Research
Original Investigation
Association Between Prolonged Graft Ischemia and Primary Graft Failure or Survival Following Lung Transplantation Joshua C. Grimm, MD; Vicente Valero III, MD; Arman Kilic, MD; Jonathan T. Magruder, MD; Christian A. Merlo, MD, MPH; Pali D. Shah, MD; Ashish S. Shah, MD Invited Commentary IMPORTANCE The effect of prolonged graft ischemia (ⱖ6 hours) on outcomes following lung
transplantation is controversial. OBJECTIVE To evaluate the effect of prolonged total graft ischemia times on long-term survival rates and the development of primary graft failure (PGF) following lung transplantation. DESIGN, SETTING, AND PARTICIPANTS In this retrospective study, the United Network for Organ Sharing database was queried for adult patients who underwent lung transplantation from May 1, 2005, through December 31, 2011. Primary stratification by the presence of prolonged graft ischemia was performed. Kaplan-Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts. A multivariable Cox proportional hazards regression model was constructed to identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model for the development of PGF was formulated in a similar fashion. MAIN OUTCOMES AND MEASURES The primary outcome of interest was 1- and 5-year survival. Secondary outcomes included PGF and other postoperative events, such as renal failure, biopsy-proven rejection, and stroke. RESULTS Of the 10 225 patients who underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%] vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs 53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts that were or were not exposed to ischemia that lasted 6 hours or more, respectively. Prolonged graft ischemia did not independently predict 1- or 5-year mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P = .37). Furthermore, prolonged ischemia did not independently predict 1-year (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05; 95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =.37). CONCLUSIONS AND RELEVANCE No association was found between prolonged total graft ischemia times and primary graft failure or survival following lung transplantation. Given the scarcity of organs and the paucity of suitable recipients, prolonged ischemia time should not preclude transplantation. It is, therefore, reasonable to consider extending the accepted period of ischemia to more than 6 hours in certain patient populations to improve organ use. Author Affiliations: Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland (Grimm, Valero, Kilic, Magruder, A. S. Shah); Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland (Merlo, P. D. Shah).
JAMA Surg. doi:10.1001/jamasurg.2015.12 Published online April 15, 2015.
Corresponding Author: Ashish S. Shah, MD, Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University, 1800 Orleans, Zayed Tower 7107, Baltimore, MD 21287 (ashah29 @jhmi.edu).
(Reprinted) E1
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 05/28/2015
Research Original Investigation
Prolonged Graft Ischemia, Graft Failure, and Survival in Lung Transplantation
L
ung transplantation provides an excellent therapeutic option for patients with end-stage pulmonary disease because it improves patients’ quality of life and duration of survival. Despite measures to reduce waiting times, such as the implementation of the lung allocation score (LAS), a paucity of suitable donors continues to negatively affect graft availability.1 Extending the accepted period of graft ischemia time may augment the supply of this scarce resource by broadening the time frame to execute longdistance organ donor recoveries. Reluctance exists, however, to universally advocate for prolonging the accepted graft ischemia time owing to the perceived increased rate of posttransplant ischemia-reperfusion injuries, which deleteriously affect graft function and can precipitate primary graft failure (PGF).2,3 Previous studies4-6 that investigated the role of graft ischemia time in lung transplantation outcomes have yielded conflicting results but are limited in their scope owing to small sample sizes and recent changes in preservation strategies and surgical technique. We evaluated a large cohort from the United Network for Organ Sharing (UNOS) database to evaluate the significance of prolonged graft ischemia times on long-term survival rates and to determine whether it was an independent predictor of PGF following lung transplantation.
Methods Patient Selection Patients aged 18 years or older who underwent initial or repeated lung transplantation from May 1, 2005, through December 31, 2011, were identified in the UNOS database. Primary stratification by a graft ischemia time of less than 6 hours or 6 or more hours was conducted. Patients who underwent heart-lung transplantation were excluded from analysis. Only the index single-lung transplantation was included for patients who underwent sequential lung transplantation. This study was approved by the Johns Hopkins Institutional Review Board.
Data Collection and Statistical Analysis Baseline donor and recipient characteristics as well as transplant-related outcomes were compared between the 2 ischemiatime cohorts. Recipient-specific variables included age, sex, LAS, race, body mass index, single or bilateral transplant, etiologic features of end-stage lung disease, diabetes mellitus status, history of previous transplant, mechanical ventilation and extracorporeal membrane oxygenation (ECMO) before transplantation, and intensive care unit (ICU) status at the time of transplant. Donor-related variables included age, body mass in-
Table 1. Baseline Recipient Characteristics Variable Age, mean (SD)
Ischemia
Original Investigation
Association Between Prolonged Graft Ischemia and Primary Graft Failure or Survival Following Lung Transplantation Joshua C. Grimm, MD; Vicente Valero III, MD; Arman Kilic, MD; Jonathan T. Magruder, MD; Christian A. Merlo, MD, MPH; Pali D. Shah, MD; Ashish S. Shah, MD Invited Commentary IMPORTANCE The effect of prolonged graft ischemia (ⱖ6 hours) on outcomes following lung
transplantation is controversial. OBJECTIVE To evaluate the effect of prolonged total graft ischemia times on long-term survival rates and the development of primary graft failure (PGF) following lung transplantation. DESIGN, SETTING, AND PARTICIPANTS In this retrospective study, the United Network for Organ Sharing database was queried for adult patients who underwent lung transplantation from May 1, 2005, through December 31, 2011. Primary stratification by the presence of prolonged graft ischemia was performed. Kaplan-Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts. A multivariable Cox proportional hazards regression model was constructed to identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model for the development of PGF was formulated in a similar fashion. MAIN OUTCOMES AND MEASURES The primary outcome of interest was 1- and 5-year survival. Secondary outcomes included PGF and other postoperative events, such as renal failure, biopsy-proven rejection, and stroke. RESULTS Of the 10 225 patients who underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%] vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs 53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts that were or were not exposed to ischemia that lasted 6 hours or more, respectively. Prolonged graft ischemia did not independently predict 1- or 5-year mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P = .37). Furthermore, prolonged ischemia did not independently predict 1-year (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05; 95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =.37). CONCLUSIONS AND RELEVANCE No association was found between prolonged total graft ischemia times and primary graft failure or survival following lung transplantation. Given the scarcity of organs and the paucity of suitable recipients, prolonged ischemia time should not preclude transplantation. It is, therefore, reasonable to consider extending the accepted period of ischemia to more than 6 hours in certain patient populations to improve organ use. Author Affiliations: Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland (Grimm, Valero, Kilic, Magruder, A. S. Shah); Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland (Merlo, P. D. Shah).
JAMA Surg. doi:10.1001/jamasurg.2015.12 Published online April 15, 2015.
Corresponding Author: Ashish S. Shah, MD, Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University, 1800 Orleans, Zayed Tower 7107, Baltimore, MD 21287 (ashah29 @jhmi.edu).
(Reprinted) E1
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archsurg.jamanetwork.com/ by a New York University User on 05/28/2015
Research Original Investigation
Prolonged Graft Ischemia, Graft Failure, and Survival in Lung Transplantation
L
ung transplantation provides an excellent therapeutic option for patients with end-stage pulmonary disease because it improves patients’ quality of life and duration of survival. Despite measures to reduce waiting times, such as the implementation of the lung allocation score (LAS), a paucity of suitable donors continues to negatively affect graft availability.1 Extending the accepted period of graft ischemia time may augment the supply of this scarce resource by broadening the time frame to execute longdistance organ donor recoveries. Reluctance exists, however, to universally advocate for prolonging the accepted graft ischemia time owing to the perceived increased rate of posttransplant ischemia-reperfusion injuries, which deleteriously affect graft function and can precipitate primary graft failure (PGF).2,3 Previous studies4-6 that investigated the role of graft ischemia time in lung transplantation outcomes have yielded conflicting results but are limited in their scope owing to small sample sizes and recent changes in preservation strategies and surgical technique. We evaluated a large cohort from the United Network for Organ Sharing (UNOS) database to evaluate the significance of prolonged graft ischemia times on long-term survival rates and to determine whether it was an independent predictor of PGF following lung transplantation.
Methods Patient Selection Patients aged 18 years or older who underwent initial or repeated lung transplantation from May 1, 2005, through December 31, 2011, were identified in the UNOS database. Primary stratification by a graft ischemia time of less than 6 hours or 6 or more hours was conducted. Patients who underwent heart-lung transplantation were excluded from analysis. Only the index single-lung transplantation was included for patients who underwent sequential lung transplantation. This study was approved by the Johns Hopkins Institutional Review Board.
Data Collection and Statistical Analysis Baseline donor and recipient characteristics as well as transplant-related outcomes were compared between the 2 ischemiatime cohorts. Recipient-specific variables included age, sex, LAS, race, body mass index, single or bilateral transplant, etiologic features of end-stage lung disease, diabetes mellitus status, history of previous transplant, mechanical ventilation and extracorporeal membrane oxygenation (ECMO) before transplantation, and intensive care unit (ICU) status at the time of transplant. Donor-related variables included age, body mass in-
Table 1. Baseline Recipient Characteristics Variable Age, mean (SD)
Ischemia
