AIM:To describe our single-centre experience in liver transplantation(LT)with the infusion of high perioperative thymoglobulin doses.The optimal dosage and timing of thymoglobulin[antithymocyte globulin(ATG)]administr...AIM:To describe our single-centre experience in liver transplantation(LT)with the infusion of high perioperative thymoglobulin doses.The optimal dosage and timing of thymoglobulin[antithymocyte globulin(ATG)]administration during LT remains controversial.Cytokine release syndrome,haemolytic anaemia,thrombocytopenia,neutropenia,fever and serum sickness are potential adverse effects associated with ATG infusion.METHODS:Between December 2009 and December 2010,16 adult non-randomized patients(ATG group),receiving a liver graft from a deceased donor,received an intraoperative infusion(4-6 h infusion)of thymoglobulin(3 mg/kg,ATG:Thymoglobuline).These patients were compared(case control approach)with 16 patients who had a liver transplant without ATG treatment(control group)to evaluate the possible effects of intraoperative ATG infusion.The matching parameters were:Sex,recipient age(±5 years),LT indication including viral status,MELD score(±5 points),international normalized ratio and platelet count(as close as possible).The exclusion criteria for both groups included the following:Multi-organ or living donor transplant,immunosuppressive therapy before transplantation,contraindications to the administration of any thymocyte globulin,human immunodeficiency virus seropositivity,thrombocytopenia[platelet<50000/μL]or leukopenia[white blood cells<1000/μL].The perioperative side effects(haemodynamic alterations,core temperature variations,colloids and crystalloids requirements,and surgical time)possibly related to ATG infusion and the thromboelastographic(TEG)evaluation of the ATG effects on coagulation,blood loss and blood product transfusion were analysed during the operation and the first three postoperative days.RESULTS:Intraoperative ATG administration was associated with longer surgical procedures[560±88 min vs 480±83 min(control group),P=0.013],an intraoperative core temperature more than 37℃(50%of ATG patients vs 6.2%of control patients,P=0.015),major intraoperative blood loss[3953±3126 mL vs 1419±940 mL(control group),P=0.05],higher red blood cell[2092±1856 mL ATG group vs 472±632 mL(control group),P=0.02],fresh frozen plasma[671±1125 mL vs 143±349 mL(control group),P=0.015],and platelet[374±537 mL vs 15.6±62.5 mL(control group),P=0.017]transfusion,and a higher requirement for catecholamines(0.08±0.07μg/kg per minutes vs 0.01±0.38μg/kg per minutes,respectively,in the ATG and control groups)for haemodynamic support.The TEG tracings changed to a straight line during ATG infusion(preanhepatic and anhepatic phases)in 81%of the patients from the ATG group compared to 6.25%from the control group(P<0.001).Patients from the ATG group compared to controls had higher post-op core temperatures(38℃±1.0℃vs 37.3℃±0.5℃;P=0.02),an increased need of noradrenaline(43.7%vs 6.25%,P=0.037),received more platelet transfusions(31.5%vs 0%,P=0.04)and required continuous renal replacement therapy(4 ATG patients vs none in the control group;P=0.10).ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure.CONCLUSION:The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.展开更多
AIM: To investigate patient and graft outcomes in isolated small bowel transplant(SBTx) recipients and immunosuppressant induction agent impact on outcomes.METHODS: A retrospective review of the perioperative data of ...AIM: To investigate patient and graft outcomes in isolated small bowel transplant(SBTx) recipients and immunosuppressant induction agent impact on outcomes.METHODS: A retrospective review of the perioperative data of patients who underwent SBTx transplant during an 8-year period was conducted. The intraoperative data were: patient demographics, etiology of short gut syndrome, hemodynamic parameters, coagulation profiles, intraoperative fluid and blood products transfused, and development of post-reperfusion. The postoperative data were: hospital/intensive care unit stays, duration of mechanical ventilation, postoperative incidence of acute kidney injury, and 1-year patient and graft outcomes. The effects of the three immunosuppressant induction agents(Zenapax, Thymoglobulin, Campath) on patient and graft outcomes were reviewed.RESULTS: During the 8-year period there were 77 patients; 1-year patient and graft survival were 95% and 86% respectively. Sixteen patients received Zenapax, 22 received Thymoglobulin, and 39 received Campath without effects on patient or graft survival(P = 0.90, P = 0.14, respectively). The use of different immune induction agents did not affect the incidence of rejection and infection during the first 90 postoperative days(P = 0.072, P = 0.29, respectively). The Zenapax group received more intraoperative fluid and blood products and were coagulopathic at the end of surgery. Zenapax and Thymoglobulin significantly increased serum creatinine at 48 h(P = 0.023) and 1 wk(P = 0.001) post-transplant, but none developed renal failure or required dialysis at the end of the first year.CONCLUSION: One-year patient and graft survival were 95% and 86%, respectively. The use of different immunosuppressant induction agents may affect the intraoperative course and short-term postoperative morbidities, but not 1-year patient and graft outcomes.展开更多
Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients. Published data support antibody induction in patients with immunologic risk to re...Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients. Published data support antibody induction in patients with immunologic risk to reduce the incidence of acute rejection(AR) and graft loss from rejection. However, the choice of antibody remains controversial as the clinical studies were carried out on patients of different immunologic risk and in the context of varying maintenance regimens. Antibody selection should be guided by a comprehensive assessment of immunologic risk, patient comorbidities, financial burden as well as the maintenance immunosuppressives. Lymphocyte-depleting antibody(thymoglobulin, ATGAM or alemtuzumab) is usually recommended for those with high risk of rejection, although it increases the risk of infection and malignancy. For low risk patients, interleukin-2 receptor antibody(basiliximab or daclizumab) reduces the incidence of AR without much adverse effects, making its balance favorable in mostpatients. It should also be used in the high risk patients with other medical comorbidities that preclude usage of lymphocyte-depleting antibody safely. There are many patients with very low risk, who may be induced with intravenous steroids without any antibody, as long as combined potent immunosuppressives are kept as maintenance. In these patients, benefits with antibody induction may be too small to outweigh its adverse effects and financial cost. Rituximab can be used in desensitization protocols for ABO and/or HLA incompatible transplants. There are emerging data suggesting that alemtuzumab induction be more successful than other antibody for promoting less intensive maintenance protocols, such as steroid withdrawal, tacrolimus monotherapy or lower doses of tacrolimus and mycophenolic acid. However, the long-term efficacy and safety of these unconventional strategies remains unknown.展开更多
文摘AIM:To describe our single-centre experience in liver transplantation(LT)with the infusion of high perioperative thymoglobulin doses.The optimal dosage and timing of thymoglobulin[antithymocyte globulin(ATG)]administration during LT remains controversial.Cytokine release syndrome,haemolytic anaemia,thrombocytopenia,neutropenia,fever and serum sickness are potential adverse effects associated with ATG infusion.METHODS:Between December 2009 and December 2010,16 adult non-randomized patients(ATG group),receiving a liver graft from a deceased donor,received an intraoperative infusion(4-6 h infusion)of thymoglobulin(3 mg/kg,ATG:Thymoglobuline).These patients were compared(case control approach)with 16 patients who had a liver transplant without ATG treatment(control group)to evaluate the possible effects of intraoperative ATG infusion.The matching parameters were:Sex,recipient age(±5 years),LT indication including viral status,MELD score(±5 points),international normalized ratio and platelet count(as close as possible).The exclusion criteria for both groups included the following:Multi-organ or living donor transplant,immunosuppressive therapy before transplantation,contraindications to the administration of any thymocyte globulin,human immunodeficiency virus seropositivity,thrombocytopenia[platelet<50000/μL]or leukopenia[white blood cells<1000/μL].The perioperative side effects(haemodynamic alterations,core temperature variations,colloids and crystalloids requirements,and surgical time)possibly related to ATG infusion and the thromboelastographic(TEG)evaluation of the ATG effects on coagulation,blood loss and blood product transfusion were analysed during the operation and the first three postoperative days.RESULTS:Intraoperative ATG administration was associated with longer surgical procedures[560±88 min vs 480±83 min(control group),P=0.013],an intraoperative core temperature more than 37℃(50%of ATG patients vs 6.2%of control patients,P=0.015),major intraoperative blood loss[3953±3126 mL vs 1419±940 mL(control group),P=0.05],higher red blood cell[2092±1856 mL ATG group vs 472±632 mL(control group),P=0.02],fresh frozen plasma[671±1125 mL vs 143±349 mL(control group),P=0.015],and platelet[374±537 mL vs 15.6±62.5 mL(control group),P=0.017]transfusion,and a higher requirement for catecholamines(0.08±0.07μg/kg per minutes vs 0.01±0.38μg/kg per minutes,respectively,in the ATG and control groups)for haemodynamic support.The TEG tracings changed to a straight line during ATG infusion(preanhepatic and anhepatic phases)in 81%of the patients from the ATG group compared to 6.25%from the control group(P<0.001).Patients from the ATG group compared to controls had higher post-op core temperatures(38℃±1.0℃vs 37.3℃±0.5℃;P=0.02),an increased need of noradrenaline(43.7%vs 6.25%,P=0.037),received more platelet transfusions(31.5%vs 0%,P=0.04)and required continuous renal replacement therapy(4 ATG patients vs none in the control group;P=0.10).ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure.CONCLUSION:The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.
基金Supported by The Department of Anesthesiology at the University of Pittsburgh Medical Center
文摘AIM: To investigate patient and graft outcomes in isolated small bowel transplant(SBTx) recipients and immunosuppressant induction agent impact on outcomes.METHODS: A retrospective review of the perioperative data of patients who underwent SBTx transplant during an 8-year period was conducted. The intraoperative data were: patient demographics, etiology of short gut syndrome, hemodynamic parameters, coagulation profiles, intraoperative fluid and blood products transfused, and development of post-reperfusion. The postoperative data were: hospital/intensive care unit stays, duration of mechanical ventilation, postoperative incidence of acute kidney injury, and 1-year patient and graft outcomes. The effects of the three immunosuppressant induction agents(Zenapax, Thymoglobulin, Campath) on patient and graft outcomes were reviewed.RESULTS: During the 8-year period there were 77 patients; 1-year patient and graft survival were 95% and 86% respectively. Sixteen patients received Zenapax, 22 received Thymoglobulin, and 39 received Campath without effects on patient or graft survival(P = 0.90, P = 0.14, respectively). The use of different immune induction agents did not affect the incidence of rejection and infection during the first 90 postoperative days(P = 0.072, P = 0.29, respectively). The Zenapax group received more intraoperative fluid and blood products and were coagulopathic at the end of surgery. Zenapax and Thymoglobulin significantly increased serum creatinine at 48 h(P = 0.023) and 1 wk(P = 0.001) post-transplant, but none developed renal failure or required dialysis at the end of the first year.CONCLUSION: One-year patient and graft survival were 95% and 86%, respectively. The use of different immunosuppressant induction agents may affect the intraoperative course and short-term postoperative morbidities, but not 1-year patient and graft outcomes.
文摘Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients. Published data support antibody induction in patients with immunologic risk to reduce the incidence of acute rejection(AR) and graft loss from rejection. However, the choice of antibody remains controversial as the clinical studies were carried out on patients of different immunologic risk and in the context of varying maintenance regimens. Antibody selection should be guided by a comprehensive assessment of immunologic risk, patient comorbidities, financial burden as well as the maintenance immunosuppressives. Lymphocyte-depleting antibody(thymoglobulin, ATGAM or alemtuzumab) is usually recommended for those with high risk of rejection, although it increases the risk of infection and malignancy. For low risk patients, interleukin-2 receptor antibody(basiliximab or daclizumab) reduces the incidence of AR without much adverse effects, making its balance favorable in mostpatients. It should also be used in the high risk patients with other medical comorbidities that preclude usage of lymphocyte-depleting antibody safely. There are many patients with very low risk, who may be induced with intravenous steroids without any antibody, as long as combined potent immunosuppressives are kept as maintenance. In these patients, benefits with antibody induction may be too small to outweigh its adverse effects and financial cost. Rituximab can be used in desensitization protocols for ABO and/or HLA incompatible transplants. There are emerging data suggesting that alemtuzumab induction be more successful than other antibody for promoting less intensive maintenance protocols, such as steroid withdrawal, tacrolimus monotherapy or lower doses of tacrolimus and mycophenolic acid. However, the long-term efficacy and safety of these unconventional strategies remains unknown.
