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Kusumoto et al 2018 Bradycardia Clinical Practice Guidelines Circulation. 2019;140:e382–e482. DOI: 10.1161/CIR.0000000000000628 August 20, 2019 e409 CLINICAL STATEMENTS AND GUIDELINES or calcium channel blocker toxicity.S5.3.2.2-3,S5.3.2.2-6, S5.3.2.2-15 High-dose insulin therapy is associated with improved heart rate, hemodynamic parameters, and mortality in beta-blocker and calcium channel blocker overdose.S5.3.2.2-3,S5.3.2.2-6,S5.3.2.2-15 The evidence base is of lower quality, consisting largely of animal studies and case reports and case series.S5.3.2.2-3 Side effects include hypoglycemia and hypokalemia, which are usually mild.S5.3.2.2-6,S5.3.2.2-15 5.3.2.3. Therapy of Digoxin Mediated Bradycardia Attributable to either SND or Atrioventricular Block Recommendations for Therapy of Digoxin Mediated Bradycardia Attributable to SND or Atrioventricular Block Referenced studies that support recommendations are summarized in Online Data Supplements 13, 14, and 15. COR LOE Recommendations IIa C-LD 1. In patients with bradycardia associated with symptoms or hemodynamic compromise in the setting of digoxin toxicity, digoxin Fab antibody fragment is reasonable to increase heart rate and improve symptoms.S5.3.2.3-1–S5.3.2.3-8 III: No Benefit C-LD 2. In patients with bradycardia associated with symptoms or hemodynamic compromise attributable to digoxin toxicity, dialysis is not recommended for removal of digoxin.S5.3.2.3-9 Synopsis Digoxin-specific antibody (Fab) is a monovalent immunoglobulin that rapidly binds to intravascular digoxin.S5.3.2.3-2 Each vial of 40 mg of digoxin Fab binds approximately 0.5 mg of digoxin, and dosage is usually dependent on the estimated amount of the digitalis preparation ingested. Repeat dosing may be necessary, particularly in the setting of chronic use attributable to the large volume of distribution. Clinical response rates to digoxin Fab are as high as 80% to 90%, particularly in the acute setting.S5.3.2.3-2 Patients with hyperkalemia or arrhythmias in the setting of digoxin serum levels of >2 mcg/L are at increased risk of death.S5.3.2.3-10 Signs and symptoms of toxicity can manifest at lower serum levels. Adverse events attributable to digoxin Fab therapy are rare and usually clinically insignificant; potassium levels should be monitored. Use of any treatment directed specifically to digoxin toxicity will depend primarily on the presence or likelihood of developing significant toxicity (Table 8). The evidence base and specific treatment considerations for digoxin mediated bradycardia are the same for SND and atrioventricular block. Recommendation-Specific Supportive Text 1. There are no RCTs of anti-digoxin Fab for treatment of digitalis overdose, but an RCT in patients with poisoning attributable to yellow oleander, a cardiac glycoside with similar clinical toxicity, showed rapid reversal of bradycardia.S5.3.2.3-11 A systematic review of the use of anti-digoxin Fab in digitalis toxicity found 10 observational series including a total 2 080 patients.S5.3.2.3-2 Studies reported a clinical response of improvement to reversal of symptoms in 50% to 90% of patients within 30 to 45 minutes.S5.3.2.3-2 Adverse effects of therapy, including heart failure, tachycardia, hypokalemia, and allergic reactions occurred in <10% of patients.S5.3.2.3-2 Clinical benefit is therefore clear in patients with life-threatening symptoms, but benefit is less certain in cases of mild toxicity. 2. A systematic review of 77 in vitro, animal, and human case reports and series comprising 84 patients found that digoxin is only slightly dialyzable,S5.3.2.3-9,S5.3.2.3-12 and dialysis is unlikely to improve the outcome of patients with digoxin toxicity.S5.3.2.3-9 Hemodialysis may be considered for treatment of associated life-threatening hyper kalemia.S5.3.2.3-13 5.3.2.4 Aminophylline or Theophylline for Bradycardia Attributable to SND Recommendations for Theophylline/Aminophylline for Bradycardia Attributable to SND Referenced studies that support recommendations are summarized in Online Data Supplements 16 and 17. COR LOE Recommendations IIa C-LD 1. In post-heart transplant patients, aminophylline or theophylline is reasonable to increase heart rate if clinically indicated.S5.3.2.4-1–S5.3.2.4-4 IIa C-LD 2. In patients with SND associated with symptoms or hemodynamic compromise in the setting of acute spinal cord injury, aminophylline or theophylline is reasonable to increase heart rate and improve symptoms.S5.3.2.4-5–S5.3.2.4-7 Synopsis The methylxanthines theophylline and aminophylline (a theophylline derivative) exert positive chronotropic effects on the heart, likely mediated by inhibition of the suppressive effects of adenosine on the sinoatrial node.S5.3.2.4-8,S5.3.2.4-9 There is no direct evidence supporting the gross effects of aminophylline or theophylline Downloaded from http://ahajournals.org by on October 7, 2026