Anesthesia for Heart, Lung, and Heart-Lung Transplantation

Recipient Selection

Potential candidates for heart transplantation generally undergo a multidisciplinary evaluation, including a complete history and physical examination, routine hematology, chemistries (to assess renal and hepatic function), viral serology, electrocardiography, chest radiography, pulmonary function tests, and right- and left-heart catheterization. Ambulatory electrocardiography, echocardiography, and nuclear gated scans are performed if necessary. The goals of this evaluation are to confirm a diagnosis of end-stage heart disease that is not amenable to other therapies and that will likely lead to death within 1 to 2 years, as well as to exclude extracardiac organ dysfunction that could lead to death soon after heart transplantation. Patients typically have New York Heart Association (NYHA) class IV symptoms and a left ventricular ejection fraction less than 20%. Although most centers eschew a strict age cutoff, the candidate should have a physiologic age younger than 60. Detecting pulmonary hypertension and determining whether it is due to fixed elevation of pulmonary vascular resistance (PVR) is crucial; early mortality because of graft failure is threefold greater in patients with increased PVR (transpulmonary gradient >15 mm Hg or PVR >5 dynes•sec•cm ⁻⁵ ). If increased PVR is detected, a larger donor heart, a heterotopic heart transplant, or a heart-lung transplant (HLT) may be more appropriate. Active infection and recent pulmonary thromboembolism with pulmonary infarction are additional contraindications to heart transplantation. The results of this extensive evaluation should be tabulated and available to the anesthesia team at all times because heart transplantation is an emergency procedure.

Donor Selection and Graft Harvest

Once a brain-dead donor has been identified, the accepting transplant center must further evaluate the suitability of the allograft. Centers generally prefer donors to be free of previous cardiac illness and younger than 35 years because the incidence of coronary artery disease markedly increases at older ages. However, the relative shortage of suitable cardiac donors has forced many transplant centers to consider older donors without risk factors and symptoms of coronary artery disease. If it is necessary and the services are available at the donor hospital, the heart can be further evaluated by echocardiography (for regional wall motion abnormalities) or coronary angiography, to complement standard palpation of the coronaries in the operating room. The absence of sepsis, prolonged cardiac arrest, severe chest trauma, and a high inotrope requirement also are important. The donor is matched to the prospective recipient for ABO blood-type compatibility and size (within 20%, especially if the recipient has high PVR); a crossmatch is performed only if the recipient's preformed antibody screen is positive.

Donors can exhibit major hemodynamic and metabolic derangements that can adversely affect organ retrieval. Most brain-dead donors will be hemodynamically unstable. Reasons for such instability include hypovolemia (secondary to diuretics or diabetes insipidus), myocardial injury (possibly a result of catecholamine storm during periods of increased intracranial pressure), and inadequate sympathetic tone because of brainstem infarction. Donors often also have abnormalities of neuroendocrine function such as low T ₃ and T ₄ levels.

Donor cardiectomy is performed through a median sternotomy, usually simultaneously with recovery of other organs such as lungs, kidneys, and liver. Just before cardiac harvesting, the donor is heparinized and an intravenous cannula is placed in the ascending aorta for administration of conventional cardioplegia. The superior vena cava (SVC) is ligated and the inferior vena cava (IVC) transected to decompress the heart, simultaneous with the administration of cold hyperkalemic cardioplegia into the aortic root. The aorta is cross-clamped when the heart ceases to eject. The heart also is topically cooled with ice-cold saline. After arrest has been achieved, the pulmonary veins are severed, the SVC is transected, the ascending aorta is divided just proximal to the innominate artery, and the pulmonary artery (PA) is transected at its bifurcation. The heart is then prepared for transport by placing it in a sterile plastic bag that is placed, in turn, in another bag filled with ice-cold saline, all of which are carried in an ice chest. Of all the regimens tested, conventional cardioplegia has proved most effective in maintaining cardiac performance. The upper time limit for ex vivo storage of human hearts appears to be approximately 6 hours.

Surgical Procedures

Orthotopic Heart Transplantation

Orthotopic heart transplantation is carried out via a median sternotomy, and the general approach is similar to that used for coronary revascularization or valve replacement. Frequently, patients will have undergone a prior median sternotomy; repeat sternotomy is cautiously performed using an oscillating saw. The groin should be prepped and draped to provide a rapid route for cannulation for cardiopulmonary bypass (CPB) if necessary. After the pericardium is opened, the aorta is cannulated as distally as possible and the IVC and SVC are individually cannulated via the high right atrium. Manipulation of the heart before institution of CPB is limited if thrombus is detected in the heart with transesophageal echocardiography (TEE). After initiation of CPB and cross-clamping of the aorta, the heart is arrested and excised ( Fig. 19.1 ). The aorta and PA are separated and divided just above the level of their respective valves, and the atria are transected at their grooves. A variant of this classic approach totally excises both atria, mandating bicaval anastomoses. This technique may reduce the incidence of atrial arrhythmias, better preserve atrial function by avoiding tricuspid regurgitation, and enhance cardiac output (CO) after transplantation.

The donor graft then is implanted with every effort to maintain a cold tissue temperature, beginning with the left atrial (LA) anastomosis. If the foramen ovale is patent, it is sutured closed. The donor right atrium is opened by incising it from the IVC to the base of the right atrial (RA) appendage (to preserve the donor sinoatrial node), and the RA anastomosis is constructed. Alternatively, if the bicaval technique is used, individual IVC and SVC anastomoses are sewn. The donor and recipient PAs are then brought together in an end-to-end manner, followed by the anastomosis of the donor to the recipient aorta. After removal of the aortic cross-clamp, the heart is de-aired via a vent in the ascending aorta. Just before weaning from CPB, one of the venous cannulae is withdrawn into the right atrium and the other removed. The patient is then weaned from CPB in the usual manner. After hemostasis is achieved, mediastinal tubes are placed for drainage, the pericardium is left open, and the wound is closed in the standard fashion.

Heterotopic Heart Transplantation

Although orthotopic placement of the cardiac graft is optimal for most patients, certain recipients are not candidates for the orthotopic operation, and instead the graft is placed in the right chest and connected to the circulation in parallel with the recipient heart. The two primary indications for heterotopic placement are significant irreversible pulmonary hypertension and gross size mismatch between the donor and recipient. Heterotopic placement may avoid the development of acute right ventricular (RV) failure in the unconditioned donor heart in the face of acutely increased RV afterload.

Donor harvesting for heterotopic placement is performed in the previously described manner, except that the azygos vein is ligated and divided to increase the length of the donor SVC; the PA is extensively dissected to provide the longest possible main and right PA; and the donor IVC and right pulmonary veins are oversewn, with the left pulmonary veins incised to create a single large orifice. The operation is performed via a median sternotomy in the recipient, but the right pleura is entered and excised. The recipient SVC is cannulated via the RA appendage, and the IVC via the lower right atrium. After arresting the recipient heart, the LA anastomosis is constructed by incising the recipient left atrium near the right superior pulmonary vein and extending this incision inferiorly and then anastomosing the respective left atria. The recipient RA-SVC is then incised and anastomosed to the donor RA-SVC, after which the donor aorta is joined to the recipient aorta in an end-to-side manner. Finally, the donor PA is anastomosed to the recipient main PA in an end-to-side manner if it is sufficiently long; otherwise, they are joined via an interposed vascular graft ( Fig. 19.2 ).

Pathophysiology Before Transplantation

The pathophysiology of heart transplant candidates is predominantly end-stage cardiomyopathy. Normally, such patients will have both systolic dysfunction (characterized by decreased stroke volume and increased end-diastolic volume) and diastolic dysfunction, characterized by an increased intracardiac diastolic pressure. As compensatory mechanisms to maintain CO fail, the increased left ventricular (LV) pressures lead to increases in pulmonary venous pressures and development of pulmonary vascular congestion and edema. A similar process occurs if RV failure also occurs. Autonomic sympathetic tone is increased in patients with heart failure, leading to generalized vasoconstriction, as well as salt and water retention. Vasoconstriction and ventricular dilation combine to substantially increase myocardial wall tension. Over time, the high levels of catecholamines lead to a decrease in the sensitivity of the heart and vasculature to these agents via a decrease in receptor density (ie, downregulation) and a decrease in myocardial norepinephrine stores.

Therapy of heart failure seeks to reverse or antagonize these processes. Almost all candidates will be maintained on diuretics; hypokalemia and hypomagnesemia secondary to urinary losses are likely, and the anesthesiologist must be alert to the possibility that a patient is hypovolemic from excessive diuresis. Another mainstay of therapy is vasodilators (such as nitrates, hydralazine, and angiotensin-converting enzyme inhibitors), which decrease the impedance to LV emptying and improve cardiac function and survival in patients with end-stage heart failure. Paradoxically, slow incremental β-blockade with agents such as the β ₁ -antagonist metoprolol also can improve hemodynamics and exercise tolerance in some patients awaiting heart transplantation. Patients who are symptomatic despite these measures often will require inotropic therapy. Digoxin is an effective but weak inotrope, and its use is limited by toxic side effects. Phosphodiesterase inhibitors such as amrinone, milrinone, and enoximone are efficacious, but chronic therapy is restricted by concerns about increased mortality in those receiving these agents. Therefore inotrope-dependent patients often are treated with intravenous infusions of β-adrenergic agonists such as dopamine or dobutamine. Patients refractory to even these measures may be supported with intraaortic balloon counterpulsation, but its use is fraught with significant vascular complications and essentially immobilizes the patient. Many patients with low CO are maintained on anticoagulants such as warfarin to prevent pulmonary or systemic embolization, especially if they have atrial fibrillation.

Pathophysiology After Transplantation

The physiology of patients after heart transplantation is of interest not only to anesthesiologists in cardiac transplant centers but to the anesthesiology community at large because a substantial portion of these patients return for subsequent surgical procedures.

Cardiac denervation is an unavoidable consequence of heart transplantation. Many long-term studies indicate that reinnervation is absent, or at best partial or incomplete, in humans. Denervation does not significantly change baseline cardiac function, but it does substantially alter the cardiac response to demands for increased CO. Normally, increases in heart rate can rapidly increase CO, but this mechanism is not available to the transplanted heart. Heart rate increases only gradually with exercise, and this effect is mediated by circulating catecholamines. Increases in CO in response to exercise are instead mostly mediated via an increase in stroke volume. Therefore maintenance of adequate preload in cardiac transplant recipients is crucial. Lack of parasympathetic innervation probably is responsible for the gradual decrease in heart rate after exercise seen in transplant recipients, rather than the usual sharp decline.

Denervation has important implications in the choice of pharmacologic agents used after cardiac transplantation. Drugs that act indirectly on the heart via either the sympathetic (ephedrine) or parasympathetic (atropine, pancuronium, edrophonium) nervous systems generally will be ineffective. Drugs with a mixture of direct and indirect effects will exhibit only their direct effects (leading to the absence of the normal increase in refractory period of the atrioventricular node with digoxin, tachycardia with norepinephrine infusion, and bradycardia with neostigmine). Thus agents with direct cardiac effects (such as epinephrine or isoproterenol) are the drugs of choice for altering cardiac physiology after transplantation. However, the chronically high catecholamine levels found in cardiac transplant recipients may blunt the effect of α-adrenergic agents, as opposed to normal responses to β-adrenergic agents.

Allograft coronary vasculopathy remains the greatest threat to long-term survival after heart transplantation. Allografts are prone to the accelerated development of an unusual form of coronary atherosclerosis that is characterized by circumferential, diffuse involvement of entire coronary arterial segments, as opposed to the conventional form of coronary atherosclerosis with focal plaques often found in eccentric positions in proximal coronary arteries. The pathophysiologic basis of this process remains elusive, but it is likely due to an immune cell-mediated activation of vascular endothelial cells to upregulate the production of smooth muscle cell growth factors. More than half of all heart transplant recipients have evidence of concentric atherosclerosis 3 years after transplant, and more than 80% at 5 years. Because afferent cardiac reinnervation is rare, a substantial portion of recipients with accelerated vasculopathy will have silent ischemia. Noninvasive methods of detecting coronary atherosclerosis are insensitive for detecting allograft vasculopathy. Furthermore, coronary angiography often underestimates the severity of allograft atherosclerosis; other diagnostic regimens such as intravascular ultrasound and dobutamine stress echocardiography may detect morphologic abnormalities or functional ischemia, respectively, in the absence of angiographically significant lesions. Therefore the anesthesiologist should assume that there is a substantial risk for coronary vasculopathy in any heart transplant recipient beyond the first 2 years, regardless of symptoms, the results of noninvasive testing, and even angiography.

Anesthetic Management