Clinical outcomes of acute respiratory distress syndrome in a university hospital

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Abstract

Background

Mortality rates of acute respiratory distress syndrome (ARDS) are different, depending on severity, etiology, and management.

Objective

To determine 7-day and 28-day mortalities, hospital length of stay (LOS), duration of mechanical ventilation (MV) of ARDS patients, and factors associated with poor outcomes.

Methods

A retrospective study was conducted to review the database of ARDS patients admitted in medical intensive care units (ICUs) at a university hospital between 2010 and 2014. The cases were identified by using International Classification of Diseases, 10th Revision (ICD-10) code-J80 ARDS.

Results

Of 266 patients, 11.7%, 44.4%, and 44% fulfilled mild, moderate, and severe ARDS criteria, respectively. The main cause of ARDS was pneumonia. The 7-day and 28-day mortalities, median LOS, and median MV duration were 31.1%, 69.3%, 18, and 11 days, respectively. Pressure control was the most favorite mode, used with average tidal volume (TV) of 8.63 (2.16) mL/kg ideal body weight (IBW). Recruitment maneuver was most frequently used as adjunctive intervention, whereas prone position was applied to 3.75% of the patients. One-third of the patients received neuromuscular blockades. The median 7-day fluid balance was +6,600 mL. The mean PaO2/FiO2 ratio during the first 3 days, cumulative fluid balance on day 3, and average daily calories during the first week were independent predictors for adjusted 7-day mortality, whereas Acute Physiology and Chronic Health Evaluation (APACHE II) score, fluid balance on day 1, cumulative fluid balance, and average daily calories during the first week were independent predictors for adjusted 28-day mortality.

Conclusions

The 28-day mortality of ARDS was high. In addition, TV and fluid balance were greater than protective limits. These findings indicated the potential improvement of ARDS outcomes in our hospital.

Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and non-cardiogenic pulmonary edema. In 1967, Ashbaugh et al. [1] reported a case series of 12 critically ill patients with tachypnea and hypoxemia accompanied by decreased lung compliance and pulmonary infiltrates on chest X-rays from different etiologies. This was the first established ARDS. Thenceforth, there was no common definition of ARDS [2], resulting in various published prevalences in intensive care units (ICUs). Until 2012, Berlin definition of ARDS was created by a consensus panel of experts (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) to simplify the diagnosis and prognosticate outcomes [3]. ARDS was defined as a clinical entity, which consisted of an acute onset (less than 1 week), bilateral opacities on computed tomography or chest radiograph, a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2 ratio) ≤300 mmHg with a minimum of 5 cm H2O positive end-expiratory pressure (PEEP), and no cardiac failure or fluid overload.

ARDS is associated with high mortality. For over 20 years, many therapeutic strategies have been provided to improve patients’ outcomes. In 2000, the ARDS network established an important study “Ventilation with lower tidal volumes as compared with traditional tidal volumes for ALI and ARDS.” The study demonstrated that the use of low tidal volume (TV; 6 mL/kg predicted weight) significantly reduced mortality from 40% to 30% and increased ventilator-free days, compared with traditional TV (12 mL/kg predicted weight) [4]. In 2010, the ACURASYS study investigators reported that the use of neuromuscular blockade (cisatracurium) in patients with early ARDS with PaO2/FiO2 ratio <150 for 48 h significantly reduced both 28-day and 90-day mortalities and increased ventilator-free days without increased incidence of ICU-acquired weakness [5]. In addition, PROSEVA study showed that prone position with lung-protective strategy reduced 28-day and 90-day mortalities and this strategy should be considered in patients with early ARDS and severe hypoxemia who have the PaO2/FiO2 ratio of <150 despite FiO2 of ≥0.6 and PEEP of ≥5 cm H2O [6].

On the contrary, some strategies did not improve survival and might be harmful to ARDS patients. There were 2 landmark studies of high-frequency oscillation ventilation (HFOV), including OSCAR and OSCILATE trials [7, 8]. The former study showed that HFOV did not reduce mortality and increased the need of sedatives and muscle relaxants. The latter study showed that HFOV increased hospital mortality (47% in the HFOV group vs 35% in the low TV with the high PEEP group) and the need of sedatives, muscle relaxants, and vasopressors. Furthermore, a recent study showed that lung recruitment with PEEP set by respiratory system compliance significantly increased 28-day and 6-month mortalities with higher incidences of barotrauma and hypotension in moderate to severe ARDS patients [9].

Besides the ventilator management, several trials demonstrated benefits of conservative fluid management in patients with ARDS [10, 11, 12, 13]. The Fluid and Catheter Treatment Trial (FACTT) demonstrated that a conservative fluid management strategy improved oxygenation, shortened duration of mechanical ventilation (MV), and ICU stay without a risk of nonpulmonary organ failure in ARDS patients [10]. However, it did not show a mortality benefit and potentially increased a risk of long-term cognitive impairment [14].

Epidemiological studies of the practice and outcomes of ARDS were mostly conducted in high-income countries, and the data in low- to middle-income countries were still limited. Moreover, some studies such as LUNG SAFE study were not focused on ARDS patients [15]. We hypothesized that routine clinical practice and outcomes of ARDS in our hospital might be different from the previous reported data from developed countries due to limited ICU resource and shortage of health care personnel. This study aimed to evaluate the clinical outcomes of ARDS patients, associated factors predicting outcomes, and current physicians’ practice in our medical ICUs.

Materials and methods

Study design

We conducted a retrospective cross-sectional study of clinical outcomes of ARDS patients and physicians’ practice in the medical ICUs at tertiary referral university teaching hospital. We included all ARDS patients admitted in the medical ICUs from September 2010 to September 2014. The patients were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) code: J80 (ARDS) and Diagnosis and Procedure Codes (ICD-9-CM) codes: 997x, 96.7. The data were collected from inpatient medical records. Only patients with fulfilled ARDS criteria (Berlin definition) were reviewed and analyzed. This study was approved by the Institutional Review Board (IRB) of the Faculty of Medicine, Chulalongkorn University, for authorization for medical record review (approval certificate no. 457/59). The clinical trial registration number is TCTR20180212002.

Eligibility criteria

ARDS patients admitted in medical ICUs at tertiary referral university teaching hospital with 14 beds in ICU between September 2010 and September 2014, using the raw data that made up the various components of the Berlin ARDS definition [3].

Statistical analyses

Acute Physiology and Chronic Health Evaluation (APACHE II) was determined at the onset of ARDS. Other recorded variables included age, sex, etiology, blood gas analysis, ventilator management, and clinical outcomes of ARDS. The primary outcome was 28-day mortality. The secondary outcomes were 7-day mortality, and other clinical outcomes were hospital length of stay (LOS) and duration of MV, and ventilator management.

SPSS (versions 22) was used to analyze the data, using odds ratio (OR), P-value, and 95% confidence intervals (CIs). Univariate and multivariate analyses (using variables with P < 0.2 in univariate analysis) for 7- and 28-day mortalities were performed using a binary logistic regression model.

Results

Between 2010 and 2014, 266 of 4,090 (6.5%) patients admitted in our medical ICUs met the Berlin criteria for ARDS diagnosis. Approximately 11.7%, 44.4%, and 44.0% of the patients fulfilled mild, moderate, and severe ARDS criteria, respectively. The severity of ARDS correlated with APACHE II score (r2 = 0.235, P < 0.001). Demographic data of the patients are summarized in Table 1.

Table 1

Characteristics of enrolled patients

OverallMild ARDSModerate ARDSSevere ARDS
N (%)266 (100.0%)31 (11.7%)118 (44.4%)117 (44.0%)
Age (years), mean ± SD54.81 ± 18.6648.84 ± 21.4053.67 ± 18.6457.54 ± 17.56
Gender, n (%)
Male153 (57.5%)16 (51.6%)66 (55.9%)71 (60.7%)
Female113 (42.5%)15 (48.4%)52 (44.1%)46 (39.3%)
BMI (kg/m2), mean ± SD22.21 ± 4.4421.91 ± 3.5921.96 ± 3.9722.56 ± 5.11
Etiology of ARDS (%)
Pneumonia217 (81.6%)26 (83.9%)100 (84.7%)91 (77.8%)
Sepsis25 (9.4%)4 (12.9%)6 (5.1%)15 (12.8%)
HLH3 (1.1%)0 (0%)2 (1.7%)1 (0.9%)
Pneumonitis10 (3.8%)1 (3.2%)4 (3.4%)5 (4.3%)
Multiple factors6 (2.3%)0 (0%)5 (4.2%)1 (0.9%)
Unspecified cause2 (0.8%)0 (0%)1 (0.8%)1 (0.9%)
Diffuse alveolar hemorrhage3 (1.1%)0 (0%)0 (0%)3 (1.1%)
APACHE II median (25%, 75% quartile)26 (22, 31)23.16 (19, 27)25.09 (21, 29)27.69 (23, 32)
PaO2/FiO2, day 1, mean ± SD122.40 ± 58.64237.88 ± 53.81138.96 ± 28.0875.29 ± 18.04
Initial mode (%)
PCV233 (87.6%)22 (71%)105 (89%)106 (90.6%)
VCV5 (1.9%)1 (3.2%)2 (1.7%)2 (1.7%)
PSV14 (5.3%)4 (12.9%)5 (4.2%)5 (4.3%)
SIMV2 (0.8%)1 (3.2%)1 (0.8%)0 (0%)
NIV7 (2.6%)2 (6.5%)1 (0.8%)4 (3.4%)
Bird mark 74 (1.5%)0 (0%)4 (3.4%)0 (0%)
Nasal high flow1 (0.4%)1 (3.2%)0 (0%)0 (0%)
Adjunctive interventions (%)
APRV15 (5.6%)1 (3.2%)4 (3.4%)10 (8.5%)
HFOV4 (1.5%)0 (0%)3 (2.5%)1 (0.9%)
Prone10 (3.8%)0 (0%)5 (4.2%)5 (4.3%)
Recruitment maneuver128 (48.1%)10 (32.3%)58 (49.1%)60 (51.3%)
PIP in PCV, day 1,31 ± 627 ± 531 ± 632 ± 6
mean ± SD (cm H2O)
TV/kg IBW day 1,8.56 ± 2.488.71 ± 2.228.45 ± 2.568.64 ± 2.47
mean ± SD (mL/kg IBW)
PEEP, day 1,10 ± 47 ± 310 ± 412 ± 5
mean ± SD (cm HO) 2
Neuromuscular blockade use (%)94 (35.3%)7 (22.6%)46 (39%)41 (35%)
Sedative drugs (%)229 (86.1%)25 (80.6%)102 (86.4%)102 (87.2%)
Morphine30 (11.3%)1 (3.2%)11 (9.3%)18 (15.4%)
Fentanyl194 (72.9%)22 (71.0%)86 (72.9%)86 (73.5%)
Midazolam197 (74.0%)20 (64.5%)87 (73.7%)90 (76.9%)
Propofol45 (16.9%)7 (22.3%)19 (16.1%)19 (16.2%)
I/O balance, day 1,2,484.94 ± 2,406.922,221.45 ± 2,202.282,161.26 ± 2,145.602,881.19 ± 2,694.55
mean ± SD (mL/day)
Total I/O balance in 3 days,5,029.31 ± 4,5503,760 ± 3,3704,370 ± 4,3066,037 ± 4,892
mean ± SD (mL/day)
Total I/O balance in 7 days,6,634.97 ± 6,718.064,615.92 ± 6,327.185,771.69 ± 6,947.388,052.71 ± 6,337.84
mean ± SD (mL/day)
Enteral calories (kcal/day), AVG in673.75 ± 546.29651.57 ± 590.71724.63 ± 533.06628.30 ± 547.78
7 days, mean ± SD
Ventilator day (days), mean ± SD16.46 ± 20.1124.77 ± 30.8816.61 ± 17.3814.11 ± 20.11
Hospital LOS (days), mean ± SD27.1 ± 26.4734.26 ± 33.6029.63 ± 25.0122.65 ± 25.26
7-day mortality, n (%)83 (31.1)4 (12.9)30 (25.4)49 (41.9)
28-day mortality, n (%)184 (69.2)16 (51.6)82 (69.5)86 (73.5)
APACHE II, Acute Physiology and Chronic Health Evaluation; APRV, airway pressure release ventilation; ARDS, acute respiratory distress syndrome; AVG, average; BMI, body mass index; HFOV, high-frequency oscillation ventilation; HLH, hemophagocytic lymphohistiocytosis; IBW, ideal body weight; I/O, intake/output; LOS, length of stay; NIV, noninvasive ventilation; PaO2/FiO2, the ratio of partial pressure arterial oxygen and fraction of inspired oxygen; PCV, pressure-controlled ventilation; PEEP, positive end-expiratory pressure; PIP, peak inspiratory pressure; PSV, pressure support ventilation; SIMV, simultaneous invasive mechanical ventilation; VCV, volume-controlled ventilation; TV, tidal volume

The majority of the ARDS patients had pneumonia and were assisted with pressure-controlled ventilation with the mean peak inspiratory pressure (PIP) and PEEP on the first day of MV of 31 ± 6 and 10 ± 4 cm H2O, respectively. The plateau pressure (Pplat) was recorded in only 4.1% of the patients. The mean TV on the first day was 8.56 ± 2.48 mL/kg ideal body weight (IBW), and the average TV during the first 3 days of MV was 8.81 ± 2.39 mL/kg IBW. Approximately 55.4% of the patients had TV on the first day of MV of >8 mL/kg IBW and 60.9% of the patients had average TV during the first 3 days of MV of >8 mL/kg IBW.

Neuromuscular blockades and sedative drugs were prescribed to 35.3% and 86.09% of the patients, respectively. Adjunctive interventions including prone position, recruitment maneuver, and rescued modes such as airway pressure release ventilation (APRV) and HFOV were applied to patients with moderate and severe ARDS (Table 1). Noticeably, recruitment maneuver was performed in a half of the patients, especially in the patients with moderate to severe ARDS. However, the incidence of pneumothorax was not different between the patients who received recruitment maneuver (79.7%) and who did not receive recruitment maneuver (82%).

Overall, the crude 7-day mortality was 31.1%, associated with age, ARDS severity, APACHE II score, PaO2/FiO2 ratio on day 1, mean PaO2/FiO2 ratio during the first 3 days, fluid balance on day 1 and cumulative fluid balance during the first 3 and 7 days, and average daily calories during the first week (Table 2). The crude 28-day mortality was 68.9%, associated with age, ARDS severity, APACHE II score, PaO2/FiO2 ratio on day 1, mean PaO2/FiO2 ratio during the first 3 days, TV/kg IBW on day 1, PIP on day 1, neuromuscular blockade use, fluid balance on day 1 and cumulative fluid balance during the first 3 and 7 days, and average daily calories during the first week (Table 2). After adjusting for confounding factors, the mean PaO2/FiO2 ratio during the first 3 days, cumulative fluid balance on day 3, and average daily calories during the first week were independent predictors for 7-day mortality, whereas APACHE II score, fluid balance on day 1, cumulative fluid balance during the first 7 days, and average daily calories during the first week were independent predictors for 28-day mortality (Table 3). Furthermore, the patients who received average daily calories during the first week of <60% of estimated daily energy requirement had a greater risk of death (OR = 3.28, 95% CI 1.79–6.01, P < 0.001). Moreover, interestingly, the risk of death within 28 days increased with increasing 7-day cumulative fluid balance as shown in Figure 1.

Table 2

Univariate analysis for 7- and 28-day mortalities

Univariate analysis7-day mortality
28-day mortality
Crude HR95% CIPCrude HR95% CIP
Age (years)1.0151.001–1.0300.041.0231.009–1.038<0.01*
Gender
Male (%)11
Female (%)0.7420.436–1.2620.270.7890.468–1.3330.38
BMI0.9940.930–1.0630.870.9670.906–1.0310.31
ARDS severity
Mild11
Moderate2.3010.744–7.1150.152.1350.954–4.7810.07
Severe4.6841.599–14.795<0.01*2.6011.151–5.8780.02*
APACHE II1.1081.060–1.159<0.01*1.1011.055–1.150<0.01*
PaO2/FiO2 ratio, day 10.9920.987–0.997<0.01*0.9970.993–1.0010.18
Mean PaO2/FiO2 ratio0.990.980–0.992<0.01*0.9940.990–0.998<0.01*
TV/kg IBW, day 10.9960.883–1.1240.950.9140.810–1.0310.14
Mean TV/kg IBW0.9240.801–1.0670.280.9170.802–1.0480.20
PEEP, day 11.0060.948–1.0670.850.9660.911–1.0240.25
Mean PEEP1.0300.965–1.1000.370.9940.931–1.0620.86
PIP, day 11.0611.004–1.1210.041.0400.983–1.1010.17
Recruitment maneuver0.9100.542–1.5290.771.3120.778–2.2110.31
Pneumothorax0.4780.226–1.0080.051.0790.553–2.1040.82
Neuromuscular blockade0.7180.412–1.2520.221.4710.840–2.5780.18
I/O balance, day 1 (L/day)1.3251.175–1.495<0.01*1.2001.063–1.354<0.01*
Total I/O balance in 3 days (L/day)1.2291.142–1.324<0.01*1.1371.066–1.212<0.01*
Total I/O balance in 7 days (L/day)1.1121.071–1.176<0.01*1.1281.077–1.181<0.01*
7-day AVG enteral calories (kcal/day)0.9980.997–0.999<0.01*0.9990.998–0.999<0.01*
APACHE II, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; AVG, average; BMI, body mass index; CI, confidence interval; HR, hazard ratio; IBW, ideal body weight; I/O, intake/output; mean PaO2/FiO2 ratio, mean PaO2/FiO2 ratio in the first 3 days; mean PEEP, mean PEEP in the first 3 days; mean TV/kg IBW, mean TV/kg IBW in the first 3 days; PaO2/FiO2 ratio, the ratio of partial pressure arterial oxygen and fraction of inspired oxygen; PEEP, positive end-expiratory pressure; PIP, peak inspiratory pressure; TV, tidal volume*Statistical significance
Figure 1
Figure 1

The increasing OR of 28-day mortality in patients who had more positive 7-day cumulative fluid balance. OR, odds ratio

Citation: Asian Biomedicine 12, 6; 10.1515/abm-2019-0029

Table 3

Multivariate analysis for 7- and 28-day mortalities

Multivariate analysis7-day mortality
28-day mortality
Adjusted HR95% CIPAdjusted HR95% CIP
Age (years)1.0040.985–1.0230.701.0020.979–1.0270.63
ARDS severity
Mild11
Moderate1.6080.308–8.3880.577.650.878–66.6620.66
Severe1.8350.204–16.5390.5914.000.715–274.1940.82
APACHE II1.0500.995–1.1080.941.1511.073–1.235<0.01*
PaO2/FiO2 ratio, day 11.0030.995–1.0110.501.0030.994–1.0130.46
Mean PaO2/FiO2 ratio0.9880.981–0.994<0.01*0.9970.989–1.0060.55
TV/kg IBW, day 11.0010.997–1.0040.68
PIP, day 11.0370.966–1.1140.32
Neuromuscular blockade1.2180.524–2.8320.65
I/O balance, day 10.9840.818–1.1820.860.8160.666–0.9980.048*
(L/day)
Total I/O balance in 3 days (L/day)1.1921.102–1.289<0.01*0.9690.802–1.1690.74
Total I/O balance in 7 days (L/day)1.0610.979–1.1500.151.1031.026–1.186<0.01*
7-day AVG enteral calories (kcal/day)0.9980.997–0.999<0.01*0.9990.998–1<0.01*
APACHE II, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; AVG, average; BMI, body mass index; CI, confidence interval; HR, hazard ratio; IBW, ideal body weight; I/O, intake/output; mean PaO2/FiO2 ratio, mean PaO2/FiO2 ratio in the first 3 days; PaO2/FiO2 ratio, the ratio of partial pressure arterial oxygen and fraction of inspired oxygen; PEEP, positive end-expiratory pressure; PIP, peak inspiratory pressure; TV, tidal volumeAdjusted age, ARDS severity, APACHE II score, mean PaO2/FiO2 ratio during the first 3 days, fluid balance on day 1 and cumulative fluid balance during the first 3 and 7 days, and AVG daily calories during the first week for 7-day moralityAdjusted age, ARDS severity, APACHE II score, PaO2/FiO2 ratio on day 1, mean PaO2/FiO2 ratio during the first 3 days, TV/kg IBW on day 1, PIP on day 1, neuromuscular blockade use, fluid balance on day 1 and cumulative fluid balance during the first 3 and 7 days, and AVG daily calories during the first week for 28-day mortality*Statistical significance

Discussion

This study demonstrated that the 28-day mortality of the ARDS patients admitted in our medical ICUs was high, compared with the mortalities in other studies [15, 16, 17, 18, 19] (Table 4). We postulated that the higher mortality rate resulted from limited ICU beds, delayed ICU admission, delayed sedative and neuromuscular blockade administration, and shortage of medical staff. Our mortality rate tended to be increasing with the greater ARDS severity; however, it was not significant. It might be explained that there were multiple factors affecting the mortality rate such as ventilator-induced lung injury, ventilator-associated pneumonia, and positive cumulative fluid balance. Noticeably, 42.3% of our patients received TV greater than 8 mL/kg IBW on the first day, compared with 30% of the patients in the PRoVENT study [19]. Moreover, there were limited data of the Pplat in our study (4%), compared with 17.2% in ALIEN [18], 40% in LUNG SAFE [15], 41% in PRoVENT [19], and 90.7% in APRONET [20]. These findings might indicate that the physicians less concerned about ventilator-induced lung injury. Furthermore, the prevalence of prone position in our severe ARDS patients was only 4%, compared with 16% in LUNG SAFE [15] and 32.9% in APRONET [20]. Prone position was infrequently used in our study because of different study periods. The PROSEVA [6] reported the mortality benefit of prone position in 2013, but we retrospectively reviewed the data between 2010 and 2014. In addition, the prevalence of the use of neuromuscular blocking agent was 35.3% in our study, higher than LUNG SAFE (21.7%) [15] due to the higher proportion of severe ARDS patients in our study. Despite the greater use of neuromuscular blockade, the mortality rate was higher, which might be from inadequate doses of this medication and no ventilator asynchrony monitoring. Recruitment maneuver was performed to 48.12% of the patients, which was quite high, compared with 20.9% in the LUNG SAFE [15]. Despite the fact that the recruitment maneuver potentially increased the risk of barotrauma and death [21, 22], our study did not show the association between the procedure and the complications. Finally, similar to other studies, there were low prevalence of HFOV, APRV, and extracorporeal membrane oxygenation (ECMO) use, which less affected the ARDS outcomes [7, 8, 23, 24, 25, 26, 27, 28, 29].

Table 4

Comparison of 28-day mortality of ARDS patients and factors possibly associated with mortality between our study and other studies including ALIEN, LUNG SAFE, PRoVENT, and APRONET

Our studyALIENLUNG SAFEPRoVENTAPRONET
[18][15][19][20]
Study period2010–20142008–200920142014–20152016–2017
28-day mortality
All severity of ARDS69.2%42.7%34.8%29%NA
Mild ARDS51.6%NA29.6%NANA
Moderate ARDS69.5%NA35.2%NANA
Severe ARDS73.5%NA40.9%NANA
Factors
TV (mL/kg IBW) on day 18.56 ± 2.487.2 ± 1.17.67.66.7
Percentage of patients with TV >8 mL/kg IBW on day 142.3%NANA30%NA
Percentage of Pplat measurement4%17.2%40%41%90.7%
Percentage of patients with prone position (in severe ARDS)4%NA16%NA32.9%
Percentage of patients receiving neuromuscular blockage35.3%NA21.7%NANA
Percentage of patients with recruitment maneuver48.1%NA20.9%NANA
Percentage of patients with ECMO0%NA3.2%NA1.9%
Percentage of patients with HFOV1.5%NA1.2%NANA
Percentage of patients with APRV5.63%NANANANA
APRV, airway pressure release ventilation; ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; HFOV, high-frequency oscillatory ventilation; IBW, ideal body weight; Pplat, plateau pressure; TV, tidal volume; NA, not available

According to the ventilator complications, barotrauma was not different between ARDS survivors and non-survivors. Nevertheless, ventilator-associated pneumonia was higher in the non-survivors group (18.4% vs 13.4%).

Besides, most of the patients had positive cumulative fluid balance, which contributed to the significantly greater mortality in our study (Figure 1). Compared with FACTT [10], our ARDS patients had cumulative fluid balance over 7 days close to the fluid balance of the patients in the liberal fluid management group (6,634.97 ± 6,718.06 mL in our study vs 6,992 ± 502 in liberal FACTT), who had worse clinical outcomes, including less ventilator-free days and deteriorated oxygenation index and lung injury score. Nevertheless, FACTT did not demonstrate the mortality risk from liberal fluid management. The different findings might be explained by the fact that there were limited data of hemodynamic status, which possibly confounded to the significantly higher mortality rate in our study.

Furthermore, our study showed that the patients receiving daily calories less than 60% of the estimated daily caloric need during the first week had higher mortality. This result was different from the findings in the EDEN study [30], which demonstrated that initial trophic enteral feeding for up to 6 days in patients with acute lung injury resulted in similar ventilator-free days, 60-day mortality, and infectious complications, compared with full enteral feeding. It might be explained that our patients with lower caloric intake possibly had more severe conditions such as hemodynamic instability or severe lung injury treated with prone position, which had an impact on mortality outcome.

Our study had limitations. Due to the retrospective design, the information was obtained from the recorded documents. Thus, there were some missing data such as height, body weight, Pplat, and driving pressure. In addition, there might be uncontrolled factors confounding to the mortality rate such as inadequate antibiotics and source control, inappropriate resuscitation of shock, or the different severity of comorbidities.

Conclusion

The 28-day mortality of ARDS was high. In addition, the average TV and fluid balance were greater than the protective limits. These findings indicated the potential improvement of ARDS outcomes in our hospital. The educational program focusing on ARDS management, follow-up, and feedback activities should be provided to our medical personnel.

Acknowledgments

A part of this study was presented at the 21st Congress of the Asian Pacific Society of Respirology and published in the poster presentation abstract in Respirology. 2016; 21(Suppl. 3):3–213.

Author contributions. Both NS and NK contributed substantially to the conception and design of this study. NS contributed to the acquisition of data. NS and NK analyzed and interpreted the data. NS drafted the manuscript. NK contributed to its critical revision. Both NS and NK approved the final version submitted for publication and take responsibility for the statements made in the published article.
Conflict of interestConflict of interest statement: The authors have completed and submitted the International Committee of Medical Journal Editors Uniform Disclosure Form for Potential Conflicts of Interest. None of the authors disclose any conflict of interest.

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  • [9]

    Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators Cavalcanti AB Suzumura ÉA Laranjeira LN Paisani DM Damiani LP et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017; 318:1335–45.

    • Crossref
    • PubMed
    • Export Citation
  • [10]

    Wiedemann HP Wheeler AP Bernard GR Thompson BT Hayden D deBoisblanc B et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354:2564–75.

    • Crossref
    • PubMed
    • Export Citation
  • [11]

    Sakr Y Vincent JL Reinhart K Groeneveld J Michalopoulos A Sprung CL et al. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005; 128:3098–108.

    • Crossref
    • PubMed
    • Export Citation
  • [12]

    Schuller D Mitchell JP Calandrino FS Schuster DP. Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome? Chest. 1991; 100:1068–75.

    • Crossref
    • Export Citation
  • [13]

    Humphrey H Hall J Sznajder I Silverstein M Wood L. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest. 1990; 97:1176–80.

    • Crossref
    • PubMed
    • Export Citation
  • [14]

    Mikkelsen ME Christie JD Lanken PN Biester RC Thompson BT Bellamy SL et al. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med. 2012; 185:1307–15.

    • Crossref
    • PubMed
    • Export Citation
  • [15]

    Giacomo B John G Tai P Eddy F Laurent B Andres E et al. Epidemiology patterns of care and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016; 315:788–800.

    • Crossref
    • PubMed
    • Export Citation
  • [16]

    Phua J Badia JR Adhikari NK Friedrich JO Fowler RA Singh JM et al. Has mortality from acute respiratory distress syndrome decreased over time?: a systematic review. Am J Respir Crit Care Med. 2009; 179:220–7.

    • Crossref
    • PubMed
    • Export Citation
  • [17]

    Zambon M Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008; 133:1120–7.

    • Crossref
    • PubMed
    • Export Citation
  • [18]

    Jesus V Jesus B Jose MA Antonio S Luis B Alfonso A et al. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011; 37:1932–41.

    • Crossref
    • PubMed
    • Export Citation
  • [19]

    Ary SN Carmen S Fabienne D Antonio A Jaume C Rogier M et al. Epidemiological characteristics practice of ventilation and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international multicentre prospective study. Lancet. 2016; 4:882–93.

    • PubMed
    • Export Citation
  • [20]

    Guerin C Beuret P Constantin JM Belani G Garcia-Olivares P Roca O et al. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Med. 2018; 44:22–37.

    • Crossref
    • PubMed
    • Export Citation
  • [21]

    Huh JW Jung H Choi HS Hong SB Lim CM Koh Y. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome. Crit Care. 2009; 13:R22.

    • Crossref
    • PubMed
    • Export Citation
  • [22]

    Meade MO Cook DJ Guyatt GH Slutsky AS Arabi YM Cooper DJ et al. Ventilation strategy using low tidal volumes recruitment maneuvers and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008; 299:637–45.

    • Crossref
    • PubMed
    • Export Citation
  • [23]

    Li JQ Li N Han GJ Pan CG Zhang YH Shi XZ et al. Clinical research about airway pressure release ventilation for moderate to severe acute respiratory distress syndrome. Eur Rev Med Pharmacol Sci. 2016; 20:2634–41.

    • PubMed
    • Export Citation
  • [24]

    Lim J Litton E Robinson H Das Gupta M. Characteristics and outcomes of patients treated with airway pressure release ventilation for acute respiratory distress syndrome: A retrospective observational study. J Crit Care. 2016; 34:154–9.

    • Crossref
    • PubMed
    • Export Citation
  • [25]

    Song S Tian H Yang X Hu Z. The clinical effect of airway pressure release ventilation for acute lung injury/acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016; 28:15–21.

    • PubMed
    • Export Citation
  • [26]

    Sud S Sud M Friedrich JO Adhikari NK. Effect of mechanical ventilation in the prone position on clinical outcomes in patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis. CMAJ. 2008; 178:1153–61.

    • Crossref
    • PubMed
    • Export Citation
  • [27]

    Calfee CS Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest. 2007; 131:913–20.

    • Crossref
    • PubMed
    • Export Citation
  • [28]

    Peek GJ Elbourne D Mugford M Tiruvoipati R Wilson A Allen E et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010; 14:1–46.

    • PubMed
    • Export Citation
  • [29]

    Peek GJ Mugford M Tiruvoipati R Wilson A Allen E Thalanany MM et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009; 374:1351–63.

    • Crossref
    • Export Citation
  • [30]

    National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Rice TW Wheeler AP Thompson BT Steingrub J Hite RD et al. Initial trophic vs full enteral feeding in patients with acute lung injury the EDEN randomized trial. JAMA. 2012; 307:795–803.

    • Crossref
    • PubMed
    • Export Citation

If the inline PDF is not rendering correctly, you can download the PDF file here.

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    Ashbaugh DG Bigelow DB Petty TL Levine BE. Acute respiratory distress in adults. Lancet. 1967; 2:319–23.

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    Bernard GR Artigas A Brigham KL Carlet J Falke K Hudson L et al. The American-European Consensus Conference on ARDS. Definitions mechanisms relevant outcomes and clinical trial coordination. Am J Respir Crit Care Med. 1994; 149:818–24.

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    ARDS Definition Task Force Ranieri VM Rubenfeld GD Thompson BT Ferguson ND Caldwall E et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012; 307:2526–33.

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    Acute Respiratory Distress Syndrome Network Brower RG Matthay MA Morris A Schoenfeld D Thompson BT et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000; 342:1301–8.

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    Papazian L Forel JM Gacouin A Penot-Ragon C Perrin G Loundou A et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010; 363:1107–16.

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    Guerin C Reignier J Richard JC Beuret P Gacouin A Boulain T et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013; 368:2159–68.

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    • PubMed
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  • [7]

    Ferguson ND Cook DJ Guyatt GH Mehta S Hand L Austin P et al. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013; 368:795–805.

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    Young D Lamb SE Shah S MacKenzie I Tunnicliffe W Lall R et al. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013; 368:806–13.

    • Crossref
    • PubMed
    • Export Citation
  • [9]

    Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators Cavalcanti AB Suzumura ÉA Laranjeira LN Paisani DM Damiani LP et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017; 318:1335–45.

    • Crossref
    • PubMed
    • Export Citation
  • [10]

    Wiedemann HP Wheeler AP Bernard GR Thompson BT Hayden D deBoisblanc B et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354:2564–75.

    • Crossref
    • PubMed
    • Export Citation
  • [11]

    Sakr Y Vincent JL Reinhart K Groeneveld J Michalopoulos A Sprung CL et al. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005; 128:3098–108.

    • Crossref
    • PubMed
    • Export Citation
  • [12]

    Schuller D Mitchell JP Calandrino FS Schuster DP. Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome? Chest. 1991; 100:1068–75.

    • Crossref
    • Export Citation
  • [13]

    Humphrey H Hall J Sznajder I Silverstein M Wood L. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest. 1990; 97:1176–80.

    • Crossref
    • PubMed
    • Export Citation
  • [14]

    Mikkelsen ME Christie JD Lanken PN Biester RC Thompson BT Bellamy SL et al. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med. 2012; 185:1307–15.

    • Crossref
    • PubMed
    • Export Citation
  • [15]

    Giacomo B John G Tai P Eddy F Laurent B Andres E et al. Epidemiology patterns of care and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016; 315:788–800.

    • Crossref
    • PubMed
    • Export Citation
  • [16]

    Phua J Badia JR Adhikari NK Friedrich JO Fowler RA Singh JM et al. Has mortality from acute respiratory distress syndrome decreased over time?: a systematic review. Am J Respir Crit Care Med. 2009; 179:220–7.

    • Crossref
    • PubMed
    • Export Citation
  • [17]

    Zambon M Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008; 133:1120–7.

    • Crossref
    • PubMed
    • Export Citation
  • [18]

    Jesus V Jesus B Jose MA Antonio S Luis B Alfonso A et al. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011; 37:1932–41.

    • Crossref
    • PubMed
    • Export Citation
  • [19]

    Ary SN Carmen S Fabienne D Antonio A Jaume C Rogier M et al. Epidemiological characteristics practice of ventilation and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international multicentre prospective study. Lancet. 2016; 4:882–93.

    • PubMed
    • Export Citation
  • [20]

    Guerin C Beuret P Constantin JM Belani G Garcia-Olivares P Roca O et al. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Med. 2018; 44:22–37.

    • Crossref
    • PubMed
    • Export Citation
  • [21]

    Huh JW Jung H Choi HS Hong SB Lim CM Koh Y. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome. Crit Care. 2009; 13:R22.

    • Crossref
    • PubMed
    • Export Citation
  • [22]

    Meade MO Cook DJ Guyatt GH Slutsky AS Arabi YM Cooper DJ et al. Ventilation strategy using low tidal volumes recruitment maneuvers and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008; 299:637–45.

    • Crossref
    • PubMed
    • Export Citation
  • [23]

    Li JQ Li N Han GJ Pan CG Zhang YH Shi XZ et al. Clinical research about airway pressure release ventilation for moderate to severe acute respiratory distress syndrome. Eur Rev Med Pharmacol Sci. 2016; 20:2634–41.

    • PubMed
    • Export Citation
  • [24]

    Lim J Litton E Robinson H Das Gupta M. Characteristics and outcomes of patients treated with airway pressure release ventilation for acute respiratory distress syndrome: A retrospective observational study. J Crit Care. 2016; 34:154–9.

    • Crossref
    • PubMed
    • Export Citation
  • [25]

    Song S Tian H Yang X Hu Z. The clinical effect of airway pressure release ventilation for acute lung injury/acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016; 28:15–21.

    • PubMed
    • Export Citation
  • [26]

    Sud S Sud M Friedrich JO Adhikari NK. Effect of mechanical ventilation in the prone position on clinical outcomes in patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis. CMAJ. 2008; 178:1153–61.

    • Crossref
    • PubMed
    • Export Citation
  • [27]

    Calfee CS Matthay MA. Nonventilatory treatments for acute lung injury and ARDS. Chest. 2007; 131:913–20.

    • Crossref
    • PubMed
    • Export Citation
  • [28]

    Peek GJ Elbourne D Mugford M Tiruvoipati R Wilson A Allen E et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010; 14:1–46.

    • PubMed
    • Export Citation
  • [29]

    Peek GJ Mugford M Tiruvoipati R Wilson A Allen E Thalanany MM et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009; 374:1351–63.

    • Crossref
    • Export Citation
  • [30]

    National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Rice TW Wheeler AP Thompson BT Steingrub J Hite RD et al. Initial trophic vs full enteral feeding in patients with acute lung injury the EDEN randomized trial. JAMA. 2012; 307:795–803.

    • Crossref
    • PubMed
    • Export Citation
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5-year IMPACT FACTOR: 0.293

CiteScore 2018: 0.30

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    The increasing OR of 28-day mortality in patients who had more positive 7-day cumulative fluid balance. OR, odds ratio

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