European Journal of Cardio-Thoracic Surgery Advance Access published April 26, 2015
ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery (2015) 1–7 doi:10.1093/ejcts/ezv155
Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality† Lay Ping Onga,*, Emily Thompsonb, Ashwin Sachdevac, B.C. Rameshd, Hazel Mused, Kirstie Wallaced, Gareth Parryd and Stephen Charles Clarka,d a b c d
Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle Upon Tyne, UK Intensive Care Unit, Freeman Hospital, Newcastle Upon Tyne, UK Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK
* Corresponding author. Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle Upon Tyne, NE7 7DN, UK. Tel: +44-7462908898; fax: +44-1912231175; e-mail: [email protected] (L.P. Ong). Received 29 September 2014; received in revised form 22 February 2015; accepted 12 March 2015
Abstract OBJECTIVES: Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. METHODS: Three hundred and eleven adult patients who underwent bilateral lung transplant between 2003 and 2013 were retrospectively reviewed. Patients were stratified according to pretransplant diagnoses and amount of blood products transfused within 24 h of transplant. All-cause mortality at the 1-year follow-up was analysed using a Cox proportional hazards regression model. RESULTS: One hundred and seventy-four male patients and 137 female patients (mean age = 41.4 ± 14.0 years) underwent bilateral lung transplant using cardiopulmonary bypass for cystic fibrosis (48.9%), fibrotic lung disease (12.2%), emphysema (27.0%), bronchiectasis (5.8%), pulmonary hypertension (1.3%) and others (4.5%). The median number of red blood cells in the first 24 h was 3 (0–40) units, fresh frozen plasma (FFP) = 2 (0–26) units and platelets = 1 (0–7) units. The unadjusted all-cause mortality at the 1-year follow-up did not appear to be different between patient subgroups stratified by the median number of units of red blood cells (P = 0.827) or FFP transfused (P = 0.456). However, 1-year mortality was adversely affected when more than the median number of units of platelets was transfused (P = 0.010). Upon adjustment for confounding variables, 1-year mortality was noted to be greater among patients transfused more than the median unit of platelets (adjusted hazard ratios: 2.3, 95% confidence interval: 1.15–4.61, P = 0.019) and those with longer bypass times (P = 0.046). No significant difference in the number of units transfused was noted when patients were stratified by pretransplant diagnosis. Predicted lung function at 3 and 6 months was not significantly affected by greater blood product use. CONCLUSIONS: Unlike general cardiothoracic surgery, blood transfusion had no effect on all-cause mortality, whereas a greater administration of platelets was observed to be associated with higher adjusted 1-year mortality. Transfusion rates were not significantly influenced by pretransplant diagnoses. Interestingly, lung function at 3 and 6 months was similar for patients who received more blood product transfusion. Keywords: Lung transplantation • Mortality • Blood products • Transfusion
INTRODUCTION Survival in lung transplantation has greatly improved with better technology and more advanced cardiorespiratory support. With regards to lung transplantation, in particular, there is little within the literature reporting on the impact of allogeneic blood transfusion (ABT) on functional and survival outcomes [1–4]. ABT carries a † Presented at the 28th Annual Meeting of the European Association for CardioThoracic Surgery, Milan, Italy, 11–15 October 2014.
significant morbidity and mortality within any surgical specialty, trauma setting or in critically ill patients [5–7]. ABT alone is associated with transfusion-related lung injury (TRALI), transfusionassociated circulatory overload (TACO), pulmonary infections, prolonged intensive care unit (ICU) stays and other morbidities [8–10]. Hence, we aimed to answer these questions: (i) is the transfusion of red blood cells (RBC), platelets or fresh frozen plasma (FFP) during the perioperative period a risk factor for mortality? (ii) Does RBC, platelet or FFP transfusion confer an increased morbidity such as prolonged ICU stay or reduced lung function? In the
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
TX & MCS
Cite this article as: Ong LP, Thompson E, Sachdeva A, Ramesh BC, Muse H, Wallace K et al. Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality. Eur J Cardiothorac Surg 2015; doi:10.1093/ejcts/ezv155.
2
L.P. Ong et al. / European Journal of Cardio-Thoracic Surgery
current climate of increasing transplant waiting lists and donor organ shortages, these answers may be invaluable in reducing further risk to the donated organ and thereby help improve outcomes for transplant patients.
MATERIALS AND METHODS Patients and study design We reviewed all patients who underwent bilateral lung transplantation in Freeman Hospital, Newcastle-upon-Tyne, UK from 2003 to 2013. All patients were under 18 years old, and retransplants were excluded. We examined clinical variables potentially related to bleeding or transfusion risk, such as patients’ age, pretransplant disease, duration of cardiopulmonary bypass (CPB), gender and the following preoperative laboratory tests: haemoglobin (Hb), activated partial thromboplastin time, prothrombin time/international normalized ratio and platelet count. The Freeman Hospital Cardiothoracic Transplant Unit patient database was utilized for this study. Any variables being examined not contained within the database were collected retrospectively from patient’s electronic or medical records. This retrospective study was approved by the Freeman Hospital and has no material ethical issues. A 10-year study period was chosen to ensure that we have a sufficient sample size to allow for robust analyses. Departmental blood transfusion protocols, ICU model of care or approach towards lung transplantation had not changed dramatically over this time period. However, aprotinin use had undergone stepwise changes over three time periods; (i) full aprotinin use (Era A: 2003–2007), (ii) aprotinin use stopped (Era B: 2008–2010) and (iii) off-licensed usage of aprotinin (Era C: 2011–2013). To address the time effect of a decade-long study and the stepwise changes in aprotinin use, these 3 separate eras were used as covariates in our analyses.
Operative methods, immunosuppression and prophylaxis The general operative principles of bilateral lung transplantation were the same but patients were under the care of different consultant surgeons, each with their own preferred surgical techniques. All operations were started at the earliest possible opportunity on an urgent basis. All operations were undertaken using CPB. All patients undergoing lung transplantation were initially administered a standardized immunosuppressive regimen of methylprednisolone, azathioprine and ciclosporin.
Statistical analyses Continuous data were reported as mean ± one standard deviation (SD) when appropriate. For continuous data, Student’s t-test and analysis of variance were used to determine whether differences among groups were significant. For categorical variables, the χ 2 test was used to determine whether differences among groups were significant. A P-value of 3, n = 152
65 25 52 9 4 4
87 13 33 9 0 10
43 ± 14 98 (62%) 251 (4–1953)
40 ± 15 76 (50%) 267 (2–1653)
67 (42%) 22 (14%)
72 (47%) 26 (17%)
362 ± 104 228 ± 47 3 (1–155) 6 (3.8%)
375 ± 124 260 ± 63 4.5 (1–127) 14 (9.2%)
74.7 ± 23 80.9 ± 24.9
78.5 ± 22.4 85.2 ± 24.2
P-values
FFP ≤ 2, n = 162
FFP > 2, n = 149
76 26 48 8 1 3
76 12 37 10 3 11
42 ± 14 91 (56%) 247.5 (4–2653)
41 ± 14 83 (56%) 285.5 (2–2002)
68 (42%) 26 (16%)
71 (48%) 22 (15%)
ns 1, n = 54
134 33 65 15 3 7
18 5 20 3 1 7
40 ± 14 144 (56%) 258 (4–2653)
47 ± 13 30 (56%) 242 (2–2002)
106 (41%) 41 (16%)
33 (61%) 7 (13%)
ns 0.004 ns ns
366 ± 119 235 ± 47 4 (1–155) 11 (4.3%)
377 ± 86 284 ± 81 8 (1–127) 9 (16.7%)
ns
ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery (2015) 1–7 doi:10.1093/ejcts/ezv155
Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality† Lay Ping Onga,*, Emily Thompsonb, Ashwin Sachdevac, B.C. Rameshd, Hazel Mused, Kirstie Wallaced, Gareth Parryd and Stephen Charles Clarka,d a b c d
Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle Upon Tyne, UK Intensive Care Unit, Freeman Hospital, Newcastle Upon Tyne, UK Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK
* Corresponding author. Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle Upon Tyne, NE7 7DN, UK. Tel: +44-7462908898; fax: +44-1912231175; e-mail: [email protected] (L.P. Ong). Received 29 September 2014; received in revised form 22 February 2015; accepted 12 March 2015
Abstract OBJECTIVES: Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. METHODS: Three hundred and eleven adult patients who underwent bilateral lung transplant between 2003 and 2013 were retrospectively reviewed. Patients were stratified according to pretransplant diagnoses and amount of blood products transfused within 24 h of transplant. All-cause mortality at the 1-year follow-up was analysed using a Cox proportional hazards regression model. RESULTS: One hundred and seventy-four male patients and 137 female patients (mean age = 41.4 ± 14.0 years) underwent bilateral lung transplant using cardiopulmonary bypass for cystic fibrosis (48.9%), fibrotic lung disease (12.2%), emphysema (27.0%), bronchiectasis (5.8%), pulmonary hypertension (1.3%) and others (4.5%). The median number of red blood cells in the first 24 h was 3 (0–40) units, fresh frozen plasma (FFP) = 2 (0–26) units and platelets = 1 (0–7) units. The unadjusted all-cause mortality at the 1-year follow-up did not appear to be different between patient subgroups stratified by the median number of units of red blood cells (P = 0.827) or FFP transfused (P = 0.456). However, 1-year mortality was adversely affected when more than the median number of units of platelets was transfused (P = 0.010). Upon adjustment for confounding variables, 1-year mortality was noted to be greater among patients transfused more than the median unit of platelets (adjusted hazard ratios: 2.3, 95% confidence interval: 1.15–4.61, P = 0.019) and those with longer bypass times (P = 0.046). No significant difference in the number of units transfused was noted when patients were stratified by pretransplant diagnosis. Predicted lung function at 3 and 6 months was not significantly affected by greater blood product use. CONCLUSIONS: Unlike general cardiothoracic surgery, blood transfusion had no effect on all-cause mortality, whereas a greater administration of platelets was observed to be associated with higher adjusted 1-year mortality. Transfusion rates were not significantly influenced by pretransplant diagnoses. Interestingly, lung function at 3 and 6 months was similar for patients who received more blood product transfusion. Keywords: Lung transplantation • Mortality • Blood products • Transfusion
INTRODUCTION Survival in lung transplantation has greatly improved with better technology and more advanced cardiorespiratory support. With regards to lung transplantation, in particular, there is little within the literature reporting on the impact of allogeneic blood transfusion (ABT) on functional and survival outcomes [1–4]. ABT carries a † Presented at the 28th Annual Meeting of the European Association for CardioThoracic Surgery, Milan, Italy, 11–15 October 2014.
significant morbidity and mortality within any surgical specialty, trauma setting or in critically ill patients [5–7]. ABT alone is associated with transfusion-related lung injury (TRALI), transfusionassociated circulatory overload (TACO), pulmonary infections, prolonged intensive care unit (ICU) stays and other morbidities [8–10]. Hence, we aimed to answer these questions: (i) is the transfusion of red blood cells (RBC), platelets or fresh frozen plasma (FFP) during the perioperative period a risk factor for mortality? (ii) Does RBC, platelet or FFP transfusion confer an increased morbidity such as prolonged ICU stay or reduced lung function? In the
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
TX & MCS
Cite this article as: Ong LP, Thompson E, Sachdeva A, Ramesh BC, Muse H, Wallace K et al. Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality. Eur J Cardiothorac Surg 2015; doi:10.1093/ejcts/ezv155.
2
L.P. Ong et al. / European Journal of Cardio-Thoracic Surgery
current climate of increasing transplant waiting lists and donor organ shortages, these answers may be invaluable in reducing further risk to the donated organ and thereby help improve outcomes for transplant patients.
MATERIALS AND METHODS Patients and study design We reviewed all patients who underwent bilateral lung transplantation in Freeman Hospital, Newcastle-upon-Tyne, UK from 2003 to 2013. All patients were under 18 years old, and retransplants were excluded. We examined clinical variables potentially related to bleeding or transfusion risk, such as patients’ age, pretransplant disease, duration of cardiopulmonary bypass (CPB), gender and the following preoperative laboratory tests: haemoglobin (Hb), activated partial thromboplastin time, prothrombin time/international normalized ratio and platelet count. The Freeman Hospital Cardiothoracic Transplant Unit patient database was utilized for this study. Any variables being examined not contained within the database were collected retrospectively from patient’s electronic or medical records. This retrospective study was approved by the Freeman Hospital and has no material ethical issues. A 10-year study period was chosen to ensure that we have a sufficient sample size to allow for robust analyses. Departmental blood transfusion protocols, ICU model of care or approach towards lung transplantation had not changed dramatically over this time period. However, aprotinin use had undergone stepwise changes over three time periods; (i) full aprotinin use (Era A: 2003–2007), (ii) aprotinin use stopped (Era B: 2008–2010) and (iii) off-licensed usage of aprotinin (Era C: 2011–2013). To address the time effect of a decade-long study and the stepwise changes in aprotinin use, these 3 separate eras were used as covariates in our analyses.
Operative methods, immunosuppression and prophylaxis The general operative principles of bilateral lung transplantation were the same but patients were under the care of different consultant surgeons, each with their own preferred surgical techniques. All operations were started at the earliest possible opportunity on an urgent basis. All operations were undertaken using CPB. All patients undergoing lung transplantation were initially administered a standardized immunosuppressive regimen of methylprednisolone, azathioprine and ciclosporin.
Statistical analyses Continuous data were reported as mean ± one standard deviation (SD) when appropriate. For continuous data, Student’s t-test and analysis of variance were used to determine whether differences among groups were significant. For categorical variables, the χ 2 test was used to determine whether differences among groups were significant. A P-value of 3, n = 152
65 25 52 9 4 4
87 13 33 9 0 10
43 ± 14 98 (62%) 251 (4–1953)
40 ± 15 76 (50%) 267 (2–1653)
67 (42%) 22 (14%)
72 (47%) 26 (17%)
362 ± 104 228 ± 47 3 (1–155) 6 (3.8%)
375 ± 124 260 ± 63 4.5 (1–127) 14 (9.2%)
74.7 ± 23 80.9 ± 24.9
78.5 ± 22.4 85.2 ± 24.2
P-values
FFP ≤ 2, n = 162
FFP > 2, n = 149
76 26 48 8 1 3
76 12 37 10 3 11
42 ± 14 91 (56%) 247.5 (4–2653)
41 ± 14 83 (56%) 285.5 (2–2002)
68 (42%) 26 (16%)
71 (48%) 22 (15%)
ns 1, n = 54
134 33 65 15 3 7
18 5 20 3 1 7
40 ± 14 144 (56%) 258 (4–2653)
47 ± 13 30 (56%) 242 (2–2002)
106 (41%) 41 (16%)
33 (61%) 7 (13%)
ns 0.004 ns ns
366 ± 119 235 ± 47 4 (1–155) 11 (4.3%)
377 ± 86 284 ± 81 8 (1–127) 9 (16.7%)
ns
