Prognostic value of time-varying dead space estimates in mechanically ventilated patients with acute respiratory distress syndrome

Abstract

Background: The dead space fraction (V_D/V_T) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of V_D/V_T. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.

Methods: This retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (${\dot{V}}_{\text{Ecorr}}$), V_D/V_T (Harris-Benedict), V_D/V_T (Siddiki estimate), and V_D/V_T (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates.

Results: A total of 392 patients (median age 66 [interquartile range: 55-77] years, median SOFA score 9 [interquartile range: 7-12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), ${\dot{V}}_{\text{Ecorr}}$ (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), V_D/V_T (Harris-Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and V_D/V_T (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while V_D/V_T (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, V_D/V_T (Siddiki estimate) and V_D/V_T (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, ${\dot{V}}_{\text{Ecorr}}$ >7.53, and V_D/V_T (Harris-Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database.

Conclusions: In cases where V_D/V_T cannot be measured directly, early time-varying estimates of V_D/V_T such as VR, ${\dot{V}}_{\text{Ecorr}}$, and V_D/V_T (Harris-Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Keywords: 28-day mortality; Acute respiratory distress syndrome; Dead space; Mechanical ventilation.

Figure 1

Flowchart of patient screening and enrollment. A total of 392 patients were included for analysis until hospital discharge or death. ARDS: Acute respiratory distress syndrome; COPD: Chronic obstructive pulmonary disease; ECMO: Extracorporeal membrane oxygenation; ICU: Intensive care unit; MV: Mechanical ventilation.

Figure 2

Trajectories of dead space estimates over the first 7 days of ventilation. The solid line represents patients who survived on the 28th day of admission (n=260 [66.3%]), and the dotted one represents those who died (n=132 [33.7%]). Dots depict the median values of these dead space estimates. *P < 0.05, ^†P < 0.01, ^‡P < 0.001. HB: V_D/V_T (Harris–Benedict); PS: V_D/V_T (Penn State estimate); SE: V_D/V_T (Siddiki estimate); V_D/V_T: The ratio of physiologic dead space to tidal volume; VE: Corrected minute ventilation; VR: Ventilatory Ratio.

Figure 3

Associations of time-varying dead space estimates with 28-day mortality after admission. A: VR and mortality. B: Corrected minute ventilation and mortality. C: V_D/V_T (Harris–Benedict) and mortality. D: V_D/V_T (Siddiki estimate) and mortality. E: V_D/V_T (Penn State estimate) and mortality. Hazard ratios are indicated by solid lines in blue, and 95% CIs by shaded areas. Significant cut-offs are shown in pink solid lines. All models were adjusted for PaO₂/FiO₂, PEEP, driving pressure, and compliance of the respiratory system. CIs: Confidence intervals; PaO₂/FiO₂: Ratio of arterial oxygen partial pressure to fractional inspired oxygen; PEEP: Positive end-expiratory pressure; V_D/V_T: The ratio of physiologic dead space to tidal volume; VR: Ventilatory Ratio.