Anaesthesia and organ transplantation

Improvements in surgical and perioperative technique, immunosuppression regimens and organ preservation over the last century have meant that organ transplantation is now considered the primary treatment for organ failure. Solid organ transplants (kidney, liver, heart, lung and pancreas) make up the majority of procedures ( Fig. 47.1 ), although the range of organs and tissues available for transplantation is continually expanding.

The improvement in long-term outcomes of transplantation means that most recipients are now able to lead a normal life after transplant. However, recipients are more likely than the general population to require elective surgery for malignancy or emergency procedures (especially for acute gastrointestinal pathological conditions). All anaesthetists require knowledge of both general and organ-specific problems relating to non-transplantation surgery in transplant recipients.

General considerations in organ transplantation

Epidemiology

The types of organs transplanted is similar in the UK, Europe and the USA (see Fig. 47.1 ). In contrast, the aetiologies of the indications for transplantation differ between healthcare systems. For example, liver transplantation in the UK is performed predominantly for alcohol-related liver disease, whereas hepatitis dominates in the USA. The success of transplantation surgery is reflected in high survival rates for all transplantation procedures ( Table 47.1 ).

Table 47.1

Patient survival after first organ transplantation

Data from UK Blood Transfusion Service, Year of Transplant 2009–2011.

	1-year survival (%)	2-year survival (%)	5-year survival (%)
Kidney (live related)	99	98	94
Kidney (DBD)	96	95	90
Kidney (DCD)	95	93	84
Liver (DBD)	93	91	82
Liver (DCD)	81	80	71
Heart	82	79	71
Lung (DBD)	82	74	59
Lung (DCD)	86	78	64
Pancreas (DBD)	96	94	81
Pancreas (DCD)	100	100	95
Simultaneous pancreas kidney (DBD)	96	93	87
Simultaneous pancreas kidney (DCD)	99	94	94

DBD, Donation after brain death; DCD, donation after circulatory death.

Transplant recipient listing/organ allocation

Defined protocols for listing potential recipients are set nationally and are important for equitable and appropriate transplantation. In general, patients who are likely to have better than 50% survival at 5 years are potential organ recipients. However, because transplantation outcome is much better than this, there remains a mismatch between the number of patients listed for transplant and those eventually receiving an organ ( Fig. 47.2 ). Many patients, even when they have been listed as potential organ recipients, will ultimately die on the waiting list.

Fig. 47.2, Trends in numbers of solid organ donors, transplants performed and patients listed for transplantation in the UK.

Organ allocation is prioritised differently across the world, with differences between healthcare systems and prognostic criteria. The majority of systems have developed organ allocation based around severity of the patient's illness, risk of death without transplantation and duration spent on a waiting list, with the overall aim being to prevent waiting list death. In the UK, ‘case of need’ also takes preference in specific cases where there is a rapidly deteriorating organ function (e.g. acute liver failure, heart failure).

Organ procurement

As the number of patients with end-stage disease increases, the organ supply/demand gap remains and the limiting factor to successful transplantation is the availability of acceptable donor organs. The mainstay of organ procurement has been from donation after brain death (DBD), often resulting from trauma. Initiatives to both increase the numbers of organs available and to increase the quality of the available organs have been applied, and include:

1.
Different sources of donation:
- a.
  Donors after circulatory death (DCD)
- b.
  Live-related donors—kidney and liver transplantation
- c.
  Split-organ donation—liver
2.
Acceptance of ‘marginal’ organs through the following:
- a.
  Better methods of organ preservation—including ex vivo perfusion techniques
- b.
  Increasing donation from older persons where outcomes are acceptable
- c.
  Improved ICU management and end-of-life care

Anaesthetic management: general principles

Organ donation procedure

Deceased donor donation

Management of the DBD donor commences in the ICU after donor death has been confirmed by neurological criteria (see Chapter 48 ). Donor management by the anaesthetist follows on directly from these donor management and end-of-life care pathways in the ICU. Management of the DCD donor commences as soon as death is pronounced and requires early intervention in terms of in vivo organ perfusion.

Acquisition of donated organs occurs in the operating theatre and requires careful haemodynamic management to ensure appropriate organ quality for subsequent transplantation. The procedure involves a midline laparotomy and sternotomy and has the potential for:

blood loss;
hypothermia;
cardiovascular instability; and
spinal reflex movements.

Appropriately experienced individuals provide donor support during the procedure. Vasoactive infusions are likely to have been commenced during ICU care and are continued during the procedure. Hypertension may also occur and requires volatile anaesthetic agents, opioids or vasodilators. Volatile anaesthetic agents may also provide some degree of ischaemic preconditioning and are often used during hepatic and cardiac donation procedures. There are inadequate data to suggest that spinal reflex responses require anaesthetic suppression. However, many anaesthetists would administer a neuromuscular blocking agent to prevent the appearance of spinal reflexes, as these may be disturbing to staff who are unfamiliar with their cause.

Live-related organ donation

Whole organ donation from a close relative has revolutionised renal transplantation; donation of part of an organ (a liver lobe) has also being introduced for liver transplant recipients. Organ donation from a previously fit individual to a patient with end-stage disease requires careful consideration of the ethical issues. Careful management of sequential procedural timing to allow immediate donor organ implantation will avoid storage injury. If these issues are fully addressed, the outcome after living-related donation is amongst the best of all transplantation procedures.

Organ transplantation procedure

Preoperative assessment of transplant recipients

Any organ allocation system that offers transplantation to patients based on end-organ disease severity requires thorough multisystem preoperative anaesthetic assessment to ensure that extended outcome benefit is not curtailed by disease of other organ systems. All transplant procedures are classified as high risk. Because the majority of postoperative deaths occur in the early perioperative period and recipients are increasing in age and comorbidities, preanaesthetic assessment is vital.

Preoperative assessment usually occurs some time before the actual operative procedure and can usefully be divided into:

(a)
specific disease—related to end-organ disease, such as hepatopulmonary syndrome, portopulmonary hypertension (liver), autonomic neuropathy (pancreas); or
(b)
non-specific disease—such as ischaemic heart disease, chronic obstructive pulmonary disease (COPD).

Assessment of eligible recipients is particularly focussed on the cardiorespiratory system. The use of functional reserve assessment by subjective (e.g. metabolic equivalents (METS) estimation) or objective (e.g. cardiopulmonary exercise testing) has been advocated in many forms of major surgery, as a decision point for more invasive forms of cardiovascular assessment (see Chapters 19 and 30 ). Renal dysfunction is a key determinant in the early recovery of many transplantation procedures, and assessment of the likely requirement for early postoperative renal support is essential. End-stage disease is associated with nutritional deficiencies that may worsen during the catabolic phase after major surgery. Preoperative information and psychological support are very important; patients may need assistance in maintaining acceptable compliance with postoperative medication regimens, which are essential for good recovery after transplantation.

Intraoperative management

Most transplantation procedures can be usefully separated into four specific phases:

1.
Dissection phase. This phase entails the removal of the diseased organ from the recipient. Blood loss is common. Preparation for acceptance of the new organ is paramount to ensure that the next phase is as short as possible.
2.
Implantation. Implantation of the donor organ occurs immediately on removal of the diseased organ. Once an organ is removed, any benefit from residual organ function is eliminated. In cardiothoracic transplantation, removal usually relies on cardiopulmonary bypass, whereas in liver/pancreas/kidney procedures, a period of no organ function is tolerated. When the donor organ is removed from the relative protective effects of the ex vivo preservation environment (cold ischaemia), the period of implantation provides a period of ‘warm ischaemia’, which is potentially damaging to subsequent organ function and must be minimised.
3.
Reperfusion. Once the organ has been surgically implanted, the blood supply has to be reconnected thus providing reperfusion of the new organ. This phase can be complicated by haemodynamic compromise caused by myocardial depression and vasodilatation; pharmacological support is often needed.
4.
Postreperfusion. Once reperfusion has been completed, the postreperfusion phase allows checking of surgical anastomosis, restoration of haemodynamic stability and optimisation of the environment for appropriate organ function.

Postoperative management

Most transplantation patients are managed in a high-dependency area after solid organ transplantation. Ensuring adequate haemodynamic support through appropriate monitoring and rapid response to changes in patient status ensures adequate organ perfusion and reduces early complications that may lead to early transplant failure.

Transplant recipients undergoing non-transplant procedures

Transplant recipients presenting for non-transplant surgery may have residual evidence of chronic disease, be immunocompromised and/or have reduced organ functional reserve. In an emergency situation the effect of acute illness may also complicate further anaesthetic management. Appropriate anaesthetic management aims for transition through the perioperative period without risk of further transplanted organ impairment or postoperative rejection.

Preoperative considerations

Transplanted organ status

The interval between organ transplantation and subsequent elective surgery determines the likelihood, nature and complexity of anaesthetic problems. Within the first 6 months after transplantation, the major considerations for the anaesthetist are those of graft rejection and acute changes in physiology. One year after successful transplantation, the risk of chronic rejection remains. Although many standard biochemical tests of renal, liver and cardiac function are normal in transplant recipients, the functional reserve of most transplanted organs is reduced.

Function of other organ systems

Although some systemic manifestations of the original organ failure are reduced by successful transplantation, residual disease in remote organs associated with pretransplant disease may remain. Cardiovascular issues are common to many multisystem diseases requiring transplantation, especially renal, pancreatic, and liver disease and are a common cause of ongoing mortality after transplantation. Paradoxically, the presence of coronary artery disease in heart transplant recipients is less likely unless rejection is present. Although most patients will have been fully investigated before transplantation, more recent investigations are usually warranted for subsequent surgical procedures.

Immunosuppression

Immunosuppressive regimens enable long-term transplantation benefit and prevent graft rejection, which usually occurs within the first year after transplantation. Older steroid-based regimens are being substituted with newer agents with fewer generalised adverse effects. As a general rule, all current immunosuppressive therapy should be continued throughout the perioperative period. However, if gastrointestinal absorption is likely to be compromised after surgery, oral immunosuppressive drugs should be converted to i.v. preparations. Complete omission of immunosuppressive regimens must be limited to the most extreme cases, where sepsis is potentially life threatening and where the risk of graft rejection becomes a secondary issue.

Presence of infection

In addition to the presence of infection causing the initial requirement for transplantation (e.g. hepatitis or cytomegalovirus infection), the development of de novo infection must be investigated. However, the diagnosis may be difficult in transplant recipients because typical presenting features may be absent. Fever may not be present, and given that some drug regimens cause leucopoenia, an increased white cell count for a particular patient may lie within the ‘normal’ range. In elective situations a recent culture screen for infection should have been performed before surgery and will guide further management. There is no evidence to support an increase in the use or duration of prophylactic perioperative antibiotics in the transplant recipient.

Intraoperative considerations

The overriding principles for anaesthetic management of transplant recipients are to reduce the degree of surgical stress, avoid injury to the transplanted organ and protect against infection.

Avoidance of surgical stress

Laparoscopic surgical techniques have the advantage of reducing surgical stress. However, especially in the case of abdominal solid organ transplants, this must be balanced with the increased intra-abdominal pressures during laparoscopy and the potential to reduce organ perfusion. Regional analgesic techniques also reduce surgical stress but may have relative contraindications if coagulation (liver), haemodynamic (cardiac) or autonomic (e.g. renal, pancreatic) dysfunction is present.

Reducing injury to transplanted organ

The use of anaesthetic agents that are non-toxic to the transplanted organ is important, given reduced organ reserve. Large volumes of radiological contrast agents, aminoglycosides and NSAIDs are best avoided in renal transplant recipients. Anaesthetic drugs rarely affect liver transplant function and, importantly, paracetamol in analgesic doses is not contraindicated. It is vital to maintain adequate perfusion of the transplanted organ, and hypovolaemia must be avoided. Minimally invasive techniques to optimise fluid balance and cardiac output are recommended in major surgery (see Chapter 30 ). Perfusion pressures must be maintained for renal transplant recipients, and direct arterial monitoring is indicated for all but the most minor procedures. Other measures to maintain organ perfusion, in addition to maintaining circulating volume, include avoidance of:

high CVPs;
high concentrations of PEEP;
excessive doses of volatile anaesthetic agents (liver);
high airway pressures (lung); and
excessive airway manipulation (lung).

Direct injury to cardiac function in heart transplant recipients is less likely during non-cardiac surgery.

Infection

Strict asepsis must be adhered to at all times, especially when inserting central venous access lines or performing regional anaesthetic techniques or during airway manipulation. Dedicated in situ total parenteral nutrition (TPN) lines should not be used for the administration of anaesthetic drugs.

Postoperative considerations

Postoperative management of transplant recipients usually requires enhanced postoperative care facilities. Analgesia is provided with regional techniques, thereby preventing the administration of i.v. or oral agents that have the potential for transplanted organ toxicity. Reduced metabolism and excretion of analgesic agents, especially opioids, may require alteration in drug dose, and more rapid-acting agents are commonly used in liver and renal transplant recipients. The administration of additional steroid doses to prevent the possibility of adrenal unresponsiveness is controversial. Some authors suggest that supplementation is not required unless the maintenance dose of steroid is more than 20 mg prednisolone per day. In the absence of clear evidence, the use of prolonged doses of steroids is best avoided.

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