- Email: [email protected]
The influence of desmopressin and vasopressors in the donor management on graft function following pancreas transplantation
The Influence of Desmopressin and Vasopressors in the Donor Management on Graft Function Following Pancreas Transplantation I. Decraemer, K. Cathenis, R. Troisi, B. deHemptinne, and U.J. Hesse ABSTRACT Introduction. The use of desmopressin and vasopressors in cadaveric organ donors is considered a risk factor for graft dysfunction following pancreas transplantation by influencing the microcirculation. The aim of this study was to investigate the influence of these substances on early graft function. Patients and methods. This single-center retrospective trial included 59 patients who underwent simultaneous or solitary pancreas transplantation. The corresponding donor charts were reviewed for the use of vasopressors and desmopressin. Impaired graft function was determined as graft thrombosis or as insulin-dependence for more then 3 days posttransplant. Daily amylase and lipase concentrations from abdominal drains were measured to quantify reperfusion pancreatitis and fistula formation. Results. Overall, pancreas thrombosis was observed in 4 of 59 (6.8%) recipients. There were no significant differences in thrombosis rate whether the donors received desmopressin (3/38 vs 1/21, P ⬎ .1) or the needed vasopressors (3/53 vs 1/9, P ⬎ .1). The number of patients who required insulin for more than 3 days posttransplant was comparable whether the donors received desmopressin (9/38 vs 4/21, P ⬎ .1), or vasopressors (9/46 vs 3/8, P ⬎ .1). At present all recipients with functioning pancreatic grafts (ie, 92.7%) are free of exogenous insulin therapy at 2 to 80 months posttransplant. The amylase/lipase concentrations of peritoneal fluid were independent of the administration of desmopressin or vasopressors in the donors. Conclusion. In this study donor desmopressin and vasopressor administration did not influence graft function after pancreas transplantation.
P
ANCREAS TRANSPLANTATION has become an accepted therapy for patients with insulin-dependent diabetes. The improving results have increased the need for suitable organ donors. The disproportion between the need and the availability of donors leads to transplantation of marginal-quality organs. Under these circumstances improved intensive care treatment of potential organ donors gains importance. Two agents used in donor management are desmopressin and vasopressors such as dopamine, noradrenaline, adrenaline, and dobutamine. Both have positive effects on the donor stabilization, but may compromise graft function after transplantation. Diabetes insipidus is observed among 77% to 88% of all brain-dead organ donors.1 Damage to the neurohypophyseal-hypothalamic axis results in imbalances of antidiuretic hormone (ADH) release leading to electrolyte, fluid, and volume shifts.1 In these cases desmopressin is administered
to prevent hypovolemia, hyponatriemia, hypotension, and microcirculatory damage to donor organs.2 Besides its antidiuretic effect, desmopressin is also recommended as a hemostatic agent in surgical procedures on high-risk patients with impaired coagulation due to its hypercoagulation potential.3 It is well known that desmopressin induces P-selectin expression4 and release of von Willebrand Factor (vWF).5 P-selectin is important in the interactions of both leukocytes6 and platelets7 with the endothelium, which may lead to reduced organ perfusion and function. Recently a report from Keck et al provided From the Department of Surgery, University of Ghent De Pintelaan, Gent, Belgium. Address reprint requests to U.J. Hesse, Department of Surgery, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.05.026
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1042
Transplantation Proceedings, 36, 1042–1044 (2004)
INFLUENCE OF DESMOPRESSIN AND VASOPRESSORS
experimental evidence for the deleterious effects of desmopressin on early graft microcirculation and function.8 The aim of the present study was to explore these findings in a clinical setting. Another aspect of donor management is the maintenance of an adequate blood pressure. A central venous pressure between 10 and 15 mm Hg should be maintained with intensive fluid resuscitation and a vasopressor if necessary.9 One of the properties of vasopressors is that they cause peripheral vasoconstriction, which could negatively influence graft perfusion and function after transplantation.10,11 On the contrary a case-control study showed less acute rejection and improved graft survival after renal transplantation when donors were pretreated with adrenergic agents.12 Although the molecular mechanisms that deliver these beneficial effects remain to be elucidated, adrenergic substances at clinically relevant concentrations have been shown to reduce the expression of endothelial adhesion molecules in vitro.13 The purpose of the present study was to investigate the effects of vasopressors and desmopressin on graft function following pancreas transplantation. PATIENTS AND METHODS This single-center retrospective trial included 62 patients who underwent simultaneous pancreas-kidney transplantation (n ⫽ 53) or solitary pancreas transplantation (n ⫽ 9) including three retransplantations, which were not considered herein. The corresponding donor charts were reviewed to note the use of vasopressors or ADH. Impaired graft function was determined to be graft thrombosis or insulin-dependence for more than 3 days posttransplant. During the first 10 days post-Tx daily amylase and lipase concentrations were measured on abdominal drains to quantify reperfusion pancreatitis and fistula formation. Fisher exact test was used for statistical evaluation.
RESULTS
Donor and recipient variables are summarized in Table 1. There were 39 men and 20 women with a mean donor age of 31.7 years (⫾11.7) and a mean ICU stay of 3.23 days (⫾2.09). Traumatic brain injuries (64%) and primary cerebrovascular lesions (32%) were the most frequent causes of death. Cold ischemia times ranged between 5 and 14 hours, with a mean of 10.0 hours (⫾2.5). Among 59 brain-dead donors 38 (64%) received desmopressin in a variety of doses (range 1 to 10 g), and 21 (35%) were not treated with this agent. Fifty one (86%) needed vasopressors and 8 (14%) did not. Thirty three (56%) donors received both. No significant differences were observed in donor or recipient characteristics whether the donors received desmopressin (Table 2) or vasopressors (Table 3). The 4 (6.8%) grafts that failed had to be removed due to thrombosis. The thrombosis rate did not differ significantly among the group that received desmopressin (3/38 vs 1/21, P ⬎ .1). Similarly, no significant difference in thrombosis rate was observed between the group that needed vasopressors (3/53 vs 1/9, P ⬎ .1). In the group that received vasopressors and
1043 Table 1. Donor and Recipient Characteristics Variable*
Donor age (years) Donor sex (males/females) Cause of death (traumatic/cerebrovascular) ICU stay (days) Desmopressin/no desmopressin Vasopressin/no vasopressors CIT (hours) Preservation (UW/HTK) Recipient sex (males/females) Recipient age (years) Duration diabetes mellitus (years) Dialysis (yes/no) Bladder/enteric drainage SPK/PAK/PTA Thrombosis/no thrombosis Insulin need/no insulin need
31.7 (11.7) 39/20 38/19 (64%/32%) 3.2 (2.1) 38/21 (64%/36%) 47/12 (80%/20%) 10.0 (2.5) 51/8 (86%/14%) 40/19 (68%/32%) 43.2 (7.4) 24.6 (8.0) 44/13 (77%/23%) 13/46 (22%/78%) 53/3/3 (90%/5%/5%) 5/51 (8.5%/91.5%) 12/42 (20%/71%)
*Mean (SD) except where marked otherwise.
desmopressin, two grafts (6.0%) had to be removed due to thrombosis. Twenty three percent of the recipients of grafts from the donors who had received desmopressin needed insulin for more than 3 days versus 20% in the other group. The number of patients who required insulin was comparable whether the donors received vasopressin (9/46 vs 3/8). In the group that received both agents, 6 (20.6%) needed insulin. Twelve of 59 (20.3%) patients needed insulin for more then 3 days post-Tx. At present all recipients with functioning pancreatic grafts (ie, 92.7%) are free of exogeneous insulin therapy at 2 to 80 months posttransplant. The amylase/lipase concentrations of peritoneal fluid were independent of the administration of desmopressin or vasopressors in the donors.
Table 2. Donor and Recipient Characteristics Relative to Donor Treatment With Desmopressin Variable*
Desmopressin (n ⫽ 38)
Controls (n ⫽ 21)
Mean age donors (years) 30.61 (⫾11.18) 33.62 (⫾12.87) Donor sex (males/females) 28/10 11/10 Cause of death (traumatic/ 12/8 26/11 cerebrovascular) ICU stay (days) 2.34 (⫾1.38) 2.74 (⫾2.33) Mean age recipients (years) 44.03 (⫾8.03) 41.71 (⫾6.06) Recipient sex (males/females) 27/11 13/18 Preservation (UW/HTK) 31/7 20/1 Duration diabetes mellitus 25.76 (7.58) 22.79 (8.44) (years) Dialysis (no/yes) 10/26 3/18 CIT (hours) 9.92 (⫾2.55) 10.53 (⫾2.49) Bladder/enteric drainage 6/32 7/14 *Mean (SD) except where marked otherwise.
P value
.40 .56 .56 .78 .25 .56 .24 .25 .33 .61 .19
1044
DECRAEMER, CATHENIS, TROISI ET AL
Table 3. Donor and Recipient Characteristics Relative to Donor Treatment With Vasopressors Variable*
Mean age donors (years) Donor sex (males/females) Cause of death (traumatic/cerebrovascular) ICU stay (days) Preservation (UW/HTK) Mean age recipient (years) Recipient sex (males/females) Duration diabetes mellitus (years) Dialysis (no/yes) CIT (hours) Bladder/enteric drainage
Vasopressors (n ⫽ 51)
Controls (n ⫽ 8)
31.7 (11.2) 29/18 29/16
31.4 (14.5) 10/2 9/3
.72 .19 .73
2.4 (1.6) 39/8 42.8 (7.4) 30/17 25.7 (7.1) 12/33 10.0 (2.6) 11/36
2.9 (2.3) 12/0 447 (7.7) 10/2 20.2 (10.0) 1/11 10.7 (2.3) 2/10
.60 .19 .35 .30 .09 .26 .31 1.00
P value
*Mean (SD) except where marked otherwise.
DISCUSSION
Two of the main problems after onset of brain death are the cessation of ADH production, resulting in diabetes insipidus, and the damage to vasomotor centres with the onset of peripheral vasodilatation, hypotonus, and reduced organ perfusion.14 The role of desmopressin in donor treatment for diabetes insipidus is controversial. The adverse effect of desmopressin on organ function in a clinical setting has been described for kidney transplantation. In a prospective randomized trial Hirschl et al2 reported that primary graft failure of kidneys from donors who had been treated with desmopressin (48.6%) was significantly different than controls (23.5%). In contrast, in a retrospective trial, Guesde et al15 found no significant change in renal function when desmopressin was used in donors. The report of Keck et al8 was the first to experimentally examine the effects of donor desmopressin administration on pancreas function after transplantation. Intravital microscopy studies on the microvasculature of the transplanted rat pancreas showed that prolonged pretreatment of donors with desmopressin led to increased platelet and leukocyte interactions with the endothelium. The expected upregulation of P-selectin was confirmed by immunohistochemistry. Finally, the study demonstrated significant histological damage to the endothelium among desmopressin-treated pancreas transplants with impaired microcirculation, delayed graft function, and increased risk of thrombosis. In contrast to these experimental findings, the present study did not show any significant effects of the administration of desmopressin on clinical pancreas thrombosis or function. Recent studies have reported a beneficial effect of donor preconditioning with dopamine on immediate and longterm graft function after renal transplantation.13 This finding could eventually lead to systematic administration of dopamine to organ donors. In contrast to studies reporting a negative influence on graft function,10,11 we did not observe any correlation between donor administration of vasopressors and early graft function.
It should be noted that the rather small sample size might have influenced the insignificant differences in outcomes. The parameters to quantify graft function (ie, rate of thrombosis and delayed graft function) were rather crude but clinically reliable. In this series, it is remarkable that the majority of donors required some treatment potentially interfering with microcirculation as has been reported by others.14 However, the organ might not have been available in the absence of desmopressin or hemodynamic support. Larger, prospective randomized trials are necessary to determine the effects of desmopressin and vasopressor administration on pancreas graft function.16,17 REFERENCES 1. Howlett TA, Keogh AM, Perry L, et al: Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy. Transplantation 47:828, 1989 2. Hirshl MM, Matzner MP, Huber WO, et al: Effect of desmopressin substitution during organ procurement on early renal allograft function. Nephrol Dial Transplant 11:173, 1996 3. Lethagen S: Desmopressin—a haemostatic drug: state-of-theart review. Eur J Anaesthesiol (Suppl)14:1, 1997 4. Kanwar S, Woodman, Poon MC, et al: Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules. Blood 86:2760, 1995 5. Borchiellini A, Fijnvandraat K, ten Cate JW, et al: Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood 88:2951, 1996 6. Raud J, Lindbom L: Leukocyte rolling and firm adhesion in the microcirculation. Gastroenterology 104:310, 1993 7. Massberg S, Enders G, Leiderer R, et al: Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P-selectin. Blood 92:507, 1998 8. Keck T, Banafsche R, Werner J, et al: Desmopressin impairs microcirculation in donor pancreas and early graft function after experimental pancreas transplantation. Transplantation 72:202, 2001 9. Soifer B, Gelb AW: The multiple organ donor: identification and management. Ann Intern Med 110:814, 1989 10. Kapur S, Bonham CA, Dodson SF, et al: Strategies to expand the donor pool for pancreas transplantation. Transplantation 67:284, 1999 11. Marshall R, Ahsan N, Dhillon D, et al: adverse effect of donor vasopressor support on immediate and one-year kidney allograft function. Surgery 120:663, 1996 12. Schnuelle P, Lorenz D, Mueller A, et al: Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int 56:738, 1999 13. Fortenberry JD, Huber AR, Owens ML: Inotropes inhibit endothelial cell surface adhesion molecules induced by interleukin1beta. Crit Care Med 25:303, 1997 14. Bodenham A, Park GR: Care of the multiple organ donor. Intensive Care Med 15:340, 1989 15. Guesde R, Barrou B, Leblanc I, et al: Administration of desmopressin in brain-dead donors and renal function in kidney recipients. Lancet 2:1178, 1998 16. Koo DD, Welsh KI, McLaren AJ, et al: Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation. Kidney Int 56:1551, 1999 17. Chapman JR, Robertson P, Allen RD: Why do pancreas transplants thrombose? Transplantation 72:182, 2001
P
ANCREAS TRANSPLANTATION has become an accepted therapy for patients with insulin-dependent diabetes. The improving results have increased the need for suitable organ donors. The disproportion between the need and the availability of donors leads to transplantation of marginal-quality organs. Under these circumstances improved intensive care treatment of potential organ donors gains importance. Two agents used in donor management are desmopressin and vasopressors such as dopamine, noradrenaline, adrenaline, and dobutamine. Both have positive effects on the donor stabilization, but may compromise graft function after transplantation. Diabetes insipidus is observed among 77% to 88% of all brain-dead organ donors.1 Damage to the neurohypophyseal-hypothalamic axis results in imbalances of antidiuretic hormone (ADH) release leading to electrolyte, fluid, and volume shifts.1 In these cases desmopressin is administered
to prevent hypovolemia, hyponatriemia, hypotension, and microcirculatory damage to donor organs.2 Besides its antidiuretic effect, desmopressin is also recommended as a hemostatic agent in surgical procedures on high-risk patients with impaired coagulation due to its hypercoagulation potential.3 It is well known that desmopressin induces P-selectin expression4 and release of von Willebrand Factor (vWF).5 P-selectin is important in the interactions of both leukocytes6 and platelets7 with the endothelium, which may lead to reduced organ perfusion and function. Recently a report from Keck et al provided From the Department of Surgery, University of Ghent De Pintelaan, Gent, Belgium. Address reprint requests to U.J. Hesse, Department of Surgery, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.05.026
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1042
Transplantation Proceedings, 36, 1042–1044 (2004)
INFLUENCE OF DESMOPRESSIN AND VASOPRESSORS
experimental evidence for the deleterious effects of desmopressin on early graft microcirculation and function.8 The aim of the present study was to explore these findings in a clinical setting. Another aspect of donor management is the maintenance of an adequate blood pressure. A central venous pressure between 10 and 15 mm Hg should be maintained with intensive fluid resuscitation and a vasopressor if necessary.9 One of the properties of vasopressors is that they cause peripheral vasoconstriction, which could negatively influence graft perfusion and function after transplantation.10,11 On the contrary a case-control study showed less acute rejection and improved graft survival after renal transplantation when donors were pretreated with adrenergic agents.12 Although the molecular mechanisms that deliver these beneficial effects remain to be elucidated, adrenergic substances at clinically relevant concentrations have been shown to reduce the expression of endothelial adhesion molecules in vitro.13 The purpose of the present study was to investigate the effects of vasopressors and desmopressin on graft function following pancreas transplantation. PATIENTS AND METHODS This single-center retrospective trial included 62 patients who underwent simultaneous pancreas-kidney transplantation (n ⫽ 53) or solitary pancreas transplantation (n ⫽ 9) including three retransplantations, which were not considered herein. The corresponding donor charts were reviewed to note the use of vasopressors or ADH. Impaired graft function was determined to be graft thrombosis or insulin-dependence for more than 3 days posttransplant. During the first 10 days post-Tx daily amylase and lipase concentrations were measured on abdominal drains to quantify reperfusion pancreatitis and fistula formation. Fisher exact test was used for statistical evaluation.
RESULTS
Donor and recipient variables are summarized in Table 1. There were 39 men and 20 women with a mean donor age of 31.7 years (⫾11.7) and a mean ICU stay of 3.23 days (⫾2.09). Traumatic brain injuries (64%) and primary cerebrovascular lesions (32%) were the most frequent causes of death. Cold ischemia times ranged between 5 and 14 hours, with a mean of 10.0 hours (⫾2.5). Among 59 brain-dead donors 38 (64%) received desmopressin in a variety of doses (range 1 to 10 g), and 21 (35%) were not treated with this agent. Fifty one (86%) needed vasopressors and 8 (14%) did not. Thirty three (56%) donors received both. No significant differences were observed in donor or recipient characteristics whether the donors received desmopressin (Table 2) or vasopressors (Table 3). The 4 (6.8%) grafts that failed had to be removed due to thrombosis. The thrombosis rate did not differ significantly among the group that received desmopressin (3/38 vs 1/21, P ⬎ .1). Similarly, no significant difference in thrombosis rate was observed between the group that needed vasopressors (3/53 vs 1/9, P ⬎ .1). In the group that received vasopressors and
1043 Table 1. Donor and Recipient Characteristics Variable*
Donor age (years) Donor sex (males/females) Cause of death (traumatic/cerebrovascular) ICU stay (days) Desmopressin/no desmopressin Vasopressin/no vasopressors CIT (hours) Preservation (UW/HTK) Recipient sex (males/females) Recipient age (years) Duration diabetes mellitus (years) Dialysis (yes/no) Bladder/enteric drainage SPK/PAK/PTA Thrombosis/no thrombosis Insulin need/no insulin need
31.7 (11.7) 39/20 38/19 (64%/32%) 3.2 (2.1) 38/21 (64%/36%) 47/12 (80%/20%) 10.0 (2.5) 51/8 (86%/14%) 40/19 (68%/32%) 43.2 (7.4) 24.6 (8.0) 44/13 (77%/23%) 13/46 (22%/78%) 53/3/3 (90%/5%/5%) 5/51 (8.5%/91.5%) 12/42 (20%/71%)
*Mean (SD) except where marked otherwise.
desmopressin, two grafts (6.0%) had to be removed due to thrombosis. Twenty three percent of the recipients of grafts from the donors who had received desmopressin needed insulin for more than 3 days versus 20% in the other group. The number of patients who required insulin was comparable whether the donors received vasopressin (9/46 vs 3/8). In the group that received both agents, 6 (20.6%) needed insulin. Twelve of 59 (20.3%) patients needed insulin for more then 3 days post-Tx. At present all recipients with functioning pancreatic grafts (ie, 92.7%) are free of exogeneous insulin therapy at 2 to 80 months posttransplant. The amylase/lipase concentrations of peritoneal fluid were independent of the administration of desmopressin or vasopressors in the donors.
Table 2. Donor and Recipient Characteristics Relative to Donor Treatment With Desmopressin Variable*
Desmopressin (n ⫽ 38)
Controls (n ⫽ 21)
Mean age donors (years) 30.61 (⫾11.18) 33.62 (⫾12.87) Donor sex (males/females) 28/10 11/10 Cause of death (traumatic/ 12/8 26/11 cerebrovascular) ICU stay (days) 2.34 (⫾1.38) 2.74 (⫾2.33) Mean age recipients (years) 44.03 (⫾8.03) 41.71 (⫾6.06) Recipient sex (males/females) 27/11 13/18 Preservation (UW/HTK) 31/7 20/1 Duration diabetes mellitus 25.76 (7.58) 22.79 (8.44) (years) Dialysis (no/yes) 10/26 3/18 CIT (hours) 9.92 (⫾2.55) 10.53 (⫾2.49) Bladder/enteric drainage 6/32 7/14 *Mean (SD) except where marked otherwise.
P value
.40 .56 .56 .78 .25 .56 .24 .25 .33 .61 .19
1044
DECRAEMER, CATHENIS, TROISI ET AL
Table 3. Donor and Recipient Characteristics Relative to Donor Treatment With Vasopressors Variable*
Mean age donors (years) Donor sex (males/females) Cause of death (traumatic/cerebrovascular) ICU stay (days) Preservation (UW/HTK) Mean age recipient (years) Recipient sex (males/females) Duration diabetes mellitus (years) Dialysis (no/yes) CIT (hours) Bladder/enteric drainage
Vasopressors (n ⫽ 51)
Controls (n ⫽ 8)
31.7 (11.2) 29/18 29/16
31.4 (14.5) 10/2 9/3
.72 .19 .73
2.4 (1.6) 39/8 42.8 (7.4) 30/17 25.7 (7.1) 12/33 10.0 (2.6) 11/36
2.9 (2.3) 12/0 447 (7.7) 10/2 20.2 (10.0) 1/11 10.7 (2.3) 2/10
.60 .19 .35 .30 .09 .26 .31 1.00
P value
*Mean (SD) except where marked otherwise.
DISCUSSION
Two of the main problems after onset of brain death are the cessation of ADH production, resulting in diabetes insipidus, and the damage to vasomotor centres with the onset of peripheral vasodilatation, hypotonus, and reduced organ perfusion.14 The role of desmopressin in donor treatment for diabetes insipidus is controversial. The adverse effect of desmopressin on organ function in a clinical setting has been described for kidney transplantation. In a prospective randomized trial Hirschl et al2 reported that primary graft failure of kidneys from donors who had been treated with desmopressin (48.6%) was significantly different than controls (23.5%). In contrast, in a retrospective trial, Guesde et al15 found no significant change in renal function when desmopressin was used in donors. The report of Keck et al8 was the first to experimentally examine the effects of donor desmopressin administration on pancreas function after transplantation. Intravital microscopy studies on the microvasculature of the transplanted rat pancreas showed that prolonged pretreatment of donors with desmopressin led to increased platelet and leukocyte interactions with the endothelium. The expected upregulation of P-selectin was confirmed by immunohistochemistry. Finally, the study demonstrated significant histological damage to the endothelium among desmopressin-treated pancreas transplants with impaired microcirculation, delayed graft function, and increased risk of thrombosis. In contrast to these experimental findings, the present study did not show any significant effects of the administration of desmopressin on clinical pancreas thrombosis or function. Recent studies have reported a beneficial effect of donor preconditioning with dopamine on immediate and longterm graft function after renal transplantation.13 This finding could eventually lead to systematic administration of dopamine to organ donors. In contrast to studies reporting a negative influence on graft function,10,11 we did not observe any correlation between donor administration of vasopressors and early graft function.
It should be noted that the rather small sample size might have influenced the insignificant differences in outcomes. The parameters to quantify graft function (ie, rate of thrombosis and delayed graft function) were rather crude but clinically reliable. In this series, it is remarkable that the majority of donors required some treatment potentially interfering with microcirculation as has been reported by others.14 However, the organ might not have been available in the absence of desmopressin or hemodynamic support. Larger, prospective randomized trials are necessary to determine the effects of desmopressin and vasopressor administration on pancreas graft function.16,17 REFERENCES 1. Howlett TA, Keogh AM, Perry L, et al: Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy. Transplantation 47:828, 1989 2. Hirshl MM, Matzner MP, Huber WO, et al: Effect of desmopressin substitution during organ procurement on early renal allograft function. Nephrol Dial Transplant 11:173, 1996 3. Lethagen S: Desmopressin—a haemostatic drug: state-of-theart review. Eur J Anaesthesiol (Suppl)14:1, 1997 4. Kanwar S, Woodman, Poon MC, et al: Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules. Blood 86:2760, 1995 5. Borchiellini A, Fijnvandraat K, ten Cate JW, et al: Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood 88:2951, 1996 6. Raud J, Lindbom L: Leukocyte rolling and firm adhesion in the microcirculation. Gastroenterology 104:310, 1993 7. Massberg S, Enders G, Leiderer R, et al: Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P-selectin. Blood 92:507, 1998 8. Keck T, Banafsche R, Werner J, et al: Desmopressin impairs microcirculation in donor pancreas and early graft function after experimental pancreas transplantation. Transplantation 72:202, 2001 9. Soifer B, Gelb AW: The multiple organ donor: identification and management. Ann Intern Med 110:814, 1989 10. Kapur S, Bonham CA, Dodson SF, et al: Strategies to expand the donor pool for pancreas transplantation. Transplantation 67:284, 1999 11. Marshall R, Ahsan N, Dhillon D, et al: adverse effect of donor vasopressor support on immediate and one-year kidney allograft function. Surgery 120:663, 1996 12. Schnuelle P, Lorenz D, Mueller A, et al: Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int 56:738, 1999 13. Fortenberry JD, Huber AR, Owens ML: Inotropes inhibit endothelial cell surface adhesion molecules induced by interleukin1beta. Crit Care Med 25:303, 1997 14. Bodenham A, Park GR: Care of the multiple organ donor. Intensive Care Med 15:340, 1989 15. Guesde R, Barrou B, Leblanc I, et al: Administration of desmopressin in brain-dead donors and renal function in kidney recipients. Lancet 2:1178, 1998 16. Koo DD, Welsh KI, McLaren AJ, et al: Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation. Kidney Int 56:1551, 1999 17. Chapman JR, Robertson P, Allen RD: Why do pancreas transplants thrombose? Transplantation 72:182, 2001