Findings of the present study indicate that in terminally ill cancer patients with hypernatremia (vs. eunatremia or hyponatremia), the prognosis is demonstrably poor. These results are aligned with outcomes of previous studies, offering added support. Based on a group of 259 cancer patients referred for palliative care, Alsirafy et al. encountered shorter median survival (8 days) and higher mortality (68%) in those with hypernatremia than in hyponatremic or eunatremic counterparts . However, multivariable analysis of well-known prognostic factors in terminal cancer patients was not done. Our data indicate that the association between hypernatremia and poor survival remains robust after controlling for other predictors of survival.
Salahudeen et al. have also reported poor clinical outcomes involving higher mortality, longer hospitalization, and greater hospital expense in patients with hypernatremia . There were some differences from our cohort of terminal patients whose life expectancies were roughly 6 months. They examined subjects admitted to a comprehensive cancer center with any stage of disease; and their focus was on iatrogenic hypernatremia, because baseline hypernatremia contributed so few patients. In our investigation, laboratory testing took place on day of admission, aimed at existing rather than acquired hypernatremia. Hence, this is perhaps the first effort to explore the prognostic utility of spontaneous hypernatremia in terminally ill cancer patients.
The prevalence of hypernatremia in patients with terminal cancer is unclear. Salahudeen and colleagues found that hypernatremia in cancer patients increased from 0.2% on admission to 2.6% during the course of hospitalization . Another study has also indicated that 8.5% of adult cancer patients referred for palliative care are hypernatremic . Similar to prior studies, we recorded a 3% prevalence of hypernatremia.
Little is known of the specific mechanism by which hypernatremia worsens survival, but there is at least one plausible explanation. Hypernatremia is generally induced by the loss of electrolyte-free water. Physiologic feedback mechanisms, such as thirst and antidiuretic hormone (ADH) release, are then promptly activated to increase water intake and minimizing additional free water loss. In a healthy population, elevated serum sodium levels return to normal range accordingly . However, feedback dysfunction in patients with terminal cancer may impede or prevent normalization of serum sodium concentrations, and many patients with terminal cancer are faced with non-replenishment of water lost through excessive sweating, vomiting, diarrhea, and nasogastric drainage . Impaired response to thirst due to diminished mental faculties or poor oral intake and subsequent dehydration may induce hypernatremia in such patients outside hospital environments. Still, there is virtually no research on hypernatremia in cancer patients. Retrospective studies of older adult patients and critically ill patients admitted to intensive care units would be helpful to understand this problem in the context of terminal cancer [16, 17]. Mental debilitation and poor oral intake create rapid declines in their general conditions . Although causality between hypernatremia and deteriorating general conditions remain in question, hypernatremic patients are extremely ill and less inclined to survive.
Certain prognostic factors, namely poor functional status, leukocytosis, and hypoalbuminemia, are well documented in past reports, but the data on effects of hyponatremia have been inconsistent. Several earlier endeavors have shown the negative prognostic aspect of hyponatremia in a variety of cancers [19, 20]. Yoon et al. have also demonstrated a relation between hyponatremia and shorter survival time in terminally ill cancer patients . However, another study has failed to support this relation in Korean patients with terminal cancer entering a hospice unit, although hampered by a relatively short median survival time (9.5 days) . To our knowledge, the present analysis offers the most fully controlled results in a comparable setting, adjusted for potential confounders. Also, our subjects survived longer than those in previous studies. Even so, we did not find hyponatremia predictive of poor survival under these conditions. Further prospective studies to explore the prognostic significance of hyponatremia are nevertheless warranted.
At present, evidence of the prognostic value of potassium disorders is sparse. Cui et al. have observed an association between serum potassium level and survival time, but significance was not reached in multivariable analysis . In our study, hyperkalemia similarly did not emerge from multivariable analysis as a significant predictor of poor prognosis. One retrospective study conducted in Taiwan cites a serum potassium level >5mg/dL as an objective index of short-term survival (7 days) in patients with advanced cancer . Still other researchers have found no prognostic significance attached to potassium imbalance [2,22].
There are acknowledged limitations to interpreting the results of our study. First, the cohort is representative of a single center only, and the number of hypernatremic patients was small. Given the prevalence of hypernatremia in terminal cancer patients, large-scale multicenter investigations would be helpful to determine the actual prognostic import of hypernatremia under such circumstances. Another drawback is the lack of sequential or interventional data on serum sodium levels. A previous study does indicate that hyponatremia normalization is prognostically beneficial in patients with advanced non-small cell lung cancers . One may thus infer that without normalization, patients with persistent hypernatremia will fare worse. Finally, we did not consider potential confounders related with symptoms such as anorexia-cachexia, delirium, dyspnea, and edema.