Mechanical Ventilation Protocol

All patients were initially ventilated with volume assisted-control ventilation (VCV) using a Drager Savina 300 ventilator prior to randomization to the APRV study arm or LTV study arm. In both groups, the mechanical ventilation goals were to maintain plateau airway pressure (P_plat) at no more than 30 cmH₂O, PaO₂ at between 55- and 100-mm Hg (or pulse oximeter between 88 and 98%), and arterial pH at â‰¥7.30 and tidal volume will be 6ml/ kg of predicted body weight (PBW) as previously described [1]. Patients will be randomized to any one of the treatment arms (LTV or APRV) as per protocol. 

Low Tidal Volume Ventilation

In the LTV group, tidal volume target  will be 6  mL/ kg PBW, with allowances for 4–8  mL/kg PBW to minimize asynchrony between the patient and ventilator; PEEP levels will be adjusted by the ARDSnet PEEP-FiO₂ table, and then tidal volume and the respiratory rate will be regulated to achieve the above target pH. When PFR is < 150, PEEP will be tittered on the basis of lowest driving pressure. 

ARPV

Patients will be transitioned from their previous volume assist-controlled ventilation to APRV with the following initial settings: high airway pressure (P_high) of at the P_plat measured during previous VCV settings, not to exceed 30 cm H₂O; low airway pressure (P_low) will be set at 5 cm H₂O (minimal pressure level was used to prevent atelectasis per standard practice); duration of release (T_low) will be set as 1.5 times of expiratory time constant and further adjusted to achieve 75% of peak expiratory flow rate. T_high will be around 5s to achieve a release frequency of 10- 14/min. 

Sedation & Analgesia

Analgesia target level was a Critical-Care Pain Observational Tool (CPOT) score of 0–2, and the sedation goal was a Richmond Agitation Sedation Scale (RASS) score of − 2 to 0. 

Rescue Therapy

Attending physicians were allowed to use rescue therapy (neuromuscular blocking agents, recruitment maneuver, prone positioning etc.) and the indication for the same will be documented. Physicians will also be allowed to cross-over ventilation protocol if required. 

Weaning form Mechanical Ventilation

Readiness for weaning will be assessed daily. Those patients are eligible for weaning, will undergo a 30-min SBT with a pressure support ventilation of 5–7 cmH₂O, PEEP of 5 cmH₂O, and FiO₂ of â‰¤40%. In the APRV group, in the first stage, P_high will be gradually reduced by 2 cmH₂O, simultaneously with a reduction in release rate by two frequencies/min, twice daily unless the patient’s cardiopulmonary function deteriorated. In the second stage, when patients achieved the criteria with a P_high of 20 cmH₂O on 40% FiO₂, same weaning protocol will be applied. When SBT is successful, attending physician will take the decision to extubate or not. 

General Management

Standard intensive care protocol as per current guidelines for general nursing care, nutrition etc. will be followed. Fluid and vasopressor management will be guided by hemodynamic variables and point of care ultrasound. Broad spectrum antibiotics will be initiated at presentation as per institute protocol and appropriate cultures (blood, urine, abdominal fluid and tracheal aspirate whenever suitable) will be sent and antibiotic therapy will be tailored accordingly. Administration of steroid and tocilizumab will be as per clinical scenario and decided by the attending physician.