Heart/Lung Transplantation

Hari R. Mallidi MD¹

Bruce A. Reitz MD¹

Daryl Oakes MD²

Linda E. Foppiano MD²

¹SURGEONS

²ANESTHESIOLOGISTS

SURGERY FOR HEART TRANSPLANTATION

SURGICAL CONSIDERATIONS

Description: Although heart transplantation has been practiced since 1967, it has had its greatest expansion since the early 1980s with the introduction of cyclosporine. Currently, there are approximately 150 transplant centers and 2,200 heart transplant procedures performed yearly in the United States. Indications for heart transplantation range from hypoplastic left heart syndrome (HLHS) in the neonate to cardiomyopathy and ischemic heart disease in the adult. Recipients usually have end-stage heart disease manifested by CHF and a prognosis of less than 1-yr survival. Many patients are on inotropic drugs or on some type of additional mechanical assist, such as the use of an intraaortic balloon pump (IABP) or an implanted LV-assist device. Current immunosuppressive protocols consist of a combination of a calcineurin inhibitor with prednisone and mycophenolate mofetil. Immunosuppression begins either immediately preop or perioperatively and will continue throughout the life of the patient. Induction immunosuppression is commenced in the operating room after protamine administration with methylprednisolone 500 mg iv and basiliximab or rATG in the ICU after transplantation. Current 1-yr survival averages 85% in most centers with 3-yr survival of approximately 80%, and a median survival approaching 10 years.

In adult heart transplantation, following median sternotomy, the pericardium is opened with care being taken to preserve the phrenic nerve. The aorta and vena cava are cannulated, the aorta is cross-clamped, and caval tapes (tourniquets to prevent VAE) are applied. The aorta and PA are then transected. This is followed by an incision through the atria, and the recipient heart is removed. The donor heart is prepared by opening the left atrium through the pulmonary veins, separating the aorta and PA. The donor heart is attached by a long, continuous suture line around the left atrium, followed by separate anastomoses to the inferior and superior vena cavae. Alternatively, the donor right atrium is anastomosed to the recipient right atrium with a single long continuous suture. Next, the PA and aorta are anastomosed to their respective recipient vessels. Multiple de-airing maneuvers are followed by aortic unclamping and rewarming and resuscitation of the heart. NSR is established and CPB D/C’d. Heparin is reversed, hemostasis is secured, and the chest is closed in a routine manner. Following chest closure, these patients will often have implanted defibrillators that will be removed. An incision is made to access the pacemaker pocket, and the device is explanted. After hemostasis is established, the pocket is closed. (See pp. 348+ for discussion of CPB.)

Neonatal heart transplantation differs in that the PA is cannulated if the ductus arteriosus is patent. Reconstruction of the aortic arch in the patient with HLHS requires CPB with deep hypothermia (< 18°C) and circulatory arrest. The heart is then excised, and the transverse aortic arch is opened beyond the ductus arteriosus to minimize risk of late coarctation.

Figure 6.4-1. The donor left atrium is sutured to the recipient left atrial remnant and the graft vessels are anastomosed.

The donor heart is prepared, with special attention given to trimming the transverse aortic tissue for subsequent reconstruction. The left and right atrium, PA, and aorta are sutured in place. The new ascending aorta and right atrium are cannulated, and CPB with rewarming is reinstituted. Chest closure is routine. (See Pediatric Transplantation p. 1468.)

Pediatric heart transplantation has become commonplace in the past 10 years. Patients often have had previous cardiac surgery, and reentry and excision of the native heart are complicated by the presence of adhesions and graft material from previous attempts at palliative/corrective surgery. Patients are often highly sensitized and may require intraoperative plasmapheresis while on cardiopulmonary bypass. Preparation for cardiopulmonary bypass is often similar to the adult heart transplant patient, and the implantation procedure is also similar. However, provisions should be made for prolonged cross-clamp times necessary for implantation in the setting of abnormal systemiccardiac or pulmonary-cardiac connections. (See Pediatric Transplantation p. 1468.)

Usual preop diagnosis: Cardiomyopathy; CAD with ischemic cardiomyopathy; CHD (e.g., HLHS or anomalous left coronary artery); end-stage valvular heart disease

▪ SUMMARY OF PROCEDURES

	Adult Heart Transplantation	Neonatal/Pediatric Heart Transplantation
Position	Supine	⇚
Incision	Median sternotomy	⇚
Special instrumentation	Ascending aortic, SVC, and IVC cannulae	Ascending aortic and right atrial cannulae
Unique considerations	Due to complete excision of the heart, use of a PA catheter is usually not feasible.	Deep hypothermia with circulatory arrest
Antibiotics	Cefazolin 1-2 g iv	Cefazolin 25-50 mg/kg iv
Surgical time	Cross-clamp: 45-60 min Surgery: 3-4 h	Circulatory arrest: 45-60 min; Cross-clamp: 80-100 min Surgery: 4-6 h
Closing considerations	Temporary AV pacing wires are occasionally placed. A PA catheter may be advanced, especially with concerns about residual pulmonary HTN and donor right heart function. An isoproterenol infusion is started intraop to keep HR = 100-110 and help improve right heart function and ↓ PVR. Inhaled NO may be used to further ↓ PVR.	Temporary ventricular pacing wire is usually placed. Temporary transthoracic left atrial line may be placed. Extensive aortic suture line requires avoidance of postop hypertensive episodes.
EBL	500-1500 mL	50-100 mL
Postop care	Cardiac ICU × 1-2 d of assisted ventilation; 2-3 d stay.	Pediatric ICU × 1-2 d of assisted ventilation; 4-5 d stay, with attention to pulmonary care.
Mortality	< 5%	⇚
Morbidity	Early acute rejection episodes from 10-21 d: 50% Infection, particularly pulmonary: 10% Pulmonary HTN with right heart dysfunction: < 10% Dysrhythmias with nodal rhythms: 5% Bleeding: 2-4% Hyperacute rejection: Rare (< 1%) Intracoronary air emboli	⇚ Respiratory problems: 20% Infection: 10% Pulmonary vasospasm with right heart dysfunction: < 10% Bleeding: 2-4%
Pain score	8-10	8-10

ANESTHETIC CONSIDERATIONS

PREOPERATIVE

Patients scheduled for heart transplantation are functionally compromised, typically with CHF, which is associated with a mortality of > 50% in 2 yr. (Studies have shown that patients with severe CHF have a mortality of 50% in 6 mo.) The progression of cardiovascular disease is usually well documented in these patients. A Hx of recent exacerbation of cardiac dysfunction should be sought, and all data should be interpreted in light of interval changes. Patients may arrive in the operating room from home or in hospital with inotropic infusions (dobutamine, milrinone) or VADS in place.

Respiratory	The presence of pulmonary HTN and ↑ PVR may be disclosed by catheterization. The severity of the abnormality and the responsiveness to specific vasodilators must be determined. Tests: Right heart catheterization
Cardiovascular	Indicators to consider include: hemodynamic status; LV EF (mortality is rapid in patients with EF < 10% and is worse for patients with EF of 10-20%, as compared with those with EF > 20%); myocardial structure and morphology, symptoms, and functional capacity; neuroendocrine status; serum sodium; and dysrhythmia. Unfortunately, while these measures show trends with mortality, they are not individually strong enough to predict a particular patient’s course. Low maximum O₂ consumption (< 10 mL/kg/min) is associated with poor survival. Normal O₂ consumption is 40 mL/kg/min. In practice, however, this measure is too severe because many patients awaiting heart transplantation have maximum O₂ consumption of 20 mL/kg/min. Dysrhythmia is a major cause of death; unfortunately electrophysiology studies of these patients may not be helpful because dysrhythmia tends to be noninducible. This phenomenon frustrates efforts to select and test antidysrhythmic drug therapy. The effectiveness of past antidysrhythmic therapy should be reviewed. Tests: ECG; cardiac catheterization; ECHO
Hematologic	Patients with dilated cardiomyopathy or previous cardiac surgery are frequently treated with anticoagulants to reduce the risk of thrombus formation, although the efficacy of this therapy has not been studied. Hepatic dysfunction may result from RV failure and may reduce synthetic function. Mild hepatic dysfunction and chronic anticoagulation may contribute to postop bleeding. The anticoagulant effect of warfarin should be reversed with FFP and vitamin K (iv or subcutaneous). Tests: Hct; PT; PTT; fibrinogen; Plts
Endocrine	Neuroendocrine abnormalities are often present in severe CHF cases. The cardiomyopathy produces low CO → compensatory sympathetic activation and renin-angiotensin activity. The result is excessive vasoconstriction with salt and H₂O retention, which further impair myocardial performance. Markedly worse survival is seen in CHF patients with serum sodium < 130. This may indicate the importance of neuroendocrine pathophysiology or may simply be evidence of the severity of the CHF. It may also simply indicate that patients with more severe CHF are treated with more diuretics. When patients are treated with an angiotensin-converting enzyme inhibitor, such as enalapril, the serum sodium is normalized, and survival chances are improved because of the slowing of the progression of CHF, not from alteration in the incidence of sudden death. Tests: Electrolytes; Cr
Laboratory	Evidence of renal and hepatic dysfunction should be sought by H&P and lab studies. Hypokalemia is generally not treated in view of the K⁺ in the graft.
Premedication	Although anxious, these patients are usually well informed and psychologically prepared to undergo heart transplantation. They respond well to the reassurance of the preop visit, and pharmacologic premedication usually is not necessary. O₂ therapy should commence prior to transport of the patient to the OR. Reassuring the family of a patient who suffers from rapidly progressive cardiac dysfunction also is valuable. The patient may be at increased risk for pulmonary aspiration of gastric contents because of the unscheduled nature of the surgery and use of oral cyclosporine immediately preop. Ranitidine (50 mg) and metoclopramide (10 mg) may be administered iv, most efficiently accomplished in the OR.

INTRAOPERATIVE

Anesthetic technique: GETA. After the patient is placed on the operating table, O₂ and noninvasive monitors are applied. Dyspnea (a complication of the supine position) can be treated by raising the back of the table. As infection is a serious complication in the immunosuppressed transplant patient, aseptic technique is extremely important. Aseptic technique is used in inserting and securing all vascular catheters. The anesthesia machine should be equipped with a supply of air to control the FiO₂.

Induction	An arterial line for BP and blood gas monitoring should be inserted, using liberal amounts of local anesthetics before induction. There are rare exceptions to this rule, but the presence of real-time BP monitoring is critical during induction. If infusion drugs (e.g., dopamine) are necessary before insertion of the CVP catheter, they can be infused temporarily through a separate peripheral iv. In patients who have a ↓ EF, it is often helpful to infuse dopamine 3-10 mcg/kg/min during induction to avoid ↓ HR and ↓ CO. Anesthesia is not induced until the team harvesting the graft reports that the donor heart appears to be normal. The patient is preoxygenated (FiO₂ = 1.0), and cricoid pressure is applied just before induction. Induction agents include fentanyl (3-5 mcg/kg) or sufentanil (1-4 mcg/kg). Propofol (0.5-1 mg/kg, titrated) or etomidate (0.1-0.2 mg/kg) is useful in permitting rapid control of the airway. Midazolam also may be used. Vecuronium (0.15 mg/kg), rocuronium 1-1.5 mg/kg should be administered immediately to permit airway control. Care must be taken to avoid bradycardia, which often results in low CO in these patients. Immediate control of the airway is crucial, as hypercarbia and hypoxia must be avoided. The patient can be expected to have a low CO, resulting in a delayed induction of anesthesia, which must be anticipated to avoid anesthetic overdosage. Hypotension should be treated promptly with inotropes (bolus and/or infusion). Fluid boluses may be poorly tolerated in patients with diminished contractility and should be administered cautiously. The usual aids for managing the unexpectedly difficult airway should be readily available. Antibiotics are administered, and additional monitors (urinary catheter with thermistor, TEE) are set up. Nasopharyngeal temperature probes are avoided because full heparinization is needed for CPB. If there is a delay in the anticipated arrival of the graft, the recipient should be covered and kept warm, and skin prep should be delayed. Additional narcotics should be administered only in immediate anticipation of the commencement of surgery.
Maintenance	Typical cumulative anesthetic doses for the entire intraop course are fentanyl 15-20 mcg/kg or sufentanil 10-15 mcg/kg; midazolam 0.15 mg/kg; vecuronium 0.3 mg/kg or rocuronium 3-5 mg/kg.
Termination of CPB	Junctional rhythm is common in the denervated transplanted heart. Isoproterenol 10-75 ng/kg/min or epinephrine 50-105 ng/kg/min may be used to achieve a HR of 100-120 bpm. Isoproterenol is also useful in providing inotropic support and pulmonary vasodilation (see below). Atropine and neostigmine do not affect HR. HTN does not produce reflex bradycardia. The graft atrium produces normally conducted P-waves if the right atrial cuff anastomosis is used. The graft-conductive tissue contains adrenergic receptors and responds normally to norepinephrine, epinephrine, and isoproterenol. Inotropic support with dopamine (2-10 mcg/kg/min), isoproterenol (10-150 ng/kg/min), and epinephrine (20-100 ng/kg/min) may be necessary, especially if pulmonary HTN promotes RV failure. Inhaled NO (20 ppm) may provide selective pulmonary vasodilation. A PA catheter may be helpful in guiding the use of inotropes and vasodilators and may be placed after CPB. After termination of CPB, TEE may be of particular value in assessing RV dysfunction, estimating PA pressures, and guiding appropriate fluid therapy, pharmacologic support, and mechanical support as necessary. RV failure may be produced by the presence of air in the RCA. Visual inspection may demonstrate this problem, and one should wait for the passage of the air and the resolution of ischemia before terminating CPB. SNP (0.2-2.0 mcg/kg/min) is used for afterload reduction. Inhaled NO, prostaglandin E1 (20-100 ng/kg/min), and NTG (0.2-2.0 mcg/kg/min) may be used for pulmonary vasodilation, especially if a preop catheterization study demonstrates responsiveness of the pulmonary circulation. Isoproterenol infusion (10-100 ng/kg/min) may provide appropriate pulmonary vasodilation, chronotropy, and inotropy. IV fluid and vasodilators must be given with particular care, as the flow produced by the denervated heart is quite sensitive to preload.
Postbypass hemorrhage	Postbypass bleeding is a common problem brought on by the preop use of anticoagulants, the depressed synthetic function of the liver in chronic heart failure, and the effects of CPB. Following administration of protamine, infusion of Plts, FFP, and RBCs may be necessary. Cryoprecipitate is needed occasionally, especially for patients with previous chest surgery. Epsilon-aminocaproic acid (EACA), or tranexamic acid may be appropriate in some cases. If bleeding persists, consider recombinant factor VIIa or FEIBA.
Immunosuppression	Methylprednisolone 500 mg is given after bypass is terminated. Daclizumab 1 mg/kg is also administered after administration of protamine, and hemostasis has been secured.
Diuresis	There may be little urine production, especially if patient received high-dose diuretics preop. Mannitol and furosemide may be needed to induce diuresis.
Transport	A Mapleson D or Jackson-Rees circuit is used in transporting the patient to the ICU. Sedation with iv infusion of propofol (20-50 mcg/kg/min) or dexmedetomidine (0.4-0.8 mcg/kg/min) may be used.
Blood and fluid requirements	Possible severe bleeding IV: 14-16 ga × 1-2 NS/LR @ 4-6 mL/kg/h	Bleeding is often a problem after termination of CPB. A second iv catheter is inserted in patients with previous chest surgery.
Monitoring	Standard monitors (see p. B-1). Arterial line CVP/PA catheter UO	Although it may be helpful to have a triple-lumen CVP line before induction for preload monitoring and infusion of potent infusion drugs, it is not essential. This line is usually inserted after the patient is intubated to avoid patient dyspnea and discomfort. A PA catheter is usually not inserted before bypass because it must be removed during surgery. An 8.5-Fr introducer is used in anticipation that a PA catheter may be necessary to manage right heart failure following the transplantation. In some institutions (not Stanford), the left IJ vein is the preferred site of cannulation, which leaves the right IJ unscarred for repeated postop endomyocardial biopsy of the transplanted heart.
	TEE	TEE is used to optimize fluid therapy, inotropic agents, vasodilators, and chronotropic agents.
Positioning	[check mark] and pad pressure points [check mark] eyes Arms padded at sides Chest roll