Mean Sodium Research Articles

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. Prospective cohort study. Eleven ICUs in Australia and New Zealand. Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. None. Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Intraoperative Factors Associated With Early Recipient Death After Adult-to-Adult Living Donor Liver Transplant.

Living donor liver transplant is the gold standard therapy for patients with terminal hepatic disorders for whom no alternative therapy is available. The primary aim was to assess different intraoperative factors that may predict early death after adult-to-adult living donor liver transplant. The secondary aim was to assess the effect of small-for-size syndrome on mortality. This retrospective multicenter cohort study was performed on records from 145 adults with cirrhosis who had received a right lobe living donor liver transplant. Patients were divided according to the occurrence of short-term mortality (death within the first month after transplant). The primary intraoperative parameters included graft weight, surgical duration, mean blood pressure, serum lactate and sodium bicarbonate, transfusions, durations of cold and warm ischemia and anhepatic phase, input and output during surgery, and portal venous pressures. There were statistically significant variations between both cohorts for number of units of packed red blood cells, durations of cold and warm ischemia and anhepatic phase, preclamp and postreperfusion portal venous pressures, average urine output, mean serum lactate, mean blood pressure, and surgical duration (P ⟨ .001). Also, there were significant differences in the number of platelets, units of fresh frozen plasma, and mean sodium bicarbonate (P = .025, .003, and .035, respectively). Of the 25 patients who died within the early postoperative period, 20 had developed small-for-size syndrome (P ⟨ .001). A variety of intraoperative risk factors may affect early posttransplant mortality, which suggests the high complexity of living donor liver transplants and the need for well-trained experienced teams to perform these surgeries.

Prognostic impact of hyponatraemia and hypernatraemia at admission and discharge in heart failure patients with preserved, mid-range and reduced ejection fraction.

Hyponatraemia is common in patients with acute heart failure (HF). To determine the impact of sodium disturbances on mortality and readmissions in HF with reduced left ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and mid-range ejection fraction (HFmrEF). This study was a prospective multicentre consecutive registry in 20 hospitals, including patients admitted due to acute HF in cardiology departments. Sodium <135 mmol/L was considered hyponatraemia, >145 mmol/L hypernatraemia and 135-145 mmol/L normal. A total of 1309 patients was included. Mean age was 72.0 ± 11.9 years, and 810 (61.9%) were male. Mean serum sodium level was 138.6 ± 4.7 mmol/L at hospital admission and 138.1 ± 4.1 mmol/L at discharge. The evolution of sodium levels was: normal-at-admission/normal-at-discharge 941 (71.9%), abnormal-at-admission/normal-at-discharge 127 (9.7%), normal-at-admission/abnormal-at-discharge 155 (11.8%) and abnormal-at-admission/abnormal-at-discharge 86 (6.6%). Hyponatraemia at discharge was more common in HFrEF (109 (20.7%)) than in HFpEF (79 (13.9%)) and HFmrEF (27 (12%)), P=0.003. The prevalence of hypernatraemia at discharge was similar in the three groups: HFrEF (10 (1.9%)), HFpEF (12 (2.1%)) and HFmrEF (4 (1.9%)), P=0.96. In multivariate analysis, abnormal sodium concentrations at hospital admission (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.15-1.76, P=0.001) and discharge (HR 1.33, 95% CI 1.08-1.64, P=0.007) were both independently associated with increased mortality and readmissions at 12 months. Hyponatraemia and hypernatraemia at admission and discharge predict a poor outcome in patients with acute HF regardless of left ventricular ejection fraction. Hyponatraemia at discharge is more frequent in HFrEF than in the other groups.

371-P: Impact of Sodium Intake on the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: Analysis of Data from the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial

Excessive sodium intake is regarded as a crucial factor related to developing and worsening of cardiovascular disease (CVD). However, epidemiological studies on this topic in patients with type 2 diabetes are sparse. We investigated the associations between sodium intake and CVD risk in Japanese patients with type 2 diabetes from the analysis of pooled data from two nation-wide prospective longitudinal studies. Data were analyzed on 2428 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 6-year risk of a CVD event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean sodium intake in quartiles ranged from 2494 mg to 6166 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&amp;lt; 2300 mg/day). After adjustment for confounders, HRs for CVD in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and CVD [Q2: 0.77 (95%CI, 0.48-1.23); Q3: 1.03 (0.65-1.63); and Q4: 1.31 (0.80-2.14), trend p = 0.131]. Results of subgroup analysis according to age showed that patients aged 39 through 59 years in the higher quartiles of sodium intake compared with the 1st quartile had a significantly higher incidence of CVD [Q2: 1.37 (0.57-3.33); Q3: 1.68 (0.70-4.03); and Q4: 4.16 (1.63-10.58), trend p = 0.004]. However, no significant association between sodium intake and CVD in participants aged over 60 years. Findings indicated that high sodium intake is associated with elevated incidence of CVD in younger patients with type 2 diabetes. Disclosure C. Horikawa: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. R. Aida: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. T. Moriya: None. A. Araki: None. Funding Japan Society for the Promotion of Science (19H04028)

432-P: Sodium Intake and Incidence of Diabetes Retinopathy in Elderly Patients with Type 2 Diabetes: Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT)

Though excessive sodium intake is regarded as a crucial factor related to developing and worsening of diabetes complications, data on this topic in elderly patients with diabetes are sparse. We investigated the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65 - 85 years. The present analysis was conducted among Japanese patients with type 2 diabetes from outpatient clinics in 39 university and general hospitals in Japan. Data were analyzed on 912 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to diabetic retinopathy, overt nephropathy, cardiovascular disease, and all-cause mortality during 6 years. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders Mean sodium intake in quartiles ranged from 2498 mg to 5910 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&amp;lt; 2300 mg/day). After adjustment for confounders, HRs for complications in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and complications. Among patients whose vegetable intake was less than the average of 268.7 g, HRs for diabetic retinopathy in patients in the 2nd, 3rd, and 4th quartiles of sodium intake compared with the 1st quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicated that high sodium intake under conditions of low vegetable intake is associated with elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes. Disclosure C. Horikawa: None. T. Moriya: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. A. Araki: None. R. Aida: None. S. Tanaka: None. C. Kamada: None. S. Tanaka: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. R. Kawasaki: None. Funding Japan Society for the Promotion of Science (19H04028)

A clinical study on dyselectrolytemia and changes in renal function in patients with 25% to 60% flame burn injury

Background: Severe fluid loss is the greatest problem faced following major thermal burn injuries accompanied by changes in the level of electrolytes. Standard fluid resuscitation derived from Parkland’s formula and body’s response to it is measured in terms of correction of dyselectrolytemia and urine output.Methods: A prospective cross sectional study involving 80 patients were included in the study with male patients being 28 and females being 52. Flame burns involving ≥25% - ≤60% of BSA presenting within 24 hours of flame burn injury were taken into account. Serial follow up of serum electrolytes was done on the day of presentation, day 2, day 3 and day 7 its effect on standard fluid resuscitation was studied.Results: Renal function is indirectly related to the percentage of flame burn, hence decreasing urine output and linear increase in serum creatinine is suggestive of increased surface area of burn. The mean serum sodium on the day of admission was roughly normal whereas as the days progressed there was significant hyponatremia with normalisation of day 7, whereas serum potassium was initially normal followed by hyperkalemia.Conclusions: An initial assessment involved calculation of percentage of total body surface area burn injury followed by of estimation of fluid requirement according to standard Parkland formula. Monitoring of electrolyte imbalance was noted for 2nd, 3rd and 7th day of hospitalisation. Derangements in these parameters were observed during course of admission followed by normalisation on the 7th day.

Daily water regime and sample sampling affect blood and urine parameter value change in healthy individuals

BackgroundHomeostasis is a mechanism for maintaining a stable inner environment in healthy participants. Blood and urine biomarkers are indicators of the subject health status. Biomarkers apply for early diagnosis, prognosis, and treatment. Understanding the effect of pre-analytical factors on biomarker range is significant for the data quality of bio-specimens, reproducibility, and minimizing potential results errors. Water as a necessary element for the normal functioning of living beings and sampling frequency as pre-analytical factors influences the homeostatic range of parameters. The purpose of the study is to examine the effect of 9-day fluid intake and 2-time sampling on concentration changes of 7-urine (freezing point depression, potassium, sodium, chloride, urea, creatinine, urate) and 17-blood (urea, creatinine, urate, glucose, C-reactive protein, leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean platelet volume, thrombocytes, potassium, sodium, and chloride) variables.MethodsParametric and non-parametric test apply to data processing with SPSS software v23.0.ResultsThe group of 23 healthy subjects was divide based on water intake (test: more than 1800 ml; control: less than 2000 ml) and gender (female: 10(43%); male: 13(57%)). The mean value of the amount of fluid consumed for the test group is 2183.33 ml, while the control is 1395.83 ml. Investigated parameters, freezing point depression, sodium, potassium, creatinine urea and urate in urine, urea, urate, glucose, hematocrit, and thrombocyte in blood show a significant difference (P < 0.01) between the first and second sampling. The difference between water intake after first sampling (P < 0.01) observes for freezing point depression, sodium, urate, and (P < 0.05) for potassium (P < 0.05), chloride (P < 0.05), creatinine (P < 0.05), urate, urea in urine and potassium (P < 0.01), and chloride (P < 0.05) in blood. Difference between gender exists for urea (P < 0.05) in urine after second sampling and urate (P < 0.01), glucose (P < 0.01/0.05), hematocrit (P < 0.01/0.05) after the first and second sampling, and mean corpuscular hemoglobin concentration (P < 0.01) after secondary sampling in blood samples.ConclusionWater intake increases the blood and urine biomarker range after the first and second sampling. Further studies should include a larger number of participants to get precise reference limits in a healthy population. Compare health and disease states to draw practical clinical conclusions.

Clinical profile and outcome of neonates admitted in sick newborn care unit with hypernatremic dehydration and association with breastfeeding in a tertiary care hospital in Northern India

Background: Neonatal hypernatremic dehydration is a very commonly seen potentially devastating condition. Inadequate breastfeeding, gastrointestinal losses, warm weather and improperly diluted mixed feeding are the main etiologies linked with neonatal hypernatremic dehydration. We conducted this study to evaluate the etiology, risk factors, clinical symptoms and outcomes of neonates admitted with hypernatremic dehydration and its association with breastfeeding from hilly region in northern India.Methods: The authors retrospectively studied records from extramural sick newborn care unit (SNCU) from April 2018 to June 2019. Inclusion criteria for the study included admitted neonates with documented hypernatremia (serum sodium level &gt;145 mmol/L). Results: Nine hundred and twenty-two neonates were admitted in sick newborn care unit during this study period. One hundred and three (13.39%) newborns were admitted with hypernatremic dehydration at the time of admission. All newborns had deranged kidney function tests at time of admission. Most commonly found presenting complaints were poor feeding (85.71%), fever (45.71%), loose stools (42.8%) and decreased urine output (8%). The mean (SD) sodium on admission was 154.04 (7.41) meq/L. The mean (SD) time taken to correct hypernatremia was 35.6 (14.6) hours. Six of total admitted newborn developed neurological complications (2 had developed cerebral venous thrombosis and 4 had developed seizures). Mortality rate was 4.4%. Top fed neonates (50.41%) had higher percentage of mean sodium level and acute kidney injury at time of admission.Conclusions: Hypernatremic dehydration is preventable and treatable condition. Looking in to and addressing etiology in a timely manner is main step in management. All mothers should be taught correct breastfeeding technique. More breast examination during prenatal and postnatal periods and careful neonatal weight record postnatally could decrease the incidence of neonatal hypernatremic dehydration. Top feeding should be discouraged and only exclusive breastfeeding for 6 months.

The Cost-Effectiveness of Congenital Adrenal Hyperplasia Newborn Screening in Brazil: A Comparison Between Screened and Unscreened Cohorts.

Background: Newborn screening for congenital adrenal hyperplasia (CAH-NBS) is not yet a worldwide consensus, in part due to inconclusive evidence regarding cost-effectiveness because the analysis requires an understanding of the short- and long-term costs of care associated with delayed diagnosis.Objective: The present study aimed to conduct a cost-effectiveness analysis (CEA) to compare the costs associated with CAH-NBS and clinical diagnosis.Methods: A decision model comparing the two strategies was tested by sensitivity analysis. The cost analysis perspective was the public health system. Unscreened patients' data were extracted from medical records of Hospital das Clinicas, Saõ Paulo, and screened data were extracted from the NBS Referral Center of São Paulo. The population comprised 195 classical patients with CAH, clinically diagnosed and confirmed by hormonal/CYP21A2 analysis, and 378,790 newborns screened during 2017. Adverse outcomes related to late diagnosis were measured in both cohorts, and the incremental cost-effectiveness ratio (ICER) was calculated. We hypothesized that CAH-NBS would be cost-effective.Results: Twenty-five screened infants were confirmed with CAH (incidence: 1:15,135). The mortality rate was estimated to be 11% in unscreened infants, and no deaths were reported in the screened cohort. Comparing the unscreened and screened cohorts, mean serum sodium levels were 121.2 mEq/L (118.3–124.1) and 131.8 mEq/L (129.3–134.5), mean ages at diagnosis were 38.8 and 17 days, and hospitalization occurred in 76% and 58% of the salt-wasting patients with the in the two cohorts, respectively. The NBS incremental cost was US$ 771,185.82 per death averted, which yielded an ICER of US$ 25,535.95 per discounted life-year saved.Conclusions: CAH-NBS is important in preventing CAH mortality/morbidity, can reduce costs associated with adverse outcomes, and appears cost-effective.

A Prospective Cohort Study on Serum Sodium and Clinical Outcome in Pediatric Nontraumatic Coma.

To study the serum sodium level and clinical outcome in pediatric nontraumatic coma. A prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from September 2015 to June 2016. Children aged < 13 y with nontraumatic coma [modified-Glasgow Coma Scale (m-GCS) score ≤ 8 or fall of ≥ 3 from baseline within 24h of admission] were included. Children who received intravenous fluids for > 24h, those with developmental delay, or died within 24h of admission were excluded. The serum sodium profile (mEq/L) in the first 72h and clinical outcome [mortality, length of stay in mechanical ventilation, PICU, and hospital] were studied. Eighty patients [Died n = 26 and Survived n = 54] were enrolled. Median [interquartile range (IQR)] age and m-GCS were 21 (4-78) mo and 9 (7-11), respectively. The mean [standard deviation (SD)] Pediatric Risk of Mortality-III (PRISM-III) was 17.7 (4). The most common etiology was acute central nervous system (CNS) infections (30%, n = 24) followed by an intracranial bleed (11.3%, n = 9). Mean (Standard error, SE) sodium levels and fluctuation of serum sodium from baseline up to 72h were similar between nonsurvivors and survivors [140.8 (1.3) vs. 139.6 (0.8), p = 0.421] and [1.2 (0.3) vs. 0.8 (0.2), p = 0.307], respectively. On multivariate analysis, the need for vasoactive therapy was an independent predictor of mortality [adjusted odds ratio = 20.78, 95% CI 4.24-101.85, p = < 0.001, R2 = 0.62]. Mean serum sodium within normal range and fluctuation of serum sodium of 0.8 to 1.2mEq/L over 72h was not associated with poor outcomes in pediatric nontraumatic coma. Vasoactive therapy was an independent predictor of mortality.

Predictors of early and late re-hospitalization and mortality in non-ST elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Regarding prognosis, acute coronary syndromes (ACS) are heterogeneous. Non-ST elevation myocardial infarction (NSTEMI) is a subtype of ACS. In-hospital (IH) and post-hospitalization (PH) risk stratification is crucial. Objective To identify predictors of IH and PH mortality (early and late), as well as predictors of early and late re-admission (RA) in our center population suffering NSTEMI, using real-life data. Methods Based on a single-center retrospective study, data collected from admissions between 1/01/2018 and 11/12/2019. Patients (pts) who survived the ACS and were discharged from the hospital were included. Concerning prognosis, we assessed 1-month M and RA (1mM and 1mRA), 6-month M and RA (6mM and 6mRA), 1-year M and RA (1yM and 1yRA). Results 268 pts with ACS, 59.7% were males and mean age was 66.4 ± 12.5 years old. NSTEMI was the diagnosis in 66.4% and ST elevation myocardial infarction (STEMI) in 31%. Mean creatinine was 1.2 ± 1ml/min, mean sodium was 138 ± 3mmol/L, mean blood urea nitrogen (BUN) was 21 ± 12mg/dL and mean haemoglobin (Hb) was 13.6 ± 1.9g/dL. 88.2% of the pts presented in Killip-Kimball class (KKC) 1, 5.7% in KKC 2, 5.7% in KKC 3 and 0.4% in KKC IV; furthermore, 4.1% of the pts presented de novo AF. Concerning coronary artery disease, 250 were submitted to coronary angiography – 18.8% had no lesions or non-significant lesions (stenosis &amp;lt;50%), 34.8% had one significant lesion, 23.2% had 2 significant lesions and 23.2% had 3 or more. Regarding left ventricle (LV) function, 70.5% of the pts had no LV dysfunction, 15.7% had mild LV impairment (LVI), 9.3% moderate LVI and 4.5% had severe LVI. 8.4% of the patients experienced IH complications, such as auriculoventricular block, heart failure, ventricular tachycardia, stroke, cardiorespiratory arrest and major haemorrhage, during hospitalization. 1mM rate was 1.9% and 1yM rate was 7.8%. KKC (p = 0.001), BUN (p = 0.007), LV function (p= 0.001) and de novo AF (p = 0.46) were predictors of 1mM. Age (p = 0.004), KKC (p = 0.031), BUN (p = 0.002), sodium (p = 0.037), creatinine (p = 0.001), Hb (p = 0.003), LV function (p &amp;lt; 0.001), de novo AF (p &amp;lt; 0.001) and occurrence of IH complications (p &amp;lt; 0.001) were predictors of 1yM. Age (p = 0.010), male gender (p = 0.19), Hb (p = 0.031), de novo AF (p &amp;lt; 0.001) and occurrence of IH complications (p = 0.001) were predictors of 1mRA. Age (p = 0.004), smoking (p = 0.040), hypertension (p = 0.040), glycemia at admission (p = 0.031), Hb (p = 0.004), LV function (p = 0.019), de novo AF (p &amp;lt; 0.001) and occurrence of IH complications (p &amp;lt; 0.001) were predictors of 1yRA. Conclusion This study suggests that de novo AF and occurrence of IH complications are very important prognosis factors regarding early and late mortality and readmission rates.

Acute heart failure: is ACTION-ICU useful?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (pts) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF as predictor of in-hospital M (IHM), post discharge early M [1-month mortality (1mM)] and 1-month readmission (1mRA), in our center population, using real-life data. Methods Based on a single-center retrospective study, data collected from pts admitted in the Cardiology department with AHF between 2010 and 2017. Pts without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used non-parametric tests, logistic regression analysis and ROC curve analysis. Results We included 300 pts admitted with AHF. Mean age was 67.4 ± 12.6 years old and 72.7% were male. 37.7% had previous history of revascularization procedures, 66.9% had hypertension, 41% were diabetic and 38% had dyslipidaemia. Mean heart rate was 95.5 ± 27.5bpm, mean systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, mean urea level at admission was 68.8 ± 40.7mg/dL, mean sodium was 137.6 ± 4.7mmol/L, mean glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. Mean ACTION-ICU score was 10.4 ± 2.3. Inotropes’ usage was necessary in 32.7% of the pts, 11.3% of the pts needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the pts were readmitted 1 month after discharge. Older age (p &amp;lt; 0.001), lower SBP (p = 0,035), presenting in KKC 4 (p &amp;lt; 0.001, OR 8.13) and need of inotropes (p &amp;lt; 0.001) were predictors of IHM in our population. Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &amp;lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the studied variables were predictive of need of IV. LVEF (OR 0.924, p &amp;lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &amp;lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &amp;lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors inotropes’ usage. ACTION-ICU was able to predict IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed ACTION-ICU performs well when predicting IHM (Area under curve (AUC) 0.729, confidence interval (CI) 0.59-0.87), inotropes’ usage (AUC 0.619, CI 0.54-0.70) and 1mM (AUC 0.705, CI 0.58-0.84). Conclusion In our population, ACTION-ICU score was able to predict IHM, 1mM and inotropes’s usage.

Efficacy, Efficiency and Security of Urea Treatment in the Syndrome of Inappropiate Antidiuretic Hormone Secretion

Introduction: In the present times, several strategies have been proposed for the treatment of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Urea has demonstrated to be an effective treatment but its use has not been extended. Our work analyzes our experience with urea in the treatment of SIADH. Material and Methods: Observational retrospective analysis of 39 patients with SIADH in which urea has been used in our hospital with pre- and post-analysis of plasmatic sodium concentrations. Results: We included 39 patients with SIADH win a mean age of 76,4 ± 15,8 years. The plasma sodium nadir was 120,0 ± 5,1 mmoL/L and at the initiation of treatment 125,2 ± 4,1 mmoL/L. Total time of treatment was 2,42 ± 3,86 months being the treatment still active in 4 patients. We observed an improvement of sodium in all patients with a mean sodium at the end of treatment of 134.3 + - 5.0 mmol/L being this values statistically significant compared to the initial sodium (p<0.01). As a matter of fact we found significant differences at one week of treatment (p<0.01), keeping sodium stable levels around 135 mmol/L during the treatment period. The treatment was stopped in 3 cases (7.7 %) by the patient, one for mild digestive symptomatology and two for limited palatability. Of them two were treated with tolvaptan and the other did not need any further treatment. There were no adverse events in the rest of the patients. From the economic perspective and considering the duration of treatment, if we compare this to the cost of tolvaptan during the same period and the same number of patients, there was a reduction of cost of 87.9 % in comparison with treatment with tolvaptan. Conclusions: In our experience urea has shown to be a safe and cost effective option in the treatment of hyponatremia caused by SIADH showing improvement in sodium levels from the first week of treatment in all patients. We think it should be considered a valid therapeutic option.

Do Counter‐Current Exchange and Glycosaminoglycan Buffering Contribute in Salt Storage in Skin of Rats?

We have previously shown that there is an osmolality and urea gradient from epidermis to dermis and subcutis. This gradient may be a result of the proposed counter-current mechanism for electrolyte homeostasis in skin. Our aims were to test whether there are gradients in salt concentration in skin generated by counter-current exchange and whether glycosaminoglycans (GAGs) can store sodium making it ‘inactive’ in relation to fluid exchange and thereby act as buffers during high salt intake. Sprague-Dawley rats were given low salt diet (LSD, <0.1% NaCl in chow and tap water), high salt diet (HSD, 8% NaCl in chow and 1% saline to drink), and DOCA-salt diet (50mg/week deoxycorticosterone acetate, 150mg/21 days and 1% saline to drink). Rats were randomly assigned to either LSD (n=15), HSD (n=7) or DOCA salt (n=8) diet for measurements of extracellular volume (ECV) in tangential sequential skin sections. Two weeks into the diet regimen the rats were anesthetized, neprectomized and given the extracellular tracer 51Cr-EDTA i.v. that was allowed 120 min circulation time. Directly thereafter, shaved back skin was further processed by cutting sequential sections of 40 µm (epidermis) and 100 µm (dermis and subcutis) thickness in a cryostat taking care to avoid evaporation. The skin sections were weighed and counted in a gamma counter and the extracellular volume found as the plasma equivalent space of 51Cr-EDTA. After counting, the samples were dried until constant weight, then eluted in ultrapure water for seven days. The eluate was analyzed in an ion chromatograph to determine sodium and potassium content in each layer. Sulfated GAGs were determined in whole skin, dermis and subcutis using Blyscan sGAG colorimetric assay to determine sGAG content. When relating sodium content to ECV we found that there was a gradient from epidermis to dermis, and that this gradient was more pronounced in the DOCA rats. The LSD group had a mean sodium of 332.7±194.3 mM in epidermis and 118.3±20.15 mM in the following layer at 140±mM, with corresponding concentrations of 219.2±52 mM and 121.1±41.4 mM in HSD, and 757.8±426.1 mM and 123.7±11.45 mM in DOCA. There was no difference in sulfated GAGs in skin between LSD, HSD and the DOCA salt group in any of the skin regions. Our results suggest that there may be a gradient of salt in the skin with a higher concentration in ECV in epidermis supporting the notion of a counter-current mechanism. However, our data do not support that an increased concentration of sulfated GAGs contribute to salt buffering during high salt conditions.

English

BACKGROUND Chronic kidney disease (CKD) is a global health problem which is progressive and asymptomatic until the end stage in recent years which is most common in patients of middle and low socio-economic status. The disease is mostly associated with diabetes or hypertension, young and middle-aged individuals living in agricultural communities and drinking well water. We want to study the clinicopathological profile of chronic kidney disease of unknown aetiology (CKDU) cases admitted in a rural tertiary care hospital. METHODS A retrospective study was conducted among fifty patients who reported with ultrasonography (USG) report showing small shrunken kidneys and / or kidney biopsy suggestive of chronic tubulointerstitial nephritis with absence of immune deposits and admitted in the Medicine department of AVBRH Hospital and JNM College of Medical Sciences, Sawangi (M) Wardha of Central India. RESULTS The mean age was 36.46 ± 10.90 years with majority of the patients between the ages of 35 to 55 years. The body mass index (BMI) of the study group was within 22.52 ± 1.96. CKDU was more commonly seen in males (64 %) as compared to females (36 %). The subjects were predominantly farmers (54 %) who used to drink well water. USG showed small shrunken kidneys in all the study subjects, which was in 100 % cases. Pesticide exposure was seen in 32 % cases. The glomerular filtration rate (GFR) revealed that 30 % of the patients were in grade II. The biochemical report revealed the mean value of haemoglobin to be 8.75 ± 1.39, mean serum urea level to be 64.96 ± 15.19, mean serum creatinine level to be 4.5 ± 2.67, mean serum sodium level to be 132.48 ± 5.83 and mean serum potassium to be 4.43 ± 0.78. The mean random blood sugar (RBS) value was 98.64 ± 19.62, serum calcium level was 8.87 ± 0.43, serum phosphorus level was 5.05±0.39 and urine protein / creatinine ratio was 0.90 ± 0.12. CONCLUSIONS This study highlights the need to review health policies and allocates resources for prevention and treatment of CKDU in Central India, Maharashtra. KEY WORDS Chronic Kidney Disease of Unknown Aetiology (CKDU), Hypertension, Diabetes, Shrunken Kidneys

Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135mmol/L or > 145mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Comparison of isotonic versus hypotonic intravenous fluid for maintenance fluid therapy in neonates more than or equal to 34 weeks of gestational age – a randomized clinical trial

Background and objectives The use of hypotonic fluids as maintenance therapy in the neonatal population has been in practice for a long time, but there is a lack of evidence for the choice of this fluid in neonates. This study compared isotonic (sodium chloride, 0.9%, and dextrose, 5%) versus hypotonic (sodium chloride, 0.15%, and dextrose, 5%) intravenous fluid for maintenance fluid therapy in neonates more than or equal to 34 weeks of gestational age. Methods In this triple-blind randomized clinical trial, we recruited 60 neonates admitted to a neonatal intensive care unit of a tertiary care children's hospital from June 2017 through May 2018 with normal baseline serum sodium levels, anticipated to require intravenous maintenance fluids for 24 hours or longer (intention-to-treat analyses). Patients were randomized to receive isotonic or hypotonic intravenous fluid at maintenance rates for 72 hours. The primary outcome was the incidence of hyponatremia (defined as serum sodium <135mEq/L) at 24 hours in both groups. The secondary outcomes were incidence of hypernatremia at 24 hours (defined as serum sodium >145 mEq/L), the incidence of hypo and hypernatremia at 48 and 72 hours, mean serum sodium at 24, 48, and 72 hours, rate of change of serum sodium during the study period, mean serum osmolality at the end of the study period, the absolute difference in osmolality during the study period, the absolute difference in weight during the study period and edema during the study period. Results Of 60 enrolled neonates, 31 received isotonic fluids and 29 received hypotonic fluids. Three patients in the hypotonic group developed hyponatremia and none in isotonic group at 24 h (RR = 0.13; 95% CI = 0.007 − 2.485; p = .106). Fourteen neonates developed hypernatremia in the isotonic group and one in hypotonic group at 24 h (RR = 13.09; 95% CI = 1.83 − 93.4; p = .0001). Conclusions Our study results do not support the hypothesis that isotonic fluid is superior to hypotonic fluid in reducing the proportion of neonates developing hyponatremia after 24 hours of intravenous fluid therapy. The proportion of neonates developing hypernatremia is significantly higher after using isotonic fluid for maintenance therapy. TRIAL REGISTRATION CTRI/2017/05/008585

UP-REGULATION OF SGLT-5 AS A CAUSE OF FRUCTOSE-INDUCED VOLUME-DEPENDENT HYPERTENSION

Objective: Excessive intake of fructose causes a variety of adverse conditions including obesity, hepatic steatosis, insulin resistance, uric acid overproduction and hypertension which is the most common and significant pathological setting. Cause of the hypertension is not known at present. This study aimed to elucidate the underlying mechanism of fructose-induced hypertension by rat model. Design and method: Male SD rats (7 weeks old) were fed by food containing 60% glucose (GLU) and 60% fructose (FRU) for 3, 6 and 12 weeks. Histological, immunohistological and molecular biological analysis, and gene chip study were applied. No difference of calorie and salt intake of individual animal was daily checked by the measured weight of remaining food. Results: Mean blood pressure and fractional sodium excretion (FENa) of FRU were both significantly higher (BP 12w-GLU: 94.8 ± 3.4 vs 12w-FRU: 103.7 ± 1.2 mmHg; FENa 12w-GLU: 0.084 ± 0.011 vs 12w-FRU: 0.059 ± 0.08%), suggesting that fructose caused ECF volume-dependent hypertension. Glomerular expansion in FRU (glomerular surface area in 12w-GLU: 7495 ± 181 vs 12w-FRU: 9831 ± 164 square micrometer) was agreed with the increase in the ECF volume. The expression of GLUT-5, fructose entry pathway, and ketohexokinase, phosphatase of fructose, in the proximal tubule were both up-regulated by fructose. As a candidate of fructose-induced salt reabsorption pathway, NHE3 was focused first because it is principal salt reabsorption pathway of proximal tubule. However, gene expression analysis, immunohistochemistry and immunoblotting of whole and phosphorylated NHE3 indicated negative results. To explore salt transporting molecules responding to fructose, gene chip analysis was conducted, and Slc5a10, corresponding to SGLT-5, showed significant up-regulation. The result was confirmed by RT-PCR (12w-GLU: 75.0 ± 5.8% vs 12w-FLU: 230.1 ± 16.0%) and in-situ hybrydization. Conclusions: Excess intake of fructose caused volume-dependent hypertension due to increased salt reabsorption through fructose-induced up-regulation of SGLT-5.

Dietary intakes of children with nephrotic syndrome.

Our multidisciplinary clinical pathway for treatment of childhood nephrotic syndrome (NS) was established with the goal of standardizing local clinical practice. This descriptive study aimed to assess nutrient intakes of children with newly diagnosed NS compared with nutrition goals defined by our pathway. Our pathway includes evidence-based recommendations that target daily intakes during corticosteroid induction therapy: energy (Estimated Energy Requirements (EER) × Sedentary Physical Activity (PA)), sodium (1 mg/kcal), calcium (Dietary Reference Intake (DRI) + 500 mg elemental calcium), and vitamin D (DRI +800-1000 IU). After dietitian-led education at initial diagnosis, 3-day food records were completed at 4 weeks post-diagnosis. Daily nutrient intakes were compared to pathway targets and DRIs. Thirty-six children (median age 4.8 years, 44% female) with newly diagnosed NS submitted food records. Mean energy and sodium intakes were 103±22% and 99±53% of pathway targets, respectively. Fourteen (39%) children exceeded pathway sodium recommendations, with four (11%) exceeding them by greater than 50%. Seven (19%) children met DRI for calcium, while six (17 %) met pathway targets for calcium. No children met DRI for vitamin D from diet alone; and only one met the target with supplementation. This is the first study to describe dietary intakes of children with newly diagnosed NS. Our clinical pathway targets for energy and sodium were achievable; however, calcium and vitamin D intakes fell short of pathway guidelines and DRIs. Prescription of supplemental calcium and vitamin D may be needed to achieve target intakes of calcium and vitamin D.

RELATION OF GRADES OF HYPONATREMIA ON SEVERITY OF BRONCHIOLITIS

Background and objectives: Hyponatremia often occurs among children with bronchiolitis. It is the most common electrolyte abnormality associated with severe disease course. Aim was to study relation between sodium levels and severity of bronchiolitis&#x0D; Methodology: Cross-sectional study was conducted on 72 infants admitted with bronchiolitis to Pediatrics ward/ICU, JMMC. Infants with recurrent respiratory or super added bacterial infections, born &lt;34weeks gestation, any chronic disorder or medications that can influence electrolyte levels or parents unwilling for consent were excluded. Severity of bronchiolitis was scored and classified into mild, moderate, severe. Sodium levels were determined and grouped (in mmol/L) into normonatremia (135-145) and hyponatremia (mild (130-134), moderate (125-129) and severe (≤124). The grade of hyponatremia with severity of bronchiolitis was compared. Chi square test was used to test the association of severity of bronchiolitis and category of hyponatremia. ANOVA test was done to compare the severity of bronchiolitis with sodium levels.&#x0D; Results: Hyponatremia was seen in 50% of cases admitted with severe bronchiolitis, which when compared to mild and moderate bronchiolitis, was statistically significant (p&lt;0.001). ANOVA showed mean sodium levels of mild, moderate and severe bronchiolitis were 138.44±1.81, 137.37±1.76 and 135.43±3.93 respectively; these were statistically significant (p&lt;0.001). A pairwise comparison between mild and moderate bronchiolitis with hyponatremia was not found to be statistically significant (p-0.769) but comparison between mild and severe bronchiolitis with hyponatremia was statistically significant (p&lt;0.001)&#x0D; Conclusion: There is statistically significant relation between hyponatremia and severity of bronchiolitis. Hyponatremia could be considered as a marker to assess the severity of bronchiolitis.&#x0D; Keywords: Bronchiolitis, Hyponatremia, Respiratory distress