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Extracorporeal Membrane Oxygenation for Respiratory Failure in the Elderly: A Review of the Extracorporeal Life Support Organization Registry

Mendiratta, Priya*; Tang, Xinyu; Collins, Ronnie T. 2nd; Rycus, Peter§; Brogan, Thomas V.; Prodhan, Parthak

doi: 10.1097/MAT.0000000000000090
Adult Circulatory Support

Extracorporeal membrane oxygenation (ECMO) support among adults is increasing; however, the role in respiratory failure in the elderly is not clearly defined. The aim of the current study is to investigate survival to hospital discharge among the elderly supported on ECMO. The Extracorporeal Life Support Organization registry database was queried, identifying all elderly patients (≥65 years of age) supported on ECMO for respiratory failure from 1990 to May 2013. The primary outcome was survival to hospital discharge. Clinical characteristics between survivors and nonsurvivors were compared. A total of 368 elderly patients treated with ECMO support for respiratory failure were identified. The median admit-to-initiation-of-ECMO time was 24.5 hours, and median duration of ECMO was 140 hours. Survival at hospital discharge was 41%. Approximately 69% of the overall ECMO usages occurred from 2010 to 2013. Nonsurvivors had significantly higher pre-ECMO peak inspiratory pressures, lower SaO2/FiO2 ratio, and higher rate of diverse complications. Among pre-ECMO therapies, vasodilators, steroids, and inhaled nitric oxide were more frequently used in survivors. Survival-to-hospital discharge rate is lower (41%) in elderly patients treated with ECMO compared with that in all adults (55%). However, given the noted survival, age should not be a firm contraindication for the use of ECMO in older patients but should be considered on a case-by-case basis.

From the *Department of Geriatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Division of Cardiology, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Arkansas; Divisions of Biostatistics and Critical Care, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Arkansas; §Extracorporeal Life Support Organization, Ann Arbor, Michigan; and Department of Pediatrics, Division of Critical Care, Seattle Children’s Hospital, Seattle, Washington.

Submitted for consideration October 6, 2013; accepted for publication in revised form April 13, 2014.

Disclosure: The authors have no conflicts of interest to report.

Correspondence: Parthak Prodhan, MD, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, AR 72205. Email: prodhanparthak@uams.edu.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass that is used in patients with respiratory and/or cardiac failure refractory to conventional therapies. Despite recent interest in ECMO therapy in adults,1–9 there are limited data on the usage of ECMO in elderly patients (>65 years of age). Saito et al. 10 have reported their experience with ECMO support for cardiac indications in adult patients. Twelve patients older than 75 years were supported with ECMO. Among those patients, six were successfully weaned from ECMO and five survived to hospital discharge. The oldest patient who survived to hospital discharge was 84 years. However, this study did not include elderly with respiratory failure.

Therefore, the current study analyzed data from the international Extracorporeal Life Support Organization’s (ELSO)11 data registry to determine characteristics of elderly patients undergoing ECMO support for respiratory failure.

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Materials and Methods

Patient Population

Data were retrospectively reviewed all patients older than 65 years treated with ECMO support in the ELSO registry between 1990 and May 2013. Only data from the initial ECMO usage were included for subjects who received ECMO support more than once. The requirement for informed consent was waived because of the retrospective nature of the study and the deidentified nature of the data. The study was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences and by the ELSO registry.

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Extracorporeal Life Support Organization Registry

The ELSO registry is a large, multicentered, international database of more than 40,000 patient-cases receiving extracorporeal life support in more than 170 centers.11 Member institutions voluntarily submit deidentified data to the registry including sex, race, nature of illness, technical details of extracorporeal support used, complications, and outcome. Quality assurance reports are issued to active ELSO member institutions on a semi-annual basis. The purpose of the registry is to provide data to the member institutions to improve care. Aggregate data without patient identifiers can be obtained and evaluated by member institutions to support clinical research. Each individual member institution approves data reporting through its local institutional review board.

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Data Variables

Independent variables were grouped before analysis as follows: demographic data, International Classification of Diseases, Ninth Revision diagnosis codes (reviewed independently by two authors: P.P. and T.V.B.) and disagreement resolved after review by a third author (P.M.), pre-ECMO course variables and therapies, ECMO course data, and associated complications while receiving ECMO support. Survival to hospital discharge was the primary end-point of the study.

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Statistical Analysis

All data were analyzed using R v3.0.1 (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were expressed as median (1st quartile, 3rd quartile) for continuous variables and percentile and frequency for categorical variables. The distributions of continuous variables were compared between patients who survived to hospital discharge and those who died with the use of the Mann–Whitney U tests, whereas the proportions of categorical variables were compared using the chi-square test. The duration of ECMO support for each diagnosis group was evaluated using Kaplan–Meier analysis. The patients who died were censored. The log-rank test was performed to compare the survival curves among seven diagnosis groups. p values greater than 0.05 were considered to be statistically significant.

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Results

Study Population

During the study period, 368 elderly patients treated with ECMO support for respiratory failure were recorded in the ELSO registry. Second ECMO usage on 15 patients (10 died before hospital discharge) and two patients with third ECMO deployments (both died before hospital discharge) were excluded from the study. The median age of the cohort was 69 years (interquartile range [IQR]: 66–73 years). The median admit-to-initiation-of-ECMO duration was 24.5 hours (IQR: 4–85 hours), and median duration of ECMO was 140 hours (IQR: 66–240 hours).

Overall, survival at hospital discharge was 41% (151/368). Figure 1 shows the temporal distribution of survivors and nonsurvivors across the study period. There were no significant differences in survival over the various eras during the study period from 1990 to 2013 in 5 years groups (p = 0.71). The number of elderly patients receiving ECMO for respiratory failure increased significantly across the study period with 69% of the ECMO usages occurring from 2010 to 2013.

Figure 1

Figure 1

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Comparison Between Survivors and Nonsurvivors

Table 1 shows the comparison of survivors and nonsurvivors in the study. Nonsurvivors had significantly higher pre-ECMO peak inspiratory pressures (PIPs), lower SaO2/FiO2 ratio and longer time from admit to initiation of ECMO, longer time from intubation to ECMO support, and longer time from discontinuation of ECMO to extubation. Duration of ECMO support did not differ between the two groups. Admission to time of initiation of ECMO support was shorter in survivors compared with that in nonsurvivors (p < 0.001). Among survivors, the median time to discharge was 329 hours (IQR: 104,768). For those on veno-venous (VV) ECMO mode, no significant differences were noted between those with dual-lumen cannula (Avalon) versus those with non-Avalon catheters for in-hospital mortality (54% [33/61] vs. 59% [99/168]; p = 0.51) and duration of ECMO (145 hours [78, 384] vs. 141 hours [66, 240]; p = 0.19). No differences in survival were noted for any of the different cannula types for both VV and veno-arterial (VA) ECMO mode (data not shown). As a marker of duration of pre-ECMO illness, the mortality by quintiles of time from admission to ECMO and time from intubation to ECMO were investigated (Table 2). There was significantly increased mortality for increasing quartiles of time from admission to ECMO support (p = 0.005), whereas no significant differences were noted for in-hospital mortality for increasing quartiles of time from intubation to ECMO (p = 0.09).

Table 1

Table 1

Table 2

Table 2

As shown in Table 3, among pre-ECMO therapies, vasodilators, steroids, and inhaled nitric oxide were more frequently used in survivors. Conversely, intra-aortic balloon pumps (IABP) were more frequently used among nonsurvivors.

Table 3

Table 3

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Complications on ECMO

Table 4 shows the differences in complications occurring during ECMO support between survivors and nonsurvivors. Nonsurvivors had a significantly higher rate of diverse complications. Overall, the median numbers of total complications were also significantly higher in nonsurvivors compared with that in survivors.

Table 4

Table 4

For culture-proven infections, except for a higher frequency of gram-positive infections among nonsurvivors (p = 0.03), there was no difference in infection types or frequencies between survivors and nonsurvivors while on ECMO (Table 5). Similarly, analyzing the data by site of infection (blood stream, urine, respiratory, or other sites) pre-extracorporeallife support urinary fungal infection was the only significantly different infection between survivors and nonsurvivors was (0/151 vs. 6/217; p = 0.04) (data not shown).

Table 5

Table 5

Among nonsurvivors, ECMO was discontinued because of lung recovery in 23% (50/216) of cases but then died subsequently before hospital discharge. Death occurred due to withdrawal of life support in 11% (24/216), hemorrhage in 6% (13/216), a diagnosis incompatible with life in 8% (17/216), and multiorgan failure in 49% (106/216).

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Discussion

ECMO usage in elderly patients has increased substantially in recent years. A survival-to-hospital discharge rate of 41% makes a strong argument to consider ECMO for respiratory failure in the elderly on a case-by-case basis.

A shorter time from admission to the initiation of ECMO support was associated strongly with improved survival to hospital discharge in the current study. Although not as strongly associated, those patients with a shorter time from intubation to the initiation of ECMO support also had improved survival. These data indicate that the initiation of ECMO support in elderly patients with respiratory failure should be considered and undertaken early in the clinical course. Other investigators have reported a similar relation between the number of mechanical ventilation days before the initiation of ECMO and survival in adult12,13 and pediatric14 groups. In a small, retrospective study of 36 adults with respiratory failure, Pranikoff et al. 12 found that survival was inversely correlated with the number of days of mechanical ventilation before ECMO. In that study, the predicted mortality rate was 50% after 5 days of mechanical ventilation. One plausible reason for these findings is that the longer duration of potential ventilator-induced lung injury before the initiation of ECMO, and the concomitant impact of organ dysfunction, may affect survival while on ECMO support. Notably, in the current cohort, the median PIPs were higher in the nonsurvivors compared with survivors before ECMO initiation, giving credence to the possibility that lung injury plays a role in the difference in survival. Unfortunately, the limitations of the ELSO registry data preclude further analysis on this finding.

Resurgence in the usage of ECMO for adults has been noted since the publication of the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, a multicenter randomized trial reported in 2009.1 In 180 subjects enrolled into the CESAR trial, the 6 months of disability-free survival was higher in the ECMO group compared with that in patients treated with conventional mechanical ventilation. The interest in the use of ECMO in adults for the treatment of refractory respiratory failure was increased as a result of successful use during the H1N1 influenza epidemic in 2009–2010.2–9 Zangrillo et al. 15 reported on 266 adult patients (representing 19.6% of overall study cohort) treated with ECMO during the H1N1 epidemic secondary to respiratory failure due to confirmed or suspected H1N1 infection. In that study, the median age was 36 years, indicating that the large majority of patients were young adults and ECMO was not offered to elderly adults. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on patient baseline features. Random-effect pooled estimates, although limited by underlying heterogeneity, suggested an overall in-hospital mortality of 27.5% (95% confidence interval: 18.4–36.7%). Overall survival figures reported by the ELSO registry for adults and older children with respiratory failure is 55% and 56%, respectively.16 Comparative survival-to-hospital-discharge rate (41%) among elderly patients is lower. Furthermore, many institutions currently use arbitrarily selected age thresholds for ECMO use, which precludes many elderly with respiratory failure and minimal comorbidities from receiving ECMO support. In light of this evidence, there is reasonable justification in offering ECMO support to the elderly on a case-by-case basis.

On the basis of clinical parameters, elderly requiring ECMO support in our view would fall in three major overlapping categories—first, the healthy elderly without any major pre-ECMO comorbidities/organ dysfunction, the second where there is significant comorbidities where most ECMO practitioners would clearly not offer ECMO support, and the third middle gray area where there are some comorbidities/organ failure. Although not having information about comorbidities/organ failure, based on our data, we can speculate that given the reasonable survival to hospital data, the first group could be considered as reasonable candidates for offering ECMO support as it is likely that a majority of the survivors would come from this group. The main issue in the decision-making process for an ECMO practitioner considering ECMO support in the elderly is what to do for the middle third group—the gray-zone patients where the case for ECMO support would most likely be made on a case-by-case basis.

Survivors received noninvasive medical therapies including vasodilators, steroids, and inhaled nitric oxide before ECMO initiation more frequently than nonsurvivors. In contrast, nonsurvivors were more likely to receive invasive cardiac support in the form of an IABP. It can be speculated that the use of these therapies may be an indicator of how aggressively patients were managed in the pre-ECMO deployment period. It is also possible that the use of vasodilators, both systemic and pulmonary, might have enhanced perfusion and thus help mitigate end-organ damage. The need for IABP could signify concomitant cardiac dysfunction which would add to the morbidity among these patients. Furthermore, despite no differences in duration of ECMO, nonsurvivors suffered more complications while on ECMO support compared with survivors.

Complications on ECMO occurred more frequently among nonsurvivors compared with survivors. Our results also indicate that nonsurvivors were more likely to have hemorrhagic complications (cannulation site, pulmonary hemorrhage, disseminated intravascular coagulation, excessive hemolysis while on ECMO support). Nonsurvivors remained more frequently on inotropes while on ECMO were more likely to have positive culture infection, central nervous system hemorrhage, metabolic issues (low or high glucose, metabolic acidosis), and renal dysfunction. Similar results have been reported in prior studies in adults supported on ECMO.17

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Study Limitations

This study is limited by the retrospective design and the nature of the ELSO registry. The study is uncontrolled and there is a lack of standardized criteria for the application of ECMO at individual centers. Reporting to the ELSO registry is voluntary and the reliability of the dataset cannot be verified/adjudicated. Variables such as patient selection and indication for ECMO initiation 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. In addition, a large percentage of the patients had diagnoses that were nonspecific and have been put in the “others” diagnosis category.

In conclusion, in the current large multicenter database, for elderly adults receiving ECMO support for respiratory indications, the survival to hospital discharge rate is 41%. Even though the use of ECMO in the elderly has increased substantially in recent years, most were excluded during the 2009–2010 H1N1 epidemic. These results make a strong argument that advanced age should not necessarily be a negative factor in consideration of ECMO in older patients. Given the lack of comorbidity data, this study remains a starting point for future investigations and discussions as there definitely would be many who would be good candidates for ECMO among the elderly as well. In general, whether ECMO may be offered in the very old, it should be decided on a case-by-case basis, which includes evaluation of multiple comorbidities.

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References

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2. Chan KK, Lee KL, Lam PK, Law KI, Joynt GM, Yan WW. Hong Kong’s experience on the use of extracorporeal membrane oxygenation for the treatment of influenza A (H1N1). Hong Kong Med J. 2010;16:447–454
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Keywords:

extracorporeal membrane oxygenation; acute respiratory failure; elderly

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