Predictors of Survival in Critically Ill Patients With Acute Respiratory Distress Syndrome (ARDS)

An Observational Study

Felix Balzer; Mario Menk; Jannis Ziegler; Christian Pille; Klaus-Dieter Wernecke; Claudia Spies; Maren Schmidt; Steffen Weber-Carstens; Maria Deja


BMC Anesthesiol. 2016;16(108) 

In This Article


In this study, we analysed early predictive values for mortality of the AECC- and Berlin definition of ARDS, PaO2/FiO2 and oxygenation index in critically ill ARDS patients at the reference centre of the Charité Berlin. We suggest that application of our standard operating procedures for ARDS treatment reduced or even eliminated the influence of previous, different treatment approaches. Among the four evaluated criteria to classify or quantify severity of ARDS, OI was found to be the most accurate parameter with respect to predictive validity.

Regarding the time of assessment, the third day after admission to our referral centre was found to represent the best compromise between earliness and accuracy of prognosis of mortality in this patient group. In the group of patients with an OI of 15 or greater on day 3, mortality was higher; length of stay (both in the ICU and hospital) and duration of mechanical ventilation were longer. Furthermore, non-survivors had a significantly longer length of stay and duration of mechanical ventilation in referring hospitals before being admitted to the ICU than survivors of ARDS.

The OI was originally designed as a predictive tool for pediatric patients with hypoxemic conditions.[13,14] Later, this factor has been taken into consideration in adults suffering from ARDS.[15,16] Our findings regarding compromised outcome in patients with an OI of 15 or greater are in line with previous findings indicating that the OI is equivalent to or even better than other mortality prediction parameters used for ARDS, and our study further substantiated this finding. We propose that the OI might be one of the preferable predictive parameters because it exclusively accounts for changes in mean airway pressure and thereby reflects invasiveness of mechanical ventilation to some extent. However, most large observational studies on predictive parameters in ARDS did not assess the OI to adjust the oxygenation ration ratio to the invasiveness of ventilation or did not report it.[17,18] Moreover, currently used categorizing systems, i.e. the AECC and the Berlin definition of ARDS, do not consider the OI in their panels of defining variables.[1,3] To include invasiveness of ventilation, a PEEP level of more or equal than five cm H2O became part of the definition. In contrast, the mean PEEP level in our study group was 17 cm H2O, which demonstrates the severity of illness in our patient population.

In contrast to OI, the PaO2/FiO2 ratio was not an independent predictor of mortality in our study. Although this parameter is often used to describe oxygenation status in critically ill patients, it also failed to predict clinical outcome at the onset of ARDS in recent studies.[19,20] In this respect, our data support the concept that the PaO2/FiO2 ratio alone might not be suitable to determine clinical outcome in ARDS. One explanation might be that the PaO2/FiO2 ratio is a highly variable index depending on ventilator settings, conditions of patients and, to a more or lesser extend, routinely performed therapeutic interventions such as bronchoscopies or positioning. FiO2 by itself, independently of PaO2/FiO2, is usually not considered to select patients regarding their risk of poor outcome in larger clinical trails. However, it has been shown that after controlling for baseline PaO2/FiO2, FiO2 was able to predict mortality.[21]

Villar and colleagues demonstrated that the PaO2/FiO2 ratio obtained 24 h after ARDS onset allowed a better risk classification when FiO2 was at least 0.5 with a PEEP of at least 10 cm H2O.[22] The OI was, however, not part of the Villar study. A side by side comparison in our study of the four different parameters on day 3 showed that the OI was the only parameter that was capable of predicting mortality in multivariate analyses. The other three, including the PaO2/FiO2 ratio, were not identified as independent predictors.

As a known fact, PEEP was not part of the AECC definition but was included in the Berlin definition for classifying ARDS. More studies were conducted to verify the predictive properties of PEEP in the definition of ARDS after the publications of AECC and Berlin guidelines. Since the Berlin definition defines the minimum of PEEP to be 5 cm H2O, many studies followed this assumption and concluded differing results. As an example, when Britos and coworkers categorized their cases as PEEP < 5 cm H2O (1.3 %) and ≥ 10 cm H2O (50 %), they found that after adjusting for PaO2/FiO2 baseline PEEP did not predict mortality.[21] In contrast, in our study the median PEEP was 17 cm H2O, which may be one of the conditions facilitating the finding of a predictable parameter when requiring a higher PEEP. Goligher and coworkers observed in a patient group with a median PEEP of 9.5 cm H2O, that positive oxygenation response to PEEP elevation may predict mortality.[23] Golighers conclusions may not be applied to our patient population that was treated with median PEEP of 17 cm H2O. In this regard, the use of a PEEP level of 5 cm H2O recommended by the Berlin definition might not be appropriate to discriminate the severity of illness and does not allow reliable mortality prediction, respectively. Furthermore, if a PEEP level of 5 cm H2O would have been applied in our patient population, it is strongly expected that the number of severe ARDS cases would increase. Hence, the number of severe cases reported in this manuscript is supposedly underestimated from this perspective. In line with aforementioned studies, this observation underlies the importance of standardized conditions for ARDS classification in order to render investigations from different settings comparable.

In our study, the third day of PaO2/FiO2 < 300 mmHg in our centre was found to represent the best compromise between earliness and accuracy of prognosis of mortality in this patient group. As a special referral centre we are sometimes unable to identify the exact onset of ARDS, which is a limitation of our study. We suggest that the very different treatment approaches in pre-treating hospitals bias comparability of patients at the time of referral to our centre. In the study by Peek and colleagues, the different treatment procedures in hospitals other than ECMO centres were considered as a major limitation when comparing patients.[24] In our opinion, algorithm-guided –and most importantly – homogeneous standard treatment approaches including ventilator settings, inhalation of nitric oxide, prone positioning or volume therapy in an ARDS centre may eliminate these confounding effects. In this context, our data suggests that length of stay in hospitals before transfer to a specialized ARDS treatment centre could impact mortality.