This study was performed in accordance with the Declaration of Helsinki adopted by the World Medical Association (2013 edition) . The study protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University (PJ-KS-KY-2020-138), Dalian, China. A written informed consent was obtained from all participants or legal guardians at the time of initial admission.
Patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Dalian Medical University from October 1, 2015 to December 30, 2017, were prospectively collected. All included patients met the diagnostic criteria of the third international consensus definitions for sepsis and septic shock (Sepsis-3), accompanied by sepsis-induced acute kidney injury with increase in creatinine or oliguria with fluid overload, and hyperkalemia [10-12, 18-20]. The exclusion criteria were as follows: less than 18 years old; pregnancy; with stomach cancer and acute bleeding; with blood system diseases [e.g., leukemia, myeloma and red blood cell diseases, including polycythemia vera, abnormal mean red blood cell volume (MCV < 80.8 or >99.2 μm3), abnormal mean hemoglobin content (MCH < 26.4 or > 34.2 pg) or abnormal mean hemoglobin concentration (MCHC < 32.0 or > 35.4 g/dL)]; with acute or chronic renal insufficiency or renal failure requiring hemodialysis; with liver cirrhosis; prior blood transfusion within 1 week before admission or during hospitalization; with anemia treated with iron and erythropoietin within 3 months before admission.
The enrolled patients with sepsis were divided into two groups. Patients in the CVVH group received CVVH treatment while those in the control group did not receive CVVH treatment due to refusal either from the patient or from legal guardians.
The control group received routine treatment according to the Surviving Sepsis Campaign guidelines, including intensive monitoring, fluid resuscitation, oxygen administration or mechanical ventilation, antimicrobial therapy (blood culture was conducted before the administration of antibiotics), vasopressor administration if necessary, glucose control, diuretics for oliguria with fluid overload, etc .
Patients in the CVVH group underwent CVVH (Golden Prisma Flex, Sweden) within 24 h after diagnosis in addition to the routine treatment. A 11.5Fr double lumen hemoﬁltration catheter (Lily Technology, Guangdong, China) was percutaneously inserted into the femoral vein or the internal jugular vein. Hemoﬁltration was performed using the PrimaFlex apparatus (ALPRI, France) equipped with an acrylonitrile and sodium methallyl sulfonate copolymer hollow-ﬁber high-ﬂux hemoﬁlter (1.5 m2, Braun Diapact, Germany), and was delivered in CVVH mode. CVVH was performed at a dose of 35 mL/kg/h for 72 h , and thereafter for 12 h per day, depending on the condition of the patient. The average blood ﬂow rates were 150-200 mL/min and the dehydration volume was 300-380 mL/h. The hemoﬁlter was changed every 48 h. The bicarbonate replacement solutions were commercially prepared by Qingshan Likang, Pharmaceutical Co. (Chengdu, China), and was pre-hemoﬁlter diluted. Unfractionated heparin as an anticoagulant or no heparinization was used. The dosage of the unfractionated heparin was adjusted according to the patient’s blood coagulation state.
The following clinical data were collected upon admission: gender, age, sites of infection, comorbidities, numbers of post-operative patients, patients using vasopressors and patients receiving mechanical ventilation, laboratory results, and survival time within 28 days. Hemoglobin, red blood cell distribution width (RDW), reticulocytes, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were measured by an automatic blood cell analyzer (XN-2000; Sysmex, Kobe, Japan). Sequential organ failure assessment (SOFA) scores were assessed on ICU admission based on age, medical history, vital signs, and laboratory results.
Peripheral venous blood (5 mL) was drawn on days 1 (before CVVH treatment), 3 and 7 of admission, centrifuged (TGL-20MS, 4℃, 2000 ×g) for 10 min, and stored at -80 °C for later analysis. Plasma IL-6, hepcidin (Uscn Life Sciences, Wuhan, China), EPO, ferritin (Abcam, Cambridge, MA, USA) and sTfR (R&D Systems, MN, USA) were detected by enzyme linked immunosorbent assay (ELISA).
Statistical analyses were performed using SPSS 23.0 (IBM, Armonk, NY, USA). Continuous variables are expressed as mean ± standard deviation (SD) for normal distribution, or median and range for skewed distribution. Categorical variables were compared using Pearson’s chi-squared or Fisher’s exact test. Continuous variables were compared by Mann-Whitney U test or t test. Cumulative survival curves were depicted using the Kaplan-Meier method and compared by log-rank test. P < 0.05 was considered to be statistically significant.