Anaesthesia for the Patient with a Transplanted Organ

Published on 27/02/2015 by admin

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Anaesthesia for the Patient with a Transplanted Organ

INTRODUCTION

There have been several advances in surgical techniques, perioperative management and immunosuppressive regimens to prevent early and late organ rejection. These have led to improvements in short and long-term outcomes after transplantation, with most patients now able to lead a relatively normal life (see Table 39.1). Furthermore, outcomes following patient re-transplantation after rejection or graft failure have improved. As a result, it is likely that non-transplant anaesthetists are more likely to encounter transplant recipients presenting for elective surgery in the future. Transplant recipients are more likely than the general population to require surgery for malignancy or emergency procedures especially for acute gastrointestinal pathology. In addition, the increased success of solid organ transplantation has led to the recipient population being older and having more comorbidities than previously. Furthermore, the use of ‘marginal’ donor organs, secondary to the relative shortage of organs, is likely to make the management of these patients more complex. In general, wherever recipients present for non-transplant surgery, the patient is likely to have both residual evidence of chronic disease, be immunocompromised and have reduced organ function. In the emergency situation, the effect of acute illness may also complicate further anaesthetic management.

Careful attention to detail in the anaesthetic management of these patients will allow a smooth transition through the current surgical problem and perioperative process without disruption of the complex immunosuppressive regimens and without the risk of rejection.

GENERAL CONSIDERATIONS

Immunosuppression

Immunosuppressive regimens are an absolute necessity in promoting long-term benefit from transplantation. The use of mainly steroid-based immunosuppressive regimens is gradually being substituted with the development of newer agents which have fewer generalized adverse effects. As a result, the complications of steroid overdose are seen less commonly and iatrogenic Cushing’s syndrome is rare. However, even newer regimens have significant adverse effects and require careful monitoring. The greatest risk of graft rejection is within the first year after transplantation, especially in the first few months. Immunosuppressive regimens may be classified as:

The characteristics, side effects and drug interactions of the main immunosuppressive agents are shown in Table 39.2.

Plasma drug monitoring is usually performed by transplant physicians and most patients presenting for elective surgery are on a stable regimen of immunosuppressive drugs. Even with stable chronic treatment these patients remain at risk of:

image increased risk of infection (see Table 39.3) – all staff should be aware of the risks of opportunistic infections and take appropriate precautions, including aseptic techniques and microbiological monitoring.

TABLE 39.3

Organisms Causing Common Opportunistic Infections in Transplant Recipients

CMV (cytomegalovirus)

Fungi – Aspergillus sp, Candida sp

Pneumocystis sp

Legionella sp

Toxoplasma sp

Listeria sp

image reduced wound healing – long-term immunosuppression also reduces the tensile strength of tissues and therefore may impair wound healing.

image major drug interactions – immunosuppressive drugs can cause interactions with a number of medications used for anaesthesia or postoperative pain relief.

image damage to other organ systems.

The presence of acute illness in combination with surgical stress is likely to create a period of instability. Early communication with the transplant team regarding immunosuppressive therapy is important to prevent large alterations of plasma drug concentrations. These may cause:

Residual Comorbidity

It is important to consider the nature of the disease process leading to the initial requirement for transplantation. Although some systemic manifestations are reduced by successful transplantation, residual disease in other organs associated with pre-transplant disease may remain (e.g. lung disease secondary to impaired liver function, cardiac disease secondary to renal failure).

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 likelihood of significant physiological changes is lower although the risk of chronic rejection always remains.

ANAESTHETIC CONSIDERATIONS

Preoperative

Presence of Infection

In addition to the presence of infection causing the initial requirement for transplantation (e.g hepatitis or CMV), the development of de novo infection must be investigated. However, the diagnosis may be difficult in these patients 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. Early discussion with microbiology colleagues should take place to assess the correct regimen for surgical prophylaxis. There is no evidence to support an increase in the use or duration of prophylactic perioperative antibiotics in the transplant recipient.

Function of Other Organ Systems

Although the status of the transplanted organ and associated system is important, the systemic effect of the disease process that created the need for transplant must also be considered. Although transplantation may reduce the effects of this disease, full reversal of major systemic disease is unlikely.

Cardiovascular issues are common to many multisystem diseases requiring transplantation especially renal, pancreatic, and liver disease and are a common cause of mortality after transplantation. Paradoxically, the presence of coronary artery disease in cardiac transplant recipients is less likely unless rejection is present. Although most patients undergoing these transplants will have had a full investigation of their cardiac status before transplantation, presentation for surgical procedures may occur sometime after the transplantation. Therefore, depending on the complexity of the surgery contemplated, more up to date investigation may be warranted. The presence and stability of diabetes must be known. As previously mentioned, systemic toxicity caused by immunosuppressive regimens, must also be considered before surgery.

Intraoperative

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

Reduce Injury to Transplanted Organ

It is vital to maintain adequate perfusion of the transplanted organ, and hypovolaemia must be avoided. Minimally invasive techniques are now available to optimize fluid balance and cardiac output and these are recommended in major surgery, where blood loss and fluid shifts are most likely. Perfusion pressures must be maintained for renal transplant recipients and direct arterial monitoring is indicated in these patients for all but the most minor procedures, especially where preoperative hypertension exists. Other measures should be used to maintain organ perfusion in addition to maintaining circulating volume, particularly in liver transplant recipients. These include the avoidance of high central venous pressures, high levels of PEEP and excessive doses of volatile anaesthetic agents. It is important to avoid high airway pressures and excessive airway manipulation to prevent organ injury in lung transplant recipients. Direct injury to cardiac function in heart transplant recipients is less likely during non-cardiac surgery.

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 non-steroidal anti-inflammatory drugs are best avoided in renal transplant recipients. Liver transplant function is rarely affected by anaesthetic drugs and, importantly, paracetamol in analgesic doses is not contraindicated.

Postoperative

Postoperative management of transplant recipients must be carefully planned and the requirement for enhanced postoperative care facilities must be considered; this depends on the preoperative status of the patients and the type of surgery. If admission to critical care is contemplated, the risk of infection must be considered and a separate cubicle may be required.

Analgesia is best provided with regional techniques, thereby preventing the administration of intravenous 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 type dose or interval 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. Although hypothalamic-pituitary axis suppression is common, the incidence of severe perioperative events including hypotension and adrenal crisis is rare. Some authors suggest that supplementation is not required unless the maintenance steroid dose is > 20 mg prednisolone per day. In the absence of clear evidence, the use of prolonged supraphysiological doses of steroids is best avoided and the continuation of chronic steroid doses with short term steroid augmentation is recommended. A dose of 25–75 mg day− 1 hydrocortisone for 24–48 h is adequate for all but the most major procedures.

SPECIFIC ISSUES

Renal

The kidney is the most commonly transplanted organ and renal transplantation has the most successful patient outcome. The success of the live-related kidney program has further increased the number of transplants being performed and allowed patients with more severe comorbidities to undergo transplantation. For these reasons, the non-transplant anaesthetist is most likely to encounter patients with a renal transplant.

Anaesthetic Considerations

Regional anaesthesia is safe in renal transplant recipients and should be considered in the first instance. However, general anaesthesia is often required and is best performed using rapid acting agents, which do not rely on renal excretion. Desflurane or isoflurane are the volatile agents of choice. Sevoflurane is also safe and early reports of high doses of fluoride ions after prolonged surgical procedures have not been shown to be harmful in humans. Serum potassium concentrations must be determined where suxamethonium is being used. All non-depolarizing neuromuscular blockers may be used but atracurium or cisatracurium have theoretical advantages, given the likelihood of reduced renal reserve. All drugs that have active intermediate metabolites (e.g. morphine) may have a prolonged action and should be used with caution. Alternatively, analgesia may be provided by regional or central neuraxial blockade. Since the transplanted kidney has no autoregulatory mechanisms, it is particularly susceptible to damage if perfusion pressure is reduced. Therefore, an appropriate blood pressure must be maintained by both the judicious use of vasopressor therapy and the assiduous avoidance of hypovolaemia, especially where dialysis has been performed before surgery. In this regard, a non-invasive monitor of fluid status with or without invasive arterial pressure monitoring is appropriate.

Liver

Liver transplantation is now the second commonest transplant surgery performed in the UK. The requirement for liver transplantation is likely to increase given the recent trend for an increased incidence of fatty liver and alcohol-related illnesses in younger individuals. The limiting factor to liver transplantation is the paucity of donor organs although live-related transplantation is now being performed in some centres in the UK. The survival rates for liver transplantation are high: 85–90% of patients survive to 1 year and 75% survive for 5 years.

Preoperative Status

Successful transplantation leads to an early return to normal hepatic function and coagulation. Drug metabolism starts earlier within hours of reperfusion in a well functioning graft. Many of the systemic manifestations of liver disease including pulmonary abnormalities return to normal postoperatively. Resolution of pleural effusions, ascites and pulmonary shunting occurs within the first few weeks. Hepatopulmonary syndrome usually resolves and oxygenation is rarely a problem in patients after transplant. Porto-pulmonary hypertension, secondary to chronic liver disease, was previously a contraindication to transplantation. However, preoperative therapy with pulmonary vasodilator therapy has allowed successful transplantation in these patients. However, complete resolution of this problem is uncommon and many patients remain on therapy. These drugs must be continued throughout the perioperative period and any factors leading to pulmonary vasoconstriction must be eliminated. The haemodynamic stigmata of chronic liver disease (systemic vasodilatation and high cardiac output) usually return to a normal level within months of transplantation but tolerance of a low systemic vascular resistance in the early postoperative period is important as long as adequate blood pressure allows. Similar to the renal allograft, lack of autoregulation makes the organ susceptible to ischaemia-reperfusion injury. Hypovolaemia, high levels of PEEP, and increased central venous pressures, may lead to worsening of liver function.

Surgical Presentation

Liver transplantation has a high incidence (15–20%) of needing early re-operation and this may not always be dealt with by the transplant team. Indications include surgical bleeding from the gallbladder bed, posterior to the liver, from any vascular anastamosis or from portal varices. Surgical bleeding may be difficult to differentiate from coagulopathy and may lead to a ‘negative’ laparotomy. However, removal of surgical packs may also necessitate intervention. Where there has been delayed normalization of coagulation, haematoma formation may lead to abdominal tamponade which must be released to avoid renal and liver compromise. There is a risk of cardiovascular collapse caused by release of tamponade and reduction of venous return and it is important to have methods available to perform rapid transfusion including adequate venous access, although many of the access lines will still be in position from the original transplant.

Hepatic artery or portal vein thrombosis may lead to graft failure and are surgical emergencies. Most centres use ultrasound investigation of the graft postoperatively to ensure vessel patency. However, a worsening metabolic acidosis and coagulopathy are signs of impending thrombosis. Early diagnosis will allow return to theatre with a chance of rescuing the threatened graft. Complete thrombosis of vessels is difficult to rectify and may need urgent re-transplantation.

Biliary tract drainage procedures (including Roux en Y formation) are often required after transplantation and especially where there has been a hepatic artery complication. Incisional hernia repair is also a common surgical intervention.

Anaesthesia

After successful liver transplantation, many of the sequelae of chronic liver disease will have resolved and functional reserve will have improved. However, ischaemic heart disease may still be present and must be investigated. Similarly, pre-transplant evidence of pulmonary hypertension should be noted and current therapy optimized if necessary. Clinical evidence of sepsis may suggest active cholangitis and this should be treated before biliary drainage procedures are performed. Recidivism after a transplant for alcoholic liver disease is common and assessment of alcohol intake must be ascertained. Preoperative investigations should include full clotting studies, liver function tests and electrolytes. The presence of ongoing viral illness is important for both theatre safety and blood cross-matching.

Further abdominal surgery may be complex and haemorrhage is a real possibility. Good venous access is mandatory. Regional anaesthesia is not contraindicated unless clotting dysfunction remains an issue. Unpredictable drug metabolism is important within the first few months after liver transplantation. However, if liver function tests have returned to baseline, it can be assumed that the response to anaesthetic drugs will be normal. Vecuronium is not contraindicated in this population, although it is probably prudent to use atracurium wherever coexisting renal disease is present. Paracetamol in standard analgesic doses is not contraindicated.

Cardiac

Preoperative Status

In contrast to renal and liver transplant recipients, the diseases that lead to the requirement for cardiac transplantation are less likely to be systemic in nature. However, the transplanted organ must not be considered normal in terms of its innervation and haemodynamic responses. Autonomic denervation leads to a loss in vagal control of the sinoatrial node and a persistent tachycardia. The ECG may show two ‘p’ waves due to remnants of the explanted organ conduction system. There may also be minor arrhythmias, bundle branch blocks and in some cases pacemaker fitting may have been necessary. Cardiac functional capacity is usually normal or minimally reduced. Early preload dependency is followed by a steady improvement in function due to an appropriate cardiac response to increased catecholamine concentrations. Indeed, most successfully transplanted patients eventually return to having a normal cardiac output, stroke volume and ejection fraction. The highest risk of rejection occurs within the first six months after transplantation and is diagnosed by myocardial biopsy. Increased troponin levels may also be associated with rejection. Chronic rejection often presents as progression of coronary artery disease without angina, due to reduction in sympathetic innervation and is angiographically present in 20% of patients, 5 years after transplantation.

Anaesthetic Considerations

Preoperatively, hypertension (often induced by Cyclosporin A) is present in two third of patients and may require adjustment of drug therapy or treatment. Permanent pacemakers must be checked before the procedure and appropriate measures taken for intraoperative management. Persistent atrial arrhythmias may suggest rejection and require further investigation.

Intraoperatively, the use of regional anaesthesia is somewhat controversial but where there is normal cardiac function, it is unlikely to cause major complications. Right internal jugular vein cannulation is best avoided since it provides venous access for frequent myocardial biopsies. Drugs affecting the autonomic system are of minimal use in these patients due to the denervation occurring after heart transplantation. A requirement for an increased chronotropic or inotropic effect requires the use of direct-acting drugs including dobutamine, ephedrine and noradrenaline. Drugs that have direct action on heart allografts are shown in Table 39.4.

TABLE 39.4

Drugs that have Direct Action on Heart Allografts

Direct-Acting Drugs – Retained Action on Denervated Heart No Activity on Denervated Heart
Dobutamine Atropine, Glycopyrrolate
Ephedrine Neostigmine
Dopamine Pancuronium
Glugacon Pyridostigmine
Digoxin
Adrenaline
Noradrenaline
Beta-blockers
Phosphodiesterase inhibitors

In the early stages after transplantation, cardiac output relies on an adequate preload. Fluid therapy should be optimized, guided by appropriate monitoring techniques (e.g. TOE, non-invasive cardiac output devices) and avoiding reductions in afterload. All current volatile and analgesic agents in judicious doses are suitable.

Pulmonary

Anaesthetic Considerations

Many of these patients will have recent pulmonary function tests available. However, a worsening of functional symptoms since previous testing requires further testing. In some cases, an echocardiogram may be appropriate to rule out concomitant cardiac disease. Baseline blood gases are useful where supplemental oxygen is required, especially in SLT recipients. Recent chest infection should trigger preoperative sputum culture with appropriate therapy and awareness for a requirement for physiotherapy.

Intraoperatively, the anaesthetist should always be aware of possible altered upper airway anatomy and airway responses in both SLT and DLT recipients. DLT (or combined heart–lung) recipients have no airway reflexes. Postoperative sputum retention and chest infection are common and extubation under deep anaesthesia is not appropriate. In addition, fluid overload may lead to pulmonary oedema due to the disruption of pulmonary lymphatics.

SLT patients retain airway and carinal responses. However, the presence of an allograft with normal structure in combination with a lung retaining the original disease process may cause specific ventilatory problems. Pulmonary blood flow preferentially diverts to the allograft and during lateral positioning, especially where the diseased lung is dependent, difficult oxygenation and overt hypoxia may occur. Different lung compliances may lead to volutrauma or barotrauma; differential lung ventilation must be considered in this situation. However, given altered airway anatomy, the siting of a double lumen tube may be very difficult and other methods of lung isolation may be required.

Pancreas

Isolated pancreas transplant alone is less common than simultaneous kidney–pancreas transplantation (SPK; the latter potentially prolongs the survival of both grafts).

Preoperative Status

Early graft function allows rapid discontinuation of exogenous insulin therapy. However, even when this occurs, stabilization of the patient on an appropriate immunosuppressive regimen may delay recovery for some weeks. Where recovery of insulin secretion is not rapid, a more prolonged period of instability is expected. Drainage of pancreatic secretions is an important component of the initial transplant procedure since exocrine secretions may cause major injury to internal organs. Drainage procedures have included enteric or urinary drainage procedures. The latter allows for measurement of urinary pancreatic amylase but where SPK has been performed, this monitoring is rarely needed as renal failure often precedes pancreatic graft failure. Furthermore, bicarbonate losses are considerable requiring intravenous replacement in the early phase. Enteric drainage allows bicarbonate reabsorption, and acidosis and dehydration are uncommon.

Anaesthetic Considerations

Preoperative blood tests must include electrolytes and especially bicarbonate where urinary drainage has been performed. Residual requirement for insulin must be noted and a similar insulin regimen to those for other diabetics presenting for surgery should be used. The systemic effects of long-term, uncontrolled diabetes may remain even after successful pancreas transplantation. Patients may have persistent ischaemic heart disease, often silent, that must be investigated where there has been recent functional deterioration. Discontinuation of antithrombotic agents prescribed after previous coronary intervention must be considered. Autonomic neuropathy is common and leads to a delay in gastric emptying, hypotension and a vagolytic response to surgery. Wherever there is a combination of anti-thrombotic medication and autonomic dysfunction, the use of regional anaesthetic must be carefully considered.

Intestinal (Including Multivisceral) Transplants

Intestinal transplants are performed in a limited number of UK centres and are indicated mainly for loss of intestinal function (surgical or non-surgical reasons). These patients have significant problems after the initial transplantation but these are commonly dealt with in specialist units. However, patients may present for incidental elective and emergency procedures in other hospitals and may pose significant practical anaesthetic problems. Parenteral nutritional support is needed in the early postoperative period and this may lead to later difficulties with venous access. Indeed, the patient’s nutritional state may remain poor for some time after transplantation. The initial transplantation makes further surgical access difficult with the risk of haemorrhage and prolonged procedures. Postoperative care in a critical care environment is advisable, given the degree of debility, ongoing nutritional requirements and the need for multidisciplinary care.

SUMMARY

The increasing number of patients obtaining long-term survival benefits after various forms of transplantation means that more will present for alternative elective and emergency surgery. General issues relate to alterations in immunosuppressive regimens, the risk of infection and rejection and the presence of systemic diseases related to the original disease process. In most circumstances, where the initial transplant has been successful, the patient will have made an appropriate return to normal capacity. Even so, the functional reserve of the transplanted organ remains limited, even where simple biochemical markers of organ function are within normal range. The transplanted organ therefore remains at serious risk of further damage wherever the stress of a major surgical procedure is applied. In addition, the issues related to specific organ disease must also be considered.

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