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Measurement of digitalis-glycoside levels in ocular tissues: a way to improve postmortem diagnosis of lethal digitalis-glycoside poisoning? II. Digitoxin.

Postmortem digitoxin levels in the choroid-retina and vitreous humor of patients who had undergone digitoxin therapy (therapeutic group) and in one case of suicidal digitoxin poisoning were measured and compared with levels in femoral vein blood, myocardium, kidney and liver. The results were interpreted in light of the medical history of each patient. The digitoxin level in the choroid-retina of the single case of suicidal poisoning was far higher than the choroid-retinal levels in the therapeutic group. In the latter, variation in choroid-retinal levels was comparable to that in the other tissues. In cases where the choroid-retina of the right and left eyes were examined, digitoxin levels in both eyes were essentially equal. There was no indication of significant changes in choroid-retinal levels due to postmortem diffusion of digitoxin into the vitreous body. Based on these results, determination of digitoxin levels in the choroid-retina could contribute to improving postmortem diagnosis of lethal digitoxin poisoning.

Adult↗

High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity.

Results of recent studies suggest that proinflammatory cytokines cause myocardial contractile dysfunction, and that the drugs used to treat heart failure modulate the production of cytokines. This study was designed to examine the effects of digoxin in a murine model of heart failure induced by viral myocarditis. Four-week-old inbred DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis virus (EMCV). Digoxin was given orally in doses of 0.1, 1 or 10 mg/kg daily from the day of virus inoculation. Interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha production in the heart were measured on day 5 after EMCV inoculation by enzyme-linked immunosorbent assay. The 14-day mortality tended to be increased in mice treated with 1 mg/kg, and was significantly increased in the group treated with 10 mg/kg per day. Myocardial necrosis and cellular infiltration on day 6 were significantly more severe in the high-dose digoxin group than in the control group. In the animals treated with 1 mg/kg digoxin, IL-1beta was significantly higher than in the control group. Intracardiac TNF-alpha levels were increased in a dose-dependent manner. These results suggest that digoxin worsens viral myocarditis, and that its use in high doses should be avoided in patients suffering from heart failure due to viral myocarditis.

Animals↗

[Behaviour of serum CPK curves in acute myocardial infarction treated with digitalis, verapamil and combined verapamil-digitalis (author's transl)].

In order to compare the effectiveness of different therapeutic regimens in reducing infarct size serial determinations of CPK activity (at 4 hourly intervals in the first 48 hours from the admission to CCU, at the 72th and at 120th hours) were performed in 100 patients with transmural AMI (53 anterior and 47 inferior) with no obvious evidence of LV failure and basal CPK levels lower than 50 U/L. 20 patients (control group) have been treated with glucose-insulin-potassium (GIK). 20 patients have been treated with GIK plus Verapamil (GIK + V). Verapamil was administered at the dose of 50 mg in continuous drip. 20 patients received GIK plus digoxin at the dose of 0.25 mg b.i.d. (GIK + D). 40 patients received GIK, Verapamil and digoxin at the above doses (GIK + V + D). Different values of CKr and infarct size (IS.) show a statistically significant difference between the various regimens, which is more evident if we consider the whole series. Infarct size was greater in patients treated with digoxin with respect to controls, while it was smaller in patients treated with Verapamil. Combined Verapamil-digoxin therapy is associated to an enzymatic behaviour not different from controls. Authors emphasize that in uncomplicated AMI digoxin causes an increase in infarct size while Verapamil reduces significantly it. Association of Verapamil allows the use of digoxin, if clinically justified, without increase in infarct size.

Adult↗

Hospitalizations with adverse events caused by digitalis therapy among elderly Medicare beneficiaries.

BACKGROUND: Digitalis products are among the agents most frequently prescribed to the elderly, yet previous studies have not provided age-, race-, and sex-specific rates of utilization of digitalis by this population. Estimates of the rate of hospitalization with an adverse reaction from digitalis therapy have varied considerably between systems relying on passive reports and those using active surveillance. METHODS: Medicare data from 1985 through 1991 and data from the 1987 National Medical Expenditure Survey were used to determine population-based estimates of the use of digitalis in elderly beneficiaries by age group, sex, and race. Hospitalization rates with an adverse event caused by digitalis therapy were calculated for those persons estimated to be using digitalis. Medicare data were used to identify the frequency of selected comorbidities among persons with an adverse event caused by digitalis therapy as well as the frequency of clinical manifestations associated with digitalis intoxication. RESULTS: Over 3 million Medicare beneficiaries were estimated to be using digitalis in 1987. A total of 202,011 hospitalizations with a coded adverse event caused by digitalis therapy were reported during the 7-year study period. Of persons estimated to be using digitalis, 8.53 per 1000 were hospitalized annually with an adverse event caused by digitalis therapy. Women, individuals with increasing age, and persons of black race, especially those with impaired renal function, were significantly (P < .05) more likely to experience hospitalization with an adverse event caused by digitalis therapy. CONCLUSION: This information may help identify categories of elderly patients who require more frequent monitoring to prevent adverse effects of digitalis therapy. Changes in the format of the hospital bill to include more diagnoses along with increased mandatory reporting of adverse drug events will improve the sensitivity of Medicare data for surveillance of adverse drug events.

Aged↗

Association of digitalis therapy with mortality in survivors of acute myocardial infarction: observations in the Beta-Blocker Heart Attack Trial.

The influence of digitalis therapy on survivors of acute myocardial infarction was examined in the placebo-treated patients from the Beta-Blocker Heart Attack Trial (BHAT). Two hundred fifty (13%) of the 1,921 placebo-treated patients were receiving digitalis at the time of randomization. Patients receiving digitalis differed from those not receiving digitalis in such baseline characteristics as age, prior history of heart failure, prior myocardial infarction and angina pectoris. They also experienced a higher proportion of in-hospital complications including pulmonary edema, persistent hypotension, atrial fibrillation and heart failure in addition to a greater prevalence of complex ventricular premature beats. The total mortality rate over a mean 25 month follow-up period for digitalis-treated patients was 20.4% compared with 8.2% for patients not receiving digitalis; the odds ratio was 2.87 (p less than 0.05). When the mortality rates were adjusted for heart failure and ventricular premature beat complexity, patients receiving digitalis again demonstrated a higher mortality rate, although the adjusted odds ratio was now lower (1.70). When the patients receiving or not receiving digitalis were compared by a multiple logistic regression analysis adjusting for 17 independent variables predictive of mortality, the use of digitalis was no longer independently predictive of total mortality (adjusted odds ratio 1.07). These data indicate that patients receiving digitalis had more extensive cardiovascular disease and greater morbidity than patients not receiving digitalis. Their subsequent higher mortality rate was probably related to these factors rather than to digitalis therapy.

Adult↗