Physiopathology, Diagnosis, and Treatment of Inappropriate ADH Secretion and Cerebral Salt Wasting Syndrome

Abstract

The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia in clinical practice. There is a well-recognized relationship between hyponatremia and increased morbidity and mortality in the medical literature, though whether SIAD confers the same mortality as other causes of hyponatremia remains unknown. The causes of SIAD comprise a wide variety of diseases, including malignancy, drugs, respiratory and central nervous system disorders among others. There have been significant advances in the treatment of SIAD in recent years, in particular since the introduction of the vasopressin-2 receptor antagonists, which provide a disease-specific tool to target the underlying pathophysiology of SIAD. The evidence base recommendations and the utility of the available therapies for SIAD are discussed in this chapter. Fluid restriction is the first line therapy for chronic SIAD recommended by all current guidelines, despite the lack of good evidence base to support its use in the medical literature. A number of key points relevant to the use of fluid restriction are presented in the manuscript which may be helpful for the physician. In addition, the evidence base to use other therapies such as demeclocycline, oral urea, furosemide, or sodium chloride tablets is very limited. Conversely, the clinical efficacy and safety of tolvaptan is supported by well-designed, randomized, placebo controlled, clinical trials. However, the cost of the therapy and the need for long term safety data may limit its use in clinical practice. Finally, we also review the management of acute hyponatremia, with a focus on the use of bolus therapy with 3% hypertonic sodium chloride for the treatment of patients with cerebral edema.