Study design This pilot study is the prospective interventional cohort study with comparison to a historical control group at a nine-bed PICU at a university referral hospital. Children with septic shock who meet the inclusion criteria will be enrolled. The HA-treated group will be enrolled between July 2021 and May 2022. The historical control group was composed of patients treated between May 2019 and May 2021. Baseline clinical severity scores were matched between the two groups. Investigators will obtained informed consent from the families of all patients. The confounding factor was controlled by matching ratio 1:3 (baseline clinical severity score matching). So sample size of intervention (HA) group was calculate about 10 cases.

Patients The HA group included children with sepsis, as defined by the Surviving Sepsis Campaign guideline 2020, who were admitted to our PICU during the study period. All children initially received routine treatment for septic shock, including intravenous fluid resuscitation, antibiotics, removal of source of infection and inotropic drugs within 6 hours after the diagnosis of sepsis. Patients were included if they: 1) are 30 days to 15 years of age, 2) require any dose of at least one vasopressor and 3) has a Pediatric Logistic Organ Dysfunction (PELOD)-2 score ≥ 10 or Pediatric Risk of Mortality (PRISM)-3 score ≥ 15. Patients receiving end-of-life support, those with uncontrolled bleeding were excluded. The historical control group included patients with sepsis who were admitted to our PICU with the same inclusion criteria and received standard treatment. Patients will be matched according to baseline clinical severity score.

Hemoadsorption (HA) treatment An HA330 disposable hemoperfusion cartridge (HA330; Jafron, Zhuhai City, China) was used with a continuous renal replacement therapy (CRRT) machine (Aquarius® or Primaflex®) in the intervention group. Investigators will select a blood circuit for each machine according to the patient's body weight. For the Aquarius machine, Aqualine S (64-mL blood volume) will be used for body weight \< 30 kg and Aqualine (105-mL blood volume) will be used for weight ≥ 30 kg. Four types of blood circuit will be utilized with the Prismaflex machine, including Prismaflex HF20 set (60 mL) for weight \< 3-11 kg, Prismaflex M60 set (93 mL) for weight 11-30 kg and Prismaflex M100 set (152 mL) for weight \> 30 kg. After rinsing with normal saline solution with heparin, priming the blood circuit and the cartridge with normal saline solution; using 5% albumin or packed red cells (PRC) when the volume of the extracorporeal circuit is more than 10% of the circulatory volume of the patient. If the albumin level is below 3.5 g/dL and hematocrit is above 30%, 5% albumin will be used for priming. If hematocrit is below 30%, PRC will be used. Vascular access will be established with ultrasound-guided insertion of a double-lumen venous catheter into the right internal jugular or femoral vein. The size of the double-lumen catheter is 8 French (Fr) for patients weighing 6-15 kg, 9-10 Fr for those weighing 15-30 kg and 11.5 Fr for those weighing \> 30 kg. HA will be performed for a maximum of 4 hours, and the second session will be started approximately 24 hours after the end of the first session. The blood flow rate will be started low and be gradually increased while monitoring real-time blood pressure and vital signs with an arterial-line monitor. After the end of the HA session, CRRT will be continued if required.

Data collection and study endpoints Demographic data, underlying disease and source of infection are extracted from patients' hospital charts. Blood gas data, type of respiratory support, dose of vasopressors and laboratory data will be recorded at baseline, 24 hours, 48 hours and 72 hours. The baseline is define as a time before HA treatment in the intervention group and when patients will be noted to have no response to initial resuscitation in the control group. The severity of organ dysfunction or failure will be expressed with the PELOD-2 score and PRISM-3 score and recorded at the four time points above. The dose of vasoactive/vasopressor agents will be expressed as the vasoactive inotropic score (VIS), calculated as: dopamine dose + dobutamine dose + (epinephrine dose × 100) + (norepinephrine dose × 100) + (milrinone dose × 10) + (vasopressin dose × 10,000), with doses expressed as mcg/kg/min for most drugs and as U/kg/min for vasopressin. The primary endpoints are the reduction in PELOD-2 and PRISM-3 scores at 72 hours, with adjustment for baseline between the HA and control groups. The secondary endpoints are the reductions in IL-6, VIS, oxygenation index, serum creatinine, base excess and lactate at 72 hours; length of PICU stay, hospital stay and mechanical ventilation; and 28-day mortality.

Laboratory methods Serum samples are analyzed by Direct Ion Selective Electrode for arterial blood gas analysis, which include the data of arterial lactate, base excess and oxygenation index. Complete blood count (CBC) are analyzed by Chemical dye, Laser scattering, SF Cube, Sheath Fluid and Impedance Method to evaluated white blood cell count (WBC) and platelets. Serum creatinine (Cr) and other blood chemistry are analyzed by Reflotron method. IL-6 is analyzed by Electrochemiluminescence immunoassay (ECLIA).

Data analysis and statistics Data analysis using the median with range (minimum-maximum) or mean ± standard deviation. Investigators will use Student's t-test analysis for continuous variables data and Fisher's exact test for categorical variables data. Within-group analysis of PELOD-2, PRISM-3, oxygenation index, VIS, creatinine, base excess, endotoxin levels and lactate will be performed with paired t-tests; between-group comparisons are performed with analysis of covariance (ANCOVA) at 72 hours, with adjustment for the baseline in each group.