Hyponatremia and fractures: should hyponatremia be further studied as a potential biochemical risk factor to be included in FRAX algorithms?

The Fracture Risk Assessment Tool (FRAX®) was developed by the WHO Collaborating Centre for metabolic bone diseases to evaluate fracture risk of patients. It is based on patient models that integrate the risk associated with clinical variables and bone mineral density (BMD) at the femoral neck. The clinical risk factors included in FRAX were chosen to include only well-established and independent variables related to skeletal fracture risk. The FRAX tool has acquired worldwide acceptance despite having several limitations. FRAX models have not included biochemical derangements in estimation of fracture risk due to the lack of validation in large prospective studies. Recently, there has been an increasing number of studies showing a relationship between hyponatremia and the occurrence of fractures. Hyponatremia is the most frequent electrolyte abnormality measured in the clinic, and serum sodium concentration is a very reproducible, affordable, and readily obtainable measurement. Thus, we think that hyponatremia should be further studied as a biochemical risk factor for skeletal fractures prediction, particularly those at the hip which carries the greatest morbidity and mortality. To achieve this will require the collection of large patient cohorts from diverse geographical locations that include a measure of serum sodium in addition to the other FRAX variables in large numbers, in both sexes, over a wide age range and with wide geographical representation. It would also require the inclusion of data on duration and severity of hyponatremia. Information will be required both on the risk of fracture associated with the occurrence and length of exposure to hyponatremia and to the relationship with the other risk variables included in FRAX and also the independent effect on the occurrence of death which is increased by hyponatremia.

Maintenance intravenous fluid prescribing practices among paediatric residents.

AIM: To investigate the sodium composition of maintenance intravenous fluids (mIVF) used by paediatric residents throughout the United States in common clinical scenarios of arginine vasopressin (AVP) excess. METHODS: We distributed an online survey to paediatric residency programmes asking what type of mIVF (0.2%, 0.45%, 0.9% NaCl or lactated Ringer's solution) they would administer in four common clinical scenarios of AVP excess (gastroenteritis, pneumonia, meningitis and postoperative) in both a 6-month-old (mo) and a 13-year-old (yo) child. RESULTS: We had 472 responses, representing 5% of the total paediatric residency population in the United States. Hypotonic mIVF were selected in 78% of children (88.2% of 6 mo and 68.5% of 13 yo). Isotonic mIVF were selected approximately twice as often for patients with meningitis as for those without (21.4% vs. 8.7% 6 mo and 42.8% vs. 27.7% 13 yo; p < 0.001). CONCLUSIONS: The majority of US paediatric residents would prescribe hypotonic mIVF in disease states associated with AVP excess. However, a significant number of residents are using isotonic mIVF. Isotonic fluids are more likely to be prescribed in older children and children with meningitis.

Phosphorus balance and mineral metabolism with 3 h daily hemodialysis.

Poor control of mineral metabolism is independently associated with mortality in patients receiving hemodialysis. We analyzed data from a 12-month, prospective, non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3 h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each) (n=51) for achievement of mineral metabolism goals and we performed a substudy of weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35% in the CHD group, P=0.0001). Percentage of patients using phosphate binders decreased from 77 to 40% among subjects on DHD, whereas these parameters did not change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was also associated with an increase in the percent of subjects achieving three or more mineral metabolism goals (for phosphorus, calcium x phosphorus and parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus control by increasing dialytic phosphorus removal while maintaining nutritional status and reducing the use of phosphate binders. The net effect allows for improved achievement of mineral metabolism goals.

Hyponatremia with hypoxia: effects on brain adaptation, perfusion, and histology in rodents.

Hypoxia appears to be a prominent component of brain damage among patients with hyponatremic encephalopathy. Effects of hypoxia on brain in the presence of hyponatremia are not known. In order to evaluate the contributions of hypoxia to brain damage, three separate experiments were conducted in three groups of rodents. Experiment I evaluated the effects of hypoxia and acute (< 4 h) hyponatremia (plasma Na < 120 mmol/l) on brain adaptation in rabbits. Experiment II evaluated the effects of hypoxia and chronic (4 days) hyponatremia on cerebral perfusion in rats. Experiment III evaluated the effects of hypoxia and chronic hyponatremia on brain histology in rats. In experiment I, rabbits with acute hyponatremia demonstrated brain adaptation with significant falls in brain Na content (by 14.2%, P < 0.01) and osmolality (by 8.3%, P < 0.01), and a rise in brain water (by 10.6%, P < 0.05). Rabbits with combined hypoxia and hyponatremia failed to demonstrate brain adaptation. In experiment II, rats with chronic hyponatremia plus hypoxia had a decrease in cerebral perfusion index by more than 50% (P < 0.01). In experiment III, 23% of hypoxic rats had brain lesions, which were in the cerebellum, thalamus, reticular formation, and basal ganglia. Hyponatremia without hypoxia resulted in no brain lesions. Hypoxia in normonatremic animals results in cerebral edema and histopathologic lesions similar to those found in rats whose plasma Na was overcorrected. Hypoxia in hyponatremic animals aggravates cerebral edema, impairs brain adaptation, and decreases cerebral perfusion.

Infectious complications of the hemodialysis access.

Infectious complications of the vascular access are a major source of morbidity and mortality among hemodialysis (HD) patients. Numerous reports implicate the vascular access in up to 48 to 73% of all bacteremias in HD patients. The incidence of vascular access-related infection is highest when central venous dialysis catheters are employed. Native arteriovenous fistulas carry the lowest risk of infection. Unfortunately, prosthetic arteriovenous grafts, which represent the most common type of HD access in the United States, have been repeatedly shown to be a risk factor for bacteremic and nonbacteremic infections. Silent infection in old nonfunctional clotted prosthetic arteriovenous grafts has recently been recognized as a frequent cause of bacteremia and morbidity among HD patients. High proportions of infections related to the vascular access are caused by staphylococcal organisms, which carry high rates of mortality, recurrence, and metastatic complications. Management of vascular access-related infection has two aspects: The first relates to the choice, duration, and mode of administration of antibiotic therapy. Empiric antibiotic therapy, guided by demographic data and severity of illness, should be employed when the causative organisms are unknown. Prolonged administration of specific parenteral antibiotics is crucial in decreasing complications of infection, especially in cases of staphylococcal bacteremia. The second aspect relates to management of the vascular access. Efforts directed toward bacteriological cure should be concurrent with efforts to preserve native venous access sites whenever possible. Efforts to prevent vascular access-related infection should focus on increasing placement of arteriovenous fistulas and minimizing insertion of central venous dialysis catheters. Careful inspection and monitoring of the vascular access is of paramount importance in early detection of vascular access site-related infections. Several new approaches aimed at preventing catheter and prosthetic graft-related infection are being explored.

Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners.

BACKGROUND: Noncardiogenic pulmonary edema is often associated with increased intracranial pressure and can be the initial manifestation of hyponatremic encephalopathy. Marathon runners tend to develop conditions that lead to hyponatremia. OBJECTIVE: To describe the development and treatment of noncardiogenic pulmonary edema in marathon runners that was associated with hyponatremic encephalopathy. DESIGN: Case series. SETTING: One university hospital and two community hospitals. PATIENTS: Seven healthy marathon runners who had a history of nonsteroidal anti-inflammatory drug use. The runners collapsed after competing in a marathon and were hospitalized with pulmonary edema. MEASUREMENTS: Plasma sodium levels, chest radiograph, electrocardiogram, cardiac enzyme levels, and magnetic resonance imaging or computed tomographic scans of the brain. RESULTS: Patients had nausea, emesis, and obtundation. The mean (+/-SD) plasma sodium level was 121 +/- 3 mmol/L, and oxygen saturation was less than 70%. Electrocardiograms and echocardiograms were normal. Chest radiographs showed pulmonary edema with a normal heart. Creatine phosphokinase-MB bands, troponin levels, and pulmonary wedge pressure were not elevated. Scanning of the brain showed cerebral edema. All patients were intubated and mechanically ventilated. Treatment with intravenous NaCl, 514 mmol/L, increased plasma sodium levels by 10 mmol/L in 12 hours. Pulmonary and cerebral edema resolved as the sodium level increased. One patient had unsuspected hyponatremic encephalopathy and died of cardiopulmonary arrest caused by brainstem herniation. All six treated patients recovered and were well after 1 year of follow-up. CONCLUSIONS: In healthy marathon runners, noncardiogenic pulmonary edema can be associated with hyponatremic encephalopathy. The condition may be fatal if undiagnosed and can be successfully treated with hypertonic NaCl.

The changing pattern of hypernatremia in hospitalized children.

OBJECTIVES: Past studies have revealed that hypernatremia occurs primarily in infants with diarrheal dehydration. With improved infant feeding practices and the advent of pediatric critical care medicine, the pattern of hypernatremia in children has likely changed. The purpose of this study was to evaluate the current pattern of hypernatremia in hospitalized children. METHODS: Medical records were reviewed for 68 patients admitted to a large urban children's hospital during a 3-year period, all with a serum sodium greater than 150 mEq/L. The etiologies, predisposing factors, and morbidity and mortality associated with hypernatremia were evaluated. RESULTS: The average patient age was 3.9 years (range, 1 day to 19. 7 years), and the peak serum sodium concentration was 159 mEq/L (range, 151-184 mEq/L). Hypernatremia was hospital acquired in 60% of children. The majority of children (71%) were admitted for reasons other than hypernatremia. In 76% of the patients, inadequate fluid intake was the main cause of hypernatremia. Gastroenteritis contributed to the hypernatremia in only 20% (14 out of 68) of children. Eleven of these were infants <1 year of age with hypernatremia on admission. Eighty-eight percent of patients (60 out of 68) suffered from neurologic impairment, critical illness, chronic disease, or prematurity before developing hypernatremia. The overall mortality was 16%. Patients in whom hypernatremia was not corrected had a significantly higher mortality than those in whom hypernatremia was corrected (4 out of 8 [50%] vs 7 out of 60 [12%]). Peak serum sodium was no different for survivors than nonsurvivors. No deaths were attributable to cerebral edema caused by correction of hypernatremia. Neurologic complications related to hypernatremia occurred in 15% of patients. CONCLUSIONS: Hypernatremia occurs in children of all ages, with the vast majority having significant underlying medical problems. Hypernatremia caused by gastroenteritis in infants has become much less common than previously reported. Hypernatremia is primarily a hospital-acquired disease, produced by the failure to administer sufficient free water to patients unable to care for themselves. Failure to correct hypernatremia may result in a high mortality rate.

Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality.

CONTEXT: Chronic hyponatremia in postmenopausal women is a common clinical problem often viewed as benign. Fluid restriction is usually the recommended therapy, largely because the extent of morbidity is unknown and because it has been postulated that intravenous (IV) sodium chloride may cause brain damage. OBJECTIVE: To compare IV sodium chloride with fluid restriction in the treatment of postmenopausal women with chronic symptomatic hyponatremia. DESIGN: Nonrandomized prospective study. SETTING: Two university medical centers and affiliated community hospitals. PATIENTS: A total of 53 postmenopausal women with chronic symptomatic hyponatremia (chronic plasma sodium <130 mmol/L in the presence of central nervous system manifestations) treated consecutively from 1988-1997 and followed up for 1 year. The mean (SD) age of the patients was 62 (11) years. INTERVENTIONS: The therapeutic interventions were IV sodium chloride before respiratory insufficiency (n = 17), IV sodium chloride after respiratory insufficiency (n = 22), and fluid restriction only (n = 14). MAIN OUTCOME MEASURES: Morbidity and neurological outcome at 4 months or longer as assessed by cerebral performance category (CPC) in relation to the therapy, initial plasma sodium level, and rate of correction. RESULTS: Chronic symptomatic hyponatremia (mean [SD] sodium level 111 [12] mmol/L) was present for 5.2 [4.5] days. Death or major morbidity occurred in 44 (83%) of 53 patients, including 10 with orthopedic injury. Twelve patients had hypoxemia (PO2 = 63 [25] mm Hg) and cerebral edema. Among patients who received IV sodium chloride before respiratory insufficiency, plasma sodium levels were increased by 22 (10) mmol/L in 35 hours and patients had a CPC of 1.0 (normal or slight disability). Among patients who received IV sodium chloride after respiratory insufficiency, plasma sodium levels were increased by 30 (6) mmol/L in 41 hours and patients had a CPC of 3.0 (1.2) (severe disability). Among patients who had fluid restriction only, plasma sodium levels were increased by 3 (2) mmol/L in 41 hours and patients had a CPC of 4.6 (0.7) (4 = persistent vegetative state; 5 = death). The outcomes did not correlate with either the initial plasma sodium level (r=0.05, P>.12) or the rate of correction (r=0.31, P>.10). CONCLUSIONS: Chronic symptomatic hyponatremia in postmenopausal women can be associated with major morbidity and mortality. Therapy with IV sodium chloride was associated with significantly better outcomes than fluid restriction.

The patient with a clotted PTFE graft developing fever.

Haemodialysis access graft infection is easily recognizable when local symptoms (warmth, swelling, pain, or drainage) predominate, and endocarditis is a well established complication of infected grafts. We report a case of bacterial endocarditis complicating silent infection in clotted haemodialysis access graft. It is suggested that, clotted non-functioning grafts may be the harbingers of silent infection, and should be suspected as the source of infection in every haemodialysis patient that presents with fever, even in the absence of clinical signs of graft site infection.

Silent infection in clotted hemodialysis access grafts.

Thrombotic and infectious complications are frequent causes of hemodialysis vascular access failure and contribute considerably to the cost of care for chronic hemodialysis patients. Although there is clear indication for removal of patent grafts in unresolved bacteremia, there are no guidelines for the management of clotted nonfunctioning grafts. To evaluate for the existence and clinical relevance of silent infection in clotted nonfunctioning hemodialysis grafts, a study was conducted with a series of 20 hemodialysis patients who presented with fever (15 patients), or fever and clinical signs of sepsis (five patients), in whom the source of infection was not immediately localized to any organ system. Comparison was made with 21 asymptomatic patients with clotted grafts who served as control subjects. All patients and control subjects came from a pool of 115 chronic hemodialysis patients in an outpatient hemodialysis unit in the Houston metropolitan area, who were on hemodialysis for a period of time ranging from 3 to 15 yr. Indium scans were performed, followed by removal of the clotted grafts in all patients and control subjects. Bacterial cultures of the recovered surgical material and blood were done concomitantly in all study participants. Indium scans showed positive uptake in or around the clotted grafts in all of the patients and in 15 of the control subjects. Purulent material was found in the grafts in all patients and in 13 of 15 indium scan-positive control subjects. When positive, blood culture pathogens were identical to those cultured from the graft material in all instances. The predominant pathogens were Staphylococcus aureus, followed by Staphylococcus epidermidis. There was no evidence of graft infection in the control subjects if indium scan was negative. Chart review dating back to the start of dialysis revealed five past infectious episodes in the patient group, compared with four in the control group. These findings suggest that clotted nonfunctioning grafts are frequent harbingers of infection. They should be suspected as the source of infection in every hemodialysis patient that presents with fever, even in the absence of clinical signs of graft site infection.