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.
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.
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).
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).
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
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.
1. Peek GJ, Mugford M, Tiruvoipati R, et al.CESAR Trial Collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation
for severe adult respiratory failure (CESAR): A multicentre randomised controlled trial. Lancet. 2009;374:1351–1363
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
3. Davies A, Jones D, Bailey M, et al. Extracorporeal membrane oxygenation
for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA. 2009;302:1888–1895
4. Forrest P, Ratchford J, Burns B, et al. Retrieval of critically ill adults using extracorporeal membrane oxygenation
: An Australian experience. Intensive Care Med. 2011;37:824–830
5. Freed DH, Henzler D, White CW, et al.Canadian Critical Care Trials Group. Extracorporeal lung support for patients who had severe respiratory failure secondary to influenza A (H1N1) 2009 infection in Canada. Can J Anaesth. 2010;57:240–247
6. Turner DA, Rehder KJ, Peterson-Carmichael SL, et al. Extracorporeal membrane oxygenation
for severe refractory respiratory failure secondary to 2009 H1N1 influenza A. Respir Care. 2011;56:941–946
7. Forrest P, Ratchford J, Burns B, et al. Retrieval of critically ill adults using extracorporeal membrane oxygenation
: An Australian experience. Intensive Care Med. 2011;37:824–830
8. Patroniti N, Zangrillo A, Pappalardo F, et al. The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: Preparation for severe respiratory emergency outbreaks. Intensive Care Med. 2011;37:1447–1457
9. Pham T, Combes A, Rozé H, et al.REVA Research Network. Extracorporeal membrane oxygenation
for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2013;187:276–285
10. Saito S, Nakatani T, Kobayashi J, et al. Is extracorporeal life support contraindicated in elderly
patients? Ann Thorac Surg. 2007;83:140–145
12. Pranikoff T, Hirschl RB, Steimle CN, Anderson HL 3rd, Bartlett RH. Mortality is directly related to the duration of mechanical ventilation before the initiation of extracorporeal life support for severe respiratory failure. Crit Care Med. 1997;25:28–32
13. Mendiratta P, Wei JY, Gomez A, et al. Cardiopulmonary resuscitation requiring extracorporeal membrane oxygenation
in the elderly
: A review of the Extracorporeal Life Support Organization registry. ASAIO J. 2013;59:211–215
14. Domico MB, Ridout DA, Bronicki R, et al. The impact of mechanical ventilation time before initiation of extracorporeal life support on survival in pediatric respiratory failure: A review of the Extracorporeal Life Support Registry. Pediatr Crit Care Med. 2012;13:16–21
15. Zangrillo A, Biondi-Zoccai G, Landoni G, et al. Extracorporeal membrane oxygenation
(ECMO) in patients with H1N1 influenza infection: A systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care. 2013;17:R30
17. Brogan TV, Thiagarajan RR, Rycus PT, Bartlett RH, Bratton SL. Extracorporeal membrane oxygenation
in adults with severe respiratory failure: A multi-center database. Intensive Care Med. 2009;35:2105–2114
Keywords:Copyright © 2014 by the American Society for Artificial Internal Organs
extracorporeal membrane oxygenation; acute respiratory failure; elderly