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

Disclosures

BMC Anesthesiol. 2016;16(108) 

In This Article

Results

The population analysed in this study comprised 442 critically-ill patients admitted for ARDS. As reflected by a median APACHE II admission score of 28 [20;35], a SAPS II admission score of 54 [39;70], a SOFA admission score of 12 [9;15] and a Charlson comorbidity index (CCI) of 3,[2–5] the study population was characterised by severe medical conditions (see Table 1 ). Along the line, patients required in median a PEEP of 17 [15;20] cmH2Obar, Pmean of 25 [21;29] cmH2O, and Ppeak of 36 [32;39] cmH2O on day 1 of protocol. Further respiratory parameters are shown in Additional file 1: Table S1 in the electronic supplement, indicating more invasive ventilation in non-survivors. In 89.3 % of all patients, prone position was applied at least once within the first three days of protocol (see Additional file 2: Table S3 for further details). Non-survivors were significantly older than survivors. Also, lengths of stay in referring institutions as well as lengths of prior mechanical ventilation were longer in non-survivors. Although the aetiology of ARDS was overall not statistically different between survivors and non-survivors, the number of patients with acute on chronic respiratory failure was higher in non-survivors; trauma and sepsis of extrapulmonary origin were more frequent in survivors. Scores for description of severity of illness on ICU admission at our centre were significantly higher in the group of non-survivors. Extracorporeal lung assist devices (ELAD) including extracorporeal membrane oxygenation (ECMO) and extracorporeal lung assist (ECLA) were applied in 256 patients (57.9 %). When ELAD was required in patient, it was set up within the first three days of protocol in 87.5 % (see Additional file 3: Table S4 for further details). Overall patient survival with ELAD was 43.0 %.

On day 1 of the protocol, 99 patients (22.4 %) presented with a PaO2/FiO2 between 200 and 300, which corresponds to the stage of acute lung injury (ALI) in the AECC definition. Respectively, PaO2/FiO2 was below 200 in the remaining 343 patients (77.6 %). Applying the three stages of the Berlin definition, this corresponds to 99 patients (22.4 %) with mild, 210 patients (47.5 %) with moderate and 133 patients (30.1 %) with severe ARDS. The median for PaO2/FiO2 (n = 411) was 137 [93;193] and 16.9 [11.6;27.4] for OI (n = 391).

The predictive validity for in-hospital mortality of the four parameters mentioned above – AECC definition, Berlin definition, PaO2/FiO2 and OI – was calculated for the first seven days on ICU (see Fig. 1). In general, the area under the curve was lowest for all four parameters on day 1 and highest on day 7. Given that we aimed to determine the earliest possible day for outcome prediction and that all parameters showed a monotonous increase until day 3, we decided to use clinical variables from that day for further analyses. As extracorporeal oxygenation was expected to have an impact on respiratory variables, sub-analyses were conducted regarding the predictive value of OI in patients with ELAD, without ELAD and in the entire patient population. As prognostic validity was highest in the group comprising all patients, we decided to evaluate all four categorizing variables regardless of possible extracorporeal oxygenation that might have been in place (see Additional file 4: Figure S1).

Figure 1.

Predicitive validity for in-hospital mortality for the first seven days of ARDS after its diagnosis for AECC and Berlin Definition of ARDS, paO2/FiO2, and oxygenation index. Area under ROC curve shown for the first seven days of ARDS by 4 categorizing options of severity of lung failure: AECC and Berlin Definition of ARDS, paO2/FiO2 and OI

On day 3 of protocol, 31 patients had a PaO2/FiO2 > 300 mmHg. 32 patients died until day 3. Including data of all patients, resulting groups of all four classifications - AECC, Berlin definition, PaO2/FiO2 and OI – based on data from day 3 were depicted as Kaplan-Meier-curves in regards to in-hospital survival (Fig. 2). For the continuous parameters PaO2/FiO2 and OI, groups were identified by calculating the cut-off values (137 for PaO2/FiO2 and 15 for OI respectively) distinguishing between survival or death according to the Youden method described above. Resulting curves in each of the four Kaplan-Meier graphs were significantly different (pLog rank < 0.001) from a univariate perspective. Multivariate regression analyses indicated that not a singular parameter may be considered for reliable mortality prediction (see Additional file 5: Table S2). Hence, stepwise backwards selection allowed the identification of clinically valid combinations of explanatory variables. In the resulting model, OI was the only one of the four investigated categorizing variables that remained significant (HR 1.03, 95 % CI 1.015–1.047, p < 0.001). With every one-point increase of OI, the risk of in-hospital death will increase by 3 %, whereas the risk of in-hospital death would increase by 36 % if the OI increased by 10 points. Use of extracorporeal lung assist devices did not prove to be an independent predictor ( Table 2 ).

Figure 2.

Survival curves for AECC and Berlin definition of acute respiratory distress syndrome, PaO2/FiO2 ratio and OI on day 3. Three hundred seventy nine patients had a PaO2/FiO2 ratio ≤ 300 mmHg on day 3 and have been grouped in the corresponding stages of the AECC (a) and Berlin definition (b). In total, PaO2/FiO2 was available for all 411 patients alive on day 3 (c). Values for FiO2/PaO2*Pmean were available for 391 patients being mechanically ventilated on that day (d). AECC: American-European Consensus Conference; F i O 2 : inspiratory fraction of oxygen; F i O 2 /P a O 2 * P mean describes oxygenation index. P a O 2 : arterial partial pressure of oxygen; P mean : mean airway pressure, OI: oxygenation index

OI – being an independent predictor in the final model of regression analysis – was then used to group patients concerning outcome criteria. Patients with an OI above the respective cut-off of 15 on day 3 had longer length of stay on ICU, longer length of hospital stay, and longer duration of mechanical ventilation. Furthermore, mortality was significantly higher, with patients less likely to be discharged to home or another facility (see Table 3 ).

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