Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score

Abstract

Oxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO₂) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO₂ were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO₂ and its interaction with other covariates were explored. A total of 199,125 PaO₂ samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO₂ samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO₂ on mortality risk was in quadratic form. There was significant interaction between PaO₂ and SAPS-I (p = 0.007). Furthermore, the main effect of PaO₂ on SOFA score was nonlinear. The study shows that the effect of PaO₂ on mortality risk is in quadratic function form, and there is significant interaction between PaO₂ and severity of illness.

Figure 1. Histogram showing the distribution of arterial oxygen partial pressure (PaO₂) in our cohort (n = 199,125).

It appears that PaO₂ is approximately normally distributed with the mean value around 100 mmHg.

Figure 2. Marginal effect of PaO₂ on mortality risk after adjustment for other covariates (all variables finally remained in the model)

. The probability of death decreases with increasing PaO₂, and reaches a nadir at a PaO₂ value of 300 mmHg. Thereafter, the probability of death rises with increasing PaO₂.

Figure 3. The relationship between PaO₂ and mortality risk at different levels of severity of illness.

Covariates except for SOFA were adjusted for in each curve. As expectedly, patients with SAPS-1 = 30 showed highest risk of death and the nadir of the curve was at the PaO₂ value of 210 mmHg. In contrast, those with SAPS-1 = 6 showed the lowest risk of death across the entire PaO₂ range, and the curve reaches a nadir at the PaO₂ value of 420 mmHg.

Figure 4. Marginal effect of PaO₂ on SOFA score after adjustment for other covariates (all variables finally remained in the model).

The SOFA score decreased monotonously with increasing PaO₂ before 450 mmHg. After that further increase in PaO₂ has no effect on reducing SOFA.