Alveolar Dead Space Fraction Discriminates Mortality in Pediatric Acute Respiratory Distress Syndrome

Abstract

Objectives: Physiologic dead space is associated with mortality in acute respiratory distress syndrome, but its measurement is cumbersome. Alveolar dead space fraction relies on the difference between arterial and end-tidal carbon dioxide (alveolar dead space fraction = (PaCO2 - PetCO2) / PaCO2). We aimed to assess the relationship between alveolar dead space fraction and mortality in a cohort of children meeting criteria for acute respiratory distress syndrome (both the Berlin 2012 and the American-European Consensus Conference 1994 acute lung injury) and pediatric acute respiratory distress syndrome (as defined by the Pediatric Acute Lung Injury Consensus Conference in 2015).

Design: Secondary analysis of a prospective, observational cohort.

Setting: Tertiary care, university affiliated PICU.

Patients: Invasively ventilated children with pediatric acute respiratory distress syndrome.

Interventions: None.

Measurements and main results: Of the 283 children with pediatric acute respiratory distress syndrome, 266 had available PetCO2. Alveolar dead space fraction was lower in survivors (median 0.13; interquartile range, 0.06-0.23) than nonsurvivors (0.31; 0.19-0.42; p < 0.001) at pediatric acute respiratory distress syndrome onset, but not 24 hours after (survivors 0.12 [0.06-0.18], nonsurvivors 0.14 [0.06-0.25], p = 0.430). Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminated mortality with an area under receiver operating characteristic curve of 0.76 (95% CI, 0.66-0.85; p < 0.001), better than either initial oxygenation index or PaO2/FIO2. In multivariate analysis, alveolar dead space fraction at pediatric acute respiratory distress syndrome onset was independently associated with mortality, after adjustment for severity of illness, immunocompromised status, and organ failures.

Conclusions: Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminates mortality and is independently associated with nonsurvival. Alveolar dead space fraction represents a single, useful, readily obtained clinical biomarker reflective of pulmonary and nonpulmonary variables associated with mortality.

Figure 1

(A) AVDSf at PARDS onset and at 24 hours in survivors and non-survivors. Data is presented as medians and IQR. P-value represents Wilcoxon rank sum tests. (B) ROC curves for AVDSf at PARDS onset (AUROC 0.76, 95% CI 0.66 to 0.85, p < 0.001) and 24 hours after PARDS onset (AUROC 0.55, 95% CI 0.42 to 0.68, p = 0.429).

Figure 2

Mortality stratified by quartiles of AVDSf at PARDS onset. P-value represents Fisher exact test.

Figure 3

AVDSf at PARDS onset and at 24 hours in patients (A) not exposed and (B) exposed to iNO.

Figure 4

(A) AVDSf at 24 hours in patients not exposed and exposed to iNO. (B) ROC curve for discriminating mortality in patients not exposed to iNO (AUROC 0.64 (95% CI 0.50 to 0.78, p = 0.060). (C) ROC curve for discriminating mortality in patients exposed to iNO (AUROC 0.42 (95% CI 0.19 to 0.64, p = 0.386).