Enteral Sodium Chloride Supplementation and Fluid Balance in Children Receiving Diuretics

The use of sodium chloride (NaCl) supplementation in children being prescribed diuretics is controversial due to concerns that supplementation could lead to fluid retention. This is a single-center retrospective study in which fluid balance and diuretic dosing was examined in children prescribed enteral NaCl supplements for hyponatremia while receiving loop diuretics. The aim of this study was to determine whether significant fluid retention occurred with the addition of NaCl. Fifty-five patients with 68 events were studied. The median age was 5.2 months, and 82% were hospitalized for cardiac disease. Daily fluid balance the seven days prior to NaCl supplementation was lower than the seven days after, with measurement of: median 17 mL/kg/day (7–26) vs. 22 mL/kg/day (13–35) (p = 0.0003). There was no change in patient weight after supplementation (p = 0.63). There was no difference in the median loop diuretic dose before and after supplementation, with the diuretic dose in furosemide equivalents of 3.2 mL/kg/day (2.3–4.4) vs. 3.2 mL/kg/day (2.2–4.7) (p = 0.50). There was no difference in the proportion of patients receiving thiazide diuretics after supplementation (56% before vs. 50% after (p = 0.10)). NaCl supplementation in children receiving loop diuretics increased calculated fluid balance, but weight was unchanged, and this was not associated with an increase in diuretic needs, suggesting clinicians did not consider the increase in fluid balance to be clinically significant.

Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics

The mechanochemical synthesis of drug–drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug–drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy–energy dispersive X-ray spectroscopy analysis (SEM–EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χMET·HCl = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χMET·HCl = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔHfus and ΔSfus) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.

Renal outcomes of diabetic patients treated with combination therapy of ACE inhibitors plus either thiazide diuretics or calcium channel blockers: comparative retrospective cohort study in Northwestern Ethiopia

ObjectiveThe study determined the comparative renal functions on patients with diabetes treated with ACE inhibitors (ACEIs) plus either thiazide diuretics or calcium channel blockers (CCBs) in Northwestern Ethiopia.DesignRetrospective cohort study design was employed to collect the data from medical records of patients with diabetes followed for 1–5 years (N=404).SettingThe medical records of patients in chronic diabetic follow-up clinics of the hospital.ParticipantsAll the patients with diabetes medical records in Northwestern Ethiopian specialised hospital.Main outcome measuresExposures were ACEIs plus thiazide diuretics or CCBs collected from March to June 2020. Outcomes were defined as declining in estimated glomerular filtration rate (eGFR) values by ≥30% from the baseline recorded from 2015 to 2019. Descriptive and analytical statistics were illustrated to compare the study groups. Kaplan-Meier with log- rank test was used to plot the survival analyses curve. Potential factors substantially associated to renal events were examined using cox proportional hazards model.ResultAbout 20% of patients developed renal events and significant numbers were from hydrochlorothiazide (HCT) users. The mean eGFR levels were significantly higher in patients on CCBs users over the follow-up years compared with HCT-based users. The CCBs users had an 18.8 mL/min/1.73 m2 higher in eGFR levels at the end of the follow-up period than HCT users (p<0.001). HCT users had shorter survival probability overtime to develop the outcomes compared with CCBs users (p=0.003). The CCBs-based regimen prevented risks of declining in renal function by 56.4% than HCT (p=0.001). Hazards of declining in eGFR levels were 93% higher for the patients with initial systolic blood pressure (SBP) levels were more than 150 mm Hg (p=0.006).ConclusionCompared with HCT, patients on CCBs had significantly prevented risks of renal events. However, both groups appeared with the same cardiovascular events. HCT-based regimen and higher initial SBP levels were significantly associated with eGFR reductions.

Diabetes Insipidus Complicating Management in a Child with COVID-19 and Multiorgan System Failure: A Novel Use for Furosemide

Judicious balance of fluids is needed for optimal management of acute respiratory distress syndrome (ARDS). Achieving optimal fluid balance is difficult in patients with disorders of fluid homeostasis such as diabetes insipidus (DI). There is little data on the use of Furosemide to aid in balancing fluid and electrolytes in patients with DI. Here, we present a critically ill 11-year-old female with developmental delay, septo-optic dysplasia, central DI, and respiratory failure secondary to COVID-19 ARDS. She required careful titration of a Vasopressin infusion in addition to IV Furosemide for successful management of fluid and electrolyte derangements. On admission, she demonstrated high-volume urine output with mild hypernatremia (serum sodium 156 mmol/L). Despite her maximum Vasopressin infusion rate of 8 mU/kg/hr, by day two of admission, she voided a total of 4 L resulting in severe hypernatremia (serum sodium 171 mmol/L). With continually high Vasopressin infusion rates, her overall fluid balance became increasingly net positive, although her hypernatremia persisted. Her ARDS continued to worsen. After 48 hours of the addition of intermittent Furosemide, successful diuresis along with resolution of hypernatremia was achieved. The combination of IV Furosemide with Vasopressin infusion resulted in tailored diuresis and more controlled titration of serum sodium levels than adjustment in Vasopressin and fluids alone. These results are in contradistinction to the published literature, which focuses on the use of thiazide diuretics in managing DI. This experience highlights the potential for loop diuretics to aid in establishing a desired fluid and electrolyte status in managing patients with both DI and ARDS.

DESIGN AND MOLECULAR DOCKING OF SULFONAMIDE DERIVATIVES

Objective: Sulfonamides are a sulfa-related group of antibiotics, which are used to treat bacterial infections and some fungal infections. Some sulfonamides are also devoid of antibacterial activity, such as thiazide diuretics, etc. In this study, an effort was made to find out some novel and potent Sulfonamide derivatives as diuretic agents. Methods: Here, 30 three-dimensional sulphonamides are designed and docking simulation with PDB ID 1AZM which was downloaded from www. rcsb. org. All the molecules were also screened through a preliminary property filter (Molinspiration Property Calculator). Results: Among the 30 different molecules designed, 5 molecules were found to have a very good affinity towards the target protein. Conclusion: These molecular properties define if a molecule can be orally active in our body.