Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear.Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653).Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66–0.92), in-hospital mortality (RR 0.81, 95% CI 0.67–0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74–0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01–1.45).Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.

Antibiotics Removal by Continuous Venovenous Hemofiltration with a Novel Asymmetric Triacetate Membrane Hemofilter: An in vitro Study

Introduction: Continuous renal replacement therapies (CRRTs) are essential in the treatment of critically ill patients with acute kidney injury and are also discussed as a supporting sepsis therapy. CRRT can affect antibiotics plasma concentrations. Objective: The effect of continuous venovenous hemofiltration (CVVH) with an asymmetric triacetate (ATA) membrane hemofilter on concentrations of antibiotics with low (meropenem), medium (vancomycin), and high (daptomycin) protein binding (PB) was investigated. Methods: 1 L human whole blood supplemented with antibiotics was recirculated and filtrated for 6 h in vitro. Clearances and sieving coefficients (SC) were determined from antibiotics concentrations measured at filter inlet, outlet, and filtrate side. Reservoir concentration data were fitted using a first-order kinetic model. Results: Meropenem and vancomycin concentrations decreased to 5–10% of the initial plasma level, while only 50% of daptomycin were removed. Clearances and SCs were (10.8 [10.8–17.4] mL/min, SC = 0.72 [0.72–1.16]) for meropenem, (13.4 [12.3–13.7] mL/min, 0.89 [0.82–0.92]) for vancomycin, and (2.1 [1.8–2.1] mL/min, 0.14 [0.12–0.14]) for daptomycin. Removal by adsorption was negligible. Conclusions: The clearances and SCs presented are comparable with findings of other authors. Meropenem and vancomycin, which exhibit low and medium PB, respectively, were strongly removed, while considerably less daptomycin was removed because of its high PB. Our results suggest that in clinical use of the tested antibiotics during CRRT with the ATA hemofilter, the same factors have to be considered for determining the dosing strategy as with filters with other commonly applied membrane materials.

Changes in hemodynamics, renal blood flow and urine output during continuous renal replacement therapies

Continuous renal replacement therapies (CRRT) affect hemodynamics and urine output. Some theories suggest a reduced renal blood flow as the cause of the decreased urine output, but the exact mechanisms remain unclear. A prospective experimental study was carried out in 32 piglets (2–3 months old) in order to compare the impact of CRRT on hemodynamics, renal perfusion, urine output and renal function in healthy animals and in those with non-oliguric acute kidney injury (AKI). CRRT was started according to our clinical protocol, with an initial blood flow of 20 ml/min, with 10 ml/min increases every minute until a goal flow of 5 ml/kg/min. Heart rate, blood pressure, central venous pressure, cardiac output, renal blood flow and urine output were registered at baseline and during the first 6 h of CRRT. Blood and urine samples were drawn at baseline and after 2 and 6 h of therapy. Blood pressure, cardiac index and urine output significantly decreased after starting CRRT in all piglets. Renal blood flow, however, steadily increased throughout the study. Cisplatin piglets had lower cardiac index, higher vascular resistance, lower renal blood flow and lower urine output than control piglets. Plasma levels of ADH and urine levels of aquaporin-2 were lower, whereas kidney injury biomarkers were higher in the cisplatin group of piglets. According to our findings, a reduced renal blood flow doesn’t seem to be the cause of the decrease in urine output after starting CRRT.

Does hemofiltration protect the brain after head trauma? An experimental study in rabbits

Background Traumatic brain injury (TBI) is one of the most frequent and severe neurological diseases. In the last few decades, significant advances have been made in TBI pathophysiology and monitoring, however new treatments have not emerged. Although the central nervous system (CNS) has been historically defined as an immunologically privileged organ, recent studies show the increasingly predominant role of inflammatory and apoptotic phenomena in the pathogenesis of TBI. Inflammatory response mediators can be eliminated with continuous renal replacement therapies (CRRT). Our aim was to investigate whether hemofiltration protects the brain after head trauma in an experimental study in animals. Methods and results A model of TBI and CVVH was performed in anesthetized New Zealand white rabbits without acute renal failure. The experimental group TBI ( +)-CVVH ( +) was compared with a TBI ( +)-CVVH (−) and a TBI (−)-CVVH ( +) control groups. Rabbits were assessed immediately (NES1) and 24 h hours after (NES2) TBI and/or CVVH using a functional Neurological Evaluation Score (NES) and histology of the brains after sacrifice. There was evidence to support a difference of NES1 comparing with the TBI (−)-CVVH ( +), but not with TBI ( +)-CVVH (−) with only 15% of the rabbits treated with CVVH and TBI showing a favorable neurological course. The final neurological outcome (mortality at 24 h) was 0%, 22% and 53% in the TBI(−) + CVVH( +), TBI( +)-CVVH(−) and TBI( +)-CVVH( +) groups respectively. The use of hemofiltration before or after TBI did not make a difference in regards the outcome of the rabbits. There was evidence in the histology to support an increase of mild ischemia, hemorrhage and edema in the experimental group compared with the other two groups. Conclusions CVVH in rabbits without renal failure used with the intention to protect the brain may worsen the prognosis in TBI.

Intermittent hemodiafiltration as a down-step transition therapy in patients with acute kidney injury admitted to intensive care unit who initially underwent continuous venovenous hemodiafiltration

Background/Aims: Continuous renal replacement therapies (CRRT) are initially employed in patients with acute kidney injury (AKI) in ICU setting. After the period of serious illness, hemodialysis is usually used as a mode of transition from CRRT. Intermittent hemodiafiltration (HDF) is not commonly applied in this scenario. Objectives: To evaluate the feasibility of using HDF as transition therapy after CVVHDF in critically patients with AKI. Methods: An observational and prospective pilot study was conducted in ICU patients with dialysis-requiring AKI. Patients were initially treated with CVVHDF and, after medical improvement, those who still needed renal replacement therapy were switched to HDF treatment. Results: Ten Patients underwent 53 HDF sessions (mean of 5.3 sessions/patient). The main cause of renal dysfunction was sepsis ( N = 7; 70%). The APACHE II mean score was 27.6 ± 6.9. During HDF treatment, the urea reduction ratio was 64.5 ± 7.5%, for β-2 microglobulin serum levels the percentage of decrease was 42.0 ± 7.8%, and for Cystatin C was 36.2 ± 6.9%. Five episodes of arterial hypotension occurred (9.4% of sessions). There were 20 episodes of electrolytic disturbance (37.7% of sessions), mainly hypophosphatemia. No pyrogenic or suggestive episode of bacteremia was observed. Conclusion: Hemodiafiltration was safe and efficient to treat critically ill patients with acute kidney injury during the transition phase from continuous to intermittent dialysis modality. Special attention should be paid regarding the occurrence of electrolytic disturbance, mainly hypophosphatemia.

P0540EFFECT OF MEMBRANE MATERIALS ON VANCOMYCIN, TEICOPLANIN AND LINEZOLID REMOVAL DURING CONTINUOUS RENAL REPLACEMENT THERAPIES: AN IN VITRO STUDY

Background and Aims In a continuous renal replacement therapy (CRRT) scenario, removal of anti-methicillin resistant Staphylococcus Aureus agents can be quantitatively important, thereby contributing to clinically relevant decreases in their plasma concentration during treatment. Extracorporeal elimination of antimicrobial agents is influenced by the dose and modality prescribed, as well as the sieving coefficient (SC) and adsorptive properties of the membrane used.The aim of this study was to document the specific SC and adsorptive capacity of three different membrane materials related to vancomycin, teicoplanin and linezolid. Method This in vitro study used a model of continuous veno-venous hemofiltration. 500 ml of whole blood from healthy donor spiked with one antibiotic under investigation was pumped (blood flow of 50 ml/min and ultrafiltrate flow of 10 ml/min) in a closed-circuit using polysulfone (PS), polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN) membranes. Samples were collected from in-flow, out-flow and ultrafiltrate lines in a 360 min period. Antibiotic concentrations were measured to calculate SCs. Mass balance analysis was assessed to evaluate the adsorptive capacity of PS, PMMA and PAN membrane related to each antibiotic. Results The SCs were substantially affected by the hemodialyzers material in the case of Vancomycin, where PMMA membrane had higher SC (SC=0.89±0.01) compared to PAN (SC=0.79±0.02) and PS (SC=0.62±0.03) membranes. The effect of material was minor for Teicoplanin (Sc=0.12±0.05 for PS, Sc=0.17±0.05 for PMMA, Sc=0.19±0.00 for PAN) and no noticeable difference within hemodialyzers was found for Linezolid (Sc=0.92±0.03 for PS, Sc=0.95±0.01 for PMMA, Sc=0.95±0.00 for PAN). In terms of adsorptive capacity, PS and PMMA membranes showed higher interaction with Vancomycin and Teicoplanin compared with PAN membrane, while a small amount of Linezolid was adsorbed by all the three filters. The cumulative adsorbed amount of PS and PMMA of Teicoplanin were also clinically relevant (99.15 mg/m2 and 51.33 mg/m2 respectively) compared to PAN membrane (9.14 mg/m2). Conclusion PS, PMMA and PAN membranes behave differently in terms of sieving and adsorptive properties related to vancomycin, teicoplanin and linezolid. These differences may have a clinical influence on vancomycin and teicoplanin removal during CRRT, while linezolid variability during CRRT hasn’t to be ascribed for membrane material.

Técnicas continuas de depuración extrarrenal. ¿Precoces o tardías? ¿Cuál es el momento idóneo para su inicio?

El desarrollo de insuficiencia renal aguda (IRA) constituye una problemática frecuente en las unidades de cuidados críticos (UCI), concretamente en las subpoblaciones ingresadas con diagnóstico de sepsis o shock séptico. En la literatura, las indicaciones de aplicación de TCRR están claras (tanto de origen renal como extrarrenal). Sin embargo, no parece claro en ningún estudio publicado previamente el momento ideal del inicio de dichas técnicas, ni la repercusión que esto tiene en la morbimortalidad. El objetivo de este ensayo clínico es analizar si existen diferencias en la mortalidad entre 2 grupos de pacientes con lesión renal aguda y shock séptico, según el inicio precoz o tardío de las TCRR. Es abierto (no hay enmascaramiento), pudiendo caer en sesgo de medición durante la medición de los datos. Los grupos de estudio fueron homogéneos, con aleatorización al azar. Sin embargo, no especifican el tipo de modalidad de TCRR utilizada. El tamaño muestral calculado inicialmente según la potencia conferida al estudio no fue alcanzado finalmente. Las mediciones fueron objetivas. Sin embargo, no aclaran por qué designan como precoz al inicio de las TCRR en las primeras 12 horas desde el desarrollo de LRA y tardío a 48 horas después. Resultados: No hay diferencias de mortalidad a los 90 días (P=0.38, no significativo). Sin embargo, en el grupo tardío un 38% no recibieron TCRR, y 17 % lo recibieron precozmente. El grupo tardío presentó de forma significativa menos días con TCRR. No hubo diferencias en días de ventilación mecánica, vasopresores ni estancia en UCI. ABSTRACT Continuous renal-replacement therapies (CRRT). Early or late? What is the ideal time to start? The development of acute kidney injury (AKI) is a frequent problem in critical care units (ICUs), specifically in subpopulations admitted with a diagnosis of sepsis or septic shock. In the literature, the indications for the application of CRRT are clear (both of renal and extrarenal origin). However, it seems unclear in any previously published study the ideal time of the beginning of these techniques, nor the impact this has on morbidity and mortality. The objective of this clinical trial is to analyze whether there are differences in mortality between 2 patients groups with AKI and septic shock, depending on the early or late onset of CRRT. It is open (no masking), and may fall into measurement bias during the measurement of the data. The study groups were homogeneous and randomized. However, they do not specify the type of CRRT mode used. The sample size initially calculated according to the power conferred on the study was not finally reached. The measurements were objective. Nonetheless, they do not clarify why they designate the early CRRT as early in the first 12 hours after the development of AKI and late 48 hours later. Results: There are no mortality differences at 90 days (P = 0.38, not significant). It seems that in the late group 38% did not receive CRRT, and 17% received it early. The late group presented significantly fewer days with CRRT. There were no differences in days of mechanical ventilation, vasopressors or ICU stay.