Effect of High volumeHemodiafiltration on Lung Oxygenation and Mechanics

Study Overview
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Brief Summary
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To evaluate improvement of sepsis patients with a new modality of treatment (HDF)

Official Title
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Effect of High Volume Hemodiafiltration on Lung Oxygenation, Lung Mechanics and Biomarkers in Mechanically Ventilated Patients With Severe Sepsis

Conditions
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Haemofiltration, Lung Mechanics, Septic Patients

Intervention / Treatment
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* Other: HVHDF
* Other: controlled


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years Severe sepsis defined by Quick SOFA score by presentation of 2 or more of the following criteria: Mental clouding: decreased glasco coma scale GCS < 15 Hypotension: Systolic blood pressure < 100 mmgH Tachypnea: respiratory rate > 22 breath/ minute Then serum lactate is analysed to confirm sepsis hypoperfusion if ≥ 2mmol/L Organs dysfunction (including one of them respiratory failure). Organ dysfunctions are defined as following: Respiratory dysfunction (criteria for ARDS): PaO2/FiO2 <200 Bilateral infiltrates in chest X-ray Resistant hypoxemia Tachypnoea (RR > 40 breath/minute) The need for invasive mechanical ventilation Excluded cardiac causes of pulmonary edema CNS failure: Decreased GCS ≥ 4 decreased points CVS dysfunction: Sustained hypotension even on very high inotropes doses (Noradrenaline >1µm/min)+ adrenaline>1.5µm/min associated with high CVP pressure > 12 mmHg and not responding to fluid challenge test to exclude hypovolemia. Cardiomegaly detected by either echocardiography assessment, or chest X-ray Resistant frequent ventricular ectopics not explained by organic causes. Liver dysfunction: Elevated total and direct bilirubin than double normal or basal levels Elevated prothrombin time > 17 seconds or INR > 1.5 Elevated liver enzymes > triple normal level Renal dysfunction: Decreased urine output < 0.5 ml/kg. Elevated creatinine level > 164 µmol/L (1.5mg/dL). Decreased creatinine clearance <50ml/minute if available. Bone marrow depression: Decreased platelets < 90 X 103/µL Decreased leukocytes <4 X 103/µL Decreased RBCs count < 4 X 106/µL Exclusion Criteria: Patient relatives' refusal Pregnancy Recent active internal hemorrhage Not mechanically ventilated. Hypersensitivity to the dialyser fluid

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A (controlled group)<br>They will not receive HVHDF treatment | Other: controlled<br>* supportive care<br>|
| Active Comparator: Group B (HVHDF group)<br>They will receive HVHDF treatment for at least 48 hours. HVHDF will be performed via indwelling central venous catheter. The blood flow will be 180-240 ml/min, and ultrafiltration rate will be 35-50 ml/kg/h during HVHF. The substitute fluid will be infused with pre-dilution. Heparin will be used for anti-coagulation, whose initial dose will be 15-25 U/kg, and maintenance dose is 5-15 U/kg/h. aPTT time maintained between 60-80 second and will be checked every 12 hours. The survival status of all of the subjects were followed up at 28 days after being diagnosed as severe sepsis. | Other: HVHDF<br>* Patients will receive HVHDF treatment for at least 48 hours. HVHDF will be performed via indwelling central venous catheter. The blood flow will be 180-240 ml/min, and ultrafiltration rate will be 35-50 ml/kg/h during HVHF. The substitute fluid will be infused with pre-dilution. Heparin will be used for anti-coagulation, whose initial dose will be 15-25 U/kg, and maintenance dose is 5-15 U/kg/h. aPTT time maintained between 60-80 second and will be checked every 12 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial oxygen pressure | change in arterial oxygen pressure (PO2) in units of millimeter mercury (mmHg) | at 0 hour, 24hours and after completion of 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lung mechanics | change in compliance (ml/cmH2O) | 0, 24, and 48 hours | 
| inflammatory biomarkers | Measure inflammatory biomarkers: Interleukin-6. | 0, 24, and 48 hours |