Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically.

PA21, a New Iron-Based Noncalcium Phosphate Binder, Prevents Vascular Calcification in Chronic Renal Failure Rats

Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

[Physical and psychological status of 60-70-year-old citizens of Bern with neurotic symptoms in childhood--a study over more than 50 years (Emmental cohort)]

The present study was undertaken to assess the influence of childhood variables (physical and emotional) to later well-being in a group of rural Swiss (Emmental Cohort). Our study is the first prospective cohort over a time period of more than 50 years. It includes 1537 children who were listed and assessed in 1942 (T1) because they had difficulties in school or were otherwise behaviorally disturbed. In 1995 (T2) more than 60% of the initial population could be reassessed by our study group. We found more subjects at T2 who had been rated as intelligent at T1. More subjects responding to T2 belonged to a higher social class, were more anxious, and had more psychosocial problems at T1. Social income at T2 is correlated to the social class at T1. More subjects have died since who were rated at T1 as being less intelligent, less neurotical, and having higher psychosocial problems. Twice as many men died than women. The emotional situation at T2 is significantly correlated to psychological well-being at T1. The somatic complaints at T2 correlate significantly to neurotic symptoms in childhood (T1). The more intelligent the children were rated at T1, the less emotional and somatic complaints were voiced at T2 and the better the psychic well-being was rated (T2). In addition, the former social milieu (T1) significantly determined somatic and psychological complaints at T2. Our data discern a significant correlation between actual status and former childhood variables more than 50 years later in a rural Swiss cohort (Emmental Cohort).

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies

BACKGROUND: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. METHODS: We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per microL, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per microL. FINDINGS: Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per microL was associated with higher rates of AIDS and death than starting therapy in the range 351-450 cells per microL (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per microL compared with initiation at 351-450 cells per microL). INTERPRETATION: Our results suggest that 350 cells per microL should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

D-dimer to Rule Out Pulmonary Embolism in Renal Insufficiency

BACKGROUND D-dimer levels are often elevated in renal insufficiency. The diagnostic accuracy of D-dimer to rule out pulmonary embolism in patients with renal insufficiency is unclear. METHODS We evaluated the data of patients presenting to our Emergency Department and receiving computed tomography angiography to rule out pulmonary embolism with measurement of D-dimer and creatinine. Glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. RESULTS There were 1305 patients included; 1067 (82%) had an estimated glomerular filtration rate (eGFR) exceeding 60 mL/min, 209 (16%) 30-60 mL/min, and 29 (2%) <30 mL/min. One hundred fifty-two patients (12%) had D-dimer below 500 μg/L. eGFR (R = -0.1122) correlated significantly with D-dimer (P <.0001). One hundred sixty-nine patients (13%) were found to have pulmonary embolism. Sensitivity of D-dimer for patients with an eGFR >60 mL/min was 96% (confidence interval [CI], 0.93-0.99) and 100% (CI, 100-100) for those with 30-60 mL/min, while specificity decreased significantly with impaired renal function. Area under the curve of the receiver operating characteristic for D-dimer was 0.734 in patients with an eGFR of >60 mL/min, and 0.673 for 30-60 mL/min. CONCLUSIONS D-dimer levels were elevated in patients with an eGFR <60 mL/min, but proved to be highly sensitive for the exclusion of pulmonary embolism. However, because almost all patients with impaired renal function had elevated D-dimer irrespective of the presence of pulmonary embolism, studies should be performed to determine renal function-adjusted D-dimer cutoffs.

Hypoglycemia is associated with increased mortality in patients with acute decompensated liver cirrhosis

PRINCIPALS The liver plays an important role in glucose metabolism, in terms of glucolysis and gluconeogenesis. Several studies have shown that hyperglycemia in patients with liver cirrhosis is associated with progression of the liver disease and increased mortality. However, no study has ever targeted the influence of hypoglycemia. The aim of this study was to assess the association of glucose disturbances with outcome in patients presenting to the emergency department with acute decompensated liver cirrhosis. METHODS Our retrospective data analysis comprised adult (≥16 years) patients admitted to our emergency department between January 1, 2002, and December 31, 2012, with the primary diagnosis of decompensated liver cirrhosis. RESULTS A total of 312 patients were eligible for study inclusion. Two hundred thirty-one (74.0%) patients were male; 81 (26.0%) were female. The median age was 57 years (range, 51-65 years). Overall, 89 (28.5%) of our patients had acute glucose disturbances; 49 (15.7%) of our patients were hypoglycemic and 40 (12.8%) were hyperglycemic. Patients with hypoglycemia were significantly more often admitted to the intensive care unit than hyperglycemic patients (20.4% vs 10.8%, P < .015) or than normoglycemic patients (20.4% vs 10.3%, P < .011), and they significantly more often died in the hospital (28.6% hypoglycemic vs 7.5% hyperglycemic, P < .024; 28.6% hypoglycemic vs 10.3% normoglycemic P < .049). Survival analysis showed a significantly lower estimated survival for hypoglycemic patients (36 days) than for normoglycemic patients (54 days) or hyperglycemic patients (45 days; hypoglycemic vs hyperglycemic, P < .019; hypoglycemic vs normoglycemic, P < .007; hyperglycemic vs normoglycemic, P < .477). CONCLUSION Hypoglycemia is associated with increased mortality in patients with acute decompensated liver cirrhosis. It is not yet clear whether hypoglycemia is jointly responsible for the increased short-term mortality of patients with acute decompensated liver cirrhosis or is only a consequence of the severity of the disease or the complications.

Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency

In the present study, we wanted to (1) evaluate whether high-sensitive troponin T levels correlate with the grade of renal insufficiency and (2) test the accuracy of high-sensitive troponin T determination in patients with renal insufficiency for diagnosis of acute myocardial infarction (AMI). In this cross-sectional analysis, all patients who received serial measurements of high-sensitive troponin T from August 1, 2010, to October 31, 2012, at the Department of Emergency Medicine were included. We analyzed data on baseline characteristics, reason for referral, medication, cardiovascular risk factors, and outcome in terms of presence of AMI along with laboratory data (high-sensitive troponin T, creatinine). A total of 1,514 patients (67% male, aged 65 ± 16 years) were included, of which 382 patients (25%) had moderate to severe renal insufficiency and significantly higher levels of high-sensitive troponin T on admission (0.028 vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T correlated inversely with the estimated glomerular filtration rate (R = -0.12, p <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to 0.51). The area under the curve of the receiver operating characteristic for all patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029) for patients with a Modification of Diet in Renal Disease estimated glomerular filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535 (SE 0.056) for patients with moderate to severe renal insufficiency presenting with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for presence of AMI of a baseline measurement of high-sensitive troponin in patients with renal insufficiency was poor and resembles tossing a coin.

High-Sensitive Troponin Measurement in Emergency Department Patients Presenting with Syncope: A Retrospective Analysis

OBJECTIVE To study the relevance of high-sensitive troponin measurements in the acute workup in patients admitted to the emergency department of a large university hospital due to syncope. METHODS In this retrospective study all patients admitted to the emergency department because of syncope of the Inselspital, University Hospital Bern between 01 August 2010 and 31 October 2012, with serial determination of high-sensitive troponin (baseline and three hours control) were included. Of all identified patients we obtained data on demographics, laboratory data, ECG as well as on outcome. A change in high-sensitive troponin in the three hours control of +/-30% compared to baseline was considered significant. RESULTS A total of 121 patients with a mean age of 67 years (SD 16) were included in the study. 79 patients (65%) were male and 42 (35%) were female. There was no significant difference in the median high sensitive-troponin level at baseline and in the three hours control (0.01 mcg/L [0.003 to 0.022] versus 0.011 mcg/L [0.003 to 0.022], p = 0.47). Median percent change in high-sensitive troponin level between baseline and control was 0% (-9.1 to 5). 51 patients (42%) had elevated high-sensitive troponin levels at baseline with 7 patients (6%) showing a dynamic of +/-30% change from the baseline measurement in the 3 hours control. 3 of these patients received coronary angiography due to the dynamic in high-sensitive troponin, none of whom needed intervention for coronary revascularization. CONCLUSIONS On basis of the current study, where no single patient took benefit from determination of high-sensitive troponin, measurement of cardiac troponins should be reserved for patients with syncope presenting with symptoms suggestive for the presence of an acute cardiac syndrome.

Hypernatremia in critically ill patients

Hypernatremia is common in intensive care units. It has detrimental effects on various physiologic functions and was shown to be an independent risk factor for increased mortality in critically ill patients. Mechanisms of hypernatremia include sodium gain and/or loss of free water and can be discriminated by clinical assessment and urine electrolyte analysis. Because many critically ill patients have impaired levels of consciousness, their water balance can no longer be regulated by thirst and water uptake but is managed by the physician. Therefore, the intensivists should be very careful to provide the adequate sodium and water balance for them. Hypernatremia is treated by the administration of free water and/or diuretics, which promote renal excretion of sodium. The rate of correction is critical and must be adjusted to the rapidity of the development of hypernatremia.

Rising serum sodium levels are associated with a concurrent development of metabolic alkalosis in critically ill patients

PURPOSE Changes in electrolyte homeostasis are important causes of acid-base disorders. While the effects of chloride are well studied, only little is known of the potential contributions of sodium to metabolic acid-base state. Thus, we investigated the effects of intensive care unit (ICU)-acquired hypernatremia on acid-base state. METHODS We included critically ill patients who developed hypernatremia, defined as a serum sodium concentration exceeding 149 mmol/L, after ICU admission in this retrospective study. Data on electrolyte and acid-base state in all included patients were gathered in order to analyze the effects of hypernatremia on metabolic acid-base state by use of the physical-chemical approach. RESULTS A total of 51 patients were included in the study. The time of rising serum sodium and hypernatremia was accompanied by metabolic alkalosis. A transient increase in total base excess (standard base excess from 0.1 to 5.5 mmol/L) paralleled by a transient increase in the base excess due to sodium (base excess sodium from 0.7 to 4.1 mmol/L) could be observed. The other determinants of metabolic acid-base state remained stable. The increase in base excess was accompanied by a slight increase in overall pH (from 7.392 to 7.429, standard base excess from 0.1 to 5.5 mmol/L). CONCLUSIONS Hypernatremia is accompanied by metabolic alkalosis and an increase in pH. Given the high prevalence of hypernatremia, especially in critically ill patients, hypernatremic alkalosis should be part of the differential diagnosis of metabolic acid-base disorders.

Evaporation of free water causes concentrational alkalosis in vitro

BACKGROUND The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.

Electrolyte disorders and in-hospital mortality during prolonged heat periods: a cross-sectional analysis

BACKGROUND Heat periods during recent years were associated with excess hospitalization and mortality rates, especially in the elderly. We intended to study whether prolonged warmth/heat periods are associated with an increased prevalence of disorders of serum sodium and potassium and an increased hospital mortality. METHODS In this cross-sectional analysis all patients admitted to the Department of Emergency Medicine of a large tertiary care facility between January 2009 and December 2010 with measurements of serum sodium were included. Demographic data along with detailed data on diuretic medication, length of hospital stay and hospital mortality were obtained for all patients. Data on daily temperatures (maximum, mean, minimum) and humidity were retrieved by Meteo Swiss. RESULTS A total of 22.239 patients were included in the study. 5 periods with a temperature exceeding 25 °C for 3 to 5 days were noticed and 2 periods with temperatures exceeding 25 °C for more than 5 days were noted. Additionally, 2 periods with 3 to 5 days with daily temperatures exceeding 30 °C were noted during the study period. We found a significantly increased prevalence of hyponatremia during heat periods. However, in the Cox regression analysis, prolonged heat was not associated with the prevalence of disorders of serum sodium or potassium. Admission during a heat period was an independent predictor for hospital mortality. CONCLUSIONS Although we found an increased prevalence of hyponatremia during heat periods, no convincing connection could be found for hypernatremia or disorders of serum potassium.

Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.