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Two Important Advances in Treatment of Respiratory Failure


Marcelo Cypel
Marcelo Cypel

Because Canada has a low rate of organ donation, and because 80% of the 200 lungs that are offered by donors each year are unsuitable for transplantation, the waiting list is continuing to lengthen. There are currently 80-100 patients on the waiting list, and 20-30 waiting patients die each year. As the population ages, more and more patients are being listed. "The challenge is not only how to increase the supply, but also how to keep the waiting patients alive, using artificial lung technology." Marcelo Cypel is attacking both problems.

Marcelo is Assistant Professor of Surgery in the Division of Thoracic Surgery and a Scientist in the Toronto General Research Institute (http://www.surgicalspotlight. ca/Article.aspx?ver=Fall_2011&f=NewStaff ). His wife Tatiana is a plastic surgeon who completed a Master’s Degree and a fellowship at the Hospital for Sick Children with Chris Forrest. Their 14 month old daughter is Rafaela. Marcelo is an enthusiastic athlete. He tries to run 3-4 times per week and plays soccer when time allows.

Ex vivo diagram
Ex vivo system

His outstanding work with Shaf Keshavjee on ex-vivo perfusion is rehabilitating lungs that are judged to be unsuitable by conventional criteria. Lungs are shipped to Toronto to be treated in the ex-vivo system (See figure 1). "We try to protect and preserve the lung, using normothermic perfusion, gene transfection, antibiotics, and anti-inflammatory agents to allow the lung to begin to repair itself. The ex-vivo perfusion circuit is particularly effective in reversing neurogenic pulmonary edema. It allows the lung to dry out and for repair of the cell tight junctions as extra-vascular water is removed." This work has earned Marcelo multiple honours as a trainee for basic science papers, oral presentations, including the McMurrich Award and the Zane Cohen Clinical Fellowship Achievement Award.

"An important area for rehabilitation of the lung is control of infection. We can clean them up, as the antibiotics have a long half life. There is no liver or kidney in the circuit to remove the antibiotics. Nevertheless, the inflammatory cells and consolidation persist as an ongoing research challenge. An effective source of rehabilitated lungs is the organs that are assessed at a distant site as suboptimal (e.g. because of infection or poor oxygenation). In the past, we would say we should not subject our recipients to lungs of questionable quality. Currently, we are reassessing these lungs, so they are brought in for perfusion. If 4-6 hours of good function can be demonstrated on the circuit, the lungs are used." "Donation after cardiac death (DCD) now accounts for 25% of lung transplants. This number has been increasing 5-10% each year. 90% of centers don’t use the DCD lungs, but the Toronto group has successfully adopted this approach. The ex-vivo perfusion system has provided an objective way to assess these organs and today DCD lung transplantation is routine at our centre. DCD is generally accepted in North America; however, only 2% of those end up donating lungs in the United States, whereas in Toronto at least 30% of DCD lungs are used for transplantation.


"The use of the Novalung as a bridge to transplant triggered Toronto General Hospital interest in further developing an Extracorporeal Lung Support Program (ECLSP). Advances in equipment and technique have contributed significantly to its usefulness. For example, avoiding cannulation of the femoral vessels allows the patients to be mobilized, reducing deconditioning and associated morbidity. The single cannula double lumen veno- venous Avalon light system can be used as a bridge to transplant or as a rescue method for overwhelming ARDS. Approximately 20 ARDS patients are rescued by this technique each year. The double lumen cannula can be inserted in the intensive care unit under fluoroscopy. The cannula is introduced through the jugular vein. Venous blood is returned to the oxygenator from the superior and inferior vena cava, with outflow to the patient from the second lumen, just above the tricuspid valve. Patients can be mobilized, eat, converse and avoid the deconditioning that has been the bane of patients with respiratory failure. In the past, patients who were dependent on the ventilator prior to transplantation often required several months of further ventilation after transplantation - not because of lung failure, but because of deconditioning. The membrane oxygenators used are more commonly the Quadrox and sometimes the Novalung. Neither requires high levels of anticoagulation."

The ECLS team is organized in three units that report to Shaf Keshavjee: Surgery- directed by Marcelo Cypel; Intensive Care by Eddy Fan; and Perfusion by Cyril Serrick. "The clear well - defined and coordinated protocols and systems of management rest the lung and eliminate idiosyncratic management. The ECLS program includes 36 professionals, surgeons, intensivists and perfusionists. "We are now much better prepared (better equipment, well trained staff, protocolized treatment) in the event of future H1N1 type endemic crisis. It is also important for other hospitals to become aware of this program, as their patients with pulmonary failure can be referred, not just for transplantation, but for salvage using the ECLS system."


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