Time spent in oxygen saturation 95–99% is associated with reduced mortality in critically ill patients with mechanical ventilation

To the Editor:

The administration of supplemental oxygen is one of the ubiquitous interventions in the intensive care unit (ICU) and can be life-saving for mechanically ventilated patients [1]. However, excessive oxygen could be detrimental. Recently, several studies comparing the effect of conservative and liberal oxygen therapy for critically ill patients did not achieve consistent results [2, 3]. Furthermore, in patients with acute respiratory distress syndrome (ARDS), conservative oxygen therapy even had a signal of increased mortality and mesenteric ischemia [4]. Of note, the target oxygen levels in these studies were not the same. It is of paramount importance to elucidate oxygen targets to guide future research. In the present study, with a big database, we aimed to evaluate the association of the proportion of time within arterial oxygen saturation (SpO₂) with hospital mortality in an ICU population with mechanical ventilation (MV).

This study used data stored in the eICU (eicu-crd.mit.edu) database [5]. Adult patients admitted to ICU for the first time with MV during the first 24 h were included. The main exposure was SpO₂, which was generally interfaced from bedside vital sign monitors as the 5-min median value. Thirteen categories of SpO₂ were generated, which were ≤ 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and 100%. The proportion of time spent (PTS) in different SpO₂ categories for each patient was defined as the percentage of the summarized time in each different SpO₂ category divided by total time. Thus, during the first 24 h, patients had SpO₂ values that fell in the 13 categories and for each patient PTS in each of the predefined categories ranged from 0 to 100%. PTS was examined as both a continuous and categorical variable. The primary outcome was hospital mortality. Multivariable logistic regression models including PTS within each of these SpO₂ categories along with the confounders were used to analyze the association of PTS-SpO₂ with mortality outcome.

A total of 25,669 patients from 186 hospitals were included (Table 1), including 21,326 (83%) survivors and 4343 (17%) non-survivors. The median fraction of inspired oxygen was 45% (IQR, 43~60%) and the median duration of MV was 3 days (IQR, 2~5 days). After adjusted for confounders, PTS-SpO₂ of ≤ 88%, 89%, 90%, 91%, 92%, 93%, and 100% were associated with a higher odds ratio for hospital mortality; PTS-SpO₂ of 95%, 96%, 97%, 98%, and 99% were associated with a lower odds ratio; and PTS-SpO₂ of 94% was not associated with hospital mortality (Fig. 1a). Based on the results, SpO₂ was divided into three categories (≤ 94%, 95–99%, and 100%). PTS-SpO₂ within categories of ≤ 94% (p < 0.001) and 100% (p < 0.001) were associated with a higher risk of hospital mortality, whereas an inverse trend was observed between PTS-SpO₂ of 95–99% (p < 0.001) and hospital mortality (Fig. 1b).

Table 1 Characteristics of study patients between survivors and non-survivors

Fig. 1

a Adjusted odds ratio for hospital mortality according to different SpO₂ categories. The proportion of time spent in thirteen different SpO₂ categories (≤ 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and 100%) was considered as a continuous variable, ranging from 0 to 100%, and was included in separate multivariable regression models along with the confounders. In total, 13 models were created. The adjusted odds ratio for each SpO₂ category and 95% confidence intervals (error bars) were calculated after adjusting for age, body mass index (obesity or non-obesity), admission diagnosis, comorbidities (diabetes mellitus, cancer), time-weighted mean FiO₂, time-weighted mean pH, time-weighted mean PaCO₂, sequential organ failure assessment score (not including the respiratory part), and use of dialysis. An odds ratio is calculated per 5% increase in time in each given category. SpO₂, arterial oxygen saturation; FiO₂, fraction of inspired oxygen; PaCO₂, partial pressure of arterial carbon dioxide. b Observed hospital mortality of four predefined time ranges (0–25%, 25–50%, 50–75%, and 75–100%) spent in three different SpO₂ categories (≤ 94%, 95–99%, and 100%). Figures on each histogram column represented the crude hospital mortality

The result of the present study was partially consistent with the British Thoracic Society guideline, which recommended the target of SpO₂ 94–98% [6]. In addition, the result could partly account for the discrepancy of the recent clinical trials of oxygen therapy, which adopted different target oxygen levels [2,3,4]. Despite several limitations to our study (e.g., retrospective design, potential residual confounders, unvalidated data from monitors, relatively short study period, lack of mode of MV, and missing data), our study provided observational evidence for a SpO₂ target range of 95–99% with real-world data. Further studies are warranted to validate the particular target.

In conclusion, the proportion of time spent in oxygen saturation 95–99% is associated with reduced mortality in critically ill patients with mechanical ventilation. These findings may have implications for the design of future trials of oxygen therapy.