In this retrospective before-and-after study, we examined the differences in ICU mortality and other outcomes between septic patients who had undergone mechanical ventilation with conventional oxygenation targets and those who had undergone mechanical ventilation with permissive hypoxia and hyperoxia avoidance. Although the latter approach did not significantly improve patient survival, it was associated with reductions in mechanical ventilation duration and ICU stay. Accordingly, permissive hypoxia and hyperoxia avoidance may help to increase patient turnover and access to ventilators. This optimization of resource utilization in the ICU is crucial for situations where ventilators and ICU beds are in low supply.
Current trials are underway to investigate the potential benefits of conservative ventilatory strategies. The Targeted OXygen therapY in Critical illness (TOXYC) study is a multicenter randomized controlled trial being conducted in the UK to compare the effects of SpO2 targets of 88–92% and ≥ 96% on outcomes in mechanically ventilated patients with respiratory failure11. Similarly, the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial in Denmark is comparing the effects of PaO2 targets of 8 kPa (60 mmHg) and 12 kPa (90 mmHg) on 90-day mortality in adults with hypoxemic respiratory failure12. In a previous before-and-after study of 105 adults who required mechanical ventilation for more than 48 hours at an Australian tertiary care hospital, it was found that an SpO2 target of 90–92% was associated with significant risk reductions for new non-respiratory organ failure and 28-day mortality when compared with conventional oxygen therapy13. In contrast, an Australian multicenter randomized controlled trial found no significant differences in ICU mortality or 90-day mortality between SpO2 targets of 88–92% and ≥ 96%. Although some studies did not detect any significant differences in outcomes between permissive hypoxia and conventional oxygenation strategies14,15, one study reported an association between permissive hypoxia and reduced mortality16. Another study found no significant associations between conservative oxygen therapy and reductions in mortality or hospital stay in septic patients17, which corroborates our findings. A retrospective cohort study conducted in the Netherlands reported that neither FiO2 nor positive end-expiratory pressure settings were reduced in 78% of mechanically ventilated ICU patients with PaO2 exceeding 120 mmHg for FiO2 targets of 0.21–0.418. We posit that permissive hypoxia and hyperoxia avoidance may contribute to the reduction of mechanical ventilation duration and ICU stay due to the continuous and aggressive management in response to each patient’s oxygenation levels.
The use of high-concentration oxygen therapy is associated with pulmonary cellular damage and decreased mucus clearance, which can depress the immune system and elevate the risk of pneumonia19. In particular, severe lung injury occurs more easily for PaO2 of 450 mmHg or more and FiO2 of 0.6 or more19. Other studies have also reported that hyperoxia after nontraumatic cardiac arrest or stroke is associated with increased mortality20, 21. An analysis of immunocompromised patients found that high-concentration oxygen therapy was significantly associated with increased complications, but not with mortality22. It should be noted that our hospital’s policy does not dictate strict oxygenation control in which targets must be met at all times. Instead, it requires that physicians adjust the oxygen fractions and/or ventilatory mode settings after recognizing the occurrence of unsupportable hypoxia and hyperoxia. We found no signs of adverse events resulting from this policy.
As our ICU uses APRV for all patients with respiratory failure, this study is characterized by its focus on APRV-treated cases. Extracorporeal membrane oxygenation was not used in our patients during the study period. Previous studies have shown that APRV allows the continuous and rapid improvement of oxygenation in ARDS patients22–24. The use of APRV in our respiratory failure patients (including ARDS patients) may have contributed to improvements in oxygenation, and warrants further investigation. In addition, neuromuscular blocking drugs were only used in 3 emergent intubation cases (pre-change: 1, post-change: 2). Prone positioning was performed for all patients in both groups by nursing staff. However, prone positioning for more than 12 hours can place a heavy workload on medical staff, and was not utilized in cases where patient safety could not be ensured. In this way, there were no prominent inter-group differences in the use of therapies that could potentially affect respiratory failure rates.
Our findings should be considered in the context of several limitations. First, this was a retrospective single-center study with a relatively small sample size, and our results may lack generalizability. Second, the before-and-after design of this study may have introduced biases such as observer bias or history bias. To reduce these potential biases and improve the validity of our findings, we employed multivariate logistic regression analyses and propensity score matching to account for variations in baseline characteristics. However, multicenter prospective studies are needed to confirm or refute our findings. Third, there may be confounding factors that were not included in analysis. For example, the analysis did not account for differences in underlying disease. Severe diseases such as chronic heart failure, obstructive and/or restrictive pulmonary disease, and chronic kidney failure would affect patient prognosis. In addition, the management of critically ill patients (e.g., early mobilization) may have improved over time, and it is possible that this and other unidentified confounding factors had influenced the mechanical ventilation duration and ICU stay during the relatively long study period. Fourth, we did not use any other ventilatory mode apart from APRV. Therefore, our results may have generalizability issues for other ventilatory modes. Finally, we could not explain why reductions in mechanical ventilation duration and ICU stay did not lead to corresponding reductions in hospital stay. In Japan, acute care hospitals also fulfill the roles that would be assumed by subacute care hospitals in other countries. Therefore, these longer hospitalization durations may have been less affected by the shorter ICU stay.