Raymond E. Weston

The pathogenesis and treatment of hyponatremia in congestive heart failure

Abstract Acute intensification of chronic congestive failure in cardiac patients on low sodium diets may lead to continued water retention, with increasing edema and hyponatremia without external loss of sodium. This sequence is illustrated by the events following development of severe respiratory infections or escape from digitalization in such patients. Such a sequence may occur also, at times, in the presence of electrocardiographic changes suggestive of digitalis toxicity but actually due to potassium depletion. This clinical course is not favorably influenced by intravenous administration of either isotonic or concentrated sodium solutions. However, increasing cardiac output by adequate digitalization or decreasing bodily metabolic demand by treatment of the underlying infection may lead to increased excretion of water in excess of sodium, decreased body weight, and restoration of more normal serum electrolyte concentrations. This sequence of events is attributed to sustained production of antidiuretic hormone, invoked by some extraosmoreceptor mechanism, whenever the cardiac output becomes inadequate for the bodys metabolic needs. The more protracted operation of this mechanism is illustrated by the progressive water retention and hyponatremia frequently observed in patients on a low sodium diet and unrestricted water intake during the terminal phase of congestive failure. A fatal outcome may be anticipated unless the cardiac output can be increased or the burden on the impaired circulation in some way diminished.

STUDIES ON INTRAVENOUS WATER DIURESIS AND NICOTINE AND PITRESSIN ANTIDURESIS IN NORMAL SUBJECTS AND PATIENTS WITH LIVER DISEASE

The fluid retention of patients with liver disease, leading to edema and ascites, has generally been attributed to primary sodium retention with secondary, obligatory water retention. However, because of the impaired water diuresis following oral hydration and the increased amounts of urinary antidiuretic activity observed in such patients, several investigators (1-4) have postulated some primary change in mechanisms influencing the release, physiological effect or inactivation of the -neurohypophyseal antidiuretic hormone. White, Rubin and Leiter (5) observed that, on the average, the maximal urine flows and periods of time required to achieve peak diuresis, during infusions of 10 ml. of intravenous glucose in water per minute, were the same in patients with liver disease and subjects with normal liver function. Furthermore, intravenous administration of 0.57 mU of Pitressin per Kg., during such wa

Studies on Water Excretion Following Intravenous Hydration and the Administration of Pitressin or Nicotine in Congestive Heart Failure

The diuretic response to intravenous infusions of 5 per cent glucose in water and the antidiuretic response to intravenous injections of nicotine salicylate and aqueous Pitressin, during maximal water diuresis, were studied in normal subjects and patients in congestive failure of varying severity. Patients in moderately severe congestive failure exhibited normal diuretic responses during the periods of intravenous hydration and normal antidiuretic responses following nicotine or Pitressin injections. Patients in more severe congestive failure failed to achieve comparable diuretic responses, following intravenous hydration; in the course of this, signs of increasing congestive failure developed, which were associated with further decrease in urine flows, at times, without any further decrease in renal hemodynamics. These studies confirm the impression that patients in moderate congestive failure have neither increased sensitivity to, nor reduced ability to, inactivate endogenous or exogenous antidiuretic hormone. In addition, the observation, that patients in more severe failure do not achieve adequate water diuresis during intravenous hydration, suggests that sustained production of antidiuretic production, independent of normal osmoreceptor control, may be contributing to their fluid retention.

Metabolic studies on the effects of ion exchange resins in edematous patients with cardiac and renal disease.

Abstract The effects of ion exchange resins on the metabolic balances of sodium, chloride, potassium, nitrogen and phosphorus were studied in eleven edematous patients with either cardiac or renal disease. Administration of 40 to 90 gm. daily of a carboxylic acid cation exchanger, two-thirds in the acid cycle and one-third in the potassium cycle, produced marked increases in fecal sodium excretion, significantly negative sodium balances, and effective loss of edema. These effects were observed even in patients in severe congestive failure on low sodium diets who exhibited evidence of actively functioning sodium-conserving mechanisms, such as negligible urinary sodium excretion and eosinopenia. As a result of removal of cation without anion, persistent hyperchloremic acidosis developed, despite the increased urinary chloride excretion and the negative chloride balance which promptly occurred in patients without organic renal disease. In patients with renal disease little chloruresis occurred and, consequently, the resulting acidosis was more severe. However, by intermittent administration of the resins and the concurrent use of mercurial diuretics, which produced loss of more chloride than sodium, mobilization of edema in the patients with renal disease was safely accomplished. In this series, addition of an anion exchanger to the resin mixture had no effect on either the acidosis or the fecal excretion of any electrolyte. The proportion of resins in the potassium cycle in carbo-resin provided sufficient additional potassium, as a rule, to prevent potassium depletion. Moreover, with gradual, resin-in-induced gastrointestinal losses, the kidney very efficiently conserved potassium by reducing the urinary excretion to less than 1 mEq./day. However, when patients on resin therapy developed anorexia and vomiting or diarrhea, the additional loss of potassium tended to produce depletion with or without hypokalemia. If signs of potassium deficit occur, oral supplementation of the patients intake with organic potassium salt mixtures permits continued resin therapy. Hyponatremia is a rare consequence of resin therapy. Since there is generally greater diuresis and weight loss than can be explained on the basis of the increased sodium excreted, this cannot represent sodium depletion per se . Whether movement of sodium into some non-extracellular site may be involved in the transient, spontaneously reversible, mild hyponatremia observed in some cardiacs during the period of hyperchloremic acidosis of resin therapy remains to be established. It is concluded that, if periodic blood studies are made throughout therapy, the administration of resins constitutes a valuable and safe addition to the treatment of resistant edema in patients with cardiac and renal disease. The value of these agents in any individual patient must be determined empirically.

Renal extraction and excretion of mercury in man following intravenously administered mercurial diuretics.

Previous studies (1) from this laboratory have indicated that urinary excretion of mercury reaches a maximal value immediately following the intravenous injection of an organic mercurial diuretic and then falls rapidly, presumably as the plasma concentration of mercury decreases. Moreover, the dynamics of mercury excretion during the first four to six hours in a given individual are quite constant on repeated measurement and are not significantly affected by certain factors which either enhance or inhibit diuresis. In the present study the mechanisms by which mercury is removed from the plasma and excreted in the urine and the relationship of this process to mercurial diuresis have been investigated in human subjects with the aid of simultaneous measurements of renal hemodynamics, urinary mercury and electrolyte excretion, and arterial and renal venous plasma mercury concentrations.

Studies on Thiomerin—A Subcutaneously Administerable Mercurial Diuretic

Results of clinical and physiologic studies with Thiomerin, a new subcutaneously administered mercurial diuretic, are presented. The data indicate a clinical diuretic efficacy comparable to that of other mercurials and a negligible systemic toxicity. Renal clearance studies demonstrate that it acts by producing a reversible depression in tubular reabsorption of electrolyte and water. The effects of intravenous and subcutaneous administration are compared.