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Intraoperative management of liver transplant patients with pulmonary hypertension
Intraoperative Management of Liver Transplant Patients With Pulmonary Hypertension Marie Csete
A
lthough pulmonary hypertension caused by liver disease is rare, anesthesiologists working in busy liver transplant (LTx) centers are likely to encounter such patients. In experienced centers, LTx patients with mild pulmonary hypertension appear not to be at significantly increased risk of intraoperative complications. However, patients with moderate to severe pulmonary hypertension represent a high-risk group of LTx candidates. Several case reports have emphasized the difficulty in treating these patients. In summary, these reports show several important points. First, autoimmune liver disease is overrepresented in this population and raises the question of whether pulmonary hypertension in this subset is really a consequence of liver disease or of the autoimmune process. Pulmonary pressure/vascular resistance drug responsiveness does not reliably predict survival during or after transplantation, and the risk of perioperative death is high. The time course of resolution of pulmonary hypertension after LTx, when it occurs, is slow (months to years). In patients whose pulmonary hypertension did improve, cardiac outputs also decreased dramatically. Finally, because we and other centers have not reported our full series (especially the less-thansuccessful outcomes), the denominator for these cases is unknown. Given this gap in knowledge, it is safe to say that LTx can reverse pulmonary hypertension associated with end-stage liver disease. However, the probability of this optimistic outcome cannot be estimated from the available data. Certainly a pooling of the national experience will give us more insight into selecting and treating these patients. Despite the relatively intensive work-ups received by LTx candidates, pulmonary hypertension may not be diagnosed until the patient is in the operating room. Diagnosis is not always possible from echocardiography, even by cardiologists who
From the UCI College of Medicine, Orange, California. Address reprint requests to Marie Csete, MD, Caltech Biology, M/C 156-29, Pasadena, CA 91125. Copyright r 1997 by the American Association for the Study of Liver Diseases 1074-3022/97/0304-0022$3.00/0
454
work closely with LTx programs. In addition, the pace of progression of pulmonary hypertension in these patients may be very rapid, and if the patient has been on a waiting list for a long time, a distant preoperative assessment may severely underestimate the extent of pulmonary hypertension at the time of LTx. The unexpected finding of pulmonary hypertension in the operating room requires complete reassessment of the decision to proceed with LTx. The options in this setting are to (1) proceed with LTx, (2) admit the patient to an intensive care unit (ICU) to reevaluate candidacy, or (3) not perform LTx. The decision to proceed should take into account the experience of the staff. Inexperienced centers may prefer to transfer the patient to a more experienced center. The donor liver is also a consideration; knowing that predicting donor function is an inexact science, it should be a liver that is expected to function well immediately. These patients can be expected not to tolerate poor graft function. After increased risk is discussed, the family’s wishes as well as the presence of exacerbating conditions, must also be considered. For example, if the patient has an inadequately treated systemic infection, delay of surgery should be considered. Finally, intraoperative assessment of drug responsiveness may help with the decision to proceed. If the patient has extremely high pulmonary artery pressures absolutely unresponsive to pharmacological manipulation, it is likely that any added increase in pulmonary pressure during surgery will lead to right heart failure. On the other hand, pulmonary vascular drug responsiveness is not a guarantee of survival. Assessment of drug responsiveness is time-consuming because many regimens should be tried. Therefore, if the donor liver ischemia time is long, this assessment may be better done at leisure in the ICU, with LTx postponed just long enough to make the evaluation. Long postponements are inadvisable because pulmonary pressures are likely to worsen. No ideal drug regimen can be recommended for these patients. Prostaglandin E1 is a reasonable first choice because it may also improve early graft function. Other vasodilators that may be useful include dobutamine, nitroglycerine, and nitroprus-
Liver Transplantation and Surgery, Vol 3, No 4 ( July), 1997: pp 454-455
Intraoperative Management of Pulmonary Hypertension
side. We have also used intravenous diltiazem in this setting with some success. Nitric oxide has been used to bridge patients through LTx.1 However, it is unlikely that patients whose pulmonary arterial pressures are unresponsive to intravenous vasodilators (which work via nitric oxide) will respond to inhaled nitric oxide. The advantage of inhaled nitric oxide may be its selectivity for the pulmonary vascular bed. The goal of therapy is to lower pressures sufficiently to allow the patient to better tolerate the likely increase in pulmonary pressures following reperfusion. The end-point of therapy differs from center to center. Some centers use pulmonary artery pressures, and others use pulmonary vascular resistance (or its index). Other centers use the transpulmonary gradient (as has been used in evaluating heart transplant patients). Because there is no evidence that changes in any of these parameters are predictive of survival, each center must adopt its own standards. Systemic hypotension or increases in pulmonary shunt may limit the amount of vasodilator the patient tolerates. During transplantation, adequate depth of anesthesia and oxygenation and treatment of acidosis obviously are standards of patient care. The acute hemodynamic effects of reperfusion may be better tolerated if clamps are removed gradually. Because tricuspid regurgitation is common, as are acute temperature fluctuations, thermodilution cardiac output measurements may be difficult to interpret, and the calculated pulmonary vascular resistance may not reflect the degree of pulmonary vascular disease. Therefore, transesophageal echocardiography may be a useful adjunct in intraoperative monitoring. The immediate postreperfusion period is the most treacherous time. In pulmonary hypertension patients who die during LTx, a characteristic series of events unfolds at that time. Pulmonary pressures
455
increase, and if the increase is severe or persistent, the right side of the heart fails, the graft becomes engorged and does not function well, and the patient cannot be resuscitated from this cycle. One center recently reported that aortic cross-clamping reversed this cycle acutely during LTx, although the patient died several days later.2 The second period of markedly increased risk is several days after transplantation,3 similar to the timing of peak incidence of perioperative myocardial infarction. For this reason, it may be prudent to remove the pulmonary artery catheter only after the patient has passed through the second high-risk period, and during that time to give particular attention to pain and stress management. Although microemboli and platelet activation are associated with some forms of pulmonary hypertension, thromboemboli are not thought to contribute to the pulmonary vascular disease associated with portal hypertension. Based on these conclusions, procoagulant drugs can be safely administered during LTx. In the best of all possible worlds, a better understanding of the mediators of postreperfusion pulmonary hypertension will lead to a safer surgical procedure for these high-risk patients. Perhaps anticytokine strategies or promotion of nitric oxide synthesis will be the kinds of therapies available in the future.
References 1. Mandell MS, Duke J. Nitric oxide reduces pulmonary hypertension during hepatic transplantation. Anesthesiology 1994;81:1538-1542. 2. Gillies BS, Perkins JD, Cheney FW. Abdominal aortic compression to treat circulatory collapse caused by severe pulmonary hypertension during liver transplantation. Anesthesiology 1996;85:420-422. 3. Cheng EY, Woehick JH. Pulmonary artery hypertension complicating anesthesia for liver transplantation. Anesthesiology 1992;77:389-392.
A
lthough pulmonary hypertension caused by liver disease is rare, anesthesiologists working in busy liver transplant (LTx) centers are likely to encounter such patients. In experienced centers, LTx patients with mild pulmonary hypertension appear not to be at significantly increased risk of intraoperative complications. However, patients with moderate to severe pulmonary hypertension represent a high-risk group of LTx candidates. Several case reports have emphasized the difficulty in treating these patients. In summary, these reports show several important points. First, autoimmune liver disease is overrepresented in this population and raises the question of whether pulmonary hypertension in this subset is really a consequence of liver disease or of the autoimmune process. Pulmonary pressure/vascular resistance drug responsiveness does not reliably predict survival during or after transplantation, and the risk of perioperative death is high. The time course of resolution of pulmonary hypertension after LTx, when it occurs, is slow (months to years). In patients whose pulmonary hypertension did improve, cardiac outputs also decreased dramatically. Finally, because we and other centers have not reported our full series (especially the less-thansuccessful outcomes), the denominator for these cases is unknown. Given this gap in knowledge, it is safe to say that LTx can reverse pulmonary hypertension associated with end-stage liver disease. However, the probability of this optimistic outcome cannot be estimated from the available data. Certainly a pooling of the national experience will give us more insight into selecting and treating these patients. Despite the relatively intensive work-ups received by LTx candidates, pulmonary hypertension may not be diagnosed until the patient is in the operating room. Diagnosis is not always possible from echocardiography, even by cardiologists who
From the UCI College of Medicine, Orange, California. Address reprint requests to Marie Csete, MD, Caltech Biology, M/C 156-29, Pasadena, CA 91125. Copyright r 1997 by the American Association for the Study of Liver Diseases 1074-3022/97/0304-0022$3.00/0
454
work closely with LTx programs. In addition, the pace of progression of pulmonary hypertension in these patients may be very rapid, and if the patient has been on a waiting list for a long time, a distant preoperative assessment may severely underestimate the extent of pulmonary hypertension at the time of LTx. The unexpected finding of pulmonary hypertension in the operating room requires complete reassessment of the decision to proceed with LTx. The options in this setting are to (1) proceed with LTx, (2) admit the patient to an intensive care unit (ICU) to reevaluate candidacy, or (3) not perform LTx. The decision to proceed should take into account the experience of the staff. Inexperienced centers may prefer to transfer the patient to a more experienced center. The donor liver is also a consideration; knowing that predicting donor function is an inexact science, it should be a liver that is expected to function well immediately. These patients can be expected not to tolerate poor graft function. After increased risk is discussed, the family’s wishes as well as the presence of exacerbating conditions, must also be considered. For example, if the patient has an inadequately treated systemic infection, delay of surgery should be considered. Finally, intraoperative assessment of drug responsiveness may help with the decision to proceed. If the patient has extremely high pulmonary artery pressures absolutely unresponsive to pharmacological manipulation, it is likely that any added increase in pulmonary pressure during surgery will lead to right heart failure. On the other hand, pulmonary vascular drug responsiveness is not a guarantee of survival. Assessment of drug responsiveness is time-consuming because many regimens should be tried. Therefore, if the donor liver ischemia time is long, this assessment may be better done at leisure in the ICU, with LTx postponed just long enough to make the evaluation. Long postponements are inadvisable because pulmonary pressures are likely to worsen. No ideal drug regimen can be recommended for these patients. Prostaglandin E1 is a reasonable first choice because it may also improve early graft function. Other vasodilators that may be useful include dobutamine, nitroglycerine, and nitroprus-
Liver Transplantation and Surgery, Vol 3, No 4 ( July), 1997: pp 454-455
Intraoperative Management of Pulmonary Hypertension
side. We have also used intravenous diltiazem in this setting with some success. Nitric oxide has been used to bridge patients through LTx.1 However, it is unlikely that patients whose pulmonary arterial pressures are unresponsive to intravenous vasodilators (which work via nitric oxide) will respond to inhaled nitric oxide. The advantage of inhaled nitric oxide may be its selectivity for the pulmonary vascular bed. The goal of therapy is to lower pressures sufficiently to allow the patient to better tolerate the likely increase in pulmonary pressures following reperfusion. The end-point of therapy differs from center to center. Some centers use pulmonary artery pressures, and others use pulmonary vascular resistance (or its index). Other centers use the transpulmonary gradient (as has been used in evaluating heart transplant patients). Because there is no evidence that changes in any of these parameters are predictive of survival, each center must adopt its own standards. Systemic hypotension or increases in pulmonary shunt may limit the amount of vasodilator the patient tolerates. During transplantation, adequate depth of anesthesia and oxygenation and treatment of acidosis obviously are standards of patient care. The acute hemodynamic effects of reperfusion may be better tolerated if clamps are removed gradually. Because tricuspid regurgitation is common, as are acute temperature fluctuations, thermodilution cardiac output measurements may be difficult to interpret, and the calculated pulmonary vascular resistance may not reflect the degree of pulmonary vascular disease. Therefore, transesophageal echocardiography may be a useful adjunct in intraoperative monitoring. The immediate postreperfusion period is the most treacherous time. In pulmonary hypertension patients who die during LTx, a characteristic series of events unfolds at that time. Pulmonary pressures
455
increase, and if the increase is severe or persistent, the right side of the heart fails, the graft becomes engorged and does not function well, and the patient cannot be resuscitated from this cycle. One center recently reported that aortic cross-clamping reversed this cycle acutely during LTx, although the patient died several days later.2 The second period of markedly increased risk is several days after transplantation,3 similar to the timing of peak incidence of perioperative myocardial infarction. For this reason, it may be prudent to remove the pulmonary artery catheter only after the patient has passed through the second high-risk period, and during that time to give particular attention to pain and stress management. Although microemboli and platelet activation are associated with some forms of pulmonary hypertension, thromboemboli are not thought to contribute to the pulmonary vascular disease associated with portal hypertension. Based on these conclusions, procoagulant drugs can be safely administered during LTx. In the best of all possible worlds, a better understanding of the mediators of postreperfusion pulmonary hypertension will lead to a safer surgical procedure for these high-risk patients. Perhaps anticytokine strategies or promotion of nitric oxide synthesis will be the kinds of therapies available in the future.
References 1. Mandell MS, Duke J. Nitric oxide reduces pulmonary hypertension during hepatic transplantation. Anesthesiology 1994;81:1538-1542. 2. Gillies BS, Perkins JD, Cheney FW. Abdominal aortic compression to treat circulatory collapse caused by severe pulmonary hypertension during liver transplantation. Anesthesiology 1996;85:420-422. 3. Cheng EY, Woehick JH. Pulmonary artery hypertension complicating anesthesia for liver transplantation. Anesthesiology 1992;77:389-392.