Calcium-Channel Blocker, Beta Blocker, and Digoxin Toxicity Management Strategies
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Calcium Channel Blocker and Beta Blocker Overdose, and Digoxin Toxicity Management - Pharmacology EXTRA Supplement (Pharmacology CME)

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Table of Contents
 
About This Issue

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. 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.

What are the similarities and differences in the clinical presentations of calcium-channel blocker, beta blocker, and digoxin toxicity?

How do findings in the history, such as the timing of ingestion, affect management?

What are the appropriate assessments, such as laboratory studies and ECG, that will best aid in diagnosis and management of patients presenting with calcium-channel blocker, beta blocker, and digoxin toxicity?

How do the techniques for management of patients with calcium-channel blocker, beta blocker, and digoxin toxicity differ? Which are the most beneficial?

What factors should be taken into consideration when determining disposition of patients with calcium-channel blocker, beta blocker, and digoxin toxicity?

Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Pathophysiology and Pharmacokinetics
    1. *Calcium Channel Blockers
    2. *Beta Blockers
    3. *Digoxin
  6. Differential Diagnosis
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. *Initial Evaluation
    2. *Evaluation of Calcium Channel Blocker and Beta Blocker Overdose
    3. *Evaluation of Digoxin Toxicity
  9. Diagnostic Studies
    1. *Laboratory Studies
      1. **Laboratory Studies for Digoxin Toxicity
    2. *Electrocardiography
      1. **Electrocardiography in Calcium Channel Blocker and Beta Blocker Overdose
    3. **Electrocardiography in Digoxin Toxicity
  10. Treatment
    1. *Treatment for Calcium Channel Blocker and Beta Blocker Overdose
      1. **Gastrointestinal Decontamination
      2. **Vasopressors
      3. **Insulin and Glucose
      4. **Glucagon
      5. **Extracorporeal Membrane Oxygenation and Intra-Aortic Balloon Pump
      6. **Lipid Emulsion Therapy
      7. **Calcium
      8. **Atropine
      9. **Phosphodiesterase Inhibitors
      10. **Sodium Bicarbonate
      11. **Pacing
      12. **Dialysis
    2. *Treatment for Digoxin Toxicity
      1. **Bowel Decontamination
      2. **Atropine
      3. **Digoxin-Specific Antibody Fragments
      4. **Electrolyte Maintenance
      5. **Pacing and Cardioversion
      6. **Extracorporeal Management
  11. Special Circumstances
    1. *Sotalol
    2. *Use of Calcium in Digoxin Toxicity
  12. Controversies and Cutting Edge
    1. *Methylene Blue
    2. *L-Carnitine
    3. *Levosimendan
  13. Disposition
  14. Summary
  15. Risk Management Pitfalls in Calcium Channel Blocker and Beta Blocker Overdose, and Digoxin Toxicity
  16. Case Conclusions
  17. Clinical Pathway for Emergency Department Management of Calcium Channel Blocker and Beta Blocker Overdose, and Digoxin Toxicity
  18. Tables and Figures
    1. Table 1. Selective and Nonselective Beta Blockers
    2. Table 2. Clinical Presentations of Digoxin Toxicity
    3. Table 3. Characteristics of Acute Versus Chronic Digoxin Toxicity
    4. Table 4. Factors Associated With Chronic Digoxin Toxicity
    5. Table 5. Electrocardiographic Manifestations of Calcium Channel Blocker and Beta Blocker Toxicity
    6. Table 6. Dysrhythmias Seen in Digoxin Toxicity
    7. Table 7. Indications for Administration of Digoxin-Specific Antibodies
    8. Table 8. Digoxin Immune Fab Dosing Calculations
    9. Figure 1. First-Degree Heart Block
    10. Figure 2. Scooped ST Segment Seen on Electrocardiogram in Digoxin Toxicity
    11. Figure 3. Junctional Rhythm Seen on Electrocardiogram in Digoxin Toxicity
    12. Figure 4. Paroxysmal Atrial Tachycardia With Variable Block Seen on Electrocardiogram in Digoxin Toxicity
    13. Figure 5. Bidirectional Ventricular Tachycardia Seen on Electrocardiogram in Digoxin Toxicity
  19. References

Abstract

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.

Case Presentations

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?

Introduction

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.

Critical Appraisal of the Literature

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.

Risk Management Pitfalls in Calcium Channel Blocker and Beta Blocker Overdose, and Digoxin Toxicity

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.

Tables and Figures

Table 1. Selective and Nonselective Beta Blockers

Table 2. Clinical Presentations of Digoxin Toxicity

References

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.

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Publication Information
Authors

Wesley Palatnick, MD, FRCPC, FACMT; Tomislav Jelic, MD, FRCPC, FACEP

Peer Reviewed By

Karan Pratap Singh, MD, MBA, FAAEM

Publication Date

September 15, 2020

CME Expiration Date

October 16, 2023

CME Credits

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.

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