Get Fit for Lung Transplant With Ambulatory Extracorporeal Membrane Oxygenation!

Organ allocation for lung transplant is currently determined by severity of disease and predicted post-transplant survival.¹ Unfortunately, due to a shortage of organs, some lung transplant candidates become so critically ill that they require invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) while on the waiting list. Management of these patients is a major clinical, economic, and ethical challenge. In fact, although severity of disease calls for prioritization, the post-transplant benefit for this subgroup of recipients has traditionally been poor, with potential waste of organs.^2–4

Pathophysiology of critical illness suggests that several factors can be modified in the management of the bridge phase to reduce risks of lung transplant candidates who significantly deteriorate. Use of minimal sedation, avoidance of intubation, and early delivery of physical and occupational therapy diminish the incidence of delirium, ventilator-associated pneumonia, diaphragm dysfunction, and neuromuscular deconditioning and can thus improve outcome.^5,6 If this is valid also for the most fragile lung transplant candidates, then maintaining them awake, spontaneously breathing, and actively performing some physical therapy, even when they require the ICU, will probably be of benefit.

Growing evidence suggests that ECMO with minimal (if any) sedation and no intubation should be preferred over traditional mechanical ventilation for bridging critically ill patients to lung transplant.⁷ Active rehabilitation during awake ECMO should probably be the next step.⁸

Rehder et al⁹ previously reported in Respiratory Care their initial positive experience with ambulatory ECMO as a bridge to lung transplant. They reviewed the medical records of 9 consecutive subjects treated with veno-venous ECMO before surgery. The first 4 subjects were deeply sedated and mechanically ventilated; they did not perform active rehabilitation. The following 5 subjects were kept awake, with or without ventilator support; they actively exercised with the aim of standing and walking as soon as possible, while receiving ECMO. Of note, some of these subjects were considered appropriate candidates for lung transplant only after a few days of active rehabilitation.⁸ All 9 subjects finally underwent lung transplantation, and 1-y survival was 100% in both groups. Ambulatory, compared with non-ambulatory, ECMO was associated with longer pre-transplant stay in the ICU (because listing was delayed until subjects could stand and walk) but shorter post-transplant stay in the ICU and in the hospital. As a result, the mean total (before and after transplant) stay in the ICU fell from 49 to 27 d (P = .01), and hospital stay fell from 98 to 49 d (P = .01).⁹ In the current issue of Respiratory Care, Bain et al¹⁰ compare the costs of treatment between those same 2 subgroups of subjects. Ambulatory ECMO was associated with nonsignificantly higher median pre-transplant costs ($88,137 vs $52,124, P = .08) but significantly lower post-transplant costs ($38,468 vs $143,407, P = .01). The individual cost of total (before and after transplant) hospital stay diminished by approximately $60,000. In other terms, clinical and economic benefits of active rehabilitation largely exceeded the increased pre-transplant resource utilization. This conclusion is rather convincing even if the study is very small, single-center, and retrospective.

Along with these benefits, awake and ambulatory ECMO carries some risks, especially if treatment is prolonged.^7,11 Some patients require urgent intubation because of worsening respiratory failure, ineffective clearance of secretions, dyspnea, and anxiety. Others suffer from major bleeding or develop sepsis and multi-organ failure and are finally delisted. Fatal decannulation is possible. For all of these reasons, implementation of awake and ambulatory ECMO requires a substantial commitment of personnel,⁹ expertise, and experience.

The complexity of the dynamic interaction between artificial (ECMO) and native (patient) lungs in clearing whole-body carbon dioxide (CO₂) production deserves one final comment. Almost 40 y ago, Kolobow et al¹² reported that in healthy and spontaneously breathing sheep, increasing artificial lung ventilation (sweep gas flow) and extracorporeal CO₂ removal resulted in a proportional decrease in native lung ventilation (spontaneous breathing frequency and tidal volume), down to apnea. As a result, arterial pH and CO₂ remained unchanged.¹² These findings were recently replicated in sheep with or without ARDS¹³ and in humans with COPD.¹⁴ Our own preliminary observations suggest that patients with end-stage pulmonary disease (awaiting lung transplant) do the same. By contrast, those with severe ARDS can respond in a less predictable manner, with some of them breathing too fast and/or too hard even when sweep gas flow is very high. Nonetheless, as a general rule, excessive extracorporeal support causes hypoventilation and reduced clearance of secretions, with secondary pulmonary atelectasis, hypoxemia, and, eventually, right heart dysfunction. Insufficient extracorporeal support produces respiratory distress, additional lung injury, systemic overinflammation, and muscular exhaustion.

In conclusion, muscle strength is a major determinant of lung transplant outcome;¹⁵ therefore, lung transplant candidates, even those who are critically ill, should “get fit” for it. Ambulatory ECMO can turn the bridge period from a risky waiting time into an opportunity to actively rehabilitate, for achieving the best outcome (and saving some money).

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