LETTERS TO THE EDITOR
Severe Complications After Bilateral Upper Extremity Transplantation: A Case Report
A
14-year-old Mexican mestizo female sustained high-tension electric burn, leading to bilateral proximal-third arm amputations. At age 17, the patient and her parents requested bilateral arm transplantation. Our institutional review board for clinical trial approved the surgery. She was healthy with no known drug allergies and her preoperative Doppler echocardiography showed normal cardiac function.
Surgery was performed on June 19, 2010. Two hours before the surgery, the patient was premedicated with methylprednisolone, chlorpheniramine, acetaminophen, and cefuroxime. As induction immunosuppressive therapy, antithymocyte globulin (ATG; 1.5 mg/kg, 90 mg total) was infused into a central vein through a 0.22-Km filter for 6 hr. Her temperature increased to 38-C at 1 hr after induction therapy and remained at this level until 2 hr before the end of the surgery. The parameters recorded during surgery are shown in Figure 1(A) and (B). The boney fixation was achieved followed by axillary artery anastomosis. Graft reperfusion was uneventful. Bleeding of 1,200 mL was permitted from each axillary vein to remove potassium and cytokines. The total ischemic time was 4 hr 47 min for the right arm and 5 hr 10 min for the left arm. The warm ischemic time was 30 min for each arm. After axillary vein anastomosis, the biceps brachii, coracobrachialis, and triceps muscles and the brachial plexus cords were reconstructed. After reperfusion of the right arm, the patient’s mean arterial blood pressure decreased, which was successfully treated by blood transfusion. After reperfusion of the left arm, she became hypotensive again and was poorly responsive to fluid resuscitation, requiring infusion of norepinephrine and vasopressin. After 17 hr of surgery, her oxygen venous saturation was 66% and her central venous pressure was 12 mm Hg. She was treated with dobutamine 2.5 Kg/kg
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per min without vasopressor, after which her SvO2 increased to 78%. The duration of surgery was 20 hr. The total blood loss was
15,050 mL, requiring transfusion of 45 units of packed red blood cells, 32 units of fresh frozen plasma, and 4 units of platelets.
FIGURE 1. Hemodynamic and chemical data. Transplantation
& Volume 98, Number 3, August 15, 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
* 2014 Lippincott Williams & Wilkins
At the end of the surgery, transplanted upper extremities had good perfusion, and the patient’s hemodynamic and clinical data were normal, except for a lactate level of 4.2 mmol/L. She remained stable at intensive care unit for the next 12 hr. The second dose of ATG (50 mg) was administered 24 hr after the first dose. Ten hours later, her heart rate increased to 110 beats per min, and because her mean arterial blood pressure decreased, norepinephrine was started. Simultaneously, there was indirect data of decreased cardiac output (SvO2, 61%; central venous pressure, 10 cm H2O), and the dobutamine was restarted (Fig. 1C). At this moment, the lactate level was 5.3 mmol/L, potassium level was 4.3 mEq/L, and creatine phosphokinase level was 1248 U/L. Subsequently, she developed Pulseless Electrical Activity, thus, we began cardiopulmonary resuscitation. Subsequently, her chest radiography showed diffuse bilateral interstitial edema, and transthoracic echocardiography showed an ejection fraction of 15% with generalized hypokinesis. Profuse salmoncolored pulmonary secretions were expelled through the endotracheal tube, and the patient ultimately expired. The patient did not undergo necropsy; however, postmortem biopsies were taken. Only the recipient’s shoulder skin showed acute inflammation, and the donor’s skin left arm showed minimal periadnexial and perivascular lymphocyte infiltrate. Cultures of the blood and pulmonary secretions were negative. The reasons for the cardiopulmonary deterioration in our patient are unclear. One possibility is that she developed a transfusion-related acute lung injury. Such reactions usually result in acute respiratory distress syndrome during or within 6 hr after the transfusion
(1). Another possibility is that she developed reperfusion syndrome. Reperfusion of a large fraction of the skeletal muscle mass may result in cardiopulmonary failure and death (2). However, her peak serum potassium level was 5 mEq/L, and peak creatine phosphokinase level was 1248 U/L. A severe case of cytokine release syndrome (CRS) secondary to ATG therapy is also possible. CRS has been described in patients treated for aplastic anemia or who have undergone kidney, liver, or pancreas transplantation (3Y6). Cytokine release syndrome typically begins 4 to 10 hr after the first or second infusion of ATG and may cause fever and cardiorespiratory dysfunction, including hypotension, acute respiratory distress syndrome, pulmonary edema, myocardial infarction, tachycardia, and death (3Y7). The causative factor of CRS is not fully understood (1). The temporal association between the rapid onset of pulmonary infiltration, heart failure, and ATG infusion in our patient was similar to the clinical courses in previously reported cases of severe CRS (4Y6). Even though the specific cause of death may not be clear, it is important to report all complications in patients undergoing vascularized composite tissue allotransplantation. Martı´n Iglesias Paulino Leal Patricia Butro´n Selene Santander-Flores Diego Rican˜o-Enciso Mario A. Gonzalez-Chavez Alberto M. Gonzalez-Chavez Leonardo Bravo-Ruiz Daniela Leo´n-Lopez Sofia Garcia-Mancilla Melina Dı´az-Morales
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Mario A. Moran-Romero Israel Espino-Gaucin Elizabeth Rodriguez-Rojas Plastic Surgery Service at Instituto Nacional de Ciencias Me´dicas y Nutricio´n Salvador Zubiran, Mexico DF, Mexico The authors declare no funding or conflicts of interest. Address correspondence to: Martin Iglesias, M.D., Monte de Antisana 47, Jardines en la Montan˜a, Tlalpan, Mexico DF 14210, Mexico. E-mail: [email protected] ‘‘Vascularized Composite Allotransplantation: Upper Extremity’’ was approved by Institutional Review Board for Clinical Trials with reference 84. Received 10 February 2014. Accepted 21 April 2014. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9803-00 DOI: 10.1097/TP.0000000000000258
REFERENCES 1.
2. 3.
4.
5. 6.
7.
Guo-Wei TU, Min-jie JU, Ming XU, et al. Antithymocyte globulin-induced acute respiratory distress syndrome after renal transplantation: a case report. Chin Med J 2012; 125: 1664. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002; 10: 620. Loushin MK, Hasinoff IK, Belani KG. A delayed cardiopulmonary reaction to an intravenous immunosuppressant thymoglobulin after pancreas transplant. Anesth Analg 2001; 93: 1260. Goligher EC, Csert-Gazdewich C, Balter M, et al. Acute lung injury during antithymocyte globulin therapy for aplastic anemia. Can Respir J 2009; 16: e3. Dean NC, Amend WC, Matthay MA. Adult respiratory distress syndrome related to antilymphocyte globulin therapy. Chest 1987; 91: 619. Busani S, Rinaldi L, Begliomini B, et al. Thymoglobulin-induced severe cardiovascular reaction and acute renal failure in a patient scheduled for orthotopic liver transplantation. Minerva Anestesiol 2006; 72: 243. Thymoglobulin (Anti-thymocyte Globulin [Rabbit]) Product Monograph. Sanofi-aventis Canada Inc. 2905 Place Louis-R.-Renaud Laval, Quebec H7V 0A3. Version 1.0 dated May 6, 2013.
A Case of Thrombotic Microangiopathy Associated With Antiphospholipid Antibody Syndrome Successfully Treated With Eculizumab
A
case of thrombotic microangiopathy (TMA) associated with antiphospholipid antibody syndrome (APS) successfully treated with eculizumab.
Antiphospholipid antibody syndrome is a multisystem disorder characterized
by vascular thrombosis and presence of circulating autoantibodies. The presence of APS can predispose to macrovascular thrombotic events, such as allograft thrombosis after kidney transplantation as well as microvascular thrombotic
renal disease (1) and is associated with a poor functional outcome in the first posttransplant year (2). Recent data have demonstrated the involvement of complement pathway in the pathogenesis of TMA because of APS nephropathy (3)
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Severe Complications After Bilateral Upper Extremity Transplantation: A Case Report
A
14-year-old Mexican mestizo female sustained high-tension electric burn, leading to bilateral proximal-third arm amputations. At age 17, the patient and her parents requested bilateral arm transplantation. Our institutional review board for clinical trial approved the surgery. She was healthy with no known drug allergies and her preoperative Doppler echocardiography showed normal cardiac function.
Surgery was performed on June 19, 2010. Two hours before the surgery, the patient was premedicated with methylprednisolone, chlorpheniramine, acetaminophen, and cefuroxime. As induction immunosuppressive therapy, antithymocyte globulin (ATG; 1.5 mg/kg, 90 mg total) was infused into a central vein through a 0.22-Km filter for 6 hr. Her temperature increased to 38-C at 1 hr after induction therapy and remained at this level until 2 hr before the end of the surgery. The parameters recorded during surgery are shown in Figure 1(A) and (B). The boney fixation was achieved followed by axillary artery anastomosis. Graft reperfusion was uneventful. Bleeding of 1,200 mL was permitted from each axillary vein to remove potassium and cytokines. The total ischemic time was 4 hr 47 min for the right arm and 5 hr 10 min for the left arm. The warm ischemic time was 30 min for each arm. After axillary vein anastomosis, the biceps brachii, coracobrachialis, and triceps muscles and the brachial plexus cords were reconstructed. After reperfusion of the right arm, the patient’s mean arterial blood pressure decreased, which was successfully treated by blood transfusion. After reperfusion of the left arm, she became hypotensive again and was poorly responsive to fluid resuscitation, requiring infusion of norepinephrine and vasopressin. After 17 hr of surgery, her oxygen venous saturation was 66% and her central venous pressure was 12 mm Hg. She was treated with dobutamine 2.5 Kg/kg
e16
www.transplantjournal.com
per min without vasopressor, after which her SvO2 increased to 78%. The duration of surgery was 20 hr. The total blood loss was
15,050 mL, requiring transfusion of 45 units of packed red blood cells, 32 units of fresh frozen plasma, and 4 units of platelets.
FIGURE 1. Hemodynamic and chemical data. Transplantation
& Volume 98, Number 3, August 15, 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
* 2014 Lippincott Williams & Wilkins
At the end of the surgery, transplanted upper extremities had good perfusion, and the patient’s hemodynamic and clinical data were normal, except for a lactate level of 4.2 mmol/L. She remained stable at intensive care unit for the next 12 hr. The second dose of ATG (50 mg) was administered 24 hr after the first dose. Ten hours later, her heart rate increased to 110 beats per min, and because her mean arterial blood pressure decreased, norepinephrine was started. Simultaneously, there was indirect data of decreased cardiac output (SvO2, 61%; central venous pressure, 10 cm H2O), and the dobutamine was restarted (Fig. 1C). At this moment, the lactate level was 5.3 mmol/L, potassium level was 4.3 mEq/L, and creatine phosphokinase level was 1248 U/L. Subsequently, she developed Pulseless Electrical Activity, thus, we began cardiopulmonary resuscitation. Subsequently, her chest radiography showed diffuse bilateral interstitial edema, and transthoracic echocardiography showed an ejection fraction of 15% with generalized hypokinesis. Profuse salmoncolored pulmonary secretions were expelled through the endotracheal tube, and the patient ultimately expired. The patient did not undergo necropsy; however, postmortem biopsies were taken. Only the recipient’s shoulder skin showed acute inflammation, and the donor’s skin left arm showed minimal periadnexial and perivascular lymphocyte infiltrate. Cultures of the blood and pulmonary secretions were negative. The reasons for the cardiopulmonary deterioration in our patient are unclear. One possibility is that she developed a transfusion-related acute lung injury. Such reactions usually result in acute respiratory distress syndrome during or within 6 hr after the transfusion
(1). Another possibility is that she developed reperfusion syndrome. Reperfusion of a large fraction of the skeletal muscle mass may result in cardiopulmonary failure and death (2). However, her peak serum potassium level was 5 mEq/L, and peak creatine phosphokinase level was 1248 U/L. A severe case of cytokine release syndrome (CRS) secondary to ATG therapy is also possible. CRS has been described in patients treated for aplastic anemia or who have undergone kidney, liver, or pancreas transplantation (3Y6). Cytokine release syndrome typically begins 4 to 10 hr after the first or second infusion of ATG and may cause fever and cardiorespiratory dysfunction, including hypotension, acute respiratory distress syndrome, pulmonary edema, myocardial infarction, tachycardia, and death (3Y7). The causative factor of CRS is not fully understood (1). The temporal association between the rapid onset of pulmonary infiltration, heart failure, and ATG infusion in our patient was similar to the clinical courses in previously reported cases of severe CRS (4Y6). Even though the specific cause of death may not be clear, it is important to report all complications in patients undergoing vascularized composite tissue allotransplantation. Martı´n Iglesias Paulino Leal Patricia Butro´n Selene Santander-Flores Diego Rican˜o-Enciso Mario A. Gonzalez-Chavez Alberto M. Gonzalez-Chavez Leonardo Bravo-Ruiz Daniela Leo´n-Lopez Sofia Garcia-Mancilla Melina Dı´az-Morales
e17
Mario A. Moran-Romero Israel Espino-Gaucin Elizabeth Rodriguez-Rojas Plastic Surgery Service at Instituto Nacional de Ciencias Me´dicas y Nutricio´n Salvador Zubiran, Mexico DF, Mexico The authors declare no funding or conflicts of interest. Address correspondence to: Martin Iglesias, M.D., Monte de Antisana 47, Jardines en la Montan˜a, Tlalpan, Mexico DF 14210, Mexico. E-mail: [email protected] ‘‘Vascularized Composite Allotransplantation: Upper Extremity’’ was approved by Institutional Review Board for Clinical Trials with reference 84. Received 10 February 2014. Accepted 21 April 2014. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9803-00 DOI: 10.1097/TP.0000000000000258
REFERENCES 1.
2. 3.
4.
5. 6.
7.
Guo-Wei TU, Min-jie JU, Ming XU, et al. Antithymocyte globulin-induced acute respiratory distress syndrome after renal transplantation: a case report. Chin Med J 2012; 125: 1664. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002; 10: 620. Loushin MK, Hasinoff IK, Belani KG. A delayed cardiopulmonary reaction to an intravenous immunosuppressant thymoglobulin after pancreas transplant. Anesth Analg 2001; 93: 1260. Goligher EC, Csert-Gazdewich C, Balter M, et al. Acute lung injury during antithymocyte globulin therapy for aplastic anemia. Can Respir J 2009; 16: e3. Dean NC, Amend WC, Matthay MA. Adult respiratory distress syndrome related to antilymphocyte globulin therapy. Chest 1987; 91: 619. Busani S, Rinaldi L, Begliomini B, et al. Thymoglobulin-induced severe cardiovascular reaction and acute renal failure in a patient scheduled for orthotopic liver transplantation. Minerva Anestesiol 2006; 72: 243. Thymoglobulin (Anti-thymocyte Globulin [Rabbit]) Product Monograph. Sanofi-aventis Canada Inc. 2905 Place Louis-R.-Renaud Laval, Quebec H7V 0A3. Version 1.0 dated May 6, 2013.
A Case of Thrombotic Microangiopathy Associated With Antiphospholipid Antibody Syndrome Successfully Treated With Eculizumab
A
case of thrombotic microangiopathy (TMA) associated with antiphospholipid antibody syndrome (APS) successfully treated with eculizumab.
Antiphospholipid antibody syndrome is a multisystem disorder characterized
by vascular thrombosis and presence of circulating autoantibodies. The presence of APS can predispose to macrovascular thrombotic events, such as allograft thrombosis after kidney transplantation as well as microvascular thrombotic
renal disease (1) and is associated with a poor functional outcome in the first posttransplant year (2). Recent data have demonstrated the involvement of complement pathway in the pathogenesis of TMA because of APS nephropathy (3)
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
