|Year : 2022 | Volume
| Issue : 3 | Page : 120-126
Age and comorbidities as predictors of hospital mortality in adult patients who receive extracorporeal membrane oxygenation therapy: A population-based study
Te-Chun Yeh1, Hsiao-Huang Chang2, Ju-O Wang3, Senyeong Kao3, Tso-Chou Lin4, Shung-Tai Ho5
1 Development and Planning Center, Taipei City Hospital, Taipei, Taiwan
2 Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
3 School of Public Health, National Defense Medical Center, Taipei, Taiwan
4 Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
5 Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung; Department of Medicine, National Defense Medical Center, Taipei, Taiwan
|Date of Submission||21-Apr-2021|
|Date of Decision||20-May-2021|
|Date of Acceptance||09-Jun-2021|
|Date of Web Publication||01-Jul-2021|
Prof. Shung-Tai Ho
Department of Medicine, National Defense Medical Center/Department of Anesthesiology, Kaohsiung Medical University Hospital, 3F., No. 14, Ln. 187, Sec. 1, Dunhua S. Rd., Da'an Dist., Taipei
Source of Support: None, Conflict of Interest: None
Background: The incidence rate of extracorporeal membrane oxygenation (ECMO) use in Taiwan has increased significantly and is now higher than the worldwide incidence since 2000. Several studies have investigated hospital mortality and the risk factors of patients receiving ECMO. Comorbidities and age were not evaluated in these studies. Aim: To investigate the impact of age and comorbidities on hospital mortality of ECMO patients. Methods: A retrospective study of ECMO patients was performed using the claims data from the Taiwan National Health Insurance Research Database. Results: A total of 5834 adult patients were included in the study, and 2270 patients (38.9%) were discharged from the hospital between 2004 and 2012. The most common comorbidities were coronary artery disease (35.7%), hypertension (32.0%), and acute myocardial infarction (28.4%). Age, interstitial lung disease, rheumatologic disease, and lymphoma were the major predictors for hospital mortality in ECMO patients. On the contrary, acute myocarditis was found to be a favorable factor. Conclusion: Our results indicated that age and comorbidities were strongly associated with hospital mortality among ECMO patients. These findings can assist ECMO specialists to improve evaluations of mortality risk, especially among elderly patients with specific comorbidities.
Keywords: Comorbidity, extracorporeal membrane oxygenation, hospital mortality, survival rate
|How to cite this article:|
Yeh TC, Chang HH, Wang JO, Kao S, Lin TC, Ho ST. Age and comorbidities as predictors of hospital mortality in adult patients who receive extracorporeal membrane oxygenation therapy: A population-based study. J Med Sci 2022;42:120-6
|How to cite this URL:|
Yeh TC, Chang HH, Wang JO, Kao S, Lin TC, Ho ST. Age and comorbidities as predictors of hospital mortality in adult patients who receive extracorporeal membrane oxygenation therapy: A population-based study. J Med Sci [serial online] 2022 [cited 2023 Feb 7];42:120-6. Available from: https://www.jmedscindmc.com/text.asp?2022/42/3/120/320374
| Introduction|| |
Extracorporeal membrane oxygenation (ECMO) is used for the management of life-threatening cardiac or pulmonary failure. Most commonly, it is used in an emergency situation after other traditional therapies have failed (Extracorporeal Life Support Organization [ELSO], 2010). Taiwan's National Health Service Insurance reimburses for ECMO use in cases of cardiogenic shock and respiratory failure, while neonatal coverage extends to meconium aspiration syndrome, hyaline membrane disease, congenital diaphragm hernia, and persistent pulmonary hypertension (since 2002).
In Taiwan, significant social events highlighted by the mass media, specifically the successful use of ECMO to treat a national celebrity, have influenced the use of ECMO. As a result, the incidence rate of ECMO use in Taiwan has increased significantly and is now higher than the worldwide incidence since 2000. Currently, over 1000 patients receive ECMO therapy in Taiwan annually.
Aging and comorbidities may potentially alter. Several studies have investigated hospital mortality and the risk factors of patients receiving ECMO; however, comorbidities and age were not evaluated in these studies. However, to the best of our knowledge, no previous study has assessed the increased risk of mortality in elderly patients with comorbidities undergoing ECMO. There have been no large-scale ECMO patient analyses in any country. As a result, this study used Taiwan's National Health Insurance Research Database (NHIRD) to investigate the hospital mortality of patients receiving ECMO by age and comorbidity to identify high-risk patients.
| Materials and Methods|| |
The protocol for this study was approved by the institutional review board of Taipei Veterans General Hospital (2013-02-011A). We conducted a population-based, retrospective study using secondary data form the NHIRD. The NHIRD data were provided by the National Health Insurance (NHI) Administration, Ministry of Health and Welfare, and managed by the National Health Research Institutes. This large database comprises all NHI claims and registration data and is available for research purposes. The database covers more than 99% of Taiwanese residents (23 million) and all patient identifications were scrambled.
We analyzed the ECMO claims data from the NHIRD between 2004 and 2012. The ECMO patients were identified from the NHIRD by a principal investigator who used the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 39.65. These data were extracted from the database and analyzed.
Measures and definitions
Between 2004 and 2012, patients who received ECMO and were 18 years of age or older were enrolled in the study. The enrolled patients were divided into five age groups: 18–34 years, 35–49 years, 50–64 years, 65–79 years and ≧80 years. The comorbidities were defined by diagnostic codes according to the ICD-9-CM codes of the diseases. To assess possible effects on mortality, 18 major diseases along with the Charlson comorbidity index (CCI) were investigated to evaluate the risk of hospital mortality on patients who received ECMO [Table 1]. Similar to previous studies, CCI was treated as a covariate in this study and was divided into four groups: 0, 1–2, 2–4, and 5 or more. CCI is a simple tool for the evaluation of comorbidity that is calculated according to the weighted scoring system established by Charlson et al. and evaluates the risk of death from comorbid diseases.
|Table 1: International Classification of Disease, Ninth Revision Clinical Modification Codes for Comorbidities|
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Categorical data are presented as a number and percentage. Pearson's Chi-square test or Fisher's exact test was used for analysis of categorical variables to compare the difference between survivors and nonsurvivors in the proportion of comorbidities. To further elucidate the risk of hospital mortality associated with age and comorbidities in ECMO patients, odds ratios (OR) and respective 95% confidence intervals (CIs) were estimated by means of multivariate logistic regression analysis. Stratification analyses were used to evaluate hospital mortality rate among different age groups of ECMO patients.
All statistical tests were two-tailed, with the level of significance set at P < 0.05. Data analysis was performed using SPSS for windows (PASW Statistics for Windows, Version 18.0. Chicago, USA.).
| Results|| |
During the period from 2004 to 2012, analysis was performed on 6543 patients who received ECMO Therapy. A total of 709 individuals (10.8%) who were less than 18 years of age were excluded from the study. A total of 5834 adult patients (1798 females, 4035 males) who received ECMO therapy were enrolled in Taiwan. The mean patient age was 56.4 ± 16.9 years. There were 781 (13.4%) patients aged 18–34 years, 1136 (19.5%) patients aged 35–49 years, 1908 (32.7%) patients aged 50–64 years, 1601 (27.4%) patients aged 65–79 years, and 408 (7.0%) patients ≧80 years. Overall, the hospital mortality rate was 61.1% (3564/5834), and there was no significant difference in mortality between male and female patients (P = 0.355). When the different age groups were explored, the ≧80 years group had the highest hospital mortality rate (72.3%), followed by the 65–79 years group (66.3%), the 50–64 years group (60.2%), the 35–49 years group (56.0%), and the 18–34 years group (54.2%). The mortality rates increased consistently in patients by age groups and were significantly different across the different age groups (P < 0.001). The CCI was categorized into four groups: 0, 1–2, 3–4, and ≧5; the hospital mortality rate by CCI categories were 55.6%, 61.1%, 67.0%, and 66.9%, respectively (P < 0.001) [Table 2].
|Table 2: Characteristics of hospital mortality in patients receiving extracorporeal membrane oxygenation|
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[Table 2] presents the frequency and percentage of ECMO patients with comorbidities in the survival and nonsurvival patients. The most common comorbidities in ECMO patients were coronary artery disease (35.7%), hypertension (32.0%), acute myocardial infarction (AMI) (28.4%), diabetes (27.1%), and chronic liver disease (8.1%). Pulmonary fibrosis (100%), scleroderma (100%), interstitial lung disease (86.2%), lymphoma (86.2%), and rheumatologic disease (e.g. systemic lupus erythematosus, rheumatoid arthritis; 74.2%) had the highest hospital mortality rates among ECMO patients.
For determination of independent risk factors for hospital mortality in ECMO patients, OR and CIs were estimated using multivariate logistic regression. Multivariate logistic analysis revealed that age, interstitial lung disease, rheumatologic disease, and lymphoma were significant risk factors for hospital mortality; acute myocarditis was found to be a protective factor [Table 3]. The likelihood of hospital mortality was significantly greater among the older age groups (35–49 years: OR = 1.269, 95% CI = 1.126–1.430; 50–64 years: OR = 1.502, 95% CI = 1.369–1.648; 65–79 years: OR = 1.954, 95% CI = 1.761–2.168; ≧80 years: OR = 2.601; 95% CI = 2.094–3.231), interstitial lung disease (OR = 4.010, 95% CI = 1.387–11.598), rheumatologic disease (OR = 2.201, 95% CI = 1.375–3.521), and lymphoma (OR = 4.416, 95% CI = 1.525–12.793). In contrast, acute myocarditis (OR = 0.687, 95% CI = 0.535–0.0.882) was associated with a significantly lower likelihood of hospital mortality.
|Table 3: Multivariate logistic regression analyses of extracorporeal membrane oxygenation mortality|
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Because elderly ECMO patients frequently have concomitant comorbidities and higher mortality rates, we performed additional analyses on the outcome of hospital mortality by age [Table 4]. Stratification analyses showed that interstitial lung disease, rheumatologic disease, and lymphoma had significantly higher odds ratios. In contrast, acute myocarditis was found to be a protective factor for the 18–64-year-olds. Among patients 65 years and older, comorbidities of acute myocarditis, interstitial lung disease, rheumatologic disease, or lymphoma had no statistically significant impact on mortality rate [Table 4]a. [Table 4]b shows that at the same age group, the mortality rate raises with the increase of the CCI, and under the same CCI, we find that ≧65-year-old patients has a higher mortality rate than those aged 18–64 years.
| Discussion|| |
Each year, over 1000 patients in Taiwan receive ECMO therapy. According to the literature, the hospital survival rate for ECMO patients is approximately 50%–60% globally.,,,,, In the ELSO registry, the reported adult survival to discharge rate or transfer after ECMO through July 2015 for cardiac failure is 42% and for respiratory failure is 58%. However, the results of this study indicate that the overall hospital survival rate is 38.9%. This discrepancy may be due to the advanced age of the patients, with 34.4% of our sample aged 65 or older, which is considerably higher compared to other studies. According to the guidelines published by the ELSO,, respiratory failure is not a specific contraindication for age but should be considered because the risk increases with age. Patient age is a contraindication for heart failure. With regard to ECMO efficacy and safety, the UK National Institute for Health and Care Excellence has announced that ECMO is currently considered efficacious and safe for pediatric patients. Current evidence indicates that ECMO is sufficiently safe for adult patients suffering from acute respiratory failure but has a risk of serious side effects and the efficacy has yet to be confirmed. For adult patients suffering acute heart failure, the findings are inconclusive. The evolution of ECMO technique allows patients with end-stage lung or heart disease to be successfully supported for prolonged periods of time while the patients await lung or heart transplantation. The successfully use of ECMO as a bridge to heart or lung transplantation was reported recently.,,,
Our study demonstrated several characteristics of ECMO survivors who were at increased risk for hospital mortality. Risk factors for hospital mortality were age, interstitial lung disease, rheumatologic disease and lymphoma. Age is a key risk factor, particularly for patients over the age of 65. Previous studies have presented similar findings,,, but did not analyze elderly patients.
The current literature has little information regarding the role of comorbidities. Some studies have presented prediction models for ECMO survival rates, using respiratory extracorporeal membrane oxygenation survival prediction score to forecast ECMO survival rates for patients with severe respiratory failure. These studies reported that age and immunocompromised status (e.g. hematologic malignancies, solid tumor, solid organ transplantation, human immunodeficiency virus, and cirrhosis) are risk factors for ECMO survival. Another study found that age is a risk factor, while acute myocarditis is a protective factor in the prediction model of survival after venoarterial ECMO (SAVE) score for cardiogenic shock patients undergoing ECMO treatment. Acute myocarditis is a recoverable and self-resolving entity as long as timely mechanical circulatory support is provided until resolution of cardiac dysfunction or as a bridge to transplant. It has a high probability of survival and hospital discharge; thus, the risk of hospital mortality is relatively low (OR = 0.687; P = 0.003). A meta-analysis of six studies found that for fulminant myocarditis patients undergoing ECMO therapy, the minimum and maximum reported rates of survival to hospital discharge were 60.0% and 87.5%, respectively. Previous studies of ECMO in adult patients with hematologic malignancies were limited to a few cases and one clinical study, which found that ECMO patients were at increased risk for severe bleeding events.
This study has several strengths. It included a large sample of 5834 ECMO therapy patients. Comprehensive comorbidity data were collected from claims data. However, this study also had several limitations. First, the study was a retrospective analysis based on NHIRD data and thus lacked detailed clinical information on some personal information on the ECMO patients such as biochemistry data (liver function and kidney function), blood pressure, and oxygenation status. Second, NHIRD did not differentiate between the type of ECMO (venoarterial ECMO and venovenous ECMO).
| Conclusion|| |
In this nationwide population-based study that assessed the impact of age and comorbidities in ECMO patients, we found that age and comorbidities were some of the most important predictors of hospital mortality. The main findings were that age, interstitial lung disease, rheumatologic disease, and lymphoma are risk factors associated with higher hospital mortality. Thus, these findings would aid ECMO specialists in better evaluating mortality risk, especially in elderly patients with specific comorbidities.
This study was based in part on data from the NHIRD provided by the NHI Administration, Ministry of Health and Welfare and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of NHI Administration, Ministry of Health and Welfare, or National Health Research Institutes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]