Dismal survival after prolonged conventional cardiopulmonary resuscitation with external chest compression and medications has prompted many institutions to consider more aggressive methods such as the use of extracorporeal membrane oxygenation (ECMO) for in-hospital cardiopulmonary resuscitation (ECPR), in attempts to improve survival in these patients.
In adults, ECMO support for in-hospital cardiac arrest after conventional CPR is associated with survival rate of 27%.1 Despite the presence of proposed guidelines, the use of ECMO for elderly patients is still controversial because advanced age is a risk factor for mortality in patients with cardiogenic shock.2 Some investigators have even suggested that age >75 years should be a contraindication for ECMO support.3,4 Among the elderly (>65 years of age), the utilization of ECPR has not been clearly defined and risk factors for survival to hospital discharge in these patients remain unreported. Therefore, we analyzed data from the international Extracorporeal Life Support Organization (ELSO)5 data registry to investigate ECPR outcomes among the elderly patients and investigate risk factors associated with in-hospital mortality.
Materials and Methods
We retrospectively reviewed all elderly patients >65 years of age requiring ECPR and listed in the ELSO registry between 1998 and 2009. No informed consent was obtained, because the data set was limited to nonidentifiable elements of information. This was approved by the Institutional Review Board at our facility and by the ELSO registry. Only data from the initial ECMO deployment were included for subjects who received ECMO support more than once. The requirement for informed consent was waived as a result of the retrospective nature of the study.
Extracorporeal Life Support Organization Registry
The ELSO registry5 was founded in 1982 and collects a limited patient data set from member institutions on extracorporeal support in children and adults. Data are collected and sent from the contributing centers with a standardized data sheet containing patient demographics, diagnosis and procedure information, ECMO technique, complications during ECMO, and patient outcomes. Currently, 110 centers (including 14 outside North America) contribute data to the registry. Each individual member institution approves data reporting through its local institutional review board.
The independent variables were grouped before analysis as follows: demographic data, International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes (reviewed by two authors independently and disagreement resolved after review by a third author), pre-ECMO course variables, pre-ECMO therapies instituted, ECMO course data, and associated complications while receiving ECMO support. Survival to hospital discharge was the primary end-point for the study.
Data were reported as frequency (n) with proportion (%), or median values with ranges. Demographic, pre-ECMO and ECMO support details, and ECMO complications were compared for patients who survived to hospital discharge with those who died. The Mann–Whitney U test was used to compare continuous data and the Fisher’s exact or Pearson’s chi-square test for categorical data. We fit a model to the time to death on ECMO, adjusting for the competing risk of coming off ECMO. The only predictor in the competing risks models was an “indicator that age was less than 75 years old.” The p values (p = 0.34 [time 1] and p = 0.41 [time 2]) are based on Fine/Gray competing risks regression. The time intervals used for this analysis were a composite of time of admission to time on ECMO support, time on ECMO support, and time off ECMO support to death. The time intervals used for this analysis were a composite of time of admission to time on ECMO support, time on ECMO support, and time off ECMO support to death. Similarly, another graph specifically for the duration of ECMO was also created. Data were received in Excel (Microsoft Inc., Redmond, WA) and then was transferred to Stata/MP 12.1 software (College Station, TX) for statistical analysis. Statistical significance was defined as a p value <0.05. The authors had full access to the data and took responsibility for its integrity.
A total of 99 elderly patients requiring ECPR were identified from the ELSO registry for the study period. Second ECMO deployments on five patients were excluded from the study. The median age of the cohort was 70 years (range 65–86 years). The median admission to time on ECMO was 32 hours (range 1–998 hours), median time on ECMO was 69 hours (range 1–459 hours), and median time off to discharge for survivors was 587 hours (range 3–2,166 hours).
Overall, survival at hospital discharge was 22.2% (22/99). There were 24.2% survivors (15/77) in the 65 to <75 years, 30.4% (7/23) in >75 years and <85 years, and 100% in the single case >85 years of age. Figure 1 shows the distribution of cases over the study period and also indicates that the number of patients receiving ECPR among the elderly has increased in the recent era.
Comparison Between Survivors and Nonsurvivors
Table 1 shows the comparison of survivors and nonsurvivors among the elderly requiring ECPR. For evaluated variables, no differences existed between survivors and nonsurvivors in demographics, era, increasing age, and pre-ECMO therapies. No differences in pre-ECMO ventilator settings, cardiopulmonary arrests, or infections were noted. Duration of ECMO support did not differ between nonsurvivors and survivors. Among listed comorbidities, only the presence of pre-ECMO acute renal failure was significantly more frequent in nonsurvivors compared with survivors (14 vs. 0; p = 0.04).
There was no significant differences (p = 0.43) in risk of death among elderly patients 65–75 years of age versus those >75 years of age for the duration of time from ECMO to hospital discharge (Figure 2). Similarly, there was no difference in risk of death among the two groups for the duration of ECMO support (p = 0.41; Figure 3).
ECMO Complications and Survival
Table 2 shows the differences in complications occurring while on ECMO support between survivors and nonsurvivors. Nonsurvivors had a significantly higher rate of cardiac tamponade while supported on ECMO compared with survivors. However, there were no significant differences in complication rates among survivors and nonsurvivors. Brain death occurred in 21% of all patients.
Survival to hospital discharge among the elderly supported by ECPR is 22.2%. These numbers are similar to those reported in adult studies, which included younger adults,1 but it appears to be better than those reported (17%) using conventional CPR. The use of ECPR in the elderly has increased in recent years; however, there has not been a substantial increase in survival, despite increasing experience. No specific risk factors could be identified that differentiated survivors from nonsurvivors among the elderly.
The survival to hospital discharge rate for ECPR users reported here is consistent with other reports in adults.1,6–9 Cardarelli et al.6 recently reported a meta-analysis of ECPR 11 observational studies from publications between 1990 and 2007 and identified 135 adults who underwent ECPR. The median age for the group was 56 years. Overall survival to hospital discharge was 40%. Survival was higher (56%) in the 17–40 years age group compared with older adults (>41 years age group; 34%). They report nine survivors (27%) among 33 patients >67 years of age. Thiagarajan et al.1 have reported overall ECPR survival to hospital discharge in all adults at 27%, and the focus of the study was not specifically in the elderly patients. Other investigators have reported variable survival rates among adults with cardiac arrest (32%),7 those with acute myocardial infarction (48%),8 cardiac diagnosis 68%,9 and mixed medical ICU population (24%).10 However, details specific to the elderly patients >65 years of age were not well documented in any of these studies.
Saito et al.11 recently reported their experience with 91 ECMO deployments among adult patients. Their cohort included 12 patients older than 75 years of age supported on ECMO, of which six patients were successfully weaned from ECMO and five survived to discharge. The oldest patient who survived to hospital discharge was 84 years of age. Based on their outcomes, the authors suggest that ECMO should be considered even for elderly patients with refractory cardiogenic shock. However, their report did not include any ECPR cases and therefore is limited in assessing outcomes for this group of patients.
This study is subject to several limitations because data are abstracted in a retrospective manner into the ELSO registry. The primary deficiency of the present study is also the uncontrolled nature and the lack of standardized criteria for the application of ECMO. As a retrospective study of registry data, it is subject to considerable bias, both in reporting and in selection as the reporting is voluntary and the robustness of the data set cannot be verified/adjudicated. Many variables including patient selection, indication for ECMO institution, and ECMO mode are neither included in the ELSO database nor standardized, but rather are center specific. Data coding and entry are performed at each institution, and many fields remain empty at the time of data submission. The preponderance of registry members represents larger volume ECMO centers and bias the results. Additionally, a large percentage of the patients had diagnoses that are rather nonspecific and have been put in the others diagnostic category. In addition, the ELSO database lacks key variables, such as tidal volume, plateau pressures, and delineation of modes of conventional ventilation both before and during the ECMO run. Diagnoses are recorded as the ICD-9 codes, which have well-described shortcomings.
In conclusion, in the present large multicenter database, elderly adults requiring ECPR achieved a 22.2% survival. The favorable ECPR survival rate was also maintained in the very old (≥75 years). These findings suggest that advanced age should not necessarily be a negative factor in the consideration of ECMO in older patients. In general, whether ECPR may be offered in the very old should be decided on a case-by-case basis, which includes evaluation of multiple comorbidities.
Supported in part by PHS grant # (NIH/NIA-1P30AG028718) and the Veterans Healthcare System.
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Keywords:Copyright © 2013 by the American Society for Artificial Internal Organs
ECMO; ECPR; elderly; outcomes