Diuretic-induced hyponatremia.

Diuretics are one of the most common causes of severe hyponatremia. Yet, despite several relevant studies and years of clinical experience, the mechanism and optimal treatment of diuretic-induced hyponatremia remain unclear. What is clear is that most cases are caused by thiazide rather than loop diuretics and that severe hyponatremia can develop very rapidly in susceptible patients. In this review, I will discuss the pathogenesis, clinical features, prevention, and treatment of diuretic-induced hyponatremia in the hope that increased awareness and understanding will reduce the incidence and complications of this potentially life-threatening syndrome.     

The challenge of hyponatremia

Treatment of hypotonic hyponatremia often challenges clinicians on many counts. Despite similar serum sodium concentrations, clinical manifestations can range from mild to life threatening. Some patients require active management, whereas others recover without intervention. Therapeutic measures frequently yield safe correction, yet the same measures can result in osmotic demyelination. To address this challenge, we present a practical approach to managing hyponatremia that centers on two elements: a diagnostic evaluation directed at the pathogenesis and putative causes of hyponatremia, the case-specific clinical and laboratory features, and the associated clinical risk; and a management plan tailored to the diagnostic findings that incorporates quantitative projections of fluid therapy and fluid losses on the patient's serum sodium, balances potential benefits and risks, and emphasizes vigilant monitoring. These principles should enable the clinician to formulate a management plan that addresses expeditiously three critical questions: Which of the determinants of the serum sodium are deranged and what is the underlying culprit? How urgent is the need for intervention? What specific therapy should be instituted and which are the associated pitfalls?     

Isotonic hyponatremia following transurethral prostate resection.

The proper treatment of hyponatremia during transurethral resection of the prostate continues to be controversial. Two cases of isotonic hyponatremia are reported here, and the literature regarding the incidence and treatment of hyponatremia during transurethral resection of the prostate is reviewed. In each case, the patient developed neurologic changes during complicated transurethral prostate resection. Despite the rapid decrease in the serum sodium concentration, serum osmolality remained normal due to the resorption of the bladder irrigant glycine. Therefore, etiologies other than cerebral edema are postulated as the cause of the neurologic manifestations. Also, the role of the osmolar gap in directing appropriate therapy is emphasized in an effort to avoid unnecessary use of hypertonic saline. Finally, an appropriate differential diagnosis of the neurologic changes seen during the transurethral resection of the prostate syndrome is discussed.     

Diuretic-associated hyponatremia

Soon after their introduction in 1957, thiazide diuretics became a recognized cause of hyponatremia. Thiazides may be the sole cause and they may exacerbate hyponatremia in patients with disorders that cause the syndrome of inappropriate antidiuretic hormone secretion. Although thiazides do not inhibit the ability to concentrate the urine, they impair diluting ability in several ways: inhibition of sodium and chloride transport at cortical diluting sites; stimulation of vasopressin release; reduction of glomerular filtration and enhanced proximal water reabsorption, which reduce delivery to the distal diluting sites; and, possibly, a direct effect on water flow in the collecting duct. Water retention caused by impaired water excretion combined with cation depletion may result in severe hyponatremia. Thiazides should be avoided in frail elderly patients with chronically high water intake or in others who depend on the excretion of maximally dilute urine to maintain fluid balance, such as patients with psychogenic polydipsia or heavy beer drinking. Inadvertent rapid correction of hyponatremia is common in thiazide-induced hyponatremia because the ability to dilute the urine is restored when the diuretic is discontinued and volume deficits are repaired. Hypokalemia, which often is present, increases the susceptibility to osmotic demyelination syndrome and replacement of potassium deficits contributes to the increase in serum sodium concentration.     

The outcome of hyponatremia in a general hospital population

To determine the prognosis of hyponatremia in an unselected population, we collected clinical and laboratory data and determined the outcome of hospitalization for all hyponatremic patients in a general hospital over a three month period. Of the 78 patients studied, 36 (46%) had CNS symptoms while 42 (54%) were asymptomatic. Using a diagnostic algorithm we classified the patients with CNS symptoms into two groups: those with CNS symptoms due to hyponatremia (11 patients) and those with CNS symptoms caused by other factors (25 patients). Twenty-one patients (27%) died during the study. The highest mortality (64%) was in patients with CNS symptoms related to factors other than hyponatremia. Patients with CNS symptoms due to hyponatremia had a mortality rate (9%) similar to that of patients without CNS symptoms (10%). These findings suggest that the relationship between hyponatremia and outcome is probably not causal. Rather, hyponatremia appears to be a marker for severe underlying disease that carries a poor prognosis.     

Severe mannitol-induced hyponatremia complicating transurethral prostatic resection.

A case is presented in which the absorption of mannitol irrigation solution across prostatic veins resulted in severe hyponatremia in a patient undergoing transurethral prostatic resection. Since hyposmolality of the extracellular fluid was not seen because of the presence of mannitol the patient was asymptomatic despite a rapid decrease in the serum sodium concentration to 99 mEq./l. The importance of distinguishing dilutional hyponatremia from hyponatremia with normal or elevated osmolality is discussed.     

The correlation of hip fracture and hyponatremia in the elderly

Background: Increasing age is considered one of the risk factors for hyponatremia. The concept of asymptomatic hyponatremia is not correct anymore as these patients have a greater risk for falls, bone fractures and attention impairment. The combination of old age and a fall is a common recipe for admission to a nursing home. Methods: We identified 249 patients 65 years of age or older who were admitted to hospital with the diagnosis of hip fracture secondary to fall, during a 3-year period. We compared their serum Na level on admission with that of controls: 44 ambulatory patients admitted for elective hip or knee replacement surgery during the same time frame. Odds ratios (ORs) were calculated using logistic regression. Results: The prevalence of hyponatremia in cases was 16.9%, versus 4.6% in controls (p=0.03). Age and hyponatremia were strongly correlated with hip fracture secondary to fall. The univariate OR for hip fracture associated with each 10-year increase in age was 5.57 (p<0.0001). After controlling for age, cases were almost 5 times as likely as controls to be hyponatremic (OR=4.80, p=0.04). Conclusions: Even mild hyponatremia in the elderly should be considered a risk factor for falls. Correction of hyponatremia in the elderly may reduce morbidity and mortality, and at the same time, it has a huge impact on socioeconomic status.     

Carbamazepine induced hyponatremia

Carbamazepine (CBZ) is a drug which can induce the syndrome of inappropriate antidiuretic hormone (SIADH). Until 1980's, there were reports regarding CBZ-induced SIADH, but it is rarely reported these days. We here report two cases of CBZ-induced SIADH. Hyponatremia in these cases was rapidly improved by withdrawal of administration of CBZ. According to the previous reports, the rate of hyponatremia in patients receiving CBZ is not small. It ranges from 48% to 31%. As CBZ is frequently used for patients with epilepsy and neuralgia, not only their blood CBZ concentration but also their serum Na level should be monitored.     

Correction of hyponatremia

The development of selective oral V2 receptor antagonists has led to confirmation of established concepts of the pathogenesis of hyponatremia and to new approaches to its treatment. V2 receptor antagonists are effective and promising agents. Their properties as specific pharmacologic tools will facilitate the treatment of the different types of hyponatremia because of the improved predictability of response, and improved control of fine tuning of responses, compared with what is achieved by current therapies. In addition, the quality of life of hyponatremic patients will improve because there will be less need for severe fluid restrictions. It is likely that these agents can be administered over prolonged periods of time.