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Respiratory Support

Prolonged Duration ECMO for ARDS

Futility, Native Lung Recovery, or Transplantation?

Rosenberg, Andrew A.*; Haft, Jonathan W.; Bartlett, Robert; Iwashyna, Theodore J.§; Huang, Steven K.§; Lynch, William R.; Napolitano, Lena M.*

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doi: 10.1097/MAT.0b013e3182a9e341
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The Berlin definition of acute respiratory distress syndrome (ARDS) stratifies severity into mild, moderate, and severe ARDS, with associated mortality rates of 20%, 41%, and 52%, respectively.1

Extracorporeal membrane oxygenation (ECMO) is recommended as a treatment strategy for severe ARDS [PaO2/FiO2 ≤ 100 mm Hg with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O] when other rescue strategies fail (Figure 1).2–4 Significant advances in ECMO allow short-term support for those with acute, reversible respiratory failure and as a bridge to transplantation in those with irreversible respiratory failure.5

Figure 1:
Treatment strategies recommended for ARDS by Berlin definition of ARDS. Mild ARDS: 200 mm Hg < PaO2/FiO2 ≤ 300 mm Hg with PEEP or CPAP ≥ 5 cm H2O; Moderate ARDS: 100 mm Hg < PaO2/FiO2 ≤ 200 mm Hg with PEEP or CPAP ≥ 5 cm H2O; Severe ARDS: PaO2/FiO2 ≤ 100 mm Hg with PEEP ≥ 5 cm H2O. ARDS, acute respiratory distress syndrome; ECCO2R, extracorporeal CO2 removal; ECMO, extracorporeal membrane oxygenation; HFO, high-frequency oscillatory ventilation; iNO, inhaled nitric oxide; NIV, noninvasive ventilation; PEEP, positive end-expiratory pressure.

Median duration of ECMO in adult severe ARDS patients is 7–10 days in most publications. In a retrospective Extracorporeal Life Support Organization (ELSO) registry study of adult respiratory failure patients requiring ECMO from 1986 to 2006 (n = 1,473), 50% survived to discharge. Duration of ECMO support did not differ between nonsurvivors (median, 133 hours; interquartile range, 50–286) and survivors (median, 150 hours; interquartile range, 81–249; p = 0.09).6

In a more recent observational study of severe ARDS patients (n = 124) over 14 years (1997–2011) from a Scandinavian ECMO center, median age was 45 (range 16–67) years and median Murray score was 3.7 (2.5–4.0). The median duration of ECMO was 215 (1–578) hours, and 88 (71%) patients were discharged alive to the referring hospitals.7

We report the clinical course of an adult patient who required prolonged duration venovenous (VV)-ECMO for severe ARDS with eventual native lung recovery as she was being evaluated for bridge to lung transplantation. This case challenges our current paradigm of consideration of futility because of irreversible lung failure at 2–4 weeks’ duration of VV-ECMO and questions the specific time at which we should consider that there is no likelihood of native lung recovery.

Case Report

A 36-year-old woman with no chronic medical comorbidities presented with a 2-week history of diffuse sharp back and chest pain, and severe dyspnea. She had a distant history of optic neuritis and pelvic abscess. Her symptoms included a dry cough, rigors, and fever reaching 103°F. She developed progressive hypoxemia requiring 70–90% high-flow face-mask oxygen. Empiric broad-spectrum intravenous antibiotics were initiated for presumed community-acquired pneumonia, with steroids. Chest computed tomography (CT) revealed multifocal consolidation and subpleural thickening indicative of inflammatory lung disease. She developed acute respiratory failure requiring intubation and mechanical ventilation. Echocardiogram revealed left ventricular hypertrophy, with ejection fraction 70%. Open right lung biopsy confirmed chronic interstitial pneumonia characterized by both fibrosis and peribronchiolar metaplasia. No pathogenic organism was identified on biopsy or cultures. She developed worsening hypoxemia/hypercarbia, despite advanced mechanical ventilation with increased PEEP, increased mean airway pressures, and inhaled nitric oxide.

The patient’s family provided informed consent for VV-ECMO. Attempted right internal jugular cannula placement was unsuccessful. Bilateral femoral vein single-lumen cannulae were placed (Figure 2; ECMO settings sweep 1, flow 2.3 L/min, 2,400 RPM). Her clinical course is summarized in Figure 3.

Figure 2:
Chest radiographs pre- and postinitiation of venovenous (VV)-extracorporeal membrane oxygenation (ECMO). A: Initial chest x-ray on transfer, patient not intubated with high FiO2 by face mask. B: Chest x-ray before ECMO cannulation. C: Bilateral femoral cannulation for VV-ECMO. Left femoral vein: 24 Fr Avalon single-lumen cannula in right atrium; right femoral vein 23 Fr Medtronic single-lumen cannula in distal inferior vena cava..
Figure 3:
Patient clinical course. ECMO, extracorporeal membrane oxygenation; VV, venovenous.

The patient demonstrated no functional native lung recovery after 2 weeks of ECMO. She was weaned to pressure support ventilation with minimal tidal volumes but was awake and alert. At 4 weeks duration of VV-ECMO, we had family/patient discussions regarding futility. They desired all aggressive care, given her young age and lack of preexisting chronic diseases. We discussed possible lung transplantation with the multidisciplinary lung transplant group, and they recommended aggressive reconditioning to be considered for transplantation.

To facilitate aggressive reconditioning and mobility for possible lung transplantation, the patient was recannulated via the right internal jugular vein with an Avalon bicaval dual-lumen cannula (Figure 4 on ECMO day 31; ECMO settings sweep 2, flow 2.9 L/min, 3,350 RPM). Ventilator settings with bifemoral VV-ECMO were pressure support 22, PEEP 5, FiO2 0.6 with arterial blood gas (ABG) 7.43, pCO2 77, PaO2 52, oxygen saturation 83% documenting significant recirculation compared with postprocedure settings of pressure support 20, PEEP 5, FiO2 0.5 with ABG 7.44, pCO2 63, PaO2 74, saturation 93%, documenting the significant benefit of reduced recirculation with the bicaval cannula.

Figure 4:
Transition from bilateral femoral extracorporeal membrane oxygenation (ECMO) cannulation to right internal jugular 27 Fr Avalon Bicaval dual-lumen venovenous-ECMO cannula placement. Severe acute respiratory distress syndrome still present.

An aggressive reconditioning regimen was implemented, which resulted in ambulation. The patient’s SpO2 and spontaneous tidal volumes increased, suggesting some recovery of native lung function (Table 1). She was successfully weaned from VV-ECMO and was decannulated (total VV-ECMO duration 5/12–7/8, 56.13 days). Her ECMO course was complicated by multiple episodes of Pseudomonas aeruginosa pneumonia and bacteremia, vancomycin-resistant enterococcus bacteremia, and bleeding requiring aminocaproic acid continuous infusion.

Table 1:
Changes in Oxygenation and Ventilation at Specific Timepoints in Patient’s Recovery Course

The patient’s native lung function continued to improve, and she was successfully weaned from mechanical ventilation (cumulative ventilator days 5/2–8/3, total 84 days). She was transferred from the surgical intensive care unit (SICU) to inpatient rehabilitation (August 17, 2012, to September 6, 2012), which culminated in her becoming independent in all activities of daily life except tub transfer and gait/walking. She was ambulating unassisted, and her tracheostomy was downsized to 6.

Twenty days after discharge from the SICU, the patient was discharged home with supplemental oxygen by tracheostomy mask. At the time of discharge, she could walk 100 feet in 6 minutes. On follow-up, bronchoalveolar lavage cultures were negative and chest x-ray showed low lung volumes with diffuse interstitial and patchy parenchymal opacities, suggesting sequelae of ARDS (Figure 5).

Figure 5:
Chest x-ray on first follow-up after hospital discharge. Low lung volumes with diffuse interstitial and patchy parenchymal opacities suggesting sequelae of acute respiratory distress syndrome (ARDS).

The patient enrolled in pulmonary rehabilitation, which was successfully completed. Follow-up chest CT (Figure 6) and pulmonary function tests (Table 2) confirmed a severe restrictive defect but with significant improvement in her native lung function. Her tracheostomy was removed on December 26, 2012, and at present, she requires supplemental oxygen only with significant exertion. Her current oxygen saturation on room air at rest is 94% compared with SpO2 80% on room air 2 months earlier. She can accomplish a 6 minute walk for 392 feet, increased from 100 feet 2 months earlier, with 6 L nasal cannula supplemental oxygen without hypoxemia. She has returned to work full-time, ambulates without assistance, and drives independently.

Table 2:
Pulmonary Function Tests at Specific Timepoints in Patient’s Recovery Course
Figure 6:
Follow-up chest computed tomography (CT) scan imaging documenting native lung structural recovery. Chest CT December 20, 2012: decreased cystic changes, persistent diffuse parenchymal abnormality, likely residua of previous acute respiratory distress syndrome (ARDS), areas of traction bronchiectasis.


This case highlights the significant challenges in the determination of whether native lung recovery will occur in patients requiring VV-ECMO for severe ARDS. We had planned to bridge this ARDS patient who required prolonged ECMO to lung transplantation, but with aggressive reconditioning and ambulation in preparation for transplant consideration, she manifested native lung recovery.

It has previously been reported that the type (hemorrhagic, neurologic, renal, pulmonary, cardiac) and number of complications during ECMO for ARDS were associated with decreased survival. Gastrointestinal or pulmonary hemorrhage and the need for renal replacement therapy were all associated with significantly increased risk of death.8 However, these complications are much less common with the use of more advanced and less thrombogenic ECMO cannulae and circuits,9 and it is not known whether this association is still true. This patient did have significant bleeding complications during her prolonged ECMO course but was successfully managed off heparin with antifibrinolytic therapy when bleeding complications occurred.

Two issues must be considered in patients requiring prolonged ECMO for ARDS: 1) whether care is futile, and 2) whether to bridge to lung transplantation. We also believe that it is of paramount importance to initiate an early mobility protocol, including ambulation, in an effort to promote native lung recovery and resolution of acute respiratory failure in patients receiving ECMO for ARDS.


Determination of futility with ECMO treatment for ARDS is a controversial issue.10 The ELSO ECMO guidelines recommend consideration of futility at 2 weeks duration of ECMO if no native lung function is present, and the patient is not a transplant candidate. The ELSO guidelines also state that fixed pulmonary hypertension in a patient with respiratory failure after several weeks of support on VV-ECMO may also be an indication of futility or at least an indication to convert to venoarterial access from VV access.11 This patient did have transient pulmonary hypertension (Table 3), which ultimately resolved as her native lung function recovered.

Table 3:
Transthoracic Echocardiogram Testing at Specific Timepoints in Patient’s Recovery Course

However, published reports describe the use of prolonged duration ECMO with patient survival. A report of two patients who required VV-ECMO (45, 52 days) for the treatment of severe hypoxemia as a result of H1N1 pneumonia complicated by invasive Aspergillosis resulted in full recovery.12 A report of successful treatment of an adult ARDS after drowning by prolonged (117 days) ECMO support confirmed complete recovery.13

Should prolonged need for ECMO support indicate futility with regard to native lung recovery? A single institution retrospective analysis of 127 patients compared three groups based on ECMO duration [0–10 days (group A, n = 76, mean duration 6 ± 2.5 days), 11–20 days (group B, n = 32, mean duration 14 ± 2.2 days), and >21 days (group C, n = 19, mean duration 29 ± 10 days)]. No differences in demographics or clinical characteristics were identified. Overall survival to discharge was 51.2%. There was a statistically significant difference in survival between groups (A = 59%, B = 31%, C = 52%; p = 0.029), but survival was not different between ECMO runs 0–10 vs. >21 days. Interestingly, the outcome after long ECMO runs was comparable with short ECMO runs, despite a longer mechanical ventilation period before ECMO initiation in group C. Multivariate logistic regression analysis revealed renal failure [odds ratio (OR), 12.1; confidence interval (CI), 3.9–30.0; p < 0.001] and inhaled nitric oxide (OR, 5.8; CI, 1.9–24.9; p = 0.002) as risk factors for mortality. Prolonged ECMO support was not an independent risk factor for increased mortality.14

A single-center study examined all children ≤18 years supported with ECMO for ≥28 days (January 1991–September 2011) at the Arkansas Children’s Hospital. Nine hundred fifty-one patients were supported with ECMO with a 30 day survival of 68%. Only 22 ECMO runs were ≥28 days, and the longest ECMO run was 1,206 hours (50 days). The average ECMO duration in this cohort was 855 ± 133 hours, with a mean intensive care unit (ICU) length of stay of 56 ± 27 days. Ten patients (45%) were successfully decannulated; six (27%) were alive 30 days after decannulation, and only four (19%) survived to hospital discharge, and all three survivors have chronic lung disease. This case series concluded that prolonged ECMO use in children with refractory cardiac or respiratory failure was associated with low survival.15

A multicenter cohort study of the Pediatric ECMO Registry for acute respiratory failure of ELSO also examined the relationship between duration of ECMO and outcome. Of 382 ECMO patients, 184 (48%) survived. The proportional survival in the patients treated for the longest duration was similar to the overall group. The cause of death was given for 168 patients: 32 neurologic; nine ECMO complications; and 30 nonpulmonary organ failure. There were 97 deaths due to elective ECMO termination; 80 occurred after the determination of futility and lack of native lung recovery. The latter deaths occurred at widely varying ECMO durations, with a median of 282 hours. However, at that same duration, 47 eventual survivors (26% of all survivors) continued on ECMO. By discriminant analysis, the survival rate was independently related (r2 = 0.18; p < 0.0001) to peak ventilator inspiratory pressure before ECMO and duration of intubation before ECMO, patient age, and the occurrence of several complications. The survival rate in patients treated with ECMO courses of >2 weeks was similar to the patients treated for shorter time. Extracorporeal membrane oxygenation was terminated in some patients for pulmonary futility at durations of ECMO associated with survival in substantial numbers of patients in whom ECMO was continued.16

These observational data suggest that ECMO duration should not be used as a sole criterion to declare futility for a patient in single-organ system respiratory failure on VV-ECMO for ARDS. Indeed, most existing data are likely confounded by severe problems of self-fulfilling prophecies about futility—after all, patients deemed to be futile are removed from ECMO.

Are there any diagnostic tests available to us to determine the likelihood of native lung recovery? Are there any therapeutic adjuncts to hasten native lung recovery? The answers to these questions are unknown at present, but it may be that the trajectory of native lung recovery is not uniform in all ARDS patients, just as in acute kidney injury, with documented differential recovery rates to native renal function. Furthermore, as in other areas such as prognosis for neurologic recovery after therapeutic temperature management for cardiac arrest or after intracranial hemorrhage, we are not simply condemned to speculate—organized data collection can bring informed evidence to bear on the problem.

At present, we are unable to predict survival for ECMO patients using the usual risk factors. We previously reported, in a cohort of 255 adult severe ARDS patients requiring ECMO, that multivariate analysis identified age, gender, pre-ECLS pH ≤7.10, pre-ECLS PaO2/FiO2 ratio, and pre-ECLS ventilator days all to be significant independent variables influencing outcome, with a logit equation to calculate the probability of fatal outcome based on these pre-ECLS variables:

function = [0.18 x (pre-ECLS ventilator days)] + [0.027 x (age)] – [0.021 x (P/F ratio)] + [2.13 x (pre-ECLS pH category)] – [0.54 x (gender category)] – 0.45(P/F ratio = PaO2/FiO2 ratio; pre-ECLS pH category = 0 if pre-ECLS pH > 7.1 or 1 if pre-ECLS pH ≤ 7.1; gender category = 0 if female or 1 if male)

The probability of fatal outcome based on pre-ECLS variables using the equation above was 80.54%. But she survived.

This suggests that not only pre-ECLS variables should be considered when discussing futility of ECMO support in severe ARDS adult patients. Following 4 weeks of ECMO support in this patient, we noted that her native lung oxygenation and ventilation slowly improved as evidenced by improving P/F ratio and oxygenation index and improved minute ventilation at lower plateau pressures (Table 1), which prompted us to continue ECMO support. Future studies must examine the utility of changes in these respiratory parameters in predicting ECMO outcome in severe ARDS. Pre-ECLS variables may not be as important in predicting outcome as the change in respiratory variables over time during ECLS treatment, and we are exploring our institutional data to examine this hypothesis further.

Bridge to Lung Transplantation

There has been increasing use of ECMO as a bridge to lung transplantation; however, chronic lung disease, particularly pulmonary fibrosis, is the most common indication not ARDS.17–21 Published case studies have described successful lung transplants for chronic lung disease after prolonged duration ECMO runs ranging from 24 to 67 days.22

Successful reports of bridging adult ARDS patients to lung transplantation with prolonged ECMO have confirmed full recovery after transplantation.23–26 The longest reported duration of ECMO was 107 days in an ARDS patient (24 year-old male trauma patient) with bridge to bilateral lung transplantation. He survived for 351 days post-transplantation and died from P. aeruginosa pneumonia.27

We believe that it is important to establish clinical guidelines and algorithms regarding diagnostic workup, suitability, and timing for consideration of lung transplantation in adult patients with ARDS who require prolonged ECMO to assist practitioners in these challenging decisions.

Early Transition to Single-Lumen ECMO Cannulation for Increased Mobility

Recent studies document that early mobility is associated with improved outcomes in acute respiratory failure.28–32 urrent advances in ECMO support, with smaller size systems and single cannula access, now allow early mobility and ambulation in adult ARDS patients who require ECMO.33

Single-vessel access with a bicaval dual-lumen VV-ECMO cannula offers sufficient gas exchange in addition to advantages over two-vessel standard cannulation, including early mobility with ambulation and significantly improved reconditioning, which may have positive effects on native lung recovery.34,35 This strategy avoids the significant deconditioning and ICU-acquired weakness that occurs in bedridden ECMO patients who require femoral venous cannulation.

In a report of 10 patients treated with ambulatory VV-ECMO, the mean ECMO duration was 20 (9–59) days. Six of 10 patients were weaned from respiratory support (n = 4) or underwent transplantation (n = 2) and survived to discharge from the hospital. The remaining four patients died of sepsis (n = 3) and withdrawal of care after renal failure (n = 1).36

If a single bicaval dual-lumen cannula is not able to be placed with initial ECMO cannulation, then we recommend transitioning to single cannula ECMO support as soon as possible to allow early mobility, reconditioning and ambulation, reduce recirculation, and facilitate native lung recovery.

We continue to have a discussion with the patient/family at 4 weeks duration of ECMO regarding possible futility. If the patient is still in single-organ system (respiratory) failure at that time, and the patient/family desire all ongoing critical care, then we continue to re-evaluate while trying to recruit native lung function, including prone positioning, recruitment maneuvers, increased PEEP and mean airway pressure, bronchoscopy for secretion clearance, and CT scan thorax to evaluate for other potential treatable etiologies of persistent hypoxemia and hypercarbia (i.e., anterior pneumothorax, hemothorax).


Prolonged ECMO duration may be more common in the future, as current recommendations are that patients with severe ARDS (PaO2/FiO2 ratio < 100) but potentially reversible lung conditions be transferred to ECMO-capable institutions. This case demonstrates unexpected native lung recovery as the patient was undergoing preparation for possible lung transplantation. The lung may have unexpected regenerative capacity with native lung recovery after prolonged mechanical support, similar to acute kidney injury and native renal recovery. We recommend redefining irreversible lung injury and futility in ECMO in the context of an organized evidence-based data collection.


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extracorporeal membrane oxygenation; acute respiratory distress syndrome; futility; prolonged; lung transplantation; lung recovery

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