Successful Treatment of a Critically Ill COVID-19 Patient Using Continuous Renal Replacement Therapy With Enhanced Cytokine Removal and Tocilizumab: A Case Report.
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SUBMITTER: Huang TT
PROVIDER: S-EPMC8215202 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFluid overload is associated with morbidity and mortality in patients receiving renal replacement therapy (RRT). We aimed to explore whether fluid overload at initiation of RRT was independently associated with mortality and whether changes in cumulative fluid balance during RRT were associated with outcome.MethodsWe retrospectively analysed the data of patients who were admitted to the multidisciplinary adult intensive care unit (ICU) in a tertiary care centre in the UK between 2012 and 2015 and received continuous RRT (CRRT) for acute kidney injury for at least 24?h. We collected baseline demographics, body mass index (BMI), comorbidities, severity of illness, laboratory parameters at CRRT initiation, daily cumulative fluid balance (FB), daily prescribed FB target, fluid bolus and diuretic administration and outcomes. The day of the lowest cumulative FB during CRRT was identified as nadir FB.ResultsEight hundred twenty patients were analysed (median age 65?years; 49% female). At CRRT initiation, the median cumulative FB was +?1772?ml; 89 patients (10.9%) had a cumulative FB?>?10% body weight (BW). Hospital survivors had a significantly lower cumulative FB at CRRT initiation compared to patients who died (1495 versus 2184?ml; p <?0.001). In the 7?days after CRRT initiation, hospital survivors had a significant decline in cumulative FB (mean decrease 473?ml per day, p <?0.001) whilst there was no significant change in cumulative FB in non-survivors (mean decrease 112?ml per day, p =?0.188). Higher severity of illness at CRRT initiation, shorter duration of CRRT, the number of days without a prescribed FB target and need for higher doses of noradrenaline were independent risk factors for not reaching a FB nadir during CRRT. Multivariable analysis showed that older age, lower BMI, higher severity of illness, need for higher doses of noradrenaline and smaller reductions in cumulative FB during CRRT were independent risk factors for ICU and hospital mortality. Cumulative FB at CRRT initiation was not independently associated with mortality.ConclusionIn adult patients receiving CRRT, a decrease in cumulative FB was independently associated with lower mortality. Fluid overload and need for vasopressor support at CRRT initiation were not independently associated with mortality after correction for severity of illness.
| S-EPMC7268712 | 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:The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.).
| S-EPMC4958154 | biostudies-literature
Project description:Background: Overfeeding can lead to multiple metabolic and clinical complications and has been associated with increased mortality in the critically ill. Continuous venovenous hemofiltration (CVVH) represents a potential source of calories that is poorly recognized and may contribute to overfeeding complications.Objective: We aimed to quantify the systemic caloric contribution of acid-citrate-dextrose regional anticoagulation and dextrose-containing replacement fluids in the CVVH circuit.Design: This was a prospective study in 10 critically ill adult patients who received CVVH from April 2014 to June 2014. Serial pre- and postfilter blood samples (n = 4 each) were drawn and analyzed for glucose and citrate concentrations on each of 2 consecutive days.Results: Participants included 5 men and 5 women with a mean ± SEM age of 61 ± 4 y (range: 42-84 y) and body mass index (in kg/m2) of 28 ± 2 (range: 18.3-36.2). There was generally good agreement between data on the 2 study days (CV: 7-11%). Mean ± SEM pre- and postfilter venous plasma glucose concentrations in the aggregate group were 152 ± 10 and 178 ± 9 mg/dL, respectively. Net glucose uptake from the CVVH circuit was 54 ± 5 mg/min and provided 295 ± 28 kcal/d. Prefilter plasma glucose concentrations were higher in patients with diabetes (n = 5) than in those without diabetes (168 ± 12 compared with 140 ± 14 mg/dL; P < 0.05); however, net glucose uptake was similar (46 ± 8 compared with 61 ± 6 mg/min; P = 0.15). Mean ± SEM pre- and postfilter venous plasma citrate concentrations were 1 ± 0.1 and 3.1 ± 0.2 mmol/L, respectively. Net citrate uptake from the CVVH circuit was 60 ± 2 mg/min and provided 218 ± 8 kcal/d.Conclusions: During CVVH there was a substantial net uptake of both glucose and citrate that delivered exogenous energy and provided ∼512 kcal/d. Failure to account for this source of calories in critically ill patients receiving nutrition on CVVH may result in overfeeding.
| S-EPMC6546225 | 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
Project description:BACKGROUND:Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. METHODS:Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n?=?8) or hemodiafiltration (CVVHDF, n?=?3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. RESULTS:A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45-94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69?L/h, CLCVVHDF: 2.71?L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3?L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ??0.88 for minimal inhibitory concentration (MIC) values ??0.5?mg/L and similar to patients without AKI. CONCLUSIONS:Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. TRIAL REGISTRATION:EudraCT, 2012-005617-39 . Registered on 7 August 2013.
| S-EPMC6296114 | biostudies-literature
Project description:BackgroundPredicting the successful weaning of acute kidney injury (AKI) patients from renal replacement therapy (RRT) has emerged as a research focus, and we successfully built predictive models for RRT withdrawal in patients with severe AKI by machine learning.MethodsThis retrospective single-center study utilized data from our general intensive care unit (ICU) Database, focusing on patients diagnosed with severe AKI who underwent RRT. We evaluated RRT weaning success based on patients being free of RRT in the subsequent week and their overall survival. Multiple logistic regression (MLR) and machine learning algorithms were adopted to construct the prediction models.ResultsA total of 976 patients were included, with 349 patients successfully weaned off RRT. Longer RRT duration (7.0 vs. 9.6 d, p = 0.002, OR = 0.94), higher serum cystatin C levels (1.2 vs. 3.2 mg/L, p < 0.001, OR = 0.46), and the presence of septic shock (28.1% vs. 41.5%, p < 0.001, OR = 0.63) were associated with reduced likelihood of RRT weaning. Conversely, a positive furosemide stress test (FST) (60.2% vs. 40.7%, p < 0.001, OR = 2.75) and higher total urine volume 3 d before RRT withdrawal (755 vs. 125 mL/d, p < 0.001, OR = 2.12) were associated with an increased likelihood of successful weaning from RRT. Next, we demonstrated that machine learning models, especially Random Forest and XGBoost, achieving an AUROC of 0.95. The XGBoost model exhibited superior accuracy, yielding an AUROC of 0.849.ConclusionHigh-risk factors for unsuccessful RRT weaning in severe AKI patients include prolonged RRT duration. Machine learning prediction models, when compared to models based on multivariate logistic regression using these indicators, offer distinct advantages in predictive accuracy.
| S-EPMC10903749 | biostudies-literature
Project description:Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (±21.7 ml/min; n = 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (±0.002 ml/min; n = 75 individual time points). Total body clearance was measured to be 14.0 ml/min (±7.0 ml/min; n = 12). The population area under the curve from 0 to 24 h (AUC0-24) was calculated as 158.5 mg · h/liter (±79.5 mg · h/liter; n = 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.).
| S-EPMC5527635 | biostudies-literature
Project description:We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis (Qu) explained some between-subject variabilities on volume of distribution (V), where [Formula: see text], and clearance (CL), where [Formula: see text], where CLpop and Vpop are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses.
| S-EPMC9764994 | biostudies-literature
Project description:Continuous renal replacement therapy (CRRT) is an important modality to support critically ill patients, and the need for CRRT treatment has been increasing. However, CRRT management is costly, and the associated resources are limited. Thus, it remains challenging to identify patients that are likely to have a poor outcome, despite active treatment with CRRT. We sought to elucidate the factors associated with early mortality after CRRT initiation. We analyzed 240 patients who initiated CRRT at an academic medical center between September 2016 and January 2018. We compared baseline characteristics between patients who died within seven days of initiating CRRT (early mortality), and those that survived more than seven days beyond the initiation of CRRT. Of the patients assessed, 130 (54.2%) died within seven days of CRRT initiation. Multivariate logistic regression models revealed that low mean arterial pressure, low arterial pH, and high Sequential Organ Failure Assessment score before CRRT initiation were significantly associated with increased early mortality in patients requiring CRRT. In conclusion, the mortality within seven days following CRRT initiation was very high in this study. We identified several factors that are associated with early mortality in patients undergoing CRRT, which may be useful in predicting early outcomes, despite active treatment with CRRT.
| S-EPMC6210947 | biostudies-literature