Digitálicos: os resultados do DIG no século XXI / Digoxin: the results of the DIG study in the XXI century / Digitálicos: los resultados del DIG en el siglo XXI

Depois da divulgação de que não houve significância estatística na mortalidade geral do estudo DIG, a indicação dos digitálicos nos esquemas de tratamento da insuficiência cardíaca congestiva (ICC) reduziu drasticamente. Estudos post hoc, que reavaliaram os dados do DIG, indicaram que um aspecto não considerado neste ensaio multicêntrico exerce influência decisiva no prognóstico dos pacientes: a concentração sérica da digoxina. Em relação àqueles que receberam placebo, a mortalidade geral e a hospitalização foram reduzidas em pacientes com concentração de digoxina inferior a 0,9 ng/ml. No primeiro trabalho que avaliou a influência dos digitálicos em modelo experimental de ICC, verificamos em nosso laboratório que ratas com síndrome congestiva secundária a infarto do miocárdio têm a sobrevida prolongada sob tratamento com digitoxina. As informações atuais recomendam que os méritos dos digitálicos continuem a ser analisados para estabelecer adequadamente sua importância no tratamento da ICC.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Después de la divulgación de que no hubo significancia estadística en la mortalidad general del estudio DIG, la indicación de los digitálicos en los esquemas de tratamiento de la insuficiencia cardíaca congestiva (ICC) se redujo drásticamente. Estudios post hoc, que reevaluaron los datos del DIG, indicaron que un aspecto no considerado en este ensayo multicéntrico ejerce influencia decisiva en el pronóstico de los pacientes: la concentración sérica de la digoxina. En relación a aquellos que recibieron placebo, la mortalidad general y la hospitalización fueron reducidas en pacientes con concentración de digoxina inferior a 0,9 ng/ml. En el primer trabajo que evaluó la influencia de los digitálicos en modelo experimental de ICC, verificamos en nuestro laboratorio que ratas con síndrome congestivo secundario a infarto de miocardio tienen la sobrevida prolongada bajo tratamiento con digitoxina. Las informaciones actuales recomiendan que los méritos de los digitálicos continúen a ser analizados para establecer adecuadamente su importancia en el tratamiento de la ICC.

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure / Níveis séricos de digoxina em pacientes com insuficiência cardíaca secundária à cardiomiopatia da doença de Chagas

INTRODUCTION: The purpose of this study was to determine digoxin serum concentrations in patients with Chagas' cardiomyopathy with chronic heart failure, because little is known concerning this laboratory test in patients with this condition. METHODS: This study focuses on 29 (29 percent) out of 101 patients with chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin therapy. Digoxin was measured by the immune-enzymatic method. RESULTS: New York Heart Association Functional Class III/IV was noted in 13 (45 percent) patients. The mean potassium serum level was 4.3± 0.5mEq/L, mean creatinine serum levels 1.4± 0.3dg/100ml, and left ventricular ejection fraction 34.7± 13.8 percent. The median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55 percent) patients had digoxin serum levels higher than 1.0ng/ml. Abnormal digoxin serum levels were verified in 13 (45 percent) patients. Digoxin serum levels correlated moderately with creatinine serum levels (r = 0.39; p< 0.03) and negatively with sodium serum levels (r= -0.38; p= 0.03). CONCLUSIONS: Digoxin serum concentration should be measured in patients with Chagas' cardiomyopathy with chronic heart failure receiving digoxin therapy due to the potential for digoxin toxicity.

INTRODUÇÃO: O propósito deste trabalho foi o de determinar a concentração sérica de digoxina em pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas porque pouco se conhece sobre os níveis séricos desse fármaco em pacientes com tal condição clínica. MÉTODOS: Foram recrutados 29 (29 por cento) de 101 pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas, os quais estavam sendo tratados com digoxina. Essa droga foi medida no soro desses pacientes pelo método imunoenzimático. RESULTADOS: Treze (45 por cento) pacientes estavam no grau III/ IV da Sociedade Nova-Iorquina de Cardiologia. Os níveis séricos de potássio médio foram 4,3± 0,5 mEq/L, a creatinina sérica média 1,4± 0,3dg/100ml, e a fração de ejeção do ventrículo esquerdo 34.7± 13. 8 por cento. Os níveis séricos médios de digoxina foram 1,27 (0,55; 1,79)ng/ml. Dezesseis (55 por cento) pacientes apresentaram níveis séricos de digoxina > 1,0ng/ml. Níveis séricos anormais de digoxina foram observados em 13 (45 por cento) pacientes. Os níveis séricos de digoxina correlacionaram moderadamente com os de creatinina (r= 0,39; p< 0,03) e negativamente com os de sodium (r= -0,38; p= 0,03). CONCLUSÕES: Os níveis séricos de digoxina devem ser medidos em pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas por causa do potencial para ocorrer toxicidade pela digoxina.

Comparison of target concentration intervention strategy with conventional dosing of digoxin.

Digoxin is a widely used drug in patients with congestive heart failure. The present study compared the quality of life of congestive heart failure patients on one year follow-up period with two different dosing of digoxin (5/7 therapy and 7/7 therapy in whom the target serum digoxin concentration is maintained). Quality of life significantly improved in intervention group thus emphasizing the need for continuous dosing of digoxin based on target concentration.

Warm versus tepid antegrade intermittent blood cardioplegia for myocardial protection during coronary artery bypass graft surgery

Controversy exists about the preferred temperature of cardioplegia to achieve an optimal oxygen supply-consumption balance for myocardial protection during the period of aortic cross-clamping in open heart surgeries. This study was designed to compare two levels of ante grade intermittent blood cardioplegia, tepid versus warm, in patients undergoing coronary artery bypass graft [CABG] surgery. This randomized study was conducted on 60 adult patients of both sexes with age range of 30-70 years, scheduled for CABG surgery with cardiopulmonary bypass [CPB]. The patients were divided into 2 equal groups according to the temperature of the cardioplegia, tepid [29°C] and warm [37°C]. After induction of general anesthesia, a pulmonary artery catheter [PAC] was inserted. After instituting CPB and applying the aortic cross-clamp, blood cardioplegia with added potassium chloride was delivered exclusively antegrade in the two groups. In the warm group, systemic temperature was maintained at 37°C by active rewarming and cardioplegia was delivered at a temperature of 37°C. In the tepid group, systemic temperature was permitted to drift passively during the operation to 32°C and temperature of cardioplegia was 29°C. CBP time and aortic cross-clamp time were recorded. Cardiac index [CI], pulmonary capillary wedge pressure [PCWP], right ventricular stroke work index [RVSWI], and left ventricular stroke work index [LVSWI]; were calculated following induction of anesthesia, before going on CPB, after coming off CPB, at the end of surgery, and 6 hours post-extubation in the ICU. Rate of spontaneous defibrillation, and the need for inotropes or intra-aortic balloon pump [IABP] following CPB were recorded. In the ICU, a 12 lead ECG was done at 2 and 24 hours and duration of mechanical ventilation and length of stay in the ICU [LOS-ICU] were recorded. Serial venous blood samples were drawn at 1, 3, 6, 12, 24, and 48 hours after aortic unclamping to determine the level of cardiac troponin I [CTnl]. Patients' characteristics were comparable in the 2 groups. CPB time and aortic cross clamp time were comparable in the 2 groups. The rate of spontaneous defibrillation was significantly higher and the number of patients who required positive inotropic support was significantly lower in the warm group than the tepid group. CI, RVSWI, and LVSWI were comparable in the 2 groups after induction of anesthesia, just before going on CPB, and 6 hours after extubation in the ICU. CI, RVSWI, and LVSWI were significantly higher in the warm group as compared to the tepid group just after coming off CPB and at the end of surgery. CTnI was higher in the tepid group as compared to the warm group and the difference was significant at 3, 6, and 12 hours after aortic unclamping. Duration of postoperative mechanical ventilation, LOS-ICU, and postoperative myocardial infarction were comparable in the 2 groups. Warm cardioplegia was superior to tepid cardioplegia in terms of myocardial protection during aortic cross-clamping in CABG surgery

Concentraciones plasmáticas de digoxina en cuatro esquemas terapéuticos de uso común en la práctica clínica / Digoxin plasma levels in patients usign four common therapeutic schedules

Background: The different therapeutic schedules used for the prescription of digoxin have little theoretical support. Aim: To measure digoxin plasma levels in patients using four different prescription schedules. Patients and methods: Four groups of patients were studied. Group I corresponded to 56 patients taking digoxin 0.25 mg/day, from Monday to Friday. Group II corresponded to 30 patients taking digoxin 0.25 mg/day, from Monday to Saturday. Group III corresponded to 53 patients taking digoxin 0.25 mg/day continuosly. Group IV corresponded to 36 patients taking digoxin 0.125 mg/day continuosly. Plasma digoxin levels were measured in two consecutive Mondays before taking the daily dose of the drug. Serum creatinine was also measured and creatinine clearance was calculated. The therapeutic plasma concentration range was set between 0.5 and 2 ng/ml. Results: Mean plasma digoxin levels were 1.15±0.8 ng/ml in group I, 1.4±0.55 ng/ml in group II, 1.68±0.7 ng/ml in group III and 1.14±0.43 ng/ml in group IV. 93 percent of patients in group I, 80 percent of patients in group I, 80 percent of patients in group II, 75 percent of patients in group III and 94 percent of patients in group IV had therapeutic digoxin levels. A low creatinine clearance, an age over 65 and interactions with other drugs were risk factors associated with supratherapeutic levels, mostly seen in group II and group III with 20 percent and 24 percent respectively. Conclusions: Most patients using digoxin with different therapeutic schedules had plasma drug levels within the therapeutic range

Cardiac surgery and plasma digoxin levels.

Cardiopulmonary bypass (CPB) can induce several haemodynamic alterations and therefore influence pharmacokinetics of various drugs. In order to assess the effect of CPB on plasma digoxin levels, these were monitored in patients undergoing open heart surgery involving CPB (n = 11), over a 24 hour period, starting just prior to commencement of surgery. For comparison, plasma digoxin was also monitored in a group of patients (n = 10) who underwent cardiac surgery not involving CPB. In 7 of the 11 patients in the CPB group, plasma digoxin levels (ng/ml) were significantly (p < 0.01) lower at the end of 24 hours (0.654 +/- 0.094) than basal levels (1.3114 +/- 0.2498). In contrast, in the non CPB group, 7 of 10 patients showed significantly higher (p < 0.001) plasma levels (ng/ml) at the end of 24 hours (0.477 +/- 0.125) as compared to basal levels (0.26 +/- 0.098). Thus, rather than the type of surgery, it appears that the pre-operative levels of plasma digoxin influence its pharmacokinetics.

Investigation into the possible mechanisms involved in altered digoxin levels in diabetic patients.

The present study was undertaken to investigate the possible factors which may contribute to the altered digoxin levels in diabetic patients. The digoxin levels were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive correlation between digoxin levels and glycosylated haemoglobin levels. All diabetic patients had serum creatinine, urea and potassium levels within normal limits. However, serum TSH levels were found to be significantly higher in diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were found to be lower in diabetics as compared to non-diabetics. Our data suggests that diabetes-mellitus causes alteration of digoxin levels. One of the causes of this increase in digoxin levels may be a tendency towards mild hypothyroidism associated with diabetes mellitus.