Mild Chronic Hyponatremia Research Articles

Does hyponatremia pose a risk factor for hip fractures in the elderly? Can a primary physician prevent it?

Fracture around the hip is amongst the most common and serious fractures in the elderly, which leads to significant morbidity and mortality. In literature, many authors noted that even mild hyponatremia adversely affects bone, leading to an increased incidence of fractures. We aim to determine whether chronic hyponatremia (>90-day duration) increases the risk of hip fracture in the elderly and whether primary care physicians can help to prevent it. During the period from January 2020 to March 2022, we identified 145 patients aged between 65 and 90 years who were admitted to the hospital with hip fractures following a fall and compared them with 140 healthy controls. We recorded sodium (Na) serum levels in all included patients at the time of arrival and consequently for 3 days and compared them with those of controls. Logistic regression was used to calculate odds ratios (ORs). We measured serum Na levels for 3 days and took the average to ascertain hyponatremia. In the study, the odds of hyponatremia were 70.3% with a confidence interval of 95% versus 3.6% in controls (P = 0.05). Age and hyponatremia were strongly associated with hip fractures following a fall. With a 5-year increase in age, the univariate OR for hip fracture increased by 5.67 (P < 0.0001). After adjusting for age, cases were nearly six times more likely to be hyponatremic than controls (OR = 4.90, P = 0.04). In our study, we noted that even mild chronic hyponatremia in old age increased the chance of falls. Addressing hyponatremia in the elderly may reduce the risk of falls and minimize hip fractures.

CNSC-03. NEURONAL INTERMEDIATE FILAMENT (NIF) ANTIBODY POSITIVE PARANEOPLASTIC SYNDROME IN A PATIENT WITH METASTATIC NEUROENDOCRINE PANCREATIC CARCINOMA AND TREATMENT WITH IPILIMUMAB/NIVOLUMAB

Abstract Immune checkpoint inhibitors, such as ipilimumab (CTL-4) and nivolumab (PD-1) have shown effectiveness in many types of neoplasia. This combination has been used as salvage immunotherapy for high grade metastatic pancreatic carcinoma. Nevertheless, severe neurologic immune-mediated adverse effects can result from the use of this treatment. We present a case of a 64-year-old woman with metastatic neuroendocrine pancreatic carcinoma with abrupt left facial and oculomotor cranial nerve palsy as well spastic tetraplegia after one dose of ipilimumab/nivolumab. She had a history of sudden onset diplopia, fever and ground-level fall a few hours after her initial dose of immunotherapy. Initial laboratory assessment showed pronounced lymphocyte predominant leukocytosis and mild chronic hyponatremia. In the following hours, she developed right mydriasis, right sided fast phase nystagmus and right central facial paralysis along with weakness and spasticity in four extremities. Neuroimaging of brain, orbits and CTL spine showed enhancement of intra-orbital and intracranial optic nerves as well chiasm, linear enhancement from C4-C7 and cauda equina, as well as abnormal signal along thoracic spinal cord and conus medullaris. Routine EEG demonstrated non-etiology specific encephalopathy. Lumbar puncture had normal opening pressure, mild pleocytosis, hyper-proteinorrhachia and normal glucose. Viral panel and cytology in the CSF were negative, and myeline basic protein was elevated. She was treated with high dose steroids which improved overall strength and CN palsies. Twenty days after initial presentation, she suddenly developed hypotension, tachypnea, and altered cognition. The patient and family opted for comfort measures only. She passed away that same day. Late report of CSF antibody panels showed positive cell-based assay for heavy and light chain NIF with a titer of 1:512. This case emphasizes the importance of recognition of anti-body mediated paraneoplastic syndromes in patients treated with immunotherapy, their appropriate treatment and prognosis.

Chronic hyponatremia in the elderly: association with geriatric syndromes (review of literature)

Hyponatremia is more common in the elderly. A number of studies suggest that even mild chronic hyponatremia is a serious danger, increasing the risks of developing geriatric syndromes, falls, low bone density, fractures, cognitive impairment, and death of all causes. Although the mechanism for the development of such complications is currently not completely clear. Questions remain about the need and methods for correcting this condition, although there is some evidence that the correction of hyponatremia improves cognitive functions, postural balance, minimizing the risk of falls and fractures. These issues are addressed in this review of the literature.

Prevalence of mild hyponatremia and its association with falls in older adults admitted to an emergency geriatric medicine unit (the MUPA unit)

BackgroundHyponatremia is the most common electrolyte disorder in older adults and it can increase morbidity and mortality. Approximately one in three older adults fall each year; mild chronic hyponatremia can predispose this group to injurious falls and fractures and serum levels of sodium can also influence bone health. Little is known regarding the association between mild chronic hyponatremia and injurious fall prevalence in elderly patients admitted to the Emergency Department (ED). Therefore, the present study investigated the link between mild hyponatremia and the risk of injurious falls in elderly patients admitted to the Emergency Geriatric Medicine Unit (The MUPA Unit).MethodsThis cross-sectional study was conducted over 4 months and included patients ≥75 years of age who were admitted to the MUPA Unit of University Hospital Center of Limoges (France). Sociodemographic factors, fall events, comorbidities, medications, and sodium levels were assessed (hyponatremia was considered as sodium level < 136 mEq/L). Additionally, the short Comprehensive Geriatric Assessment (short-CGA), the Frailty score on the Short Emergency Geriatric Assessment (SEGA), and the Katz Activity of Daily Living (ADL) scale were administered.ResultsOf the 696 cases included in the final analysis, the mean age was 86.1 ± 5.6 years and 63.1% were female. The prevalence of falls was 27.9% (95% confidence interval [CI]: 24.6–31.2%) and that of mild hyponatremia was 15.9% (95% CI: 13.2–18.6%). The prevalence rate of mild hyponatremia was 13.2% (95% CI: 10.1–16.3%) in patients without falls and 26.1% (95% CI: 19.8–32.4%) in patients admitted for falls. Mild hyponatremia was significantly associated with falls (P < 0.001) and the adjusted odds ratio (OR) was 3.02 (95% CI: 1.84–4.96).ConclusionsBecause mild hyponatremia might be a risk factor for injurious falls and ED admission, determination of sodium levels during basic biomarker assessment on ED admission could be an important component of fall prevention strategies for the elderly.

Mild Chronic Hyponatremia and Osteoporotic Fractures Risk in Elderly

Low serum sodium levels were associated with increased prevalence of osteoporosis and fractures. The aim of the study was to assess the relationship between serum sodium and bone mineral density and/or osteoporotic fractures� prevalence in elderly people. A total number of 260 patients (23 men / 237 women), aged 66.5 � 12.8 years, were retrospectively assessed. Serum sodium levels were measured in all patients. Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). Results: serum natremia was 140.3 � 4.4 mmol/L; prevalence of hyponatremia was 7.3%; frailty fractures were present in 117 out of 260 patients (45%). Patients with fractures had lower serum sodium levels as compared to patients without fractures (139 � 3.9 vs. 141.5 � 4.6 mmol/L, p [ 0.001). Patients with osteoporosis (n = 179) also showed lower natremia as compared to patients with normal BMD and osteopenia (n = 81): 139.9 � 4.7 vs. 141.2 � 3.8 mmol/L, p = 0.035. In patients admitted in the hospital for fractures (n = 92), prevalence of hyponatremia was 13.04%. Hyponatremic patients had significantly higher prevalence of fractures (73.7% vs. 42.7%, p = 0.0147) as compared to normonatremic patients. Odds ratio (OR) for fractures in patients with hyponatremia was 3.75 [95% C.I.: 1.3-10.75], p = 0.0138; OR for hip fractures in patients with hyponatremia was 3.65 [95% C.I.: 1.38-9.64], p = 0.0089. Both incidence and prevalence of hyponatremia increase with age, especially in patients treated with diuretics. Several clinical studies found an association between mild chronic hyponatremia in elderly and increased odds ratio of osteoporosis at the total and at femoral neck; the study also showed an increased odds ratio for all fractures and for hip fractures in hyponatremic patients. Elderly people at risk of osteoporotic fractures should have sodium serum measured.

Electrolyte disturbances in geriatric patients with focus on hyponatremia

Disturbances of water and electrolyte balance are commonly encountered in older patients due to a multitude of physiological changes and preexisting morbidities with hyponatremia being the most common disorder. Even mild chronic hyponatremia can lead to cognitive deficits and gait instability and is associated with an increased rate of falls and fractures. Additionally, experimental and epidemiological data suggest that hyponatremia promotes bone resorption and therefore increases the risk of osteoporosis. Furthermore, osteoporosis and sarcopenia can be stimulated by hypomagnesemia. Hypernatremia often only results in unspecific symptoms but the condition is associated with a clearly increased mortality. As electrolyte disturbances have a high prevalence in the geriatric population and can contribute to geriatric syndromes and frailty, relevant electrolyte alterations should be excluded in all geriatric patients, in particular after a change in medication schedules.

Mild prolonged chronic hyponatremia and risk of hip fracture in the elderly.

Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 ± 5 mmol/L in hyponatremic patients and 139 ± 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking.

Complications and management of hyponatremia.

Hyponatremia causes significant morbidity, mortality, and disability. This review considers the literature of the past 18 months to improve understanding of these complications and to identify therapeutic strategies to prevent them. Acute hyponatremia causes serious brain swelling that can lead to permanent disability or death. A 4-6 mEq/l increase in serum sodium is sufficient to reverse impending herniation. Brain swelling is minimal in chronic hyponatremia, and to avoid osmotic demyelination, correction should not exceed 8 mEq/l/day. In high-risk patients, correction should not exceed 4-6 mEq/l/day. Inadvertent overcorrection of hyponatremia is common and preventable by controlling unwanted urinary water losses with desmopressin. Even mild chronic hyponatremia is associated with increased mortality, attention deficit, gait instability, osteoporosis, and fractures, but it is not known if the correction of mild hyponatremia improves outcomes. Controlled trials are needed to identify affordable treatments for hyponatremia that reduce the need for hospitalization, decrease hospital length of stay, and decrease morbidity. Such trials could also help answer the question of whether hyponatremia causes excess mortality or whether it is simply a marker for severe, lethal, underlying disease.

Mild Chronic Hyponatremia in the Ambulatory Setting: Significance and Management.

Mild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.

Mild hyponatremia is associated with functional and cognitive decline in chronic hemodialysis patients.

A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment. To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period. Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS < 80 and impaired executive function as a Trails A performance time > 75 seconds and Trails B > 180 seconds. 56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS < 80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V < 1.2, p = 0.023), high plasma phosphorus levels (p > 6 mg/dL, p = 0.034), and hyponatremia (Na < 135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002). A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH.

Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.

Management of hyponatremia in various clinical situations.

Hyponatremia is the most common electrolyte abnormality in both inpatient and outpatient settings. The condition primarily results from the combination of impaired free water excretion due to elevated vasopressin levels in conjunction with a source of free water intake. Recent studies have revealed that even mild and asymptomatic hyponatremia is associated with deleterious consequences. It is an independent risk factor for mortality and is also associated with increased length of hospitalization and hospital costs. Even mild chronic hyponatremia can result in subtle neurologic impairment and bone demineralization, leading to falls and associated bone fractures in the elderly. Hyponatremia can be a difficult condition to treat, with varying therapeutic strategies based on the etiology, severity, duration, and extent of neurologic symptoms. The ideal magnitude of correction is also controversial, as both inadequate therapy and overly aggressive therapy can result in neurologic injury. Formulas that have been devised to aid in the treatment of hyponatremia can be inaccurate in that they fail to adequately account for the renal response to therapy. Hyponatremic encephalopathy is the most serious complication of hyponatremia, and can result in permanent neurologic impairment or death if left untreated. Individuals most at risk for developing hyponatremic encephalopathy are postmenarchal women, children under 16years of age, patients with central nervous system disease or hypoxemia, and patients in the postoperative setting. The preferred therapy for hyponatremic encephalopathy is a 100-ml bolus of 3% sodium chloride (513mEq/L) administered in repeated doses until symptoms reverse, with the goal of increasing the serum sodium 5-6mEq/L. Vasopressin (V2) antagonists (vaptans) are not appropriate for the management of acute hyponatremic encephalopathy, as the onset of action is not sufficiently rapid and the increase in sodium is not predictable. Vaptans are primarily indicated for the treatment of asymptomatic hyponatremia due to SIAD that is refractory to conventional measures.

The use of vasopressin receptor antagonists in hyponatremia

Introduction: Considerable data have recently characterized hyponatremia as fairly common in the intensive care and general hospital settings. Moreover, mounting evidence suggests the association of mild degrees of hyponatremia with untoward neurocognitive and musculoskeletal outcomes. A key development in our ability to treat hyponatremia was the introduction and approval of aquaretics (vaptans). These vasopressin receptor antagonists work by increasing electrolyte-free water excretion and thus raising serum sodium concentration.Areas covered: This review presents a diagnostic approach for hyponatremia and discusses some therapeutic considerations. It displays new evidence linking mild chronic hyponatremia with unfavorable outcomes and examines the available treatment options and their limitations and strengths. New data on vaptans and their potential role to treat hyponatremia in different clinical settings are reviewed.Expert opinion: Vaptans are likely to play an important role in treating hyponatremia, given their clinical efficacy and tolerability. High cost remains an impediment for vaptans, and more studies are needed to further define their best use in hyponatremic patients.

Hyponatremia

In addition to the causes of gait disturbances in old age that were listed in the article I wish to mention another cause of gait disturbances that has hardly received any attention but is clinically highly relevant. Patients with mild chronic hyponatremia fall notably more frequently than patients with normal serum concentrations of sodium. Hyponatremia affects gait more strongly than a blood alcohol concentration of 0.6 g/L. Gait disturbances are reversible after the hyponatremia has been corrected (1). In older patients, hyponatremia is associated with fractures (2). Hyponatremia is twice as common in patients with fractures as in those admitted without fractures. The cause of the gait disturbance is “hyponatremic encephalopathy,” which is probably the result of a decrease of important, functional, intracellular osmolytes in the brain, such as glutamate and glutamine, in the context of volume adaptation of the brain (3). Further, signs of a reversible decrease in peripheral nerve conduction velocity has been observed in hyponatremia. According to a large study, 14.5% of patients have hyponatremia on admission to hospital (4). Often this is associated with certain medications. Often, patients develop hyponatremia while receiving treatment with hydrochlorothiazide (HCT), after taking medications that have a neurological effect (antidepressants), or while being treated with carbamazepine. It is likely that the number of hospital admissions owing to falls could be reduced if we paid more attention to hyponatremia and reacted appropriately. Diagnostic and therapeutic algorithms are available for this purpose.

Salt-free diet and pregnancy-related central pontine myelinolysis: “To diet or not?”

Central pontine myelinolysis (CPM) is a rare medical condition that has primarily been associated with alcoholism, chronic malnutrition, certain surgical procedures, and serum sodium imbalances with rapid correction [1]. The condition has also been reported to be pregnancy-related, however complicated by hyperemesis gravidarum [2, 3], resulting in electrolyte disturbances, including hypokalemia [2] and possible hyponatremia [3]. Our present case further points out that CPM with minimal symptoms, could develop in normal pregnancy and could only be related to habitual salt-free diet. A previously healthy, normotensive, 38-year-old Greek female, gravida 1, 28 weeks pregnant, complained of right hemifacial paresthesias of increasing intensity over 10 days and was referred by her gynecologist for further evaluation. She had a 2-year history of salt-free diet, due to personal dietary habits, as well as no alcohol use. The neurological examination was normal, except for mild, right facial hypesthesia over the second trigeminal division. Extensive hematological and biochemical tests, including serum B12, folate, potassium, calcium, homocysteine, collagen, liver, kidney, venereal, viral, immunological disease, protein S and C, anticardiolipin antibodies, lupus anticoagulant and coagulation studies were either normal or unrevealing except for serum sodium level of 130 mmol/l (normal range 135–145 mmol/l). Brain MRI demonstrated a prominent hyperintensity in the central pons on T2 (Fig. 1a), FLAIR (Fig. 1b) and diffusion (Fig. 1c) weighted images (WI) and was compatible with CPM [1, 2]. The pontine lesion was not detected on T1WI and no contrast was given due to the pregnancy. Subsequently, CSF examination (cytochemistry, antibodies detection, electrophoresis) provided normal findings. She was only consulted to return to a ‘‘normal salt’’ diet and was discharged from the hospital. Two months later, after an uncomplicated delivery, the patient gave birth to a normal baby, the facial paresthesias had completely resolved, the serum sodium level was 142 mmol/l, nevertheless repeat MRI showed partial resolution of the central pontine hyperintensity on T2 (Fig. 2a), FLAIR (Fig. 2b) and diffusion WI (Fig. 2c). T1WI remained unrevealing, even after gadolinium infusion. Although there are mechanisms proposed for the pathogenesis of CPM [1], the exact pathophysiology remains unknown [1, 2]. In low serum sodium situations water flowing freely across cell membranes, causes vasogenic brain edema [1, 2] and indeed early pathological changes in CPM typically show microscopic intramyelinic edema and not demyelination [4]. In correcting the hyponatremia, if the rate of rise in tonicity is faster than the rate at which organic osmoles can be synthesized and/or transported into the cells, the cells will shrink and brain dehydration results in injury to oligodendrocytes [1, 2], with predilection of the lesion to the pons [1]. Nevertheless, there is still some controversy because CPM has been described in patients with normal serum sodium concentrations [3]. Additionally, patients with mild–chronic hyponatremia and slowly progressive replacement can also develop CPM, suggesting that some background predisposition is essential to the disease development [5]. The prognosis of CPM cases is highly variable, sometimes even fatal [1, 6] and other times P. Ioannidis (&) G. Balamoutsos D. Karacostas B’ Department of Neurology, AHEPA University Hospital, 54636 Thessaloniki, Greece e-mail: ioannidispanos@yahoo.gr

Bone Disease as a New Complication of Hyponatremia

Brain injury is the main result of acute symptomatic hyponatremia, and it is associated with significant morbidity and mortality (1,2). The symptoms of hyponatremic encephalopathy primarily result from cerebral edema, which is caused by an influx of water into the brain down a concentration gradient (2). Patients at high risk for this complication include postoperative patients, young female individuals, children, and patients with hypoxia or central nervous system disease (1–3); however, although the brain seems to be the main target for hyponatremia, it can no longer be considered the only organ affected by this condition. Recent information indicates that the systemic effects of hyponatremia also affect other organs. Lung abnormalities, such as respiratory failure as a consequence of hyponatremic encephalopathy, have been described (4). One distinct aspect of this condition is the so-called Ayus-Arieff syndrome: A form of noncardiogenic pulmonary edema secondary to increased intracranial pressure from cerebral edema (5–7). Can bone abnormalities be a consequence of hyponatremia? In 1999, our group noted that for a large percentage of elderly women, orthopedic injury was the presenting manifestation of hyponatremic encephalopathy (8). It has subsequently been confirmed that mild chronic hyponatremia, mean serum sodium (SNa) 128 mEq/L, in adults can result …

Response to Letter Regarding Article, “Heart Failure Is a Risk Factor for Orthopedic Fracture: A Population-Based Analysis of 16 294 Patients”

HomeCirculationVol. 120, No. 2Response to Letter Regarding Article, “Heart Failure Is a Risk Factor for Orthopedic Fracture: A Population-Based Analysis of 16 294 Patients” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, “Heart Failure Is a Risk Factor for Orthopedic Fracture: A Population-Based Analysis of 16 294 Patients” Sean van Diepen, MD and Justin A. Ezekowitz, MBBCh, MSc Sumit R. Majumdar, MD, MPH and Finlay A. McAlister, MD, MSc Jeffrey A. Bakal, PhD Sean van DiepenSean van Diepen Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada Search for more papers by this author and Justin A. EzekowitzJustin A. Ezekowitz Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada Search for more papers by this author Sumit R. MajumdarSumit R. Majumdar Division of General Medicine, Department of Medicine, University of Alberta, Edmonton, Canada Search for more papers by this author and Finlay A. McAlisterFinlay A. McAlister Division of General Medicine, Department of Medicine, University of Alberta, Edmonton, Canada Search for more papers by this author Jeffrey A. BakalJeffrey A. Bakal Canadian VIGOUR Center, University of Alberta, Edmonton, Canada Search for more papers by this author Originally published14 Jul 2009https://doi.org/10.1161/CIRCULATIONAHA.109.850834Circulation. 2009;120:e12Reeder and Anderson suggest that hyponatremia and falls may be responsible for the observed association between heart failure (HF) and fractures.1 Whereas it is certainly possible that hyponatremia may explain some of the observed association between HF and fracture, the studies they cite either did not report the prevalence of HF2 or specifically excluded patients with HF.3 Thus, whether an association between hyponatremia and falls exists in patients with chronic HF is unknown.Our study adds to published basic and clinical research implicating hyperaldosteronism, elevated parathyroid hormone, and low vitamin D levels in patients with HF with low bone-mineral density.4–5 A limitation of studies using administrative datasets such as ours is a lack of laboratory values and direct information on the cause of falls. Thus, we cannot examine the association between serum sodium levels and fall risk. We excluded or controlled for fall risk factors, and a matching analysis was performed in our study in an attempt to control for unmeasured variables; the results remain unaltered, strengthening the conclusions of our study. Nevertheless, Reeder and Anderson’s suggestion is worthy of evaluation in subsequent studies.DisclosuresNone. References 1 van Diepen S, Majumdar SR, Bakal JA, McAlister FA, Ezekowitz JA. Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16 294 patients. Circulation. 2008; 118: 1946–1952.LinkGoogle Scholar2 Gankam Kengne F, Andres C, Sattar L, Melot C, Decaux G. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM. 2008; 101: 583–588.CrossrefMedlineGoogle Scholar3 Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006; 119: e1–e8.CrossrefGoogle Scholar4 Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso V, McMahon DJ. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med. 1997; 103: 197–207.CrossrefMedlineGoogle Scholar5 Chhokar VS, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, Smith RA, Gerling IC, Weber KT. Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation. 2005; 22: 111: 871–878.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 14, 2009Vol 120, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.109.850834 Originally publishedJuly 14, 2009 PDF download Advertisement SubjectsCongenital Heart Disease

Is Asymptomatic Hyponatremia Really Asymptomatic?

Consequences of hyponatremia are generally mild and remain unnoticed by both physician and patient. When water restriction, usually prescribed to avoid water intoxication, fails to normalize serum sodium values, clinicians will tolerate mild stable hyponatremia (especially when serum sodium is >125 mEq/L [1 mEq/L = 1 mmol/L]). In a recent study, we observed that mild chronic hyponatremia contributes to an increased rate of falls, probably due to impairment of attention, posture, and gait mechanisms. Eight attention tests were used to assess 16 patients with asymptomatic hyponatremia (mean serum sodium, 128 ± 3 mEq/L) due to syndrome of inappropriate antidiuretic hormone secretion. On attention tests for visual and auditory stimuli, there was an increase in mean response latency of 58 msec ( P <0.001) and an increase in total error number of 20% ( P <0.001). The results of 3 stereotyped steps on a platform “in tandem” with eyes open, expressed as total traveled way of center of pressure, was also different in patients with hyponatremia (mean serum sodium, 128 ± 3 mEq/L) when compared with normonatremic patients (1.3 vs 1 m; P <0.003). Noteworthy, in volunteers of similar age, after mild alcohol intake (0.55 g/kg body weight), attention and gait tests were less affected. In another series of 122 consecutive patients hospitalized from the emergency room with mild hyponatremia, approximately 21% were admitted for falls. After controlling for age, sex, and other known risk factors for falls, the adjusted odds ratio for falls in patients with hyponatremia was 67, compared with a control group. These data show that the concept of asymptomatic hyponatremia does not withstand a detailed epidemiologic analysis of falls or of sensitive posture, gait, and attention tests.

Mild Chronic Hyponatremia Is Associated With Falls, Unsteadiness, and Attention Deficits

Objective The study objective was to determine the eventual consequences (falls, unsteadiness, and cognitive impairment) of mild chronic hyponatremia, which is generally considered as asymptomatic. Methods In a case-control study, we focused on the incidence of falls among 122 patients (mean age 72 ± 13 years) with asymptomatic chronic hyponatremia (mean serum sodium concentration [SNa] 126 ± 5 mEq/L), who were admitted to the medical emergency department, compared with 244 matched controls. To explore the mechanisms of the excess of falls, we prospectively asked 16 comparable patients (mean age 63 ± 15 years; SNa ± 2 mEq/L) to perform 8 attention tests and a gait test consisting of 3 steps “in tandem,” in which we measured the “total traveled way” by the center of pressure or total traveled way. Thereafter, the patients were treated and tested again (50% of the patients were tested first with normal SNa to avoid learning biases). Results Epidemiology of falls: Twenty-six patients (21.3%) of 122 were admitted for falls, compared with only 5.3% of the control patients (adjusted odds ratio: 67; 95% confidence: 7.5-607; P <.001). The frequency of falls was the same regardless of the level of hyponatremia. Gait: The total traveled way by the center of pressure significantly increased in hyponatremia (1336 ± 320 mm vs 1047 ± 172 mm with normal SNa; P = .003). Attention tests: The mean response time was 673 ± 182 milliseconds in hyponatremia and 615 ± 184 milliseconds in patients with normal SNa (difference: 58 milliseconds, P <.001). The total error number in hyponatremia increased 1.2-fold ( P = .001). These modifications were comparable to those observed after alcohol intake in 10 volunteers. Conclusions Mild chronic hyponatremia induces a high incidence of falls possibly as the result of marked gait and attention impairments. Treating these patients might prevent a considerable number of hospitalizations.