Chapter 95 Heart and lung transplantation
The first successful cardiac transplantation was performed at Groote Schuur, South Africa in 1967 and was followed by operations in other pioneer cardiac centres worldwide. However, it was not until the introduction of ciclosporin (cyclosporine) in 1979 that consistently improved long-term survival was achieved. To date, more than 70 000 cardiac transplantations have been performed in over 200 centres. Further improvements in immunosuppression therapy, surgical technique, detection and treatment of rejection, and general improvements in anaesthesia and postoperative care contributed to the sustained improvements, especially in centres concentrating experience and expertise above a critical mass. Typical survival figures following cardiac transplantation are in the order of 80% survival at 1 year, 70% after 5 years and 50% at 10 years.
With cardiac and lung transplantation accepted as standard treatment for a range of end-stage cardiopulmonary diseases, a large number of recipients may potentially develop critical illness, unrelated or directly related to their original condition. Around 40% of cardiac transplant recipients are readmitted to hospital within 1 year, at least a third requiring admission to intensive care units (ICUs).1 Many of these patients present to the ICUs of non-transplant centres, especially as the number of centres performing transplantation is apparently falling. Therefore, all critical care practitioners need to be aware of the principles of management of the transplant recipient.
CARDIAC TRANSPLANTATION
The main issue with cardiac transplantation revolves around donor availability (Table 95.1). The numbers of potential recipients who fulfil internationally accepted criteria2 (Table 95.2) vastly outnumber the available donors, so the great majority of patients with severe end-stage heart failure inevitably die before a suitable donor heart becomes available.
Table 95.1 Illustration of the disparity between transplant operations and numbers of patients on the UK transplant registry
| Organ transplanted | UK recent annual total | UK registered potential recipients |
|---|---|---|
| Heart | 50–60 | 90–100 |
| Lung | 50 | 275 |
| Heart and lung | 5 | 20 |
Source: www.uktransplant.org.uk.
Table 95.2 Criteria to select cardiac transplant recipients
NYHA, New York Heart Association; PAOP, pulmonary artery occlusion pressure (or ‘wedge’ pressure); PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance.
The cardiac equivalent of dialysis, for the maintenance of the potential renal transplant recipient until an organ is available, is simply not feasible. However, there has been progress in the medical and surgical management of severe heart failure, some of which are highly specialised treatments with limited availability and some more routine and commonplace (Table 95.3). The use of inotropic drugs such as β-agonists (e.g. dobutamine), catecholamines (e.g. epinephrine) and phosphodiesterase inhibitors (e.g. milrinone) to support the failing heart and circulation is widely practised, as is the use of intra-aortic balloon pump (IABP) counterpulsation. These treatment options are, of course, highly invasive but may be used as rescue therapy in a patient with severe or end-stage cardiac failure who may be waiting for a transplant but in whom some event such as infection of worsening myocardial ischaemia has resulted in a catastrophic deterioration. The response of the failing heart to β-agonists may be disappointing because of the tendency to β-receptor downregulation from chronic overstimulation. In these cases the phosphodiesterase inhibitor drugs such as milrinone and enoximone may have greater and more sustained potency because of their intracellular site of action.
Table 95.3 Non-transplant or bridge to transplant treatment of severe cardiac failure
| Treatment modality | Notes | Applicability |
|---|---|---|
| Angiotensin-converting enzyme (ACE) inhibitors | Reduce cardiac work and improve output – beware exacerbation of renal failure | Ward setting to establish, then as outpatient |
| β-Blockers5,6 | Improve β-receptor numbers and function | Ward setting to establish, then as outpatient |
| Inotropic support | Rescue therapy – rescue and restabilisation sometimes possible – requires central vascular access | CCU or ICU |
| Intra-aortic balloon pump counterpulsation | Rescue therapy combined with inotropes – may restabilise and thus temporary but invasive | CCU or ICU |
| Antiarrhythmic treatments – implantable defibrillators and advanced pacing, e.g. resynchronisation7 | Where recurrent or severe arrhythmias threaten life or cause general destabilisations | Cardiac centre with facilities for electrophysiology |
| Surgical interventions | Routine (e.g. coronary artery bypass) or complex (e.g. anterior ventricular remodelling, mitral reconstruction where severe mitral regurgitation complicates cardiomyopathy) | Specialised cardiac centre |
| Ventricular assist devices (VAD)8 | Short- and medium-term mechanical support for the failed heart – extremely invasive – usually holding stage or bridge to transplant | Specialised cardiac centre |
| Totally implanted artificial heart9,10 | Longer term version of VAD – ultimately may be instead of transplant | Specialised cardiac centre, then possibly home |
CCU, coronary care unit; ICU, intensive care unit.
Some patients who have been deemed inoperable in conventional terms may still benefit from cardiac surgical interventions, though in the setting of severe chronic cardiac failure the risk of death, serious morbidity and prolonged postoperative critical illness may be considered prohibitive. Sometimes a degree of reversible myocardial ischaemia may be demonstrated by thallium scanning and guide subsequent coronary artery bypass grafting. In some cases, the degree of secondary mitral valve regurgitation caused by dilatation of the left ventricle may become a haemodynamically significant lesion of itself and reconstruction of the mitral valve or remodelling of the left ventricle may prove beneficial. In extreme cases of cardiac decompensation and where other organ functions are maintained (an unusual combination) the use of mechanical assistance4 to support the heart and buy time for a donor heart to become available (‘bridge to transplant’) or to provide support while a severe but temporary process (such as some viral myocarditis episodes) subsides (‘bridge to recovery’) may be undertaken in highly specialised centres. The logical conclusion is to develop permanent mechanical support devices obviating the need for transplantation but this goal appears to be a long way in the future. The cost of such therapy in both financial and human terms has to be considered in the context of general health economics. These episodes are still at best pioneering, extremely invasive, draining on the resources of critical care, blood transfusion and pharmacy, and of limited outcome benefits. On the other hand, it can be argued that earlier use of potent mechanical assistance at a stage that other organs have yet to be irretrievably damaged should be more widely attempted and, by inference, outside the major cardiac specialist centres.
DONORS AND RECIPIENTS
Most countries have seen a progressive gradual decline in the numbers of cardiac transplantations performed as a result of decreasing donor availability. Measures to optimise the donor pool for all solid organ transplants and care of potential donors are discussed elsewhere. Donor selection criteria are summarised in Table 95.4.
Table 95.4 General criteria to select cardiac transplant donors
THE TRANSPLANT PROCEDURE
The anaesthetic and perioperative care of these patients is not materially different from any major cardiac surgery and the important principles are well described in the literature.11–13 However, the coordination of the timing of surgery with the arrival of the donor heart, management of the excised donor graft and the immunosuppression protocol are all crucial factors. Organ preservation after harvesting from the donor is especially important and the main factor appears to be limiting the total ischaemic time to less than 4 hours (6 hours at the extreme). The recipient may have to be called in from home and may have a full stomach. The recipient may be elated or extremely anxious, or both.
PHYSIOLOGY AND PHARMACOLOGY OF THE DENERVATED HEART (Table 95.5)
At surgery, the sinoatrial (SA) node of the recipient is retained but does not activate the grafted heart across the suture line. The donor heart has its own SA node but this is not innervated. It may be possible to discern two discrete P waves on the electrocardiogram (ECG). The donor SA node controls the graft heart rate. In the absence of autonomic innervation, only drugs or manoeuvres that act directly on the heart will have an effect. For example, the Valsalva manoeuvre or carotid sinus massage will not affect heart rate, but drugs such as adrenaline (epinephrine), noradrenaline (norepinephrine) and isoprenaline (isoproterenol) exert a positive inotropic and chronotropic effect and β-adrenergic blockers will depress myocardial function. Quinidine and digoxin will influence conductivity through their direct effects only.
Table 95.5 The pharmacology of the denervated heart
| Drug | Effect on recipient | Mechanism |
|---|---|---|
| Digoxin | Normal increase in contractility; minimal effect on AV node | Direct myocardial effect; denervation |
| Adenosine | Fourfold increase in sinus and AV node blocking effect | Denervation supersensitivity |
| Atropine | None | Denervation |
| Epinephrine | Increased contractility and chronotropy | Denervation supersensitivity |
| Norepinephrine | Increased contractility and chronotropy | Denervation supersensitivity |
| Isoprenaline | Normal chronotropic effect | |
| Glyceryl trinitrate | No reflex tachycardia | Baroreflex disruption |
| Quinidine | No vagolytic effect | Denervation |
| Verapamil | AV block | Direct effect |
| Nifedipine | No reflex tachycardia | Denervation |
| β-Blockers | Increased antagonistic effect | Denervation |
| Pancuronium | No tachycardia | Denervation |
| Neostigmine, succinylcholine | No bradycardia | Denervation |
The denervated heart retains its intrinsic control mechanisms,14 e.g. a normal Frank–Starling response to volume loading, normal conductivity and intact α- and β-adrenergic receptors, possibly with enhanced responsiveness.
Denervation results most importantly in an atypical response to exercise, hypovolaemia and hypotension. Any increase in cardiac output from increased heart rate or contractility depends on an increasing venous return and circulating catecholamines, and the response may be delayed. During exercise, muscle contraction increases venous return and the increased circulating catecholamines increase the heart rate. This is a gradual response and, as exercise ceases, the heart rate and cardiac output slowly fall as the catecholamine and the response levels decrease.15 In pathological states, the transplanted heart is especially dependent on adequate filling volumes, and attention to preload is critical.
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