European Journal of Internal Medicine 25 (2014) e45–e46

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Letter to the Editor Prevalence and in-hospital mortality of hyponatremia: A cohort study Keywords: Hyponatremia Prevalence Elderly In-hospital mortality

Hyponatremia contributes substantially to the global burden of electrolyte disorders, with an estimate 15–20% of inpatients affected. Gait disorders, falls, confusion, seizures, respiratory arrest, and coma are altogether common causes of morbidity in people with hyponatremia. Although it is difficult to estimate precisely how prevalent this trajectory to death is, as many as 4–10% of deaths from hyponatremia may occur in the hospital setting [1–3]. All patients admitted to the Unit of Internal Medicine of our hospital for any causes over the last year (2034 patients, 71.9% older than 65 yrs) were included in this retrospective study. On admission, serum sodium (measured) and plasma osmolality (calculated) were recorded as a routine examination. Table 1 summarizes the data. Hypotonic hyponatremia (HHN) was detected in 284 patients (13.9%). Of these, 225 (79.2%) had mild HHN (130–134 mmol/L), 39 (13.7%) had moderate HHN (125–129 mmol/L), and 20 (7%) had severe HHN (less than 125 mmol/L). We couldn't establish whether HHN was acute or chronic, because of the design of the study. The median age of patients with HHN (79 yrs, range 27–100) was similar to that of the whole population (76 yrs, range 15–103), with no significant difference in gender (male to female ratio: 0.94). Interestingly, we observed a prevalence of females only in the group of symptomatic HHN (male to female ratio: 0.63), especially when hyponatremia was severe (male to female ratio: 0.53), in accordance with previous studies [2,3], even though the underlying mechanism of this phenomenon has not yet been completely elucidated [4]. Conversely, the reason why the elderly are more susceptible to develop HHN is very likely associated with the aging-related impairment of water excretory capacity and the increased exposure to drugs and diseases associated with HHN [3,5]. Furthermore, besides a gradual decrease in physiological reserve, at least a quarter of people older than 85 yrs are estimated to have the clinical condition of frailty, a state of vulnerability to poor resolution of homeostasis, including water homeostasis, after minor stressor events, with increase of disability and falls [6]. In our series, 235 patients were incidentally found to be hyponatremic and deemed to be asymptomatic (82.7%). The remaining 49 hyponatremic patients (17.3%) were symptomatic. Of course, such a discrepancy could be more apparent than real [7], especially in the setting of elderly inpatients. Of the 49 patients with symptomatic HHN, 26 presented with neurological symptoms (disorientation, seizures, agitation, delirium, confusion,

gait and postural disorders), 13 with falls and trauma (bone fractures or contusions), and 10 with falls without consequences. Severe HHN was present in 20 patients. Surprisingly, of these only 12 had symptomatic hyponatremia associated with evident changes in mental status, seizures, or falls with trauma. However, it is important to highlight that distinguishing symptoms of hyponatremia from symptoms due to underlying diseases is not so easy as expected in an elderly ill inpatient. Furthermore, severe HHN is not synonymous with acute symptomatic HHN. For instance, the chronic use of drugs able to cause inappropriate antidiuresis may sometimes lead to severe HHN (b125 mmol/L) with minor symptoms. On the other hand, 37 patients with mild or moderate HHN had neurological disorders and falls, with or without bone fractures, suggesting a putative relationship between HHN and gait disorders and, perhaps, bone fractures [8,9]. Although the research of the different causes of hyponatremia is beyond the aim of our study, it is of note that most patients with symptomatic HHN (69.4%) were assuming at home diuretics, serotonin re-uptake inhibitors, sodium valproate, haloperidol, or other common drugs related to the development of HHN. We found hospital-associated hyponatremia (HAH) in 96 patients (33.8%). Of these, 89 developed hospital-acquired hyponatremia and 7 hospital-aggravated hyponatremia, from mild–moderate to severe. A defect of water excretion can arise during the hospitalization as a result of antidiuresis (due to medications, pain, severe nausea), organ failure, or infusion of electrolyte-free solutions [3]. Hyponatremia is independently associated with in-hospital mortality [1–3]. There is evidence that any abnormality in water and sodium homeostasis is associated with a poor outcome in certain clinical scenarios, such as congestive heart failure, myocardial infarction, liver cirrhosis, metastatic cancer, cardiovascular diseases, pneumonia, sepsis, and surgical procedures [3,5,8]. In our series, total in-hospital mortality was 4.7% (95 cases), while in the group of hyponatremic patients (24 cases) it was almost two-fold higher (8.5%), with a moderate prevalence of females (male to female ratio: 0.84). The percentage of inpatients with mild (70.8%), moderate (25%), or severe (4.2%) HHN who died was similar to that recorded on admission (79.2%, 13.7%, and 7%, respectively), even though patients with moderate HHN on admission seemed to be a little more subject to in-hospital mortality than patients with mild or severe HHN. In our series, metastatic cancer (9 patients), heart failure (6 patients), liver cirrhosis (3 patients), and sepsis (3 patients) were the most frequent diseases associated with HHN and death. It is difficult to establish whether HHN independently contributes to in-hospital mortality or simply reflects the disease severity; only prospective randomized studies in different groups of patients with HHN, including those with cancer, heart failure, cirrhosis, and drug-induced hyponatremia, could answer this question. Another critical point emerging from our retrospective study is the high percentage of patients (21.8%) discharged with mild or, in two cases, moderate HN. In Europe, shortening hospital length of stay and reducing inpatient beds are common policy objectives, with subsequent

http://dx.doi.org/10.1016/j.ejim.2014.03.013 0953-6205/© 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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Letter to the Editor

Table 1 Prevalence and in-hospital mortality in the cohort study.

No. of patients (%) Median age Age group N79 yrs N69 yrs N84 yrs b70 yrs N65 yrs Sex Males Females Crude in-hospital mortality

Hospital-associated HHN Hospital-acquired HHN Hospital-aggravated HHN HHN on admission Symptomatic HHN

Falls Falls with trauma Neurologic disorders Asymptomatic HHN HHN at discharge

Total

HHN

Mild HHN

Moderate HHN

Severe HHN

2034 (100%) 76 (15–103)

284 (13.9%) 79 (27–100)

225 (79.2%)

39 (13.7%)

20 (7%)

787 (38.7%) 1343 (66%) 468 (23%) 691 (33.9%) 1463 (71.9%)

58 (7.4%) 217 (16.2%) 68 (14.7%) 67 (9.7%) 230 (15.7%)

989 (48.6%) 1045 (51.4%) 95 (4.7%)

136 (47.9%) 148 (52.1%) 24 (8.5%) 13 ♀ (54.2%) 11 ♂ (45.8%) 96 (33.8%) 89 (31.3%) 7 (2.5%) 195 (68.7%) 49 (17.3%) 30 ♀ (61.2%) 19 ♂ (38.8%) 10 13 26 235 (82.7%) 62 (21.8%)

113 (50.2%) 112 (49.8%) 17 (70.8%)

16 (41%) 23 (59%) 6 (25%)

7 (35%) 13 (65%) 1 (4.2%)

29 (59.2%)

8 (16.3%)

12 (24.5%)

HHN: hypotonic hyponatremia.

increase of care intensity for inpatients and some concerns about the safety of health care as well. That being said, the retrospective design of our study does not permit to explain the reason why a high percentage of our patients were discharged with uncorrected HHN. However, in the real life this phenomenon could be more frequent than expected, especially in the era of constraint of health expenditure growth. In conclusion, our data confirm that HHN is all but a rare event in inpatients and increases in-hospital mortality. The need of developing new clinical practice guideline on diagnosis and treatment of hyponatremia is indeed a very welcome effort [10].

Conflict of interest statement All the authors disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organization within three years of beginning the submitted work that could inappropriately influence, or perceived to influence, their work. All the authors realize that the submission of their manuscript implies that the work described has not been published previously, that it is not under consideration for publication elsewhere, and that its publication is approved by all authors and explicitly by the responsible authorities where the work has been carried out.

References [1] Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010;170:294–302. [2] Waikar SS, Mount DB, Curhan GC. Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am J Med 2009;122:857–65.

[3] Mohan S, Go S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med 2013;126:1127–37. [4] Hajjar I, Graves JW. Hyponatremia in older women. J Clin Hypertens 2004;6:37–9. [5] Mannesse CK, Vondeling AM, van Marum RJ, van Solinge WW, Egberts TCG, Jansen PAF. Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: a systematic review. Age Res Rev 2013;12:165–73. [6] Clegg A, Young J, Iliffe S, Rikkert Olde, Rockwood K. Frailty in elderly people. Lancet 2013;381:752. [7] Decaux G. Is asymptomatic hyponatremia really asymptomatic? Am J Med 2006;119:S79–82. [8] Renneboog B, Musch W, Vandermergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficit. Am J Med 2006;119:71.e1–8. [9] Hoorn EJ, Rivadeneira F, Van Meurs JB, Ziere G, Bh Stricker, Hofman A, et al. Mild hyponatremia as a risk factor for fractures: the Rotterdam study. J Bone Mineral Res 2011;26:1822–8. [10] Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170: G1–G47.

Giovanna Elmi Stefania Zaccaroni Vincenzo Arienti Unità di Medicina Interna, Dipartimento Medico Ospedale Bellaria, Azienda USL di Bologna, Italy Marco Faustini-Fustini IRCCS, Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria, Via Altura, 3, 40139 Bologna, Italy Corresponding author. Tel.: +39 0516225062; fax: +39 0516225477. E-mail addresses: [email protected], [email protected]. 10 March 2014

Prevalence and in-hospital mortality of hyponatremia: a cohort study.

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