The contribution of plasma urea to total osmolality during iatrogenic fluid reduction in critically ill patients

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water, or an active osmole-producing mechanism similar to that in aestivating animals where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult ICU patients in the post-resuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR) and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea and glucose to eOSM expressed as proportions of eOSM were calculated. 241 patients were included. eOSM increased (median change 7.4 mOsm/kg (IQR −1.9–18) during the study. The of sodium's and potassium's proportions of eOSM decreased (P < 0.05 and P < 0.01 respectively), whereas the urea's proportion increased (P < 0.001). Urea's proportion of eOSM was higher in patients with negative vs. positive fluid balance. The urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea's proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea's proportion of eOsm was higher in patients not surviving to 90 days. In stabilized ICU patients the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals. ClinicalTrials.org Identifier: NCT03972475

MO656CORRELATION BETWEEN CHANGES IN THE BODY FLUID VOLUME CALCULATED BY THE URIC ACID KINETIC MODEL AND CHANGES IN THE BODY WEIGHT*

Background and Aims Uric acid (UA) is a solute unable to cross the cell membranes in general tissues by any of simple diffusion, facilitated diffusion or active transport. These facts imply that UA distribution volume (UDiV) equals to the extracellular fluid volume (ECFV). We have developed a method for calculating UDiV from serum uric acid levels before and after hemodialysis based on a uric acid kinetic model (Shinzato T, Int J Artif Organs 2020). Urea is evenly distributed throughout the body fluids. Therefore, the total body fluid volume (TBFV) can be calculated by using the same method as the calculation of UDiV for the serum urea level. The remaining body fluid volume, which is TBFV minus UDiV, is considered to reflect the intracellular fluid volume (ICFV). In this study, we clarified the relationship between the amount of change over time in UDiV and ICFV calculated by the uric acid kinetic model and the amount of change over time in the actual body weight of hemodialysis patients. Method Subjects were 1,101 patients with chronic maintenance hemodialysis. UDiV and ICFV before and after dialysis were calculated for two time points, December 2019 and June 2020. Results The amount of change in UDiV per body during the dialysis session showed a very good correlation with the amount of body weight change during the same dialysis (UDiV change = 0.950 x body weight change - 0.158, R-square 0.90, p < 0.0001). The amount of change in ICFV during the 6 months from December 2019 to June 2020 showed a good correlation with the amount of change in post-dialysis body weight during the same period (ICFV change = 0.270 x post-dialysis body weight change + 0. 240, R-square 0.21, p <0.0001). Conclusion These results suggest that the body fluid volume calculated by the uric acid kinetic model has high accuracy.

P1195ASSESSMENT OF BODY FLUID VOLUME USING THE BIOIMPEDANCE METHOD IN PERITONEAL DIALYSIS PATIENTS

Background and Aims ppropriate maintenance of body fluid balance in peritoneal dialysis (PD) patients is important for the amelioration of cardiovascular complications and prognosis. In recent years, the usefulness of body fluid measurement with the bioimpedance method in PD patients has been reported. Meanwhile, peritoneal permeability plays an important role in maintaining body fluid balance in PD patients. In the present study, we examined the correlation between peritoneal permeability and body fluid volume in PD patients. Method A total of 58 patients who were undergoing PD at our hospital (42 men and 16 women; mean age, 68 ± 16.2 years; mean dialysis history, 63.5 ± 144.9 months; 25 DM and 35 non-DM patients). Overhydration (OH), total body water (TBW) volume, extracellular water (ECW) volume, and lean tissue mass (LTM) were measured using a body composition analyzer (BCM Fresenius Medical Care Japan). At the same time, peritoneal permeability was measured with fast peritoneal equilibration test to determine the dialysate-to-plasma ratio for creatinine (D/P-Cr), and its correlations with sex, age, age at the time of introduction of dialysis, dialysis history, diabetes history, brain natriuretic peptide (BNP) level, high-sensitivity troponin I (hsTnI) level, blood pressure, body weight, residual kidney function, and ultrafiltration were examined. Results The mean OH was 2.53 ± 2.44 L, and 8 patients (13.8%) had an OH of ≤1.1 L. The results of the multivariate analysis revealed that OH positively correlated with the presence or absence of diabetes, ultrafiltration, D/P-Cr, BNP level, hsTnI level, TBW, and ECW, but showed no correlation with sex, dialysis history, age, age at the time of introduction of dialysis, residual renal function, or LTM. Furthermore, the subjects were assigned to D/P-Cr ≥ 0.65 and ≤0.65 groups. In the former, OH correlated with diabetes and male sex by being negatively correlated with age and age at the time of introduction of dialysis and positively correlated with BNP level, hsTnI level, TBW, and ECW. However, in the D/P-Cr ≤ 0.65 group, OH positively correlated with BNP level and ECW. Conclusion Our results suggest that youth, complications of DM, and men are at risk for fluid overload in PD patients with increased peritoneal permeability.

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study

Abstract Background : Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcome and death from any cause. While treatment with sulfonylurea reduces microvascular complications in diabetes, it increases cardiovascular hospitalization or mortality in combination with metformin. In the present study, we assessed the effects of empagliflozin and glimepiride, a commonly prescribed sulfonylurea, on endothelial function using flow–mediated dilation (FMD) to estimate arteriosclerosis and cardiovascular events in patients with type 2 diabetes. Methods : In this prospective, open-label, randomized, parallel-group study, 58 patients with type 2 diabetes received metformin and glargine before bedtime for 12 weeks. This was followed by additional treatment with either 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), measured prior to and after 12 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. Results : Analysis of the empagliflozin group ( n = 30) and glimepiride group ( n = 28) showed no significant differences in DFMDs (empagliflozin, −0.19 ± 2.34%; glimepiride, −0.37 ± 2.77%; P = 0.79). Similarly, changes in glycated hemoglobin (HbA1c) were similar between the two groups. However, significant difference in body weight changes were observed between the two groups (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). In addition, an analysis of the body composition revealed that body fluid volume significantly decreased after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, –0.33 ± 0.72 L; P = 0.03). Conclusions : Empagliflozin did not improve endothelial function when compared to glimepiride in patients with type 2 diabetes but decreased their body fluid volume. This suggested that the coronary protective effect of empagliflozin is not derived by protection of the endothelial function but rather from reduction in the risk of heart failure. Trial Registration : This trial was registered on September 13, 2016; UMIN000024001 . Keywords: Empagliflozin, Endothelial function, Glimepiride, Diabetes, Flow–mediated dilation

PERUBAHAN MEAN ARTERIAL PRESSURE (MAP) PASIEN HIPERGLIKEMIA KRISIS DENGAN TERAPI REHIDRASI

: Rehydration therapy aims to replace the volume of circulating tissue perfusion due to hyperosmolarity in crisis hyperglycemia patients. The administration of fluid therapy to patients with crisis hyperglycemia can trigger cerebral edema due to the mechanism of decreased osmolarity in cerebral tissue. Efforts to monitor the emergence of cerabral edema with MAE monitoring. MAE is an indicator of CPP if there is a drastic increase in MAP which will result in an increase in CPP and increase the risk of cerebral edema. This study aims to determine the difference in MAP in hyperglycemic crisis patients with fluid rehydration therapy from the first minute of administration to the last minute of administration by accumulating the amount of fluid given in that time period. A retrospective comparative category research design. The study sample consisted of 28 respondents. Based on data analysis using repeated anova, there was a difference in MAP in hyperglycemic crisis patients who received fluid rehydration therapy from the lowest amount to the highest number during therapy. Changes in the value of MAP in this study for all the amount of therapy in the normal range starting from the MAP before the therapy approaching the less or minimum value until MAP at the end of therapy at the maximum limit of the normal value of MAP. This indicates that the administration of therapy in this study will increase the amount of body fluid volume and increase in MAP without causing signs of cerebral edema. Keyword : Rehydration Therapy, MAP (Mean Arterial Pressure), hyperglycemia crisisAbstrak : Terapi rehidrasi bertujuan untuk mengganti volume sirkulasi perfusi jaringan akibat adanya hiperosmolaritas pada pasien hiperglikemia krisis. Pemberian terapi cairan pada pasien hiperglikemia krisis bisa memicu terjadinya edema cerebral akibat mekanisme penurunan osmolaritas pada jaringan cerebral. Upaya monitoring munculnya edema cerabral dengan pematauan MAE. MAE merupakan salah satu indikator terhadap CPP apabila di dapatkan adanya peningkatan MAP yang drastis akan berakibat peningkatan CPP dan meningkatkan resiko edema cerebral. Penelitian ini bertujuan mengetahui perbedaan MAP pada pasien krisis hiperglikemia dengan terapi rehidrasi cairan mulai dari menit pertama pemberian sampai menit terakhir pemberian dengan mengakumulasi jumlah cairan yang diberikan pada periode waktu tersebut. Desain penelitian kategori komparatif retrospektif. Berdasarkan uji analisa data dengan menggunakan repeated anova didapatkan ada perbedaan MAP pada pasien krisis hiperglikemia yang mendapatkan terapi rehidrasi cairan mulai jumlah terendah sampai jumlah tertingi selama terapi diberikan. Perubahan nilai MAP dalam penelitian ini untuk semua jumlah terapi dalam batas normal dimulai dari MAP sebelum terapi yang mendekati nilai kurang atau minimum sampai dengan MAP pada akhir terapi pada batas maksimal dari nilai normal MAP. Hal ini menandakan pemberian terapi pada penelitian ini akan meningkatkan jumlah volume cairan tubuh dan peningkatan MAP tanpa menyebakan tanda edema cerebral.Kata Kunci : Terapi rehidrasi, MAP (Mean Arterial Pressure), hiperglikemia krisis

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study

Background: Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes and death from any cause. Alternatively, treatment with sulfonylurea reduces microvascular complications in diabetes but appears to increase cardiovascular hospitalization or mortality in combination with metformin. Therefore, in the present study, we assessed the effects of empagliflozin and glimepiride, a sulfonylurea, on endothelial function using flow–mediated dilation (FMD) to estimate arteriosclerosis and cardiovascular events in patients with type 2 diabetes. Methods: In this prospective, open-label, randomized, parallel-group comparison, 58 patients with type 2 diabetes were administered metformin and glargine before bedtime for 12 weeks, followed by the random addition of 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), which was measured prior to and following 12 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. Results: Analysis of the empagliflozin group (n = 30) and glimepiride group (n = 28) showed no significant differences in DFMDs (empagliflozin, −0.19 ± 2.34%; glimepiride, −0.37 ± 2.77%; P = 0.79). Likewise, glycated hemoglobin (HbA1c) changes were similar between the two groups. Body weight changes significantly differed (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). However, analysis of the body composition revealed that body fluid volume significantly decreased only after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, –0.33 ± 0.72 L; P = 0.03). Conclusions: Empagliflozin did not improve endothelial function compared with glimepiride in patients with type 2 diabetes, but decreased their body fluid volume. This suggested that the coronary protective effect of empagliflozin is not derived by protecting endothelial function but rather from reducing the risk of heart failure.

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study

Background: Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes and death from any cause. Alternatively, treatment with sulfonylurea reduces microvascular complications in diabetes but appears to increase cardiovascular hospitalization or mortality in combination with metformin. Therefore, in the present study, we assessed the effects of empagliflozin and glimepiride, a sulfonylurea, on endothelial function using flow–mediated dilation (FMD) to estimate arteriosclerosis and cardiovascular events in patients with type 2 diabetes. Methods: In this prospective, open-label, randomized, parallel-group comparison, 58 patients with type 2 diabetes were administered metformin and glargine before bedtime for 12 weeks, followed by the random addition of 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), which was measured prior to and following 12 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. Results: Analysis of the empagliflozin group (n = 30) and glimepiride group (n = 28) showed no significant differences in DFMDs (empagliflozin, −0.19 ± 2.34%; glimepiride, −0.37 ± 2.77%; P ＝ 0.79). Likewise, glycated hemoglobin (HbA1c) changes were similar between the two groups. Body weight changes significantly differed (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). However, analysis of the body composition revealed that body fluid volume significantly decreased only after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, –0.33 ± 0.72 L; P = 0.03). Conclusions: Empagliflozin did not improve endothelial function compared with glimepiride in patients with type 2 diabetes, but decreased their body fluid volume. This suggested that the coronary protective effect of empagliflozin is not derived by protecting endothelial function but rather from reducing the risk of heart failure.