Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration

A radioimmunoassay for serum digoxin concentration has been used to study the interrelationships of circulating levels of the drug and various factors in the clinical setting in 48 hospitalized patients with cardiac rhythm disturbances due to digoxin intoxication. 131 patients on maintenance doses of digoxin without toxicity and 48 patients with equivocal evidence of digoxin excess were also studied and compared with the toxic group.Patients with cardiac rhythm disturbances due to digoxin intoxication tended to be older and to have diminished renal function compared with the nontoxic group; body weight, serum potassium concentration, underlying cardiac rhythm, and nature of cardiac disease were not significantly different for the groups as a whole. Despite comparable mean daily digoxin dosages, digoxin intoxicated patients had a mean serum digoxin concentration of 3.7 +/-1.0 (SD) ng/ml, while nontoxic patients had a mean level of 1.4 +/-0.7 ng/ml (P < 0.001), 90% of patients without evidence of toxicity had serum digoxin concentrations of 2.0 ng/ml or less, while 87% of the toxic group had levels above 2.0; the range of overlap between the two groups extended from 1.6 to 3.0 ng/ml. Patients with atrioventricular block as their principal toxic manifestation had a significantly lower mean serum digoxin concentration than those in whom ectopic impulse formation was the chief rhythm disturbance.Patients with equivocal evidence of digoxin excess had received comparable daily maintenance doses of digoxin but had a mean serum concentration of 1.9 +/-0.8 ng/ml, intermediate between those of the nontoxic (P < 0.005) and toxic (P < 0.001) groups. Renal function as judged by mean blood urea nitrogen concentration was also intermediate.The data indicate that knowledge of the serum digoxin concentration, weighed in the clinical context, is useful in the management of patients receiving this drug.     

阿奇霉素对地高辛血药浓度的影响

目的 探讨阿奇霉素对地高辛血药浓度的影响.方法长期口服地高辛且血药浓度稳定在0.5～2.0 ng/mL的心力衰竭患者316例,其中158例纳入试验组(口服或静脉滴注阿奇霉素),余下158例纳入对照组(未接受阿奇霉素治疗);酶放大免疫法测定试验组使用阿奇霉素前后的外周血地高辛浓度,并与对照组进行比较.结果 试验组患者在使用阿奇霉素5 d后地高辛血药浓度由(1.1±0.5)ng/mL升高至(1.5±0.5)ng/mL(P<0.05),大于2.0 ng/mL者13例(占8.2%);老年(≥60岁)患者地高辛浓度增高尤其明显(P<0.01).试验组地高辛浓度为(1.5±0.5)ng/mL,高于对照组的(1.1±0.3)ng/mL(P<0.05).结论 阿奇霉素可导致地高辛血药浓度升高,尤其是老年患者;应避免同时使用阿奇霉素和地高辛,减少毒性反应.     

Clinical utility of serum digoxin level tests in hospitalized elderly patients

To assess the clinical utility of serum digoxin tests in the elderly and to ascertain the use by physicians of test results, digoxin levels were obtained from 77 consecutive, elderly patients (means age 72 years) taking digoxin on admission to a rehabilitation hospital. Blood samples were drawn the morning following admission (prior to the administration of digoxin) and were repeated in two weeks. Signs or symptoms of digoxin toxicity were seen in all 13 patients with levels above the therapeutic range. Of 38 patients with therapeutic levels, 16 had signs or symptoms compatible with underdigitalization or digoxin toxicity. Physicians were significantly more likely to respond to both the initial and follow-up serum digoxin test result when the first test result was above the therapeutic range.     

Monitoring Digoxin Therapy: THE USE OF PLASMA DIGOXIN CONCENTRATION MEASUREMENTS IN THE DIAGNOSIS OF DIGOXIN TOXICITY

The usefulness of measuring plasma digoxin concentrations inthe diagnosis of digoxin toxicity has been assessed in 83 in-patients.The mean plasma digoxin concentration in clinically toxic patientswas significantly higher than the mean concentration in non-toxicpatients. The overlap between the groups, however, was extensiveand could partly be accounted for by hypokalaemia in those toxicpatients whose plasma digoxin concentration was less than 3ng/ml. There was, in addition, a higher incidence of hyperkalaemia,without obvious cause, in toxic patients than in non-toxic patients.Consideration of the incidence of various non-cardiec factors,specifically plasma potassium concentration>5·0 mmol/l,plasma creatinine concentration > 150 µmol/l, dailymaintenance dose > 6 µg/kg, and age > 60 years,led to the development of guidelines to aid in the diagnosisof digoxin toxicity. Patients with plasma digoxin concentration> 3 ng/ml or with hypokalaemia should be considered probablytoxic and those with plasma digoxin concentration 3 ng/ml inthe absence of hypokalaemia should only be considered toxicif they have at least two of the non-cardiac factors outlinedabove. Plasma digoxin concentrations could not be predictedwith more than 31 per cent certainty by considering the magnitudeof those non-cardiac factors.     

Digoxin remains useful in the management of chronic heart failure

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.     

Digitalis therapy in practice: correlation between clinical evaluation and plasma digoxin concentration (author's transl)]

In a prospective study 73 patients on maintenance digitalis treatment at the Paracelsus Institute, Bad Hall, were clinically examined and the dosage of the drug was adjusted according to cardiac symptoms. The clinical effects were correlated to digoxin concentrations measured on the day following admission to hospital and on the 21st day of treatment. The following practical conclusions were reached: 1. More than 50% of the patients were underdigitalized. 2. There is often no indication for digitalis therapy in patients with a low daily maintenance digoxin dosage and normal renal funciton. 3. The usual recommended maintenance dosage of digoxin provides serum digoxin levels in the lower region of the therapeutic range. 4. Patients with symptoms of decompensation taking an average dosage of digoxin need more digitalis. There is generally no danger of toxicity when the dosage is increased. 5. The serum digoxin concentration in patients with slightly reduced renal function lies in the upper region of the therapeutic range with usual doses of digoxin.     

Evidence-based Therapeutic Drug Monitoring for Indinavir

The HIV protease inhibitor indinavir presents a wide inter-individual variability related to an intense hepatic metabolism. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of indinavir could improve patient care. It was reported that indinavir virological efficacy in HIV-infected patients with wild-type virus was significantly associated with trough concentrations >?100-150 ng/mL. Concerning the exposure-toxicity relationship, the risk of occurrence of nephrotoxicity was more frequently associated with trough concentrations >?500-1?000 ng/mL. Studies with concentration-controlled indinavir therapy suggest that therapeutic drug monitoring allows to achieve safe and effective concentrations, therefore, the level of evidence of the interest of indinavir therapeutic drug monitoring is highly recommended when indinavir is not associated with ritonavir and recommended when ritonavir is combined with ritonavir.     

Digoxin and bepridil: pharmacokinetic and pharmacodynamic interactions

The influence of bepridil on steady-state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double-blind study. Subjects were assigned to one of two groups of 24 subjects each: One group received placebo 1, while the other received digoxin, 0.375 mg/day, loaded with doubled doses on days 1 and 2, for 14 days. After 7 days the groups were subdivided into four groups of 12 subjects each and received concurrent dosing of digoxin with either placebo 2 or bepridil, 300 mg/day, loaded with 900 mg on day 8. Mean (+/- SD) SDCs rose during concurrent bepridil dosing from 0.93 +/- 0.22 to 1.25 +/- 0.25 ng/ml (P less than 0.001). Noninvasive cardiovascular parameters from ECG, systolic time intervals, and electrical impedance cardiography were not influenced by the placebos. Digoxin and bepridil reduced heart rate and prolonged the PQ interval because of negative chronotropic and dromotropic properties. Positive inotropism from digoxin shortened the corrected electromechanical systole (QS2c) and the preejection period and increased impedance cardiography [(dZ/dt)/RZ index]; the opposite effects occurred after bepridil, indicating negative inotropism. The QT interval corrected for heart rate (QTc) showed a similar pattern of changes, as did QS2c for each drug. Concurrent dosing of both drugs resulted in an addition of their chronotropic effects, whereas the dromotropic effects of each drug alone was not intensified. The strengthened digoxin effect from the increased SDC diminished the negative inotropic effect of bepridil. Overall, drug coadministration resulted in a nearly unchanged digoxin-induced positive inotropism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digoxin concentration in saliva and plasma in infants, children, and adolescents with heart disease

Background

Because of its narrow therapeutic index, therapeutic monitoring of digoxin is important in the management of infants and children receiving the drug for cardiac failure or arrhythmias, or following accidental ingestion. Whether saliva can replace plasma in the therapeutic monitoring of digoxin therapy in children is unclear.

Objective

This study assessed the value of determining saliva digoxin concentration in infants, children, and adolescents.

Methods

Infants, children, and adolescents receiving digoxin for various indications, whose digoxin dosage had remained unchanged for ≥10 days, and whose compliance was good according to the parents were enrolled. Digoxin concentration was measured in paired specimens of citric acid-stimulated mixed saliva and plasma obtained simultaneously.

Results

Eighteen children (10 boys, 8 girls; mean [SD] age, 42.3 [53.1] months [range, 2 months-14 years]) were included in the study. Digoxin therapy was administered for cardiac failure due to dilated cardiomyopathy in 9 patients (50.0%), ventricular septal defect in 4 (22.2%), supraventricular tachycardia in 3 (16.7%), and after cardiac surgery in 2 (11.1%). Digoxin concentration in the 20 paired specimens obtained varied from 0.0 to 0.92 ng/mL (mean [SD], 0.25 [0.26] ng/mL) in saliva and from 0.27 to 1.54 ng/mL (mean [SD], 0.77 [0.40] ng/mL) in plasma. The mean plasma/saliva digoxin concentration ratio was 2.8.

Conclusions

This study of infants, children, and adolescents receiving digoxin for a variety of indications and whose dose was unchanged for ≥10 days showed that marked individual variability in the saliva/plasma concentration ratio precludes the use of saliva in predicting the plasma digoxin concentration. The value of saliva digoxin (as opposed to plasma digoxin) measurements in the assessment of the cardiac effects of the drug in children remains to be determined.     

1180例次地高辛血药浓度测定结果的分析

目的对2000年1月至2011年12月期间地高辛血药浓度监测情况进行分析,旨在为临床合理用药提供药学服务.方法采用荧光免疫偏振法(FPIA)监测地高辛血药浓度,对1180例次血药浓度监测结果进行比较分析.结果地高辛安全有效血药浓度范围是0.5~2.0ng/ml,1180例次地高辛血药浓度测定值在安全有效浓度范围699例次(占59.2%),低于血药浓度范围下限(<0.5ng/ml)336例次(占28.5%),高于血药浓度范围上限(>2.0ng/ml)145例次(占12.3%).结论影响地高辛血药浓度及疗效的因素诸多,临床使用地高辛时应根据患者生理、病理状况以及药物相互作用,及时监测血药浓度,并根据监测数据和影响因素调整给药方案,实施个体化给药.     

Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: a potential use for digoxin intoxication.

BACKGROUND: A beta(2)-microglobulin adsorption column used for the treatment of dialysis-related amyloidosis removes serum beta(2)-microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin. METHODS: In vivo clearance of digoxin with the beta(2)-microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the beta(2)-microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin. RESULTS: Digoxin concentration was reduced from 1.11 +/- 0.25 ng/mL to 0.57 +/- 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the beta(2)-microglobulin column was about 145 +/- 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed in vitro, and the capacity of the beta(2)-microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 +/- 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the beta(2)-microglobulin column. CONCLUSION: These data suggested that the beta(2)-microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.     

Evidence-based Therapeutic Drug Monitoring of lopinavir

The HIV protease inhibitor lopinavir presents a wide inter-individual variability related to liver and intestinal metabolism involving CYP3A. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of lopinavir could improve patient care. In na?ve or pretreated HIV-infected patients, no relationship could be evidenced between virological efficacy and trough lopinavir concentration, most likely because concentrations are above inhibitory concentrations. Although data are limited, patients with elevated triglycerides and cholesterol had trough lopinavir concentrations >8?000 ng/mL. These data suggest that the level of evidence of interest of lopinavir therapeutic drug monitoring is may be recommended in some situations such as children, pregnant women, pretreated patients if the number of mutations is <5, when coadministration with drug with metabolizing enzyme inducing properties is warranted and toxicity.     

219例地高辛血药浓度监测结果及不良反应分析

目的：对本院2015年1～9月地高辛血药浓度监测结果进行回顾性分析,为临床合理用药提供参考。方法采用全自动免疫分析仪对219例口服地高辛患者进行血药浓度的检测,并对监测结果及药品不良反应（ADR ）进行统计、分析。结果地高辛血药浓度在0．5‐2．0ng／mL有153例（1．03±0．31ng／mL）,发生7例不良反应;＜0．5ng／mL有30例（0．3±0．13ng／mL）;＞2．0 ng／mL有36例（3．06±0．78 ng／mL）,共9例不良反应。结论及时有效的监测地高辛血药浓度,实行个体化治疗,降低不良反应发生率。     

Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients.

We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.     

Pharmacokinetic interaction of sparfloxacin and digoxin

Sparfloxacin, a broad-spectrum, oral fluoroquinolone antimicrobial agent, has a long elimination half-life that permits once-daily administration. Antibiotics may increase the oral bioavailability of digoxin, leading to increases in its plasma concentration. Since patients treated with sparfloxacin may be receiving concurrent treatment with digoxin, the possibility of an interaction between sparfloxacin and digoxin was examined in a double-masked, placebo-controlled, multiple-dose, two-way crossover study in 24 healthy male volunteers between 20 and 49 years of age. All subjects were given digoxin 0.3 mg once daily throughout the 20-day study. Sparfloxacin (or placebo) was given as a 400-mg loading dose on day 1, followed by single 200-mg daily doses for 9 days, with crossover to the alternate treatment on days 11 through 20. Plasma levels of digoxin were analyzed by validated radioimmunoassay, and plasma levels of sparfloxacin were analyzed by validated high-performance liquid chromatography. Concomitant administration of sparfloxacin and digoxin was generally well tolerated. Mean values for steady-state area under the concentration-time curve over 24 hours for the 2 treatments were virtually identical: 28.4 ng/h per mL(-1) for digoxin administered with placebo and 28.9 ng/h per mL(-1) for digoxin administered concomitantly with sparfloxacin. Mean steady-state maximum plasma concentrations were 3.91 and 3.59 ng/mL for digoxin with placebo and digoxin with sparfloxacin, respectively. Mean steady-state trough plasma digoxin concentrations for the 2 treatments were 0.87 and 0.89 ng/mL, respectively. Mean times to steady-state maximum plasma concentrations were identical at 0.89 hours for both treatments. Mean steady-state oral clearance was 10.6 L/h for digoxin alone and 10.4 L/h for digoxin with sparfloxacin. Thus administration of sparfloxacin in combination with digoxin did not alter the pharmacokinetics of digoxin in healthy male volunteers aged 20 to 49 years. Steady-state plasma sparfloxacin concentrations were consistent with those obtained in other multiple-dose phase I studies, suggesting that digoxin does not alter the steady-state pharmacokinetics of sparfloxacin.     

Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay

Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a digoxin pool prepared from patients receiving digoxin with various amounts of these herbal supplements and then measured digoxin concentrations again using both digoxin immunoassays. We observed modest apparent digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent digoxin in the range of 0.31-0.57 ng/ml), but no apparent digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of digoxin pool were further supplemented with these herbal supplements, digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml digoxin) increase in digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free digoxin does not eliminate the modest interferences of these herbal supplements in serum digoxin measurement by the Digoxin III assay.     

Population pharmacokinetic investigation of digoxin in Japanese neonates

OBJECTIVE: To establish the role of patient characteristics in estimating doses of digoxin for neonates using routine therapeutic drug monitoring data. METHOD: The steady-state blood level data (n = 129) after repetitive oral administration in 71 hospitalized neonates were analysed using Nonlinear Mixed Effects Modelling (nonmem), a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a one-compartment open pharmacokinetic model. The effect of a variety of developmental and demographic factors on digoxin disposition was investigated. RESULTS: Estimates generated by nonmem indicated that the clearance of digoxin (CL/F; L/h) was influenced by the demographic variables: total body weight (TBW), gestational age (GA) and neonate clearance factor (trough serum concentration of digoxin; Conc). These influences could be modelled by the equation CL/F = 0.0261 x TBW (kg)0.645 x Conc (ng/mL)(-0.724) x GA (weeks)0.8. The interindividual variability in digoxin clearance was modelled with proportional errors. The estimated coefficient of variation was 7.0%, and the residual variability was 13.1%. CONCLUSION: Clinical application of the model to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve the desired therapeutic effect. However, the digoxin dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug.     

Comparing the toxicity of digoxin and digitoxin in a geriatric population: should an old drug be rediscovered?

BACKGROUND: Little information is available regarding toxicity rates of the two available forms of cardiac glycosides (digoxin, digitoxin) when used in elderly patients. METHODS: We retrospectively analyzed the charts of all patients more than 60 years of age who were chronically managed with a cardiac glycoside and were hospitalized during the period January 1995 through January 1998. Toxicity was defined as any clinical event that required either a reduction in dose of the drug or its discontinuance. RESULTS: Toxicity occurred among 7.6% of hospitalizations in which digitoxin was used, compared with 18.3% of hospitalizations in which digoxin was used. In multivariate analysis, the odds of toxicity adjusted for other clinical characteristics were three times greater for patients taking digoxin than for patients taking digitoxin. CONCLUSION: Hospitalized elderly patients taking digitoxin had a lower rate of toxicity than those taking digoxin.     

Digoxin Toxicity with Normal Digoxin and Serum Potassium Levels: Beware of Magnesium,the Hidden Malefactor

Background

In recent years, digoxin use has been on the decline, with decreased incidence of digoxin toxicity. Hence, digoxin toxicity, when it occurs, remains an elusive diagnosis to emergency physicians.

Objective

To present a case of digoxin toxicity with normal levels of digoxin and serum potassium, but with severe hypomagnesemia.

Case Report

A 66-year-old woman presented with junctional tachycardia and ectopic atrial tachycardia. She was known to have congestive cardiac failure on diuretic therapy. Her serum digoxin level was within the normal range (2.4 nmol/L [normal = 1.9–2.6]) along with a normal serum potassium level (3.9 mmol/L [normal = 3.5–5]). However, there was severe hypomagnesemia (0.39 mmol/L [normal = 0.65–1.25]) precipitating digoxin-induced dysrhythmia, which responded well to intravenous magnesium therapy.

Conclusion

This case reiterates that digoxin toxicity can occur in patients with normal digoxin and potassium levels, and in such patients, magnesium needs to be checked and treated to prevent potentially life-threatening dysrhythmias.