Role of Ascorbic Acid Infusion in Critically Ill Patients With Transfusion Related Acute Lung Injury

• Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
• The minimum required sample size is estimated to be 40 patients for each group.
• Full written informed consent will be taken from all patients or their next of kin to participate in this study.
• All patients will be subjected directly at time of enrollment to the following;

• Complete history taking and demographic data
• The potential recipient risk factors for TRALI.
• The initial cause of ICU admission and the blood products received.
• Complete physical examination including chest auscultations.
• Vital signs
• Routine laboratory investigations
• Brain natriuretic peptide level
• Troponin T
• Hypoxic index
• Acute Physiology and Chronic Health Evaluation version II (APACHE II) score.
• Sequential Organ Failure Assessment (SOFA) score.
• Kidney Disease Improving Global Outcomes (KDIGO) criteria.
• Child Pugh score.
• Chest radiography and transthoracic echocardiography.
• Samples will be drawn to measure the initial values of ascorbate level, plasma IL-8, IL-10, IL-1β, SOD, MDA and serum CRP.
• Eighty patients with confirmed TRALI (n=80) will be enrolled from critical care units (tertiary hospitals). Then, in addition to their supportive and standard care, they will be randomized (computer sheet) into two groups:

• ASTRALI (AScorbic acid in TRALI) group (n=40) will receive 2.5 gm vitamin C intravenously every 6 hrs for 96 hrs from diagnosis.
• Control group (n=40) will receive placebo in similar regimen.
• All patients will be followed up and treated during the study time. All relevant routine investigations, supportive measures, medications and ventilatory data will be recorded.
• All possible adverse events will be monitored, recorded and managed directly. Hyperoxaluria, microscopic calcium-oxalate crystallization or oxalate nephropathy will be monitored, recorded and managed directly.
• After 96 hrs, resampling for ascorbate level and the same biomarkers will be done.
• Measuring the study secondary outcomes will include vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality.
• Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.

Inclusion criteria

• Adult (18 - 64 years) critically ill patients diagnosed with transfusion related acute lung injury (TRALI), at the time of enrollment or maximum 6 hours before, according to the National Heart, Lung and Blood Institute (NHLBI) Working Group definitions and or the Canadian Consensus Conference criteria (29, 30) as the following criteria;

• No evidence of ALI prior to transfusion.
• Onset of ALI ≤ 6 hours following cessation of transfusion.
• Hypoxemia, defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mmHg or oxygen saturation ≤ 90% on room air.
• Radiographic evidence of bilateral infiltrates.
• No evidence of left atrial hypertension.

Exclusion criteria

• Pregnancy or breastfeeding.
• Hypernatremia or known hypersensitivity to the study drug.
• Parenteral nutrition (total/partial) containing vitamin C.
• Active renal stone or history of urolithiasis.
• Acute Kidney Injury.
• Glucose 6 phosphate dehydrogenase deficiency, iron and copper storage diseases.
• Immunocompromised patients (cancer or patients on immunosuppressive drugs).
• Moribund patient not expected to survive 24 hours .
• Home mechanical ventilation (via tracheotomy or noninvasive) except for Continuous Positive Airway Pressure/ Bilevel Positive Airway Pressure (CPAP/BIPAP) used only for sleep-disordered breathing .