Effects Of The Same Effluent Flow Rate In CVVH And CVVHDF On The Outcomes Of Critical Ill Patients With Sepsis-induced AKI

Objective: Sepsis commonly contributes to critically ill patients withacute kidney injury(AKI); however, the related studies remains limited.Although CRRT therapy has its unique advantages, the treatment withstandard dose of continuous renal-replacement therapy(CRRT) did not reducemortality obviously as expected. Thus, researchers began to explore the newmethod of increasing the plasma clearance to improve the elimination ofsepsis-related inflammatory mediators, which increasing ultrafiltration rate.However, standard dose which ultrafiltration rate of1-2L/h with predilutionlasted more than15years. Until2000, Ronco et al. reported that ultrafiltrationrate increases to35ml/kg/h may provide clinical benefit in patients with AKI.Subsequently, a number of studies about treatment dose of CRRT in patientswith sepsis-induced AKI had been performed. In two large multicentrerandomized controlled studies, ATN Study and Renal Study reported that incritical ill patients with acute kidney injury there was no significant differenceon mortality between the higher-intensity group and lower-intensity group. Itis still difficult to reach consensus in treatment dose of CRRT. The differentunderstanding and application of treatment model and actual therapeutic dosemaybe cause different results. This study was a single center randomizedcontrolled trial, in which critically ill adults with sepsis-induced AKI wererandomly assigned into continuous venovenous hemofiltration (CVVH) groupand continuous venovenous hemodiafiltration (CVVHDF) group in the formof pretdilution with the same effluent flow of50ml/kg/h. Comparison of28-day mortality, duration of CRRT and mechanical ventilation, and days inICU and hospital were performed. The recovery of renal function in ICU andsolute clearance of urea nitrogen,creatinine and β2-M were also compared. The relationship between effluent volume and therapeutic dose was analysised toprovide the basis for clinical.Methods: Critical ill patients with sepsis-induced AKI were enrolledfrom intensive-care unit of Hebei medical university affiliated fourth hospitalbetween May1,2011,and February29,2012. Patients were randomly dividedinto CVVH group and CVVHDF group in the form of pretdilution with thesame effluent f low of50ml/kg/h.14patients were randomly assigned toCVVH, and9to CVVHDF. In the both groups replacement fluid wasdelivered into the extracorporeal circuit before the filter (i.e., predilution). Theratio of dialysate to replacement fluid of1:1in the CVVHDF group. Theeffluent flow prescribed was based on the patient's body weight at the time ofrandomization and was50ml per kilogram per hour. Changes of temperature(T), heart rate (HR), center vein pressure (CVP), mean arterial pressure(MAP), PaO2, FiO2, blood routine, and electrolyte analysis were recorded atthe following time points: pre-CRRT (T0),6h (T1),12h (T2),24h (T3),48h(T4),72h (T5) of CRRT, in order to calculate Oxygenation Index (OI=PaO2/FiO2), acute physiology and chronic health evaluation (APACHE II)score. At the same time, peripheral venous blood and effluent sample werecollected. Levels of BUN, Cr in plasma and effluent were measured bymicroetch. Levels of β2-M in plasma and effluent were measured byRadioimmunoassay (RIA). Auxiliary examination such as bedside chest,bedside ultrasound, and CT were performed if needed. filter time, effluentvolume, days of CRRT treatment, mechanical ventilation, and ICU stay, totalhospital stay were also recorded. The primary outcome was death within28days after randomization. The secondary outcome included days of CRRTtreatment, mechanical ventilation, ICU stay, total hospital stay, and soluteclearance.Results:1Baseline characteristics of the study patientsOf the25patients considered for the study,2did not fit the entry criteriaor refused to give their consent. Therefore,23patients (5women,18men) were enrolled. Patients were randomly divided into two groups (14CVVH,9CVVHDF). No significant differences were present for gender, age. and serumconcentrations of BUN, Cr, and β2-M at baseline (P＞0.05). APACHE II scorein the CVVH group were higher than in the CVVHDF group (P＜0.05). Thenumber of organ dysfunction in patients ranging from2to6. Primary focal ofinfection were respective in the lung, abdominal and thoracic cavity. The mainpathogenic microbial was gram-negative bacteria.2The index changes0f patients during treatmentThere were no significant differences with solute concentration (BUN, Cr,β2-M) in plasma between two groups at the T0time point (P＞0.05). Afterrandomization, solute concentration (BUN, Cr, β2-M) in plasma and soluteconcentration (BUN, Cr) in effluent had no differences at different time points(P＞0.05). While β2-M concentration of CVVH group in effluent were higherthan it of CVVHDF group at different time points (P＜0.05).3Treatment dose and solute clearanceThe actual effluent volume, dose delivered and the actual therapeuticdose did not differ significantly (P>0.05). The6-hour solute clearance of BUNand creatinine after randomization had no differences (P＞0.05), While6-hoursolute clearance of β2-M in the CVVH group was significantly higher than itin the CVVHDF group (P＜0.001).4Type of anticoagulant received and filter timeThe proportion of preflush with heparin saline only, anticoagulation withheparin and no anticoagulant between two groups had no significantdifferences (P>0.05). The filter time had no significant difference between twogroups (P>0.05).5Treatment outcomesThe28-day mortality after randomization in the CVVH group (57.1%)and CVVHDF group (66.7%) had no significant difference (P>0.05). Days ofCRRT treatment, mechanical ventilation, ICU stay, and total hospital stay hadno significant difference (P>0.05). The rate of recovery of renal function inICU and dependence on CRRT had no significant difference (P>0.05). 6Complications of therapyThe proportion of patients with platelet reduction caused by applicationof heparin had no significant difference (P>0.05), and the treatment of CRRThad no disruption because of the platelet reduction. Patients in both groups hadno bleeding complication.Conclusions:1With the same intensity (effluent flow rate of50ml/kg/h) in critical illpatients with sepsis-induced AKI, there were no difference on28-daymortality in CVVH and CVVHDF. The rate of recovery of renal function inICU and days of CRRT treatment, mechanical ventilation, ICU stay and totalhospital stay had no significant differences.2Effluent volume can not accurately reflect the delivere dose. To reachultrafiltration rate of35ml/kg/h (according to the predilution and downtime),the effluent volume should be increased appropriatly.3Small solute clearances had no differences in the two groups. Whilemiddle-molecule Clearance were significantly higher with the use of CVVHthan CVVHDF.4For critically ill patients with sepsis-induced AKI, CVVH should beselected prior to achieve preferable solute clearance of inflammatorymediators.