In an adult with atrial fibrillation on warfarin who overdosed on diltiazem (480 mg) and candesartan (8 mg) two hours ago and now presents with tachycardia (~125 bpm), chest tightness, and serum potassium of 5.5 mEq/L, what is the immediate management?

Immediate Management of Diltiazem and Candesartan Overdose with Hyperkalemia

Immediate Stabilization and Monitoring

In this patient with combined calcium-channel blocker and ARB overdose presenting with tachycardia and hyperkalemia, the first priority is aggressive hemodynamic support with intravenous calcium, high-dose insulin-euglycemia therapy, and continuous cardiac monitoring, while simultaneously treating the potassium of 5.5 mEq/L.

Hemodynamic Support for Diltiazem Toxicity

• Administer intravenous calcium chloride 1 g (or calcium gluconate 3 g) over 5 minutes, repeated every 10-20 minutes as necessary to reverse the pharmacological effects of calcium-channel blocker overdose 1
• Initiate continuous calcium infusion at 2 g per hour for up to 10-24 hours if initial boluses are insufficient, with monitoring for hypercalcemia 1
• The effectiveness of calcium administration has been inconsistent in diltiazem overdose, but it remains first-line therapy and may enhance responsiveness to atropine 1

High-Dose Insulin Therapy

• Start high-dose insulin-euglycemia therapy as the most effective treatment for calcium-channel blocker toxicity causing hemodynamic compromise, though specific protocols are not detailed in the provided evidence 1
• Administer inotropic agents (dopamine or dobutamine) if cardiac failure develops, as diltiazem overdose commonly causes myocardial depression 1

Management of Tachycardia

• The paradoxical tachycardia (~125 bpm) in diltiazem overdose likely represents compensatory response to hypotension or direct toxic effects 1
• Do not administer additional rate-control agents (beta-blockers, additional calcium-channel blockers) as these will worsen hemodynamic compromise 2
• If bradycardia develops instead, administer atropine 0.6-1.0 mg IV, and if unresponsive, cautiously give isoproterenol 1

Hyperkalemia Management (K+ 5.5 mEq/L)

Immediate Cardiac Protection

• Administer intravenous calcium (already indicated for diltiazem toxicity) which simultaneously provides membrane stabilization for hyperkalemia 2
• Obtain immediate 12-lead ECG to assess for hyperkalemic changes (peaked T-waves, QRS widening, PR prolongation) that would indicate more aggressive therapy 2

Potassium Reduction

• Administer 10 units regular insulin IV with 25-50 g dextrose (D50W) to shift potassium intracellularly
• Give nebulized albuterol 10-20 mg for additional intracellular potassium shift
• Consider sodium bicarbonate 50-100 mEq IV if metabolic acidosis is present
• The potassium of 5.5 mEq/L is elevated but not immediately life-threatening; however, it must be corrected before any cardioversion attempts 2

Critical Contraindications and Safety Considerations

Absolute Contraindications in This Patient

• Never administer additional diltiazem, verapamil, or beta-blockers in the setting of calcium-channel blocker overdose, as this will precipitate cardiovascular collapse 2, 3
• Avoid digoxin as it may worsen AV conduction abnormalities and increase risk of ventricular arrhythmias in the setting of hyperkalemia 2
• Do not perform cardioversion until potassium is normalized, as hyperkalemia increases risk of ventricular tachyarrhythmias that may be difficult to terminate 2

Warfarin Considerations

• The patient's warfarin therapy increases bleeding risk but does not alter acute overdose management
• Monitor for signs of bleeding given potential need for invasive procedures (central line placement, pacing)

Monitoring Requirements

• Continuous cardiac telemetry to detect bradycardia, heart block, or ventricular arrhythmias 1
• Frequent blood pressure measurements (every 5-15 minutes initially) to assess response to vasopressors 1
• Serial potassium levels every 2-4 hours until normalized
• Serum calcium levels during continuous calcium infusion to prevent hypercalcemia 1
• Blood glucose monitoring every 30-60 minutes if insulin therapy is used

Advanced Interventions if Initial Therapy Fails

For Refractory Hypotension

• Escalate to vasopressors (dopamine or norepinephrine) with dosing based on hemodynamic response 1
• Consider intravenous fluids for volume resuscitation, though use cautiously given risk of pulmonary edema 1

For High-Degree AV Block

• Treat initially as bradycardia with atropine and isoproterenol 1
• Transcutaneous or transvenous pacing should be immediately available for fixed high-degree AV block unresponsive to pharmacologic therapy 1

For Refractory Toxicity

• Plasmapheresis or charcoal hemoperfusion may hasten diltiazem elimination in severe overdose, though data are limited 1
• Peritoneal dialysis and hemodialysis are not effective for diltiazem removal 1

Gastrointestinal Decontamination

• Administer activated charcoal if the patient presents within 1-2 hours of ingestion and can protect their airway 1
• Consider gastric lavage only if presentation is within 1 hour and the overdose is potentially life-threatening 1
• Given the 2-hour time frame since ingestion, decontamination may have limited benefit but should still be considered

Disposition and Ongoing Care

• Admit to intensive care unit for continuous monitoring and titration of vasoactive medications
• Diltiazem's extensive metabolism causes blood levels to vary over tenfold, limiting usefulness of drug levels 1
• Most diltiazem overdose patients recover with supportive care, though fatalities have occurred, particularly with multi-drug ingestions 1
• Monitor for delayed complications over 24-48 hours as diltiazem effects may be prolonged

Common Pitfalls to Avoid

• Do not assume tachycardia requires rate control – in calcium-channel blocker overdose, tachycardia is often compensatory and treating it may precipitate cardiovascular collapse
• Do not delay calcium administration while waiting for laboratory confirmation of hypocalcemia – empiric calcium is indicated in all significant calcium-channel blocker overdoses 1
• Do not use cardioversion for atrial fibrillation until potassium is corrected to normal range (>4.0 mEq/L) 2
• Do not give additional AV nodal blocking agents (beta-blockers, additional calcium-channel blockers, digoxin) as these are contraindicated in this setting 2