Ann Thorac Surg 2001;71:1194-1197
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Successful cardiac transplantation with methanol or carbon monoxide-poisoned donors
Michael J. Bentley, BSca,
John C. Mullen, MDa,
Steven R. Lopushinskya,
Dennis L. Modry, MDa
a Division of Cardiothoracic Surgery, The University of Alberta, Edmonton, Alberta, Canada
Accepted for publication November 3, 2000.
Address reprint requests to Dr Mullen, Departments of Surgery & Pediatrics, The University of Alberta Hospital, 2D2. 18 WC Mackenzie Health Sciences Centre, 8440 112 St, Edmonton, AB T6G 2B7, Canada
e-mail: jmullen{at}ualberta.ca
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Abstract
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Background. Patients succumbing to methanol or carbon monoxide poisoning are usually rejected for heart donation. Increasing demand for donors has lead to the expansion of acceptance criteria and increased use of the marginal donor.
Methods. We transplanted hearts from donors who had had methanol intoxication in three cases and carbon monoxide exposure in two cases. Standard donor evaluation criteria and transplantation techniques were used.
Results. All of the transplants were successful. Three of the recipients required significant inotropic support for a few days postoperatively; however, all of the hearts functioned well over the intermediate and long term. Two recipients (1 from each group) died of complications other than heart failure (1.5 and 2 years postoperatively).
Conclusions. Successful heart transplantation can be achieved using the hearts from patients succumbing to methanol or carbon monoxide poisoning. Routine evaluation of cardiac function and myocardial damage is adequate for screening these donors. Hearts from methanol-poisoning victims may require longer inotropic support postoperatively before complete recovery, but can provide excellent long-term function and results.
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Introduction
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Heart transplantation is a common treatment for end-stage heart disease. It has been estimated that 18% of patients die while awaiting heart transplantation [1], which is largely a result of donor shortage. As waiting lists continue to grow, it is becoming increasingly necessary to maximize the donor pool by broadening acceptance criteria. Patients succumbing to various types of poisoning have historically been considered unacceptable for heart donation. Reports are now surfacing in the literature regarding the use of hearts from poisoned donors [2–13]. In the last 15 years, we have performed 293 heart transplants. This report details our use of 5 donors who had had acute poisoning resulting in brain death. Three donors succumbed to methanol intoxication and 2 to carbon monoxide (CO) exposure.
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Patients and methods
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Methanol poisonings
Case 1
A 24-year-old man with a history of alcohol abuse was transferred to the emergency department deeply comatose and exhibiting signs of severe central nervous system damage. Investigations revealed a metabolic acidosis, elevated serum glucose, markedly elevated creatine kinase (normal CK-MB), an ethanol level of 20 mmol/L, and a very high methanol level of 52 mmol/L. Despite aggressive intervention, he deteriorated to a state of brain death 21 hours after admission. Echocardiography and electrocardiography (ECG) were normal. Before donor retrieval, he was normotensive on dopamine 14 µg/kg per minute (blood pressure [BP] = 120/50 mm Hg with central venous pressure [CVP] of 2 mm Hg). The kidneys and pancreas were also harvested, but the lungs and liver were declined.
The recipient was a 47-year-old overweight man (92 kg) with ischemic cardiomyopathy and a long history of congestive heart failure. His pulmonary vascular resistance (PVR) was normal at 1.7 Woods units. Implantation was performed in a standard fashion with an ischemic time of 1 hour 44 minutes. Separation from bypass was difficult because of right ventricular dysfunction. He required high-dose inotropic support of dopamine 10 µg/kg per minute, dobutamine 20 µg/kg per minute, epinephrine 0.25 µg/kg per minute, and levophed 0.35 µg/kg per minute.
Inotropes were gradually weaned over the course of 2 days. His postoperative course was complicated by pneumonia, which was successfully treated. He was discharged in good condition 15 days postoperatively. He experienced dramatic symptomatic improvement (NYHA class I), but unfortunately died 18 months later from accelerated graft atherosclerosis.
Case 2
The donor was an overweight 37-year-old man (85 kg) with a history of alcohol abuse. He presented to hospital having had a respiratory arrest; after resuscitation, investigations revealed severe methanol intoxication (44 mmol/L). Despite aggressive medical management, he deteriorated and was pronounced brain dead 18 hours after admission. An ECG revealed nonspecific ST changes, but his echocardiogram was normal with good ventricular function. He initially required dopamine 8 µg/kg per minute (BP = 88 mm Hg systolic, CVP = 9 mm Hg). The liver, kidneys, and pancreas were also harvested.
The recipient was a 30-year-old man with a dilated cardiomyopathy and congestive heart failure. He had elevated pulmonary artery pressure (53/33 mm Hg) and increased PVR (3.5 Woods units). The transplant was uneventful, with a donor ischemic time of 3 hours 47 minutes. The postoperative course was uneventful and he was discharged in good condition on the tenth postoperative day. He has continued to enjoy an excellent long-term result (6-year follow-up).
Case 3
The donor was a previously healthy 32-year-old woman who had had accidental methanol poisoning. She presented comatose in the emergency department 36 hours after ingestion. At this time, her methanol level was 27 mmol/L, ethanol level was less than 2 mmol/L and she was in a state of profound metabolic acidosis (pH < 6.8). She deteriorated to a state of brain death 18 days later. She required significant inotropic support (levophed 0.25 µg/kg per minute and dopamine 9 µg/kg per minute). Echocardiography revealed a normal heart with slightly reduced contractility. The ECG was unremarkable. The liver and kidneys were also harvested.
The recipient was a 16-year-old boy with a complex history of congenital heart disease and multiple operations. Before transplantation, he was in biventricular congestive heart failure with low cardiac output and pulmonary edema, and was dependent on inotropic agents.
The transplant procedure was technically difficult because of the dense adhesions from previous repairs. The coarcted transverse arch was also repaired with a section of donor arch under circulatory arrest. Substantial inotropic support, consisting of dopamine 20 µg/kg per minute, dobutamine 20 µg/kg per minute, epinephrine 0.6 µg/kg per minute, and norepinephrine 0.8 µg/kg per minute, was required to wean the patient off bypass and the chest was stented open. The donor ischemic time was 3 hours 13 minutes.
The patient was weaned off inotropic agents and his chest was closed 3
days postoperatively. Acute renal failure and hepatic dysfunction gradually resolved, and he was discharged home in good condition 40 days postoperatively. Long-term follow-up (4 years) has been uncomplicated, and he has had a complete recovery.
Carbon monoxide exposures
Case 4
The donor was a previously healthy 25-year-old woman who had had smoke inhalation in a house fire. She was trapped for approximately 30 minutes and was found in cardiac and respiratory arrest. She was resuscitated at the scene. Upon admission to the emergency department, she required another 45-minute period of cardiopulmonary resuscitation (CPR). She was eventually stabilized and weaned from epinephrine to dopamine 15 µg/kg per minute (BP = 118/64 mm Hg and CVP = 10 mm Hg). She was declared brain dead 6 hours after admission. Echocardiography revealed a structurally normal heart with hyperdynamic ventricles. The ECG was normal. At the time of harvest, she required dopamine 11 µg/kg per minute (BP = 106/50 mm Hg and CVP = 10 mm Hg). Her kidneys and pancreas were also harvested; however, her liver and lungs were refused because of CO toxicity.
The recipient was a 43-year-old man who had been hospitalized numerous times with severe coronary artery disease and dilated ischemic cardiomyopathy. He was in the intensive care unit dependent on inotropic agents because of biventricular failure. The transplant procedure was uncomplicated, requiring amrinone 10 µg/kg per minute and epinephrine 0.1 µg/kg per minute to come off bypass. The donor ischemic time was 1 hour 53 minutes. He was weaned off inotropic agents 4 days later. His recovery was excellent with no complications. He was discharged on the 15th postoperative day. Long-term follow-up (7 years) has been uncomplicated except for a single episode of acute rejection 1 month postoperatively.
Case 5
The donor was a 46-year-old man with a history of depression. He was found asystolic in his garage with the car running and was resuscitated after 10 minutes of CPR. He was declared brain dead 8 hours after admission as a result of CO poisoning. Echocardiography was normal except for mild-to-moderate mitral valve regurgitation. Cardiac catheterization was normal. Hemodynamics before organ harvest were excellent (BP = 119/69 mm Hg) with no inotropic support.
The recipient was a 33-year-old man with Marfan’s syndrome. He had end-stage cardiomyopathy related to complications of Marfan’s syndrome and previous cardiac operation. Catheterization revealed aneurysmal dilation of the left main coronary artery and a localized calcific aneurysm of the innominate artery with a false lumen above the Dacron graft that was attached to the undersurface of the transverse aortic arch. Transplantation was uncomplicated, requiring minimal inotropic support postoperatively. Donor ischemic time was 1 hour 59 minutes. He was discharged on the 13th postoperative day, but was readmitted 6 days later with a new acute aortic dissection of the transverse arch and descending aorta. This dissection was repaired successfully, and he enjoyed an excellent result for the next 2 years. He subsequently died from a further dissection of the descending aorta. A summary of these cases is presented in Tables 1, 2, and 3.
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Results
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Methanol poisoning
Methanol intoxication is characterized by profound acidosis resulting from the metabolic formation of formic acid and formaldehyde [14]. Toxicity commonly manifests in the gastrointestinal, nervous, and ocular systems [15]. Little information is available in the literature on the effect of methanol on the human heart. We could find only one report of methanol intoxication causing cardiac failure [2]. Cardiac dysfunction during acute phase poisoning is characterized by a dilated and diffusely hypokinetic left ventricle as seen on echocardiography. Electrocardiographic changes include heart block and T wave abnormalities; however, creatine kinase levels remain normal, and along with the ECG pattern, provide evidence against ischemic changes. Severe cardiac failure usually resolves completely apart from persistent diffuse T wave abnormalities. Animal studies have shown cardiac dilation and myocyte degeneration in response to methanol exposure [16]. A study in dogs demonstrated that intravenous methanol reduced cardiac output, stroke volume, and systemic arterial pressure, and increased total peripheral resistance [17]. Extrapolating these results to humans must be done cautiously, however, as methanol metabolism varies considerably between species [3].
These findings would seem to argue against heart donation in these circumstances, and it has been common practice to reject organs exposed to methanol intoxication [4, 5]. However, Hanston and coworkers [6] performed a successful heart transplant with such an organ. Despite a positive 5-year result, the authors suggested that methanol intoxication should be a contraindication to heart donation, as the associated metabolic acidosis may lead to myocyte degeneration.
We have successfully transplanted three hearts from donors who had ingested lethal quantities of methanol. None of the donors had cardiac arrest. Two donors were dependent on significant inotropic support at the time of explanation. In one of these cases, the recipient had a difficult operation and recovery, but was eventually discharged in stable condition. Another recipient had a difficult operation and recovery because of preoperative multisystem organ failure, multiple risk factors, and the complexity of the operation (four previous cardiac operations). He eventually recovered and was discharged and continues to enjoy an excellent long-term result. In both of these cases, significant inotropic support was required for a few days postoperatively. The third donor exhibited ECG abnormalities and experienced a period of hypotension before explantation. The recipient experienced no intraoperative or postoperative complications.
Carbon monoxide exposure
Carbon monoxide causes tissue hypoxia in three ways: (1) CO has 200 times the affinity for hemoglobin as oxygen; (2) CO shifts the oxygen dissociation curve left, decreasing the amount of oxygen released to the tissues; and (3) CO directly effects cellular respiration by competing with oxygen for cytochrome A3 [18]. The tissues most affected are those most sensitive to oxygen deprivation, specifically the central nervous system and the myocardium [9, 19–21]. Individual susceptibility varies [21] and symptoms depend on degree of exposure (concentration, duration, and ventilation volume), tissue metabolic demands, concurrent anemia, and preexisting atherosclerosis [19]. Typical effects of CO poisoning on the heart include punctiform and diffuse hemorrhage throughout, especially in the septum and papillary muscles [8, 21, 22]. These are findings consistent with any type of tissue anoxia [8, 9]. Effect on cardiac function varies in onset and severity [19] and is usually transient, resolving when carboxyhemoglobin returns to a nontoxic level [8]. Common ECG changes include sinus tachycardia, nonspecific ST segment depression, T wave inversions or flattening, and premature atrial and ventricular beats [7, 8]. Echocardiographic findings may include abnormal left ventricular wall motion and mitral valve prolapse resulting from papillary muscle dysfunction [23]. In cases of severe myocardial injury, cardiac enzymes will be elevated as seen after myocardial infarction [8]. Electrocardiographic and echocardiographic changes may be persistent in these cases [21, 24].
Authors have reported mixed results with these heart donors [6–13]. Karwande and associates [9] first reported an unsuccessful cardiac transplant in 1989 with a donor heart exposed to CO. This donor had had a number of cardiac arrests before harvesting. Subsequent transplantations have been more successful [6–8, 10–13], with only one report of postoperative heart failure being partly related to CO toxicity [6, 13]. Most of these donors initially exhibited abnormal ECGs, which normalized spontaneously before explantation. All donors had normal echocardiograms on admission and required minimal to no inotropic support at the time of harvest. Some donors required CPR immediately following injury.
We have successfully transplanted two hearts from donors who had fatal CO exposure. Both donors required CPR, but neither exhibited echocardiographic or ECG abnormalities. One donor was dependent on significant inotropic support at the time of explantation. Both recipients enjoyed uneventful operations and recoveries.
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Comment
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Successful heart transplantation can be achieved using the hearts from patients succumbing to methanol or CO poisoning. Routine evaluation of cardiac function and myocardial damage is adequate for screening these donors. Hearts from methanol-poisoning victims may require longer inotropic support postoperatively before the recipient’s complete recovery, but can provide excellent long-term function and results. Increasing waiting lists and their associated mortality remain an impetus to broaden our acceptance criteria of "marginal" donor hearts.
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References
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Abstract
Introduction
