- Email: [email protected]
Cardiac Transplantation From a Carbon Monoxide Intoxicated Donor
Cardiac Transplantation From a Carbon Monoxide Intoxicated Donor S. Martìn-Suàrez, E. Mikus, E. Pilato, M. Bacchini, C. Savini, F. Grigioni, F. Coccolo, G. Marinelli, P.M. Mikus, and G. Arpesella ABSTRACT Heart transplantation is a demonstrated successful and life-saving treatment for an increasing number of patients. The growth of heart transplantation surgery is limited by the relative lack of suitable donors, and the increasing demand has lead to the expansion of acceptance criteria. Patients succumbing to carbon monoxide (CO) poisoning are usually considered not suitable organ donors and they are routinely rejected in many centers. Although organs from CO poisoning donors have been occasionally used, cardiac transplantation in this scenario remains very uncommon. We report the successful heart transplantation from a CO intoxicated donor, who was previously refused by two other transplantation teams. Standard donor evaluation criteria, transplantation techniques and management were used. Limited cases are described in literature. The present case may increase awareness among emergency department physicians, as well as transplantations teams, that patients dying of CO exposure may be acceptable cardiac donors.
O
NE of the greatest achievements in modern medicine is the ability to transplant organs. Improvements in surgical techniques, survival, and development of drugs to treat rejection, have led to a growing number of transplantation in the recent years. However, this trend has slowed down, due to the lack of donors. Organ procurement is limited by many exclusion criteria, resulting in a relative stable number of donors in spite of an increasing number of individuals waiting for organ transplantation. Patients succumbing to carbon monoxide (CO) poisoning, which is a common cause of toxicologic mortality, are usually rejected for heart donation. Many authors classify these patients as “inadvisable” or “nontraditional” donors. Because CO poisoning is a leading cause of accidental or suicidal death, routine rejection of victims, usually young and otherwise healthy people, could exclude thousand of potential organ donors per year.1 In Italy, CO intoxication is the cause of nearly 6000 hospitalizations and more than 350 deaths per year. The mechanisms of tissue damage are as follows: (1) oxygen delivery to the tissues is reduced due to high chemical affinity of CO to hemoglobin (more than 200 times greater than oxygen) resulting in the shift of the oxyhemoglobin dissociation curve to the left (Haldane effect)2, and (2) CO strongly binds to myoglobin, interfering with oxygen transportation to mitocondria. Cardiovascular manifestations of CO poisoning are characterized by ischemic EKG changes in 30% of the cases (only 16% of patients present
with a completely normal EKG) and elevation on cardiac biomarkers in 35% of the cases.3 Even more, when myocardial injury occurs, long-term survival is reduced.4 However, since successful organ transplantation from donors who were brain dead as a result of CO poisoning are reported in literature,5,6,7,8 the contention that this poisoning automatically contraindicates donation of organs, including the heart, may be unfounded. In the present paper, we illustrate a case of successful cardiac transplantation from a victim of CO poisoning. CASE REPORT A 20-year-old female with a history of smoking 10 cigarettes per day as the only cardiovascular risk factor, was found at home. She fainted in the bathroom where an electronic heater was working. The girl, presented with a characteristic “pink” skin pigmentation, deeply comatose, and with severe central nervous system damage. The patient was in respiratory arrest while cardiac activity was still present. The patient was intubated and immediately transferred to the hospital. A few hours after admission to the intensive care unit, she was declared brain dead. Post-anoxic encephalopathy due to CO From the Cardiac Surgery Department (S.M.-S., E.M., E.P., M.B., C.S., G.M., P.M.M., G.A.), and Cardiology Department (F.G., F.C.), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy. Address reprint requests to Sofia Martìn-Suàrez, U.O. Cardiochirurgia, Ospedale S.Orsola-Malpighi, Via Massarenti 9, CAP 40138, Bologna, Italy. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.03.155
Transplantation Proceedings, 40, 1563–1565 (2008)
1563
1564 poisoning was clinically diagnosed. Carboxyhemoglobin (COHb) levels were high even if these data were not available. Echocardiography documented a normal left ventricle, not dilated, with normal wall thickness and contractility and with an ejection fraction (EF) of 60%. Atria and right cavities were normal as well as all valvular apparati. Blood Pressure (BP) was 110/62 mm Hg, central venous pressure (CVP) 7 mm Hg, EKG was on sinus rhythm without any ischemic sign and the heart rate (HR) was 94 bpm. Neither inotropic support nor vasopressor drugs were needed. The peak of cardiac biomarkers, were 51 mg/dL of creatine kinase myoglobin (CKMB) with a CK level of 1430 mg/dL and a troponin I of 0.03 ng/mL. An observation period of 6 hours was started to certify death. Organs were offered to different transplantation teams. The heart was offered to us after being declined by two other cardiac transplantation centers. The donor characteristics, blood group and somatic characteristics, were suitable for one of our patients on the waiting list for cardiac transplantation. Never before in our institute, and after 16 years of cardiac transplantation experience (more than 430 procedures performed), had a donor who died from CO intoxication been offered. A multidisciplinary team (cardiologists and cardiac surgeons) discussed the case. In light of the donor data (haemodynamics, cardiac markers, lack of inotropes and echocardiography), we decided that the heart was appropriate for transplantation. The liver and kidneys were also accepted for transplantation by other teams. The recipient was a 35-year-old male affected, since 1996, by hypertrophic cardiomyopathy and on the waiting list since 2004. On March 2007, the cardiac transplantation form the CO poisoning donor was successfully achieved. Postoperative course was uneventful. Cardiac performance was satisfactory from the very beginning, with low-dose isoprenaline infusion as the only inotropic support. Cardiac index was around 3.8 l/min/m2 and the EF was 75%.
DISCUSSION
The increasing amount of patients requiring cardiac transplantation and the currently small pool of donors has lead to an expansion of acceptable donor criteria. CO poisoning is responsible for a high number of intoxication deaths in United States,1,13 as well as in Europe. In Italy, in 5 years (1985–1988) 1744 deaths were due to CO poisoning (data form the Italian Statistics Department, ISTAT). The high affinity of hemoglobin for CO is 200 times greater than that for oxygen. Formation of COHb interferes with oxygen transportation to cells’ mitocondrias. Oxygen tissue delivery is further restricted due to the shift to the left of the oxygen disassociation curve. The CO also inhibits cellular respiration interfering with the cytochrome oxidase system. CO poisoning results in profound tissue hypoxia followed by necrosis. Even if myocardial damage may be present in nearly 40% of poisoned individuals, the most common cause of death is anoxic brain injury. A high percentage of CO intoxication deaths do not have signs of myocardial injury.3 The use of cardiac allografts from donors succumbing to CO poisoning is still controversial, and a few reports about their use are contradictory.8,9 In 1989, an unsuccessful cardiac transplantation with a donor heart exposed to CO was first reported.9 However, most of the time cardiac
MARTÌN-SUÀREZ, MIKUS, PILATO ET AL
arrest happened before organ harvesting. In 1997 Hanston et al10 –11 reported one case of sudden graft failure, probably related to CO toxicity. Other authors, have reported good results using cardiac grafts.5,6,7,8,12 Smith et al8 reported two cases of satisfactory cardiac transplantation: one donor experienced rabdomyolysis and required vasopressors, and the other experienced CPR before organ harvesting. The authors suggested new criteria to minimize risks in the use of CO-exposed hearts: normal EKG, satisfactory echocardiography, minimal increase of cardiac biomarkers, minimal inotropic support, relatively short ischemic time, favorable phenotype (weight-height) donor-recipient matching, and avoidance of recipients with pulmonary hypertension. Regarding long-term survival, little data are available, but individual cases reported suggested that survival of patients transplanted with organs (not only heart, but also liver and kidneys) procured from carefully selected CO poisoned donors, may be comparable to that of patients transplanted from nonintoxicated donors.5–14 In the present paper, a successful cardiac transplantation from a CO-poisoned donor is described. Previous reports have been found in literature, but decision-making criteria for the harvest of such organs are poorly defined. Demonstration of this circumstances is that, before the donation was offered to our cardiothoracic transplantation department, two other teams, judged the allograft unsuitable for transplantation because of the cause of the death. The good performance of the heart as well as the absence of myocardial damage (normal EKG, negative biomarkers, etc) lead us to accept the graft. We agree with other authors that patients with brain death caused by CO poisoning should be considered appropriate donors for heart (as well as other organs) transplantation. These potential donors should be given aggressive supportive care until decisions about organ transplantation are finalized. The acceptance of hearts (or even lungs, as already reported15) from CO-poisoning victims may increase the number of potential donors, which is of great relevance at a time when the number of organs for donation continue to be in short supply and disproportionate to the demand. REFERENCES 1. Colbb N, Etzel RA: Unintentional carbon monoxide-related deaths in the United States, 1979 –1988. JAMA 266:659, 1991 2. Turini GM: Effect of carbon monoxide on the oxyhemoglobin dissociation curve. Circulation 63:253A, 1981 3. Satran D, Henry CR, Adkinson C, et al: Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 45:1513, 2005 4. Henry CR, Satran D, Lindgren B, et al: Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA 295:398, 2006 5. Roberts JR, Bain M, Klachko MN, et al: Succesful heart transplantation from a victim of carbon monoxide poisoning. Ann Emerg Med 25:652, 1995 6. Bentley MJ, Mullen JC, Lopushinsky SR, et al: Succesful cardiac transplantation with methanol or carbon monoxide-poisoned donors. Ann Thorac Surg 71:1194, 2001
CARDIAC TRANSPLANTATION 7. Koerner MM, Tenderich G, Minami K, et al: Extended donor criteria: use of cardiac allograft after carbon monoxide poisoning. Transplantation 63:1358, 1997 8. Smith JA, Bergin PJ, Williams TJ, et al: Successful heart transplantation with cardiac allograft exposed to carbon monoxide poisoning. J Heart Lung Transplant 11:698, 1992 9. Karwande SV, Hopfenbeck JA, Renlund DG, et al: An avoidable pitfall in donor selection for heart transplantation. J Heart Transplant 8:422, 1989 10. Hanston P, Vekemans MC, Vanormelingen P, et al: Organ procurement after evidence of brain death in victims of acute poisoning. Trransplant Proc 29:3341, 1997 11. Hanston P, Vekemans MC, Squifflet JP, Mahieu P: Organ
1565 transplantation from victims of carbon monoxide poisoning. Ann Emerg Med 27:673, 1996 12. Iberer F, Koenigsrainer A, Wasler A: Cardiac allograft harvesting after carbon moxide poisoning: report of a successful orthotopic heart transplantation. Heart Lung Transplant 12:499, 1993 13. Weaver LK: Carbon monoxide poisoning. Crit Care Clin 15:297, 1999 14. Leikin JB, Heyn-Lamb R, Aks S, et al: The toxic patient as a potential organ donor. Am J Emerg Med 12:151, 1994 15. Shennib H, Adoumie E, Fraser R: Succesful transplantation of a lung allograft from a carbon monoxydepoisoninig victim. J Heart Lung Transplant 11:68, 1992
O
NE of the greatest achievements in modern medicine is the ability to transplant organs. Improvements in surgical techniques, survival, and development of drugs to treat rejection, have led to a growing number of transplantation in the recent years. However, this trend has slowed down, due to the lack of donors. Organ procurement is limited by many exclusion criteria, resulting in a relative stable number of donors in spite of an increasing number of individuals waiting for organ transplantation. Patients succumbing to carbon monoxide (CO) poisoning, which is a common cause of toxicologic mortality, are usually rejected for heart donation. Many authors classify these patients as “inadvisable” or “nontraditional” donors. Because CO poisoning is a leading cause of accidental or suicidal death, routine rejection of victims, usually young and otherwise healthy people, could exclude thousand of potential organ donors per year.1 In Italy, CO intoxication is the cause of nearly 6000 hospitalizations and more than 350 deaths per year. The mechanisms of tissue damage are as follows: (1) oxygen delivery to the tissues is reduced due to high chemical affinity of CO to hemoglobin (more than 200 times greater than oxygen) resulting in the shift of the oxyhemoglobin dissociation curve to the left (Haldane effect)2, and (2) CO strongly binds to myoglobin, interfering with oxygen transportation to mitocondria. Cardiovascular manifestations of CO poisoning are characterized by ischemic EKG changes in 30% of the cases (only 16% of patients present
with a completely normal EKG) and elevation on cardiac biomarkers in 35% of the cases.3 Even more, when myocardial injury occurs, long-term survival is reduced.4 However, since successful organ transplantation from donors who were brain dead as a result of CO poisoning are reported in literature,5,6,7,8 the contention that this poisoning automatically contraindicates donation of organs, including the heart, may be unfounded. In the present paper, we illustrate a case of successful cardiac transplantation from a victim of CO poisoning. CASE REPORT A 20-year-old female with a history of smoking 10 cigarettes per day as the only cardiovascular risk factor, was found at home. She fainted in the bathroom where an electronic heater was working. The girl, presented with a characteristic “pink” skin pigmentation, deeply comatose, and with severe central nervous system damage. The patient was in respiratory arrest while cardiac activity was still present. The patient was intubated and immediately transferred to the hospital. A few hours after admission to the intensive care unit, she was declared brain dead. Post-anoxic encephalopathy due to CO From the Cardiac Surgery Department (S.M.-S., E.M., E.P., M.B., C.S., G.M., P.M.M., G.A.), and Cardiology Department (F.G., F.C.), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy. Address reprint requests to Sofia Martìn-Suàrez, U.O. Cardiochirurgia, Ospedale S.Orsola-Malpighi, Via Massarenti 9, CAP 40138, Bologna, Italy. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.03.155
Transplantation Proceedings, 40, 1563–1565 (2008)
1563
1564 poisoning was clinically diagnosed. Carboxyhemoglobin (COHb) levels were high even if these data were not available. Echocardiography documented a normal left ventricle, not dilated, with normal wall thickness and contractility and with an ejection fraction (EF) of 60%. Atria and right cavities were normal as well as all valvular apparati. Blood Pressure (BP) was 110/62 mm Hg, central venous pressure (CVP) 7 mm Hg, EKG was on sinus rhythm without any ischemic sign and the heart rate (HR) was 94 bpm. Neither inotropic support nor vasopressor drugs were needed. The peak of cardiac biomarkers, were 51 mg/dL of creatine kinase myoglobin (CKMB) with a CK level of 1430 mg/dL and a troponin I of 0.03 ng/mL. An observation period of 6 hours was started to certify death. Organs were offered to different transplantation teams. The heart was offered to us after being declined by two other cardiac transplantation centers. The donor characteristics, blood group and somatic characteristics, were suitable for one of our patients on the waiting list for cardiac transplantation. Never before in our institute, and after 16 years of cardiac transplantation experience (more than 430 procedures performed), had a donor who died from CO intoxication been offered. A multidisciplinary team (cardiologists and cardiac surgeons) discussed the case. In light of the donor data (haemodynamics, cardiac markers, lack of inotropes and echocardiography), we decided that the heart was appropriate for transplantation. The liver and kidneys were also accepted for transplantation by other teams. The recipient was a 35-year-old male affected, since 1996, by hypertrophic cardiomyopathy and on the waiting list since 2004. On March 2007, the cardiac transplantation form the CO poisoning donor was successfully achieved. Postoperative course was uneventful. Cardiac performance was satisfactory from the very beginning, with low-dose isoprenaline infusion as the only inotropic support. Cardiac index was around 3.8 l/min/m2 and the EF was 75%.
DISCUSSION
The increasing amount of patients requiring cardiac transplantation and the currently small pool of donors has lead to an expansion of acceptable donor criteria. CO poisoning is responsible for a high number of intoxication deaths in United States,1,13 as well as in Europe. In Italy, in 5 years (1985–1988) 1744 deaths were due to CO poisoning (data form the Italian Statistics Department, ISTAT). The high affinity of hemoglobin for CO is 200 times greater than that for oxygen. Formation of COHb interferes with oxygen transportation to cells’ mitocondrias. Oxygen tissue delivery is further restricted due to the shift to the left of the oxygen disassociation curve. The CO also inhibits cellular respiration interfering with the cytochrome oxidase system. CO poisoning results in profound tissue hypoxia followed by necrosis. Even if myocardial damage may be present in nearly 40% of poisoned individuals, the most common cause of death is anoxic brain injury. A high percentage of CO intoxication deaths do not have signs of myocardial injury.3 The use of cardiac allografts from donors succumbing to CO poisoning is still controversial, and a few reports about their use are contradictory.8,9 In 1989, an unsuccessful cardiac transplantation with a donor heart exposed to CO was first reported.9 However, most of the time cardiac
MARTÌN-SUÀREZ, MIKUS, PILATO ET AL
arrest happened before organ harvesting. In 1997 Hanston et al10 –11 reported one case of sudden graft failure, probably related to CO toxicity. Other authors, have reported good results using cardiac grafts.5,6,7,8,12 Smith et al8 reported two cases of satisfactory cardiac transplantation: one donor experienced rabdomyolysis and required vasopressors, and the other experienced CPR before organ harvesting. The authors suggested new criteria to minimize risks in the use of CO-exposed hearts: normal EKG, satisfactory echocardiography, minimal increase of cardiac biomarkers, minimal inotropic support, relatively short ischemic time, favorable phenotype (weight-height) donor-recipient matching, and avoidance of recipients with pulmonary hypertension. Regarding long-term survival, little data are available, but individual cases reported suggested that survival of patients transplanted with organs (not only heart, but also liver and kidneys) procured from carefully selected CO poisoned donors, may be comparable to that of patients transplanted from nonintoxicated donors.5–14 In the present paper, a successful cardiac transplantation from a CO-poisoned donor is described. Previous reports have been found in literature, but decision-making criteria for the harvest of such organs are poorly defined. Demonstration of this circumstances is that, before the donation was offered to our cardiothoracic transplantation department, two other teams, judged the allograft unsuitable for transplantation because of the cause of the death. The good performance of the heart as well as the absence of myocardial damage (normal EKG, negative biomarkers, etc) lead us to accept the graft. We agree with other authors that patients with brain death caused by CO poisoning should be considered appropriate donors for heart (as well as other organs) transplantation. These potential donors should be given aggressive supportive care until decisions about organ transplantation are finalized. The acceptance of hearts (or even lungs, as already reported15) from CO-poisoning victims may increase the number of potential donors, which is of great relevance at a time when the number of organs for donation continue to be in short supply and disproportionate to the demand. REFERENCES 1. Colbb N, Etzel RA: Unintentional carbon monoxide-related deaths in the United States, 1979 –1988. JAMA 266:659, 1991 2. Turini GM: Effect of carbon monoxide on the oxyhemoglobin dissociation curve. Circulation 63:253A, 1981 3. Satran D, Henry CR, Adkinson C, et al: Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 45:1513, 2005 4. Henry CR, Satran D, Lindgren B, et al: Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA 295:398, 2006 5. Roberts JR, Bain M, Klachko MN, et al: Succesful heart transplantation from a victim of carbon monoxide poisoning. Ann Emerg Med 25:652, 1995 6. Bentley MJ, Mullen JC, Lopushinsky SR, et al: Succesful cardiac transplantation with methanol or carbon monoxide-poisoned donors. Ann Thorac Surg 71:1194, 2001
CARDIAC TRANSPLANTATION 7. Koerner MM, Tenderich G, Minami K, et al: Extended donor criteria: use of cardiac allograft after carbon monoxide poisoning. Transplantation 63:1358, 1997 8. Smith JA, Bergin PJ, Williams TJ, et al: Successful heart transplantation with cardiac allograft exposed to carbon monoxide poisoning. J Heart Lung Transplant 11:698, 1992 9. Karwande SV, Hopfenbeck JA, Renlund DG, et al: An avoidable pitfall in donor selection for heart transplantation. J Heart Transplant 8:422, 1989 10. Hanston P, Vekemans MC, Vanormelingen P, et al: Organ procurement after evidence of brain death in victims of acute poisoning. Trransplant Proc 29:3341, 1997 11. Hanston P, Vekemans MC, Squifflet JP, Mahieu P: Organ
1565 transplantation from victims of carbon monoxide poisoning. Ann Emerg Med 27:673, 1996 12. Iberer F, Koenigsrainer A, Wasler A: Cardiac allograft harvesting after carbon moxide poisoning: report of a successful orthotopic heart transplantation. Heart Lung Transplant 12:499, 1993 13. Weaver LK: Carbon monoxide poisoning. Crit Care Clin 15:297, 1999 14. Leikin JB, Heyn-Lamb R, Aks S, et al: The toxic patient as a potential organ donor. Am J Emerg Med 12:151, 1994 15. Shennib H, Adoumie E, Fraser R: Succesful transplantation of a lung allograft from a carbon monoxydepoisoninig victim. J Heart Lung Transplant 11:68, 1992