24-hour Urine Output Research Articles

P-1252. Individualizing Antibiotic Therapy: Pharmacokinetic Approach to Evaluate and Optimize dosing of Meropenem in Critically Ill Sepsis Patients

Abstract Background The optimization of antibiotic dosing poses a considerable challenge, particularly in cases of Sepsis with acute renal impairment requiring continuous renal replacement therapy (CRRT). This study centers on the widely prescribed broad-spectrum beta-lactams, specifically meropenem, recognizing its extensive use in severe and complex clinical scenarios. The primary objectives of this study is to formulate new guidelines facilitating dose individualization, thus enhancing therapeutic outcomes for this critical population. Meropenem dosing recommendations for sepsis shock patients with acute renal impairment Methods Three studies were conducted based on specific hypotheses. The initial study involved a comprehensive systematic literature review aimed at critically evaluating the existing evidence regarding the dosing regimens of meropenem. Subsequently, Studies 2 and 3 were undertaken as observational, prospective, open-labeled, multicenter pharmacokinetic investigations within the Intensive Care Unit of a prominent tertiary care hospital in Coimbatore, India. The study cohort comprised thirty patients administered with meropenem experiencing septic shock with acute renal impairment requiring continuous renal replacement therapy. Population Pharmacokinetic models were meticulously developed, validated, and subjected to Monte Carlo simulations for comprehensive analysis. Results A comprehensive literature review exposed the limitations of current dosing recommendations, pointing to varied sickness severities, renal function levels, admission diagnostics, CRRT settings, and disparate pharmacokinetic (PK) methodologies. For meropenem, a crucial relationship between 24-hour urine output and total clearance emerged. Oligoanuric patients (< 100mL/24h) displayed a 30% decrease in total clearance compared to those with preserved diuresis ( >500mL/24h). Monte Carlo simulations supported tailored dosing recommendations, addressing bacterial susceptibility and patient diuresis status. Conclusion For optimal antibiotic dosing, our findings highlight the importance of considering clinical and demographic factors, including 24-hour urine output and patient weight. These insights can be implemented at the bedside to help navigate the complexities of antibiotic optimization within the Intensive Care Unit. Disclosures All Authors: No reported disclosures

An interpretable machine learning model for predicting in-hospital mortality in ICU patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in ICU, significantly associated with poor outcomes. However, there is currently a lack of reliable and interpretable tools for assessing the risk of in-hospital mortality in VAP patients. This study aims to develop an interpretable machine learning (ML) prediction model to enhance the assessment of in-hospital mortality risk in VAP patients. This study extracted VAP patient data from versions 2.2 and 3.1 of the MIMIC-IV database, using version 2.2 for model training and validation, and version 3.1 for external testing. Feature selection was conducted using the Boruta algorithm, and 14 ML models were constructed. The optimal model was identified based on the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, and specificity across both validation and test cohorts. SHapley Additive exPlanations (SHAP) analysis was applied for global and local interpretability. A total of 1,894 VAP patients were included, with 12 features ultimately selected for model construction: 24-hour urine output, blood urea nitrogen, age, diastolic blood pressure, platelet count, anion gap, body temperature, bicarbonate level, sodium level, body mass index, and whether combined with congestive heart failure and cerebrovascular disease. The random forest (RF) model showed the best performance, achieving an AUC of 0.780 in internal validation and 0.724 in external testing, outperforming other ML models and common clinical scoring systems. The RF model demonstrated robust and reliable performance in predicting in-hospital mortality risk for VAP patients. The developed online tool can assist clinicians in efficiently assessing VAP in-hospital mortality risk, supporting clinical decision-making.

A study of the difference in biochemical metabolism between patients with unilateral and bilateral upper urinary tract stones

Bilateral upper urinary tract stones are more likely to lead to impairment of renal function, but few biochemical metabolic studies of bilateral upper urinary tract stones have been reported. We collected clinical data from 555 patients with upper urinary tract stones admitted to Beijing Tsinghua Changgung Hospital from June 2020 to June 2024, and divided them into unilateral and bilateral stone groups by CT scans, analysed the metabolic differences between unilateral and bilateral stone groups by statistical methods, and used multifactorial logistic regression analysis to explore the risk factors that might affect the formation of bilateral stones. A total of 281 cases of unilateral and 274 cases of bilateral stones were identified. The proportion of male patients in the bilateral group was higher than that in the unilateral group (P < 0.05). The most prevalent major stone component was calcium oxalate monohydrate (48.1%), with a significantly higher prevalence of cystine stones observed in the bilateral stone group (1.8%) compared to the unilateral stone group (0.4%) (P < 0.05). Blood uric acid, blood BUN, blood creatinine, urine pH, and 24-hour urine output were higher in the bilateral stone group than in the unilateral group (P < 0.05). The most prevalent metabolic abnormality was low urine volume (45.7%). Bilateral stone group had higher proportion of patients with hyperuricemia (P < 0.05). The results of the multivariate logistic regression analysis showed that male gender (OR 1.489, 95% CI 1.028–2.157) and hyperuricemia (OR 1.662, 95% CI 1.113–2.482) were associated with an increased risk of bilateral stone formation (P < 0.05). There are significant differences in biochemical metabolism between unilateral and bilateral upper urinary tract stones. The most common metabolic abnormality in patients with urolithiasis is low urine output, and aggressive water intake is effective in preventing stone formation. For patients with hyperuricemia, a strict dietary regimen is imperative to mitigate the likelihood of bilateral stone formation.

Efficacy of acupuncture for pregnancy with early-onset ovarian hyperstimulation syndrome: study protocol for a randomised controlled clinical trial

IntroductionAlthough ovarian hyperstimulation syndrome (OHSS) is a common complication primarily seen in patients undergoing in vitro fertilisation-embryo transfer, there is no recognised effective treatment to manage it, especially for pregnant...

Abstract 4140120: Artificial intelligence-driven morbidity prediction in acute kidney injury after acute type A aortic dissection surgery

Background: Acute kidney injury (AKI) often complicates acute type A aortic dissection (ATAAD), with elevated comorbidity rates and a significant tie to in-hospital mortality. Identifying risk factors early can mitigate AKI severity. Research Questions: This research endeavors to develop and corroborate predictive models leveraging Machine Learning (ML) techniques from Artificial Intelligence to forecast AKI occurrences in ATAAD-afflicted individuals. Methods: The study employed various machine learning (ML) algorithms including Gradient Boosting Machine (GBM), LightGBM, Random Forest (RF), K-Nearest Neighbors (KNN), Multi-Layer Perceptron Neural Network (MLP-NN), Naive Bayes (NB), Logistic Regression (LR), and ensemble methods (combining LR&amp;LightGBM), employing tenfold cross-validation. Model performance was evaluated using SHapley Additive exPlanations (SHAP). A web-based tool for predicting AKI incidence was developed using Streamlit, based on the most effective model. The analysis involved 1350 ATAAD patients, among whom 586 (43.4%) developed post-operative AKI. Patients were divided into two cohorts: 85% for training and 15% for testing, with 126 features included in the predictive model. Results: Incorporating top 10 features, LightGBM (AUROC=0.886, 95% CI 0.841-0.930) excelled in predictive accuracy, calibration, and clinical utility, identifying key factors such as ventilation time in ICU, hourly urine output post-surgery, diuretic use, Scr, heart rate, urea, administration of recombinant human brain natriuretic peptide and ebrantil, MCHC, and blood glucose as associated with ATAAD-AKI. Conclusion(s): These ML models are robust tools for predicting AKI in ATAAD patients, with LightGBM's superior predictive ability standing out. They offer valuable support for clinical decision-making in ATAAD management, helping optimize postoperative strategies to minimize AKI occurrence after surgery.

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney failure, contributing to elevated morbidity and mortality rates in individuals with diabetes. Despite its potential renoprotective effects, the molecular mechanism by which gastrodin (GSTD) impacts DN remains unclear. To investigate this, mice were initially induced with DN via intraperitoneal streptozotocin (STZ) injection (50mg/kg) and subsequently treated with varying doses of GSTD (5, 10, 20mg/kg). Furthermore, the potential molecular mechanism of GSTD in mitigating DN was explored in vivo in conjunction with compound C, an inhibitor of 5'-AMP-activated protein kinase (AMPK). Subsequently, the blood weight, fasting blood glucose levels, and renal injury markers of DN-afflicted mice were assessed. Additionally, renal tissues were subjected to quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to evaluate inflammatory factor levels, colorimetric assays to measure renal malondialdehyde (MDA) levels, and immunoblotting analysis to examine AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The results demonstrated that a 6-week GSTD regimen effectively improved metabolic manifestations associated with DN, including reductions in fasting blood glucose levels, 24-hour urine output, renal indices, amelioration of glomerular histopathological abnormalities, diminished glycogen accumulation, and fibrosis. Furthermore, DN-afflicted renal tissues exhibited decreased MDA levels and elevated expression of AMPK/Nrf2 pathway-associated proteins. The beneficial effects of GSTD on DN and its protein modulation were reversed upon co-intervention with compound C. Together, our findings imply that GSTD improves DN by activating the AMPK/Nrf2 pathway, thereby mitigating STZ-induced renal damage, inflammatory responses, and oxidative stress.

Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.

Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

Abstract 36: Ablation of T-Lymphocyte β-Arrestins Reduces Inflammation and Increases Salt Retention in the Absence of Blood Pressure Changes Following Angiotensin II Infusion

Introduction: T-cells contribute to hypertension (HT) development. Among several G-protein coupled receptors regulating T-cell function, it has been hypothesized that some subpopulations use the angiotensin II (ANG II) type 1 receptor (AT 1 R) to modulate immune responses in HT. Selective ablation of AT 1 Rs in T-cells paradoxically increases hypertensive end-organ damage (EOD). While AT 1 Rs typically induces classical G-protein signaling, recent studies have uncovered a protective signaling cascade via β-arrestin ( ARRB ) proteins. We hypothesize that T-cell ARRB s mediate an anti-hypertensive and anti-inflammatory role in response to ANG II, decreasing EOD in HT. Methods: Breeding CD4-Cre mice with Arrb1 -Flox or Arrb2 -Flox mice generated lines with T-cell-specific deficiency of Arrb1 or Arrb2 genes. Hypertensive conditions modeling kidney damage consisted of unilateral nephrectomy, 4% salt diet, and continuous infusion of 1 mg/kg/min ANG II (UNX/HSD/ANG). Age/sex-matched Cre - littermates were used as controls (WT). Blood pressure (BP) was measured at baseline and for the following three weeks using radiotelemetry. Results: At baseline, there were no significant differences in systolic BP between groups (WT:124.1±8.0 mmHg; CD4 Arrb1-null :125.4±8.1; CD4 Arrb2-null :128.7±3.1; p =0.37; n=12/10/8). Three weeks of UNX/HSD/ANG equally increased systolic BP in all groups (WT:178.0±14.0 mmHg; CD4 Arrb1-null :174.8±26.3; CD4 Arrb2-null :179.9±11.1; p =0.86; n=7/9/7). Despite similar BPs, CD4 Arrb2-null mice demonstrated less renal inflammation than WT after four weeks of UNX/HSD/ANG, with a reduction in interleukin-1α protein (3.8±3.2 vs. 8.3±2.8 p &lt;0.05; n=4/6) and a trend towards decreased tumor necrosis factor-α transcript (0.63-fold change vs. 1.9, p =0.051; n=10/8). Furthermore, CD4 Arrb1-null mice increased 24-hour voluntary water intake compared to WT (15.7±3.4 mL vs. 12.2±1.6; p &lt;0.05; n=12/7), and 24-hour urine output (10.0±3.7 mL/d vs. 6.8±1.5; p &lt;0.05; n=11/8). However, there was no difference in sodium excretion during this period (1.9±0.5 eq/d vs. 1.7±0.1; p =0.14; n=11/7). Interestingly, 4 hours after intraperitoneal saline injection, CD4 Arrb1-null mice excreted significantly less sodium compared to WT (5.6±3.5% vs . 31.4±10.6%; p &lt;0.05; n=4/5). Conclusion: Contrary to our hypothesis, these data suggest that T-cell Arrb s do not protect against the hypertensive response to ANG II, but instead play a complicated role in the modulation of hydromineral balance and inflammation.

The Urine Output Response to Low-Dose Diuretic Challenge Predicts Tolerance to Negative Fluid Balance in Mechanically Ventilated, Critically Ill Patients.

Background and objective Although early diuretic use and negative fluid balance (NFB) have been associated with lower mortality in mechanically ventilated patients, some patients are not tolerant to NFB. Little is known about whether urine output response after the diuretic administration predicts NFB tolerance in mechanically ventilated patients. Hence, we conducted this study to look into this. Methods This was a single-center, prospective, observational study. We included mechanically ventilated patients who were hemodynamically stable with bilateral pulmonary opacities on chest radiography and planned to be diuresed per our fluid removal protocol. In the protocol, a low dose of furosemide adjusted to each patient's estimated glomerular filtration rate (eGFR) was administered, and then we started to measure urine outputs hourly for four hours. Tolerance to NFB was defined as "absence of hypotension, fluid resuscitation and vasopressors use, and acute kidney injury during fluid removal". We investigated whether the urine output predicts the tolerance to NFB during fluid removal treatment. Results A total of 60 mechanically ventilated patients were included. Notably, 80% (48/60) of the patients were tolerant to NFB. All hourly and cumulative urine output measurements during the first four hours after the first diuretic administration were significantly higher in the NFB-tolerant group than in the non-tolerant group. Among all hourly and cumulative urine output measurements, the first four-hour cumulative urine output showed the highest area under the receiver operating characteristic curve (AUC) of 0.83 for predicting the tolerance to NFB. Multivariate logistic regression analysis adjusted for the urine output two hours before the diuretic use showed that each 100-mL increase in the first four-hour cumulative urine output was significantly associated with an increased odds ratio (OR) of the tolerance to NFB [adjusted odds ratio (aOR): 1.53; 95% CI: 1.11-2.15]. Conclusions Based on our findings, the first four-hour cumulative urine output after the first low dose of diuretic administration might help predict tolerance to NFB during fluid removal treatment in mechanically ventilated, critically ill patients.

Prognostic value of first 24-hour urine output in patients with acute myocardial infarction in intensive care units: a retrospective study based on the MIMIC-IV database.

To investigate the effect of first 24-hour (24-h) urine output (UO) on in-hospital and 1-year mortality in patients admitted to intensive care units due to acute myocardial infarction. This was a retrospective cohort study based on the medical information mart for intensive care IV database involving patients admitted to intensive care units due to acute myocardial infarction. Patients were classified as low UO (LUO), high UO (HUO), and middle UO with a first 24-h UO below 800ml, over 2500ml, or in between, respectively. The primary outcome was in-hospital mortality and the secondary outcome was 1-year mortality. A total of 4337 patients were involved. Taking middle UO group as reference, after adjusting for confounders including age, gender, height, weight, comorbidity, occurrence of cardiogenic shock, revascularization, blood pressure, creatinine, N-terminal pro-brain natriuretic peptide, and use of loop diuretics, LUO was independently associated with higher in-hospital mortality [odds ratio 4.05, 95% confidence interval (CI): 3.12-5.26], while HUO was an independent protective factor (odds ratio 0.52, 95% CI: 0.35-0.77). In the multivariant Cox regression model, LUO was an independent risk factor for 1-year mortality (hazard ratio 2.65, 95% CI: 2.16-3.26), while HUO did not show significant association. In patients admitted to intensive care units due to acute myocardial infarction, first 24-h UO <800ml was a strong predictor for higher in-hospital and 1-year mortality, while first 24-h UO over 2500ml was associated with lower in-hospital mortality but not long-term mortality.

#1651 Urinary oxygen partial pressure: closely associated with hourly urine output induced by furosemide in patients with acute renal injury

Abstract Background and Aims Urine oxygen level, an indicator of kidney medullar oxygenation, is promising for predicting the onset of acute kidney injury (AKI). Furosemide, a commonly used diuretic in ICU, significantly increases urine output and is believed to change kidney medullar oxygenation. We monitored the longitudinal change of urinary oxygen partial pressure during bolus or pump administration of furosemide, aiming to describe the reaction pattern in an AKI-susceptible patient population. Method The prospective observational pilot study included seven adult patients in the ICU because of cardiac surgery or sepsis. We monitored the continuous urinary oxygen partial pressure for 8-24 hours through a device placed between the urinary catheter and collecting bag during furosemide administration, recorded hourly urine output simultaneously from a urine bag, and followed the patients in the hospital for the onset and development of AKI. Results We recruited three female patients and four male patients with an average age of 54 years and a medium of 5 days in ICU with an AKIN stage I of AKI during their hospital stay. None of them developed more severe stage AKI or required any kidney replacement therapy. We found a reverse correlation pattern between hourly urine output and urinary oxygen partial pressure. Specifically, the urine oxygen level dropped during urine volume increase caused by furosemide bolus administration and abolished by furosemide administration through a pump with more stable urine output. The paired t-test showed a significant increase in average urine oxygen level (mean difference = 21.2 mmHg, p = 0.044) recorded during the “high hourly urine output” period compared to the “low hourly urine period”. Conclusion We first found a drop in urinary oxygen partial pressure during the high urine output period elicited by bolus furosemide administration. It shed light on the confounding factors in AKI predicating during possible furosemide administration.

Mortality rates among adult critical care patients with unusual or extreme values of vital signs and other physiological parameters: a retrospective study.

We evaluated relationships of vital signs and laboratory-tested physiological parameters with in-hospital mortality, focusing on values that are unusual or extreme even in critical care settings. We retrospectively studied Philips Healthcare-MIT eICU data (207 U.S. hospitals, 20142015), including 166,959 adult-patient critical care admissions. Analyzing most-deranged (worst) value measured in the first admission day, we investigated vital signs (body temperature, heart rate, mean arterial pressure, and respiratory rate) as well as albumin, bilirubin, blood pH via arterial blood gas (ABG), blood urea nitrogen, creatinine, FiO2 ABG, glucose, hematocrit, PaO2 ABG, PaCO2 ABG, sodium, 24-hour urine output, and white blood cell count (WBC). In-hospital mortality was ≥50% at extremes of low blood pH, low and high body temperature, low albumin, low glucose, and low heart rate. Near extremes of blood pH, temperature, glucose, heart rate, PaO2 , and WBC, relatively. Small changes in measured values correlated with several-fold mortality rate increases. However, high mortality rates and abrupt mortality increases were often hidden by the common practice of thresholding or binning physiological parameters. The best predictors of in-hospital mortality were blood pH, temperature, and FiO2 (scaled Brier scores: 0.084, 0.063, and 0.049, respectively). In-hospital mortality is high and sharply increasing at extremes of blood pH, body temperature, and other parameters. Common-practice thresholding obscures these associations. In practice, vital signs are sometimes treated more casually than laboratory-tested parameters. Yet, vitals are easier to obtain and we found they are often the best mortality predictors, supporting perspectives that vitals are undervalued.

Assessment of Mitochondrial Function in a Mouse Model of Mild Chronic Kidney Disease Induced by High-Fat and High-Salt Diet

Intro: Kidneys are known for high energy demands involved in active transport and are thus highly oxidative organs, consuming the second-highest amount of oxygen per gram of tissue at rest (only exceeded by the heart). Chronic kidney disease (CKD) is a complex disorder that presents substantial challenges in understanding its pathophysiological mechanisms, including mitochondrial alterations. However, there are no established mouse models that recapitulate the CKD phenotype observed in humans.Hypothesis: We hypothesized that a high-fat, high-salt diet would induce a mild CKD phenotype and mitochondrial dysfunction in mice. Methods: We subjected C57Bl/6 mice to a high-fat (42%) and high-salt (8% NaCl) diet (HF/HNaCl) or standard chow diet for 16 weeks (n=4 per group). Additionally, we conducted comprehensive investigations into mitochondrial function, focusing on state 3 mitochondrial oxygen consumption (Oroboros O2K) and adenosine triphosphate (ATP) production (Horiba Fluoromax). Differences between groups were determined using Student’s t-tests. Results: HF/HNaCl feeding resulted in polyurea indicated by an increase in 24-hour urine output (Chow: 1.5 ± 0.2 mL; HF/HNaCl: 3.7 ± 0.8 mL; p=0.05) and a 30% reduction in glomerular filtration rate compared to chow-fed animals (Chow: 911.2 ± 107.8 μL/min/100g; Hf/HNaCl: 639.5 ± 25.9 μL/min/100g; p=0.08), indicative of the development of mild kidney disease. Although subtle changes were observed in mitochondrial oxygen consumption and ATP production, the alterations were not statistically significant. Discussion: Our findings suggest that the induced mild CKD state via the dietary regimen led to moderate renal impairment without substantial impacts on mitochondrial respiratory capacity and ATP synthesis. The establishment of this mouse model provides a valuable platform for further investigations into the complex interplay between renal dysfunction and mitochondrial dynamics in the context of mild CKD, offering insights that may pave the way for the development of targeted therapeutic interventions for this prevalent and debilitating condition. This project was supported by grants from the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury

Introduction: AKI is a frequent complication of critical illness and portends poor outcome. CCL14 is a validated predictor of persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 h. Methods: In pooled data from 2 studies of critically ill patients with KDIGO stage 2–3 AKI, CCL14 was measured by NEPHROCLEAR™ CCL14 Test on the Astute 140® Meter (low, intermediate, and high categories [1.3 and 13 ng/mL]). Average hourly urine output over 48 h, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed and logistic regression models. Results: Of the 497 subjects with median age of 65 (56–74) years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, hourly urine output over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis, CCL14 risk category was independently associated with low urine output on day 2 per KDIGO stage 3 (adjusted for diuretic use and baseline clinical variables), and composite of dialysis or death within 7 days (adjusted for urine output within 48 h of CCL14 measurement). Conclusions: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 h, oliguria on day 2, and dialysis within 7 days.

Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure

The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95%CI: 0.41-1.02; P=0.06). Dapagliflozin was associated with reduced loop diuretic doses (560mg [Q1-Q3: 260-1,150mg] vs 800mg [Q1-Q3: 380-1,715mg]; P=0.006) and fewer intravenous diuretic up-titrations (P≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P=0.03) and urine output (P=0.005), expediting hospital discharge over the study period. Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute HeartFailure [DICTATE-AHF]; NCT04298229).

Adjusting Acute Kidney Injury Kidney Disease: Improving Global Outcomes Urine Output Criterion for Predicted Body Weight Improves Prediction of Hospital Mortality.

Based on the Kidney Disease: Improving Global Outcomes (KDIGO) definitions, urine output, serum creatinine, and need for kidney replacement therapy are used for staging acute kidney injury (AKI). Currently, AKI staging correlates strongly with mortality and can be used as a predictive tool. However, factors associated with the development of AKI may affect its predictive ability. We tested whether adjustment for predicted (versus actual) body weight improved the ability of AKI staging to predict hospital mortality. A total of 3279 patients who had undergone cardiac surgery in a university hospital were retrospectively analyzed. AKI was staged according to KDIGO criteria (standard staging) and after adjustment for hourly urine output adjusted by predicted body weight for each patient and each day of their hospital stay. The incidence of AKI (all stages) was 43% (predicted body weight adjusted) and 50% (standard staging), respectively (P < .001). In sensitivity-specificity analyses for predicting hospital mortality, the area under the curve was significantly higher after adjustment for predicted body weight than with standard staging (P = .002). Compared to standard staging, adjustment of urine output for predicted body weight increases the specificity and improves prediction of hospital mortality in patients undergoing cardiac surgery.

The Efficacy and Safety of Intravenous Colistin Plus Aerosolized Colistin Versus Intravenous Colistin Alone in Critically Ill Trauma Patients With Multi-Drug Resistant Gram-Negative Bacilli Infection.

Gram-negative bacteria (GNB) with potential multiple drug resistance (MDR) have emerged as a major group of organisms causing ventilator-associated pneumonia (VAP). Higher concentrations are deposited directly in the lungs when antibiotics are given via inhalation, minimizing systemic side effects. This study aims to compare the efficacy and safety of intravenous plus aerosolized colistin versus intravenous (IV) colistin alone in critically ill trauma patients who reported MDR-GNB infection on endotracheal aspirate culture. A hundred patients were recruited in the Intensive Care Unit, Trauma Centre, Institute of Medical Sciences, Banaras Hindu University, Varanasi, and randomly assigned to the control (n=50) group, which received IVcolistin plus aerosolized colistin and the intervention group (n = 50), which received IVcolistin alone. Changes in total leucocyte count (TLC), renal function test (RFT), endotracheal aspirate culture, 24-hour urine output, length of ICU stay, and 28-day ICU mortality were investigated. Patients receiving intravenous plus nebulized colistin therapy had a better outcome compared to IV colistin alone in terms of faster eradication of MDR-GNB infection. A rise in serum urea and creatinine levels was seen in both groups, which were significantly higher, along with a decrease in urine output in the group receiving intravenous colistin alone. No significant difference was observed in serum sodium and potassium levels in the RFT protocol, length of ICU stay, or 28-day ICU mortality. Intravenous nebulized colistin could be considered a better alternative therapy for VAP caused by multi-drug-resistant Gram-negative bacteria in the ICU in terms of faster microbiological cure and lesser nephrotoxicity.

MiR-497 Prevents Septic Kidney Injury and Improves Immune Function Through Inhibition of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Pathway

Abnormal expression of miR-497 is related to the progression of septic renal injury. This study aimed to identify the protective effect of miR-497 on septic renal injury and immune function. We established a rat model of septic renal injury with sham-operated group and treated rats with culture solution of miR-497, gentianella acuta (positive control group), miR-497 plus JAK/STAT pathway agonist, and distilled water (model group). After treatment, urine output and renal histopathological changes were detected. Flow cytometry and RT-qPCR determined the levels of serum Scr, BUN, KIM-1, NGAL, IgG, IgA, and IgM, and evaluated the CD4+T, CD8+T, NK cell activity. Western blot assessed the activity of JAK/STAT signaling pathway. The model group and pathway agonist group had the highest 24-hour urine output, serum Scr, BUN, KIM-1, and NGAL levels, followed by miR-497 group and positive control group, and sham-operated group. The CD4+T, and NK cell activity was reduced with a drop in IgG, IgA, IgM levels in rats with septic renal injury, but treatment with miR-497 or gentianella acuta restored the cell activity and Ig levels and addition of JAK/STAT pathway agonist would further decrease the immune cell activity. There was no difference between the model group and pathway agonist group, miR-497 group and positive control group (p &lt; 0.05). Following miR-497 group, and sham-operated group, the expression of miR-497 in model group, pathway agonist group, and positive control group was lowest (p &lt; 0.05). As the expression of JAK and STAT did not vary among five groups (p &gt; 0.05), we found highest expression of p-JAK and p-STAT levels in model group, positive control group, and pathway agonist group, and lowest expression in sham-operated group. miR-497 inhibits the activity of JAK/STAT signaling, up-regulates the activity of CD4+T, NK cells and levels of IgG, IgA, IgM, while inhibiting CD8+T cells activity to improve immune function. In conclusion, miR-497 attenuates septic kidney injury through inhibiting KIM-1 and NGAL expression, indicating that miR-497 and JAK/STAT pathways may be potential therapeutic targets for treating septic kidney injury.

The relationship between commencement of continuous renal replacement therapy and urine output, fluid balance, mean arterial pressure and vasopressor dose

Background and objectives: The effect of initiating continuous renal replacement therapy (CRRT) on urine output, fluid balance and mean arterial pressure (MAP) in adult intensive care unit (ICU) patients is unclear. We aimed to evaluate the impact of CRRT on urine output, MAP, vasopressor requirements and fluid balance, and to identify factors affecting urine output during CRRT. Design: Retrospective cohort study using data from existing databases and CRRT machines. Setting: Medical and surgical ICUs at a single university-associated centre. Participants: Patients undergoing CRRT between 2015 and 2018. Main outcome measures: Hourly urine output, fluid balance, MAP and vasopressor dose 24 hours before and after CRRT commencement. Missing values were estimated via Kaplan smoothing univariate time-series imputation. Mixed linear modelling was performed with noradrenaline equivalent dose and urine output as outcomes. Results: In 215 patients, CRRT initiation was associated with a reduction in urine output. Multivariate analysis confirmed an immediate urine output decrease (-0.092 mL/kg/h; 95% confidence interval [CI], -0.150 to -0.034 mL/kg/h) and subsequent progressive urine output decline (effect estimate, -0.01 mL/kg/h; 95% CI, -0.02 to -0.01 mL/kg/h). Age and greater vasopressor dose were associated with lower post-CRRT urine output. Higher MAP and lower rates of net ultrafiltration were associated with higher post-CRRT urine output. With MAP unchanged, vasopressor dose increased in the 24 hours before CRRT, then plateaued and declined in the 24 hours thereafter (effect estimate, -0.004 μg/kg/ min per hour; 95% CI, -0.005 to -0.004 μg/kg/min per hour). Fluid balance remained positive but declined towards neutrality following CRRT implementation. Conclusions: CRRT was associated with decreased urine output despite a gradual decline in vasopressor and a positive fluid balance. The mechanisms behind the reduction in urine output associated with commencement of CRRT requires further investigation.

FRI351 Pituitary Stalk Epidermoid Cyst: A Rare Cause Of Diabetes Insipidus

Abstract Disclosure: J.T. Batch: None. F. Warda: None. P. Natter: None. R. Makary: None. G.Y. Gandhi: None. Introduction: Epidermoid cysts are benign squamous epithelial cysts filled with keratin. They are rarely found in the central nervous system, constituting 0.2-1.8% of intracranial masses, with the majority located in the cerebellopontine angle. Case Report: A 34-year-old female presented with blurred vision, debilitating headaches, milky breast discharge, and no menstrual periods for three years. Prolactin was mildly high on two occasions at 40.3 and 52.8 ng/mL (3.0-30.0 ng/mL). Estradiol was low at 15 pg/ml in the setting of inappropriately normal FSH (10.1 mIU/mL) and LH (5.8 mIU/mL). ACTH, cortisol, TSH, free thyroxine, and IGF-1 were in the normal range. A pregnancy test was negative. A 1:100 diluted prolactin did not detect the hook effect. MRI revealed a 1.8 x 1.4 x 1.4 cm suprasellar mass centered along the pituitary stalk with peripheral enhancement and central cystic vs. necrotic components. It caused a mass effect on the optic chiasm. Formal visual field testing revealed a left inferior temporal defect. Subsequently, the patient reported increased thirst (consuming 4-5 L of water daily) and urination (confirmed with a 24-hour urine output of 4 L). Following 12 hours of overnight water deprivation, morning labs confirmed diabetes insipidus with high serum sodium of 146 mmol/L, high serum osmolality of 306 mOsm/kg, and low urine osmolality of 204 mOsm/Kg. Initiation of oral DDAVP 0.1 mg nightly resulted in a resolution of nocturia and dramatic improvement in thirst. The patient underwent transsphenoidal resection, during which the neurosurgeon identified a suprasellar cystic lesion with classic epidermoid pearl white material. The lesion and capsule were resected, and patient started on dexamethasone 6 mg IV every 6 hours to prevent chemical meningitis. Pathology was consistent with an epidermoid cyst. Prolactin stained several cells, possibly from compression of the pituitary stalk by the epidermoid cyst. Postoperatively, the patient had severe headaches, and photophobia thought to be associated with chemical meningitis. Lumbar puncture revealed elevated CSF neutrophils and aseptic culture. The patient was continued on dexamethasone with slow taper upon discharge. DDAVP was increased to 0.1 mg twice daily as polyuria and polydipsia worsened. Discussion: There have been six reported cases of epidermoid cysts involving the pituitary stalk. Visual disturbance and headaches are common, while galactorrhea and amenorrhea are uncommon. Preoperative polyuria can be a frequent presenting symptom that can evolve into permanent postoperative diabetes insipidus. Surgical resection is the treatment of choice. It may be difficult to achieve complete excision due to the adherence of the cyst wall to the adjacent structures. The most common complications after resection include chemical meningitis (noted in our patient), hydrocephalus, infectious meningitis, and cranial nerve palsies. Presentation: Friday, June 16, 2023