Clinical Judgment Is the Key to Determining Treatment for Hyponatremia

An article in Current Medical Research & Opinion summarized international guidelines from professional organizations concerning the management of hyponatremia.

Hyponatremia is the most common electrolyte imbalance encountered in clinical practice and is common in elderly patients. The recommendations for using pharmacological therapy for the treatment of hyponatremia differ worldwide.

New data on the relationship between hyponatremia and increased mortality, morbidity, and length of hospital stay has been published frequently over the past two years. However, the publications differ in some of their basic recommendations. These differences are substantial and not just related to different treatment thresholds. The differing opinions can be confusing for physicians who don’t routinely treat hyponatremia.

The indications for treatment of hyponatremia by pharmacological therapy vary worldwide. Differing opinions and approaches are likely because differing availability of drugs worldwide leads to different or no experience with the use of certain prescriptions; utilization of differing methodologies in the review of existing data; and divergent interpretation of the evidence.

The only pharmacological therapy approved across three continents for the treatment of hyponatremia is the class of vasopressin receptor antagonists known as vaptans. However, recommendations for using these agents differ substantially worldwide.

The European Medicines Agency (EMA) has approved tolvaptan for the treatment of hyponatremia caused by the syndrome of inappropriate anti-diuretic hormone secretion (SIADH.) The Japanese Ministry of Health has only approved mozavaptan for the treatment of a specific etiology of SIADH. While tolvaptan is approved in Japan for various conditions it is not for approved for hyponatremia. In Canada vaptans are approved for clinically significant non-hypovolemic hyponatremia. The US Food and Drug Administration approved two vaptans: tolvaptan and conivaptan for treatment of both euvolemic (ie, SIADH) and hypervolemic (ie, edema-forming states), but has restricted the use of tolvaptan in patients with liver disease.

The EMA has approved tolvaptan for all SIADH patients with clinically significant hyponatremia. Japan has only approved mozavaptan for hyponatremia associated with tumors>3.5 cm. The FDA has limited tolvaptan use to patients with serum [Na+] less than 125 mmol/L unless patients are symptomatic and have resisted attempts to correct hyponatremia by fluid restriction. Health Canada set a higher limit of <130 mmol/L for initiation of therapy with tolvaptan.

Worldwide, all entities approve of pharmacological therapy for hyponatremia in SIADH. Despite approval for hyponatremia due to SIADH by all regulatory agencies the indications vary substantially.

Review of current worldwide guidelines indicates that there is no one treatment for hyponatremia, but rather physicians must individualize treatment to fit the patient’s unique situation. Different situations predicate different therapeutic approaches.

Fluid restriction has been the mainstay of therapy for hyponatremia due to SIADH since the first description of this disease in 1957. However, there is a need for pharmacological therapies for hyponatremia patients who fail, or are predicted to fail, attempts at fluid restriction and those who can’t realistically be fluid restricted.

Some patients with transient SIADH secondary to pneumonia may successfully respond to a few days of fluid restrictions. However other patients with various medical complications will require pharmacological therapy.

Clinical practice guidelines are developed based on a critical analysis of published medical literature and supplemented by expert opinion. Therefore there are a number of reasons why recommendations differ from different countries and organizations.

There is a wide spectrum of clinical scenarios of hyponatremic patients that exemplify that when caring for these patients there is no one recommended treatment. Therapy should be individualized to each patient’s unique situation.

In conclusion, it is clinical judgment rather than guidelines that should dictate the treatment regimen physicians make for their patients.

Bridget Barry Thias is a Dallas-based healthcare writer.