A Multicenter, Randomized, Controlled Phase IIb Trial of Avoidance of Hyperoxemia during Cardiopulmonary Bypass.

BACKGROUND: Cardiac surgery utilizing cardiopulmonary bypass (CPB) is one of the most common forms of major surgery. Cardiac surgery-associated multiorgan dysfunction (CSA-MOD) is well recognized and includes acute kidney injury (AKI), hepatic impairment, myocardial damage, and postoperative neurologic deficit. Pathophysiology of CSA-MOD involves numerous injurious pathways linked to the use of CPB including oxidative stress and formation of reactive iron species. During cardiac surgery with CPB, arterial return blood is oxygenated to supranormal levels. This study aimed to determine whether the avoidance of arterial hyperoxemia decreased oxidative stress and reduced the severity of the multiorgan dysfunction in patients undergoing cardiac surgery utilizing CPB. METHODS: The study was a multicenter, open-label, parallel-group, randomized controlled study of the avoidance of arterial hyperoxemia versus usual care in patients undergoing cardiac surgery involving CPB. Primary outcome was the incidence and severity of AKI. Secondary outcomes included serum biomarkers for CSA-MOD, duration of mechanical ventilation, and length of intensive care and hospital stay. RESULTS: A total of 298 patients were randomized and analyzed at two hospitals in New Zealand and Australia. Mean PaO2 was significantly different between groups during CPB. There was no difference in the development of AKI (intervention arm 72.0% vs. usual care 66.2%; difference, -5.8% [95% CI, -16.1 to 4.7%]; P = 0.28), other markers of organ damage, or intensive care unit and hospital length of stay. CONCLUSIONS: Avoiding modest hyperoxemia during CPB failed to demonstrate any difference in AKI, markers of organ damage, or length of stay.

Management of severe acute respiratory distress syndrome in Australia and New Zealand (SAGE-ANZ): An observational study.

Objective: Acute respiratory distress syndrome (ARDS) is associated with significant mortality, morbidity, and cost. We aimed to describe characteristics and management of adult patients admitted to intensive care units (ICUs) in Australia and New Zealand with moderate-severe ARDS, to better understand contemporary practice. Design: Bi-national, prospective, observational, multi-centre study. Setting: 19 ICUs in Australia and New Zealand. Participants: Mechanically ventilated patients with moderate-severe ARDS. Main outcome measures: Baseline demographic characteristics, ventilation characteristics, use of adjunctive support therapy and all-cause mortality to day 28. Data were summarised using descriptive statistics. Results: 200 participants were enrolled, mean (±SD) age 55.5 (±15.9) years, 40% (n = 80) female. Around half (51.5%) had no baseline comorbidities and 45 (31%) tested positive for COVID-19. On day 1, mean SOFA score was 9 ± 3; median (IQR) PaO2/FiO2 ratio 119 (89, 142), median (IQR) FiO2 70% (50%, 99%) and mean (±SD) positive end expiratory pressure (PEEP) 11 (±3) cmH2O. On day one, 10.5% (n = 21) received lung protective ventilation (LPV) (tidal volume ≤6.5 mL/kg predicted body weight and plateau pressure or peak pressure ≤30 cm H2O). Adjunctive therapies were received by 86% (n = 172) of patients at some stage from enrolment to day 28. Systemic steroids were most used (n = 127) followed by neuromuscular blockers (n = 122) and prone positioning (n = 27). Median ventilator-free days (IQR) to day 28 was 5 (0, 20). In-hospital mortality, censored at day 28, was 30.5% (n = 61). Conclusions: In Australia and New Zealand, compliance with evidence-based practices including LPV and prone positioning was low in this cohort. Therapies with proven benefit in the treatment of patients with moderate-severe ARDS, such as lung protective ventilation and prone positioning, were not routinely employed.