While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.
A 44-year-old man with a history of atrial fibrillation and major depressive disorder presents to the ED via EMS after collapsing at home. His initial vital signs are as follows: blood pressure, 92/40 mm Hg; heart rate, 41 beats/min; respiratory rate, 14 breaths/min; and fingerstick glucose, 112 mg/dL. His GCS score is 15. You begin volume resuscitation, and obtain the patient's history. EMS personnel said they saw an empty pill bottle near where the patient was found, but they did not bring it with them, so the police return to the patient’s home to retrieve the bottle. The patient says that he has not been taking any antidepressants recently, and he has been taking metoprolol for rate control of his atrial fibrillation. Upon completion of your primary survey, and after administering a liter of normal saline, you find the patient’s GCS score has deteriorated to 8, his heart rate to 38 beats/min, and his blood pressure to 84/32 mm Hg. The nurse informs you that she can no longer feel a carotid pulse. Could this be an overdose? What drugs can cause a bradycardic arrest? And how reliable was this patient in reporting his history?
Just then, an 83-year-old woman with generalized weakness and a past medical history of heart failure is brought into the ED by her daughter. She has sinus bradycardia at 33 beats/min, and her blood pressure is 94/52 mm Hg. She states that she was recently started on an ACE inhibitor, and her cardiologist told her that her baseline creatinine clearance has declined significantly. You learn that she is also on digoxin for heart failure, so you order a digoxin level. While waiting for the results, you consider whether this patient’s clinical presentation is an acute indication for digoxin immune fab. You also consider what the precipitating factor to her presumed digoxin toxicity might be.
Later that evening, a 32-year-old woman is brought to your ED via EMS after her boyfriend found her slumped over in a chair. He states that they were arguing last evening and that she was quite upset. Her boyfriend provides her medical history that is significant for migraine headaches, and he knows that she is taking verapamil for them. Her fingerstick glucose is normal, her heart rate is 28 beats/min, and her blood pressure is 74/36 mm Hg. You consider what the best initial step in management of this patient would be and wonder if she overdosed on the verapamil. Is there a role for GI decontamination? What about hemodialysis?
Due to the increased prevalence of cardiovascular disease in the United States,1 cardiovascular medications (especially calcium channel blockers [CCBs] and beta blockers) are some of the most prescribed therapeutic agents on the market.2 There has also been a rise in the number of toxicity cases from these medications. The 2017 report of the American Association of Poison Control Centers found that cardiovascular medications accounted for > 107,000, or 4.24%, of all toxicity cases reported and nearly 8% of fatalities.3 Of the cardiovascular agents, CCBs were most often implicated in fatal cases, with 37 deaths. The availability of sustained-release formulations of these drugs appears to have contributed to the increase in morbidity and mortality from CCB overdose. Beta blocker toxicity resulted in 18 deaths. Digoxin toxicity was reported in 1851 patients, with 25 deaths.3
Identifying and treating patients exhibiting toxic effects of these agents can be complex. Standard Advanced Cardiovascular Life Support protocols used for the resuscitation of patients in cardiac arrest may be insufficient due to the complex physiologic changes that occur with poisoning from these agents, and specialized treatments are often necessary. This supplement presents the current evidence on best practices in the diagnosis and management of CCB, beta blocker, and digoxin toxicity.
A search of literature from 1990 to 2020 was conducted in PubMed and Ovid MEDLINE® using the search terms beta blocker toxicity/poisoning, calcium channel blocker toxicity/poisoning, digitalis toxicity/poisoning, and digoxin toxicity/poisoning. The Cochrane Database of Systematic Reviews was also searched. While more than 1000 papers were found, only 144 were of sufficient quality to be included in this review. In an attempt to provide the most current recommendations, most studies that were conducted prior to 1990 were excluded. An attempt was made to use literature with human patients rather than animal models. Performing high-quality randomized studies in the acutely poisoned patient is difficult, which is important to remember when reviewing the toxicology literature. Most of the evidence in the toxicology literature is case reports, small studies, or retrospective reviews, which have been included here when necessary.
3. “The patient was asymptomatic, so I discharged her home immediately after the treatment was completed.”
Asymptomatic patients who have overdosed on a short-acting CCB or beta blocker should be observed for a period of at least 6 hours. If they remain asymptomatic, they may be discharged. Patients who become symptomatic must be treated and admitted for monitoring. Patients who have ingested sustained-release formulations should be observed for effects for up to 24 hours.
6. “My ED staff was worried about giving so much insulin to the patient who overdosed on a beta blocker.”
Patients with either CCB or beta blocker toxicity may require very high doses of insulin (up to 1 unit/kg/hr, which is 70 unit/hr in a 70-kg patient) to support the heart metabolically during shock states. Due to the high dosing required for this therapy, clinical staff should be reassured regarding the dosing and educated to avoid errors or complications. Additional dosing checks should be conducted by multiple staff members.
7. “The patient wasn’t bradycardic, so I thought it couldn’t be a CCB or beta blocker overdose.”
The ECG is essential in evaluation of a patient with suspected cardiovascular toxicity. While bradycardia is commonly seen, a wide variety of dysrhythmias and heart blocks are possible. Other ECG findings include normal sinus rhythm, sinus tachycardia, PR prolongation, variable atrioventricular blocks, junctional rhythms, bundle branch blocks, and QT prolongation.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study will be included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.
Tips from the creator:
Why to Use
Digoxin immune Fab (DigiFab®, Digibind®) is an effective antidote for acute, acute on chronic, and chronic digoxin toxicity. It is also indicated for poisoning from other cardioactive steroids.
When to Use
The DigiFab® dosing tool is intended to assist with dose calculation for digoxin immune Fab, and does not provide comprehensive or definitive drug information. Always check dosing of any drug and consult a pharmacist when necessary.
Scott Lucyk, MD
Frequent premature ventricular complexes may be closely followed by ventricular dysrhythmias.
Potassium abnormalities, specifically hypokalemia, may worsen digoxin toxicity, even at therapeutic digoxin levels. If hyperkalemia is mild, correction is not advised, as treatment with digoxin immune Fab will decrease potassium concentrations. Treatment to lower serum potassium concentrations should be performed prior to digoxin immune Fab administration only if (1) hyperkalemia is believed to be worsening atrioventricular nodal block and bradycardia, and (2) digoxin immune Fab is not immediately available. If hypokalemia is present, cautious correction should be performed prior to the administration of digoxin immune Fab. If there is worsening toxicity/dysrhythmia, or if toxicity does not improve with correction of hypokalemia, digoxin immune Fab should be immediately administered. Do not administer calcium salts to patients with hyperkalemia secondary to digoxin toxicity. Transcutaneous and especially transvenous pacing should be avoided in patients with digoxin toxicity due to risk for precipitating dysrhythmias.
The therapeutic range for serum digoxin level is 0.8 to 2.0 ng/mL (1.0-2.6 nmol/L). In the case of acute poisoning with serum digoxin level confirmed at > 10 ng/mL, an empiric dose (10-20 vials) should be administered. Additional considerations for treatment of digoxin toxicity include:
The relationship between serum potassium concentrations and mortality in patients treated for digitoxin toxicity was investigated at the Fernand Widal Toxicology Center in Paris between 1967 and 1972.
Among patients with digitoxin toxicity, the majority of whom (81 of 91 patients) took digitoxin with suicidal intent, all patients with an initial serum potassium level > 5.5 mEq/L died, whereas all patients with an initial serum potassium level < 5 mEq/L survived (Bismuth 1973).
In 1990, Antman et al conducted a nationwide, prospective, open-label, multicenter clinical trial of 148 patients with potentially life-threatening digitalis intoxication who were treated with purified digoxin-specific Fab fragments. Resolution of all signs and symptoms of digitalis toxicity occurred in 119 patients (80%), 14 patients (9%) showed improvement, and 15 patients (10%) showed no response, though this group included moribund patients and patients who were retrospectively believed to not be suffering from digitalis toxicity. Among the 56 patients with cardiac arrest who were treated with Fab fragments, 30 patients (54%) survived hospitalization.
Frédéric Lapostolle, MD
Wesley Palatnick, MD, FRCPC, FACMT; Tomislav Jelic, MD, FRCPC, FACEP
Karan Pratap Singh, MD, MBA, FAAEM
September 15, 2020
October 15, 2023
4 AMA PRA Category 1 Credits.™ Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 4 Pharmacology CME credits, subject to your state and institutional approval.
Date of Original Release: September 15, 2020. Date of most recent review: September 1, 2020. Termination date: September 15, 2023.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME.
Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 4 Pharmacology CME credits, subject to your state and institutional requirements.
Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians.
Target Audience: This enduring material is designed for emergency medicine physicians, physician assistants, nurse practitioners, and residents.
Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical decision-making based on the strongest clinical evidence; (2) cost-effectively diagnose and treat the most critical presentations; and (3) describe the most common medicolegal pitfalls for each topic covered.
CME Objectives: Upon completion of this activity, you should be able to: (1) describe the pathophysiology of calcium channel blocker and beta blocker overdose, and digoxin toxicity; (2) recognize the symptoms and utilize appropriate diagnostic assessments for patients presenting with calcium channel blocker and beta blocker overdose, and digoxin toxicity; and (3) apply appropriate management for patients with calcium channel blocker and beta blocker overdose, and digoxin toxicity.
Discussion of Investigational Information: As part of the journal, faculty may be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration–approved labeling. Information presented as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product.
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Commercial Support: This supplement to Emergency Medicine Practice did not receive any commercial support.
Earning Credit: Read the PDF and complete the CME test online.
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