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  • Research article
  • Open Access
  • Open Peer Review

ECMO use and mortality in adult patients with cardiogenic shock: a retrospective observational study in U.S. hospitals

BMC Emergency Medicine201818:20

https://doi.org/10.1186/s12873-018-0171-8

  • Received: 3 December 2017
  • Accepted: 21 June 2018
  • Published:
Open Peer Review reports

Abstract

Background

Extracorporeal membrane oxygenation (ECMO) is increasingly used in resuscitation of critically ill patients with documented improved survival. Few studies describe ECMO use in cardiogenic shock. This study examines ECMO use and identifies variables associated with mortality in patients treated for cardiogenic shock in US hospitals.

Methods

A retrospective observational study of the US Nationwide Emergency Department Sample (NEDS) database of 2013 was conducted. Weighted visits for cardiogenic shock (discharge diagnosis) with ECMO use were included. Collected data was analyzed and variables associated with mortality were identified.

Results

A total of 922 weighted patients with cardiogenic shock and ECMO were included. Mean age was 50.8 years. They were more commonly males (66.3%; n = 658). Slightly over half (51.0%, n = 506) survived to hospital discharge. Mean charges per patient were $589,610.5. Mean length of stay was 21.8 days.

Increased mortality was associated with presence of respiratory diseases (OR = 3.83), genitourinary diseases (OR = 4.97), undergoing an echocardiogram (OR = 4.63), and presenting during seasons other than Fall. Lower mortality was noted in patients with injury and poisoning (OR = 0.47), in those who underwent certain vascular procedures (OR = 0.49) and those with increasing length of stay (OR = 0.90).

Conclusion

Mortality in patients with cardiogenic shock remains high despite ECMO use. Season of admission (other than Fall) and presence of specific comorbidities (Respiratory and genitourinary diseases) are associated with increased mortality in this population. Familiarity with these variables can help identify patients at higher risk of death and can help improve outcomes further in cardiogenic shock.

Keywords

  • Extracorporeal circulation
  • Extracorporeal membrane oxygenation
  • Shock, cardiogenic
  • Emergency service, hospital
  • Resuscitation
  • Critical illness

Background

Mechanical cardiopulmonary assistance, which is often utilized as an integral part of certain invasive cardiac surgeries, is increasingly used in resuscitation of patients in intensive care settings and emergency departments [112]. Prolonged cardiopulmonary assistance is called extracorporeal membrane oxygenation (ECMO) or extracorporeal life support (ECLS) and is a sophisticated and resource-intensive intervention for critically ill patients with cardiac or respiratory dysfunction [11, 12]. ECMO and ECLS are often used interchangeably [13].

There are two types of ECMO – veno-venous (VV) and veno-arterial (VA) ECMO – depending on differences in vascular access. During VV ECMO, blood is extracted from the vena cava or right atrium and returned oxygenated to the right atrium. During VA ECMO, blood is extracted from the right atrium and returned oxygenated to the arterial system, most commonly the iliac artery. VA ECMO provides hemodynamic support in addition to respiratory support [11].

Although ECMO use is more commonly described in the pediatric population, ECMO use in adults for cardiac and respiratory indications more recently became the largest contributing group in the Extracorporeal Life Support Organization Registry, which was established to improve quality and outcome of ECMO use [4, 12]. ECMO is used for various cardiac or pulmonary diseases including: post-cardiotomy, myocarditis, acute coronary syndrome or refractory cardiac arrest, as a bridge to heart/lung transplant, cardiogenic shock, respiratory failure, trauma/drowning as well as other conditions [14]. In 2015, cardiogenic shock was found to be the most common diagnosis associated with ECLS use in adults with VA ECMO, occurring in 60.7% of such patients [4]. Cardiogenic shock is a clinical condition of inadequate tissue perfusion due to cardiac dysfunction that is associated with persistent hypotension and end organ damage. Cardiogenic shock often results from myocardial infarction but can also result from other cardiac diseases such as myocarditis, pericarditis, and cardiomyopathy [15].

ECMO use improves survival in patients with cardiac disease with survival rates ranging from 20 to 50% [110]. ECMO also increases 30-day survival rates when used to bridge patients in cardiogenic shock to coronary intervention procedures [16]. Additionally, ECMO improves outcomes in patients with cardiac arrests – mainly survival without neurologic deficit – when added to cardiopulmonary resuscitation (CPR) [3, 17].

Contraindications for VA ECMO in cardiac failure do exist and include the following: ethical considerations and patient’s will, no bridging goal, severe aortic regurgitation, aortic dissection, severe peripheral artery disease (iliac), left ventricular thrombus (relative contraindication) [18]. Despite several observational and registry studies on ECMO use, few studies describe the extent of ECMO use in patients with cardiogenic shock. This study examines cardiogenic shock presentations that involved ECMO use and identifies variables associated with mortality in this U.S. hospital population sample.

Methods

Data and materials

NEDS is a product of Healthcare Cost and Utilization Project (HCUP) under the auspices of the Agency for Healthcare Research and Quality (AHRQ) [19]. It is the largest U.S. all-payer ED database, combining medical and non-clinical data from both national and state sources. Data from this stratified sample is accrued from 945 hospital-owned EDs located across 30 States and the District of Columbia, reflecting approximately 20% of all hospital-based EDs located in the United States. The following stratification variables were used to weight data per HCUP specifications: U.S. Census region, urban-rural location, ownership, and teaching status of the hospital as well as trauma center designation [20]. This stratified sample of patients is statistically weighted using the above stratification variables to approximate and examine national estimates. Weighting of sample compensates for different probabilities of selection as part of the dataset sample. As per requirements for publishing HCUP data and to safeguard patients’ privacy, data on any variable with size less than or equal to 10 are excluded.

Study design and population

This retrospective study used the 2013 public release dataset of the US Nationwide Emergency Department Sample (NEDS) database. The 2013 NEDS dataset contains information on weighted 134,869,015 ED visits. Patients were included in this study if they met the following criteria: Adult patients (age 18 or older) who presented with cardiogenic shock and underwent ECMO procedure and died in the ED or were admitted to the same hospital during the selected visit.

Data definitions

The NEDS data elements include: demographic patient information; mechanism, intent, and severity of injury; admission and discharge status; payment source; healthcare expenses and general hospital characteristics. The AHRQ Clinical Classifications Software (CCS) was used to select all patients with cardiogenic shock. CCS is a tool for grouping patient diagnoses and procedures into a convenient number of clinically meaningful categories similar and equivalent to than the International Classification of Diseases (ICD) coding system.

The following CSS codes are specific for cardiogenic shock: CCS 97, CCS 100, CCS 101, CCS 103, CCS 106, CCS 107, CCS 108 [12]. A list of Equivalent ICD-9 CM codes and variable classification is included (See attachment, Additional File 1 which illustrates code and variable classifications). Additionally, the ICD-9 CM procedure code 39.65 was used to gather all patients who underwent ECMO procedure.

Chronic diseases and procedures with frequencies less than 10% were removed from the analysis and were not displayed results. Injury severity score (ISS) is considered as the gold standard trauma severity score to predict morbidity, increased hospital stay and mortality in trauma patients. An ISS score greater than 15 is historically used as a cutoff value for severe trauma injury [21]. This study used a more conservative cut off value for ISS of > 8 since very few patients had an ISS score greater than 15. Previous studies have also shown that increasing injury severity (ISS of > 8) is associated with increased hospital stay and ICU admission [22].

AHRQ provides a database and a software tool, called the Chronic Condition Indicator (CCI), that allows for the identification of chronic diseases using ICD-9 CM coding. CCI was utilized in this study for the purposes of investigating presence of chronic conditions according to body system categories affected. According to CCI, the definition of a chronic disease is “a medical condition which lasts for twelve months or longer with either one of the following criteria being met: (1) the medical condition restricts self-care, independent living, and social interaction; (2) the medical condition results in the need of ongoing medical intervention.”

Additionally, NEDS categorizes ICD-9 CM procedure codes into four broad categories labeled as either major or minor and therapeutic or diagnostic. An ICD-9 CM procedure is classified as “minor if the procedure is a non-operating room procedure and major if the procedure is a valid operating room procedure by the Diagnosis Related Group (DRG) grouper” (an ICD-9 CM grouping system). CCS procedure codes were also used to examine most common procedures other than ECMO.

Statistical analysis

IBM-SPSS 24 was used to carry out descriptive analysis on the socio-demographic, clinical and hospital characteristics. Mean with associated 95% confidence intervals (CI) was used for continuous variables, while frequencies, percentages and 95% CI were used for categorical variables.

The standard statistical methods that treat the data as being emerged from a simple random sampling data were inappropriate for the NEDS survey design and would yield biased estimates, overly-narrow confidence levels and misleading significance tests due to the type I error generated from the biased results. The Rao-Scott chi-square test, a modified version of the Pearson’s chi-square test, as well as a general linear model (GLM) for complex sampling (CS) were used to assess the significance of the statistical association of the independent categorical and continuous variables respectively between the two groups (those who survived and those who did not). Logistic regression was conducted to identify significant associations with mortality in ECMO patients with cardiogenic shock. Variables that were significantly different between the two groups when compared by outcome (mortality) were included in the multivariate analysis.

All estimates (means, percentages, odds ratio and confidence intervals) were drawn by complex sampling methods, particularly, CSTABULATE, CSDESCRIPTIVES, CSGLM and CSLOGISTIC to adjust for the NEDS survey design and to ensure the results are accurate. CSTABULATE is a complex sample procedure that produces analysis for categorical variables. CSDESCRIPTIVES and CSGLM are two different complex sample procedures that allow for analysis of continuous variables at the univariate and bivariate levels respectively. Lastly, the Complex Samples Logistic Regression procedure, CSLOGISTIC, performs logistic regression for samples drawn by complex sampling methods.

Complex sampling design of the study resulted in decimal places among sample frequencies. To avoid rounding errors and for the sake of clarity, variables were restored to discrete format by discarding decimals. In addition, a maximal value for total sample frequency was capped at 992 patients. Analysis was verified using HCUPnet, a free on-line query system based on data from HCUP [23]. Lastly, a p-value of < 0.05 was used to indicate statistical significance.

Results

A total of 8,605,807 weighted adult visits were admitted to the emergency department with cardiogenic shock. Of those, 992 weighted adult patient visits included an ECMO procedure yielding a rate of 0.1 per 1000 ED visits for cardiogenic shock.

The mean age of the study population was 50.8 years (95%CI 48.8–52.7). Patients were more commonly males (66.3%; 95%CI 60.3–71.8). Visits were equally distributed across all four seasons and were mainly during the weekday (Monday through Friday) (70.6%, n = 700). Over half of visits were to large metropolitan hospitals (fringe 39.4%, n = 389 and central 29.1%, n = 287). Private insurance (47.8%, n = 472) as well as Medicare and Medicaid (43.6%, n = 430) were the most common primary expected payer types. (Table 1).
Table 1

Characteristics of Study Population

Continuous Variables

Range

Median (IQR)

Mean (95% CI)

Age (years)

18–90

54 (23)

50.8

(48.8–52.7)

Categorical Variables

Count (N = 992)

Percent (95% CI)

Gender (male)

658

66.3 (60.3–71.8)

Median household incomea

 $1 - $37,999

126

13.2 (9.8–17.6)

 $38,000 - $47,999

238

25.1 (19.9–31.0)

 $48,000 - $63,999

238

25.0 (20.2–30.7)

 $64,000 or more

348

36.7 (31.1–42.6)

Season of admission

 Winter

223

23.2 (18.3–29.0)

 Spring

244

25.4 (20.5–31.0)

 Summer

259

27.0 (21.8–33.0)

 Autumn

234

24.3 (19.5–29.9)

Admission day

 Monday - Friday

700

70.6 (64.7–75.8)

 Saturday - Sunday

292

29.4 (24.2–35.3)

Patient locationb

 Large central metropolitan

287

29.1 (24.4–34.3)

 Large fringe metropolitan

389

39.4 (34.5–44.5)

 Medium metropolitan

147

14.9 (11.5–19.0)

 Small metropolitan

66

6.6 (4.1–10.7)

 Micropolitan

51

5.1 (3.2–8.1)

 Not metropolitan or micropolitan

48

4.9 (3.0–7.9)

Primary expected payer

 Private insurance

472

47.8 (41.6–54.1)

 Medicare & Medicaid

430

43.6 (37.3–50.1)

 Self-pay

60

6.1 (3.8–9.7)

 Other

25

2.5 (1.1–5.5)

aAccording to national quartile for patient ZIP code derived from ZIP Code-demographic data obtained from Claritas

bAccording to National Center for Health Statistics (NCHS) Urban-rural code

All patients had diseases of the circulatory system, and most patients had diseases of the respiratory system (82.7%, n = 820) as well as endocrine, nutritional, and metabolic diseases/immunity disorders (80.1%, n = 795) (Table 2). Few patients had injury diagnosis reported on record (14.2%, n = 141). The most frequent injury reported was suffocation injury (1.9%, n = 19) followed by falling injury (1.5%, n = 15). Only 5.3% (n = 52) had increased injury severity defined by an ISS of 9 or greater. The mean for total charges (both ED and inpatient services) was $589,610.5 (95% CI 512,270.0 – 666,950.9). The mean hospital length of stay was 21.8 days (95% CI 19.0–24.6).
Table 2

Chronic Conditions, Injuries, and Outcomes of Sample Patients

Categorical Variables

  

Count (N = 992)

Percent (95% CI)

Chronic conditions body system indicator

 Circulatory system

  

992

100

 Respiratory system

  

820

82.7 (77.5–86.9)

 Endocrine/nutritional/metabolic/immunity

  

795

80.1 (74.7–84.6)

 Symptoms, signs, and ill-defined conditions

  

779

78.5 (73.1–83.1)

 Genitourinary system

  

724

72.9 (67.1–78.1)

 Blood and blood-forming organs

  

636

64.1 (58.0–69.7)

 Injury and poisoning

  

617

62.2 (56.3–67.7)

 Digestive system

  

414

41.8 (35.8–47.9)

 Infectious and parasitic disease

  

393

39.7 (33.7–45.9)

 Health status/contact with health services factors

  

383

38.6 (33.1–44.4)

 Nervous system and sense organs

  

313

31.5 (26.1–37.5)

 Mental disorders

  

186

18.8 (14.3–24.2)

Injury diagnosis reported on record

 No injury diagnoses reported

  

851

85.8 (80.8–89.7)

 Injury is reported

  

141

14.2 (10.3–19.2)

Injuries Specified by the NEDS Database

 Injury by suffocation

  

19

1.9 (0.8–4.4)

 Injury by falling

  

15

1.5 (0.5–4.1)

More than one injury diagnosis

    

 One or no injury diagnosis reported

  

938

94.5 (90.9–96.7)

 More than one injury diagnosis

  

54

5.5 (3.3–9.1)

Unintentional injury indicated

 Intention not specified

  

924

93.1 (89.2–95.6)

 Unintentional injury

  

68

6.9 (4.4–10.8)

Injury severity scorea

   

90.3 (85.9–93.5)

 No injury severity score

  

896

4.4 (2.4–7.8)

 1–8

  

44

5.3 (3.0–9.0)

 9–75

  

52

 

Disposition of patient

 Admitted to same hospital

  

992

100

 Survival to discharge

  

506

51.0 (44.8–57.1)

 Died in the ED/hospital

  

486

49.0 (42.9–55.2)

Continuous Variables

Frequency

Range

Median (IQR)

Mean (95% CI)

Total chargesb (USD$)

988

3773–4,292,990

409,138 (468,598)

589,610.5 (512,270.0 – 666,950.9)

Length of stay (days)

992

0–131

16 (24)

21.8 (19.0–24.7)

aAssigned by ICPIC Stata program

bTotal charges are for accumulated ED and Inpatient services

In addition to ECMO, patients with cardiogenic shock underwent different types of procedures (Table 3). By procedure class, all patients had major therapeutic procedures on record since ECMO procedure is categorized as major therapeutic. Most patients (89.1%, n = 884) also had minor therapeutic procedures. The most common procedure other than ECMO was respiratory intubation and mechanical ventilation (56.7%, n = 562).
Table 3

Extracorporeal Membrane Oxygenation Among Cardiogenic Shock: Procedures

Procedure class for inpatient

Count (N = 992)

Percent (95% CI)

 Minor diagnostic

534

53.8 (47.8–59.7)

 Minor therapeutic

884

89.1 (84.6–92.4)

 Major diagnostic

62

6.2 (3.8–10.1)

 Major therapeutic

992

100

Specific procedures using CCS codes

Count (N = 992)

Percent (95% CI)

 Circulator system procedures

  Extracorporeal circulation auxiliary to open heart proceduresa

992

100

  Other operating room heart proceduresb

510

51.4 (45.3–57.5)

  Diagnostic cardiac catheterization; coronary arteriography

231

23.3 (18.6–28.9)

  Conversion of cardiac rhythm

183

18.4 (14.4–23.3)

  Heart valve procedures

179

18.1 (13.9–23.1)

  Coronary artery bypass graft (CABG)

150

15.1 (11.5–19.6)

  Other non-operating room therapeutic cardiovascular procedures

123

12.4 (9.0–16.9)

  Percutaneous transluminal coronary angioplasty (PTCA)

113

11.4 (8.1–15.8)

  Echocardiogram

107

10.8 (7.6–15.3)

  Swan-Ganz catheterization for monitoring

102

10.2 (7.2–14.4)

  Blood transfusion

220

22.2 (17.9–27.2)

 Respiratory system procedures

  

  Respiratory intubation and mechanical ventilation

562

56.7 (50.5–62.7)

  Other operating room procedures on respiratory system and mediastinum

182

18.4 (14.0–23.7)

  Diagnostic bronchoscopy and biopsy of bronchus

135

13.6 (10.0–18.3)

  Tracheostomy; temporary and permanent

111

11.2 (7.8–15.9)

 Other procedures

  Other operating room proceduresb

365

36.8 (31.1–42.9)

  Other vascular catheterization; not heart

330

33.3 (27.8–39.3)

  Other therapeutic proceduresc

207

20.9 (16.5–26.1)

aThis CCS procedure code also includes ICD-9 procedure code 39.65 for ECMO procedures

bExamples include operations on valves and septa of the heart, heart vessels, and the heart and pericardium

cSpecifically procedures on vessels other than head/neck

dNervous, ophthalmic, gastrointestinal procedures not otherwise specified

For Patients who underwent ECMO, there were significant differences between those who survived to hospital discharge and those who did not. Table 4 lists only the statistically significant variables between the two groups and which included age, season of admission, presence of certain chronic conditions and certain procedures, whether injury was reported, total charges, and length of stay (LOS). Those who survived were slightly younger than those who did not (49.5 vs 52.1, years respectively p = 0.009) and had significantly higher total hospital charges for services as well as total length of stay.
Table 4

Comparison of Study Groups Stratified by Outcome (Mortality)

 

Survival to Discharge

(N = 506)

Mortality

(N = 486)

 

Categorical Variablesa

Count

Percent (95% CI)

Count

Percent (95% CI)

p-value

Season of admission

 Winter

85

17.4 (11.7–25.2)

138

29.2 (21.8–37.8)

0.006

 Spring

104

21.3 (15.0–29.1)

140

29.7 (22.2–38.5)

 

 Summer

140

28.7 (21.3–37.5)

119

25.2 (18.2–34.0)

 

 Autumn

159

32.6 (25.6–40.3)

75

15.9 (10.3–23.7)

 

Chronic conditions

506

100

487

100

 

 Respiratory system

389

76.9 (69.1–83.2)

431

88.6 (81.4–93.3)

0.014

 Injury and poisoning

375

74.2 (65.9–81.0)

242

49.7 (41.1–58.3)

< 0.001

 Genitourinary system

305

60.4 (51.7–68.4)

419

86.0 (79.6–90.7)

< 0.001

 Digestive system

178

35.3 (27.5–43.9)

236

48.5 (39.8–57.3)

0.034

 Nervous system & sense organs

127

25.1 (18.4–33.4)

186

38.2 (30.1–46.9)

0.025

Injury diagnosis

 No injury diagnoses

392

77.7 (69.3–84.3)

459

94.3 (88.7–97.2)

< 0.001

 Injury is reported

113

22.3 (15.7–30.7)

28

5.7 (2.8–11.3)

 

Procedures

     

 Other operating room proceduresb

225

44.5 (36.0–53.3)

140

28.8 (21.4–37.6)

0.012

 Tracheostomyc

82

16.1 (10.5–23.9)

30

6.1 (3.0–12.1)

0.015

 Echocardiogram

36

7.1 (3.8–12.9)

71

14.7 (9.5–22.0)

0.05

Continuous Variablesd

Count

Mean (95% CI)

Count

Mean (95% CI)

p-value

Age (years)

506

49.5 (46.8–52.1)

487

52.1 (49.3–54.9)

0.009

Total chargese (USD)

501

695,089.0 (560,971.1-829,206.8)

487

480,927.5 (398,015.8-563,839.2)

< 0.001

Length of stay (days)

506

28.8 (24.4–33.1)

487

14.6 (11.5–17.6)

< 0.001

aThe p-values for the categorical variables were calculated using the Rao-Scott chi-square test of the complex sample procedure

bSpecifically procedures on vessels other than head and neck

cTemporary and permanent

dThe p-values for the continuous variables were calculated using the general linear model of the complex sample procedure

eTotal charges are for accumulated ED and Inpatient services

Table 5 shows the variables associated with mortality in ECMO patients. Having diseases of either the respiratory system (OR = 3.83, 95%CI 1.76–8.31) or genitourinary system (OR = 4.97, 95%CI 2.39–10.33) as well as undergoing an echocardiogram (OR = 4.63, 95%CI 1.300–16.504) were significantly associated with increased mortality. Higher mortality was also associated with visits during all seasons when compared to autumn.
Table 5

Mortality with ECMO use in Cardiogenic Shocka

 

Odds Ratio

95% CI

p-value

CCIb - Nervous system and sense organs diseases

1.22

0.64–2.32

0.541

CCI - Respiratory system diseases

3.83

1.76–8.31

0.001

CCI - Digestive system diseases

1.72

0.82–3.61

0.150

CCI - Genitourinary system diseases

4.97

2.39–10.33

< 0.001

CCI - Injury and poisoning

0.47

0.24–0.94

0.032

Injury diagnosis reported

0.45

0.15–1.36

0.156

Tracheostomy; temporary and permanent

0.46

0.14–1.48

0.190

Other operating room proceduresc

0.49

0.24–1.00

0.048

Echocardiogram

4.63

1.30–16.50

0.018

Season of admission (Autumn)

   

 Winter

8.85

3.39–23.11

< 0.001

 Spring

5.44

2.16–13.73

< 0.001

 Summer

4.02

1.54–10.46

0.005

Age (1 year)

1.01

1.00–1.04

0.239

Length of Stay (1 day)

0.94

0.90–0.98

0.003

Total chargesd (per $10,000)

1.01

1.00–1.02

0.069

aVariables included in the model are: significant chronic conditions and procedures found at the bivariate level, injury diagnosis, season of admission, age, and total charges

bCCI denotes body system categories affected by chronic conditions

cSpecifically procedures on vessels other than head and neck

dTotal charges are for accumulated ED and Inpatient services

Conversely, having a chronic disease of injury and poisoning (OR = 0.382, 95%CI 0.191–0.765), undergoing other operating room procedures on vessels other than head and neck (OR = 0.49, 95%CI 0.24–1.00), as well as increasing total charges (OR = 0.993 95%CI 0.988–0.999) were associated with decreased mortality.

Discussion

ECMO use is increasing in adult patients with cardiogenic shock, but few studies that describe ECMO use or associations with mortality in this population are available. This study is the first to use the largest US ED database, NEDS, to describe socio-demographic, clinical, and hospital characteristics for patients with cardiogenic shock who underwent ECMO.

This study also described patterns of ECMO use and outcomes of patients with cardiogenic shock. ECMO was used in 0.1 per 1000 ED/hospital visits with cardiogenic shock in 2013. Survival to hospital discharge was 51%. This finding is consistent with survival rates from previous studies that range from 20 to 50% [110].

The mean age of patients who presented to US EDs with cardiogenic shock and who underwent ECMO was 50.8 years (95%CI 48.4–52.7). Previous studies have shown similar characteristics [12, 24]. Maxwell et al. examined national ECMO use between the years 1998 to 2009 and found an overall mean age of 53.9 ± 0.4 years and a mean age of 48.9 ± 0.8 years among those with cardiogenic shock specifically [12]. Schmidt et al., on the other hand, analyzed ECMO use only for refractory cardiogenic shock between the years of 2003 and 2013 and found a mean age of 54 years (range 39–64) [24].

ECMO use as expected was mostly in large metropolitan hospitals. ECMO is considered a complex procedure and is fraught with complications such as stroke, neurologic complications, lower extremity ischemia, fasciotomy or compartment syndrome, amputation, acute kidney injury, renal replacement therapy, significant infection, major or significant bleeding and re-thoracotomy for bleeding or tamponade [14, 18]. Thus, it is usually reserved for when conventional treatments have failed and is usually undertaken in larger specialized centers.

Seasonal variation in mortality among patients presenting with cardiogenic shock and undergoing ECMO procedure was also identified in this study. The association of seasonal patterns on both hospital admission and mortality has been previously examined and described among patients with cardiovascular disease. Previous studies have reported increased adverse effects (hospital admission and mortality) during colder months (up to 10–20% increased mortality) [2527]. Similarly, our study shows that the winter season was associated with the highest mortality (OR: 8.85; 95%CI: 3.39–23.11). Reasons for these seasonal variations though not directly identified in our study are multiple and complex, involving both physiologic and behavioral causes. Previously identified causes include sudden cold acclimatization, change in dietary patters, change in physical activity, changes in mental health, vitamin D deficiency, increased air pollution, and increased incidence of infectious disease [26].

This study also identified variables associated with mortality in patients with cardiogenic shock requiring ECMO. In addition to previously described associated clinical variables, the study examined different socioeconomic and system level factors that might be affecting mortality in this population. Patients with specific chronic conditions such as diseases of the respiratory system or the genitourinary system were more likely to die. This was expected given that patients with multiple organ dysfunction syndrome require ventilator support or dialysis and are more likely to die. These findings are similar to previous studies where pre-ECMO predictive survival score (SAVE-score) in patients with refractory cardiogenic shock identified chronic renal failure as risk factor associated with mortality [24].

The study also examined the costs and impact associated with ECMO use. The mean total charges for cardiogenic shock visits with ECMO procedure was $589,610.5 (95%CI $512,270.0 – $666,950.9) per admission. This mean is more than 10 times the national mean cost of patients with cardiogenic shock post ST-Elevation Myocardial Infarction in 2010 ($45,625) [28]. The mean length of stay for the study population was 21.8 days (95%CI 19.0–24.7). Both the mean cost and mean length of stay are higher than what Maxwell et al. previously reported on resource use trends in ECMO between 1998 and 2009 where the mean total hospital charges was $344,009 ± $30,707 per admission and the mean length of stay was 18.3 ± 1.3 days [12]. Resources utilization with ECMO seem to be increasing without an associated increase in survival benefit. Future research is therefore needed to document trends in survival and the impact of ECMO use on outcomes of patients suffering from cardiogenic shock and from other conditions. ECMO is just one of several mechanical assist devices used in cardiogenic shock. Other devices include intra-aortic balloon pumps (IABP) and LV assist devices (LVADs). ECMO however, is the only intervention that compensates for both the right and left heart function as well as lung function. As such, ECMO decreases requirements for catecholamine, vasodilator, and mechanical ventilation in the treatment of cardiogenic shock and reduces the complications that are usually associated with these treatment modalities [18, 29]. ECMO use therefore holds promise for use in selected cardiogenic shock patients and further prospective studies are recommended.

The limitations of this study are directly related to structural features of the NEDS database. First, ICD-9 CM codes do not differentiate between VA or VV ECMO. This may be resolved with future use of ICD-10 CM codes. Second, information on the duration of ECMO use or timing of initiation is not available and costs are allocated to the whole hospital admission and not to a specific resource. Other limitations are related to the retrospective nature of the study. The quality and quantity of the data depends on the knowledge and experience of the coder, the completeness and accuracy of the patient record, and the state requirements. The study findings portray however trends in ECMO use for cardiogenic shock from a large sample from US based hospitals and can be generalized to other hospitals from similar settings.

Conclusion

Mortality in adult patients with cardiogenic shock remains high despite ECMO use. Season of admission (other than Fall) and presence of specific comorbidities (Respiratory and genitourinary diseases) are associated with increased mortality in this population. Familiarity with patients’ characteristics and variables associated with mortality after ECMO use is important to improve outcomes further in cardiogenic shock. With rising costs and resources utilization, future research should focus on the impact of ECMO use on survival and on outcomes of patients with critical illnesses including but not limited to cardiogenic shock.

Abbreviations

AHRQ: 

Agency for Healthcare Research and Quality

CCS: 

Clinical Classifications Software

CI: 

confidence intervals

CPR: 

Cardiopulmonary Resuscitation

ECLS: 

extracorporeal life support

ECMO: 

Extracorporeal membrane oxygenation

ED: 

emergency department

ELSORIR: 

Extracorporeal Life Support Organization Registry International Report

HCUP: 

Healthcare Cost and Utilization Project

IABP: 

include intra-aortic balloon pumps

ICD: 

International Classification of Diseases

IRB: 

Institutional Review Board

LOS: 

length of stay

LVADs: 

LV assist devices

NEDS: 

Nationwide Emergency Department Sample

VA: 

veno-arterial

VV: 

veno-venous

Declarations

Funding

There are no sources of funding for the research reported.

Availability of data and materials

The data that support the findings of this study are available from HCUP but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of HCUP. More information can be accessed via: www.hcup-us.ahrq.gov/nedsoverview.jsp.

Authors’ contributions

ME provided substantial involvement in the conception, design, and execution of the manuscript as well as reviewing and revising the manuscript for its credible content. RE provided substantial involvement in the design, and execution of the manuscript as well as drafting and revising the manuscript. RB provided substantial involvement in design and reviewing the manuscript as well as analysis of data. All authors read and approved the final manuscript.

Ethics approval and consent to participate

An exemption for the use of this de-identified dataset was obtained from the institutional review board (IRB) office at the American University of Beirut. This database is defined as limited data set under the HIPAA Privacy Rule and as such is de-identified prior to use and is waived from consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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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 Emergency Medicine, American University of Beirut Medical Center, P.O. Box - 11-0236, Riad El Solh, Beirut, 1107 2020, Lebanon
(2)
Emergency Medical Services and Prehospital Care Program, American University of Beirut Medical Center, Beirut, Lebanon

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