Hyponatremia in Hospitalized Cancer Patients and Its Impact on Clinical Outcomes

Division of Internal Medicine, University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
American Journal of Kidney Diseases (Impact Factor: 5.9). 02/2012; 59(2):222-8. DOI: 10.1053/j.ajkd.2011.08.029
Source: PubMed


Hyponatremia is the most common electrolyte abnormality in clinical practice, yet little is known about its frequency in patients with cancer or its impact on their clinical outcomes.
Retrospective analysis of prospectively collected data.
Patients with cancer admitted to the University of Texas M.D. Anderson Cancer Center in 2006 for 3 months.
Serum sodium levels categorized as eunatremia (serum sodium, 135-147 mEq/L) and mild (134-130 mEq/L), moderate (129-120 mEq/L), and severe (<120 mEq/L) hyponatremia.
(1) Length of hospital stay and (2) 90-day mortality.
In 4,702 admissions in 3,357 patients with cancer, hyponatremia (serum sodium <135 mEq/L) was noted in 47% of admissions. It was mild in 36%, moderate in 10%, and severe in 1%. Hyponatremia was acquired during the hospital stay in 24%. Using the first admission data, mean length of stay was 5.6 ± 5.0 days for patients with eunatremia and 9.9 ± 9.2, 13.0 ± 14.1, and 11.5 ± 12.6 days for those with mild, moderate, and severe hyponatremia, respectively. The respective HRs in the multivariate Cox model for longer hospital stay, using patients with eunatremia as reference, were 1.92 (95% CI, 1.75-2.13; P < 0.01), 2.94 (95% CI, 2.56-3.45; P < 0.01), and 2.32 (95% CI, 1.32-4.00; P = 0.01). 283 (8.4%) deaths occurred during 90 days, and in the multivariate model, the respective HRs for 90-day mortality for mild, moderate, and severe hyponatremia were 2.04 (95% CI, 1.42-2.91; P < 0.01); 4.74 (95% CI, 3.21-7.01; P < 0.01), and 3.46 (95% CI, 1.05-11.44; P = 0.04). These findings were consistent when analyses were repeated with sodium levels in tertiles.
Observational study, retrospective, inability to adjust for all comorbid conditions.
Hyponatremia in patients with cancer is associated with longer hospital stay and higher mortality. Whether long-term correction of hyponatremia would improve these outcomes remains to be determined.

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Available from: Amit Lahoti, Jun 12, 2014
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    • "The relationship between hyponatremia and increased mortality has been recognized, primarily in patients with heart failure and liver cirrhosis [3-7]. Recent studies have additionally revealed this association in a wide variety of diseases including myocardial infarction [2,8], pulmonary embolism [9], cancer [2,10] and pneumonia [11], and in patients in perioperative settings [1,12] and those in intensive care units [13]. Similar observations have been made in chronic kidney disease (CKD) patients with [14-16] and without end-stage renal disease (ESRD) [17]. "
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    ABSTRACT: Hyponatremia is associated with increased mortality in chronic kidney disease with and without end-stage renal disease (ESRD). Increasing evidence suggests that hyponatremia is not only a marker of severe underlying disease, but also a direct contributor to mortality. However, specific pathogenesis or diseases contributing to mortality in the hyponatremic population are unknown. This study aimed to clarify the relationship between serum sodium level (sNa) and infection risk in ESRD patients. This observational cohort study included 332 patients on maintenance hemodialysis in our dialysis unit in May 2009. The mean of 3 monthly measurements of glucose-corrected sNa before each dialysis session in May, June, and July 2009 was applied as baseline sNa. The primary endpoint was first infection-related hospitalization (IRH), and the secondary endpoint was death of any cause. Data were analyzed using Cox hazards modeling, adjusted for baseline demographics and characteristics, or laboratory data. Patients were followed until transfer, kidney transplantation, death, or study end on January 31, 2013. Mean sNa was 138.9 mEq/L (1st tertile: <138.0, n = 104; 2nd tertile: 138.0-140.0, n = 116; 3rd tertile: >140.0, n = 112). During 39.5 months' mean follow-up, 57 patients experienced IRH (56.4/1,000 patient-years overall; 89.7/1,000 in 1st tertile; 57.9/1,000 in 2nd tertile; 28.0/1,000 in 3rd tertile), and 68 patients died. The hazard ratio (HR) for IRH was higher for the 1st and 2nd tertiles than the 3rd tertile (unadjusted HR, 3.20; 95% confidence interval (CI), 1.54-6.64; p = 0.002; adjusted HR, 2.36; 95% CI, 1.10-5.04; p = 0.027; and unadjusted HR, 2.07; 95% CI, 0.98-4.40; p = 0.058; adjusted HR, 2.11; 95% CI, 0.99-4.51; p = 0.054 respectively). In a continuous model, higher sNa was associated with lower risk of IRH (adjusted HR, 0.90; 95% CI, 0.81-0.99; p = 0.040), and lower all-cause mortality (adjusted HR, 0.91; 95% CI, 0.83-1.00; p = 0.049). Lower sNa is an independent predictor of higher risk for infection-related hospitalization in maintenance hemodialysis patients. Infectious disease may partially account for the increased mortality observed in the hyponatremic population with ESRD.
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  • American Journal of Kidney Diseases 02/2012; 59(2):168-9. DOI:10.1053/j.ajkd.2011.12.004 · 5.90 Impact Factor
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    ABSTRACT: Hyponatremia, a common electrolyte abnormality in oncology practice, may be a negative prognostic factor in cancer patients based on a systematic analysis of published studies. The largest body of evidence comes from small-cell lung cancer (SCLC), for which hyponatremia was identified as an independent risk factor for poor outcome in six of 13 studies. Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with SCLC than with other malignancies. SIADH may be driven by ectopic production of arginine vasopressin (AVP) by tumors or by effects of anticancer and palliative medications on AVP production or action. Other factors may cause hypovolemic hyponatremia, including diarrhea and vomiting caused by cancer therapy. Hyponatremia may be detected on routine laboratory testing before or during cancer treatment or may be suggested by the presence of mostly neurological symptoms. Treatment depends on several factors, including symptom severity, onset timing, and extracellular volume status. Appropriate diagnosis is important because treatment differs by etiology, and choosing the wrong approach can worsen the electrolyte abnormality. When hyponatremia is caused by SIADH, hypertonic saline is indicated for acute, symptomatic cases, whereas fluid restriction is recommended to achieve a slower rate of correction for chronic asymptomatic hyponatremia. Pharmacological therapy may be necessary when fluid restriction is insufficient. The orally active, selective AVP receptor 2 (V(2))-receptor antagonist tolvaptan provides a mechanism-based option for correcting hyponatremia caused by SIADH or other conditions with inappropriate AVP elevations. By blocking AVP effects in the renal collecting duct, tolvaptan promotes aquaresis, leading to a controlled increase in serum sodium levels.
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