In this episode, I’ll discuss the treatment of calcium channel blocker overdose in adult patients.
Consensus recommendations for the management of calcium channel blocker poisoning in adults have been published in the journal Critical Care in October 2016.
The recommendations emphasize the role of poison centers (1-800-222-1222 in the US) and address which types of in-hospital interventions should be considered for adults with a potentially toxic ingestion of a calcium channel blocker (CCB).
Observation of asymptomatic patients
The consensus recommendations define a potentially toxic dose of calcium channel blockers as any amount above a therapeutic dose. In asymptomatic patients who have ingested a potentially toxic dose of CCB, the recommendations are for 24-hour observation in a hospital setting.
If the patient ingested the CCB within 1 hour of presentation, activated charcoal might be considered.
Strongly recommended first-line treatments for CCB toxicity
– IV calcium chloride 1 to 2 grams every 10 to 20 minutes. If IV calcium gluconate is used, the dose is 3-6 grams every 10 to 20 minutes.
– High-dose insulin therapy if myocardial dysfunction is present. High-dose insulin therapy has positive inotropic effects in patients with CCB toxicity. Intensive monitoring and concomitant glucose infusions are required to prevent hypoglycemia and hypokalemia when using high-dose insulin therapy.
Start with a bolus of 1 unit / kg IV of regular insulin followed by an infusion of 1 unit / kg / hr. Infuse dextrose 10% at a rate that maintains euglycemia. Replace potassium with IV supplementation to keep the serum potassium normal.
– Use IV infusions of norepinephrine or epinephrine if the patient is in shock. Use your local protocols for vasopressor dosing but keep in mind that CCB toxicity patients may require high vasopressor doses. For a review of vasopressors in general, listen to episode 5.
Weakly recommended first-line treatments for CCB toxicity
– Use of high-dose insulin therapy as monotherapy.
– Use of high-dose insulin therapy even if myocardial dysfunction is not present.
– Use dobutamine or epinephrine in the presence of cardiogenic shock.
– Use atropine in the presence of symptomatic bradycardia or conduction disturbances. The IV dose is 0.5mg atropine every 3–5 minutes until a few doses have been given.
Treatments to avoid CCB toxicity
– Don’t use dopamine for the treatment of shock. The authors cite several cases of inconsistent hemodynamic improvement with dopamine.
– Don’t use vasopressin as monotherapy in the presence of cardiogenic shock. The authors cite several cases of worsened survival in animal models with vasopressin.
Fluid resuscitation
No formal evidence-graded recommendation for fluid resuscitation was made. However, the workgroup stated they considered fluid administration as a first-line therapy, with continued administration as long as the patient demonstrates evidence of fluid responsiveness.
Recommendations for patients who are refractory to first-line treatments
– If myocardial dysfunction persists despite high-dose insulin therapy of 1 unit / kg / hour, the dose may be titrated up to 10 units / kg / hour. As the insulin dose rises, the glucose and potassium replacement will need to intensify.
– If the patient has unstable bradycardia or high-grade AV block, consider pacing. Start with transcutaneous pacing and if this is effective convert to transvenous pacing.
– Consider IV lipid emulsion rescue therapy. Lipid emulsion for drug toxicity has been covered previously in episodes 30 and 86. The authors declined to recommend a specific dose of IV lipid emulsion. I would consider using the updated IV lipid emulsion dosing guidelines from the American College of Medical Toxicology:
1) A 20 % lipid emulsion (e.g., Intralipid) should be administered as a 1.5 mL/kg bolus. The bolus should be administered over 2–3 minutes. A repeat bolus can be considered if there is a failed response to the first bolus.
2) The bolus may be followed immediately by an infusion of 20 % lipid emulsion at a rate of 0.25 mL/kg/min. After 3 minutes of this infusion rate, response to the bolus and initial infusion should be assessed. If there has been a significant response, the infusion rate may be adjusted to 0.025 mL/kg/min (i.e., 1/10 the initial rate). This recommendation is based on concerns for adverse effects from extremely high cumulative rates of lipid infusion, and a desire to be able to monitor the impact of initial therapy in a dynamic enteral overdose situation. Blood pressure, heart rate, and other available hemodynamic parameters should be recorded at least every 15 minutes during the infusion.
3) If there is an initial response to the bolus followed by the re-emergence of instability during the lowest-dose infusion, the infusion rate could be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. There is no known maximal dose, but other authors have suggested a maximum dose of 10 mL/kg.
Refractory shock or cardiac arrest
– For patients in refractory shock or cardiac arrest, the authors recommended venoarterial extracorporeal
membrane oxygenation in centers where the treatment is available.
– The authors did not feel there was sufficient data to support a recommendation for the use of an Impella or ventricular assist device.
– For patients who experience a cardiac arrest, the authors recommend administering IV calcium and IV lipid therapy – even if already administered, in addition to standard advanced cardiac life-support.
What’s missing?
Notably absent from the recommendations were treatments such as glucagon and methylene blue. The authors state that an appendix exists that explains the absence of these therapies from the recommendations however at the time of this writing the appendix is not available on the journal website. My best guess is the lack of robust data to support the safety and efficacy of either treatment specifically for CCB toxicity.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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