When to hold digoxin heart rate
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Since joining the American Society of Consultant Pharmacists in 1977, I have developed a number of Policy and Procedures manuals for a large number of skilled nursing facilities (SNFs), assisted living facilities (ALFs), and personal care facilities. Each time, I have included a section dealing with digoxin monitoring, which would carry the statement "Take Apical Pulse (A/P) daily before administering. Hold if A/P is below 60 beats/minute and notify attending physician." Show
About 9 months ago, an epiphany occurred as I was checking medication administration records at one of the facilities where I serve as a consultant pharmacist. I noticed that residents with a diagnosis of hypertension being treated with antihypertension medications had their blood pressure (B/P) monitored once a week, and other residents had vitals signs (temperature, B/P, respiration, and weight) checked once a month. I also noticed that A/P for residents taking digoxin was performed daily, as required by the Policy and Procedures manual. As I thought back, however, I could recall digoxin being "held" only once or twice during my career as a consultant pharmacist. Why were medication nurses in every SNF and ALF across the United States checking A/P daily? My next step was to question medication nurses, assistant directors of nursing, and directors of nursing (DONs) about their experiences regarding digoxin monitoring. Most nurses I questioned had been in practice for at least 10 years, and none could remember "holding" digoxin more than once or twice, compared with the hundreds of doses they had administered during their career. They also indicated that digoxin was "held" when the A/P was 58 or 59 beats/minute, and that it was back to normal (over 60) the next day. Therefore, the probability was that the nurse miscounted or only checked the pulse for 30 seconds and multiplied by 2 to get the beats/minute. As I continued my research, I found that physicians, nurses, and pharmacists had their initial experience with digoxin in the hospital setting, while a particular patient was being digitalized. During that time in the hospital, the A/P rate was critical in helping to determine the correct digoxin dose. Once the patient was properly dosed with the medication and discharged from the hospital to his or her home (or a recuperative facility), such close monitoring was not required. Indeed, patients discharged to their home generally are not instructed to monitor their A/P every day. As a result of this research, I developed the following parameters for digoxin monitoring, which were approved by the DON and the medical director. NOTE: When an order for any digitalis glycoside (digoxin) is prescribed for a resident, his or her pulse rate is to be checked once a week and recorded on the Medication Administration Record. If the resident's apical pulse is less than 60, the medication is to be given as ordered and the apical pulse is to be monitored daily for three (3) days (continuing to administer the medication). If the apical pulse rate continues at less than 60 after three (3) days, the medication is to be held and the attending physician notified of the three (3)-day apical pulse rate. I have monitored the residents in a 300-bed continuing care community during the last 9 months, and I can report that not a single dose of digoxin has been "held." The resulting time saved by the medication nurse may not seem significant, but in the course of a month or a year a great deal of time may be saved by this change. More important is the psychological impact on the medication nurse. A/P monitoring is one less procedure to be performed, with the time being spent on other care for the patient. Pharmacists and nurses should reevaluate routine tasks, such as digoxin monitoring, to determine whether or not those tasks add a positive outcome to patient care. In this instance, with digoxin monitoring, I believe not only that patient care can be improved without sacrificing quality patient care, but that nursing time for patient care may also be enhanced. Mr. Vogenberg is a semiretired pharmacist based in Langhorne, Pa. Can J Hosp Pharm. 2017 Sep-Oct; 70(5): 391–394. Can J Hosp Pharm. 2017 Sep-Oct; 70(5): 391–392. Published online 2017 Oct 31. Cardiac glycosides—including digoxin—have been used for centuries to treat patients with heart disease, including those with atrial fibrillation.1 However, the role of digoxin in the management of atrial fibrillation has recently been challenged, and its prominence in consensus guidelines minimized.2 Yet, digoxin does have a role and remains one of the treatment options, as an adjunct to a β-blocker or calcium-channel blocker, to control heart rate, especially in patients with atrial fibrillation and heart failure with reduced ejection fraction (HFrEF).2 The purpose of this article is to reaffirm digoxin’s position as a treatment option for patients with atrial fibrillation. Efficacy in Controlling Ventricular ResponseDigoxin lowers the heart rate by enhancing vagal tone, which leads to slowing of sinoatrial and atrioventricular nodal conduction and thereby a reduction in heart rate.1 Additionally, digoxin increases baroreceptor sensitivity, leading to sympatholytic activity, which may also contribute to the heart rate–slowing effects observed.1 An appropriately individualized dose of digoxin can yield effective heart rate control while minimizing adverse effects in patients with atrial fibrillation. To rapidly lower heart rate in these patients, a weight-based loading dose (about 10 µg/kg) of digoxin should be given.1 Digoxin has a large volume of distribution, but distribution to the site of action (i.e., the heart) is prolonged, delaying the onset of activity and the peak effect on heart rate.1 Thus, the loading dose should be given in divided doses every 6–8 h.1 Renal clearance accounts for the majority of digoxin’s elimination, although it is also a substrate for P-glycoprotein, which accounts for some nonrenal clearance.1 For patients whose renal function is preserved, the half-life of digoxin is about 36 h, but the half-life can be longer than 4 days in patients with severe renal impairment.1 Although numerous dosing methods exist, all require adjustments based on weight (specifically, ideal body weight) and renal function, and the potential for drug–drug interactions (e.g., concomitant therapy with P-glycoprotein inhibitors) must also be accounted for in determining the dose of digoxin.1 Typical maintenance doses of digoxin in patients with atrial fibrillation range from 0.0625 to 0.25 mg daily.1 Failure to account for one or more of the factors that influence digoxin dose increases the likelihood of adverse effects and may explain, in part, the observed associations between digoxin use and mortality risk. Digoxin is most useful for heart rate control in patients with atrial fibrillation and HFrEF, where it is typically given as an adjunct to concomitant β-blocker therapy.2,3 In patients with atrial fibrillation and HFrEF, digoxin is advantageous because, unlike other agents (e.g., β-blockers, calcium-channel blockers), it does not have negative inotropic effects, nor does it lower blood pressure.2 Additionally, because digoxin enhances vagal tone, it may have utility in controlling ventricular response in patients with sedentary lifestyles. As monotherapy, digoxin effectively improves control but not variability of heart rate, in part because it is less effective in controlling exercise-induced increases in heart rate.3,4 The clinician can overcome heart rate variability and achieve more effective control by combining digoxin with another heart rate control agent.2–4 Digoxin Failing Clinicians/Patients, or Clinicians Failing Digoxin/Patients?Poor understanding of digoxin’s limitations can lead to inappropriate use of this agent in patients with atrial fibrillation and may explain, in part, recent reports of associations between digoxin use and increased mortality.5,6 In the acute care setting, the peak effect of digoxin is delayed by several hours (about 3–6 h) because of the prolonged distribution phase and the required loading dose regimen (3 divided doses over 12–16 h).1,2 Given the availability of more rapid-acting therapies (β-blockers and calcium-channel blockers by IV administration), digoxin is not optimal as monotherapy to rapidly reduce heart rate but can be an effective adjunct to other therapies.2 Digoxin is relatively ineffective at controlling heart rate in highly sympathetic states, such as exercise.3,4 In patients with atrial fibrillation who exercise frequently or who have high sympathetic tone (e.g., those with hyperthyroidism, critical illness), digoxin monotherapy is not expected to be very effective as a heart rate control agent, a limitation that can be overcome through combination therapy.2–4 Another limitation—one that is often overlooked by clinicians—is the relatively flat dose–effect relation for heart rate control in atrial fibrillation.3,4 In one study, no significant differences in resting heart rate were observed between low-dose digoxin (0.25 mg daily, mean serum digoxin concentration 0.81 ng/mL [conversion to SI units: 1 ng/mL = 1.281 nmol/L]) and high-dose digoxin (0.5 mg daily, mean serum digoxin concentration 1.71 ng/mL).4 Despite evidence to the contrary, clinicians often inappropriately target higher serum digoxin concentration, incorrectly believing it will lead to better heart rate control, when in fact this strategy may increase the risk of adverse events, including death. Digoxin, Mortality Risk, and Serum Digoxin ConcentrationOver the past decade, numerous studies have suggested that digoxin use in patients with atrial fibrillation increases mortality risk.5,6 A meta-analysis of 11 observational studies found that the use of digoxin in patients with atrial fibrillation was associated with a 17% higher risk of death than among those not treated with digoxin.5 However, 2 additional meta-analyses yielded conflicting results regarding the association between digoxin and mortality risk.6,7 Thus, associations between digoxin use and increased mortality are, at best, inconclusive. Many of the digoxin–mortality analyses failed to account for the influence of serum digoxin concentration on mortality.5–7 In patients with HFrEF treated with digoxin, serum digoxin concentration below 1.0 ng/mL has been associated with reduced mortality relative to placebo, whereas an increased mortality risk has been observed at serum digoxin concentration of 1.0 ng/mL or above.8 Most studies evaluating the use of digoxin in patients with atrial fibrillation generally achieved serum digoxin concentration of about 1.2 ng/mL, above the threshold associated with increased mortality in patients with HFrEF. Indeed, the only digoxin–mortality study that reported serum digoxin concentration found that patients who died had higher levels than survivors (1.2 ng/mL versus 0.9 ng/mL, p < 0.001).9 Another study found that patients with atrial fibrillation treated with the combination of digoxin and dronedarone had higher cardiovascular mortality than those treated with digoxin alone; serum digoxin concentrations were significantly higher in the combination group (1.1 ng/mL versus 0.7 ng/mL, p < 0.0001).10 If an association between digoxin use and mortality risk exists, serum digoxin concentration is likely an important risk factor. ConclusionIn appropriate patients (e.g., those with atrial fibrillation with HFrEF) and at low doses (targeting serum digoxin concentration < 1.0 ng/mL), digoxin is an effective heart rate control agent, when given as an adjunct to other control therapies. However, improper patient selection and the use of unnecessarily high doses may lead to poor efficacy and increased risk of adverse events. References1. DiDomenico RJ, Page RL., 2nd . Chapter 13: Digoxin. In: Murphy J, editor. Clinical pharmacokinetics. 6th ed. Bethesda (MD): American Society of Health-System Pharmacists; 2017. pp. 239–50. [Google Scholar] 2. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–76. doi: 10.1016/j.jacc.2014.03.022. [PubMed] [CrossRef] [Google Scholar] 3. Nikolaidou T, Channer KS. Chronic atrial fibrillation: a systematic review of medical heart rate control management. Postgrad Med J. 2009;85(1004):303–12. doi: 10.1136/pgmj.2008.068908. [PubMed] [CrossRef] [Google Scholar] 4. Lang R, Klein HO, Weiss E, David D, Sareli P, Levy A, et al. Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation. Chest. 1983;83(3):491–9. doi: 10.1378/chest.83.3.491. [PubMed] [CrossRef] [Google Scholar] 5. Ouyang AJ, Lv YN, Zhong HL, Wen JH, Wei XH, Peng HW, et al. Meta-analysis of digoxin use and risk of mortality in patients with atrial fibrillation. Am J Cardiol. 2015;115(7):901–6. doi: 10.1016/j.amjcard.2015.01.013. [PubMed] [CrossRef] [Google Scholar] 6. Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 2015;36(28):1831–8. doi: 10.1093/eurheartj/ehv143. [PubMed] [CrossRef] [Google Scholar] 7. Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GYH, et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451. doi: 10.1136/bmj.h4451. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 8. Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Alban IB, Colucci WS, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27(2):178–86. doi: 10.1093/eurheartj/ehi687. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 9. Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, et al. Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol. 2015;8(1):49–58. doi: 10.1161/CIRCEP.114.002292. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 10. Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ PALLAS Investigators. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014;7(6):1019–25. doi: 10.1161/CIRCEP.114.002046. [PubMed] [CrossRef] [Google Scholar] Can J Hosp Pharm. 2017 Sep-Oct; 70(5): 392–394. Published online 2017 Oct 31. THE “CON” SIDEDigoxin has long been used for the management of various conditions, including atrial fibrillation, but we would argue that it should join the ranks of drugs such as reserpine, guanethidine, and bretylium, which are no longer used because of a relative lack of efficacy and concerns about safety. Although digoxin has been used for hundreds of years, clinicians’ understanding of its effects, in particular its mechanism of action, has evolved over time. It was once thought that digoxin was effective for converting atrial fibrillation to sinus rhythm, maintaining sinus rhythm, and preventing vagally mediated paroxysmal atrial fibrillation. However, it has been shown that digoxin is not effective in any of these situations.1 Small observational trials and randomized controlled trials with short follow-up periods (days to weeks) have demonstrated that digoxin decreases resting ventricular rate,2 yet rate control is not the only goal of therapy for a patient with atrial fibrillation. In today’s management of atrial fibrillation, symptom control and quality of life are important goals, and the impact of digoxin on these end points is not well studied. Other problems that limit digoxin’s usefulness are its slow onset of action in the acute scenario and its ineffectiveness in physically active individuals and those with high sympathetic tone. The 2014 atrial fibrillation guideline of the American College of Cardiology, American Heart Association, and Heart Rhythm Society and the 2016 guideline of the Canadian Cardiovascular Society do not recommend digoxin as a first-line rate control agent.3,4 They acknowledge that although digoxin is commonly used, there are only select patients in whom it will be effective. In addition to lack of efficacy, the guidelines raise concern that digoxin may increase mortality, as seen in various retrospective analyses of randomized controlled trials and cohort studies. One example is the ATRIA-CVRN study, a retrospective cohort study that included 14 787 adult patients from the Kaiser Permanente California database who had a diagnosis of atrial fibrillation but no heart failure with reduced ejection fraction (HFrEF).5 The patients were matched for age, sex, and a high-dimensional propensity score. Incident digoxin use was independently associated with increased mortality (8.3 versus 4.9 per 100 person-years, p < 0.001). A similar finding was shown in registry data for 9619 patients with atrial fibrillation collected from 174 sites in the United States.6 That study found that incident digoxin use was associated with subsequent death among patients who had atrial fibrillation but not HFrEF (propensity-adjusted hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.12–3.56). A meta-analysis by Qureshi and others7 included data from retrospective analyses and observational trials published between 1997 and 2013. Using a random-effects model, the authors found a 27% increase in risk of mortality for individuals who used digoxin relative to those who did not (pooled HR 1.27, 95% CI 1.19–1.36, p < 0.001).7 This association between digoxin and increased all-cause mortality appeared to be more prominent for patients who had atrial fibrillation without HFrEF (pooled HR 1.47, 95% CI 1.25–1.73, p < 0.001) than for patients having both atrial fibrillation and HFrEF (pooled HR 1.21, 95% CI 1.07–1.35, p = 0.002). Another meta-analysis that included contemporary data (2008–2015) also demonstrated that digoxin use was associated with a higher risk of mortality for all patients with atrial fibrillation (HR 1.23, 95% CI 1.16–1.31, p < 0.000 01), but when the data were stratified, the higher risk was limited to patients who had atrial fibrillation without HFrEF (HR 1.38, 95% CI 1.12–1.71, p = 0.003); it did not occur among those with both atrial fibrillation and HFrEF (HR 1.08, 95% CI 0.99–1.18, p = 0.09).8 In one meta-analysis that examined the efficacy and safety of digoxin in patients with HFrEF and/or atrial fibrillation, there was no increase in mortality associated with digoxin use.9 However, this conclusion was based upon an analysis that was limited to randomized controlled trials (risk ratio [RR] 0.99, 95% CI 0.93–1.05), and these trials did not include patients with atrial fibrillation who did not have heart failure. In other analyses that did include such patients, there was an increased risk of mortality in the digoxin group (for example, RR 1.18, 95% CI 1.09–1.26, in propensity matched studies). The authors did not draw any conclusions regarding the effect of digoxin on mortality in patients with atrial fibrillation who do not have HFrEF. There seems to be a strong signal that digoxin may be harmful when used for rate control in patients with atrial fibrillation without HFrEF. It should be noted that this information comes from retrospective analyses and observational data, not randomized controlled trials. Consequently, it is important to recognize that some but not all confounders may be accounted for in either the propensity matching or risk adjustments that were used in the analyses. In addition, there is inherent bias, as it is not known why digoxin was prescribed for these individuals. Despite these limitations, clinicians should be concerned about using digoxin in this population. Although one might think that only a small number of patients will receive digoxin, given that the guidelines relegate this agent to second-line or add-on therapy, it is used commonly. For example, in some recent trials of stroke prevention involving patients with atrial fibrillation, rates of digoxin use ranged from 29% to 39%.10,11 Another meta-analysis on this topic is being planned,12 but the results will be subject to the limitations of the existing publications. A randomized controlled trial on the effect of digoxin on all-cause mortality in patients who have atrial fibrillation with or without HFrEF (most urgently the latter) would provide better information. The RATE-AF trial, a comparison of bisoprolol and digoxin as rate control agents, is currently recruiting participants, and results are expected in 2019.13 Although this trial will provide some information on a variety of efficacy-related end points (e.g., SF-36 measured quality of life, 6-min walk test, heart rate), it is unlikely to provide information on mortality because of its small sample size (160 participants). Furthermore, an adequately sized trial is unlikely to be performed, for several reasons: the challenge of participant recruitment when there is a potential for harm, the large sample size required when mortality is an end point, and the need to secure funding for such a trial. Given this reality, clinicians need to act on the information available. With a lack of efficacy data and concerns about safety, particularly among patients without HFrEF, we assert that digoxin should be added to the list of “DO NOT USE” drugs. References1. Falk RH, Leavitt JI. Digoxin for atrial fibrillation: a drug whose time has gone? Ann Intern Med. 1991;114(7):573–5. [PubMed] [Google Scholar] 2. Redfors A. The effect of different digoxin doses on subjective symptoms and physical working capacity in patients with atrial fibrillation. Acta Med Scand. 1971;190(4):307–20. [PubMed] [Google Scholar] 3. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–76. [PubMed] [Google Scholar] 4. Macle L, Cairns J, Leblanc K, Tsang T, Skanes A, Cox JL, et al. CCS Atrial Fibrillation Guidelines Committee. 2016 focused update of the Canadian Cardiovascular Society guidelines for the management of atrial fibrillation. Can J Cardiol. 2016;32(10):1170–85. [PubMed] [Google Scholar] 5. Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, et al. Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol. 2015;8(1):49–58. [PMC free article] [PubMed] [Google Scholar] 6. Allen LA, Fonarow GC, Simon DN, Thomas LE, Marzec LN, Pokorney SD, et al. ORBIT-AF Investigators. Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort. J Am Coll Cardiol. 2015;65(25):2691–8. [PMC free article] [PubMed] [Google Scholar] 7. Qureshi W, O’Neal WT, Soliman EZ, Al-Mallah MH. Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation. Cardiol J. 2016;23(3):333–43. [PubMed] [Google Scholar] 8. Chamaria S, Desai AM, Reddy PC, Olshansky B, Dominic P. Digoxin use to control ventricular rate in patients with atrial fibrillation and heart failure is not associated with increased mortality. Cardiol Res Pract. 2015;2015:314041. [PMC free article] [PubMed] [Google Scholar] 9. Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GYH, et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451. [PMC free article] [PubMed] [Google Scholar] 10. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. [PubMed] [Google Scholar] 11. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. [PubMed] [Google Scholar] 12. Sethi NJ, Safi S, Feinberg J, Nielsen EE, Gluud C, Jakobsen JC. Digoxin versus placebo, no intervention, or other medical interventions for atrial fibrillation and atrial flutter: a protocol for a systematic review with meta-analysis and trial sequential analysis. Syst Rev. 2017;6(1):71. [PMC free article] [PubMed] [Google Scholar] 13. University of Birmingham. Rate control therapy evaluation in permanent atrial fibrillation (RATE-AF) [trial registration] Bethesda (MD): National Institutes of Health; 2015. Feb 27, [updated 2017 May 5; cited 2017 Jun 14]. Available from: www.clinicaltrials.gov/ct2/show/NCT02391337?term=digoxin&cond=%22Arrhythmias%2C+Cardiac%22&rank=5. [Google Scholar] Articles from The Canadian Journal of Hospital Pharmacy are provided here courtesy of Canadian Society Of Hospital Pharmacists When should you not take digoxin heart rate?Check your pulse before you take your digoxin. If your pulse is under 60 beats per minute, wait 5 minutes. Then check your pulse again. If it's still under 60, call your healthcare provider.
In which situation would the nurse hold digoxin?The nurse should hold a dose of Digoxin and notify the physician if the INFANT'S heart rate is less than 90-110 bpm.
Can you give digoxin with high heart rate?Digoxin can also help people who have a rapid or irregular heartbeat. This can be caused by a heart problem called atrial fibrillation. Digoxin helps by slowing down and controlling the heart rate.
Can you give digoxin with bradycardia?Taking digoxin with ivabradine, a heart failure drug, can increase your risk of side effects. These side effects include bradycardia (a slowed heart rhythm). If you need to take these drugs together, your doctor may monitor you closely.
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