ROX Index And SpO2/FiO2 Ratio For Predicting High-flow Nasal ...

Discussion

In this multicenter cohort study in tertiary hospitals in Korea, we evaluated the factors associated with HFNC failure and mortality in COVID-19 patients requiring HFNC. We found an HFNC failure rate as high as 53% and an overall mortality of HFNC-treated patients of 24% at referral. After HFNC application, the ROX index and SF ratio between the HFNC success group and the HFNC failure group were significantly different. Age and SF ratio at 1 h after HFNC initiation were significantly associated with HFNC failure. Furthermore, the SF ratio at 1 h and 4 h after HFNC initiation had an acceptable predictive ability for HFNC failure. Mortality of COVID-19 patients was significantly associated with older age and higher SOFA score.

Since the advent of SARS-CoV-2, there have been reports on the usefulness of the ROX index to predict intubation risk in COVID-19 patients receiving HFNC [14–19]. Studies have demonstrated that ROX indices at 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h after HFNC initiation were consistently lower in the HFNC failure group than in the HFNC success group. The AUCs of the ROX indices at 4 h or 6 h after HFNC initiation ranged from 0.70–0.798 [14, 17, 18]. In our study, the predictive function of the ROX index was not remarkable. Compared with those of previous studies, our cohort included relatively older patients with moderate hypoxemia. In addition, ROX indices after HFNC initiation were higher than those reported in previous studies. We attribute the low predictive power of the ROX index to the rapid worsening of respiratory failure in older patients. In cases of acute deterioration in older COVID-19 patients that is not adequately reflected by the ROX index, more accurate or easily applicable alternatives are needed. Furthermore, as the PaO2/FiO2 ratio can be more accurate than the SpO2/FiO2 ratio, a modified ROX index using the PaO2/FiO2 ratio to respiratory rate may be a better prognostic factor that needs validation in the future [20].

Catoire et al. [21] suggested that the AUCs of the SF ratio for PF ratio of 300 and 400 mmHg were high (0.918 and 0.901), which could be used as a hypoxemia screening tool in the emergency department. Using multivariable logistic regression analysis, Patel et al. [22] found that the SF ratio is a significant predictor of intubation risk in COVID-19- related hypoxemic patients. In our study, the SF ratios after HFNC initiation had an acceptable predictive power (AUC: 0.762 and 0.733). Hu et al. [23] reported that both the ROX index at 6 h and the SF and PF ratios at 6 h are accurate predictors of HFNC failure (AUC: SF ratio of 0.786 and PF ratio of 0.749). Arterial blood gas analysis cannot be performed frequently because COVID-19 patients are isolated in a closed room and the number of healthcare personnel is limited. Moreover, respiratory rate may be difficult to objectively monitor because the accuracy of respiratory rate measurements by healthcare professionals is suboptimal [23]. On the other hand, the SF ratio can be calculated by objectively measuring pulse oximetry and FiO2; therefore, we suggest that SF ratios can be a useful tool for predicting intubation in COVID-19 patients.

Whether delayed intubation is associated with higher mortality in COVID-19 patients remains controversial. Physicians managing COVID-19 patients may attempt to avoid intubation whenever possible because of the risk of aerosol dispersion, ventilator-associated pneumonia, or complications, such as unplanned extubation. A recent study revealed no association between time-to-intubation and mortality or further lung injury in critically ill COVID-19 patients [24]. In contrast, Hyman et al. [25] reported that the timing of intubation is significantly associated with mortality, with an adjusted hazard ratio for mortality of 1.03 for each day of delay in intubation. Self-inflicted lung injury associated with delayed intubation could also aggravate lung damage [26], resulting in higher mortality. In addition, 73% of hypoxemia cases and 18% of cardiac arrest cases occurred during emergency intubation of COVID-19 patients [27]. These events are more likely to occur when intubation is performed during aggravated hypoxemia due to delayed intubation. The results of this study indicate that older age and higher SOFA score are important factors for mortality in COVID-19 patients receiving HFNC. Therefore, close observation is required to avoid delayed intubation in older patients with higher SOFA score.

This study has some limitations. First, owing to the retrospective nature of this study, the ROX index may have been calculated inaccurately because of errors in measuring respiratory rate. In addition, respiratory rate can often be neglected owing to time constraints and lack of clinical resources [28]. Therefore, given the availability of limited resources due to the COVID-19 pandemic, our results suggest that the SF ratio can be a useful alternative. Second, the timing of intubation was not standardized at each center. Physicians’ experience may have played a crucial role in the decision of intubation. However, the intubation criteria are not significantly different between COVID-19 and conventional respiratory failure and trained board-certified intensivists oversaw decision-making. Third, this study included relatively small number of patients who received HFNC. We performed a post-hoc power analysis with a sample size of 133 and type 1 error of 0.05, achieving a power of 86% for HFNC failure prediction. The post-hoc power analysis ensures sufficient power of the sample size. Nonetheless, prospective randomized controlled studies with a larger number of patients and standardized protocols are needed in the future.