The relationship between ventilatory ratio (VR) and 28-day hospital mortality by restricted cubic splines (RCS) in 14,328 mechanically ventilated ICU patients

Abstract

Background: Previous studies found that high levels of ventilatory ratio (VR) were associated with a poor prognosis due to worse ventilatory efficiency in acute respiratory distress syndrome patients. However, relatively few large studies have assessed the association between VR and intensive care unit (ICU) mortality in the general adult ventilated population.

Methods: The present study is a retrospective cohort study. Patients mechanically ventilated for more than 12 h were included. VR was calculated based on a previously reported formula. Restricted cubic spline models were used to fit the relationship between VR and mortality risks.

Results: A total of 14,328 mechanically ventilated ICU patients were included in the study, of which 1311 died within 28 days. The results of the study are as follows: (1) In the general adult ventilated population, VR was positively associated with 28-day mortality when VR ≥ 1.3 (increase of 0.1 per VR; HR 1.05, p < 0.001). The same tendency was also observed in the populations of severe hypoxemia with a PaO₂/FiO₂ (P/F) ratio < 200 mmHg. (2) However, in the population with a P/F ratio ≥ 200, a J-shaped dose-response association between VR and the risk of mortality was observed, with the risk of death positively associated with VR when VR ≥ 0.9 (10% increase in HR for every 0.1 increase in VR, p = 0.000) but negatively associated with VR when VR < 0.9 (10% decrease in HR for every 0.1 increase in VR, p = 0.034). In the population of P/F ratio ≥ 200 with VR less than 0.9, compared to the survival group, the nonsurvival group had a lower level PCO₂ (33 mmHg [29.1, 37.9] vs. 34.4 mmHg [30.6, 38.5]), rather than a significant level of measured minute ventilation or P/F ratio.

Conclusions: VR was positively associated with the risk of death in the general ICU population; however, VR was inversely associated with 28-day mortality in the population with a P/F ratio ≥ 200 and low VR . Further research should investigate this relationship, and VR should be interpreted with caution in clinical practice.

Keywords: ICU mortality; Restricted cubic spline; Ventilatory ratio.

Fig. 1

Flow chart for patient selection and inclusion and exclusion criteria in this study

Fig. 2

Association between VR and mortality in the total ICU population. a Scatter plot showing the relationship between VR and ICU days. The blue line with the gray area represents the 95% confidence intervals for the fitted nonlinear trend (p < 0.001). b VR in survivor and nonsurvivor group. The VR levels were significantly higher in the nonsurvivor group than in the survivor group by the Mann–Whitney nonparametric test (p < 0.0001). c The curve of HR versus VR using univariable Cox regression with restricted cubic splines. A Cox model with restricted cubic splines identified the lowest mortality risk when VR was 1.3. There were significant positive correlations between VR and HR for VR larger than 1.3 (increase of 0.1 per VR; HR 1.05, 95% CI 1.04–1.07). d The curve of HR versus VR using multivariable Cox regression with restricted cubic splines. The curve indicated a nadir of 1.3 even after adjusting for PEEP and the P/F ratio, and a highly positive correlation between VR and HR was also observed when VR was greater than 1.3 (increase of 0.1 per VR; HR 1.11, 95% CI 1.08–1.14). Cubic spline curves are shown as a solid line, with the shaded area representing the 95% confidence intervals

Fig. 3

The nonlinear relationship of VR and the risk of 28-day mortality fit by univariate and multivariate Cox regression with RCS analyses. a Univariate Cox regression with RCS analyses showed that the risk of death remained unchanged until VR = 1.3 in patients with a P/F ratio < 200. When VR was greater than 1.3, the risk of death increased significantly with increasing VR (p < 0.001). b Multivariate Cox regression indicated that the nadir of the curve was 1.3 even though PEEP and the P/F ratio were adjusted in patients with a P/F ratio ≤ 200. c + d In patients with a P/F ratio ≥ 200, both univariate Cox regression (c) and multivariate Cox regression (d) indicated that the relationship between VR and the risk of death appeared as a J-shaped curve, with the lowest risk of mortality at VR = 0.9. When the VR was greater than 0.9, HR was positively correlated with VR, whereas negative correlations between VR and HR were identified when VR was less than 0.9. Shaded areas represent 95% confidence intervals

Fig. 4

Survival analysis in different PCO₂ groups of patients with a P/F ratio ≥ 200. In the population with a P/F ratio ≥ 200, survival analysis showed that the survival rate of the group with VR ≥ 0.9 was higher than that of VR < 0.9 (p = 0.000) (a). Supgroup analysis revealed a similar trend in patients with PCO₂ < 35 mmHg as that in total population (p = 0.018) (b). However, no significant differences existed in the overall survival for the subgroup with PCO₂ 35–45 mmHg (p = 0.493) (c) and PCO₂ > 45 mmHg (p = 0.170) (d)