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Primary cardiac allograft failure after donor carbon monoxide poisoning treated with biventricular assist device
CASE REPORTS
Primary Cardiac Allograft Failure After Donor Carbon Monoxide Poisoning Treated With Biventricular Assist Device Inez E. R. Rodrigus, MD,a Vivianne Conraads, MD,b Bram J. Amsel, MD,b and Adriaan C. Moulijn, MD, PhDa Because of the current donor shortage, organ selection criteria are being progressively liberalized. We present a case of carbon monoxide poisoning in a multiorgan donor that led to primary cardiac allograft failure. A biventricular assist device was used as a bridge to recovery. J Heart Lung Transplant 2001;20:1345–1348.
C
onfronted with disparities in the demand for and supply of donor organs, transplant surgeons are inclined to consider marginal donors. Supported by reports on the use of hearts from carbon monoxide (CO)-intoxicated donors, we decided to accept such a heart.1–5 The literature contains no reports of primary allograft failure of a CO-intoxicated donor heart that was supported with biventricular assist device (BVAD) with successful outcome after mitral valve replacement.
CASE REPORT Donor History The donor heart came from a 31-year-old man who died after smoke inhalation in a house fire. He required a short period of cardiopulmonary resuscitation. His carboxyhemoglobin (COHb) level was 36% on admission and decreased to 4% after hyperbaric oxygen therapy. Echocardiography and electrocardiography (ECG) revealed normal cardiac From the Departments of aCardiac Surgery and bCardiology, University Hospital Antwerp, Edegem, Belgium. Submitted January 10, 2001; accepted May 29, 2001. Reprint requests: Inez E.R. Rodrigus, MD, Department of Cardiac Surgery, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Telephone: 32-3-821-31-29. Fax: 32-3-830-20-99. E-mail: [email protected] Copyright © 2001 by the International Society for Heart and Lung Transplantation. 1053-2498/01/$–see front matter PII S1053-2498(01)00331-X
function. Creatine kinase (CK) was 710 U/liter (normal values, 55 to 170) and CK-MB was 33 U/liter (normal values, 1 to 16). Bedside troponin-T measurement was negative. After 48 hours, the victim was declared brain dead, and his heart, kidneys, liver, and pancreas were procured for transplantation. At the time of inspection, myocardial contractility was acceptable with a moderate dose of dopamine (8 g/kg/min). Myocardial preservation was achieved with Bretscnheider solution (Custodiol, Dr. F. Ko ¨hler, Chemie GmbH; Alsbach-Ha¨hnlein, Germany).
Recipient History The recipient was a 62-year-old man with ischemic cardiomyopathy, an ejection fraction of 11%, and no pulmonary hypertension. He had been listed for transplantation for 2 months. Orthotopic heart transplantation was performed with a warm ischemic time of 40 minutes and a total ischemic time of 120 minutes. A smooth operative procedure and the proximity of the local donor hospital contributed to this short ischemic time. Weaning from cardiopulmonary bypass (CPB) however was unsuccessful despite additional reperfusion, rapid atrioventricular pacing, maximal inotropic support, and intraaortic balloon counterpulsation. The Abiomed BVS 5000 biventricular assist device was implanted. Transmyocardial biopsy showed normal cardiac tis1345
The Journal of Heart and Lung Transplantation December 2001
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FIGURE 1 Electrocardiogram and arterial pressure recordings: (A) first weaning attempt on post-operative Day 3, on 10g/kg/min of dobutamine with 2.5-liter biventricular assist device (BVAD) flow, and (B) final weaning on post-operative Day 5, on 5 g/kg/min of dobutamine with 2-liter BVAD flow.
sue. Allograft function improved gradually on serial echocardiography within 24 hours. A first weaning attempt on the 3rd post-operative day was unsuccessful, but we saw improved myocardial function on the 5th post-operative day (Figure 1 A and B). Complete weaning was however not possible because of severe mitral regurgitation with chordal rupture caused by the left atrial cannula, which inadvertently was placed too deep through the orifice of the mitral valve, as seen on transesophageal echocardiography (Figure 2). The patient was put
on CPB for mitral valve exploration after cold crystalloid cardioplegia. We observed erosion of the left ventricular wall, caused by the left atrial cannula, with chordal rupture of the posterior leaflet. A Carpentier Edwards Perimount pericardial mitral valve (Baxter Xenomedica; Horw, Switzerland) was implanted, followed by successful weaning from CPB. Aspergillus fumigatus pneumonia complicated recovery and was treated with amphotericin B and itraconazole. Acute renal failure required temporary hemodialysis. After 3 months, the patient was
The Journal of Heart and Lung Transplantation Volume 20, Number 12
FIGURE 2 Transesophageal echocardiography: left
atrial cannula (large arrow) traversing the mitral valve with chordal rupture (small arrow).
discharged with excellent cardiac function. Three years after transplantation, he is in good physical condition. Kidneys, pancreas, and liver from the same donor showed normal primary function.
DISCUSSION Treatment of CO poisoning is directed toward relieving tissue hypoxia and removing CO from the body. For severe CO poisoning with COHb ⬎ 40%, hyperbaric oxygen therapy is strongly advocated.6 The pathophysiology of CO poisoning is complex and involves hypoxic stress because of interference with oxygen transport to the cells, caused by CO’s greater affinity for hemoglobin than that of oxygen, a shift to the left in the oxyhemoglobin curve, and a direct effect on mitochondrial cellular respiration.7 Carbon monoxide can also affect leukocytes, platelets, and the endothelium, inducing a cascade of effects that result in oxidative injury. Therefore, COHb levels are valuable for confirming CO exposure but cannot be used to stratify the severity of poisoning.8 Furthermore, COHb levels do not fully represent the impact of CO poisoning, because they are often drawn after resuscitation with oxygen and after transportation of the victim to a trauma center. Tissues with the highest metabolic rates (nervous system and heart) are most susceptible to the detrimental effects of CO. Although increased levels of cardiac enzymes (CK-MB) suggest myocardial injury, we accepted this donor heart because of normal ECG, normal cardiac function on echocardiography, and normal bedside troponin-T measurement.9
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Tritapepe et al10 discussed the mechanisms of reversible cardiac dysfunction after CO exposure, hypothesizing a syndrome that resembles myocardial stunning, which can be interpreted as primary mitochondrial impairment. These lesions can be demonstrated only by electron microscopy as ultrastuctural lesions: deposits of glycogen associated with swollen and altered mitochondria, intracellular edema, focal contracture bands, and myofilament disarray. Data on cardiac allografts harvested from COintoxicated donors are sparse. Koerner et al1 published the largest single-center experience, 5 cardiac transplantations with allografts from CO-poisoned donors. Surgical technical problems caused 1 immediate post-operative death, a second recipient died from infection, and a third recipient died from adenocarcinoma of the pancreas 4 months after transplantation. The overall 3-year survival rate was 40%. Roberts et al2 reported on a CO-poisoned donor, treated with hyperbaric oxygen therapy. The initial ECG demonstrated an intraventricular conduction defect with non-specific ST-T–segment and T-wave changes. They did not mention serial cardiac enzymes and echocardiography. The initial cardiac function was good, but 1 year after transplantation, the patient presented with acute allograft rejection. The patient died after retransplantation. Hantson et al3 reported a negative outcome after transplantation of the heart of a CO-poisoned donor, with initial successful weaning from CPB but death from right ventricular dysfunction after 15 hours. Three other successful transplantations have been reported.4,5 With this report, we add another successful case to the experience with CO-intoxicated donor hearts. Unfortunately, our recipient initially could not be weaned from CPB because of primary cardiac allograft failure. Therefore we supported the patient with an Abiomed BVS 5000 BVAD. Karwande et al11 reported on a similar patient, supported by BVAD with the use of centrifugal pumps, but with negative outcome. Few authors have reported on the use of BVAD after transplantation for primary graft failure. Reiss et al12 reported on 12 patients treated with mechanical circulatory support after heart transplantation. Two patients were supported for primary graft failure (1 with the Thoratec BVAD system and another by the Abiomed left ventricular assist device) with successful outcome after retransplantation in 1. Jagger et al13 reported on the successful use of a Thoratec BVAD in a patient who received
The Journal of Heart and Lung Transplantation December 2001
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a donor heart with decreased function, possibly because of phenothiazine use. Cardiac recovery was seen on serial echocardiography after 18 days. Albes et al recently reported on implantation of a biventricular Berlin Heart for primary cardiac allograft failure caused by right ventricular dysfunction with fixed pulmonary vascular resistance, and successful weaning 1 week after transplantation.14 We found no reports on chordal rupture and mitral regurgitation caused by the left atrial cannula of an assist device. This complication can be avoided by using left ventricular apical cannulation with the smaller 36F, malleable cannula.15 Goldstein et al16reported on a successful mitral valve and tricuspid valve replacement after cardiac transplantation, and included limited worldwide experience with valvular replacement after cardiac transplantation. We did not try to repair the valve, but replaced the valve with a bioprosthesis to limit a second ischemic period in this vulnerable heart. In summary, despite some successful reports on using CO-poisoned donor hearts for transplantation, extreme caution is warranted. Normalization of COHb levels does not imply full recovery of energydepleted myocytes. However, cardiac dysfunction can be reversible if caused by stunning, and BVAD implantation should be considered in case of primary allograft failure. Incorrect assist-device cannula placement demands repositioning to avoid valvular damage. REFERENCES 1. Koerner MM, Tenderich G, Minami K, et al. Extended donor criteria: use of cardiac allografts after carbon monoxide poisoning. Transplantation 1997;63:1358 – 60. 2. Roberts JR, Bain M, Klachko MN, Seigel EG, Wason S.
3.
4.
5.
6. 7.
8. 9.
10.
11.
12.
13.
14.
15. 16.
Successful heart transplantation from a victim of carbon monoxide poisoning. Ann Emerg Med 1995;26:652–5. Hantson PH, Vekemans MC, Squifflet JP, Mahieu P. Organ transplantation from victims of carbon monoxide poisoning. Ann Emerg Med 1996;27:673– 4. Smith JA, Bergin PJ, Williams TJ, Esmore DS. Successful heart transplantation with cardiac allografts exposed to carbon monoxide poisoning. J Heart Lung Transplant 1992;11: 698 –700. Iberer F, Ko ¨ningsrainer A, Wasler A, Petutschnigg B, Auer T, Tscheliessnigg K. Cardiac allograft harvesting after carbon monoxide poisoning. Report of a successful orthotopic heart transplantation. J Heart Lung Transplant 1993;12:499 –500. Ilano AL, Raffin TA. Management of carbon monoxide poisoning. Chest 1990;97:165–9. Goldbaum LR, Orellano T, Dergel E. Mechanism of the toxic action of carbon monoxide. Am Clin Lab Sci 1976;6: 372– 6. Hardy KR, Thom SR. Pathophysiology of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613–29. Katus HA, Remppis A, Neumann FJ, et al. Diagnostic efficiency of troponin T measurement in acute myocardial infarction. Circulation 1991;83:902–12. Tritapepe L, Macchiarelli G, Rocco M, et al. Functional and ultrastructural evidence of myocardial stunning after acute carbon monoxide poisoning. Crit Care Med 1998;26:797– 801. Karwande SV, Hopfenbeck JA, Renlund DG, Burton NA, Gay WA. An avoidable pitfall in donor selection for heart transplantation. J Heart Lung Transplant 1989;8:422– 4. Reiss N, El-Banayosy A, Kizner L, et al. Mechanical circulatory support after heart transplantation. Cor Europaeum 1997;6:82– 4. Jagger J, Fullerton DA, Campbell DN, et al. Cardiac allograft failure: successful use of biventricular assist device. Ann Thorac Surg 1995;60:1409 –11. Albes JM, Eckstein FS, Heinemann MK, Ziemer G. Successful weaning of a transplanted heart from biventricular assist device. Ann Thorac Surg 2000;70:277– 8. Jett GK. Left ventricular apical cannulation for circulatory support. J Card Surg 1998;13:51–5. Goldstein DJ, Garfein ES, Aaronson K, Zuech N, Michler RE. Mitral valve replacement and tricuspid valve repair after cardiac transplantation. Ann Thorac Surg 1997;63:1463–5.
Primary Cardiac Allograft Failure After Donor Carbon Monoxide Poisoning Treated With Biventricular Assist Device Inez E. R. Rodrigus, MD,a Vivianne Conraads, MD,b Bram J. Amsel, MD,b and Adriaan C. Moulijn, MD, PhDa Because of the current donor shortage, organ selection criteria are being progressively liberalized. We present a case of carbon monoxide poisoning in a multiorgan donor that led to primary cardiac allograft failure. A biventricular assist device was used as a bridge to recovery. J Heart Lung Transplant 2001;20:1345–1348.
C
onfronted with disparities in the demand for and supply of donor organs, transplant surgeons are inclined to consider marginal donors. Supported by reports on the use of hearts from carbon monoxide (CO)-intoxicated donors, we decided to accept such a heart.1–5 The literature contains no reports of primary allograft failure of a CO-intoxicated donor heart that was supported with biventricular assist device (BVAD) with successful outcome after mitral valve replacement.
CASE REPORT Donor History The donor heart came from a 31-year-old man who died after smoke inhalation in a house fire. He required a short period of cardiopulmonary resuscitation. His carboxyhemoglobin (COHb) level was 36% on admission and decreased to 4% after hyperbaric oxygen therapy. Echocardiography and electrocardiography (ECG) revealed normal cardiac From the Departments of aCardiac Surgery and bCardiology, University Hospital Antwerp, Edegem, Belgium. Submitted January 10, 2001; accepted May 29, 2001. Reprint requests: Inez E.R. Rodrigus, MD, Department of Cardiac Surgery, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Telephone: 32-3-821-31-29. Fax: 32-3-830-20-99. E-mail: [email protected] Copyright © 2001 by the International Society for Heart and Lung Transplantation. 1053-2498/01/$–see front matter PII S1053-2498(01)00331-X
function. Creatine kinase (CK) was 710 U/liter (normal values, 55 to 170) and CK-MB was 33 U/liter (normal values, 1 to 16). Bedside troponin-T measurement was negative. After 48 hours, the victim was declared brain dead, and his heart, kidneys, liver, and pancreas were procured for transplantation. At the time of inspection, myocardial contractility was acceptable with a moderate dose of dopamine (8 g/kg/min). Myocardial preservation was achieved with Bretscnheider solution (Custodiol, Dr. F. Ko ¨hler, Chemie GmbH; Alsbach-Ha¨hnlein, Germany).
Recipient History The recipient was a 62-year-old man with ischemic cardiomyopathy, an ejection fraction of 11%, and no pulmonary hypertension. He had been listed for transplantation for 2 months. Orthotopic heart transplantation was performed with a warm ischemic time of 40 minutes and a total ischemic time of 120 minutes. A smooth operative procedure and the proximity of the local donor hospital contributed to this short ischemic time. Weaning from cardiopulmonary bypass (CPB) however was unsuccessful despite additional reperfusion, rapid atrioventricular pacing, maximal inotropic support, and intraaortic balloon counterpulsation. The Abiomed BVS 5000 biventricular assist device was implanted. Transmyocardial biopsy showed normal cardiac tis1345
The Journal of Heart and Lung Transplantation December 2001
1346
FIGURE 1 Electrocardiogram and arterial pressure recordings: (A) first weaning attempt on post-operative Day 3, on 10g/kg/min of dobutamine with 2.5-liter biventricular assist device (BVAD) flow, and (B) final weaning on post-operative Day 5, on 5 g/kg/min of dobutamine with 2-liter BVAD flow.
sue. Allograft function improved gradually on serial echocardiography within 24 hours. A first weaning attempt on the 3rd post-operative day was unsuccessful, but we saw improved myocardial function on the 5th post-operative day (Figure 1 A and B). Complete weaning was however not possible because of severe mitral regurgitation with chordal rupture caused by the left atrial cannula, which inadvertently was placed too deep through the orifice of the mitral valve, as seen on transesophageal echocardiography (Figure 2). The patient was put
on CPB for mitral valve exploration after cold crystalloid cardioplegia. We observed erosion of the left ventricular wall, caused by the left atrial cannula, with chordal rupture of the posterior leaflet. A Carpentier Edwards Perimount pericardial mitral valve (Baxter Xenomedica; Horw, Switzerland) was implanted, followed by successful weaning from CPB. Aspergillus fumigatus pneumonia complicated recovery and was treated with amphotericin B and itraconazole. Acute renal failure required temporary hemodialysis. After 3 months, the patient was
The Journal of Heart and Lung Transplantation Volume 20, Number 12
FIGURE 2 Transesophageal echocardiography: left
atrial cannula (large arrow) traversing the mitral valve with chordal rupture (small arrow).
discharged with excellent cardiac function. Three years after transplantation, he is in good physical condition. Kidneys, pancreas, and liver from the same donor showed normal primary function.
DISCUSSION Treatment of CO poisoning is directed toward relieving tissue hypoxia and removing CO from the body. For severe CO poisoning with COHb ⬎ 40%, hyperbaric oxygen therapy is strongly advocated.6 The pathophysiology of CO poisoning is complex and involves hypoxic stress because of interference with oxygen transport to the cells, caused by CO’s greater affinity for hemoglobin than that of oxygen, a shift to the left in the oxyhemoglobin curve, and a direct effect on mitochondrial cellular respiration.7 Carbon monoxide can also affect leukocytes, platelets, and the endothelium, inducing a cascade of effects that result in oxidative injury. Therefore, COHb levels are valuable for confirming CO exposure but cannot be used to stratify the severity of poisoning.8 Furthermore, COHb levels do not fully represent the impact of CO poisoning, because they are often drawn after resuscitation with oxygen and after transportation of the victim to a trauma center. Tissues with the highest metabolic rates (nervous system and heart) are most susceptible to the detrimental effects of CO. Although increased levels of cardiac enzymes (CK-MB) suggest myocardial injury, we accepted this donor heart because of normal ECG, normal cardiac function on echocardiography, and normal bedside troponin-T measurement.9
1347
Tritapepe et al10 discussed the mechanisms of reversible cardiac dysfunction after CO exposure, hypothesizing a syndrome that resembles myocardial stunning, which can be interpreted as primary mitochondrial impairment. These lesions can be demonstrated only by electron microscopy as ultrastuctural lesions: deposits of glycogen associated with swollen and altered mitochondria, intracellular edema, focal contracture bands, and myofilament disarray. Data on cardiac allografts harvested from COintoxicated donors are sparse. Koerner et al1 published the largest single-center experience, 5 cardiac transplantations with allografts from CO-poisoned donors. Surgical technical problems caused 1 immediate post-operative death, a second recipient died from infection, and a third recipient died from adenocarcinoma of the pancreas 4 months after transplantation. The overall 3-year survival rate was 40%. Roberts et al2 reported on a CO-poisoned donor, treated with hyperbaric oxygen therapy. The initial ECG demonstrated an intraventricular conduction defect with non-specific ST-T–segment and T-wave changes. They did not mention serial cardiac enzymes and echocardiography. The initial cardiac function was good, but 1 year after transplantation, the patient presented with acute allograft rejection. The patient died after retransplantation. Hantson et al3 reported a negative outcome after transplantation of the heart of a CO-poisoned donor, with initial successful weaning from CPB but death from right ventricular dysfunction after 15 hours. Three other successful transplantations have been reported.4,5 With this report, we add another successful case to the experience with CO-intoxicated donor hearts. Unfortunately, our recipient initially could not be weaned from CPB because of primary cardiac allograft failure. Therefore we supported the patient with an Abiomed BVS 5000 BVAD. Karwande et al11 reported on a similar patient, supported by BVAD with the use of centrifugal pumps, but with negative outcome. Few authors have reported on the use of BVAD after transplantation for primary graft failure. Reiss et al12 reported on 12 patients treated with mechanical circulatory support after heart transplantation. Two patients were supported for primary graft failure (1 with the Thoratec BVAD system and another by the Abiomed left ventricular assist device) with successful outcome after retransplantation in 1. Jagger et al13 reported on the successful use of a Thoratec BVAD in a patient who received
The Journal of Heart and Lung Transplantation December 2001
1348
a donor heart with decreased function, possibly because of phenothiazine use. Cardiac recovery was seen on serial echocardiography after 18 days. Albes et al recently reported on implantation of a biventricular Berlin Heart for primary cardiac allograft failure caused by right ventricular dysfunction with fixed pulmonary vascular resistance, and successful weaning 1 week after transplantation.14 We found no reports on chordal rupture and mitral regurgitation caused by the left atrial cannula of an assist device. This complication can be avoided by using left ventricular apical cannulation with the smaller 36F, malleable cannula.15 Goldstein et al16reported on a successful mitral valve and tricuspid valve replacement after cardiac transplantation, and included limited worldwide experience with valvular replacement after cardiac transplantation. We did not try to repair the valve, but replaced the valve with a bioprosthesis to limit a second ischemic period in this vulnerable heart. In summary, despite some successful reports on using CO-poisoned donor hearts for transplantation, extreme caution is warranted. Normalization of COHb levels does not imply full recovery of energydepleted myocytes. However, cardiac dysfunction can be reversible if caused by stunning, and BVAD implantation should be considered in case of primary allograft failure. Incorrect assist-device cannula placement demands repositioning to avoid valvular damage. REFERENCES 1. Koerner MM, Tenderich G, Minami K, et al. Extended donor criteria: use of cardiac allografts after carbon monoxide poisoning. Transplantation 1997;63:1358 – 60. 2. Roberts JR, Bain M, Klachko MN, Seigel EG, Wason S.
3.
4.
5.
6. 7.
8. 9.
10.
11.
12.
13.
14.
15. 16.
Successful heart transplantation from a victim of carbon monoxide poisoning. Ann Emerg Med 1995;26:652–5. Hantson PH, Vekemans MC, Squifflet JP, Mahieu P. Organ transplantation from victims of carbon monoxide poisoning. Ann Emerg Med 1996;27:673– 4. Smith JA, Bergin PJ, Williams TJ, Esmore DS. Successful heart transplantation with cardiac allografts exposed to carbon monoxide poisoning. J Heart Lung Transplant 1992;11: 698 –700. Iberer F, Ko ¨ningsrainer A, Wasler A, Petutschnigg B, Auer T, Tscheliessnigg K. Cardiac allograft harvesting after carbon monoxide poisoning. Report of a successful orthotopic heart transplantation. J Heart Lung Transplant 1993;12:499 –500. Ilano AL, Raffin TA. Management of carbon monoxide poisoning. Chest 1990;97:165–9. Goldbaum LR, Orellano T, Dergel E. Mechanism of the toxic action of carbon monoxide. Am Clin Lab Sci 1976;6: 372– 6. Hardy KR, Thom SR. Pathophysiology of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613–29. Katus HA, Remppis A, Neumann FJ, et al. Diagnostic efficiency of troponin T measurement in acute myocardial infarction. Circulation 1991;83:902–12. Tritapepe L, Macchiarelli G, Rocco M, et al. Functional and ultrastructural evidence of myocardial stunning after acute carbon monoxide poisoning. Crit Care Med 1998;26:797– 801. Karwande SV, Hopfenbeck JA, Renlund DG, Burton NA, Gay WA. An avoidable pitfall in donor selection for heart transplantation. J Heart Lung Transplant 1989;8:422– 4. Reiss N, El-Banayosy A, Kizner L, et al. Mechanical circulatory support after heart transplantation. Cor Europaeum 1997;6:82– 4. Jagger J, Fullerton DA, Campbell DN, et al. Cardiac allograft failure: successful use of biventricular assist device. Ann Thorac Surg 1995;60:1409 –11. Albes JM, Eckstein FS, Heinemann MK, Ziemer G. Successful weaning of a transplanted heart from biventricular assist device. Ann Thorac Surg 2000;70:277– 8. Jett GK. Left ventricular apical cannulation for circulatory support. J Card Surg 1998;13:51–5. Goldstein DJ, Garfein ES, Aaronson K, Zuech N, Michler RE. Mitral valve replacement and tricuspid valve repair after cardiac transplantation. Ann Thorac Surg 1997;63:1463–5.