Skip to content

Advertisement

  • Research
  • Open Access

Improvement in the survival rates of extracorporeal membrane oxygenation-supported respiratory failure patients: a multicenter retrospective study in Korean patients

  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 7,
  • 8,
  • 9,
  • 10,
  • 11,
  • 12,
  • 13,
  • 14,
  • 15,
  • 16 and
  • 1Email authorView ORCID ID profile
Contributed equally
Critical Care201923:1

https://doi.org/10.1186/s13054-018-2293-5

  • Received: 27 June 2018
  • Accepted: 12 December 2018
  • Published:

Abstract

Background

Although the utilization of extracorporeal membrane oxygenation (ECMO) is increasing and its technology is evolving, only a few epidemiologic reports have described the uses and outcomes of ECMO. The aim of this study was to investigate the changes in utilization and survival rate in patients supported with ECMO for severe respiratory failure in Korea.

Methods

This was a multicenter study on consecutive patients who underwent ECMO across 16 hospitals in Korea. The records of all patients who required ECMO for acute respiratory failure between 2012 and 2015 were retrospectively reviewed, and the utilization of ECMO was analyzed over time.

Results

During the study period, 5552 patients received ECMO in Korea as a whole, and a total of 2472 patients received ECMO at the participating 16 hospitals. We analyzed 487 (19.7%) patients who received ECMO for respiratory failure. The number of ECMO procedures provided for respiratory failure increased from 104 to 153 during the study period. The in-hospital survival rate increased from 30.8% to 35.9%. The use of prone positioning increased from 6.8% to 49.0% (p < 0.001), and the use of neuromuscular blockers also increased from 28.2% to 58.2% (p < 0.001). Multiple regression analysis showed that old age (OR 1.038 (95% CI 1.022, 1.054)), use of corticosteroid (OR 2.251 (95% CI 1.153, 4.397)), continuous renal replacement therapy (OR 2.196 (95% CI 1.135, 4.247)), driving pressure (OR 1.072 (95% CI 1.031, 1.114)), and prolonged ECMO duration (OR 1.020 (95% CI 1.003, 1.038)) were associated with increased odds of mortality.

Conclusions

Utilization of ECMO and survival rates of patients who received ECMO for respiratory failure increased over time in Korea. The use of pre-ECMO prone positioning and neuromuscular blockers also increased during the same period.

Keywords

  • Extracorporeal membrane oxygenation
  • Utilization
  • Survival

Background

Extracorporeal membrane oxygenation (ECMO), which provides respiratory and/or cardiac support, allows treatment of patients with refractory gas-exchange abnormalities [1]. The use of ECMO to support patients with respiratory failure is increasing worldwide following the use of ECMO for severe acute respiratory failure during the 2009 influenza A pandemic [25]. Recently, the EOLIA trial reported that in patients with severe acute respiratory distress syndrome (ARDS) there was no significant difference in 60-day mortality between patients who received early ECMO and those who received conventional mechanical ventilation that included ECMO as rescue therapy [6]. However, crossover to ECMO occurred in 28% of patients in the conventional group, who showed a high mortality rate of 57%. This suggests that ECMO can be used in severe ARDS patients who do not benefit from conventional treatment.

Survival of patients who received ECMO is also gradually increasing over time [7]. A recent epidemiologic report in Germany showed that ECMO utilization for severe respiratory failure significantly increased from 2007 until 2012, and in-hospital survival increased over time as well [8]. Sauer et al. [9] reported that the annual rates of ECMO cases increased by 433% from 2006 to 2011 in the United States, and that, albeit not statistically significant, there was an improving trend in the survival rate as well. In a single-center study in Korea, the survival rates associated with the ECMO procedure increased between 2009 and 2011 [10]. However, as we have previously reported, there was a discrepancy in the survival rate between those of the Extracorporeal Life Support Organization (ELSO) registry and Korean ECMO patients [11]. The in-hospital survival rate of ECMO-treated patients with acute respiratory failure was 46% from 2014 to 2015 in Korea, whereas the survival rate was 58% in the ELSO registry patients [7]. Also, we have suggested that age is an important factor in the survival of patients who received ECMO. Therefore, we sought to determine whether there has been an improvement in the survival rate of patients who received ECMO support for acute respiratory failure in Korea. Specifically, we evaluated the changes over time in the survival rates of patients supported with ECMO for severe respiratory failure and the factors associated with the survival rate.

Methods

Study design

This was a multicenter study of consecutive patients who received ECMO at 16 hospitals in Korea. The records of all patients who required ECMO for acute respiratory failure between 2012 and 2015 were retrospectively reviewed and the utilization of ECMO was analyzed over time. The decision to use ECMO was made at the discretion of the attending physicians at each center without standardization. The study protocol was approved by the institutional review board of Asan Medical Center, and by the local institutional review boards of all other participating centers. The requirement for informed consent was waived due to the retrospective design of the study.

Data collection

Data were collected from electronic medical records of patients older than 19 years who received ECMO support. Included variables were as follows: demographic information, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at intensive care unit (ICU) admission, etiology of respiratory failure, cardiac arrest, immunocompromised status, central nervous system (CNS) dysfunction, pre-ECMO hemodynamic data, mechanical ventilation parameters, and arterial blood gas data. Immunocompromised status and CNS dysfunction were defined according to the RESP study [12]. Immunocompromised status included hematological malignancies, solid tumors, solid-organ transplantation, high-dose or long-term corticosteroid and/or immunosuppressant use, and human immunodeficiency virus infection. CNS dysfunction included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome. We collected information on adjunctive therapy such as the use of vasopressors, steroids, continuous renal replacement therapy (CRRT), prone positioning, nitric oxide, bicarbonate infusion, and neuromuscular blockers. We also collected data such as the ECMO mode, ECMO duration, duration of mechanical ventilation to ECMO initiation, hospital stay, and tracheotomy. The ECMO mode was categorized as veno-venous, veno-arterial, and veno-arteriovenous. Outcome variables of the study were survival at discharge and ECMO weaning (survival within 48 h after weaning from ECMO).

Statistical analysis

Demographics, pre-ECMO parameters, and outcomes were compared between 2012 and 2015. Differences with p < 0.05 were considered statistically significant. Categorical variables are expressed as the number (percentage). Continuous variables are expressed as the median (interquartile range). Pearson’s chi-square test or Fisher’s exact test was used to compare categorical data. The Kruskal–Wallis test was used to compare medians between groups.

Multiple logistic regression analysis using the backward elimination method was performed to identify the factors associated with survival at discharge. Candidate variables for inclusion in the multiple logistic regression model were chosen from the univariate analysis; variables with p < 0.1 in the univariate analyses were included in the multivariate analysis, and collinearity was assessed before the multivariate analysis. Calibrations of the models were evaluated with the Hosmer–Lemeshow goodness-of-fit test. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM Corporation, Armonk, NY, USA).

Results

Baseline characteristics of the study population

During the study period (2012–2015), 5552 patients received ECMO support in Korea. ECMO support was given to 2472 patients in the participating 16 hospitals. We analyzed 487 (19.7%) patients who received ECMO specifically for respiratory failure. The annual number of ECMO cases at 16 institutions varied widely: eight centers had fewer than 20 cases per year and the other eight centers had more than 30 cases per year, with two of those centers having had more than 120 cases per year.

The patients’ median age was 58 years (range 45–66 years), and the median body mass index was 22.2 kg/m2 (range 20.6–23.2 kg/m2). Pre-ECMO mechanical ventilation was provided in 92.2% of patients and corticosteroid therapy was used in 16.8% of patients. Prone positioning was applied in 29.5% of patients and neuromuscular blockers were used in 45.4% of patients. The majority of patients were initially supported with veno-venous ECMO (88.1%), and the median duration of support was 8 days (interquartile range (IQR) 4, 18 days). Survival and weaning rates were 38.8% and 57.1%, respectively (Table 1).
Table 1

Baseline characteristics of patients supported with ECMO for respiratory failure

Variable

Total (n = 487)

Age (years)

58 (45, 66)

Male

321 (65.9)

Body mass index (kg/m2)

22.2 (20.6, 23.2)

APACHE II score

21 (15, 28)

SOFA score

8 (5, 12)

PRESERVE score

5 (4, 6)

RESP score

0 (−2, 2)

Etiology of ARF

 Viral pneumonia

47 (9.7)

 Bacterial pneumonia

127 (26.1)

 COPD and asthma

8 (1.6)

 Trauma and burn

25 (5.1)

 Asphyxia

13 (2.7)

 Acute exacerbation of ILD

61 (12.5)

 Chronic respiratory failure

24 (4.9)

 ARDS

44 (9.0)

 Airway obstruction

28 (5.7)

 Other respiratory failure

110 (22.6)

Immunocompromiseda

122 (25.2)

CNS dysfunctionb

24 (5.0)

Vasopressor

301 (63.0)

Corticosteroid

82 (16.8)

Cardiac arrest

74 (15.2)

CRRT

83 (17.0)

Mechanical ventilation

449 (92.2)

Prone positioning

143 (29.5)

Pre-ECMO rescue therapy

 Nitric oxide

127 (26.2)

 Bicarbonate infusion

53 (11.0)

 Neuromuscular blocker

230 (45.4)

Vital signs

 MAP (mmHg)

70 (58, 84)

 Heart rate (/min)

112 (95, 128)

 Respiratory rate (/min)

22 (18, 28)

ECMO type

 Veno-venous

429 (88.1)

 Veno-arterial

42 (8.6)

 Veno-arteriovenous

14 (2.9)

 Other

2 (0.4)

Arterial blood gases

 pH

7.28 (7.17, 7.38)

 PaO2 (mmHg)

61 (51, 76)

 PaCO2 (mmHg)

51 (39, 65)

 HCO3 (mEq/L)

23 (19, 29)

 SaO2 (%)

88 (79, 93)

Ventilation parameters

 PaO2/FiO2

65 (53, 90)

 FiO2

100 (90, 100)

 PEEP (cmH2O)

10 (6, 12)

 PIP (cmH2O)

28 (24, 32)

 Tidal volume (ml/kg)

7 (6, 9)

 Driving pressure (cmH2O)

18 (15, 24)

 Minute ventilation (L/min)

9.6 (7.4, 12.4)

Interval MV–ECMO (days)

1 (0, 5)

ECMO duration (days)

8 (4, 18)

Hospital stay (days)

35 (18, 61)

Tracheostomy

199 (41.8)

Weaning rate

278 (57.1)

Survival rate

189 (38.8)

Values expressed as median (interquartile range) or n (%)

ECMO extracorporeal membrane oxygenation, APACHE Acute Physiology and Chronic Health Evaluation, SOFA Sequential Organ Failure Assessment, PRESERVE Predicting Death for Severe Acute Respiratory Distress Syndrome on Veno-venous ECMO, RESP Respiratory Extracorporeal Membrane Oxygenation Survival Prediction, ARF acute respiratory failure, ARDS acute respiratory distress syndrome, COPD chronic obstructive pulmonary disease, ILD interstitial lung disease, CNS central nervous system, CRRT continuous renal replacement therapy, MAP mean arterial pressure, PaO2 partial pressure of arterial oxygen, PaCO2 partial pressure of arterial carbon dioxide, HCO3 bicarbonate, SaO2 oxygen saturation, FiO2 fraction of inspired oxygen, PEEP positive end-expiratory pressure, PIP peak inspiratory pressure, MV mechanical ventilation

a“Immunocompromised” included hematological malignancies, solid tumors, solid-organ transplantation, high-dose or long-term corticosteroid and/or immunosuppressant use, and human immunodeficiency virus infection

b“CNS dysfunction” included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome

Demographics, pre-ECMO parameters, and outcomes over time

The number of ECMO procedures for respiratory failure increased from 104 to 153 during the study period (Fig. 1). There were no significant differences in age, sex, APACHE II score, SOFA score, immunocompromised status, CNS dysfunction, cardiac arrest, CRRT, use of nitric oxide and bicarbonate infusion, PaO2/FiO2 ratio, ECMO duration, and duration of mechanical ventilation to ECMO initiation between groups. Use of prone positioning increased from 6.8% to 49.0% (p < 0.001) and the use of neuromuscular blockers also increased from 28.2% to 58.2% (p < 0.001; Table 2). Although the survival rate remained relatively low, it increased over time from 30.8% to 35.9% (p = 0.005; Table 3). Post-hoc analysis showed that the survival rate in 2014 was significantly higher than the rates in 2012 and 2015.
Fig. 1
Fig. 1

Number of ECMO procedures and weaning and survival rates of patients who received ECMO for acute respiratory failure. ECMO extracorporeal membrane oxygenation

Table 2

Demographic features of survivors and nonsurvivors supported with ECMO for respiratory failure

Variable

2012 (n = 104)

2013 (n = 100)

2014 (n = 130)

2015 (n = 153)

p value

Age (years)

59 (49, 69)

60 (45, 68)

58 (43, 66)

57 (45, 63)

0.199

Male

69 (66.3)

71 (71.0)

93 (71.5)

88 (57.5)

0.050

Body mass index (kg/m2)

22.6 (20.4, 24.6)

22.9 (19.7, 25.0)

22.1 (21.0, 22.9)

22.0 (20.5, 22.9)

0.073

APACHE II score

21 (16, 27)

22 (16, 29)

21 (15, 30)

19 (14, 26)

0.162

SOFA score

8 (5, 12)

8 (5, 11)

8 (5, 12)

8 (6, 12)

0.842

PRESERVE score

5 (4, 7)

6 (4, 7)

5 (3, 6)

5 (3, 6)

0.245

RESP score

0 (−2, 2)

0 (−2, 2)

0 (−2, 2)

1(−1, 3)

0.497

Etiology of ARF

    

0.001

 Viral pneumonia

7 (6.7)

8 (8.0)

11 (8.5)

21 (13.7)

 

 Bacterial pneumonia

33 (31.7)

16 (16.0)

37 (28.5)

41 (26.8)

 

 COPD and asthma

1 (1.0)

2 (2.0)

4 (3.1)

1 (0.7)

 

 Trauma and burn

1 (1.0)

4 (4.0)

10 (7.7)

10 (6.5)

 

 Asphyxia

0 (0.0)

3 (3.0)

8 (6.2)

2 (1.3)

 

 Acute exacerbation of ILD

8 (7.7)

17 (17.0)

13 (10.0)

23 (15.0)

 

 Chronic respiratory failure

11 (10.6)

4 (4.0)

6 (4.6)

3 (2.0)

 

 ARDS

13 (12.5)

14 (14.0)

7 (5.4)

10 (6.5)

 

 Airway obstruction

10 (9.6)

6 (6.0)

4 (3.1)

8 (5.2)

 

 Other respiratory failure

20 (19.2)

26 (26.0)

30 (23.1)

34 (22.2)

 

Immunocompromiseda

26 (25.2)

21 (21.4)

34 (26.2)

41 (26.8)

0.799

CNS dysfunctionb

3 (2.9)

3 (3.1)

8 (6.2)

10 (6.5)

0.413

Vasopressor

48 (46.2)

59 (59.0)

96 (75.6)

98 (66.7)

< 0.001

Corticosteroid

22 (21.2)

21 (21.0)

23 (17.7)

16 (10.5)

0.068

Cardiac arrest

8 (7.7)

19 (19.0)

24 (18.5)

23 (15.0)

0.080

CRRT

20 (19.2)

19 (19.0)

20 (15.4)

24 (15.7)

0.783

Mechanical ventilation

94 (90.4)

83 (83.0)

125 (96.2)

147 (96.1)

< 0.001

Prone positioning

7 (6.8)

3 (3.1)

58 (44.6)

75 (49.0)

< 0.001

Pre-ECMO rescue therapy

 Nitric oxide

29 (28.2)

22 (22.4)

42 (32.3)

34 (22.2)

0.197

 Bicarbonate infusion

11 (10.7)

12 (12.2)

14 (10.8)

16 (10.5)

0.975

 Neuromuscular blocker

29 (28.2)

32 (32.7)

80 (61.5)

89 (58.2)

< 0.001

Values expressed as median (interquartile range), mean ± standard deviation, or n (%)

ECMO extracorporeal membrane oxygenation, APACHE Acute Physiology and Chronic Health Evaluation, SOFA Sequential Organ Failure Assessment, PRESERVE Predicting Death for Severe Acute Respiratory Distress Syndrome on Veno-venous ECMO, RESP Respiratory Extracorporeal Membrane Oxygenation Survival Prediction, ARF acute respiratory failure, COPD chronic obstructive pulmonary disease, ILD interstitial lung disease, ARDS acute respiratory distress syndrome, CNS central nervous system, CRRT continuous renal replacement therapy

a“Immunocompromised” included hematological malignancies, solid tumors, solid-organ transplantation, high-dose or long-term corticosteroid and/or immunosuppressant use, and human immunodeficiency virus infection

b“CNS dysfunction” included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome

Table 3

Pre-ECMO parameters of patients supported with ECMO for respiratory failure

Variable

2012 (n = 104)

2013 (n = 100)

2014 (n = 130)

2015 (n = 153)

p value

Vital signs

 MAP (mmHg)

74 (62, 89)

72 (59, 86)

63 (56, 72)

70 (57, 84)

0.001

 Heart rate (/min)

112 (98, 125)

116 (101, 131)

107 (94, 125)

112 (94, 129)

0.462

 Respiratory rate (/min)

26 (20, 30)

24 (20, 30)

20 (16, 26)

20 (16, 26)

< 0.001

ECMO type

    

0.003

 Veno-venous

96 (92.3)

95 (95.0)

113 (86.9)

125 (81.7)

 

 Veno-arterial

4 (3.8)

2 (2.0)

11 (8.5)

25 (16.3)

 

 Veno-arteriovenous

3 (2.9)

2 (2.0)

6 (4.6)

3 (2.0)

 

 Other

1 (1.0)

1 (1.0)

0 (0.0)

0 (0.0)

 

Arterial blood gases

 pH

7.31 (7.17, 7.43)

7.25 (7.17, 7.36)

7.26 (7.15, 7.37)

7.29 (7.18, 7.38)

0.081

 PaO2 (mmHg)

60 (52, 74)

66 (56, 79)

62 (50, 75)

61 (46, 76)

0.211

 PaCO2 (mmHg)

52 (40, 62)

56 (41, 72)

51 (39, 71)

47 (36, 59)

0.013

 HCO3 (mEq/L)

24.3 (21.1, 31.0)

24.1 (19.9, 29.5)

22.4 (18.1, 27.9)

22.0 (18.2, 25.5)

0.003

 SaO2 (%)

88 (83, 92)

89 (85, 94)

88 (79, 93)

87 (75, 93)

0.243

Ventilation parameters

 PaO2/FiO2

62 (53, 80)

72 (59, 96)

65 (53, 90)

65 (48, 97)

0.131

 FiO2

100 (100, 100)

100 (90, 100)

100 (80, 100)

100 (80, 100)

0.069

 PEEP (cmH2O)

10 (6, 12)

8 (5, 12)

10 (6, 10)

10 (7, 12)

0.119

 PIP (cmH2O)

28 (24, 33)

30 (25, 34)

28 (23, 33)

28 (24, 31)

0.382

 Tidal volume (ml/kg)

389 (298, 575)

420 (321, 513)

444 (340, 600)

428 (299, 518)

0.255

 Driving pressure (cmH2O)

18 (14, 24)

20 (16, 25)

18 (15, 23)

18 (15, 21)

0.077

 Minute ventilation (L/min)

10.9 (7.8, 14.6)

9.6 (7.7, 12.7)

9.5 (7.2, 12.2)

9.3 (6.8, 12.0)

0.035

Interval MV–ECMO (days)

2 (0, 7)

1 (0, 5)

1 (0, 5)

2 (0, 5)

0.090

ECMO duration (days)

7 (4, 14)

8 (5, 22)

8 (3, 13)

7 (4, 24)

0.305

Hospital stay (days)

32 (17, 47)

34 (19, 65)

39 (18, 73)

34 (17, 60)

0.318

Tracheostomy

32 (30.8)

38 (38.0)

61 (48.8)

68 (46.3)

0.023

Weaning rate

56 (53.8)

50 (50.0)

86 (66.2)

86 (56.2)

0.075

Survival rate

32 (30.8)

35 (35.0)

67 (51.5)

55 (35.9)

0.005

Values expressed as mean ± standard deviation, or n (%)

ECMO extracorporeal membrane oxygenation, MAP mean arterial pressure, PaO2 partial pressure of oxygen, PaCO2 partial pressure of carbon dioxide, HCO3 bicarbonate, SaO2 oxygen saturation, FiO2 fraction of inspired oxygen, PEEP positive end-expiratory pressure, PIP peak inspiratory pressure, MV mechanical ventilation

Factors associated with mortality in patients supported with ECMO

Multiple regression analysis was performed using age, sex, year, APACHE II score, SOFA score, immunocompromised status, CNS dysfunction, corticosteroid, CRRT, prone positioning, nitric oxide, neuromuscular blocker, PaCO2, peak inspiratory pressure, driving pressure, and ECMO duration. Old age (OR 1.038 (95% CI 1.022, 1.054)), use of corticosteroid (OR 2.251 (95% CI 1.153, 4.397)), CRRT (OR 2.196 (95% CI 1.135, 4.247)), driving pressure (OR 1.072 (95% CI 1.031, 1.114)), and prolonged ECMO duration (OR 1.020 (95% CI 1.003, 1.038)) were associated with increased odds of mortality (Table 4).
Table 4

Univariate and multivariate analyses for mortality of ECMO

Variable

OR (95% CI)

p value

OR (95% CI)

p value

Age (years)

1.043 (1.029, 1.056)

< 0.001

1.038 (1.022, 1.054)

< 0.001

Male

0.720 (0.487, 1.064)

0.099

  

Year

0.645 (0.444, 0.939)

0.022

  

Body mass index (kg/m2)

0.982 (0.927, 1.040)

0.527

  

APACHE II score

1.032 (1.010, 1.054)

0.004

  

SOFA score

1.020 (0.978. 1.065)

0.358

  

Immunocompromised

1.335 (0.868, 2.054)

0.188

  

CNS dysfunction

1.274 (0.534, 3.038)

0.585

  

Vasopressor

1.254 (0.857, 1.836)

0.243

  

Corticosteroid

1.914 (1.130, 3.242)

0.016

2.251 (1.153, 4.397)

0.018

Cardiac arrest

1.050 (0.630, 1.747)

0.852

  

CRRT

2.102 (1.233, 3.581)

0.006

2.196 (1.135, 4.247)

0.019

Prone positioning

1.054 (0.705, 1.575)

0.798

  

Nitric oxide

1.853 (1.194, 2.875)

0.006

  

Bicarbonate infusion

1.521 (0.820, 2.820)

0.183

  

Neuromuscular blocker

1.186 (0.821, 1.711)

0.363

  

VV ECMO mode

0.810 (0.456, 1.439)

0.472

  

pH

0.800 (0.244, 2.618)

0.712

  

PaO2 (mmHg)

0.998 (0.993, 1.003)

0.433

  

PaCO2 (mmHg)

1.007 (0.999, 1.015)

0.083

  

PaO2/FiO2

0.999 (0.996, 1.002)

0.447

  

PEEP (cmH2O)

0.968 (0.918, 1.020)

0.219

  

PIP (cmH2O)

1.070 (1.034, 1.107)

< 0.001

  

Tidal volume (ml/kg)

0.999 (0.998, 1.000)

0.175

  

Driving pressure (cmH2O)

1.078 (1.039, 1.118)

< 0.001

1.072 (1.031, 1.114)

< 0.001

Minute ventilation (L/min)

1.022 (0.969, 1.077)

0.428

  

Interval MV–ECMO (days)

1.024 (0.998, 1.050)

0.068

  

ECMO duration (days)

1.016 (1.003, 1.029)

0.017

1.020 (1.003, 1.038)

0.021

ECMO extracorporeal membrane oxygenation, OR odds ratio, CI confidence interval, APACHE Acute Physiology and Chronic Health Evaluation, SOFA Sequential Organ Failure Assessment, CNS central nervous system, CRRT continuous renal replacement therapy. VV veno-venous, PaO2 partial pressure of oxygen, PaCO2 partial pressure of carbon dioxide, FiO2 fraction of inspired oxygen, PEEP positive end-expiratory pressure, PIP peak inspiratory pressure, MV mechanical ventilation

The median age was older in the nonsurvivors (61 years; IQR 52, 69 years) than in survivors (51 years; IQR 37, 62 years) (p < 0.001). The survival rate decreased with age, with patients older than 60 years having a survival rate of 30.8% (Fig. 2). ECMO duration was significantly longer in the nonsurvivors (9 days; interquartile range (IQR) 4, 22 days) than in survivors (7 days; IQR 3, 13 days) (p = 0.002). Compared with the survival rate within 2 weeks of ECMO support, the overall survival rate after 2 weeks of ECMO support showed a significant decrease from 43.4% to 27.8% (p = 0.001).
Fig. 2
Fig. 2

Survival rates of ECMO patients according to age (years) (p < 0.001) and ECMO duration (p = 0.001). ECMO extracorporeal membrane oxygenation

Discussion

This multicenter study was conducted to evaluate the change in survival rates of patients who received ECMO support for acute respiratory failure in Korea. Utilization of ECMO for respiratory failure increased over time, and the survival rate was improved with increasing use of adjunctive management. Also, patient age and the duration of ECMO were significantly associated with survival.

A notable change during the study period was that the administration of neuromuscular blockades and use of prone positioning before ECMO had significantly increased from 28.2% to 58.2% and from 6.8% to 49.0%, respectively. Papazian et al. [13] reported that early use of neuromuscular blockades in patients with severe ARDS may improve survival. In the ELSO registry-based RESP study, neuromuscular blockade agents before ECMO were independently associated with hospital survival [12]. In addition, in patients with severe ARDS, early application of prolonged prone positioning was significantly associated with improved survival [14]. Schmidt et al. [15] demonstrated that use of prone positioning before ECMO was also associated with survival. These results are in accordance with those in a recent systematic review and meta-analysis [16]. Moreover, for patients with severe ARDS, prone positioning before and during ECMO may be helpful for weaning from ECMO [17, 18]. Another distinctive finding was the change in pre-ECMO ventilator parameters. In recent years, the driving pressure was lower and minute ventilation was decreased. Therefore, improvement in hospital survival of ECMO-supported patients with respiratory failure might be the result of increasing experience with ECMO over time, including evolving adjuvant therapies and improved management of mechanical ventilation.

The results of this study showed that the number of ECMOs carried out for respiratory failure increased from 104 to 153 from 2012 to 2015, and that the in-hospital survival rate increased from 30.8% to 35.9% during the same period. The overall survival rate of 39% in ECMO-supported respiratory failure patients in Korea is lower than the reported rate of 58% in the ELSO registry [7]. Meanwhile, an ECMO epidemiologic study performed in Germany reported that from 2012 to 2014 the in-hospital survival had steadily increased and the rate of survival was approximately 40%, which is similar to our findings [8]. In addition, Sauer et al. [9] reported that in the United States the survival rate of the patients who received ECMO was approximately 40%. In the German study, approximately 80% of patients were older than 40 years and increasing numbers of older patients had received ECMO. In the US study, the mean age of the patients who received ECMO was 50 years, which is higher than that of the patients included in the ELSO registry. Taken together, the discrepancies in demographics between the patients of ECMO centers not included in the ELSO and those in the ELSO registry may explain the difference in survival rates. Also, another explanation for the relatively low survival rate of Korean ECMO patients could be the infrequent use of prone positioning. The use of prone positioning and use of neuromuscular blockers were low compared with those in the EOLIA trial [6], in which prone positioning was applied in 90% of patients in the conventional ventilator support group, who showed a 54% survival rate. The relatively low survival rate in Korean ECMO patients may be due to excessive use of ECMO in patients who may have shown good response to prone positioning. Accordingly, the use of prone positioning is gradually increasing in Korea.

Another interesting finding of our study was that the survival rate was associated with the ECMO duration. The survival rate of patients who required prolonged ECMO (longer than 14 days) was significantly lower than that of patients who had shorter ECMO duration (28% vs 43%, respectively, p = 0.001). Recently, Posluszny et al. [19] reported that ECMO duration was inversely correlated with the survival rate in ECMO-supported patients with respiratory failure; the survival rate in patients who had longer ECMO duration was 10% lower than that in those with shorter ECMO duration. Nonetheless, the investigators suggested that prolonged ECMO was not futile because there was a significant improvement in survival from 37% to 49% in recent years. On the other hand, the aforementioned German epidemiologic study reported that prolonged ECMO was associated with poorer outcome; that the survival rate rapidly declined to 20% within 10 days after ECMO initiation [8]. Therefore, further studies are needed to provide a more solid association between ECMO duration and the survival rate.

Our study has several limitations. This study was retrospective and had a relatively short study period. Because not all patients treated with ECMO for respiratory failure in Korea were included, selection bias is possible. In addition, long-term outcomes and quality of life could not be assessed, which warrants an extended observation period of our study populations or further epidemiologic studies. Despite such limitations, our current multicenter study, which is not based on the ELSO registry, provides information on the change in the survival rate of ECMO patients with respiratory failure and the factors associated with survival, and adds to the understanding of survival in patients who receive ECMO due to respiratory failure.

Conclusions

This multicenter study performed in Korea showed that utilization of ECMO for respiratory failure had increased over time, and that the survival rates of ECMO-supported respiratory failure patients had improved with increasing utilization of adjunctive management. Patient age and duration of ECMO were significantly associated with survival at discharge.

Notes

Abbreviations

APACHE: 

Acute Physiology and Chronic Health Evaluation

ARDS: 

Acute respiratory distress syndrome

CNS: 

Central nervous system

CRRT: 

Continuous renal replacement therapy

ECMO: 

Extracorporeal membrane oxygenation

ELSO: 

Extracorporeal Life Support Organization

ICU: 

Intensive care unit

IQR: 

Interquartile range

OR: 

Odds ratio

SOFA: 

Sequential Organ Failure Assessment

Declarations

Acknowledgements

Not applicable.

Funding

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea (HC15C1507).

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

S-BH conceived of and designed the study. MSB, S-ML, CRC, WHC, Y-JC, ShP, S-MK, J-SJ, SYP, YjC, BJK, J-HK, JYO, SHP, J-WY, YSS, and S-BH contributed the primary data. MSB conducted the data analyses. MSB, S-ML, CRC, Y-JC, J-SJ, and S-BH contributed to interpretation of results. MSB, S-ML, and S-BH prepared the first draft of the manuscript, and all authors revised the draft for important intellectual content. All authors approved the final manuscript submitted for publication.

Ethics approval and consent to participate

The study protocol was approved by the institutional review boards of Medical Center, Seoul National University, Samsung Medical Center, Pusan National University Yangsan Hospital, Seoul National University Bundang Hospital, Hallym University Sacred Heart Hospital, Soonchunhyang University Hospital, Korea University Anam Hospital, Chonbuk National University Hospital, Chungbuk National University, Ulsan University Hospital, Bundang CHA Hospital, Kyung Hee University Hospital at Gangdong, Dongguk University Ilsan Hospital, Gyeongsang National University, and Hallym University Kangnam Sacred Heart Hospital. The need for informed consent was waived due to the retrospective design of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
(2)
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
(3)
Department of Critical Care Medicine, Samsung Medical Center, Seoul, Republic of Korea
(4)
Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan-si, Gyeongsangnam-do, Republic of Korea
(5)
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
(6)
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea
(7)
Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Republic of Korea
(8)
Department of Thoracic and Cardiovascular Surgery, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
(9)
Department of Internal Medicine, Chonbuk National University Hospital, Jeonju-si, Jeollabuk-do, Republic of Korea
(10)
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University College of Medicine, Sanggye Paik Hospital, Seoul, Republic of Korea
(11)
Division of Pulmonology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
(12)
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Bundang CHA Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
(13)
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University, Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea
(14)
Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital, Gangdong, Seoul, Republic of Korea
(15)
Department of Internal Medicine, College of Medicine, Gyeongsang National University Hospital, Jinju, Gyeonsangnam-do, Republic of Korea
(16)
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Republic of Korea

References

  1. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905–14.View ArticleGoogle Scholar
  2. Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, Forrest P, Gattas D, Granger E, Herkes R, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA. 2009;302(17):1888–95.View ArticleGoogle Scholar
  3. Holzgraefe B, Broome M, Kalzen H, Konrad D, Palmer K, Frenckner B. Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure. Minerva Anestesiol. 2010;76(12):1043–51.PubMedGoogle Scholar
  4. Patroniti N, Zangrillo A, Pappalardo F, Peris A, Cianchi G, Braschi A, Iotti GA, Arcadipane A, Panarello G, Ranieri VM, et al. The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med. 2011;37(9):1447–57.View ArticleGoogle Scholar
  5. Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA. 2011;306(15):1659–68.View ArticleGoogle Scholar
  6. Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018;378(21):1965–75.View ArticleGoogle Scholar
  7. Thiagarajan RR, Barbaro RP, Rycus PT, McMullan DM, Conrad SA, Fortenberry JD, Paden ML. Extracorporeal Life Support Organization Registry International Report 2016. ASAIO J. 2017;63(1):60–7.View ArticleGoogle Scholar
  8. Karagiannidis C, Brodie D, Strassmann S, Stoelben E, Philipp A, Bein T, Muller T, Windisch W. Extracorporeal membrane oxygenation: evolving epidemiology and mortality. Intensive Care Med. 2016;42(5):889–96.View ArticleGoogle Scholar
  9. Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased by 433% in adults in the United States from 2006 to 2011. ASAIO J. 2015;61(1):31–6.View ArticleGoogle Scholar
  10. Kim G-W, Koh Y, Lim C-M, Huh JW, Jung SH, Kim JB, Hong S-B. The effect of an improvement of experience and training in extracorporeal membrane oxygenation management on clinical outcomes. Korean J Intern Med. 2018;33(1):121–9.View ArticleGoogle Scholar
  11. Baek MS, Chung CR, Kim HJ, Cho WH, Cho Y-J, Park S, Park SY, Kang BJ, Kim J-H, Park SH, et al. Age is major factor for predicting survival in patients with acute respiratory failure on extracorporeal membrane oxygenation: a Korean multicenter study. J Thoracic Dis. 2018;10(3):1406–17.View ArticleGoogle Scholar
  12. Schmidt M, Bailey M, Sheldrake J, Hodgson C, Aubron C, Rycus PT, Scheinkestel C, Cooper DJ, Brodie D, Pellegrino V, et al. Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score. Am J Respir Crit Care Med. 2014;189(11):1374–82.View ArticleGoogle Scholar
  13. Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–16.View ArticleGoogle Scholar
  14. Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–68.View ArticleGoogle Scholar
  15. Schmidt M, Zogheib E, Roze H, Repesse X, Lebreton G, Luyt CE, Trouillet JL, Brechot N, Nieszkowska A, Dupont H, et al. The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intensive Care Med. 2013;39(10):1704–13.View ArticleGoogle Scholar
  16. Vaquer S, de Haro C, Peruga P, Oliva JC, Artigas A. Systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome. Ann Intensive Care. 2017;7(1):51.View ArticleGoogle Scholar
  17. Kim WY, Kang BJ, Chung CR, Park SH, Oh JY, Park SY, Cho WH, Sim YS, Cho YJ, Park S, et al. Prone positioning before extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: a retrospective multicenter study. Med Int. 2018. Epub ahead of print 5 July 2018. https://doi.org/10.1016/j.medin.2018.04.013.
  18. Guervilly C, Hraiech S, Gariboldi V, Xeridat F, Dizier S, Toesca R, Forel JM, Adda M, Grisoli D, Collart F, et al. Prone positioning during veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults. Minerva Anestesiol. 2014;80(3):307–13.PubMedGoogle Scholar
  19. Posluszny J, Rycus PT, Bartlett RH, Engoren M, Haft JW, Lynch WR, Park PK, Raghavendran K, Napolitano LM. Outcome of adult respiratory failure patients receiving prolonged (>/=14 days) ECMO. Ann Surg. 2016;263(3):573–81.View ArticleGoogle Scholar

Copyright

© The Author(s). 2019

Advertisement