Predictors of mortality in acute lung injury during the era of lung protective ventilation

Abstract

Background: Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary predictors of mortality, such as respiratory compliance and the arterial oxygen tension to inspired oxygen fraction ratio (PaO 2 /FiO 2 ). Methods: Demographic, clinical, laboratory and pulmonary variables were recorded in 149 patients with ALI/ ARDS. Significant predictors of mortality were identified in bivariate analysis and these were entered into multivariate analysis to identify independent predictors of mortality. Results: Hospital mortality was 41%. In the bivariate analysis, 17 variables were significantly correlated with mortality, including age, APACHE II score and the presence of cirrhosis. Pulmonary parameters associated with death included PaO 2 /FiO 2 and oxygenation index ((mean airway pressure6FiO 2 6100)4PaO 2 ). In unadjusted analysis, the odds ratio (OR) of death for PaO 2 /FiO 2 was 1.57 (CI 1.12 to 3.04) per standard deviation decrease. However, in adjusted analysis, PaO 2 /FiO 2 was not a statistically significant predictor of death, with an OR of 1.29 (CI 0.82 to 2.02). In contrast, oxygenation index (OI) was a statistically significant predictor of death in both unadjusted analysis (OR 1.89 (CI 1.28 to 2.78)) and in adjusted analysis (OR 1.84 (CI 1.13 to 2.99)). Conclusions: In this cohort of patients with ALI/ARDS, OI was an independent predictor of mortality, whereas PaO 2 / FiO 2 was not. OI may be a superior predictor because it integrates both airway pressure and oxygenation into a single variable.Despite advances in our understanding of the pathophysiology and treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high; approximately 30-60% of patients die before hospital discharge.1-3 Lung protective ventilation, a strategy that targets lower tidal volumes (Vt) and limits plateau pressure (P plat ) to less than 30 cm H 2 O is the only clinical intervention that has shown a mortality benefit in large randomised trials. Observational studies performed before widespread application of lung protective ventilation identified demographic, pulmonary specific and clinical variables that predict mortality in ALI/ ARDS.2 3 6-9These included age, Severe Acute Physiology Score (SAPS II), Acute Physiology and Chronic Health Evaluation (APACHE II) score, cirrhosis, immunosuppression and pulmonary specific variables, including the arterial oxygen tension to fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio, 9 respiratory system compliance (Crs) 3 and oxygenation index (OI).7 To our knowledge, no large study of mortality predictors has been conducted in North America since the implementation of the lung protective ventilation. Thus we conducted a retrospective study of these variables t...

Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial

“…OI has been found to be independently predictive of mortality in patients with ARDS. 19 Secondary outcomes were OI at days 3 and 14, physiological indices of pulmonary function, as measured by respiratory compliance (Crs) and PaO2/FiO2 ratio at days 3, 7 and 14, as well as a change in the sequential organ failure assessment (SOFA)…”

“…There were significantly fewer ventilator-free days in the KGF compared to the placebo group (1 [0-17] versus 20 [13][14][15][16][17][18][19][20][21][22] [95% CI 1·1 -6·8]; P = 0·02). ICU and hospital mortality were also higher in the KGF group.…”

“…In addition, in the KGF group compared to the placebo group the duration of ICU stay (22 [14-34] versus 12 [10][11][12][13][14][15][16][17][18][19] days; P = 0·001) and hospital stay (Table 4) were also increased From randomization to day 90, the probability of survival (online supplement Figure e1a) or breathing without assistance (online supplement Figure e1b) was higher in the placebo group.…”

“…OI is a physiological index of the severity of ALI and measures both impaired oxygenation and the amount of mechanical ventilation delivered. We and others have shown OI is independently predictive of mortality in patients with ALI (Fort, Farmer et al 1997;Seeley, McAuley et al 2008). We have chosen day 7 as we expect this time interval will minimise the competing effects of death and extubation, while allowing a sufficient time interval f or a biological effect to occur.…”

“…There was no significant difference between the two groups in OI at day 7 (the primary outcome) or in any other secondary physiological outcomes. The KGF group, compared to placebo, had fewer median ventilatorfree days (1 [0-17] versus 20 [13][14][15][16][17][18][19][20][21][22] days; difference -8 days, 95% CI -17--2; P < 0·001), a longer median duration of ventilation in survivors (16 [13-30] versus 11 [8][9][10][11][12][13][14][15][16] days; difference 6 days, 95% CI 2-14; P = 0·002) and a higher mortality at 28 days (31·0% versus 9·7%; risk ratio 3·2 95% CI 1·0-10·7; P = 0·054).…”