Precision net ultrafiltration dosing in continuous kidney replacement therapy: a practical approach.
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ABSTRACT:
SUBMITTER: Murugan R
PROVIDER: S-EPMC10684837 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Precision net ultrafiltration dosing in continuous kidney replacement therapy: a practical approach.
Murugan Raghavan R Kashani Kianoush K Palevsky Paul M PM
Intensive care medicine experimental 20231128 1
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Project description:Background: An early net ultrafiltration (NUF) rate may be associated with prognosis in patients receiving continuous kidney replacement therapy (CKRT). In this study, we tested whether high or low early NUF rates in patients treated with CKRT were associated with increased mortality. Methods: We conducted a retrospective, observational study among all patients in the Medical Information Mart for Intensive Care IV database who received CKRT for more than 24 h within 14 days after intensive care unit admission. We defined the early (initial 48 h) NUF rate as the amount of fluid removal per hour adjusted by the patients' weight and took it as a classified variable (low rate: <1.6, moderate rate: 1.6-3.1 and high rate: > 3.1 ml/kg/h). The association between 28-day mortality and the NUF rate was analyzed by logistic regression and mediation analyses. Results: A total of 911 patients were included in our study. The median NUF rate was 2.71 (interquartile range 1.90-3.86) ml/kg/h and the 28-day mortality was 40.1%. Compared with the moderate NUF rate, the low NUF rate (adjusted odds ratio 1.56, 95% CI 1.04-2.35, p = 0.032) and high NUF rate (adjusted odds ratio 1.43, 95% CI 1.02-2.01, p = 0.040) were associated with higher 28-day mortality. The putative effect of high or low NUF rates on 28 day mortality was not direct [adjusted average direct effects (ADE) for a low NUF rate = 0.92, p = 0.064; adjusted ADE for a high NUF rate = 1.03, p = 0.096], but mediated by effects of the NUF rate on fluid balance during the same period [adjusted average causal mediation effects (ACME) 0.96, p = 0.010 for a low NUF rate; adjusted ACME 0.99, p = 0.042 for a high NUF rate]. Moreover, we found an increase trend in the NUF rate corresponding to the lowest mortality when fluid input increased. Conclusion: Compared with NUF rates between 1.6-3.1 ml/kg/h in the first 48 h of CKRT, NUF rates > 3.1 and <1.6 ml/kg/h were associated with higher mortality.
| S-EPMC8674682 | biostudies-literature
Project description:BackgroundFluid overload, a critical consequence of acute kidney injury (AKI), is associated with worse outcomes. The optimal fluid removal rate per day during continuous renal replacement therapy (CRRT) is unknown. The purpose of this study is to evaluate the impact of the ultrafiltration rate on mortality in critically ill patients with AKI receiving CRRT.MethodsThis was a retrospective cohort study where we reviewed 1398 patients with AKI who received CRRT between December 2006 and November 2015 at the Mayo Clinic, Rochester, MN, USA. The net ultrafiltration rate (UFNET) was categorized into low- and high-intensity groups (<35 and ≥35 mL/kg/day, respectively). The impact of different UFNET intensities on 30-day mortality was assessed using logistic regression after adjusting for age, sex, body mass index, fluid balance from intensive care unit (ICU) admission to CRRT initiation, Acute Physiologic Assessment and Chronic Health Evaluation III and sequential organ failure assessment scores, baseline serum creatinine, ICU day at CRRT initiation, Charlson comorbidity index, CRRT duration and need of mechanical ventilation.ResultsThe mean ± SD age was 62 ± 15 years, and 827 (59%) were male. There were 696 patients (49.7%) in the low- and 702 (50.2%) in the high-intensity group. Thirty-day mortality was 755 (54%). There were 420 (60%) deaths in the low-, and 335 (48%) in the high-intensity group (P < 0.001). UFNET ≥35 mL/kg/day remained independently associated with lower 30-day mortality (adjusted odds ratio = 0.47, 95% confidence interval 0.37-0.59; P < 0.001) compared with <35 mL/kg/day.ConclusionsMore intensive fluid removal, UFNET ≥35 mL/kg/day, among AKI patients receiving CRRT is associated with lower mortality. Future prospective studies are required to confirm this finding.
| S-EPMC7886538 | biostudies-literature
Project description:IntroductionContinuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality.MethodsWe studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h.ResultsWe studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46-1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00-1.20 mL/kg/h, 1.21-1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13-1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness.ConclusionEarly UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association.
| S-EPMC10911164 | biostudies-literature
Project description:BackgroundRegionally anticoagulated continuous renal replacement therapy with citrate is the first choice for critically ill patients with acute kidney injury. If citrate that reaches the patient exceeds the metabolic capacity, metabolic alkalosis will follow. Bicarbonate from the treatment fluids will also reach the patient and add to the bicarbonate load. Net buffer load is a parameter calculated by the dialysis machine software from the treatment fluid contents, the fluid flows and the filter properties. Each time the treatment settings are altered the net buffer load will be re-calculated. This parameter is integrated as a static safety parameter in the Prismax version 3 software, and will guide the operator on a possible development of metabolic alkalosis with the current settings.MethodsAlgorithms for estimating the net buffer load were developed. Hourly clinical data from electronic medical records from 60 patients' continuous renal replacement treatments at the Adult Intensive Care Unit, Skåne University Hospital, Lund, Sweden was used to simulate net buffer load. The relation between net buffer load and acid base status at steady state was evaluated. Net buffer load was also calculated from three previous studies for comparison to our present cohort.ResultsThe mean net buffer load was +0.09 ±0.04 mmol/h/kg in the present cohort, and comparable to historic cohorts from literature. We could not establish a correlation to steady state arterial bicarbonate. The pre blood pump citrate containing replacement fluid flow rate was affecting net buffer load most of all parts of the dialysis circuit, with a r2 Pearson correlation coefficient of 0.65 (p<0.001).ConclusionThe net buffer load parameter can alert the operator on the expected impact of the dialysis circuit on patient's acid base status. It was possible to calculate realistic net buffer load values during 60 CRRT treatments.
| S-EPMC11781738 | biostudies-literature
Project description:Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.
| S-EPMC8259476 | biostudies-literature
Project description:ImportanceContinuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death.ObjectiveTo characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults.Design, setting, and participantsThis international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023.ExposurePatient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation.Main outcomes and measuresMAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed.ResultsAmong 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04).Conclusions and relevanceIn this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.
| S-EPMC10891477 | biostudies-literature
Project description:The altered pharmacokinetics of renally cleared drugs such as meropenem in critically ill patients receiving continuous renal replacement therapy (CRRT) might impact target attainment. Model-informed precision dosing (MIPD) is applied to individualize meropenem dosing. However, most population pharmacokinetic (PopPK) models developed to date have not yet been evaluated for MIPD. Eight PopPK models based on adult CRRT patients were identified in a systematic literature research and encoded in NONMEM 7.4. A data set of 73 CRRT patients from two different study centers was used to evaluate the predictive performance of the models using simulation and prediction-based diagnostics for i) a priori dosing based on patient characteristics only and ii) Bayesian dosing by including the first measured trough concentration. Median prediction error (MPE) for accuracy within |20%| (95% confidence intervals including zero) and median absolute prediction error (MAPE) for precision ≤ 30% were considered clinically acceptable. For a priori dosing, most models (n = 5) showed accuracy and precision MPE within |20%| and MAPE <35%. The integration of the first measured meropenem concentration improved the predictive performance of all models (median MAPE decreased from 35.4 to 25.0%; median MPE decreased from 21.8 to 4.6%). The best predictive performance for intermittent infusion was observed for the O'Jeanson model, including residual diuresis as covariate (a priori and Bayesian dosing MPE within |2%|, MAPE <30%). Our study revealed the O'Jeanson model as the best-predicting model for intermittent infusion. However, most of the selected PopPK models are suitable for MIPD in CRRT patients when one therapeutic drug monitoring sample is available.
| S-EPMC10190255 | biostudies-literature
Project description:Doripenem dosing regimens for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF) were devised based on an established efficacy criterion (free plasma doripenem concentrations above the minimum inhibitory concentration [fT > MIC] of 1 mg/L for ≥35% of the dosing interval) while maintaining exposure below that with the highest studied dose of 1000 mg infused over 1 hour every 8 hours in healthy subjects. Simulations were utilized to assure ≥90% probability of achieving the efficacy criterion with the recommended doripenem regimens. Inflated intersubject variability of 40% (coefficient of variation) was used for pharmacokinetic parameters (representative of clinical variation) and nonrenal clearance was doubled to account for potential changes with acute renal insufficiency. Results indicate that a reduction in doripenem dose will be needed for critically ill patients receiving CVVH or CVVHDF. This work was conducted to fulfill a health authority request and resulted in the addition of dosing recommendations to the Doribax Summary of Product Characteristics.
| S-EPMC3409546 | biostudies-literature
Project description:Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population.
| S-EPMC4940534 | biostudies-literature
Project description:Rationale & objectiveClinical practice guidelines recommend delivering a continuous renal replacement therapy (CRRT) dose of 20 to 25mL/kg/h. However, practice patterns nationwide are highly variable; this inconsistent prescribing may lead to errors in medication dosing and increase rates of electrolyte and acid-base abnormalities. We describe an initiative to standardize CRRT practice patterns and reduce dosing variability.Study designQuality improvement study.Setting & participantsAdult patients treated with CRRT at the University of Colorado Hospital between January 2016 and October 2017.Quality improvement activitiesAn assessment of the magnitude of the variability in CRRT dosing and the following specific interventions were implemented during the course of 1 year: (1) modification of the electronic medical record (EMR) to include calculated average 24-hour dose in real time, (2) modification of the CRRT procedure note to include comments on dosing, (3) modification of the CRRT order set to display calculations, and (4) yearly educational sessions for renal fellows outlining CRRT-specific dosing targets.OutcomesThe primary outcome was weekly percentage of CRRT treatments with an average delivered daily dose of 20 to 25mL/kg/h. Process and balancing outcomes included CRRT flowsheet accuracy, documentation of rates of delivered dose, and nursing satisfaction.Analytical approachRates of weekly CRRT dosing in compliance with national guidelines were determined and used to create run charts showing compliance rates before and after the quality improvement interventions.ResultsAmong 837 treatments before the intervention, 279 (33%) daily CRRT sessions achieved an average dose of 20 to 25mL/kg/h. Following implementation of interventions, 631 of 952 (66%) treatments achieved this goal. Week-to-week variation in dosing was significantly reduced.LimitationsA single-center study generating data that may not be generalizable to institutions with different CRRT nursing models or different EMR systems.ConclusionsChanges to the EMR and documentation templates and education of CRRT providers about dosing were associated with doubling of the rate of appropriate CRRT dosing and reduction in dosing variability.
| S-EPMC6939344 | biostudies-literature