Corticosteroid therapy in deceased liver donation
CCCF ePoster library. DAragon F. 11/11/19; 283448; EP44 Disclosure(s): Nothing to disclose
Frederick DAragon
Frederick DAragon
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Abstract
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ePoster
Topic: Retrospective or Prospective Cohort Study or Case Series

D'Aragon Frederick1,2, Chasse Michael3, Lamontagne Francois2,4, Frenette Anne-Julie5,6, Cook Deborah7,8, Ibrahim Quazi7, Breau Ruth7, Kutsogiannis Jim9, Shahin Jason10, Ball Ian11,12, English Shane13, Basmaji John11, Merilo Luis7, Hanna Steven7, Meade Maureen7,8 on behalf of the Canadian Critical Care Trials Group and Canadian Donation and Transplantation Research Program
 
1Department of Anesthesiology, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
2Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
3Department of Medicine (Critical Care), Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
4Department of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
5Pharmacy faculty, Universite de Montreal, Montreal, Quebec, Canada
6Hopital Sacre-Coeur de Montreal, Montreal, Quebec, Canada
7Department of Health Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
8Department of Medicine, McMaster University, Hamilton, Ontario, Canada
9Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
10Department of Medicine, McGill University, Quebec, Canada
11Department of Medicine, Western University, London, Ontario, Canada
12Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
13Department of Medicine (Critical Care), University of Ottawa, Ontario, Canada
 
 



Introduction
Corticosteroids are often administered to neurologically deceased donors (NDD) prophylactically. While corticosteroids may improve liver transplant outcomes, this practice is not founded on strong scientific proof of benefit. Most RCTs administered steroids between 3 to 6 hours before organ recovery. We hypothesize that earlier administration of corticosteroids may be more beneficial than delayed therapy, on the rate of liver recovery for deceased donation.
 
Objectives
To compare NDD liver donors to non-liver donors, describing corticosteroid administration; and to analyze the association between time of first corticosteroid dose and liver recovery
 
Methods
This study is a secondary analysis of the Canada-DONATE cohort study, a 12-month, National, prospective study in 32 hospitals from which 5 have a liver transplant program. We enrolled 622 consecutive adult deceased donors from 2015 to 2018. Data collection from hospital records and organ donation databases spanned a period starting 1 day before consent to the time of organ recovery (prospectively) or the time that all organs were declined. For this analysis, we included potential NDD liver donors, defined as those for which the liver was offered to a transplant program based on local organ donation organization criteria. Time of first dose was defined as the number of hours between consent to organ donation and administration of the first dose of steroids. We present unadjusted data, compared using Chi-square analyses and Student-T or Mann-Whitney U tests. We used multivariable logistic regression model to determine predictors of liver recovery. In the univariate analysis, factors affecting liver recovery with p value <0.2 were selected for the multivariable model, and we forced in the corticosteroid variable. In the final model, factors with a p value < 0.05 were considered statistically significant.
 
Results
The DONATE study includes 407 NDD donors. Of these, 376 (92.4%) donors' livers were offered to transplant programs and 262 (64.4%) donors proceed to liver donation. Liver donors were younger (48.1 [+18.2] years old vs 54.3 [+15.7] p=0.002), lower AST (56.0  U/L median vs 80.0 p = 0.006), ALT (36.0 U/L vs 54.0, p= 0.005) and bilirubin (11.0 umol/L vs 15.0], p=0.007) (Table 1). Beside thyroid hormone (183 [69.8%] vs 66 [57.9%], p=0.024) there was no difference in care between donors and non-liver donors (Table 2). Methylprednisolone (94.3%) was the type of steroid most often administered followed by hydrocortisone (2.1%). Time of corticosteroid initiation was comparable in liver donors and non-donors (2.5 [-5.6, 7.0] hours vs 2.4 [-2.0, 7.5], p= 0.475). In the regression model, predictors of liver recovery were body mass index (OR: 0.91 [0.85, 0.97] p= 0.005) and AST at baseline (OR: 0.86 [0.76, 0.97] p=0.014).

Conclusion
Neither the administration of corticosteroids nor the timing of initiation were associated with liver recovery. While it has been hypothesized that the massive release of pro-inflammatory molecules after neurological death may be alleviated by corticosteroid therapy to the donor, and therefore timing of administration may be important, many other factors influence the rate of liver recovery. The Canada-DONATE program has laid the foundation for an RCT, the first now under development to analyze prophylactic treatment of deceased donors to improve liver graft function in recipients.
 


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ePoster
Topic: Retrospective or Prospective Cohort Study or Case Series

D'Aragon Frederick1,2, Chasse Michael3, Lamontagne Francois2,4, Frenette Anne-Julie5,6, Cook Deborah7,8, Ibrahim Quazi7, Breau Ruth7, Kutsogiannis Jim9, Shahin Jason10, Ball Ian11,12, English Shane13, Basmaji John11, Merilo Luis7, Hanna Steven7, Meade Maureen7,8 on behalf of the Canadian Critical Care Trials Group and Canadian Donation and Transplantation Research Program
 
1Department of Anesthesiology, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
2Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
3Department of Medicine (Critical Care), Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
4Department of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
5Pharmacy faculty, Universite de Montreal, Montreal, Quebec, Canada
6Hopital Sacre-Coeur de Montreal, Montreal, Quebec, Canada
7Department of Health Evidence & Impact, McMaster University, Hamilton, Ontario, Canada
8Department of Medicine, McMaster University, Hamilton, Ontario, Canada
9Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
10Department of Medicine, McGill University, Quebec, Canada
11Department of Medicine, Western University, London, Ontario, Canada
12Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
13Department of Medicine (Critical Care), University of Ottawa, Ontario, Canada
 
 



Introduction
Corticosteroids are often administered to neurologically deceased donors (NDD) prophylactically. While corticosteroids may improve liver transplant outcomes, this practice is not founded on strong scientific proof of benefit. Most RCTs administered steroids between 3 to 6 hours before organ recovery. We hypothesize that earlier administration of corticosteroids may be more beneficial than delayed therapy, on the rate of liver recovery for deceased donation.
 
Objectives
To compare NDD liver donors to non-liver donors, describing corticosteroid administration; and to analyze the association between time of first corticosteroid dose and liver recovery
 
Methods
This study is a secondary analysis of the Canada-DONATE cohort study, a 12-month, National, prospective study in 32 hospitals from which 5 have a liver transplant program. We enrolled 622 consecutive adult deceased donors from 2015 to 2018. Data collection from hospital records and organ donation databases spanned a period starting 1 day before consent to the time of organ recovery (prospectively) or the time that all organs were declined. For this analysis, we included potential NDD liver donors, defined as those for which the liver was offered to a transplant program based on local organ donation organization criteria. Time of first dose was defined as the number of hours between consent to organ donation and administration of the first dose of steroids. We present unadjusted data, compared using Chi-square analyses and Student-T or Mann-Whitney U tests. We used multivariable logistic regression model to determine predictors of liver recovery. In the univariate analysis, factors affecting liver recovery with p value <0.2 were selected for the multivariable model, and we forced in the corticosteroid variable. In the final model, factors with a p value < 0.05 were considered statistically significant.
 
Results
The DONATE study includes 407 NDD donors. Of these, 376 (92.4%) donors' livers were offered to transplant programs and 262 (64.4%) donors proceed to liver donation. Liver donors were younger (48.1 [+18.2] years old vs 54.3 [+15.7] p=0.002), lower AST (56.0  U/L median vs 80.0 p = 0.006), ALT (36.0 U/L vs 54.0, p= 0.005) and bilirubin (11.0 umol/L vs 15.0], p=0.007) (Table 1). Beside thyroid hormone (183 [69.8%] vs 66 [57.9%], p=0.024) there was no difference in care between donors and non-liver donors (Table 2). Methylprednisolone (94.3%) was the type of steroid most often administered followed by hydrocortisone (2.1%). Time of corticosteroid initiation was comparable in liver donors and non-donors (2.5 [-5.6, 7.0] hours vs 2.4 [-2.0, 7.5], p= 0.475). In the regression model, predictors of liver recovery were body mass index (OR: 0.91 [0.85, 0.97] p= 0.005) and AST at baseline (OR: 0.86 [0.76, 0.97] p=0.014).

Conclusion
Neither the administration of corticosteroids nor the timing of initiation were associated with liver recovery. While it has been hypothesized that the massive release of pro-inflammatory molecules after neurological death may be alleviated by corticosteroid therapy to the donor, and therefore timing of administration may be important, many other factors influence the rate of liver recovery. The Canada-DONATE program has laid the foundation for an RCT, the first now under development to analyze prophylactic treatment of deceased donors to improve liver graft function in recipients.
 


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