Continuous Venovenous Hemodiafiltration Research Articles

Hypercitratemia is a mortality predictor among patients on continuous venovenous hemodiafiltration and regional citrate anticoagulation

The use of regional citrate anticoagulation (RCA) in liver failure (LF) patients can lead to citrate accumulation. We aimed to evaluate serum levels of citrate and correlate them with liver function markers and with the Cat/Cai in patients under intensive care and undergoing continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA). A prospective cohort study in an intensive care unit was conducted. We compared survival, clinical, laboratorial and dialysis data between patients with and without LF. Citrate was measured daily. We evaluated 200 patients, 62 (31%) with LF. Citrate was significantly higher in the LF group. Dialysis dose, filter lifespan, systemic ionized calcium and Cat/Cai were similar between groups. There were weak to moderate positive correlations between Citrate and indicators of liver function and Cat/Cai. The LF group had higher mortality (70.5% vs. 51.8%, p = 0.014). Citrate was an independent risk factor for death, OR 11.3 (95% CI 2.74–46.8). In conclusion, hypercitratemia was an independent risk factor for death in individuals undergoing CVVHDF-ARC. The increase in citrate was limited in the LF group, without clinical significance. The correlation between citrate and liver function indicators was weak to moderate.

The efficacy and safety of continuous blood purification in neonates with septic shock and acute kidney injury: a two-center retrospective study.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP. Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high.

A pilot study of intensive short-time continuous renal replacement therapy to substitute maintenance hemodialysis during transitional period of COVID-19.

There is a lack of perfect solutions for maintenance hemodialysis (MHD) in patients with a high transmission risk of SARS-CoV-2. MHD patients with a high risk of SARS-CoV-2 transmission from April 1 to June 30, 2022, were recruited. We performed 4-h continuous renal replacement therapy with Prismaflex dialysis machine and ST100 suite using continuous venovenous hemodiafiltration (CVVHDF) mode with a fluid exchange volume of 8000 mL/h. Forty-five MHD patients were included with a median dialysis age of 91 months. Overall spKt/V reached 0.96 ± 0.19. Urea reduction ratio was 50.29 ± 7.60% with the ultrafiltration of 2.18 ± 0.79 kg. Dry weight was significantly inversely correlated with spKt/V (R = -0.563, p < 0.001). Female gender was a significant positive factor of spKt/V. Preheating of replacement solution using an incubator solved the complication of shivering in most patients. Intensive short-time CVVHDF may be considered as an alternative for routine MHD during COVID-19 transitional period.

Sugammadex-Induced Anaphylactic Shock Reversed With Short-Term Continuous Veno-Venous Hemodiafiltration: A Case Report

Anaphylaxis is a life-threatening, systemic, hypersensitivity reaction, manifested by urticaria, hypotension, and respiratory symptoms. Antigens that are cleared renally may have protracted exposure in patients with impaired renal function, resulting in prolonged and refractory anaphylactic shock. After administration of sugammadex, a 47-year-old man developed prolonged, refractory anaphylactic shock, with anuria due to acute kidney injury. The patient was treated with continuous, short-term, veno-venous hemodiafiltration. Initiating this therapy in patients with refractory anaphylactic shock and anuria due to an antigen that is excreted renally can expedite recovery.

The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19

Introduction: Midazolam-based continuous intravenous sedation in patients admitted to the intensive care unit (ICU) was a necessity during the COVID-19 pandemic. However, benzodiazepine-based sedation is associated with a high incidence of benzodiazepine-related delirium and additional days on mechanical ventilation. Due to the requirement of high midazolam doses in combination with the impaired renal clearance (CL) of the pharmacological active metabolite 1-OH-midazolam-glucuronide (10% compared to midazolam), ICU patients with COVID-19 and continuous renal replacement therapy (CRRT) were at risk of unintended prolonged sedation. Several CRRT-related factors may have influenced the delivered CL of midazolam and its metabolites. Therefore, the aim of the study was to identify and describe these CRRT-related factors. Methods: Pre-filter blood samples and ultrafiltrate samples were collected simultaneously. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide plasma samples were analyzed using an UPLC-MS/MS method. The prescribed CRRT dose was corrected for downtime and filter integrity using the urea ratio (urea concentration in effluent/urea concentration plasma). CL of midazolam and its metabolites were calculated with the delivered CRRT dose (corrected for downtime and saturation coefficient [SD]). Results: Three patients on continuous venovenous hemodialysis (CVVHD) and 2 patients on continuous venovenous hemodiafiltration (CVVHDF) were included. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations were 2,849 (0–6,700) μg/L, 153 (0–295) μg/L, and 27,297 (1,727–39,000) μg/L, respectively. The SD was 0.03 (0.02–0.03) for midazolam, 0.05 (0.05–0.06) for 1-OH-midazolam, and 0.33 (0.23–0.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0–1.7) mL/min for midazolam, 2.7 (0–3.5) mL/min for 1-OH-midazolam, and 15.7 (4.0–27.7) mL/min for 1-OH-midazolam-glucuronide. Conclusions: Midazolam and 1-OH-midazolam were not removed during CVVHD and CVVHDF. However, 1-OH-midazolam-glucuronide was removed reasonably, approximately up to 43%. CRRT modality, filter integrity, and downtime affect this removal. These data imply a personalized titration of midazolam in critically ill patients with renal failure and awareness for the additional sedative effects of its active metabolites.

Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration.

(1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022-May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fCss) were calculated. Meropenem total clearance (CLtot) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CLtot was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fCss/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fCss was 19.9 mg/L (17.4-28.0 mg/L). Median (IQR) CLtot was 3.89 L/h (3.28-5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8-44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

The Impact of Continuous Veno-Venous Hemodiafiltration on the Efficacy of Administration of Prophylactic Doses of Enoxaparin: A Prospective Observational Study.

Critically ill patients frequently require continuous renal replacement therapy (CRRT). During CRRT, particles up to 10 kDa in size, such as enoxaparin, may be removed. The aim of this study was to determine if patients receiving prophylactic doses of enoxaparin and treated with continuous veno-venous hemodiafiltration (CVVHDF) reach prophylactic values of anti-Xa factor activity. In this observational trial, we compared two groups: 20 patients treated with CVVHDF and 20 patients not treated with CVVHDF. All of them received prophylactic doses of 40 mg of enoxaparin subcutaneously. Anti-Xa factor activity was determined on the third day of receiving a prophylactic dose of enoxaparin. The first blood sample was taken just before the administration of enoxaparin, and other samples were taken 3 h, 6 h, and 9 h after the administration of a prophylactic dose of enoxaparin. At 3 and 6 h after administration of enoxaparin in both groups, we observed a significant increase in anti-Xa factor activity from baseline, with the peak after 3 h of administration. There were no significant differences in the numbers of patients who had anti-Xa factor activity within the prophylactic range between CVVHDF and control groups. CVVHDF has only a mild effect on the enoxaparin prophylactic effect measured by anti-Xa factor activity. Thus, it seems there is no need to increase the dose of enoxaparin for patients requiring CVVHDF.

Continuous venovenous hemodiafiltration versus standard medical therapy for the prevention of rhabdomyolysis-induced acute kidney injury: a retrospective cohort study

AimTo determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and analyze the related health economics.MethodsThis retrospective cohort study involved 9 RM patients without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (CVVHDF + SMT group). Nine matched RM patients without AKI treated with SMT only served as controls (SMT group). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the CVVHDF + SMT group, biochemical data were compared at different time points.ResultsAt 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the CVVHDF + SMT group than in the SMT group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 CVVHDF + SMT-group patient who died of acute myocardial infarction. In the CVVHDF + SMT group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF.ConclusionsAlthough CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve biochemical indices like serum myoglobin, serum creatine kinase, creatinine, blood urea nitrogen, and lactate dehydrogenase or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the CVVHDF + SMT group.

#5623 PERITONEAL DIALYSIS AND POSTOPERATIVE OUTCOMES IN CHILDREN AFTER CARDIAC SURGERY: A SINGLE-CENTER COHORT STUDY

Abstract Background and Aims Acute kidney injury (AKI) is a frequent complication in neonates and infants after congenital heart disease surgery, with great impact on morbidity and mortality. Peritoneal dialysis (PD) is the renal replacement therapy of choice, as it allows continuous gentle ultrafiltration with minimal impact on hemodynamic status. However, there is no standardized prescription. The present study aimed to describe our experience of using PD in the management of AKI after cardiac surgery in pediatric patients and the postoperative outcomes. Method Single-center cross-sectional study including 21 children undergoing cardiac surgery between 2017 and 2022, in a congenital heart disease reference center. Demographic and clinical data were collected from the electronic records. Results Of the 21 patients treated with PD, 11 were female. Mean age was 32 ± 45 days and median weight was 3.4 kg (IQR 0.5). All pregnancies had been full-term with a mean birth weight of 3.2 ± 0.3 kg. No congenital urinary tract anomalies had been previously documented. Previous history of AKI was present in 2 patients. Transposition of the great arteries was the most common surgical indication (52%). RACHS-1 score was ≥4 in 12 patients and median PRISM-IV score was 6.5% (IQR 6). Cardiopulmonary bypass was performed in 19 patients with a mean time of 181 ± 72 minutes and a mean aortic clamping time of 94 ± 29 minutes. All patients required inotropic support after cardiac surgery with ≥2 drugs, for 197 ± 136 hours. Median time with mechanical ventilation support was 126 hours (IQR 288) and median length of stay at the intensive care unit (ICU) was 9 days (IQR 15.3).The indications for PD initiation were anuria (66.7%), oliguria (23.8%) and fluid overload (9.5%). Median time between cardiac surgery and AKI diagnosis was 2.5 hours (IQR 8.8) and between AKI diagnosis and PD initiation was 1.8 hours (IQR 4.3). Median duration under dialysis was 2 days (IQR 3.5). Exchange volume of dialysate varied between 6 and 15 mL/kg at the beginning of PD. In 11 patients, this volume was progressively increased to a maximum of 60 mL/kg (minimum: 30 mL; maximum: 120 mL). Continuous veno-venous hemodiafiltration was required in 3 patients, mainly due to mechanical catheter dysfunction. Complications related to PD occurred in 5 patients: 1 patient developed peritonitis, 1 patient had mechanical catheter dysfunction and 3 patients had peri-catheter leak. Complete recovery of renal function was achieved in 14 patients. Longer time on PD was associated with lower weight before surgery (p = 0.04), longer time on mechanical ventilation and inotropic support (p &amp;lt; 0.001), and longer stay at the ICU (p &amp;lt; 0.001). Time on inotropic support could predict time on PD using a multiple regression model (adjusted R2 = 59%, p = 0.003), adjusted to cardiopulmonary bypass time, time on mechanical ventilation support and weight before surgery (adjusted ß = 0.7, p = 0.005). Eight patients died during hospitalization, due to multiorgan failure (38%), cardiogenic shock (38%), disseminated intravascular coagulation (13%) and septic shock (13%). Longer cardiopulmonary bypass time was associated with in-hospital mortality (149 ± 53 vs 235 ± 46, p = 0.004). Both the time between AKI diagnosis and PD initiation and the time on PD were not associated with in-hospital mortality. Conclusion Our study suggests that PD is a safe and effective dialysis modality in the management of post-cardiac surgery AKI in pediatric population. Early identification of high-risk infants is important to implement preventive measures.

#4125 CHANGES OF MEDICAL COSTS AND NUMBER OF USES OF CONTINUOUS RENAL REPLACEMENT THERAPY UNTIL RECENT SIX YEARS IN SOUTH KOREA

Abstract Background and Aims Continuous renal replacement therapy (CRRT) is a necessary dialysis treatment method applied to patients with acute renal injury at intensive care unit. In South Korea, the use of such CRRT is increasing, and the cost of health insurance used for CRRT is also increasing. In this study, the pattern and medical costs increase of CRRT usage until recent 6 years were investigated. Method From 2016 to 2021, the number of CRRT claims was investigated using data from the National Health Insurance Review and Assessment Service. CRRT costs is applied by a resource-based relative value score in Korea. CRRT can be charged as continuous venovenous hemodialysis, continous venovenous hemofiltration, and continuous venovenous hemodiafiltration depending on the treatment mode. The CRRT cost differs from the very day and the next day's cost, and the cost of the very day includes the femoral hemodialysis catheter insertion cost, which is higher than the next day's cost. Results CRRT medical practice is gradually increasing. The number of CRRT the very day increased from 15,640 cases in 2016 to 20,883 cases in 2021, and it continues to increase from 81,649 cases CRRT the next day in 2016 to 121,376 cases CRRT the next day in 2021. The CRRT relative value score is higher than the conventional hemodialysis(HD) and the CRRT relative value score is 9715 points higher than the conventional HD 1065 points. The total cost of CRRT increased by about KRW 52.5 billion (approximately 38,363,171 dollars) in 2021 from about KRW 17.3 billion (approximately 12,641,578 dollars) in 2016. In addition to CRRT medical practice costs, dialysis fluid, anticoagulant costs, and material costs are added, and so actual CRRT-related costs are more expensive. Conclusion CRRT is essential and it seems necessary to consider medical practices or medical costs that are important for essential medical care. CRRT is a high-cost treatment method that requires definitive guidelines or consensus on the initiation and discontinuation of CRRT.

#6306 SUSTAINED LOW-EFFICIENCY DIALYSIS VERSUS CONTINUOUS VENO-VENOUS HEMODIAFILTRATION OUTCOME IN CRITICALLY ILL PATIENTS

Abstract Background and Aims Acute kidney injury due to sepsis is the most common cause of AKI in critical care settings. Different modalities of renal replacement therapies (RRT) have been used to manage this condition including Continuous Renal Replacement Therapy (CRRT) and sustained low efficiency dialysis (SLED). The aim of this work was to compare the outcome of SLED and CRRT in the form of continuous veno-venous hemodiafiltration (CVVDHF) as methods of dialysis in sepsis induced AKI. Method We retrospectively analysed data from 120 patients; 20 patients received CVVHDF to manage AKI in the context of sepsis, 47 patients received SLED to manage AKI in the context of sepsis and the third group included 53 patients who have been treated with SLED to manage AKI not due to sepsis. Age was found to be significantly higher in sepsis induced AKI patients treated with SLED than patients treated with CVVHDF (65±10.1# 59.5±9.3 y, p = 0.03). Sex distribution or incidences of hypertension, diabetes mellitus, malignancy or liver disease were not statistically different between groups. Results Unadjusted 30 day mortality was 44.7% (21pt) in the SLED group Vs 50% (10pt) in the CVVHDF group, p = 0.07. Adjusted mortality was not statically significant between SLED and CVVHDF (OR 0.97, CI = 0.95-1.06). Hypotension occurred more frequently in patients treated with SLED (24 pt = 51.1% #5 pt = 25%, p &amp;lt; 0.001).Clotting occurred more frequently in the CVVHDF group as compared to SLED group (7 pt = 35% Vs 4pt = 8.5% p &amp;lt; 0.001). Conclusion Sustained low efficiency dialysis (SLED) and CVVHDF had comparable 30 day mortality as modalities of RRT in critically ill Patients with sepsis induced AKI. SLED still an attractive alternative to CRRT modalities due to lower cost and lower incidence of complications. Further larger studies are recommended.

A 15-Year Retrospective Study of Supportive Extracorporeal Therapies Including Plasma Exchange and Continuous Venovenous Hemodiafiltration of 114 Adults with Acute Liver Failure Awaiting Liver Transplantation.

BACKGROUND Recently, there has been a recommendation to utilize a combination of supportive extracorporeal therapies, specifically plasma exchange and continuous venovenous hemodiafiltration, in patients with acute liver failure. This 15-year retrospective study aimed to evaluate supportive extracorporeal therapy, including plasma exchange and continuous venovenous hemodiafiltration, for 114 adults with acute liver failure awaiting liver transplant. MATERIAL AND METHODS In this retrospective study, the medical records of 1288 adult patients who underwent liver transplantation and 161 adult patients who received alternative therapy were analyzed; 114 patients who received combined supportive extracorporeal therapy for acute liver failure were included in the study. Biochemical laboratory data were compared before and after therapy. RESULTS The study included 50 male and 64 female patients. The first group (34 patients) recovered with liver transplantation, and 4 patients died in the first year after liver transplantation. In the second group (80 patients), 66 patients recovered without liver transplantation, while 14 patients died within the first 2 weeks after therapy. All patients showed significant reductions in serum hepatic function tests (alanine transaminase, aspartate transaminase, and total bilirubin), ammonia, and prothrombin time/international normalized ratio after discontinuation of combined supportive extracorporeal therapy (P<0.01). There was also a significant improvement in the hemodynamic parameter. CONCLUSIONS This combined extracorporeal therapy can be used as a supportive treatment for both recovery and bridge to liver transplantation in patients with acute liver failure. In addition, treatment can be continued until liver regeneration and until a usable donor is found.

RENAL8: Hypertonic Bicarbonate during Continuous Renal Replacement Therapy in Acute Liver Failure

Introduction: Acute liver failure (ALF) is particularly alarming when presenting with vasodilated shock and multi-organ system failure. Standard manufactured hemofiltration fluid (sodium [Na+] = 140 mEq/L) would result in hyponatremia in vivo. We present a case study of hypertonic NaHCO3 infusion to address simultaneous serum Na+ target and correction of acidemia during continuous therapy. Case Presentation: A 42-year-old female with a history of seizures, and heavy alcohol use presented from outside the hospital for evaluation of stroke-like symptoms and subsequent mechanical fall. Urgent head CT was non-contributory. She was found to be in acute liver failure with total bilirubin 4.7, AST: 15,525 ALT: 5,727, ammonia 267 umol/L [reference range: 18-72], acetaminophen level 29 mcg/mL [reference range 10-30], Na+ 128 mEq/L, lactate >20 mmol/L, PT INR 8.1, PH 7.0 on blood gas and a negative ethanol level/salicylate/urine drug screen. After emergent intubation for encephalopathy and multiorgan system failure, she required multiple vasopressors (epinephrine, vasopressin, and norepinephrine), and received N-acetylcysteine protocol, with intravenous bicarbonate infusion and broad-spectrum antibiotic. High dose continuous veno-venous hemodiafiltration (CVVHDF) was initiated via Baxter PrisMax platform and global effluent dosing of 58mL/kg/hr with post-filter 3% NaCl at a rate of 100 mL/hr to reach goal serum sodium of 140 mEq/dL. [3% NaCl infusion rate calculation: (target infused Na – 140 mEq/L)/ (513 mEq/L – 140 mEq/L) x hemofiltration rate (mL/h)]. She also received Therapeutic Plasma Exchange for ALF for 5 daily sessions using fresh frozen plasma. She continued to have ongoing acidosis with a lactate of 11.7 mmol/L, and serum bicarbonate of 17 mEq/L. On Hospital Day 6, 3% NaCl was changed to hypertonic NaHCO3 drip [4.2% NaHCO3 solution (500 mEq/L in 1L of D5W) at a rate of 100 mL/hr, replacing 3% NaCl on a 1:1 ratio mL/mL]. After 24 hours she had improvement in metabolic acidosis with improvement in serum bicarbonate from 17 to 24 mEq/L, pH of 7.34 to 7.40; pCO2 32 to 42, HCO3 17 to 25 mmHg and serum Na 133 to 140 mEq/L. Unfortunately, on hospital day 8 developed worsening shock requiring vasopressors; a repeat abdominal imaging noted high-grade small bowel obstruction with ischemic bowel and pneumatosis intestinalis and was transitioned to comfort care. Discussion: While CVVHDF can address elevated ammonia in ALF, infused standard therapy fluid (Na+ = 140 mEq/L) would equilibrate serum Na+ to 133 - 135 mEq/L, in the presence of plasma proteins. Post-filter hypertonic saline infusion during CVVHDF would enable simultaneous clamping of serum Na+ to the appropriate target level. Due to heavier molecular size, 4.2% NaHCo3 results in identical Na+ delivery of 3% saline along with the added benefit of improving acidosis. Clinical studies are desirable to define optimal serum Na+ concentrations during CVVDF in various clinical settings.

A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients

ObjectivesTo develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients. MethodsHospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS). Population PK analysis and Monte Carlo simulations were performed to determine the probability of target attainment (PTA). ResultsOne hundred and forty-two patients received intravenous polymyxin B (1.33–6 mg/kg/day), providing 681 plasma samples. Twenty-four patients were on renal replacement therapy, including 13 on continuous veno-venous hemodiafiltration (CVVHDF). A 2-compartment model adequately described the PK with body weight as a covariate on the volume of distribution that affected Cmax, but it did not impact clearance or exposure. Creatinine clearance was a statistically significant covariate on clearance, although clinically relevant variations of dose-normalized drug exposure were not observed across a wide creatinine clearance range. The model described higher clearance in CVVHDF patients than in non-CVVHDF patients. Maintenance doses of ≥2.5 mg/kg/day or ≥150 mg/day had a PTA ≥90% (for non-pulmonary infections target) at a steady state for minimum inhibitory concentrations ≤2 mg/L. The PTA at a steady state for CVVHDF patients was lower. DiscussionFixed loading and maintenance doses of polymyxin B seemed to be more appropriate than weight-based dosing regimens in patients weighing 45–90 kg. Higher doses may be needed in patients on CVVHDF. Substantial variability in polymyxin B clearance and volume of distribution was found, suggesting that therapeutic drug monitoring may be indicated.

Urinary neutrophil gelatinase-associated lipocalin and plasma IL-6 in discontinuation of continuous venovenous hemodiafiltration for severe acute kidney injury: a multicenter prospective observational study

BackgroundPatients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF.MethodsThis prospective observational study was conducted in seven university-affiliated ICUs. For urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma IL-6 measurements, samples were collected at initiation, 24 h, 48 h after, and CVVHDF discontinuation in adult patients with severe AKI. The outcomes were deaths during CVVHDF and CVVHDF dependence.ResultsA total number of 133 patients were included. Twenty-eight patients died without CVVHDF discontinuation (CVVHDF nonsurvivors). Urinary NGAL and plasma IL-6 at the CVVHDF initiation were significantly higher in CVVHDF nonsurvivors than in survivors. Among 105 CVVHDF survivors, 70 patients were free from renal replacement therapy (RRT) or death in the next 7 days after discontinuation (success group), whereas 35 patients died or needed RRT again (failure group). Urinary NGAL at CVVHDF discontinuation was significantly lower in the success group (93.8 ng/ml vs. 999 ng/ml, p < 0.01), whereas no significant difference was observed in plasma IL-6 between the groups. Temporal elevations of urinary NGAL levels during the first 48 h since CVVHDF initiation were observed in CVVHDF nonsurvivors and those who failed in CVVHDF discontinuation.ConclusionsUrinary NGAL at CVVHDF initiation and discontinuation was associated with mortality and RRT dependence, respectively. The serial changes of urinary NGAL might also help predict the prognosis of patients with AKI on CVVHDF.Graphical

Pharmacokinetics/pharmacodynamics of cefiderocol administered by continuous infusion in a case series of critically ill patients with carbapenem-resistant Acinetobacter baumannii infections undergoing continuous venovenous haemodiafiltration (CVVHDF)

ObjectivesTo assess the pharmacokinetics/pharmacodynamics (PK/PD) of cefiderocol administered by continuous infusion (CI) in a case series of critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections undergoing continuous venovenous haemodiafiltration (CVVHDF). MethodsCritically ill patients receiving cefiderocol by CI during CVVHDF for documented bloodstream infections (BSIs), ventilator-associated pneumonia (VAP), and/or complicated intrabdominal infections (cIAIs) caused by CRAB and undergoing therapeutic drug monitoring (TDM) from February 2022 to January 2023 were retrospectively assessed. Cefiderocol concentrations were determined at steady-state, and the free fraction (fCss) was calculated. Cefiderocol total clearance (CLtot) was determined at each TDM assessment. fCss/MIC ratio was selected as a PD determinant of cefiderocol efficacy and defined as optimal (>4), quasi-optimal (1–4), and suboptimal (<1). ResultsFive patients with documented CRAB infections (two BSI+VAP, two VAP, and one BSI+cIAI) were included. The maintenance dose of cefiderocol was 2 g q8h over 8 h by CI. Median average fCss was 26.5 mg/L (21.7–33.6 mg/L). Median CLtot was 4.84 L/h (2.04–5.22 L/h). Median CVVHDF dose was 41.1 mL/kg/h (35.5–44.9 mL/kg/h), and residual diuresis was reported in 4/5 cases. Optimal PK/PD target was attained in all cases, with a median cefiderocol fCss/MIC ratio of 14.9 (6.6–33.6). ConclusionCI of full doses of cefiderocol could be a useful strategy to attain aggressive PK/PD targets for the treatment of severe CRAB infections in critically ill patients undergoing high-intensity CVVHDF and who have residual diuresis.

Postoperative Hyperuricemia—A Risk Factor in Elective Cardiosurgical Patients

Hyperuricemia is a well-known cardiovascular risk factor. The aim of our study was to investigate the connection between postoperative hyperuricemia and poor outcomes after elective cardiac surgery compared to patients without postoperative hyperuricemia. In this retrospective study, a total of 227 patients after elective cardiac surgery were divided into two groups: 42 patients with postoperative hyperuricemia (mean age 65.14 ± 8.9 years) and a second group of 185 patients without it (mean age 62.67 ± 7.45 years). The time spent on mechanical ventilation (hours) and in the intensive care unit (days) were taken as the primary outcome measures while the secondary measure comprised postoperative complications. The preoperative patient characteristics were similar. Most of the patients were men. The EuroSCORE value of assessing the risk was not different between the groups nor the comorbidities. Among the most common comorbidities was hypertension, seen in 66% of all patients (69% in patients with postoperative hyperuricemia and 63.7% in those without it). A group of patients with postoperative hyperuricemia had a prolonged time of treatment in the intensive care unit (p = 0.03), as well as a prolonged duration of mechanical ventilation (p < 0.01) and a significantly higher incidence of the following postoperative complications: circulatory instability and/or low cardiac output syndrome (LCOS) (χ2 = 4486, p < 0.01), renal failure and/or continuous venovenous hemodiafiltration (CVVHDF's) (χ2 = 10,241, p < 0.001), and mortality (χ2 = 5.22, p < 0.01). Compared to patients without postoperative hyperuricemia, elective cardiac patients with postoperative hyperuricemia have prolonged postoperative treatment in intensive care units, extended durations of mechanically assisted ventilation, and a higher incidence of postoperative circulatory instability, renal failure, and death.

Switching from continuous veno-venous hemodiafiltration to intermittent sustained low-efficiency daily hemodiafiltration (SLED-f) in pediatric acute kidney injury: A prospective cohort study.

Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step-down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low-efficiency daily dialysis with pre-filter replacement (SLED-f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED-f as a transition step-down therapy after CKRT in critically ill pediatric patients with acute kidney injury. A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi-organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED-f. Eleven patients underwent 105 SLED-f sessions (mean of 9.55 +/- 4.90 sessions per patient), as a part of step-down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED-f, urea reduction ratio was 64.1 +/- 5.3%, Kt/V was 1.13 +/- 0.1, and beta-2 microglobulin reduction was 42.5 +/-4%. Incidence of hypotension and requirement of escalation of inotropes during SLED-f was 18.18%. Filter clotting occurred twice in one patient. SLED-f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU.

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

PurposeTo explore pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for treating difficult-to-treat resistant Gram-negative (DTR-GN) infections in critical patients undergoing continuous venovenous haemodiafiltration (CVVHDF). Materials and methodsPatients treated with CI ceftazidime-avibactam for DTR-GN infections during CVVHDF were retrospectively assessed. Ceftazidime and avibactam concentrations were measured at steady-state and the free fraction (fCss) was calculated. Total clearance (CLtot) of both agents were calculated and the impact of CVVHDF intensity was assessed by linear regression. The joint PK/PD target of ceftazidime-avibactam was defined as optimal when both fCss/MIC≥4 for ceftazidime and fCss/CT > 1 for avibactam were achieved. Relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed. ResultsEight patients with DTR-GN infections were retrieved. Median fCss were 84.5 (73.7–87.7 mg/L) for ceftazidime and 24.8 mg/L (20.7–25.8 mg/L) for avibactam. Median CLtot was 2.39 L/h (2.05–2.96 L/h) for ceftazidime and 2.56 L/h (2.12–2.98 L/h) for avibactam. Median CVVHDF dose was 38.6 mL/h/kg (35.9–40.0 mL/kg/h). CLtot were linearly correlated with CVVHDF dose (r = 0.53;p = 0.03, and r = 0.64;p = 0.006, respectively). The joint PK/PD targets were optimal granting microbiological eradication in all the assessable cases. ConclusionCI administration of 1.25–2.5 g q8h ceftazidime-avibactam may allow prompt attainment and maintenance of optimal joint PK/PD targets during high-intensity CVVHDF.