Effect of Intravenous Dexamethasone and Inhaled Budesonide versus Intravenous Dexamethasone Alone on Lung Injury Score in patients with Acute Respiratory Distress Syndrome – A Prospective, Double Blind, Randomized trial

**Aim of the study:**The aim of this study is to compare the effect of intravenous (IV) Dexamethasone in combination with inhalational Budesonide versus IV Dexamethasone alone on lung injury scores in patients with Acute Respiratory Distress Syndrome (ARDS).

We hypothesize that in patients with moderate-severe ARDS, Combination of IV Dexamethasone and inhalational budesonide is superior to IV Dexamethasone alone in decreasing lung injury score up to Day 7.

**Primary objective:**To evaluate the effect of IV Dexamethasone alone and combination of IV Dexamethasone and inhaled budesonide on the Mean lung injury score from days 1 to 7 in patients with early moderate to severe ARDS.

**METHODOLOGY:**The patients will be screened and enrolled in the study after randomization if they meet the inclusion criteria. The patients enrolled after getting signed written informed consent will be randomized in a 1:1 ratio to the following 2 groups - Group DB (IV Dexamethasone plus budesonide nebulization) and Group D (IV Dexamethasone alone). The antibiotic therapy and the supportive treatment will not be protocolized in both the groups but the standard of care will be advised to follow by the treating physician.  Both the treatment arms will receive the following standard ventilatory management – Tidal volume 4-6 ml/kg predicted body weight, plateau pressure <30 cmH2O, Respiratory rate to maintain PaCO2 between 35 and 50 mmHg and PEEP and FiO2 combination to maintain PaO2 > 60 mmHg and peripheral oxygen saturation of >90%. The optimal compliance method will be employed to determine the PEEP level. This method involves incrementally increasing PEEP from 0, 4, 6, 8, 10, 12 and 14 cmH2O, with an 8-minute ventilation period at each PEEP level to assess the driving pressure (DP) during incremental PEEP(DP=Pplat-PEEP). To find the optimal PEEP, when two PEEP values result in the same minimum DP, then the corresponding minimum PEEP value will be selected. Restrictive fluid strategy will be followed in both the study groups. Group DB will receive IV Dexamethasone at a dose of 20 mg once daily from days 1 to 5 which will be reduced to 10 mg once daily from days 6 to 10 and Budesonide nebulization at a dose of 2 mg every 12 hours from Days 1 to 10 after randomization. Both IV Dexamethasone and Budesonide nebulization will be administered for up to 10 days or until extubating, whichever occurs earlier. Nebulization will be provided by vibrating mesh nebulizer. Group D will receive IV Dexamethasone at a dose of 20 mg once daily from Days 1 to 5 after randomization, followed by 10 mg from Days 6 to 10 or until extubating, whichever occurs earlier. Additionally, they will receive nebulization with normal saline every 12 hours to maintain blinding up to Day 10 or until extubating, whichever occurs earlier. Data from the lung mechanics (Tidal volume ml/kg of predicted body weight, peak pressure, plateau pressure, respiratory rate), gas exchange (P/F ratio, PaCO2, oxygenation index) and hemodynamic variables (Blood pressure, heart rate and need for vasoactive agents) will be recorded at baseline and at days 1,3,5,7 and 10. On each day, highest and lowest values of each of the above parameters will be recorded. Lung Injury Score and Sequential Organ Failure Assessment score will be calculated at baseline and Days 1 to 7 after randomization. Inflammatory markers, including C-Reactive Protein and Interleukin 6, will be assessed at baseline and on days 3, 7, and 10 of the study periods. Number of prone sessions in each patient will be recorded. Patients will be followed up till day 28 after randomization to look for the number of ventilator free days. Glycemic control will be monitored in all the patients.  Patients will be assessed daily on readiness for weaning.