title: Normothermic ex vivo lung perfusion in clinical lung transplantation.
abstract: BACKGROUND
  More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP.
  
  
  METHODS
  In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital.
  
  
  RESULTS
  During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP.
  
  
  CONCLUSIONS
  Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
authors.affiliation: Toronto Lung Transplant Program, University of Toronto, ON, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Yeung
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Masaki
authors.initials: M
authors.lastname: Anraku
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.forename: Wojtek
authors.initials: W
authors.lastname: Karolak
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Jane
authors.initials: J
authors.lastname: Laratta
authors.forename: Sassan
authors.initials: S
authors.lastname: Azad
authors.forename: Mindy
authors.initials: M
authors.lastname: Madonik
authors.forename: Chung-Wai
authors.initials: CW
authors.lastname: Chow
authors.forename: Cecilia
authors.initials: C
authors.lastname: Chaparro
authors.forename: Michael
authors.initials: M
authors.lastname: Hutcheon
authors.forename: Lianne G
authors.initials: LG
authors.lastname: Singer
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yasufuku
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Pierre
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005240:Feasibility Studies; D006085:Graft Survival; D006801:Humans; D008168:Lung / Q000502:physiology*; D016040:Lung Transplantation; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods; D010477:Perfusion / Q000379:methods*; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D015656:Respiratory Mechanics; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting; D014655:Vascular Resistance; D055815:Young Adult