- Email: [email protected]
Organs transplanted from intoxicated donors
Organs Transplanted From Intoxicated Donors E. Duque, J. Duque, J. Henao, G. Mejia, J. Arango, I. Arroyave, L. Pen a, R. Tobón, J. Carvajal, G. Zuluaga, A. Garcia, E. Sanı´n, J. Gutiérrez, A. Velásquez, and M. Arbeláez ABSTRACT Purpose. The purpose of our study was to evaluate short- and long-term results of transplants from cadaver donors who have died of poisoning by various substances. Materials and Methods. The actuarial survival rate of organs from intoxicated donors was calculated using the Kaplan-Meier method. Results. Among the 507 donors between January 1998 and December 2002, 5 (0.98%) had a cause of brain death of poisoning, namely, organo-phosphates (n ⫽ 2), methanol (n ⫽ 1), cyanide (n ⫽ 1) and acetylsalicilic acid (n ⫽ 1), from whom were procured 10 kidneys, 1 liver, 2 corneas, and 1 set of bones. The follow up for patients receiving solid organs was 15.2 months (range, 0 – 48 months). At 3 months, 90% of kidneys had normal function. No delayed graft function rejection episodes or major complications were reported in any recipient. None showed evidence of acute or chronic poisoning. Two died, 1 early mortality was due to anesthetic complications and the other at 17 months to an unknown cause. Actuarial kidney survival rates were 90% and 80% at 12 and 24 months, respectively. The liver recipient was well at the end of follow up. Conclusion. Using organs of poisoned donors is feasible with comparable graft survival rates to other recipient.
T
HE SHORTAGE of organs for transplantation and the high number of potential recipients who die on transplant waiting lists have made it necessary to extend the criteria for donor selection to include individuals who die of intoxication with certain drugs or industrial products.1 The use of intoxicated donors to expand the organ pool has been poorly explored with few reports2 that do not permit the formulation of definite inclusion or exclusion criteria. Although intoxicated donors are not common (0.8%) in the National Transplant Organization register (NTO),3 they represent a possible alternative to diminish the organ deficit. We decided to include cadaver donors who died of intoxication with organophosphates, methanol, acetylsalicylic acid (ASA), and cyanide. Possible complications from the use of these types of donors include the following: acute tubular necrosis and rhabdomyolysis from methanol, direct neurotoxicity by induction of cellular oxidative stress and lipid peroxidation systems, which occur to the greatest extent in the brain due to cyanide and tubular injury with proteinuria from ASA.4 –7
PATIENTS AND METHODS Among 507 organ donors procured between January 1998 and December 2002, 5 (0.98%) had brain death from intoxication with the following: organophosphates (n ⫽ 2); methanol (n ⫽ 1); cyanide (n ⫽ 1) or ASA (n ⫽ 1). None of them had any disease prior to the intoxication. Brain death was pronounced in accordance with Colombian Law. Two clinical evaluations were made within 6 hours, 1 of which had to be done by a neurosurgeon or neurologist. The evaluating physicians were not part of the transplant group. After a physical examination that showed absence of brainstem reflexes, namely, no reaction to painful stimuli in the cranial nerve territories, mydriasis, absence of corneal, cough, gas,
From the Transplant Group, University of Antioquia, San Vicente de Paul University Hospital, Medellı´n, Colombia, South America. Address reprint requests to Edison Duque, MD, Transplant Coordinator, Transplant Group, University of Antioquia, San Vicente de Paul University Hospital, Calle 64 # 51-70, Medellin, Colombia, South America. E-mail: [email protected]; [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.06.017
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1632
Transplantation Proceedings, 36, 1632–1633 (2004)
INTOXICATED DONORS
1633 Table 1. Intoxicated Donors
Donor/Toxic
1 2 3 4 5
Organophosphate Organophosphate Cyanide Methanol ASA
Age (y)/ Gender
IngestionDeath (d)
Dopamine (/kg/min)
AST/ALT (mg%)
Serum Creatinine mg%
18/F 29/F 24/M 41/M 26/F
2 7 1 2 2
8 8 8 12 10
Not available 24/60 110/49 27/21 62/31
0.8 1.2 1.3 1.0 0.6
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; F, female; M, male.
oculovestibular, and oculocephalic reflexes) and absence of spontaneous breathing, brain death was pronounced and a written family consent for donation sought. Cerebral blood flow tests and electroencephalogram were not required for the brain death diagnosis in adults, but transcranial Doppler was performed on donors who died due to ASA, cyanide, or methanol intoxication. In every case it was compatible with brain death. Donors were evaluated by the transplant coordination team. Laboratory examinations were performed to evaluate renal and hepatic functions, electrolytes, coagulation, and viral infections. No hepatic or renal ultrasounds were made. The donors were 2 men and 3 women of mean age 26 ⫾ 8.5 years. Their mean serum creatinine level was 1.0 ⫾ 0.29 mg% (0.6 –1.3). Dopamine was used in all donors. Diuresis was always present during donor care (Table 1). The results from the use of these organs for transplantation was evaluated by calculating patient and graft actuarial survival using the Kaplan-Meier method, with WinTx, our own transplant group’s statistical program.
RESULTS
Ten renal transplantations were performed with the organs procured from the donors included in this study. The mean age of the recipients was 44.5 ⫾ 8.3 years. The mean serum creatinine level at the time of transplantation was 10.0 ⫾ 3.3 mg% (7.0 –15.3). Serum creatinine level was measured at 3, 6, 12, 18, and 24 months posttransplantation. At month 6 the mean serum creatinine level was 1.2 ⫾ 0.4 mg% (Table 2). Actuarial patient and graft survivals were calculated over 24 months (Table 3). One-year patient survival rate was 89%, lower than that of NTO register (95.2%)3 and lower than that of United Network for Organ Sharing (UNOS) (94.7%).3 One-month graft survival rate was 90%, similar to the UNOS (91.2%)3 and better than that of the NTO register (86%).3 In our population, there were no differences between patient and graft survival. Patients were followed for a mean of 26.0 ⫾ 23.0 months Table 2. Mean Serum Creatinine mg% in Renal Transplant Recipients Mo
Patients Studied
Mean Serum Creatinine ⫾ SD (range)
0 3 6 12 18 24
10 8 6 6 3 3
10.0 ⫾ 3.3 (7.0–15.3) 1.4 ⫾ 0.3 (1.1–1.9) 1.2 ⫾ 0.4 (0.6–1.8) 1.4 ⫾ 0.5 (1.0–2.4) 1.0 ⫾ 0.2 (0.9–1.2) 1.2 ⫾ 0.1 (1.2–1.3)
(range, 0 –36 months). Five recipients lived outside Medellin, so that they were followed for a shorter period (range, 2–13 months). There were no episodes of graft rejection nor delayed graft function. There were no hepatic, renal, hematological, nor pulmonary complications. There was no evidence of acute or chronic toxicity. Two of the 10 patients died 1 immediately after surgery due to anesthetic complications and the other at 17 months after surgery because of unknown reasons. DISCUSSION
These results suggest that use of organs procured from poisoned donors is feasible and secure, in the cases of organophosphates, cyanide, methanol, and ASA. There is no contraindication for kidney transplantation. We have not found any signs of poisoning in our patients. The survival of our patients is as good as that of other transplant centers. Although the incidence of these donors is low, they represent a safe choice to reduce organ scarcity. Table 3. Actuarial Survival of Patients and Grafts Mo
Patients (n ⫽ 10)
Grafts (n ⫽ 10)
1 6 12 18 24
0.90 0.89 0.89 0.75 0.75
0.90 0.89 0.89 0.75 0.75
REFERENCES 1. López-Navidad A, Caballero F, Gonzalez-Segura C, et al: Clin Transplant 16:151, 2002 2. Hantson P, Vekemans MC, Squifflet JP, et al: Transpl Int 8:185, 1995 3. Naya M, Miranda B, Cuende N, et al: Transplantation 69:S335, 2000 4. Sharma A: Toxic alcohols. In Goldfrank’s Toxicologic Emergency, 7th ed. New York: McGraw Hill; 2002, p 983 5. Ravishankar DK, Kashi SH, Lam FT: Clin Transplant 12:143, 1998 6. Kerns W II, Isom G, Kirk MA: Cyanide and hydrogen sulfide. In Goldfrank’s Toxicologic Emergency, 7th ed, New York: McGraw Hill; 2002, p 1500 7. Flommenbaum NE, Lewin NA, Howland MA, et al: Salicylates. In Goldfrank’s Toxicologic Emergency, 7th ed. New York: McGraw Hill; 2002, p 510
T
HE SHORTAGE of organs for transplantation and the high number of potential recipients who die on transplant waiting lists have made it necessary to extend the criteria for donor selection to include individuals who die of intoxication with certain drugs or industrial products.1 The use of intoxicated donors to expand the organ pool has been poorly explored with few reports2 that do not permit the formulation of definite inclusion or exclusion criteria. Although intoxicated donors are not common (0.8%) in the National Transplant Organization register (NTO),3 they represent a possible alternative to diminish the organ deficit. We decided to include cadaver donors who died of intoxication with organophosphates, methanol, acetylsalicylic acid (ASA), and cyanide. Possible complications from the use of these types of donors include the following: acute tubular necrosis and rhabdomyolysis from methanol, direct neurotoxicity by induction of cellular oxidative stress and lipid peroxidation systems, which occur to the greatest extent in the brain due to cyanide and tubular injury with proteinuria from ASA.4 –7
PATIENTS AND METHODS Among 507 organ donors procured between January 1998 and December 2002, 5 (0.98%) had brain death from intoxication with the following: organophosphates (n ⫽ 2); methanol (n ⫽ 1); cyanide (n ⫽ 1) or ASA (n ⫽ 1). None of them had any disease prior to the intoxication. Brain death was pronounced in accordance with Colombian Law. Two clinical evaluations were made within 6 hours, 1 of which had to be done by a neurosurgeon or neurologist. The evaluating physicians were not part of the transplant group. After a physical examination that showed absence of brainstem reflexes, namely, no reaction to painful stimuli in the cranial nerve territories, mydriasis, absence of corneal, cough, gas,
From the Transplant Group, University of Antioquia, San Vicente de Paul University Hospital, Medellı´n, Colombia, South America. Address reprint requests to Edison Duque, MD, Transplant Coordinator, Transplant Group, University of Antioquia, San Vicente de Paul University Hospital, Calle 64 # 51-70, Medellin, Colombia, South America. E-mail: [email protected]; [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.06.017
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1632
Transplantation Proceedings, 36, 1632–1633 (2004)
INTOXICATED DONORS
1633 Table 1. Intoxicated Donors
Donor/Toxic
1 2 3 4 5
Organophosphate Organophosphate Cyanide Methanol ASA
Age (y)/ Gender
IngestionDeath (d)
Dopamine (/kg/min)
AST/ALT (mg%)
Serum Creatinine mg%
18/F 29/F 24/M 41/M 26/F
2 7 1 2 2
8 8 8 12 10
Not available 24/60 110/49 27/21 62/31
0.8 1.2 1.3 1.0 0.6
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; F, female; M, male.
oculovestibular, and oculocephalic reflexes) and absence of spontaneous breathing, brain death was pronounced and a written family consent for donation sought. Cerebral blood flow tests and electroencephalogram were not required for the brain death diagnosis in adults, but transcranial Doppler was performed on donors who died due to ASA, cyanide, or methanol intoxication. In every case it was compatible with brain death. Donors were evaluated by the transplant coordination team. Laboratory examinations were performed to evaluate renal and hepatic functions, electrolytes, coagulation, and viral infections. No hepatic or renal ultrasounds were made. The donors were 2 men and 3 women of mean age 26 ⫾ 8.5 years. Their mean serum creatinine level was 1.0 ⫾ 0.29 mg% (0.6 –1.3). Dopamine was used in all donors. Diuresis was always present during donor care (Table 1). The results from the use of these organs for transplantation was evaluated by calculating patient and graft actuarial survival using the Kaplan-Meier method, with WinTx, our own transplant group’s statistical program.
RESULTS
Ten renal transplantations were performed with the organs procured from the donors included in this study. The mean age of the recipients was 44.5 ⫾ 8.3 years. The mean serum creatinine level at the time of transplantation was 10.0 ⫾ 3.3 mg% (7.0 –15.3). Serum creatinine level was measured at 3, 6, 12, 18, and 24 months posttransplantation. At month 6 the mean serum creatinine level was 1.2 ⫾ 0.4 mg% (Table 2). Actuarial patient and graft survivals were calculated over 24 months (Table 3). One-year patient survival rate was 89%, lower than that of NTO register (95.2%)3 and lower than that of United Network for Organ Sharing (UNOS) (94.7%).3 One-month graft survival rate was 90%, similar to the UNOS (91.2%)3 and better than that of the NTO register (86%).3 In our population, there were no differences between patient and graft survival. Patients were followed for a mean of 26.0 ⫾ 23.0 months Table 2. Mean Serum Creatinine mg% in Renal Transplant Recipients Mo
Patients Studied
Mean Serum Creatinine ⫾ SD (range)
0 3 6 12 18 24
10 8 6 6 3 3
10.0 ⫾ 3.3 (7.0–15.3) 1.4 ⫾ 0.3 (1.1–1.9) 1.2 ⫾ 0.4 (0.6–1.8) 1.4 ⫾ 0.5 (1.0–2.4) 1.0 ⫾ 0.2 (0.9–1.2) 1.2 ⫾ 0.1 (1.2–1.3)
(range, 0 –36 months). Five recipients lived outside Medellin, so that they were followed for a shorter period (range, 2–13 months). There were no episodes of graft rejection nor delayed graft function. There were no hepatic, renal, hematological, nor pulmonary complications. There was no evidence of acute or chronic toxicity. Two of the 10 patients died 1 immediately after surgery due to anesthetic complications and the other at 17 months after surgery because of unknown reasons. DISCUSSION
These results suggest that use of organs procured from poisoned donors is feasible and secure, in the cases of organophosphates, cyanide, methanol, and ASA. There is no contraindication for kidney transplantation. We have not found any signs of poisoning in our patients. The survival of our patients is as good as that of other transplant centers. Although the incidence of these donors is low, they represent a safe choice to reduce organ scarcity. Table 3. Actuarial Survival of Patients and Grafts Mo
Patients (n ⫽ 10)
Grafts (n ⫽ 10)
1 6 12 18 24
0.90 0.89 0.89 0.75 0.75
0.90 0.89 0.89 0.75 0.75
REFERENCES 1. López-Navidad A, Caballero F, Gonzalez-Segura C, et al: Clin Transplant 16:151, 2002 2. Hantson P, Vekemans MC, Squifflet JP, et al: Transpl Int 8:185, 1995 3. Naya M, Miranda B, Cuende N, et al: Transplantation 69:S335, 2000 4. Sharma A: Toxic alcohols. In Goldfrank’s Toxicologic Emergency, 7th ed. New York: McGraw Hill; 2002, p 983 5. Ravishankar DK, Kashi SH, Lam FT: Clin Transplant 12:143, 1998 6. Kerns W II, Isom G, Kirk MA: Cyanide and hydrogen sulfide. In Goldfrank’s Toxicologic Emergency, 7th ed, New York: McGraw Hill; 2002, p 1500 7. Flommenbaum NE, Lewin NA, Howland MA, et al: Salicylates. In Goldfrank’s Toxicologic Emergency, 7th ed. New York: McGraw Hill; 2002, p 510