Fig. 5

Protocol for initiation, escalation, weaning and discontinuation of study drug. The study drug (milrinone or placebo – D5W) is initiated after documentation of hypoxemia (oxygenation index – OI ≥ 10 or oxygen saturation index – OSI ≥ 5), in the absence of hypotension and other exclusion criteria. A fluid bolus (10 ml/kg of lactated Ringers solution or normal saline) is recommended prior to study drug initiation. The starting dose is 0.33 μg/kg/min. After 2–4 h of therapy at this dose, study drug is escalated to 0.66 μg/kg/min in the absence of hypotension (mean systemic BP ≥ 35 mmHg and vasoactive inotrope score ≤ 30). The maximum duration of therapy is 72 h. Study drug is weaned to 0.33 μg/kg/min when study discontinuation criteria are met (two OIs < 7 or two OSIs <3.5 at least an hour apart). After 2 h of study drug infusion at 0.33 μg/kg/min, study drug can be discontinued. The presence of any severe and life threatening serious adverse events (SAE) necessitates immediate cessation of study drug. Open label milrinone is permitted after cessation of study drug