Sustained-Release Verapamil Overdose Refractory to Calcium and Atropine

Why the standard drugs have not worked.

• Atropine blocks muscarinic receptors at the sinoatrial and atrioventricular nodes. Verapamil blocks the L-type calcium channel in the nodal and myocardial cells - the block is downstream of the muscarinic receptor, so atropine has little to oppose. It is worth trying once, but failure is expected in significant verapamil poisoning.
• Calcium raises extracellular calcium and can increase the gradient across the channel, which helps in mild-to-moderate poisoning. In a large ingestion the channels are blocked in a use-dependent way and calcium alone cannot restore intracellular calcium flux; its effect is transient and dose-limited. Continue it as an infusion, but do not expect it to reverse shock.

Next step: hyperinsulinaemic euglycaemia therapy (HIET). In verapamil and other cardiogenic poisonings the shocked myocardium switches from fatty acid to carbohydrate metabolism; insulin is the hormone that drives glucose into the stunned cardiomyocyte and improves contractility and peripheral perfusion. It is the intervention with the best evidence after calcium in refractory calcium-channel blocker poisoning.

How to start it:

• Bolus 1 unit/kg of regular insulin with 25 g of glucose (or 0.5 g/kg of dextrose), then infuse 0.5–1 unit/kg/h titrated to haemodynamic response, together with a dextrose infusion (0.5 g/kg/h) to keep glucose between 5 and 10 mmol/L.
• Monitor capillary glucose every 15–30 minutes initially, and potassium hourly: insulin drives potassium intracellularly and hypokalaemia can be profound. Replace below 3.0 mmol/L.
• Use a central line if possible; a large peripheral line is acceptable while the central access is being obtained. Watch for fluid overload.
• Continue the calcium infusion and add noradrenaline if the mean arterial pressure remains below 65 mmHg.

Challenge the premise. 'Stable at 6 hours' is not a valid endpoint for a sustained-release verapamil overdose. Sustained-release preparations produce delayed and prolonged absorption, often with a second peak; the classic teaching that a calcium-channel blocker overdose can be cleared after 6 asymptomatic hours applies to immediate-release formulations. This patient already has bradycardia, a first-degree block and hypotension at 6 hours, which is established toxicity, not an absence of it. Cardiovascular collapse can occur abruptly and is difficult to reverse without pacing or extracorporeal support, neither of which this hospital has.

Disposition. She needs a monitored bed with continuous ECG, invasive or at least frequent non-invasive blood pressure, and a nurse who can recognise and call for help. Minimum observation is 24 hours from ingestion with a normal ECG, normal blood pressure and no symptoms; with ongoing bradycardia and hypotension, observation continues until the ECG and haemodynamics have been normal for at least 24 hours, often longer.

Handling the disagreement, professionally:

• Speak to the intensivist directly, present the ingestion, the formulation, the current ECG and pressures, and the predictable trajectory; frame it as a request for advice and shared risk rather than a complaint.
• Ask the intensivist to document their refusal in the notes, and document your own risk assessment.
• Escalate to the consultant physician or clinical director on call if a monitored bed is refused.
• Contact the toxicology unit now (not when she deteriorates) for a second opinion and to arrange transfer if local monitoring is inadequate.
• Do not discharge her, and do not move her to an unmonitored ward to resolve the bed dispute.

Reassess the basics first. Confirm the infusions are actually running at the intended rate, that the glucose and potassium are safe, that she is not hypothermic or hypovolaemic, and that the ECG is genuine rather than artefact. Then:

1. Escalate HIET to the upper end of the range (up to 1 unit/kg/h, and in refractory cases higher with specialist advice), and maximise the calcium infusion within safe limits, watching for hypercalcaemia and bradyarrhythmia.
2. Vasopressors. Noradrenaline to maintain mean arterial pressure above 65 mmHg; adrenaline is a reasonable alternative and adds β-agonist inotropic support. Escalate early rather than in small increments.
3. Pacing. Transcutaneous pacing can be attempted; in verapamil poisoning it often fails to capture or does not improve output because the myocardium itself is poisoned, but it is worth a trial while transvenous access is arranged. Transvenous pacing is preferable, though this hospital cannot provide it - another reason to transfer.
4. Sodium bicarbonate is not specific for calcium-channel blockers but may help if the QRS widens with hyperkalaemia or a sodium-channel component; it is not a substitute for the measures above.
5. Extracorporeal support is the definitive rescue when pharmacology fails. Because it is not available locally, this is the trigger to make the transfer happen: contact the toxicology unit and the ECMO-capable centre, stabilise as far as possible with HIET, calcium and vasopressors, and move her with a doctor and monitor. Prognosis after cardiac arrest from calcium-channel blockers is poor without extracorporeal support, so the transfer decision must be made before arrest, not after.
6. Do not give more atropine - it has already failed twice and delays effective treatment.