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Crit Care
Critical Care
1364-8535
1466-609X
BioMed Central London

5038
10.1186/s13054-024-05038-3
Matters Arising
Association between arterial oxygen partial pressure and mortality in sepsis
Ding Xinyuan
Chen Shangzhong csz19871103@126.com

https://ror.org/02kzr5g33 grid.417400.6 0000 0004 1799 0055 Department of Intensive Care, Zhejiang Hospital, No. 1229, Gudun Road, Hangzhou, 310013 Zhejiang People’s Republic of China
3 9 2024
3 9 2024
2024
28 2915 7 2024
13 7 2024
© The Author(s) 2024
2024
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pmcTo the editor,

The appropriate arterial oxygen partial pressure (PaO2) in sepsis patients has been investigated in dozens of studies. However, no consensus has been reached. In a recent study [1], Dr. Hyun et al. investigated the association between PaO2 and mortality in critically ill sepsis patients. Data on PaO2 of 4147 sepsis patients from the Korea Sepsis Alliance Registry (KSA) during the first three days was extracted, and patients were divided into conservative PaO2 group (< 80mmHg) and liberal PaO2 group (≥ 80mmHg). Statistical methods, including propensity score matching, mixed linear model, and competitive risk models, were used to explore potential causal relationships. The results showed higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality than conservative PaO2. Several issues should be noted when interpreting these findings.

First, dividing the entire cohort into groups based on the cut-off value of one continuous variable is a common strategy in observational studies. In the current research, a cut-off value of 80 mmHg of PaO2 was used. However, the results may be biased when the correlation between PaO2 and mortality is non-linear. For instance, previous studies [2, 3] have pointed out that there may be a U-shaped correlation between PaO2 and death, which means either extremely high or low PaO2 may be associated with increased mortality compared to normal PaO2. In this case, whether there is a difference between the conservative and liberal PaO2 groups can be significantly affected by the cut-off value. For instance, in the current study, the restrictive cubic spline between PaO2 and mortality showed that the PaO2 with the lowest mortality possibility was around 100mmHg. Thus, when using 80mmHg as the cut-off value, the comparison between conservative (PaO2min < 80mmHg) and liberal (PaO2min ≥ 80mmHg) PaO2 groups was actually comparing the low PaO2 group with the normal PaO2 group combined with the high PaO2 group (< 80mmHg vs. (80 – 110mmHg +  > 110mmHg)), which thus lead to a potentially biased result that liberal PaO2 was associated with low mortality rate. Similarly, the difference in mortality rate between the two groups may also be affected by the proportion of patients with high PaO2. In the current study, we noted that the PaO2 was relatively low even in the liberal PaO2 group (median values were 107, 110, and 106 during three days). In the case of a low proportion of patients with high PaO2, using 80mmHg as the cut-off value may actually be the comparison between the low PaO2 group and the normal PaO2 group, which may also be one factor for the inconsistent results of previous studies.

Second, there may be some statistical issues that also need to be noted. For instance, we note that a total of 4147 patients were included. However, in the multivariable COX regression analysis, only patients (n = 2422) matched in the propensity score matching (PSM) were included. Theoretically, implementing regression analysis only in the matched cohorts may reduce the variability of the cohort, which may result in a biased result. For instance, the PaO2 in the matched cohorts was relatively low (median values were 107, 110, and 106 during three days). Thus, whether higher PaO2 (such as PaO2 > 180mmHg) was associated with poor prognosis cannot be inferred. Another minor issue is that the author used the 5th percentiles of PaO2 as the reference point in restricted cubic spline analysis. This seems a little inappropriate as the selected cut-off point of PaO2 was around 100 mmHg.

Finally, we thank Dr. Hyun et al. for their great work, and we hope our opinions will help interpret these findings.

Acknowledgements

Not applicable.

Author contributions

Dr. Xinyuan Ding raised the clinical issue and Dr. Shangzhong Chen wrote the letter. All authors have review and approved the letter. Dr. Xinyuan Ding raised the clinical issue and Dr. Shangzhong Chen wrote the letter. All authors have review and approved the letter.

Funding

None.

Availability of data and materials

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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