Oxford Handbook of Anaesthesia (3 edn)
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General principles
The majority of patients who present for liver transplantation have either acute hepatic failure or end-stage liver disease. A small proportion undergo transplantation for other conditions, including polycystic liver disease, hepatoma, and metabolic liver disease which could give rise to future liver failure or catastrophic systemic illness (e.g. Wilson's disease). Most transplants are performed semi-electively in those with end-stage disease. Wordwide, the commonest indication for hepatic transplantation is post-hepatitis C cirrhosis. This is likely to change in the future as more effective antiviral therapies become available.
Preoperative assessment includes investigation/treatment of:
Jaundice, hyponatraemia, ascites, pleural effusions
Diabetes
Renal failure
Systemic vasodilatation with hypotension and cardiac failure
Poor nutritional state and reduced muscle mass
Portopulmonary syndromes (associated severe portal and pulmonary hypertension leading to right ventricular failure and potential cardiac arrest intraoperatively)
Hepatopulmonary syndromes (hypoxia and intrapulmonary shunting occurs in 0.5–4% of patients with cirrhotic liver disease)
Varices (oesophageal, gastric, rectal, abdominal wall)
Coagulopathy (prolonged prothrombin time, low platelet count, fibrinolysis)
Haemodynamic instability can result from cardiac involvement in the underlying process (e.g. alcoholic cardiomyopathy), from pericardial effusions, and from circulatory failure due to dilatation and low SVR. Anaemia resulting in a low plasma viscosity further reduces SVR.
Surgical techniques vary, but there are a number of common features:
Stage 1 of the operation is dissection (which involves laparotomy) and haemostasis (including ligation of varices). The liver is exposed, its anatomy defined, and slings placed around the major vessels.
Stage 2 of the operation is the anhepatic phase during which the hepatic artery, portal vein, hepatic veins, and bile duct are divided. Two main techniques are used for hepatectomy and implantation of the donor liver:
Division of the hepatic veins with caval preservation, followed by a ‘piggy back’ implant, where the new liver, with its own attached vena cava, is anastomosed, cava-to-cava, with the recipient's native vena cava. This can be done side-to-side or end-to-side. Surgery is performed with the native vena cava side-clamped, so that surgery can be completed while preserving venous return from the lower part of the body.
Removal of the liver with its included portion of vena cava, followed by implantation of the new liver by anastomosis of the donor vena cava (above and below the liver) into the position of the original cava. The second technique is used less commonly, as the native has to be cross-clamped at both points of division. Venous return during this phase is severely compromised leading to haemodynamic instability. Venovenous bypass is employed in some centres to facilitate venous return from the lower part of the body (femoral vein to right internal jugular or brachiocephalic vein).
Anastomoses are then made between donor and recipient portal vein. During this stage, patients with acute liver failure may become profoundly hypoglycaemic, although this is less common in patients being transplanted for chronic liver disease.
Stage 3 of the procedure is the post-reperfusion phase, beginning with the re-establishment of blood flow through the liver (portal vein to vena cava). This may be accompanied by a massive reperfusion syndrome, comprising release of cytokines, complement activation, transient reduction in core temperature, arrhythmias, and hypotension. Immediately after reperfusion, there is a rapid elevation in plasma K+ as it is washed out of the liver graft (although usually minor, this can sometimes reach 8–9mmol/l with poorer quality grafts). Preservation solution constituents, including adenosine, may also have a clinically important effect (bradycardia, hypotension).
As the cell membranes of the graft begin to function normally, electrolyte gradients are restored and a fall in plasma K+ ensues (sometimes producing ventricular ectopic beats). Hypotension at this stage results from myocardial depression and subsequently vasodilatation. Myocardial depression usually resolves within 2 or 3min, but the vasodilatation may persist for several hours. Following reperfusion, the hepatic artery is re-anastomosed and finally the bile duct reconstructed, either by direct duct-to-duct anastomosis or by construction of a Roux loop.
Liver transplantation
Procedure | Transplantation of entire liver |
Time | 4–10h |
Pain | Variable, but less than other comparable procedures (e.g. gastrectomy, thoracotomy). Back pain/shoulder pain may be a feature. PCA (occasionally epidural) effective |
Position | Supine, one or both arms out |
Blood loss | Extremely variable. 0–4000ml, X-match 10U (initially, then use uncrossmatched blood if necessary) and FFP 0–12U. Cell saver mandatory (typically reinfuse 2000ml) |
Practical techniques | ET, IPPV—details below |
Procedure | Transplantation of entire liver |
Time | 4–10h |
Pain | Variable, but less than other comparable procedures (e.g. gastrectomy, thoracotomy). Back pain/shoulder pain may be a feature. PCA (occasionally epidural) effective |
Position | Supine, one or both arms out |
Blood loss | Extremely variable. 0–4000ml, X-match 10U (initially, then use uncrossmatched blood if necessary) and FFP 0–12U. Cell saver mandatory (typically reinfuse 2000ml) |
Practical techniques | ET, IPPV—details below |
Preoperative
Includes investigation and correction of the factors mentioned above.
Usual tests include: FBC, U&Es, clotting, ECG, echocardiogram, stress ECG/dobutamine stress echo, chest radiograph, liver/chest CT, spirometry, immunology, virology, and hepatic angiographic MRI scan.
Preoperative fluids are not routinely administered except in patients with renal impairment and hyperacute liver failure (dextrose-based solutions).
Perioperative
Establish peripheral venous and arterial access before induction.
Induce anaesthesia (propofol, thiopental, etomidate) and relaxant (atracurium, vecuronium). Vasopressors may be required.
Ventilate to normocarbia using oxygen-enriched air and volatile agent (isoflurane, desflurane, sevoflurane). Establish infusion of an opioid agent (alfentanil, remifentanil, fentanyl). Patients undergoing transplantation for fulminant liver failure are at risk of raised intracranial pressure. In this patient group volatile agents must be avoided and TCI propofol used. ICP monitoring may be used depending upon the jaundice–encephalopathy interval (0–7d always—raised ICP in 70% of cases, 7–28d occasionally—raised ICP in 20%, 28–90d seldom—raised ICP in 4%).
Establish central venous monitoring. Transoesophageal echocardiography (TOE) is used in some centres. Insert a large-bore nasogastric tube. In patients with suspected pulmonary hypertension there may be a role for pulmonary artery catheterisation.
Lines for venovenous bypass can either be placed by the surgical team using femoral cut downs, or be inserted percutaneously, using extra-corporeal membrane oxygenation lines (21Fr in the right internal jugular and right femoral veins). These are used for both venovenous bypass and large vascular access. Venovenous bypass uses heparin-bonded circuitry, so systemic anticoagulation is unnecessary.
The patient's temperature must be rigorously maintained as hypothermia quickly develops, especially during the anhepatic phase or with massive transfusion. A forced warm air blanket should be placed over the patient's head, upper chest, and arms, and another over the legs.
Fluids are administered by a rapid infusion system and are warmed through a counter-current heating mechanism (e.g. Level-1® system with high-flow disposables and high-flow taps, allowing transfusion of 600ml/min at body temperature). Perioperatively and postoperatively, the Hct is maintained between 0.26 and 0.32 by infusion of blood, and the right ventricular end-diastolic volume index maintained at 140ml/m2 by infusion of other colloidal fluids as appropriate.
FFP is transfused approximately 2U per unit of blood transfused. Clotting is monitored and fine-tuned by thromboelastography.
Antifibrinolytic agents are commonly administered—tranexamic acid (15mg/kg bolus, then 5mg/kg/h by infusion) is given during the anhepatic phase.
A glucose-containing solution is infused continuously to maintain blood sugar.
K+ and Ca2+ should be monitored regularly during surgery and supplemented when required to maintain normal values. Hypocalcaemia is common during the anhepatic phase as a result of chelation with unmetabolised citrate. This can lead to cardiac depression and poor clotting. Recheck electrolytes immediately prior to graft reperfusion.
Severe metabolic acidosis is common but rarely needs correction. At the start of reperfusion, a bolus dose of 10mmol calcium is administered to protect the patient against the cardiac effects of potassium released from the liver graft. Progressive hypotension follows reperfusion. This may be severe and require small incremental IV doses of adrenaline (50µg) to maintain mean arterial pressure at a clinically acceptable value (above 70mmHg). In severely ill patients, an infusion of noradrenaline may subsequently be required.
Coagulopathy with defibrination and thrombocytopenia may also occur at graft reperfusion. Treatment includes bolus doses of antifibrinolytic drugs and platelets, as guided by the thromboelastograph. The haemodynamic and biochemical mayhem of graft reperfusion should resolve rapidly in the event of a functioning liver graft. Persisting acidosis or hypocalcaemia are suggestive of graft primary non-function, which represents a transplantation emergency. This may necessitate urgent retransplantation.
There is no proven strategy for avoiding renal failure, other than optimising fluid balance and avoiding nephrotoxins. In patients at particlarly high risk, avoidance of nephrotoxic immunopsuppressants (such as ciclosporin, tacrolimus) in the early postoperative period may have a role.
Postoperative
Patients should be managed on ICU. Early extubation is often feasible. As a result of improved techniques, the mean intensive care stay post-transplant can be reduced to 6hr.
Analgesia: PCA/epidural/paravertebral blocks have all been used to good effect. Epidural analgesia is possible in only a minority of cases because of coagulopathy. Avoid NSAIDs (interaction with calcineurin inhibitors to induce renal failure).
Postoperative fluids: maintenance fluid/nasogastric feed at 1.5ml/kg/h. Give blood/HAS/FFP to maintain CVP at 10–12mmHg, Hct at 0.26–0.32, and PT <23s.
Bleeding postoperatively is relatively uncommon (5–10%).
Graft primary non-function occurs in up to 5% of cases, requiring retransplantation.
Hepatic artery thrombosis occurs in 0.5–5% of cases. Thrombectomy may be attempted, but super-urgent retransplantation may be necessary.
Other postoperative problems include sepsis (10–20%) and acute rejection (up to 40%). These are managed medically with good results.
Immunosuppression is usually started with standard triple therapy (steroid/azathioprine/tacrolimus) and then tailored to the individual. Other drugs in current use include ciclosporin, mycophenolate mofetil, sirolimus, and basiliximab.
Long-term results of liver transplantation are encouraging. One-year survival figures in major centres now run between 85% and 95%, with a good long-term quality of life.
Hepatic resection
Procedure | Resection of liver tissue |
Time | 2–6hr |
Pain | As for transplantation. Epidural more common |
Position | Supine, arms out |
Blood loss | 1000ml, X-match 10U |
Practical techniques | ET, IPPV. Details below and on p. 572 |
Procedure | Resection of liver tissue |
Time | 2–6hr |
Pain | As for transplantation. Epidural more common |
Position | Supine, arms out |
Blood loss | 1000ml, X-match 10U |
Practical techniques | ET, IPPV. Details below and on p. 572 |
The major indication for hepatic resection is metastatic colorectal adenocarcinoma. Most patients presenting for hepatic resection are otherwise relatively fit. Stigmata of liver disease and significant jaundice are unusual, except in those presenting for radical hepatic resection for cholangiocarcinoma, where some patients require biliary stenting or drainage preoperatively to reduce jaundice prior to major surgery. The principles underlying anaesthesia for this group of patients are similar to those for any patient undergoing a major laparotomy.
Major liver resection usually results in 30–75% of functional hepatic tissue being removed. As the remaining hepatocytes function poorly for some days following surgery, short-acting drugs should be used.
Drugs that might compound postoperative hepatic encephalopathy, or which rely on hepatic metabolism, should be avoided (e.g. benzodiazepines).
Most resections are accomplished with minimal blood loss but unexpected catastrophic haemorrhage may occur.
Resection commences with perihepatic dissection and identification of vascular anatomy.
Intraoperative diagnostic ultrasound is often used to pinpoint lesions requiring resection.
Bleeding occurs from either vascular inflow (portal vein, hepatic artery) or venous back bleeding. Branches of the hepatic artery and portal vein to the segment of liver to be resected have usually been ligated, so inflow bleeding should not be a major problem. In practice, the line of resection often passes through a watershed area, between vital and devitalised tissue, and remaining inflow bleeding may require additional control by intermittent cross-clamping of vascular inflow to the rest of the liver (the so-called Pringle manoeuvre). This results in a degree of ischaemia-reperfusion injury to the remaining liver tissue, and potentially poor postoperative liver function. This can be minimised by ischaemic preconditioning and the use of intermittent rather than continuous clamping.
Very radical liver resections are now possible where the liver is totally excised and dissected ex vivo following perfusion with ice-cold preservation solution. Healthy parts of the liver are then attached to a Gore-Tex® vena cava graft and reimplanted. This is a prolonged and difficult procedure and anaesthetically similar to a liver transplantation.
Preoperative
As for any major abdominal surgery, but including screening of liver function and coagulation.
Perioperative
Patients undergoing major liver resection should have large venous access. Arterial pressure monitoring is common but no longer universal as surgical techniques have improved. Central venous pressure monitoring, at one time universal, is now used on the basis of clinical need—in major centres, the surgeon and anaesthetist can predict those cases where it is likely to be unnecessary.
Thoracic epidural analgesia is utilised to good effect postoperatively, though there is controversy (but few data) on the risks posed by postoperative coagulopathy.
The anaesthetic technique employed should be aimed at preserving hepatic blood flow and minimising liver injury. Artificial ventilation of the lungs with oxygen-enriched air and a volatile agent is the best way of achieving this. Isoflurane and desflurane are associated with the best preservation of hepatic blood flow.
Fluid management
Maintenance of a high central venous pressure used to be common to reduce the risk of air embolism, but it is associated with an increased risk of venous back bleeding.
A reduced central venous pressure substantially reduces bleeding. This approach has dramatically reduced transfusion requirements, with no reported adverse consequences, despite the theoretically increased risk of air embolus. Techniques for reducing the central venous pressure include epidural boluses and either head up (reverse Trendelenburg) or head-down (Trendelenburg) tilt. Tilt in either direction can potentially reduce the pressure in the cava at the level of the hepatic veins. It is the author's own practice to use head-up tilt, aiming for CVP of 0–2mmHg and systolic BP of 70–80mmHg.
Intraoperative blood sampling allows accurate transfusion replacement. Fresh frozen plasma is occasionally also required in cases of massive haemorrhage, in cases where there is a prolonged hepatic inflow cross-clamp time, or where very little hepatic tissue remains. However, intraoperative coagulopathy is relatively uncommon. Peak disturbances in clotting are seen on postoperative days 2–3. As with patients undergoing liver transplantation, active warming measures should be taken to maintain the patient's temperature and minimise any coagulopathy.
Postoperative
Patients should initially be managed in an HDU. Coagulopathy and encephalopathy may develop postoperatively in those who have undergone very major resections. This has practical implications for the timing of removal of epidural catheters, etc—which may require FFP cover.
The overall results of radical hepatic resection are very encouraging, with many cases treated that were previously considered inoperable. Many remain disease-free 5yr following resection. In those cases where recurrences arise, further hepatic resection is often possible.
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