Dataset Information

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial.

ABSTRACT:

Background

Myoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance.

Methods

In this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal replacement therapy were randomized 1:1 into an intervention arm using continuous veno-venous hemodialysis with high cutoff dialyzer and a control arm using continuous veno-venous hemodiafiltration postdilution with high-flux dialyzer. Regional citrate anticoagulation was used in both groups to maintain the extracorporeal circuit. The concentrations of myoglobin, urea, creatinine, ?2-microglobulin, interleukin-6 and albumin were measured before and after the dialyzer at 1 h, 6 h, 12 h, 24 h and 48 h after initiating continuous renal replacement therapy.

Results

Thirty-three patients were allocated to the control arm (CVVHDF with high-flux dialyzer) and 35 patients to the intervention arm (CVVHD with high cutoff dialyzer). Myoglobin clearance, as a primary endpoint, was significantly better in the intervention arm than in the control arm throughout the whole study period. The clearance values for urea and creatinine were higher in the control arm. There was no measurable albumin clearance in both arms. The clearance data for ?₂-microglobulin and interleukin-6 were non-inferior in the intervention arm compared to those for the control arm. Dialyzer lifespan was 57.0 [38.0, 72.0] hours in the control arm and 70.0 [56.75, 72.0] hours in the intervention arm (p?=?0.029).

Conclusions

Myoglobin clearance using continuous veno-venous hemodialysis with high cutoff dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation.

Trial registration

German Clinical Trials Registry (DRKS00012407); date of registration 23/05/2017. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012407 .

SUBMITTER: Weidhase L

PROVIDER: S-EPMC7659077 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial.

Weidhase Lorenz L de Fallois Jonathan J Haußig Elena E Kaiser Thorsten T Mende Meinhard M Petros Sirak S

Critical care (London, England) 20201111 1

<h4>Background</h4>Myoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance.<h4>Methods</h4>In this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal r ...[more]

PMID: 33176824

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Project description:BackgroundRegional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques.MethodsIn this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD.ResultsMean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups.ConclusionCVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer.Trial registrationGerman Clinical Trials Register (DRKS00005254, registered 26th November 2013).

Project description:BackgroundThe bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers.MethodsProportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between ?2-microglobulin (?2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO.FindingsIn HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48-0.92, p = 0.015), 0.64 (95%CI: 0.44 - 0.95, p = 0.03), 0.61 (95%CI: 0.41 - 0.90, p = 0.012), 0.53 (95%CI: 0.28 - 1.02, p = 0.057) relative to minimally reused LF ones for all cause, cardiovascular, cardiac and infectious mortality respectively. These relationships reversed for extensively reused membranes (p for interaction between reuse and flux < 0.001, p = 0.005) for death from all cause and cardiovascular causes, while similar trends were noted for cardiac and infectious mortality (p of interaction between reuse and flux of 0.10 and 0.08 respectively). Reduction of ?2M explained only 1/3 of the effect of minimally reused HF dialyzers on all cause mortality, while non-?2M related factors explained the apparent attenuation of the benefit with more extensively reused dialyzers. Meta-regression of HEMO and MPO estimated an adjusted HR of 0.63 (95% CI: 0.51-0.78) for non-reused HF dialyzers compared with non-reused LF membranes.ConclusionsThis secondary analysis and synthesis of two large hemodialysis trials supports the widespread use of HF dialyzers in clinical hemodialysis over the last decade. A mechanistic understanding of the effects of HF dialysis and the reuse process on dialyzers may suggest novel biomarkers for uremic toxicity and may accelerate membrane technology innovations that will improve patient outcomes.

Project description:BACKGROUND: The study aimed to investigate the pharmacokinetics of intravenous ciprofloxacin and the adequacy of 400 mg every 12 hours in critically ill Intensive Care Unit (ICU) patients on continuous veno-venous haemodiafiltration (CVVHDF) with particular reference to the effect of achieved flow rates on drug clearance. METHODS: This was an open prospective study conducted in the intensive care unit and research unit of a university teaching hospital. The study population was seven critically ill patients with sepsis requiring CVVHDF. Blood and ultrafiltrate samples were collected and assayed for ciprofloxacin by High Performance Liquid Chromatography (HPLC) to calculate the model independent pharmacokinetic parameters; total body clearance (TBC), half-life (t1/2) and volume of distribution (Vd). CVVHDF was performed at prescribed dialysate rates of 1 or 2 L/hr and ultrafiltration rate of 2 L/hr. The blood flow rate was 200 ml/min, achieved using a Gambro blood pump and Hospal AN69HF haemofilter. RESULTS: Seventeen profiles were obtained. CVVHDF resulted in a median ciprofloxacin t1/2 of 13.8 (range 5.15-39.4) hr, median TBC of 9.90 (range 3.10-13.2) L/hr, a median Vdss of 125 (range 79.5-554) L, a CVVHDF clearance of 2.47+/-0.29 L/hr and a clearance of creatinine (Clcr) of 2.66+/-0.25 L/hr. Thus CVVHDF, at an average flow rate of ~3.5 L/hr, was responsible for removing 26% of ciprofloxacin cleared. At the dose rate of 400 mg every 12 hr, the median estimated Cpmax/MIC and AUC0-24/MIC ratios were 10.3 and 161 respectively (for a MIC of 0.5 mg/L) and exceed the proposed criteria of >10 for Cpmax/MIC and > 100 for AUC0-24/MIC. There was a suggestion towards increased ciprofloxacin clearance by CVVHDF with increasing effluent flow rate. CONCLUSIONS: Given the growing microbial resistance to ciprofloxacin our results suggest that a dose rate of 400 mg every 12 hr, may be necessary to achieve the desired pharmacokinetic-pharmacodynamic (PK-PD) goals in patients on CVVHDF, however an extended interval may be required if there is concomitant hepatic impairment. A correlation between ciprofloxacin clearance due to CVVHDF and creatinine clearance by the filter was observed (r2 = 0.76), providing a useful clinical surrogate marker for ciprofloxacin clearance within the range studied. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52722850.

Dataset Information

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial.

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