14.6.18 Heart transplantation

The first paediatric heart transplant was performed by Denton Cooley in 1984. Nowadays, just under 500 such procedures are carried out every year, which is 10 times fewer than in adults [5]. This figure remained stable in the past twelve years. The aetiological indications are as follows, by order of frequency [2].
 

• Congenital heart disease (inoperable lesions, palliative options exhausted). This is the most common indication in children aged under 1 year. The majority of patients are suffering from univentricular heart.
• Cardiomyopathy (dilated, restrictive, hypertrophic). This is the most common indication in patients aged over 1 year (50-65% of cases).
• Retransplantation (irreversible rejection, vasculopathy of the graft); late indication.
• Cardiac neoplasm (rare)

The main functional indications are terminal systemic ventricular failure (stage D), major growth retardation linked to heart failure (stage C), untreatable arrhythmias, and restrictive cardiomyopathy associated with pulmonary hypertension [11]. Transplantation is contraindicated in several scenarios [9].
 

• Irreversible multisystem disease, cancerous disease;
• Severe or irreversible pulmonary hypertension (PVR ≥ 5 Wood U) – a lung or heart-lung transplant may be considered in such cases;
• Severe cerebrovascular disease;
• Young age is not a limiting factor since 25% of recipients are aged between 20 days and 12 months [3].
• ABO incompatibility – due to the immature immune system of children aged under one year and due to their deficiency of antibodies against donors’ antigens, ABO-incompatible vital organs may be transplanted with the same survival rate as compatible organs. Plasmapheresis for extraction of antibodies is only necessary in 10% of cases [12]. Therefore, if no compatible donors are available, young children may be transplanted with hearts that are not compliant with the ABO system if their isoagglutinin titer is ≤ 1:4 and if the usual immunosuppression regimen is strictly followed (ATG, tacrolimus, mycophenolate mofetil, and steroids).

The graft can withstand a maximum period of 4-5 hours’ ischaemia between clamping of the aorta in the donor and unclamping of the aorta in the recipient. The transplantation technique is the same as for adults: aortic and distal bicaval cannulation, total resection of the heart leaving only the posterior wall of the LA in place with the insertion of the four pulmonary veins (Figure 14.74). The procedure comprises five anastomoses:
 

• Posterior wall of the graft LA to the posterior wall of the recipient's LA encompassing the anastomosis of the pulmonary veins. This reconstruction is sometimes performed in two stages for the two groups of right and left pulmonary veins.
• Graft aorta to the recipient's aorta.
• Graft SVC to the recipient's SVC.
• Graft IVC to the recipient's IVC.
• Graft pulmonary artery to the recipient's PA. These 3 final anastomoses may be performed while the heart is beating after the aorta is unclamped to reduce the ischaemia time for the graft.

In congenital heart disease cases, the graft taken from the donor must include a sufficient length of aorta and venae cavae to enable adequate reconstruction, as the donor's vessels will not necessarily match those of the recipient (transposition of the great arteries, truncus arteriosus). In cases of hypoplastic LV, the entire aortic arch is reconstructed with the donor’s aortic arch. After cavopulmonary anastomoses (Glenn, Fontan), the venae cavae are reconstructed with those of the donor and anastomosed very distally. The size of the graft roughly matches that of the recipient because donors are chosen with weight between 80% and 160% of the recipient’s weight. The graft grows normally in the recipient, consistent with its host’s own growth.


Figure 14.74: Surgical technique for orthotopic heart transplantation. A: Shumway's method – the body of the atria is kept in place. The donor's atria are grafted over them, hence the excess tissue and very large atrial chambers. B: Sievers’ bicaval technique. Only the posterior wall of the LA is left in place with the four pulmonary veins. The body of the RA and LA is resected. An anastomosis is performed between the donor's venae cavae and those of the recipient [Source: Kaplan JA, ed. Cardiac Anesthesia, 4th edition. Philadelphia: WB Saunders Co, 1999, p 993].

In the postoperative period, the younger the child, the higher the mortality rate: 6% > 10 years and 15% < 1 year. The main causes of death are graft failure, infection and multiple organ failure. Subsequently, one third of all deaths is linked to coronary heart disease developing in the graft. Once the immediate high-risk period is over, the attrition curve is lower, although the survival rate depends on the indication [3,4,6,7,11].
 

• Mean survival: 80% at 5 years and 70% at 10 years [7,11].
• After palliation for univentricular heart: survival at 1, 10 and 20 years of 73%, 58% and 49% respectively [8].
• After Fontan procedure: 71% survival at 5 years [10].
• Graft loss in the first 36 months: 6.4% – survival is ensured by a ventricular assist device.
• Long-term complications: chronic renal failure (39% of cases), acute rejection (34%), infection (34%), vasculopathy (10%) [1,13].

Although immunosuppression protocols vary significantly among institutions, all are based on the same substances [9].
 

• Induction: methylprednisolone, OKT3 (monoclonal antibody), basiliximab, daclizumab;
• Maintenance: prednisone, cyclosporin, tacrolimus;
• Rejection: methylprednisolone;
• Adjuvant: azathioprine, mycophenolate mofetil, sirolimus, everolimus.

All these regimens include a perioperative component: corticosteroids prior to unclamping the aorta or azathioprine on induction, and cyclosporin or antilymphocyte serum once the patient is off bypass. Many centres only administer steroids intraoperatively, with other drugs administered 24 hours later. The protocol in force must imperatively be followed (see Chapter 17 – Immunosuppression).

Anaesthesia for transplantation

The maximum ischaemic time tolerated by the graft is < 5 hours between clamping the aorta in the donor and unclamping it in the recipient. Since the recipient has already spent long periods in intensive care and undergone several surgical procedures, vascular access is difficult. It is therefore important to take the child to the surgical unit sufficiently early for equipment to be set up without causing any stress and for avoiding any waiting time between the graft's arrival and its implantation. It is essential to have a good knowledge of the child's surgical record in order to choose appropriate vascular puncture sites (e.g. subclavian artery sacrificed for a Blalock shunt). Some children are given an infusion of inotropes or vasodilators. These substances are not discontinued prior to CPB.

The induction technique is designed for a child with ventricular failure. It is adapted for the child's specific congenital pathology [2]. It is based on a combination of midazolam (0.05-0.1 mg/kg IV) and fentanyl (5-10 mcg/kg IV). Etomidate (0.1-0.3 mg/kg IV) is an excellent alternative as it has no haemodynamic effects and its suppression of cortisol synthesis is free of consequences given the doses of steroids administered as part of immunosuppression. Ketamine is not a good option because its direct negative inotropic effect, which is normally concealed by sympathetic stimulation, becomes apparent if the child is exhausted by a long period of heart disease and perfusion of catecholamines. Thiopental and propofol should be avoided due to the associated reduction in afterload and cardiodepressant effect. In the absence of a venous line, mask induction with sevoflurane is possible. However, this requires great dexterity to avoid an overdose, which can occur quickly and prompts a significant negative inotropic effect. Post-intubation, children are normoventilated with a nasal cuffed tube at a low level of intrathoracic pressure. Since they do not generally suffer from severe pulmonary hypertension, it is not necessary to hyperventilate them. Transplantations are often emergencies; therefore children are not always fasting. It might be necessary to perform a modified rapid sequence with vecuronium (0.3 mg/kg), rocuronium (1.2 mg/kg) or succinylcholine (1-2 mg/kg).

The remaining equipment is set up once the tracheal tube is secured.
 

• Two wide-gauge venous lines;
• Arterial catheter (possibly PiCCO);
• 2-3 lumen central venous line. Some centres avoid the right internal jugular vein to leave it intact for subsequent myocardial biopsies;
• TEE - essential for assessing biventricular function, blood volume, and anastomoses post-transplantation;
• NIRS – ScO₂ indicates actual cerebral oxygenation as well as O₂ delivery to the tissues in general. It is valuable in the event of temporary circulatory arrest;
• If necessary, a transthoracic catheter is placed surgically in the LA post-CPB;
• A number of serious drawbacks may result from using a Swan-Ganz pulmonary artery catheter: some pathologies prevent its passage, catheter needs to be removed before transplantation and reinserted after weaning from CPB, risk of arrhythmia, risk of infection.

Maintenance anaesthesia is provided by fentanyl (50-75 mcg/kg) or sufentanil (5-7.5 mcg/kg) and midazolam (0.05-0.1 mg/kg) or sevoflurane (< 1 MAC).

Intrapericardial dissection and cardiectomy may be difficult and highly haemorrhagic due to previous surgery, especially if a ventricular assist device has previously been used, and due to peculiar anatomy, which varies depending on the underlying pathology. The operation is performed under hypothermic CPB (25-28°C), sometimes with periods of circulatory arrest (< 30 minutes) for some configurations of venous and aortic anastomoses. Actual transplantation starts with anastomosis of the LA followed by the anastomosis of the aorta and then reconstruction of the vena cavae and pulmonary artery.

The ideal cardiac rhythm for weaning from CPB is 130-150 BPM in neonates or infants and 100-110 BPM in older children. Once the patient is off bypass, biventricular dysfunction is common. This is linked to several problems [9].
 

• Donor: hypodynamic condition, acute intracranial hypertension (sympathetic storm).
• Graft: traumatic myocardial contusion, ischaemia and reperfusion lesions, quality of organ preservation (removal, duration, temperature, etc.).
• Hyperacute rejection – generally due to ABO incompatibility. Only alternative: circulatory assistance.
• RV failure: right-sided failure is common if the recipient's PVR was high prior to surgery or if a Fontan circulation was in place. Liberal inotropic support must be provided and tailored to RV performance – dobutamine, epinephrin and milrinone, levosimendan. Ventilation is focused on lowering PVR: FiO₂ 0.8, slight hypocapnia (PaCO₂ 30-35 mmHg, pH 7.5), NO (10-40 ppm), prostaglandin by aerosol (PGI2 5-50 ng/kg/min). The RV may also fail following a mechanical obstruction, like kinking of the PA anastomosis or obstruction of the pulmonary veins.
• Bradycardia linked to denervation of the transplanted heart: isoprenaline (0.01-0.03 mcg/kg/min), pacemaker [2].
• Blood loss: extensive haemorrhage often persists after administration of protamine, requiring the use of various agents based on coagulation tests (ACT, thromboelastogram, Rotem™, etc.): fibrinolysis inhibitor, transfusions, fibrinogen, platelets, clotting factors.
• If necessary due to right-sided failure or oedema post-CPB, the sternum is left open for 24 hours. However, this situation is particularly critical for immunosuppressed patients.

Postoperative immunosuppression usually comprises methylprednisolone (10-20 mg/kg) in gradually decreasing doses, an antilymphocytic agent (mycophenolate mofetil), a calcineurin inhibitor (cyclosporin, tacrolimus), and an antilymphocyte serum. Transvenous myocardial biopsies (preferably via the right internal jugular vein) are generally performed at day 7-10, at 3 and 6 months, and thereafter in the event of any acute rejection.

Anaesthesia for transplanted patients

Children having received a heart transplant exhibit specific characteristics linked to the graft and immunosuppression [3,9].
 

• Arterial hypertension in 65% of cases (due to corticosteroids and cyclosporin);
• Atrial and ventricular arrhythmias (55% of cases); 10-20% of children are dependent on a pacemaker;
• Hyperlipidaemia (26% of cases);
• Coronary artery disease (10% of cases) following endothelial disease resulting in extensive myo-intimal hyperplasia;
• Renal dysfunction (10%);
• Infection, lymphoma, cholelithiasis, pancreatitis.

These factors give rise to a number of unusual constraints during anaesthesia for children undergoing non-cardiac surgery [2].
 

• They must be managed in a way that ensures strict asepsis.
• Preload and afterload must remain very stable to maintain adequate coronary perfusion.
• Tachycardia must be avoided.
• The heart is denervated and only responds to circulating endogenous catecholamines, which require several minutes to take effect. The heart is only sensitive to direct stimulants (dobutamine, epinephrin, isoprenaline) and not to indirect agents (dopamine, ephedrine). Reflex tachy/bradycardia is absent.
• Cardiac output is highly dependent on preload due to diastolic dysfunction.
• Bradycardia does not respond to atropine, glycopyrrolate or scopolamine. The systemic response to glycopyrrolate and neostigmine is preserved. Pancuronium bromide has no cardio-acceleratory effect and fentanils do not prompt bradycardia.
• Immunosuppression is continued unchanged perioperatively. If the child is still receiving steroids, perioperative supplementation is provided (hydrocortisone 1-2 mg/kg IV).
• Prophylactic antibiotic therapy is necessary.

Once the patient is off bypass, biventricular dysfunction is common. Right-sided failure is usual if the recipient's PVR was high prior to surgery (major L-to-R shunting). Liberal inotropic support must be provided and tailored to RV performance – dobutamine, epinephrin and milrinone, levosimendan. Ventilation is focused on lowering PVR: FiO₂ 0.8, slight hypocapnia (PaCO₂ 30-35 mmHg), NO (10-40 ppm). Isoprenaline (0.01-0.03 mcg/kg/min) is very useful in the event of bradycardia due to denervation of the transplanted heart [2]. Extensive blood loss often persists after administration of protamine, requiring the use of various agents based on coagulation tests (ACT, thromboelastogram, Rotem™, etc.): fibrinolysis inhibitor, transfusions, fibrinogen, platelets, clotting factors, potentially factor VIIa. If necessary due to right-sided failure or oedema post-CPB, the sternum is left open for 24 hours. However, this situation is particularly critical for immunosuppressed patients.

 

 

© BETTEX D, BOEGLI Y, CHASSOT PG, June 2008, last update May 2018