Cardiac arrhythmias induced by hypokalaemia and potassium loss during maintenance digoxin therapy.

Abstract

Twelve patients with congestive heartfailure receiving maintenance therapy with digoxin and potent diuretics were followed closely during development of hypokalaemia and potassium loss. Cardiac arrhythmias compatible with digoxin toxicity developed in 6 patients in the presence of stable, normal serum digoxin concentrations. The mechanisms involved in the development of the rhythm disturbances are discussed with regard to hypokalaemia, intracellular potassium loss, intra-/extracellular potassium gradients and digoxin, and the significance of maintaining a normal potassium balance in this setting is stressed.It is generally accepted that hypokalaemia and diuretics were subjected to a potassium depleting potassium loss may promote digitalis toxicity in regimen and followed closely for development of patients with congestive heart failure receiving cardiac arrhythmias while serum digoxin concenmaintenance treatment with digitalis. However, trations were controlled. while this situation was frequent in earlier studies of digitalis toxicity (Lown and Levine, 1954; Jorgensen and Sorensen, 1970), hypokalaemia and Methods potassium loss were not observed as causes of Twelve patients with advanced congestive heart failure digitalis intoxication in more recent reports (Belier admitted to Medical Department B, Rigshospitalet et al., 1971; Evered and Chapman, 1971). Though Copenhagen, were selected for study according to the this new trend may reflect better treatment with following criteria: 1) The subjects had received mainregard to maintenance of potassium balance during tenance digoxin therapy for at least one month and digitalis therapy in particular in patents on chronic showed normal serum digoxin levels, 2) the patients diuretic therapy, it seems also possible that the were in a stable situation on maintenance diuretic diu i ttreatment, and 3) the subjects presented normal serum risks involved m hypokalaemia and potassium loss potassium concentrations and were apparently in a in this setting have been overestimated in the past. stable potassium balance while receiving a standard In earlier studies of digitalis toxicity in man the supplement of potassium chloride of 3 g daily or a relative role of digitalis overdosage and of acute potassium sparing drug as additional diuretic if required. or chronic hypokalaemia or potassium loss have The series consisted of 5 men and 7 women; mean age not been precisely defined, and more recent studies 57,7 years. The clinical diagnoses were rheumatic in dogs have not supported the concept that valvular disease in 6 patients, ischaemic heart disease hypoksaaemia sensitizes the myocardim to digi-in 4, and cardiomyopathy in 2. The patients received talis during condition representinmamtenance treatment with digoxin in a dose range tallsdunrng conditions representing tne nearest from 0.125 to 0 50 mg daily and frusemide 80 to 160 mg practical approximation to the situation of patients or bumetanide 4 to 6 mg per day. on chronic diuretic therapy (Kleiger, Vitale, and With their inform...

Digoxin Toxicity Compared With Myocardial Digoxin and Potassium Concentration

“…& Harrison, 1967;Prindle, Skelton, Epstein & Markus, 1969), who suggested that hypokalemia facilitates the myocardial uptake of digoxin. This might however also be due to a reduced elimination rate (Steiness, unpublished observations tendency to increasing plasma digoxin concentration during potassium loss was recently found in digitalized patients (Steiness & Olesen, 1976). Even though the steady state myocardial concentration was higher in group 1 than in the other groups, the increase of all myocardial digoxin concentrations from 0 to 10 min was very similar in groups 1, 2 and 4, whereas it was significantly higher in group 3.…”

“…Hypokalemia and potassium depletion may also promote toxicity, for example in patients with congestive heart failure receiving both diuretics and maintenance treatment with digitalis. This was evident in some studies (Lown & Levine, 1954;J0rgensen & S0rensen, 1970; Steiness & Olesen, 1976), whereas in others hypokalemia was not associated with toxicity (Beller et al, 1971;Evered & Chapman, 1971). It is still unknown whether hypokalemia itself promotes digitalis toxicity and the aim of the present investigation was therefore to study the relationship between the myocardial uptake of digoxin, and the potassium levels in plasma and myocardium, after a non-toxic intravenous digoxin dose in digitalized dogs.…”

2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

“…287 The risk of electrolyte depletion is markedly enhanced when 2 diuretics are used in combination. The loss of electrolytes is related to enhanced delivery of sodium to distal sites in the renal tubules and the exchange of sodium for other cations, a process that is potentiated by activation of the renin-angiotensin-aldosterone system.…”

Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

“…It seems that a pharmacodynamic effect of digitalis is influenced by potassium so that the lower potassium concentration increases the positive inotropic response considerably (Prindle et al, 1969). Furthermore, it is known that hypokalaemia increases the risk of myocardial digitalis toxicity (Steiness & Olesen, 1976). The digitalis toxicity is supposed to be correlated with the inhibition of the membrane (Na+ + K+) ATPase (Okita, 1977).…”