Liver International ISSN 1478-3223
LIVER TRANSPLANTATION
Safely expanding the donor pool: brain dead donors with history of temporary cardiac arrest 1, Juergen W. Treckmann1, Dieter P. Hoyer1, Andreas Paul1, Fuat Saner1, Anja Gallinat1, Zoltan Mathe 1 1 2 3 Maren Schulze , Gernot M. Kaiser , Ali Canbay , Ernesto Molmenti and Georgios C. Sotiropoulos1 1 General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany 2 Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany 3 Department of Surgery, North Shore University Hospital, Manhasset, NY, USA
Keywords donor pool – donor resuscitation – extended donor criteria – risk assessment Abbreviations ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CA donors, donors with history of cardiac arrest; CA, cardiac arrest; CIT, cold ischaemic time; DRI, donor risk index; EAD, early allograft dysfunction; ET DRI, eurotransplant donor risk index; HTK, histidine-tryptophan-ketoglutarate; ICU, intensive care unit; INR, international normalized ratio; labMELD, laboratory Model for End stage Liver Disease; LT, liver transplantation; No CA donors, donors without history of cardiac arrest; PNF, primary nonfunction; UW, University of Wisconsin; cGT, gamma-glutamyl transpeptidase. Correspondence Dieter P. Hoyer, MD, University Hospital Essen, Department of General, Visceral and Transplantation Surgery, Hufelandstr. 55, 45127 Essen, Germany Tel: +0049 201 723 84002 Fax: +0049 201 723 1113 e-mail: [email protected]
Abstract Background & Aims: Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. Methods: We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. Results: We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1–150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. Conclusion: This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.
Received 11 November 2014 Accepted 9 December 2014 Handling Associate Editor: Vincent Wong DOI:10.1111/liv.12766 Liver Int. 2015; 35: 1756–1763
Despite the rapid progress in the field of liver transplantation (LT), organ shortage remains a pivotal limitation. The persistently high wait list mortality (1–6) demands urgent new ways to increase the donor pool. Aggressive utilization of live donors (7), donation after circulatory death (8, 9) and split graft transplantation (10, 11) have benefitted specific patient
1756
populations. Nonetheless, brain dead donors constitute the greatest source of organs in the Western world (12). Efforts to increase the number of such donors have led to the acceptance of organs previously considered suboptimal (13, 14) based on their potentially increased morbidity and mortality (15, 16). The sequelae of cardiac arrest (CA) and re-establishment of circulation (by cardiopulmonary resusciLiver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Hoyer et al.
Cardiac arrest in brain dead donors
Key Points
Surgical procedure and immunosuppression
Cardiac arrest in brain dead liver donors adds additional ischaemic injury to cold/warm ischaemic times. Impact on graft survival remains speculative. 884 patients (8.7% donors with history of cardiac arrest) were evaluated. Organs from donors with history of cardiac arrest demonstrated more severe preprocurement injury, similar survival and less hepatocellular injury after liver transplantation compared to controls. The only independent risk factor for graft/patient survival in donors with history of cardiac arrest was the cold ischaemic time. This analysis represents the largest cohort of donors with history of cardiac arrest, demonstrating feasibility to utilize these organs, potentially expanding the donor pool.
All organ procurements were carried out by specialized local teams according to the standards of the local procurement organizations within the different Eurotransplant regions. The decision to obtain a liver biopsy for precise microscopic assessment of steatosis or just to perform a macroscopic assessment was made by the accepting transplant surgeon at our centre and upon availability. LT was carried out with standard techniques. Venovenous bypass was not used. Liver transplantation was performed with cava replacement and end-to-end-anastomosis of the portal vein, hepatic artery and bile duct. Perioperative intensive care and immunosuppression therapy was standardized in all patients. Immunosuppression consisted of 1000 mg methylprednisolone intraoperatively followed by a triple regimen of calcineurin-inhibitors (adjusted in accordance to the trough level of the drug), corticosteroids and mycophenolate mofetil.
tation) have been studied thoroughly. The general poor outcomes frequently observed after cardiopulmonary resuscitation illustrate the severity of such ischaemic injury (17, 18). Cardiac arrest in organ donors prior to procurement can potentially induce an ischaemic insult with deleterious effects on graft quality. Hypothetically, these organs may have impaired regeneration and a lower tolerance of the obligatory cold and warm ischaemic times. Traditionally, history of CA in liver donors has been rated as additional risk. The aim of our study was to analyse the influence of CA and resuscitation in liver donors and to attempt to identify prognostic factors of outcome. Patients and methods Study population
This retrospective, single-centre cohort study was approved by the local ethics committee of the University Hospital Essen and followed the Declaration of Helsinki from 1975. The ethics committee waived informed consent because of the retrospective design. We evaluated data corresponding to all LTs performed from September 2003 to December 2011 at the University Hospital of Essen, Germany. Recipients 2000 IU/L within the first 7 days (19). Each case was classified as ‘EAD’ or ‘no EAD.’ For recipients who died within 7 days after LT, laboratory and clinical parameters up to the time of death were considered for classification. Definition of primary nonfunction (PNF)
Primary non-function was defined as posttransplant liver dysfunction requiring retransplantation or leading to death within 7 days. Definition of rescue allocation
Livers refused by more than three different centres for allocated candidates with the highest MELD scores on the national waiting list were characterized as ‘organ rescue offers.’ These grafts were then either offered to the nearest centre with a suitable recipient or allocated to the first centre to accept them (multiple-refusal/competitive rescue offer procedure). ‘Organ rescue offers’ were also occasionally encountered in instances of donor instability, prolonged cold ischaemic time (CIT) or unfavourable logistic reasons.
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Hoyer et al.
Cardiac arrest in brain dead donors
Basic donor and recipient factors and technical factors for analysis
The following donor and recipient factors were analysed: Recipient: age, gender, weight, height, BMI, pretransplant mechanical ventilation, pretransplant ICU stay, pretransplant haemodialysis, laboratory Model for End stage Liver Disease (labMELD) score before LT, ‘high-urgency’-listing, length of surgical procedure, warm ischaemic time and type of LT (first/retransplantation). Donor: age, gender, weight, height, BMI, cause of death (cerebrovascular accident, hypoxia, trauma, others), CIT, ICU length of stay, need of vasopressor therapy (low =0.5 lg/kg/min), biopsy proven steatosis (total, macrovesicular, microvesicular), rescue offer allocation, organ quality as assessed by the procurement team (good, moderate, poor), split liver transplantation, organ preservation solution used during procurement (HTK, UW), last laboratory values prior to procurement (AST, ALT, cGT, bilirubin, INR, creatinine, serum sodium), Donor Risk Index (DRI), number of CA and cardiopulmonary resuscitations, total duration of all CA, duration of last CA, number of days from last CA to LT.
procurement was 11.5 (range: 1–150) min, a median time of 3 (range: 1–21) days prior to LT. In eight cases only, the last resuscitation was carried out more than 7 days prior to LT. CA donor characteristics
Mean donor risk index of accepted organs was 1.7 (range: 0.8–2.7). 50% of donors were male. Mean age was 49.7 ± 12.9 years, with a median BMI of 25 (range: 12.4–35.2) kg/m2, and a median length of ICU stay of 3 (range: 0.5–20.5) days. Vasopressor support at the time of procurement was as follows: 8 (13.8%) none, 14 (24.1%) low, 30 (51.7%) moderate and 6 (10.3%) high. Cause of death was cerebrovascular event in 36 (48%), hypoxia in 25 (33.3%), trauma in 12 (16%) and other reasons in 2 (2.7%). Liver quality as described by the procurement team was ‘good’ in 51 (77.3%), ‘acceptable’ in 14 (21.2%) and ‘poor’ in 1 (1.5%). Median macrovesicular steatosis (as documented by histological analysis) was 2 (range: 0–20) %. Perfusion solution used for preservation of the grafts was HTK in 21 (30%) and UW in 49 (70%). Median cold ischaemic time (CIT) was 8 (range: 3.3–13) h. A total of 39 (79.6%) of all CA donor grafts were allocated as ‘rescue offers’.
Statistical analysis
Data were expressed as mean and standard deviation and as median and range values where appropriate. Continuous variables were analysed by the Student’s t-test or the Mann–Whitney U test. Graft and patient survival were calculated using the Kaplan–Meier method and compared with the log-rank test. Multivariable analyses were performed with logistic regression and cox proportional hazard models. Variables with P < 0.05 by univariable analysis were included in the multivariable analysis (20). Differences in P less than 0.05 were considered to be statistically significant. Statistical analyses were performed using JMP (version 10.0.0 SAS, SAS Institute Inc., Cary, NC, USA). Results
Seventy-seven (n = 77, 8.7%) of the 884 consecutive adult liver transplant recipients performed at our Institution between September 2003 and December 2011 received organs from donors with a history of CA before procurement. Median follow-up was 30.9 (0–104.9) months. Cardiac arrest and cardiopulmonary resuscitations in donors before procurement
Median number of CA with cardiopulmonary resuscitation prior to procurement was 1 (range: 1–3). Median total resuscitation time was 16.5 (range: 1–150) min. Median duration of the last resuscitation prior to
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Characteristics of recipients of CA donor livers
Mean age of recipients of CA donor allografts was 49.7 ± 12.9 years. A total of 44 (57.1%) recipients were men. Median BMI was 24.5 (range: 14.8–34.5) kg/m2, and median labMELD at the time of LT was 17.9 (range: 6.4–40). Most patients did not receive ICU treatment prior to LT (median 0, range: 0–15 days). 3 (3.9%) subjects required haemodialysis before LT. Twenty-one (28%) were listed as ‘Status 1a’, and 10 (13%) were retransplantations. Mean time of surgical implantation was 314.1 ± 95.9 min, with a mean warm ischaemic time of 32.6 ± 10.5 min. Differences between CA donors and no CA donors
Table 1 illustrates the univariable analysis of characteristics of recipients, CA donors and no CA donors. Organs from CA donors showed a significantly higher incidence of transplantation into ‘status 1’ recipients (28% CA donors vs 17.7% no CA donors; P = 0.028), and allocation as ‘rescue offers’ (79.6 vs. 55.9%; P = 0.005). UW was utilized in 70% and HTK in 30% of CA donors. In no CA donors, UW was utilized in 24.9% and HTK in 74.1% of cases (P < 0.001). CIT was significantly longer in CA donors than in no CA donors (8.00 vs. 7.01 hours; P = 0.016). Donor age was significantly lower in CA donors (45 vs. 53 years; P > 0.001). CA donors had a significantly shorter length of ICU stay before procurement (3.0 vs. 3.7 days; P = 0.047) and demonstrated significantly different causes of death. Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Hoyer et al.
Cardiac arrest in brain dead donors
Moreover, CA donors had significantly higher last AST (90 vs. 45 U/L; P < 0.001) and ALT (67.5 vs. 30 U/L; P < 0.001) values prior to procurement. Patient outcome
Outcome after LT was stratified based on donor history of CA. 3-month, 1-year and 5-year graft survival for CA and no CA donors was 72.3%, 69.6% and 51.9% vs. 67.7%, 60.7% and 51.9% respectively (P = 0.612) (Fig. 1A). 3 month, 1 year and 5 year recipient survival for CA and no CA donor organs was 78.8%, 76% and 57.2% vs 72.1%, 65.1% and 53% respectively
(P = 0.435) (Fig. 1B). There was no difference in the incidence of PNF (CA donors 9.1% vs. no CA donors 7.8%; P = 0.69) and EAD (CA donors 36.5% vs. no CA donors 41.7%; P = 0.348). Length of ICU stay after LT was 7 days for the CA and 5.5 days for the no CA donor groups (P = 0.331). Median hospital stay was 24.5 days and 23 days for recipients of CA and no CA donors respectively (P = 0.111). Peak AST level after LT in the first three postoperative days was significantly lower in the CA donor group (886 U/L vs. 1321 U/L; P = 0.031). Peak ALT in the first 3 days after LT was not different among both groups (CA donor 808 U/L, no CA donor 887 U/L; P = 0.484).
Table 1. Recipient and donor data
Recipient data Male gender Age (years) BMI (kg/m²) Pre-LT-ICU (days) Pre-LT-mechanical Ventilation (days) ‘status-1’–listing labMELD Warm ischaemia time (minutes) Time for surgical procedure (minutes) Donor data Donor Risk Index Cold ischaemia time (hours) Rescue offer allocation Male gender Age (years) BMI (kg/m²) Graft quality as assessed by surgeon Good Acceptable Poor ICU-stay (days) Vasopressor support No Low Moderate High Cause of death Cerebrovascular Trauma Hypoxia Other Perfusion solution HTK UW Last AST (U/L) Last ALT (U/L) Last bilirubin (lmol/L) Last cGT (U/L) Last INR Last creatinine (lmol/L) Last serum sodium (mmol/L)
noCA n = 807
CA n = 77
482 (60.1) 52.8 (18.8–74.1) 25.9 (15.2–35) 0 (0–60) 0 (0–48) 136 (17.7%) 18.4 (6.4–40) 32 (12–273) 285 (90–789)
44 (57.1) 51.4 (20.6–68.6) 24.5 (14.8–34.5) 0 (0–15) 0 (0–15) 21 (28%) 17.9 (6.4–40) 32 (10–60) 312.5 (173–567)
0.772 0.598 0.501 0.153 0.259 0.028 0.239 0.428 0.269
1.69 (0.85–3.4) 7.01 (0.9–28.5) 382 (55.9%) 399 (51%) 53 (3–88) 25.3 (11.2–35)
1.65 (0.82–2.7) 8 (3.3–13) 39 (79.6%) 38 (50%) 45 (3–75) 25 (12.4–35.2)
0.5386 0.016 0.005 0.898
LIVER TRANSPLANTATION
Safely expanding the donor pool: brain dead donors with history of temporary cardiac arrest 1, Juergen W. Treckmann1, Dieter P. Hoyer1, Andreas Paul1, Fuat Saner1, Anja Gallinat1, Zoltan Mathe 1 1 2 3 Maren Schulze , Gernot M. Kaiser , Ali Canbay , Ernesto Molmenti and Georgios C. Sotiropoulos1 1 General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany 2 Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany 3 Department of Surgery, North Shore University Hospital, Manhasset, NY, USA
Keywords donor pool – donor resuscitation – extended donor criteria – risk assessment Abbreviations ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CA donors, donors with history of cardiac arrest; CA, cardiac arrest; CIT, cold ischaemic time; DRI, donor risk index; EAD, early allograft dysfunction; ET DRI, eurotransplant donor risk index; HTK, histidine-tryptophan-ketoglutarate; ICU, intensive care unit; INR, international normalized ratio; labMELD, laboratory Model for End stage Liver Disease; LT, liver transplantation; No CA donors, donors without history of cardiac arrest; PNF, primary nonfunction; UW, University of Wisconsin; cGT, gamma-glutamyl transpeptidase. Correspondence Dieter P. Hoyer, MD, University Hospital Essen, Department of General, Visceral and Transplantation Surgery, Hufelandstr. 55, 45127 Essen, Germany Tel: +0049 201 723 84002 Fax: +0049 201 723 1113 e-mail: [email protected]
Abstract Background & Aims: Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. Methods: We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. Results: We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1–150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. Conclusion: This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.
Received 11 November 2014 Accepted 9 December 2014 Handling Associate Editor: Vincent Wong DOI:10.1111/liv.12766 Liver Int. 2015; 35: 1756–1763
Despite the rapid progress in the field of liver transplantation (LT), organ shortage remains a pivotal limitation. The persistently high wait list mortality (1–6) demands urgent new ways to increase the donor pool. Aggressive utilization of live donors (7), donation after circulatory death (8, 9) and split graft transplantation (10, 11) have benefitted specific patient
1756
populations. Nonetheless, brain dead donors constitute the greatest source of organs in the Western world (12). Efforts to increase the number of such donors have led to the acceptance of organs previously considered suboptimal (13, 14) based on their potentially increased morbidity and mortality (15, 16). The sequelae of cardiac arrest (CA) and re-establishment of circulation (by cardiopulmonary resusciLiver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Hoyer et al.
Cardiac arrest in brain dead donors
Key Points
Surgical procedure and immunosuppression
Cardiac arrest in brain dead liver donors adds additional ischaemic injury to cold/warm ischaemic times. Impact on graft survival remains speculative. 884 patients (8.7% donors with history of cardiac arrest) were evaluated. Organs from donors with history of cardiac arrest demonstrated more severe preprocurement injury, similar survival and less hepatocellular injury after liver transplantation compared to controls. The only independent risk factor for graft/patient survival in donors with history of cardiac arrest was the cold ischaemic time. This analysis represents the largest cohort of donors with history of cardiac arrest, demonstrating feasibility to utilize these organs, potentially expanding the donor pool.
All organ procurements were carried out by specialized local teams according to the standards of the local procurement organizations within the different Eurotransplant regions. The decision to obtain a liver biopsy for precise microscopic assessment of steatosis or just to perform a macroscopic assessment was made by the accepting transplant surgeon at our centre and upon availability. LT was carried out with standard techniques. Venovenous bypass was not used. Liver transplantation was performed with cava replacement and end-to-end-anastomosis of the portal vein, hepatic artery and bile duct. Perioperative intensive care and immunosuppression therapy was standardized in all patients. Immunosuppression consisted of 1000 mg methylprednisolone intraoperatively followed by a triple regimen of calcineurin-inhibitors (adjusted in accordance to the trough level of the drug), corticosteroids and mycophenolate mofetil.
tation) have been studied thoroughly. The general poor outcomes frequently observed after cardiopulmonary resuscitation illustrate the severity of such ischaemic injury (17, 18). Cardiac arrest in organ donors prior to procurement can potentially induce an ischaemic insult with deleterious effects on graft quality. Hypothetically, these organs may have impaired regeneration and a lower tolerance of the obligatory cold and warm ischaemic times. Traditionally, history of CA in liver donors has been rated as additional risk. The aim of our study was to analyse the influence of CA and resuscitation in liver donors and to attempt to identify prognostic factors of outcome. Patients and methods Study population
This retrospective, single-centre cohort study was approved by the local ethics committee of the University Hospital Essen and followed the Declaration of Helsinki from 1975. The ethics committee waived informed consent because of the retrospective design. We evaluated data corresponding to all LTs performed from September 2003 to December 2011 at the University Hospital of Essen, Germany. Recipients 2000 IU/L within the first 7 days (19). Each case was classified as ‘EAD’ or ‘no EAD.’ For recipients who died within 7 days after LT, laboratory and clinical parameters up to the time of death were considered for classification. Definition of primary nonfunction (PNF)
Primary non-function was defined as posttransplant liver dysfunction requiring retransplantation or leading to death within 7 days. Definition of rescue allocation
Livers refused by more than three different centres for allocated candidates with the highest MELD scores on the national waiting list were characterized as ‘organ rescue offers.’ These grafts were then either offered to the nearest centre with a suitable recipient or allocated to the first centre to accept them (multiple-refusal/competitive rescue offer procedure). ‘Organ rescue offers’ were also occasionally encountered in instances of donor instability, prolonged cold ischaemic time (CIT) or unfavourable logistic reasons.
1757
Hoyer et al.
Cardiac arrest in brain dead donors
Basic donor and recipient factors and technical factors for analysis
The following donor and recipient factors were analysed: Recipient: age, gender, weight, height, BMI, pretransplant mechanical ventilation, pretransplant ICU stay, pretransplant haemodialysis, laboratory Model for End stage Liver Disease (labMELD) score before LT, ‘high-urgency’-listing, length of surgical procedure, warm ischaemic time and type of LT (first/retransplantation). Donor: age, gender, weight, height, BMI, cause of death (cerebrovascular accident, hypoxia, trauma, others), CIT, ICU length of stay, need of vasopressor therapy (low =0.5 lg/kg/min), biopsy proven steatosis (total, macrovesicular, microvesicular), rescue offer allocation, organ quality as assessed by the procurement team (good, moderate, poor), split liver transplantation, organ preservation solution used during procurement (HTK, UW), last laboratory values prior to procurement (AST, ALT, cGT, bilirubin, INR, creatinine, serum sodium), Donor Risk Index (DRI), number of CA and cardiopulmonary resuscitations, total duration of all CA, duration of last CA, number of days from last CA to LT.
procurement was 11.5 (range: 1–150) min, a median time of 3 (range: 1–21) days prior to LT. In eight cases only, the last resuscitation was carried out more than 7 days prior to LT. CA donor characteristics
Mean donor risk index of accepted organs was 1.7 (range: 0.8–2.7). 50% of donors were male. Mean age was 49.7 ± 12.9 years, with a median BMI of 25 (range: 12.4–35.2) kg/m2, and a median length of ICU stay of 3 (range: 0.5–20.5) days. Vasopressor support at the time of procurement was as follows: 8 (13.8%) none, 14 (24.1%) low, 30 (51.7%) moderate and 6 (10.3%) high. Cause of death was cerebrovascular event in 36 (48%), hypoxia in 25 (33.3%), trauma in 12 (16%) and other reasons in 2 (2.7%). Liver quality as described by the procurement team was ‘good’ in 51 (77.3%), ‘acceptable’ in 14 (21.2%) and ‘poor’ in 1 (1.5%). Median macrovesicular steatosis (as documented by histological analysis) was 2 (range: 0–20) %. Perfusion solution used for preservation of the grafts was HTK in 21 (30%) and UW in 49 (70%). Median cold ischaemic time (CIT) was 8 (range: 3.3–13) h. A total of 39 (79.6%) of all CA donor grafts were allocated as ‘rescue offers’.
Statistical analysis
Data were expressed as mean and standard deviation and as median and range values where appropriate. Continuous variables were analysed by the Student’s t-test or the Mann–Whitney U test. Graft and patient survival were calculated using the Kaplan–Meier method and compared with the log-rank test. Multivariable analyses were performed with logistic regression and cox proportional hazard models. Variables with P < 0.05 by univariable analysis were included in the multivariable analysis (20). Differences in P less than 0.05 were considered to be statistically significant. Statistical analyses were performed using JMP (version 10.0.0 SAS, SAS Institute Inc., Cary, NC, USA). Results
Seventy-seven (n = 77, 8.7%) of the 884 consecutive adult liver transplant recipients performed at our Institution between September 2003 and December 2011 received organs from donors with a history of CA before procurement. Median follow-up was 30.9 (0–104.9) months. Cardiac arrest and cardiopulmonary resuscitations in donors before procurement
Median number of CA with cardiopulmonary resuscitation prior to procurement was 1 (range: 1–3). Median total resuscitation time was 16.5 (range: 1–150) min. Median duration of the last resuscitation prior to
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Characteristics of recipients of CA donor livers
Mean age of recipients of CA donor allografts was 49.7 ± 12.9 years. A total of 44 (57.1%) recipients were men. Median BMI was 24.5 (range: 14.8–34.5) kg/m2, and median labMELD at the time of LT was 17.9 (range: 6.4–40). Most patients did not receive ICU treatment prior to LT (median 0, range: 0–15 days). 3 (3.9%) subjects required haemodialysis before LT. Twenty-one (28%) were listed as ‘Status 1a’, and 10 (13%) were retransplantations. Mean time of surgical implantation was 314.1 ± 95.9 min, with a mean warm ischaemic time of 32.6 ± 10.5 min. Differences between CA donors and no CA donors
Table 1 illustrates the univariable analysis of characteristics of recipients, CA donors and no CA donors. Organs from CA donors showed a significantly higher incidence of transplantation into ‘status 1’ recipients (28% CA donors vs 17.7% no CA donors; P = 0.028), and allocation as ‘rescue offers’ (79.6 vs. 55.9%; P = 0.005). UW was utilized in 70% and HTK in 30% of CA donors. In no CA donors, UW was utilized in 24.9% and HTK in 74.1% of cases (P < 0.001). CIT was significantly longer in CA donors than in no CA donors (8.00 vs. 7.01 hours; P = 0.016). Donor age was significantly lower in CA donors (45 vs. 53 years; P > 0.001). CA donors had a significantly shorter length of ICU stay before procurement (3.0 vs. 3.7 days; P = 0.047) and demonstrated significantly different causes of death. Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Hoyer et al.
Cardiac arrest in brain dead donors
Moreover, CA donors had significantly higher last AST (90 vs. 45 U/L; P < 0.001) and ALT (67.5 vs. 30 U/L; P < 0.001) values prior to procurement. Patient outcome
Outcome after LT was stratified based on donor history of CA. 3-month, 1-year and 5-year graft survival for CA and no CA donors was 72.3%, 69.6% and 51.9% vs. 67.7%, 60.7% and 51.9% respectively (P = 0.612) (Fig. 1A). 3 month, 1 year and 5 year recipient survival for CA and no CA donor organs was 78.8%, 76% and 57.2% vs 72.1%, 65.1% and 53% respectively
(P = 0.435) (Fig. 1B). There was no difference in the incidence of PNF (CA donors 9.1% vs. no CA donors 7.8%; P = 0.69) and EAD (CA donors 36.5% vs. no CA donors 41.7%; P = 0.348). Length of ICU stay after LT was 7 days for the CA and 5.5 days for the no CA donor groups (P = 0.331). Median hospital stay was 24.5 days and 23 days for recipients of CA and no CA donors respectively (P = 0.111). Peak AST level after LT in the first three postoperative days was significantly lower in the CA donor group (886 U/L vs. 1321 U/L; P = 0.031). Peak ALT in the first 3 days after LT was not different among both groups (CA donor 808 U/L, no CA donor 887 U/L; P = 0.484).
Table 1. Recipient and donor data
Recipient data Male gender Age (years) BMI (kg/m²) Pre-LT-ICU (days) Pre-LT-mechanical Ventilation (days) ‘status-1’–listing labMELD Warm ischaemia time (minutes) Time for surgical procedure (minutes) Donor data Donor Risk Index Cold ischaemia time (hours) Rescue offer allocation Male gender Age (years) BMI (kg/m²) Graft quality as assessed by surgeon Good Acceptable Poor ICU-stay (days) Vasopressor support No Low Moderate High Cause of death Cerebrovascular Trauma Hypoxia Other Perfusion solution HTK UW Last AST (U/L) Last ALT (U/L) Last bilirubin (lmol/L) Last cGT (U/L) Last INR Last creatinine (lmol/L) Last serum sodium (mmol/L)
noCA n = 807
CA n = 77
482 (60.1) 52.8 (18.8–74.1) 25.9 (15.2–35) 0 (0–60) 0 (0–48) 136 (17.7%) 18.4 (6.4–40) 32 (12–273) 285 (90–789)
44 (57.1) 51.4 (20.6–68.6) 24.5 (14.8–34.5) 0 (0–15) 0 (0–15) 21 (28%) 17.9 (6.4–40) 32 (10–60) 312.5 (173–567)
0.772 0.598 0.501 0.153 0.259 0.028 0.239 0.428 0.269
1.69 (0.85–3.4) 7.01 (0.9–28.5) 382 (55.9%) 399 (51%) 53 (3–88) 25.3 (11.2–35)
1.65 (0.82–2.7) 8 (3.3–13) 39 (79.6%) 38 (50%) 45 (3–75) 25 (12.4–35.2)
0.5386 0.016 0.005 0.898
