To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).

Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality. Cox regression analysis assessed the risk of mortality across different MPP levels, adjusting for potential confounders. Subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings.

A total of 2318 patients with SA-AKI were stratified into five MPP trajectories by GBTM. Patients in Traj-1 and Traj-2, characterized by consistently low MPP (<60 mmHg), demonstrated markedly higher 90-d mortality (62.86% and 26.98%). RCS curves revealed a non-linear inverse relationship between MPP and 90-d mortality, identifying 60 mmHg as the optimal threshold. Patients with MPP ≤ 60 mmHg exhibited significantly elevated 90-d mortality compared to those with MPP > 60 mmHg (29.81% vs. 20.88%). Cox regression analysis established Traj-1 and Traj-2 as independent risk factors for increased mortality relative to Traj-3 (60-70 mmHg), with hazard ratios (HRs) of 4.67 (95%-CI 3.28-6.67) and 1.45 (95%-CI 1.20-1.76). MPP > 60 mmHg was significantly associated with reduced 90-d mortality (HR 0.65, 95%-CI 0.55-0.77). Subgroup and PSM analyses supported these findings.

Dynamic MPP trajectory serves as a valuable prognostic biomarker for SA-AKI. Early monitoring of MPP trends offers critical insights into renal perfusion management, potentially improving outcomes in SA-AKI.

Background: Although lactated Ringer's (LR) solution is widely used in managing patients with acute kidney injury (AKI), its specific impact on mortality remains unclear. This retrospective cohort study aimed to evaluate the effects of LR administration on survival outcomes in severely ill patients with AKI. Methods: Critically ill patients with AKI were identified using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Propensity score matching (PSM) was employed to address baseline discrepancies between patients who received LR and those who did not. The association of LR administration with survival, duration of hospitalization and intensive care unit (ICU) stay, requirement for renal replacement therapy (RRT), renal function recovery, and hyperkalemia was analyzed using restricted mean survival time (RMST), logistic regression, and linear regression models. Results: A total of 5620 patients with AKI were included. Following PSM, LR administration was associated with prolonged survival at 28 and 90 days compared to non-LR use (28-day survival increase: 1.12 days, 95% confidence interval [CI] 0.62-1.63, p < 0.001; 90-day survival increase: 3.73 days, 95% CI 1.70-5.76, p < 0.001). The survival benefit became more pronounced, with higher LR use linked to more remarkable 90-day survival. However, LR administration did not significantly affect renal function recovery or hyperkalemia incidence. Conclusion: Administering LR to critically ill patients with AKI was associated with improved survival at both 28 and 90 days.

This study aimed to explore the role of peritoneal dialysis (PD) in patients with acute kidney injury (AKI) in relation to metabolic and fluid control, outcome and risk factors for death.

We performed a retrospective cohort study collecting data from a large reference Center in Brazil on patient characteristics, hospitalization, PD prescription and delivery, clinical outcomes and laboratory exams. We evaluated all patients who had been consecutively treated by PD between January 2004 and January 2024.

Four hundred eighty-seven patients were included. Median age was 64.02 ± 15 years, most of the patients were hospitalized in the intensive care unit (ICU) and needed vasoactive drugs and mechanical ventilation. Sepsis was the main cause of AKI followed by cardiorenal syndrome type 1. Uremia was the main indication for dialysis, followed by the need to meet metabolic and fluid demands. Blood urea nitrogen and creatinine levels stabilized after a median of four dialysis sessions. Fluid removal increased progressively and stabilized at around 2.320 ± 0.91 ml after four sessions. Mechanical complications occurred in 9.2% and peritonitis in 6.2% of patients. Regarding AKI outcome, 34.9% recovered renal function, 6.8% remained on dialysis for over 30 days, and 55.8% died. Technique failure occurred in 19.9% of the cases and the main cause was a mechanical complication. Age, hepatorenal syndrome, APACHE score and dropout from PD due to insufficient fluid control were identified as risk factors for death, while cardiorenal syndrome, need to meet metabolic and fluid demand as indication of dialysis, and negative fluid balance after 4 sessions of PD were identified as protective factors.

PD may be an effective solution for AKI patients, allowing adequate metabolic and fluid control. Age, APACHE score, hepatorenal syndrome and dropout from PD were associated with death, while cardiorenal syndrome, need to meet metabolic and fluid demands as indication of dialysis, and negative fluid balance were positive prognostic factors.

Capillary leakage is common in critical illness and can lead to intravascular hypovolemia and edema. Fluid balance, however, is crucial to optimize cardiac preload, vascular filling and tissue perfusion. Intravenously administered fluids are rapidly distributed to the extravascular spaces and further increase edema with consecutive harm for impeded wound healing, weakness, distribution of pharmaceutics to the third space and patient discomfort. We hypothesized that manual decongestive therapy (MDT) followed by elastic bandaging increases cardiac preload and reduces interstitial edema and thus, offers a promising approach to restore the imbalance in fluid distribution between the interstitium and the intravascular space in critically ill patients.

From November 2021 to May 2023, 34 critical ill requiring advanced hemodynamic monitoring with thermodilution-calibrated pulse contour analysis were randomized to either standard care or MDT followed by elastic bandaging for 24 h. Global end-diastolic volume index (GEDI) as a marker of the cardiac preload was measured 15, 30, 60 min and 24 h after MDT. Wrist and ankle circumferences were measured as markers of the extent of local interstitial edema.

In the intervention group, a significant increase in Δ GEDI was observed 15 min [median 48 (IQR 82) to median -19 (IQR 39)], 60 min [median 75 (IQR 106.5) to median -11 (IQR80)] and 24 h [median 107 (IQR 153) to median -16 (IQR 114)] after the study intervention compared to the control group. After 24 h ankle [median 23.5 (IQR 5) cm to median 24 (IQR 6) cm, p < 0.0001] and wrist] median 18 (IQR 2) cm to median 19 (IQR 2) cm, p < 0.0001] circumferences were increased significantly in the control group. In the intervention group a significant reduction in the ankle circumference [median 24.5 (IQR 5) cm to median 24 (IQR 4.5) cm, p < 0.0001] and a significant reduction in the wrist circumference [median 20 (IQR 3.8) cm to median 18 (IQR 3.5) cm, p < 0.0001], was observed after 24 h.

MDT increases cardiac preload and helps to reduce interstitial fluid overload and edema in critically ill patients.

This prospective randomized controlled trial was registered at the German Clinical Trials Register DRKS00026226 on 17/09/2021.

The role of loop diuretics in patients with acute kidney injury (AKI) is controversial. This study examined the association between the use of loop diuretics and prognosis in critically ill patients with AKI.

This study used data from the medical information mart for the intensive care IV database. Adult critically ill patients with AKI were included in the analysis. Patients were partitioned into two groups based on their use of loop diuretics in the ICU, and potentially confounding variables between the two groups were balanced using propensity score matching (PSM). We used time-dependent Cox proportional hazards regression, logistic regression, and Hodges-Lehman estimator to assess the impact of loop diuretics on all-cause mortality, renal replacement therapy (RRT) use, and the length of hospital stay, respectively.

This study included a cohort of 19,671 patients. After PSM, both groups consisted of 6200 patients. The use of loop diuretics was associated with a lower risk of in-hospital mortality (HR, 0.672; 95% CI 0.597-0.757; P < 0.001), lower in-ICU mortality (HR, 0.375; 95% CI 0.315-0.446; P < 0.001), and lower odds of in-hospital RRT (OR, 0.472; 95% CI 0.400-0.555; P < 0.001). A sensitivity analysis using the original cohort (HR, 0.624; 95% CI 0.561-0.693; P < 0.001) and weighted cohort (HR, 0.654; 95% CI 0.582-0.736; P < 0.001) also demonstrated lower in-hospital all-cause mortality.

The use of loop diuretics is associated with a substantial reduction in mortality among critically ill patients with AKI.

Fluids administered as drug diluents with intravenous (IV) medicine constitute a substantial fraction of fluids in inpatients. Whether physicians are aware of fluid volumes administered with IV antibiotics for patients with suspected infections is unclear. Moreover, whether this leads to adjustments in 24-hour fluid administration/antibiotics is unknown.

This cross-sectional interview-based study was conducted in three emergency departments. Physicians were interviewed after prescribing around-the-clock IV antibiotics for ≥24 hours to patients with suspected infection. A structured interview guide assessed the physicians' awareness, considerations, and practices when prescribing IV antibiotics. The 24-hour antibiotic fluid volume was calculated.

We interviewed 100 physicians. The 24-hour fluid volume administered with IV antibiotics was 400 mL (interquartile range, 300-400 mL). Overall, 53 physicians (53%) were unaware of the fluid volume administered with IV antibiotics. Moreover, 76 (76%) did not account for the antibiotic fluid volume in the 24-hour fluid administration, and 96 (96%) indicated that they would not adjust prescribed fluids after receiving information about 24-hour antibiotic fluid volume administered for their patient. No comorbidities associated with fluid intolerance were the primary reason for not adjusting prescribed fluids/ antibiotics. Approximately 79 (79%) opted for visibility of fluid volumes administered with IV antibiotics in the medical record.

The majority of physicians were unaware of fluid volumes administered as a drug diluent with IV antibiotics. The majority chose not to make post-prescribing adjustments to their planned fluid administration; they regarded their patient as fluid tolerant. The physicians opted for visibility of fluid volumes administered as diluents during the prescribing process.

This study developed and validated a stacked ensemble machine learning model to predict the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis.

A retrospective study based on patient data from public databases.

This study analysed 1295 patients with acute pancreatitis complicated by septicaemia from the US Intensive Care Database.

From the MIMIC database, data of patients with acute pancreatitis and sepsis were obtained to construct machine learning models, which were internally and externally validated. The Boruta algorithm was used to select variables. Then, eight machine learning algorithms were used to construct prediction models for acute kidney injury (AKI) occurrence in intensive care unit (ICU) patients. A new stacked ensemble model was developed using the Stacking ensemble method. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, accuracy, recall and F1 score. The Shapley additive explanation (SHAP) method was used to explain the models.

AKI in patients with acute pancreatitis complicated by sepsis.

The final study included 1295 patients with acute pancreatitis complicated by sepsis, among whom 893 cases (68.9%) developed acute kidney injury. We established eight base models, including Logit, SVM, CatBoost, RF, XGBoost, LightGBM, AdaBoost and MLP, as well as a stacked ensemble model called Multimodel. Among all models, Multimodel had an AUC value of 0.853 (95% CI: 0.792 to 0.896) in the internal validation dataset and 0.802 (95% CI: 0.732 to 0.861) in the external validation dataset. This model demonstrated the best predictive performance in terms of discrimination and clinical application.

The stack ensemble model developed by us achieved AUC values of 0.853 and 0.802 in internal and external validation cohorts respectively and also demonstrated excellent performance in other metrics. It serves as a reliable tool for predicting AKI in patients with acute pancreatitis complicated by sepsis.

Acute kidney injury (AKI) is associated with an increased risk of morbidity, mortality, and healthcare expenditure, posing a major challenge in clinical practice, and affecting about 50% of patients in the intensive care unit (ICU), particularly the elderly and those with pre-existing chronic comorbidities. In health, intra-renal blood flow is maintained and auto-regulated within a wide range of renal perfusion pressures (60-100 mmHg), mediated predominantly through changes in pre-glomerular vascular tone of the afferent arteriole in response to changes of the intratubular NaCl concentration, i.e. tubuloglomerular feedback. Several neurohormonal processes contribute to regulation of the renal microcirculation, including the sympathetic nervous system, vasodilators such as nitric oxide and prostaglandin E2, and vasoconstrictors such as endothelin, angiotensin II and adenosine. The most common risk factors for AKI include volume depletion, haemodynamic instability, inflammation, nephrotoxic exposure and mitochondrial dysfunction. Fluid management is an essential component of AKI prevention and management. While traditional approaches emphasize fluid resuscitation to ensure renal perfusion, recent evidence urges caution against excessive fluid administration, given AKI patients' susceptibility to volume overload. This review examines the main characteristics of AKI in ICU patients and provides guidance on fluid management, use of biomarkers, and pharmacological strategies.

Septic shock is a significant challenge in the management of patients with burns and traumatic injuries when complicated by infection, necessitating prompt and effective haemodynamic support. This review provides a comprehensive overview of current strategies for vasopressor and fluid management in septic shock, with the aim to optimize patient outcomes. With regard to vasopressor management, we elaborate on the pharmacologic profiles and clinical applications of catecholamines, vasopressin derivatives, angiotensin II, and other vasoactive agents. Noradrenaline remains central to septic shock management. The addition of vasopressin, when sequentially added to noradrenaline, offers a non-catecholaminergic vasoactive effect with some clinical benefits and risks of adverse effects. Emerging agents such as angiotensin II and hydroxocobalamin are highlighted for their roles in catecholamine-resistant vasodilatory shock. Next, for fluid management, crystalloids are currently preferred for initial resuscitation, with balanced crystalloids showing benefits over saline. The application of albumin in septic shock warrants further research. High-quality evidence does not support large-volume fluid resuscitation, and an individualized strategy based on haemodynamic parameters, including lactate clearance and capillary refill time, is recommended. The existing knowledge suggests that early vasopressor initiation, particularly noradrenaline, may be critical in cases where fluid resuscitation takes inadequate effect. Management of refractory septic shock remains challenging, with novel agents like angiotensin II and methylene blue showing potential in recent studies. In conclusion, Further research is needed to optimize haemodynamic management of septic shock, particularly in developing novel vasopressor usage and fluid management approaches.

Background: We investigated the accuracy of predicting preload responsiveness by means of a passive leg raising test (PLR) using the perfusion index (PI) in critically ill patients showing signs of hypoperfusion in a resource-limited setting. Methods: We carried out a prospective observational single center study in patients admitted for sepsis or severe malaria with signs of hypoperfusion in Chattogram, Bangladesh. A PLR was performed at baseline, and at 6, 24, 48, and 72 h. Preload responsiveness assessed through PI was compared to preload responsiveness assessed through cardiac index (CI change ≥5%), as reference test. The primary endpoint was the accuracy of preload responsiveness prediction of PLR using PI at baseline; secondary endpoints were the accuracies at 6, 24, 48, and 72 h. Receiver operating characteristic (ROC) curves were constructed. Results: The study included 34 patients admitted for sepsis with signs of hypoperfusion and 10 patients admitted for severe malaria. Of 168 PLR tests performed, 143 had reliable PI measurements (85%). The best identified PI change cutoff to discriminate responders from non-responders was 9.7%. The accuracy of PLR using PI in discriminating a preload responsive patient at baseline was good (area under the ROC 0.87 95% CI 0.75-0.99). The test showed high sensitivity and negative predictive value, with comparably lower specificity and positive predictive value. Compared to baseline, the AUROC of PLR using PI was lower at 6, 24, 48, and 72 h. Restricting the analysis to sepsis patients did not change the findings. Conclusions: In patients with sepsis or severe malaria and signs of hypoperfusion, changes in PI after a PLR test detected preload responsiveness. The diagnostic accuracy was better when PI changes were measured at baseline.

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The medication regimen complexity intensive care unit (MRC-ICU) score has previously been associated with pharmacist workload and fluid overload. The purpose of this study was to determine the relationship of MRC-ICU score with pharmacist-driven fluid stewardship recommendations as a means of establishing its role in risk stratifying critically ill patients for pharmacist intervention.

Adult patients admitted to the medical ICU and followed by the academic pharmacy team were included in this retrospective, single-center cohort study. Patient and pharmacist data were collected via electronic medical record and surveillance tool, respectively. MRC-ICU and sequential organ failure assessment (SOFA) scores were captured at ICU admission. The primary outcome was correlation between MRC-ICU score and number of pharmacist-driven fluid stewardship recommendations. Secondary outcomes included the relationships between MRC-ICU score, accepted recommendations, and patient outcomes (fluid overload and length of stay [LOS]). Descriptive statistics were calculated for each variable. Spearman's rank-order correlation was used.

Of 168 patients, 22 (13%) experienced fluid overload. Median MRC-ICU and SOFA scores were 13 and 7, respectively, and were higher for patients experiencing fluid overload than for those without fluid overload. MRC-ICU had a weakly positive correlation with the number of pharmacist-driven fluid stewardship recommendations (ρ = 0.200; P = 0.010), fluid overload (ρ = 0.167; P = 0.030), and ICU LOS (ρ = 0.354; P < 0.001). These relationships remained true when looking at only the fluid stewardship recommendations that were accepted by the team.

MRC-ICU displayed a weakly positive correlation with pharmacist workload, suggesting its potential use in identifying patients likely to benefit from pharmacist intervention.

Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.

In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UFNET ≥ 100 ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25 ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.

Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.

In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Secondary mitral regurgitation (MR) is a common valvular heart disease burdening the prognosis of patients with co-existing chronic heart failure. Transcatheter edge-to-edge mitral valve repair (MV-TEER) is a minimally invasive treatment option for high-risk patients. However, the effects of MV-TEER on expanded hemodynamics, tissue perfusion, and quality of life, particularly in patients with advanced renal failure, remain underexplored.

This prospective, single-center study evaluated the impact of MV-TEER on hemodynamics, renal function, and quality of life in 45 patients with severe MR. Non-invasive bioimpedance monitoring with NICaS® was used to assess hemodynamics pre- and 3-5 days post-procedure. Quality of life was assessed using the EQ-5D-3L questionnaire before and 3 months post-procedure. For further analysis, patients were divided into subgroups based on the estimated baseline glomerular filtration rate (eGFR < 35 mL/min vs. eGFR ≥ 35 mL/min).

A significant reduction in systemic vascular resistance (SVR; p = 0.003) and an increase in eGFR (p = 0.03) were observed in the entire cohort after MV-TEER, indicating improved tissue perfusion. Notably, particularly patients with eGFR < 35 mL/min showed a significant increase in cardiac output (CO; p = 0.035), cardiac index (CI; p = 0.031), and eGFR (p = 0.018), as well as a reduction in SVR (p = 0.007). Consistent with these findings, quality of life significantly improved, with the EQ-5D-3L index and EQ-VAS score increasing from 0.44 to 0.66 (p < 0.001) and from 51.7% to 62.9% (p < 0.001).

Acute kidney injury (AKI) occurs frequently in the neurocritical intensive care unit and is associated with greater morbidity and mortality. AKI and its treatment, including acute kidney replacement therapy, can expose patients to a secondary greater brain injury. This study aimed to explore the role of peritoneal dialysis (PD) in neurocritical AKI patients in relation to metabolic and fluid control, complications related to PD and outcome.

Neurocritical AKI patients were treated by PD (prescribed Kt/V = 0.40/session) using a flexible catheter and a cycler and lactate as a buffer.

A total of 58 patients were included. The mean age was 61.8 ± 13.2 years, 65.5% were in the intensive care unit, 68.5% needed intravenous inotropic agents, 72.4% were on mechanical ventilation, APACHE II was 16 ± 6.67 and the main neurological diagnoses were stroke (25.9%) and intracerebral haemorrhage (31%). Ischaemic acute tubular necrosis (iATN) was the most common cause of AKI (51.7%), followed by nephrotoxic ATN AKI (25.8%). The main dialysis indications were uraemia and hypervolemia. Blood urea and creatinine levels stabilised after four sessions at around 48 ± 11 mg/dL and 2.9 ± 0.4 mg/dL, respectively. Negative fluid balance and ultrafiltration increased progressively and stabilised around 2.1 ± 0.4 L /day. Weekly delivered Kt/V was 2.6 ± 0.31. The median number of high-volume PD sessions was 6 (4-10). Peritonitis and mechanical complications were not frequent (8.6% and 10.3%, respectively). Mortality rate was 58.6%. Logistic regression identified as factors associated with death in neurocritical AKI patients: age (odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.09-2.16, p = 0.001), nephrotoxic AKI (OR = 0.78, 95% CI = 0.69- 0.95, p = 0.03), mechanical ventilation (OR = 1.54, 95% CI = 1.17-2.46, p = 0.01), intracerebral haemorrhage as main neurological diagnoses (OR = 1.15, 95% CI = 1.09-2.11, p = 0.03) and negative fluid balance after two PD sessions (OR = 0.94, 95% CI = 0.74-0.97, p = 0.009).

Our study suggests that careful prescription may contribute to providing adequate treatment for most neurocritical AKI patients without contraindications for PD use, allowing adequate metabolic and fluid control, with no increase in the number of infectious, mechanical and metabolic complications. Mechanical ventilation, positive fluid balance and intracerebral haemorrhage were factors associated with mortality, while patients with nephrotoxic AKI had lower odds of mortality compared to those with septic and ischaemic AKI. Further studies are needed to investigate better the role of PD in neurocritical patients with AKI.

Patients with chronic kidney disease (CKD) often have impaired immune function, making them more prone to infections that can lead to sepsis. The coexistence of these conditions can result in decreased hemoglobin levels and is associated with a higher mortality rate. To investigate whether the transfusion of red blood cells (RBCs) improves the prognosis of septic patients with concomitant CKD and to explore the indications for red blood cell transfusion. This retrospective cohort study utilizes data from the MIMIC-IV (v2.0) database. The study enrolled 6,604 patients with sepsis and concomitant CKD admitted to the Intensive Care Unit (ICU). Propensity score matching (PSM) was applied to adjust for confounding factors. Multivariate Cox regression analysis revealed an association between RBC transfusion and a decreased risk of 28-day mortality (HR: 0.61, 95% CI: 0.54-0.70, P < 0.001). Following a meticulous 1:1 propensity score matching analysis between the two cohorts, the matched population revealed a notable decrease in 28-day mortality within the RBC transfusion group (HR: 0.60, 95% CI: 0.51-0.71; P < 0.001). Additionally, we observed that a SOFA score ≥ 5, a Base Excess (BE) value < 3, and an estimated Glomerular Filtration Rate (eGFR) < 30 may be considered when evaluating the potential need for RBC transfusion. This study demonstrated an association between RBC transfusion and decreased 28-day mortality in patients with sepsis accompanied by CKD. The patient's BE value, SOFA score, and eGFR are crucial factors influencing the treatment outcome and should be considered when deciding on RBC transfusion.

Continuous renal replacement therapy (CRRT) used in cardiac surgery-associated acute kidney injury (CSA-AKI) may have different characteristics from other diseases. We reviewed the medical records of patients with CSA-AKI requiring CRRT who underwent cardiac surgery from January 2020 to September 2021. Patients with AKI caused by other reasons who received CRRT during the same period were also evaluated. A total of 28 patients with CSA-AKI and 12 patients with AKI caused by other reasons were enrolled in this study. Compared with AKI patients caused by other reasons, patients with CSA-AKI were found to have lower mean arterial pressure, higher level of bilirubin, higher vasoactive-inotropic score, and larger daily diuretic dosage. The patients with CSA-AKI were prescribed CRRT earlier than the patients with AKI caused by other reasons. There was a significant difference in the CRRT anticoagulation method between patients with CSA-AKI and patients with AKI caused by other reasons. Six patients with CSA-AKI were treated with regional citrate anticoagulation (RCA), and the other 22 patients were treated with low molecular weight heparin or without anticoagulants. The timing of CRRT initiation in patients with CSA-AKI is earlier than that in patients with AKI caused by other reasons. Although RCA is recommended as the preferred anticoagulant for patients without contraindications, patients with CSA-AKI often have circulatory dysfunction and severe liver damage, so the risk of citrate accumulation is greater, whether to use RCA should be determined according to the individual condition of the patient.

In patients with acute kidney injury (AKI), fluid balance management often relies on the prescription and achievement of fluid removal using intermittent renal replacement therapy (IRRT). This study aimed to describe characteristics associated with the failure to achieve target fluid removal (FATFR).

This is a retrospective cohort study including IRRT sessions of conventional duration (<5 hours) performed for AKI in the intensive care unit (ICU) from 2017 to 2022 at a tertiary academic center. FATFR-50% was defined as fluid removal of <50% of the prescribed target. Characteristics of patients and sessions, as well as outcomes at 90 days were collected. The causes of FATFR were manually adjudicated.

A total of 291 patients and 1280 IRRT sessions in the ICU were included. FATFR-50% occurred in 7.3% of sessions and 19.2% of patients had at least one session with FATFR-50% during the first week of IRRT. Sessions with FATFR-50% were characterized by a higher occurrence of intradialytic hypotension (24.2% vs 60.2%, P < .001) and a higher planned fluid removal (6.19 vs 5.27 m/kg/h, P = .02). Multiple episodes of FATFR-50% were associated with a positive cumulative fluid balance (β 3876 (CI 2053-5899) P < .001). At 90-day follow-up, FATFR-50% during the first week after IRRT initiation was independently associated with fewer ICU- and hospital-free days, as well as with a higher risk of mortality (odds ratio 2.01 CI 1.04-3.89, P = .04).

FATFR occurs in about one out of five critically ill patients within the first week of IRRT and is associated with adverse clinical outcomes.

Chloride transfers during continuous renal replacement therapy (CRRT) have not been adequately described and may differ based on CRRT technique. We aimed to measure chloride mass transfer (JS,Cl) during CRRT and identify associated determinants.

We performed a two-centre, prospective, observational study in France and Australia in ICU patients with CRRT initiated for <24 h. Patients received continuous veno-venous hemofiltration (CVVH) or continuous veno-venous haemodialysis (CVVHD, with citrate-CaCl2 regional anticoagulation). Over a 24 h period, plasma and effluent chloride concentrations were measured every 4 h to compute chloride mass transfer (JS,Cl, in mmol.min-1) using a modality-specific model, with negative value indicating chloride transfer towards the patient. Secondary outcomes were the identification of CRRT settings associated with JS,Cl (using multivariate mixed effects regression). Results are presented with median (interquartile range).

Between February 2021 and August 2022, we enrolled 37 patients (64 [56-71] years, 67% male), for a total of 20 CVVHD and 20 CVVH sessions. Over 24 h, plasma chloride concentrations were significantly higher, and JS,Cl significantly lower during CVVHD, compared to CVVH (-0.10 [-0.33 to 0.15] vs. 0.01 [-0.10 to 0.13] mmol.min-1, p < 0.05). With both modalities, net ultrafiltration (QUFNET) and plasma chloride concentrations were the principal determinants of JS,Cl, with higher QUFNET being associated with an increase in JS,Cl during CVVHD. Also, CVVHD sessions demonstrated a concentration gradient between the plasma and the effluent chamber of -6 [-9 to -4] mmol.L-1. Finally, CaCl2 reinjection during CVVHD accounted for 35% [32-60%] of total JS,Cl in sessions with a negative JS,Cl.

Compared to CVVH, CVVHD with regional citrate anticoagulation was associated with greater chloride mass transfer to the patient and higher plasma chloride concentrations. This was due to high dialysate chloride concentrations and CaCl2 reinjection. This effect could only be controlled by high net ultrafiltration flow rates.

Acute kidney injury (AKI) is one of the most frequent and prognostic-relevant complications of cardiogenic shock (CS) complicating myocardial infarction (MI). Mechanical circulatory assist devices (MCS) like left ventricular Impella microaxial pump have increasingly been used in the last decade for stabilization of hemodynamics in those patients. Moreover, a protective effect of Impella on renal organ perfusion could recently be demonstrated. However, data identifying early risk predictors for developing AKI during Impella support in CS are rare. Data of hemodynamics and renal function from 50 Impella patients (January 2020 and February 2022) with MI-related CS (SCAI stage C), were retrospectively analyzed using e.g. multivariate logistic regression analysis as well as Kaplan-Meier curves and Cox regression analysis. 30 patients (60%) developed AKI. Central venous pressure as an indicator for venous congestion (OR 1.216, p = 0.02), GFR at admission indicating existing renal damage (OR 0.928, p = 0.002), and reduced central venous oxygen saturation (SvO2) as a marker for decreased tissue perfusion (OR 0.930, p = 0.029) were independently associated with developing an AKI. The 30-day mortality rate was significantly higher in patients with AKI stage 3 (Stage 1: 0%, Stage 2: 0%, Stage 3; 41.6%, p = 0.014) while AKI stage 3 (HR 0.095, p = 0.026) and norepinephrine dosage (HR 1.027, p = 0.008) were independent predictors for 30-day mortality. AKI as a complication of MI-related CS occurs frequently with a major impact on prognosis. Venous congestion, reduced tissue perfusion, and an already impaired renal function are independent predictors of AKI. Thus, timely diagnostics and a focused treatment of the identified factors could improve prognosis and outcome.

In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.Trial registration: Not applicable.

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.

Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.

Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care.

Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion.

Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation.

Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible.

Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Renal non-recovery is known to have negative prognostic implications in patients suffering from acute kidney injury (AKI). Nevertheless, the identification of biomarkers for predicting renal non-recovery in sepsis-associated AKI (SA-AKI) within clinical settings remains unresolved. This study aims to evaluate and compare the predictive ability for renal non-recovery, use of kidney replacement therapy (KRT) in the Intensive Care Unit (ICU), and 30-day mortality after SA-AKI by two urinary biomarkers, namely C-C motif chemokine ligand 14 (CCL14) and [TIMP-2]•[IGFBP7].

We prospectively screened adult patients who met the criteria for AKI stage 2-3 and Sepsis-3.0 in two ICUs from January 2019 to May 2022. Patients who developed new-onset SA-AKI after ICU admission were enrolled and urinary biomarkers including [TIMP-2]•[IGFBP7] and CCL14 were detected at the time of SA-AKI diagnosis. The primary endpoint was non-recovery from SA-AKI within 7 days. The secondary endpoints were the use of KRT in the ICU and 30-day mortality after SA-AKI. The individual discriminative ability of [TIMP-2]•[IGFBP7] and CCL14 to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC).

141 patients with stage 2-3 SA-AKI were finally included, among whom 54 (38.3%) experienced renal non-recovery. Urinary CCL14 exhibited a higher predictive capability for renal non-recovery compared to [TIMP-2]•[IGFBP7], with CCL14 showing an AUC of 0.901, versus an AUC of 0.730 for [TIMP-2]•[IGFBP7] (P = 0.001). Urinary CCL14 and [TIMP-2]•[IGFBP7] demonstrated a moderate predictive value for the need for KRT in ICU, with AUC values of 0.794 and 0.725, respectively; The AUC of [TIMP-2]•[IGFBP7] combined with CCL14 reached up to 0.816. Urinary CCL14 and [TIMP-2]•[IGFBP7] exhibited poor predictive power for 30-day mortality, with respective AUC values of 0.623 and 0.593.

Urinary CCL14 had excellent predictive value for renal non-recovery in SA-AKI patients. For predicting the use of KRT in the ICU, the predictive capability of urinary [TIMP-2]•[IGFBP7] or CCL14 was fair. However, a combination of [TIMP-2]•[IGFBP7] and CCL14 showed good predictive ability for the use of KRT.

Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce.

FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors.

CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status.

Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.

Compared to the invasive technique, non-invasive monitoring of arterial pressure favors easier and faster implementation while potentially sacrificing some reliability. This may be particularly true for the Clearsight™ system (Edwards Lifesciences), which enables continuous monitoring. We evaluated the risk factors for its poor performance.

Patients with an arterial catheter and stable mean arterial pressure (MAP) over a 5-min period were included. Six pairs of invasive and Clearsight measurements of MAP were collected and the bias between the two techniques was calculated. Poor performance of the Clearsight™ system was defined as either a failure to measure and display MAP or displaying an erroneous MAP (individual bias > 5 mmHg). Fingertip perfusion was assessed using the plethysmographic perfusion index (PI) and the capillary refill time (CRT).

Among 152 ICU patients (MAP of 81 ± 14 mmHg, norepinephrine in 78 [51%]), 78 (51%) experienced a poor performance of the Clearsight™ system: failure to display MAP in 19 (13%) patients, and erroneous value displayed in 59 (44%). In multivariate analysis, PI ≤ 0.85% (adjusted odds ratio [aOR] = 2.94 [95% confidence interval (95%CI):1.34;6.45]), CRT > 4 s (aOR = 5.28 [95%CI 1.39;20.05]), and the presence of hand edema (aOR = 2.06 [95%CI 1.01;4.21]) were associated with a higher likelihood of poor performance. Cardiac arrhythmia (aOR = 1.39 [95%CI 0.64;3.02]) and other tested variables were not associated with poor performance.

Half of the included patients exhibited poor Clearsight™ system performance. Our results caution against using finger cuff arterial pressure monitoring in patients with low PI (≤0.85%), protracted CRT (>4 s), or hand edema.

ClinicalTrials.gov, NCT04269382, Dr. G. Muller, February 13, 2020. https://classic.

gov/ct2/show/NCT04269382.

Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU).

A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model.

Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance.

Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

In a group of children admitted to the paediatric intensive care unit (PICU) receiving continuous kidney replacement therapy (CKRT), we aim to evaluate the data about their hemodynamic, ventilation and analgo-sedation profile in the first 24 h of treatment and possible associations with mortality.

Retrospective cohort study of children admitted to the PICU of the University Hospital of Padova undergoing CKRT between January 2011 and March 2021. Data was collected at baseline (T0), after 1 h (T1) and 24 h (T24) of CKRT treatment. The differences in outcome measures were compared between these time points, and between survivors and non-survivors.

Sixty-nine patients received CKRT, of whom 38 (55%) died during the PICU stay. Overall, the vasoactive inotropic score and the adrenaline dose increased at T1 compared to T0 (p = 0.012 and p = 0.022, respectively). Compared to T0, at T24 patients showed an improvement in the following ventilatory parameters: Oxygenation Index (p = 0.005), Oxygenation Saturation Index (p = 0.013) PaO2/FiO2 ratio (p = 0.005), SpO2/FiO2 ratio (p = 0.002) and Mean Airway Pressure (p = 0.016). These improvements remained significant in survivors (p = 0.01, p = 0.027, p = 0.01 and p = 0.015, respectively) but not in non-survivors. No changes in analgo-sedative drugs have been described.

CKRT showed a significant impact on hemodynamics and ventilation in the first 24 h of treatment. We observed a significant rise in the inotropic/vasoactive support required after 1 h of treatment in the overall population, and an improvement in the ventilation parameters at 24 h only in survivors.

Scrub typhus is a vector-borne infection caused by the obligate intracellular organism Orientia tsutsugamushi. In some cases, scrub typhus can result in severe complications, multiorgan failure and death.

To study the clinical and laboratory profiles of patients who succumbed to scrub typhus.

A prospective cohort study was conducted from August 2019 through April 2023 on scrub typhus patients admitted to our hospital. Clinical and laboratory parameters of all the patients were recorded, and blood samples were drawn. To confirm scrub typhus, a nested polymerase chain reaction (nPCR) was performed in collected samples. Viable amplicons were sequenced, and phylogenetic analyses were performed to identify infecting genotypes.

A total of 261 patients were enrolled. Of these, nine (3.45%) patients succumbed at a median (Interquartile Range) duration of 5 (1.5, 10.5) days after admission. Sepsis with septic shock (9, 100%) and acute kidney injury (AKI) (6, 66%) were noted among the succumbed patients. All the succumbed patients (100%) required intensive care admission, inotropic and ventilatory support. While 5 (55%) patients required dialysis, two (22%) required blood transfusion. Three (33%) patient samples were co-positive for Leptospira IgM, and four (44%) patients had superinfection with Candida tropicalis, multi-drug-resistant (MDR) E. Coli sepsis, pan drug-resistant (PDR) Acinetobacter Baumanii, and Klebsiella pneumoniae. Phylogenetic analysis revealed Orientia tsutsugamushi Japanese Gilliam-variant (JG-v) like (50%), Karp-like (37.5%), and Japanese Gilliam (JG) like (12.5%) strains among succumbed patients.

Delay in scrub typhus diagnosis can result in severe complications, septic shock, and multisystem organ failure, culminating in death.

Acute kidney injury is classified by urine output into non-oliguric and oliguric variants. Non-oliguric acute kidney injury has lower morbidity and mortality and accounts for up to 64% of acute kidney injury in hospitalized patients. However, the incidence of non-oliguric acute kidney injury in the trauma population and whether the 2 variants of acute kidney injury share the same risk factors is unknown. We hypothesized that oliguria would be present in the majority of acute kidney injury in severely injured trauma patients and that unique risk factors would predispose patients to the development of oliguria.

Patients admitted to the trauma intensive care unit and diagnosed with an acute kidney injury between 2016 to 2021 were identified. Cases were categorized based on urine output into oliguric (<400 mL per day) and non-oliguric (>400 mL per day) disease. Risk factors, management, and outcomes were compared. Logistic regression was used to identify risk factors associated with oliguria.

A total of 227 patients met inclusion criteria. Non-oliguric acute kidney injury accounted for 74% of all cases and was associated with greater survival (78% vs 35.6%, P < .001). Using logistic regression, female sex, vasopressor use, and a greater net fluid balance at 48 hours were all predictive of oliguria (while controlling for age, race, shock index, massive transfusion, operative intervention, cardiac arrest, and nephrotoxic medication exposure).

Non-oliguria accounts for the majority of post-traumatic acute kidney injury and is associated with improved survival. Specific risk factors for the development of oliguric acute kidney injury include female sex, vasopressor use, and a higher net fluid balance at 48 hours.

The evaluation and management of fluid balance are key challenges in critical care patients who require renal replacement therapies because cumulative fluid balance is an independent factor that increases morbidity and mortality in different clinical scenarios.

One of the strategies when fluid overload is refractory to diuretics is extracorporeal fluid removal (i.e., net ultrafiltration [UFNET] during kidney replacement therapy). However, problems with UFNET without individualized assessment are cardiovascular events and intradialytic hypotension, events that contribute to decreasing organ perfusion and sympathetic stress. Therefore, we must consider and try to predict the best timing for the start of ultrafiltration and find the point where the patient is most tolerant to ultrafiltration, making a simile to the concept of fluid tolerance.

UFNET is a continuous and dynamic process, going through moments of tolerance and intolerance to ultrafiltration; as nephrologists, we must take the necessary measures to move through this period.

Capillary leak syndrome (CLS) represents a phenotype of increased fluid extravasation, resulting in intravascular hypovolemia, extravascular edema formation and ultimately hypoperfusion. While endothelial permeability is an evolutionary preserved physiological process needed to sustain life, excessive fluid leak-often caused by systemic inflammation-can have detrimental effects on patients' outcomes. This article delves into the current understanding of CLS pathophysiology, diagnosis and potential treatments. Systemic inflammation leading to a compromise of endothelial cell interactions through various signaling cues (e.g., the angiopoietin-Tie2 pathway), and shedding of the glycocalyx collectively contribute to the manifestation of CLS. Capillary permeability subsequently leads to the seepage of protein-rich fluid into the interstitial space. Recent insights into the importance of the sub-glycocalyx space and preserving lymphatic flow are highlighted for an in-depth understanding. While no established diagnostic criteria exist and CLS is frequently diagnosed by clinical characteristics only, we highlight more objective serological and (non)-invasive measurements that hint towards a CLS phenotype. While currently available treatment options are limited, we further review understanding of fluid resuscitation and experimental approaches to target endothelial permeability. Despite the improved understanding of CLS pathophysiology, efforts are needed to develop uniform diagnostic criteria, associate clinical consequences to these criteria, and delineate treatment options.

Ceftazidime is commonly used as a key antibiotic against Pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate the impact of obesity and renal function on ceftazidime plasma concentrations and dosing regimen in ICU patients.

All consecutive adult patients from six ICUs, treated with continuous ceftazidime infusion and under therapeutic drug monitoring evaluation, were included. Obesity was defined as BMI ≥30 kg/m². Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The ceftazidime recommended target for plasma concentrations was between 35 and 80 mg/L.

A total of 98 patients (45 obese), with an average weight of 90 (±25) kg, were included. Mean GFR was 84.1 (±40.4) mL/min/1.73 m2. Recommended ceftazidime plasma concentrations were achieved for only 48.0% of patients, with median dosing regimen of 6 g/day. Obese patients had lower ceftazidime plasma concentrations compared with non-obese patients (37.8 versus 56.3 mg/L; P = 0.0042) despite similar dosing regimens (5.83 g/day versus 5.52 g/day, P = 0.2529). Almost all augmented renal clearance patients were underdosed despite ceftazidime dosing of 6.6 (±0.8) g/day. Weight-based ceftazidime dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR.

Obese ICU patients required significantly greater ceftazidime doses to achieve the target range. A tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

Background Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). Conclusions Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.

Background and Objectives: Early improvements to graft function are crucial for good outcomes in kidney transplantation (kTx). Various factors can influence early graft function. This study aimed to evaluate the pre- and post-transplant hydration statuses of kTx recipients using bioimpedance analysis (BIA) and lung ultrasonography (LUS) and to investigate the hydration status' relationship with the function of the transplanted kidney during the first year after transplantation. Materials and Methods: This observational prospective cohort study included deceased kidney recipients transplanted in the Hospital of the Lithuanian University of Health Sciences between September 2016 and January 2023. BIA and LUS were performed before transplantation, on days 3 and 7, and at discharge. Data on recipient and donor clinical characteristics were collected. Graft function was evaluated according to the serum creatinine reduction ratio and the need for dialysis. Hydration status was evaluated by calculating B-lines (BL) on LUS and the ratio of extracellular/total body water on BIA. Results: Ninety-eight kTx recipients were included in the study. Patients with immediate graft function (IGF) were compared to those with slow or delayed graft function (SGF + DGF). Recipients in the SGF + DGF group had a higher sum of BL on LUS before transplantation. After transplantation in early postoperative follow-up, both groups showed hyperhydration as determined by BIA and LUS. After one year, recipients with no BL before transplantation had better graft function than those with BL. Logistic regression analysis showed that having more than one BL in LUS was associated with a 2.5 times higher risk of SGF or DGF after transplantation. Conclusions: This study found that lung congestion detected by LUS before kTx was associated with slower graft recovery and worse kidney function after 1 year. Meanwhile, the hyperhydration status detected by BIA analysis did not correlate with the function of the transplanted kidney.

Background: This study aims to investigate the effects of goaldirected fluid therapy on the development of acute kidney injury in the perioperative period in patients undergoing cardiopulmonary bypass. Methods: Between November 2019 and May 2021, a total of 60 patients (46 males, 14 females; mean age: 62.5±9.6 years; range, 44 to 76 years) who were scheduled for elective coronary artery bypass grafting or valve surgery under cardiopulmonary bypass were included in the study. The patients were divided into two groups as the study group (Group S, n=30) and control group (Group C, n=30). The patients in Group C were treated with standard therapy, while the patients in Group S were treated with goal-directed fluid therapy. The Kidney Disease: Improving Global Outcomes (KDIGO) classification and renal biomarkers were used for the evaluation of acute kidney injury. Results: Acute kidney injury rates were similar in both groups (30%). Postoperative fluid requirement, intra-, and postoperative erythrocyte suspension requirements were significantly lower in Group S than Group C (p=0.002, p=0.02, and p=0.002, respectively). Cystatin-C was lower in Group S (p<0.002). The kidney injury molecule-1, glomerular filtration rate, and creatinine levels were similar in both groups. The length of hospital stay was longer in Group C than Group S (p<0.001). Conclusion: Although goal-directed fluid therapy does not change the incidence of acute kidney injury in patients undergoing cardiac surgery, it can significantly decrease Cystatin-C levels. Goal-directed fluid therapy can also decrease fluid and erythrocyte requirements with shorter length of hospital stay.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.