Modern CRRT systems are associated with lower risk of hypothermia.

One risk of continuous renal replacement therapy (CRRT) is inadvertent hypothermia (IH), which is defined as a non-therapeutic core temperature decrease below normal. In continuous renal replacement therapy, heat loss will always occur from blood pumped through the dialysis circuit to cooler environment, predisposing for hypothermia. Blood flow and effluent flows are the most important parameters causing heat loss. We investigated and compared the novel TherMax warmer to previous generation technologies during CRRT in a multicenter setting. This was a prospective observational multicenter study with historic single-center controls. The study group consisted of 100 patients in eight Swedish ICUs with clinical indication for CRRT, using the PrisMax platform and TherMax warmer. Both patient and set warmer temperatures were recorded hourly for the first 24 h. The presence of treatment hours in hypothermia (< 36.0 Celsius) and the difference between set warmer temperature and measured patient temperature in the multi-center study cohort were compared to a matched single-center historic control cohort treated with the old Prismaflex platform and adjacent Barkey warmer. In the TherMax group 77/100 (77.0%) of patients, and for controls 26/86 (30.2%) of patients were free of hypothermia (Chi square, p < 0.001). The mean number of hours spent in hypothermia was (mean ± SD) 0.66 ± 1.60 and 6.92 ± 7.79 h in the TherMax and control groups, respectively (Chi square p < 0.001). In the study group the patient temperature was higher than the set temperature on the warmer with a difference of Δ0.47 ± 0.80 °C (minor difference), whereas in the control group the set temperature on the warmer was higher than the patient temperature with a difference of Δ4.55 ± 1.00 °C (over-correction). The novel TherMax warmer technology protected against hypothermia and was significantly more accurate than the Barkey warmer.

Validation of Cefiderocol Package Insert Dosing Recommendation for Patients Receiving Continuous Renal Replacement Therapy: A Prospective Multicenter Pharmacokinetic Study.

Background: Cefiderocol is the first antibiotic with effluent flow rate-based dosing recommendations outlined in the product label for patients receiving continuous renal replacement therapy (CRRT). We aimed to investigate the population pharmacokinetics of cefiderocol among patients receiving CRRT and validate these dosing recommendations. Methods: A multicenter, prospective cefiderocol pharmacokinetic study among intensive care unit patients receiving CRRT was conducted (2022-2023). Blood sampling was performed at steady-state and cefiderocol concentrations were assayed by validated liquid chromatography-tandem mass spectrometry. Population pharmacokinetic analyses were conducted in Pmetrics using R software. The free time above the minimum inhibitory concentration (f T > MIC) and total daily area under the concentration time curve (AUCdaily) were calculated. Results: Fourteen patients with effluent flow rates ranging from 2.1 to 5.1 L/h were enrolled. Cefiderocol concentrations best fitted a 2-compartment model. Mean ± standard deviation (SD) parameter estimates for clearance, central compartment volume, and intercompartment transfer constants (k12 and k21) were 3.5 ± 1.5 L/hour, 10.7 ± 8.4 L, 3.9 ± 1.8 hours-1, and 2.2 ± 2.2 hours-1, respectively. With simulations based on product label dosing recommendations, all patients achieved 100% fT > MIC up to MIC 8 mg/L with an AUCdaily (mean ± SD) of 1444 ± 423 mg × hour/L. Cefiderocol was well tolerated among the 14 patients. Conclusions: The current package insert dosing recommendations resulted in pharmacodynamically optimized cefiderocol exposures. Cefiderocol concentrations exceeded relevant MIC breakpoints in all patients at each effluent flow rate, and AUCdaily was within the range observed in patients in the phase 3 clinical trials, suggestive of a safe and therapeutic drug profile.

The evolution of public attention in acute kidney injury and continuous renal replacement therapy: trends analysis from 2004 to 2024.

Background: Acute kidney injury (AKI) and the need for Continuous Renal Replacement Therapy (CRRT) are critically important health concerns. This study analyzes global and regional Internet search queries to understand public attention in AKI and CRRT over time. Methods: We used Google Trends™ to analyze search queries for AKI and CRRT from January 2004 to March 2024. The study examined global trends and detailed insights from the United States, including state-by-state breakdowns. We identified patterns, peaks of attention, and temporal trends in public attention, comparing regional variations across the US and top-ranking countries worldwide. Results: Global attention in AKI peaked in October 2022, with Portugal, Zambia, and Spain showing the highest regional attention. Within the United States, peak attention was in February 2008. Tennessee, Pennsylvania, and West Virginia were the top states that paid attention to AKI. Attention in CRRT peaked globally in March 2024. South Korea, Saudi Arabia, and Bahrain have led the global attention to CRRT. In the United States, peak attention was in April 2020. West Virginia, Tennessee, and Kentucky showed the highest state-specific attention in CRRT. Conclusions: This study reveals significant temporal and geographical variations in online search patterns for AKI and CRRT, suggesting evolving public attention to these critical health issues. This knowledge can guide the development of targeted public health initiatives, enhance medical education efforts, and help healthcare systems tailor their approach to improving awareness and outcomes in kidney health across diverse populations.

Clinical efficacy of oXiris-continuous hemofiltration adsorption in septic shock patients: A retrospective analysis.

OBJECTIVE: This study aimed to assess the clinical impact of oXiris-continuous hemofiltration adsorption on patients with septic shock and their prognosis. DESIGN: A retrospective study. PARTICIPANTS: Septic shock patients. INTERVENTIONS: The oXiris group underwent hemofiltration adsorption using oXiris hemofilters and septic shock standard treatment, while the control group received septic shock standard treatment. MAIN VARIABLES OF INTEREST: The changes in inflammatory indicators and short-term mortality rate were evaluated. Propensity score matching (PSM) was conducted based on the 1:2 ratio between the oXiris and control groups to account for any baseline data differences. RESULTS: Results showed that after 24 h, 48 h, and 72 h of treatment, PCT, IL-6, and hs-CRP levels in the oXiris group were significantly lower than those in the control group (P < 0.05). However, there were no significant differences in norepinephrine equivalents and organ function status (APACHE II score, SOFA score, Lac) between the two groups at the same time points. The 72-h mortality rate (21.88% vs. 34.04%) and the 7-day mortality rate (28.12% vs. 44.68%) were lower in the oXiris group compared to the control group, but not statistically significant. The 28-day mortality rate did not show a significant difference between the two groups (53.19% vs. 56.25%). CONCLUSIONS: oXiris continuous hemofiltration adsorption technology may reduce the levels of inflammatory factors in patients with septic shock; however, it does not appear to enhance organ function or improve the 28-day mortality rate in these patients.

Edoxaban pharmacokinetics during in vitro continuous renal replacement therapy.

BACKGROUND: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. METHODS: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. RESULTS: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. CONCLUSION: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

Mechanical support for the treatment of fulminant myocarditis combined with cardiac arrest and MODS in children: A case report and review.

A 13 years and 1 month old child was admitted to the hospital with fulminant myocarditis. After admission, the child's condition deteriorated rapidly, with a rapid drop in blood pressure, alternating malignant arrhythmias, such as ventricular tachycardia and ventricular fibrillation, and then developed rapid cardiac arrest, which lasted for 62 min. Moreover, the child developed multiple organ failure (heart, kidney, brain, lungs, liver, gastrointestinal tract, and inflammatory system) with internal environmental disturbances, indicating critical conditions. After emergency extracorporeal membrane oxygenation (ECMO) and an intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT) was administered to dehydrate and maintain homeostasis of the internal environment. The treatment plan was adjusted in a timely manner by performing standardized and detailed comprehensive respiratory, circulatory, anti-infection, volume, anticoagulation, skin, and physical rehabilitation treatments. The patient was transferred to the ICU 15 days later. The patient was successfully discharged from the hospital and resumed normal studies and life without any neurological sequelae. This case is the first study of ECMO combined with IABP and CRRT for the treatment of fulminant myocarditis combined with cardiac arrest and multiple organ failure in children, which has not yet been reported in the literature. The duration of the cardiac arrest in this case was extremely long (62 min), and the patient had a good prognosis for the resumption of normal life and growth. This case suggests the need for early recognition of fulminant myocarditis and early initiation of devices for circulatory function support, such as ECMO and IABP. Additionally, early initiation of CRRT can assist in precise volume management, reduce cerebral edema, stabilize the internal environment, and reduce organ functional damage, which is a strong guarantee of treatment.

Transfer learning-enabled outcome prediction for guiding CRRT treatment of the pediatric patients with sepsis.

Continuous renal replacement therapy (CRRT) is a life-saving procedure for sepsis but the benefit of CRRT varies and prediction of clinical outcomes is valuable in efficient treatment planning. This study aimed to use machine learning (ML) models trained using MIMIC III data for identifying sepsis patients who would benefit from CRRT. We first selected patients with sepsis and CRRT in the ICU setting and their gender, and an array of routine lab results were included as features to train machine learning models using 30-day mortality as the primary outcome. A total of 4161 patients were included for analysis, among whom there were 1342 deaths within 30 days. Without data augmentation, extreme gradient boosting (XGBoost) showed an accuracy of 64.2% with AUC-ROC of 0.61. Data augmentation using a conditional generative adversarial neural network (c-GAN) resulted in a significantly improved accuracy (82%) and ROC-AUC (0.78%). To enable prediction on pediatric patients, we adopted transfer learning approaches, where the weights of all but the last hidden layer were fixed, followed by fine-tuning of the weights of the last hidden layer using pediatric data of 200 patients as the inputs. A significant improvement was observed using the transfer learning approach (AUCROC = 0.76) compared to direct training on the pediatric cohort (AUCROC = 0.62). Through this transfer-learning-facilitated patient outcome prediction, our study showed that ML can aid in clinical decision-making by predicting patient responses to CRRT for managing pediatric sepsis.

The first time devastating food poisoning happened in Taiwan - Bongkrekic acid poisoning.

Bongkrekic acid (BKA), a rarely happened foodborne toxin by Burkholderia gladioli pathovar cocovenenans (Burkholderia cocovenenans) might leads to devastating life-threatening condition after eating meal contaminated BKA. Unbelievable event from March 19, 2024, to March 24, 2024, there was an outbreak of BAP in a luxury shopping area of eastern Taipei, Taiwan. Most of the victims are young to middle-aged people who made a tour over there and ate the cooked wet rice noodles. Of them, 13 males and 20 females, aged 40.9 ± 14.7 years old visited or were sent by ambulances to the emergency department presenting with watery diarrhea, and vomiting. Some progressed to severe hepatic and renal failure, altered mental status, disseminated intravascular coagulation, and fatalities within several hours within 2 days. The primary health workers especially emergency physicians need to keep in mind of BKA poisoning is quite different in presentations from other infectious colitis commonly seen before. Knowing the toxic-kinetic and toxic-dynamic mechanisms is important to farseeing the presentation of these BAP patients. Throughout this outbreak, we gathered abundant experiences in mitigating and managing these debilitated patients. Aggressively supportive care and early liver transplantation if there is no concurrent inflammatory process and the patient's condition is tolerable to surgical intervention saves lives. For food safety education, it is crucial to enhance our understanding of inhibiting BKA production and promote proper food preservation methods and a suitable environment to ensure food safety.

Sterile water and regional citrate anticoagulation: A simple CRRT strategy for safe correction of severe hyponatraemia.

BACKGROUND: Hyponatraemia is a prevalent electrolyte disturbance observed in critically ill patients. The rapid correction of low plasma sodium levels by continuous renal replacement therapy (CRRT) carries the risk of developing osmotic demyelination syndrome (ODS), which can be prevented by implementing an individualized CRRT method. AIM: This study aims to introduce a CRRT protocol for the safe and gradual correction of severe hyponatraemia. STUDY DESIGN: This retrospective case series study was conducted in an intensive care unit (ICU). All four patients with severe hyponatraemia (<125 mmol/L) and renal failure between October 1, 2022, and September 30, 2023, were treated by CRRT with sterile water and regional citrate anticoagulation (RCA). Data on patient demographics, laboratory biochemical parameters, urine outputs and CRRT-related adverse events were collected. Laboratory parameters and urine outputs were compared by paired t-tests before and after CRRT. RESULTS: After CRRT, sodium levels were significantly increased (112.7 ± 6.7 vs. 141.9 ± 2.8 mmol/L, p = .005). Abnormal urine outputs, potassium, creatinine and bicarbonate were corrected (p for all <.05). Safe and gradual correction of hyponatraemia and internal environmental dysregulation was achieved in all patients without any complications related to CRRT, particularly ODS. CONCLUSION: It is a novel and simple strategy to correct severe hyponatraemia effectively while ensuring the safety of patients that can be easily implemented by experienced nurse staff. RELEVANCE TO CLINICAL PRACTICE: The sterile water-based protocol for postfilter dilution is safe to correct severe hyponatraemia with RCA and can be easily performed by experienced critical care nurses according to the precalculated formula. CRRT-trained, experienced ICU nurses are competent to initiate and adjust sterile water infusion discretely to prevent overcorrection of hyponatraemia.

A Case Report of Hemophagocytic Lymphohistiocytosis Masquerading as Sepsis.

Profound inflammation due to cytokine storm is often the underlying cause of death in patients with hemophagocytic lymphohistiocytosis (HLH). Sepsis, while a precipitant, is also the great masquerader that may hide early signs of HLH. Prompt recognition is important to prevent rapid clinical decline and death. A patient presented with two weeks of unremitting fever of 103°F, dysuria, bilateral flank pain, and confusion. Obstructive uropathy and pyelonephritis were treated with a Foley catheter and antibiotics. There were abnormal developments during his hospitalization including a deep vein thrombus despite prophylactic anticoagulation. Antibiotics and Foley management did not improve fevers or renal injury so he eventually required continuous renal replacement therapy and blood product transfusions. In rapid progression, the patient developed pancytopenia, neutropenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia suspicious for HLH. A bone marrow biopsy was consistent with progressive T-cell lymphoma, the likely cause of secondary HLH. Antineoplastics, corticosteroids, and opportunistic prophylaxis were pursued. Unfortunately, the cytopenias worsened, and the patient developed shock with hypoxemia and hypotension, followed by cardiac arrest and demise.

Outcomes of continuous renal replacement therapy versus peritoneal dialysis as a renal replacement therapy modality in patients undergoing Venoarterial extracorporeal membrane oxygenation.

INTRODUCTION: The optimal modality for renal replacement therapy (RRT) in patients venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. This study aimed to compare outcomes between continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD) in VA-ECMO patients. METHODS: This single-center retrospective study included VA-ECMO patients who developed AKI and subsequently required CRRT or PD. Data on patient demographics, comorbidities, clinical characteristics, RRT modality, and outcomes were collected. The primary outcome was in-hospital mortality, with secondary outcomes including length of stays, RRT durations, and complications associated with RRT. RESULTS: A total of 43 patients were included (72.1% male, mean age 58.2 ± 15.7 years). Of these, 21 received CRRT and 22 received PD during ECMO therapy. In-hospital mortality rates did not significantly differ between CRRT and PD groups (80.9% vs 90.9%, p = 0.35). However, PD was associated with a higher incidence of catheter-related complications, including malposition (31.8% vs 4.7%, p = 0.046), infection (22.7% vs 4.7%, p = 0.19), and bleeding (18.2% vs 9.5%, p = 0.66), respectively. CONCLUSION: Among patients receiving VA-ECMO-supported RRT, our study revealed comparable in-hospital mortality rates between CRRT and PD, although PD was associated with a higher incidence of catheter-related complications.

Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. METHODS: A multicentre retrospective study across four major tertiary care centres. RESULTS: As many as 183 ALF patients (median age, 23 years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen per cent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. CONCLUSIONS: Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

A case report of metformin-associated lactic acidosis.

Key Clinical Message: Metformin-associated lactic acidosis is a rare but serious complication in patients with type 2 diabetes, especially those with multiple health conditions. Prompt recognition and treatment, including potential renal replacement therapy, are crucial for managing severe acidosis and improving patient outcomes. Abstract: Metformin (MTF) is commonly prescribed as a first-line treatment for diabetes, effectively preventing microvascular and macrovascular complications. However, metformin-associated lactic acidosis is a rare yet severe complication, associated with a mortality rate of up to 50%. We encountered a case involving a 73-year-old woman with type 2 diabetes, mental illness, and hypothyroidism, who developed life-threatening lactic acidosis while on metformin therapy. Upon presenting to the emergency department with complaints of weakness, nausea, and decreased urination for 5 days, she also reported abdominal pain and shortness of breath. Hypotension was noted with a blood pressure of 80/50 mmHg. Initial laboratory results revealed severe acidosis, prompting discontinuation of MTF. Despite resuscitation efforts and vasopressor therapy, severe acidemia persisted, leading to the initiation of renal replacement therapy. Following treatment with continuous renal replacement therapy, her acidemia resolved, and she was discharged from the hospital on the sixth day without complications, with normal kidney function.

Dual Dialysis for Post-bilateral Orthotopic Lung Transplantation Hyperammonemia.

Hyperammonemia is a metabolic disorder characterized by supraphysiologic ammonia (NH3) concentrations in the blood. Although usually seen in adults with liver disease, hyperammonemia is a notable complication in 4.1% of lung transplants. It is associated with cerebral edema and neurological dysfunction and carries up to 75% mortality in critically ill patients. Opportunistic infections caused by Mycoplasma and Ureaplasma species have been implicated as the cause of this metabolic disturbance. Literature in neonates has shown that renal replacement therapy (RRT) is the best choice for treating patients with neurologic manifestations of hyperammonemia, in cases of NH3 clearance than continuous renal replacement therapy (CRRT). In contrast, continuous venovenous hemodialysis (CVVHD) is usually better tolerated for patients with hemodynamic instability for NH3 clearance. NH3 is a small molecule whose clearance mirrors urea in dialysis. Even though RRT can be a treatment modality for hyperammonemia in adults and neonates, there is very little literature on adults. We present a unique case demonstrating improvement in neurologic manifestations of hyperammonemia by using both IHD and CVVHD in an adult patient.

Liver transplantation for acute liver failure and acute-on-chronic liver failure.

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF.

The impact of extracorporeal support on antimicrobial pharmacokinetics in critically ill neonatal and paediatric patients: A systematic review.

OBJECTIVES: Infections represent a major risk for critically ill neonatal and paediatric patients requiring extracorporeal life-saving support such as extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapies (CRRT). Patient outcomes rely on achieving target antimicrobial concentrations. In critically ill adults on extracorporeal support, suboptimal antimicrobial concentrations have been shown to be common. Our objective was to systematically review antimicrobial pharmacokinetic studies in critically ill term neonatal and paediatric patients receiving ECMO and/or CRRT and compare them to similar cohorts of patients not receiving ECMO or CRRT. METHODS: Studies published between 1990 and 2022 were identified through systematic searches in PUBMED, Embase, Web of Science, Medline, Google Scholar and CINAHL. Studies were included which provided antimicrobial pharmacokinetic parameters (volume of distribution and clearance) in the neonatal and paediatric patients receiving ECMO and/or CRRT. Studies were excluded if no antimicrobial pharmacokinetic parameters were described or could be calculated. RESULTS: Forty-four pharmacokinetic studies were identified describing 737 patients, with neonatal patients recruited in 70% of the ECMO studies and <1% of the CRRT studies. Of all the studies, 50% were case reports or case series. The pharmacokinetics were altered for gentamicin, daptomycin, ceftolozane, micafungin, voriconazole, cefepime, fluconazole, piperacillin, and vancomycin, although considerable patient variability was described. CONCLUSION: Significant gaps remain in our understanding of the pharmacokinetic alterations in neonatal and paediatric patients receiving ECMO and CRRT support.

Analysis of metabolic alterations as 30 days intensive care mortality predictors for patients undergoing continuous renal replacement therapy.

BACKGROUND: Acute kidney injury patients on continuous renal replacement therapy are subjected to alterations in metabolism, which in turn are associated with worse clinical outcome and mortality. The aim of this study is to determine which metabolism indicators can be used as independent predictors of 30 days intensive care unit (ICU) mortality. METHODS: This was a prospective observational study on critical care patients on renal replacement therapy. Integrated approach of metabolism evaluation was used, combining the energy expenditure measured by indirect calorimetry, bioelectrical impedance provided fat free mass index (FFMI), amino acid and glucose concentrations. ICU mortality was defined as all cause 30 days mortality. Regression analysis was conducted to determine the conventional and metabolism associated predictors of mortality. RESULTS: The study was conducted between the 2021 March and 2022 October. 60 high mortality risk patients (APACHE II of 22.98 ± 7.87, 97% on vasopressors, 100% on mechanical ventilation) were included during the period of the study. The rate of 30 days ICU mortality was 50% (n = 30). Differences across survivors and non-survivors in metabolic predictors were noted in energy expenditure (kcal/kg/day) (19.79 ± 5.55 vs 10.04 ± 3.97 p = 0.013), amino acid concentrations (mmol/L) (2.40 ± 1.06 vs 1.87 ± 0.90 p = 0.040) and glucose concentrations (mmol/L) (7.89 ± 1.90 vs 10.04 ± 3.97 p = 0.010). No differences were noted in FFMI (23.38 ± 4.25 vs 21.95 ± 3.08 p = 0.158). In the final linear regression analysis model, lower energy expenditure (exp(B) = 0.852 CI95%: 0.741-0.979 p = 0.024) and higher glucose (exp(B) = 1.360 CI95%: 1.013-1.824 p = 0.041) remained as independent predictors of the higher mortality. CONCLUSION: The results of the study imply strong association between the metabolic alterations and ICU outcome. Our findings suggest that lower systemic amino acid concentration, lower energy expenditure and higher systemic glucose concentration are predictive of 30 days ICU mortality.

Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.

INTRODUCTION: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. METHODS: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. RESULTS: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). CONCLUSION: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

Efficacy and safety of ertapenem dosing in patients with ESBL producing Enterobacterales infections utilizing renal replacement therapies.

PURPOSE: The clinical efficacy and safety of ertapenem use in patients undergoing renal replacement therapies (RRT) are not well-documented. Therefore, we aimed to investigate the safety and efficacy of ertapenem in patients with sepsis secondary to Enterobacterales who are undergoing RRT. METHODS: A retrospective cohort study was conducted on patients who met the inclusion criteria at our hospital between May 2015 and December 2021. The primary endpoint was 30-day mortality. Secondary endpoints included clinical cure, microbiologic cure, recurrence rate, and incidence of seizures. RESULTS: During the study period, 158 patients met the inclusion criteria. Of these, 86 were male (54.4%), the mean age was 66.4 ± 13.8 years, and the mean weight was 77 ± 22.4 kg. The most common diagnosis was bacteremia in 48 (30.4%) subjects, followed by urinary tract infection in 39 (24.7%) subjects, and pneumonia in 35 (22.2%) patients. The most isolated pathogens were Escherichia coli, followed by Klebsiella species. The median ertapenem dose was 0.5 g intravenously (IV) daily in those who received intermittent hemodialysis (IHD) and 1 g IV daily for those who received continuous veno-venous hemofiltration (CVVH). The 30-day mortality rate was 24%, the clinical cure rate was 89.2%, the microbiologic cure rate was 82%, the 30-day recurrence rate was 41.1%, and the incidence of seizures was 2.5%. Multivariate logistic regression analysis indicated that age (OR 1.04 [95% CI: 1.003-1.075]), being critically ill at therapy initiation (OR 2.9 [95% CI: 1.1-7.5]), and Enterobacterales other than Klebsiella species and Escherichia coli (OR 3.8 [95% CI: 1.1-12.5]) were significant independent risk factors associated with mortality in this population. Ertapenem dose was not associated with mortality. CONCLUSION: Our findings suggest that the commonly used doses of ertapenem in patients undergoing IHD and CVVH are clinically effective but may pose a higher risk of seizures. A comprehensive pharmacokinetic study is needed to determine the most effective and safe dose for this population.

Type B Lactic Acidosis Secondary to Metastatic Liver Cancer in the Setting of Normal Renal Function: A Case Report and Literature Review.

Lactic acidosis occurs from an overproduction of lactate or decreased metabolism. It is common in critically ill patients, especially those with hematological conditions such as multiple myeloma, leukemia, and lymphoma. There are two types of lactic acidosis, Type A and Type B, with Type B presenting more commonly in hematological conditions that require prompt diagnosis and treatment of the underlying condition. We present a case of a 43-year-old male with Type B lactic acidosis secondary to stage IV colon cancer with metastasis to the liver. Initial laboratory work was significant for lactic acid of 16.52 mmol/L. Arterial blood gas (ABG) showed pH 7.26, pCO2 21 mmHg, pO2 111 mmHg, and HCO3 9 mEq/L, revealing an anion gap and metabolic acidosis with compensatory respiratory alkalosis. Initially, the patient was treated with aggressive fluid management, IV antibiotics, and sodium bicarbonate; however, his lactic acid continued to rise. The recommendation was made for urgent dialysis. Despite treatments, the prognosis is poor.