charcoal hemoperfusion or hemodialysis, as 
theophylline has low volume of distribution without extensive protein binding. High 
efficiency hemodialysis as effective as charcoal hemoperfusion
• Control of seizures with benzodiazepines. Phenytoin should be avoided as it is not 
effective and may worsen mortality
• Correction of electrolyte abnormalities (hypokalemia, hypomagnesemia and 
hypophosphatemia)
• IV Esmolol or amiodarone for cardiac arrhythmia, after correction of electrolyte 
abnormalities
• Hypotension should be treated with IV fluids and/or noradrenaline. IV propranolol or 
esmolol may reverse hypotension as it is caused by β2-adrenergic effects
• Hypercalcemia usually responds to fluid resuscitation
• Hyperglycemia responds to fluids and/or insulin administration

Additional Examiner Comments: 
Several candidates failed to recognise theophylline poisoning. Many candidates failed to read the stem and did not give a rationale for their diagnosis. Management of theophylline toxicity was discussed poorly.

Discussion

Let us interpret these data systematically.

• Sounds like an overdose
• Clinical features include:
  • Seizures
  • Nausea and vomiting
  • Hypotension/shock
  • Atrial tachyarrhythmia
• Biochemistry demonstrates:
  • Hypokalemia
  • Hypomagnesemia
  • Hypophosphataemia
  • Hyperglycaemia
  • Hypercalcemia
  • Lactic acidosis
  • Renal failure

So, sounds like a theophylline overdose. As the collegely rightly pointed out, there is no way this old guy could have cosumed enough salmeterol to make him this sick.

In general, the features of theophylline overdose are as follows:

Symptoms	Signs	Biochemistry
Nausea Vomiting Elevated mood Agitation, anxiety Hallucinations	Tachypnoea Tachycardia Hypotension Widened pulse pressure Tremor Seizures Increased muscle tone Fasciculations	Hypokalemia Hypomagnesemia Hypophosphataemia Hyperglycaemia Hypercalcemia Lactic acidosis Respiratory alkalosis Rhabdomyolysis

As for the management:

Decontamination

• Repeated doses of activated charcoal (MDAC)

Enhanced elimination

• Charcoal haemoperfusion

Antidotes

• Strangely, SVT does not respond to adenosine. Goldfranks' Manual (2007 edition, p. 557) recommends calcium channel blockers as a more effective antiarrhythmic therapy (a β-blocker would be just as good but the patient will inevitably be somebody with either asthma or COPD). 

Supportive management

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)