There are 3 major types of liver transplantation (LT): cadaveric orthotopic LT (OLT), where a whole organ is transplanted from a deceased donor (most common); cadaveric OLT by split LT, where the recipient receives 1 lobe of the liver from a deceased donor; and live donor OLT, where the donor undergoes either a right or left hepatic lobectomy. In the case of split or living donor liver transplants, adult recipients usually receive the larger right lobe; children are ordinarily transplanted the smaller left lobe.
OLT requires surgical anastomosis of the hepatic artery, portal vein, bile duct, and inferior vena cava from donor to recipient, and postoperative complications are often related to dysfunction at these anastomotic sites.
Recovery in the Immediate Postoperative Period
Most of the patients after LT, even after an uncomplicated operating room course, are monitored in the ICU. Uncomplicated cases usually transfer to an inpatient liver transplant unit within 24 to 72 hours but complicated cases may require ICU care for weeks. Fifteen percent to 20% of liver transplant patients are taken back to the operating room during the transplant admission. The main reasons for reoperation include postoperative bleeding, vascular and biliary complications, and intraabdominal sepsis.
In the ICU, frequent hemodynamic assessments are commonly performed using vital signs and noninvasive monitoring (eg, ultrasonography). A preexisting pulmonary artery catheter is utilized if placed intraoperatively for more hemodynamically challenging cases or those with pulmonary hypertension. Vital signs, intake, output, physical changes in drain output, bile production (if a biliary drain [eg, T-tube] is present), abdominal drain (eg, Jackson–Pratt) output, and any signs of postoperative bleeding are recorded hourly. The initial postoperative level of liver biochemistries, that is, alanine transaminase (ALT), aspartate aminotransferase (AST), and bilirubin, may not correlate with liver function in the first day or first 2 days after transplant. Therefore, most centers rely on the serial assessment of international normalized ratio (INR) and lactate along with complete blood count, arterial blood gas, electrolytes, glucose, blood urea nitrogen, and creatinine as well as the liver biochemistries (ALT, AST, bilirubin, and alkaline phosphatase) analyzed every 6 hours within the first 2 days. The clinical picture (eg, hemodynamics, renal function, and neurological status) also provides important information about graft function.
Increased INR is usually not treated with fresh frozen plasma (FFP) because it may mask allograft dysfunction and potentially increase the incidence of hepatic artery thrombosis (HAT) or portal vein thrombosis. Thrombocytopenia is also very common after LT, however platelet transfusions are also avoided because they may increase the chances of HAT. If there is significant bleeding, FFP and platelet transfusions may be indicated but the decision to transfuse should be made in concert with the transplant surgeon.
Assessment of Liver Graft Function
Graft edema, any unusual or discolored appearance of the allograft in the operating room, inability of the patient to raise the core body temperature, hemodynamic instability, hypoglycemia, dramatic increases in potassium, prothrombin time or INR, and lactate all signal inadequate allograft function. Inadequate urine output or acute kidney injury is also common in this setting, but may be caused by factors other than graft dysfunction such as acute tubular necrosis (ATN) or immunosuppressive drugs such as cyclosporine or tacrolimus.
Doppler ultrasonography (DUS) is routinely done on the first postoperative day to assess patency of the hepatic arteries and portal veins to rule out HAT, stenosis, or portal vein thrombosis. DUS also assesses for fluid collections, hematomas, and abscesses. As the hepatic artery supplies blood to the biliary ducts, HAT is associated with bile leaks. Follow up DUS is performed if the initial findings are equivocal or there is a sudden deterioration in graft function or elevation of LFTs.
Split cadaveric and live donor lobe transplants may be associated with initially higher ALT and AST due to raw liver surfaces as well as more prolonged lactate and INR elevation due to smaller liver mass relative to recipient size. Elevated INR may also occur in standard cadaveric OLT when the overall liver mass is small. Recipients of split and living donor transplants often become hypophosphatemic and require rigorous phosphorus supplementation due to the metabolic needs of regenerating liver tissue.
Recognition and Management of Early Complications
Sepsis—The risk of infections is increased after LT and bacterial infections are more common than fungal infections. Deep surgical space infections and biliary leaks are common sources of infection. All potential sites for infection should be explored and, if possible, eliminated (catheters, hematomas, or fluid collections suspicious for abscess).
Respiratory Complications—Patients that are critically ill prior to LT are at increased risk for prolonged mechanical ventilation due to debilitating conditions and concomitant loss of muscle mass. Those with liver graft dysfunction, extrahepatic organ dysfunction, or sepsis are also more likely to require prolonged ventilator support. Transient severe pulmonary edema may occur due to systemic inflammatory response syndrome (SIRS) or sepsis, or much less commonly transfusion-related lung injury. Although pneumonia is possible early after LT, pulmonary infiltrates are usually due to noncardiogenic pulmonary edema from systemic inflammation or sepsis originating from the abdomen. Patients intubated postoperatively for more than 7 to 10 days should be evaluated for tracheostomy.
Hepatopulmonary syndrome (HPS) is defined by the triad of liver dysfunction or portal hypertension, abnormal gas exchange, and evidence of pulmonary vascular shunts resulting in hypoxemia. Patients with HPS have an increased length of stay in the ICU (median 4 days) and hospital (median 39 days). LT may be curative, however, the median time to cessation of oxygen is 4.5 months in some series. Right pleural effusions are common after liver transplant due to operation near the right diaphragm, but do not usually cause respiratory failure. Postoperative right pneumothorax may occur less commonly.
Cardiovascular Complications—Liver failure typically results in a hyperdynamic circulation with elevated cardiac index and low blood pressure. A patient receiving a transplant before severe liver failure is manifest, for example, hepatic tumors or living-related donor recipients, may not have a hyperdynamic circulation. If present prior to LT, the hyperdynamic state does not resolve immediately after LT and may persist for weeks or longer. Mild to moderate portopulmonary hypertension in the setting of high cardiac output (CO) usually resolves with successful LT.
The majority of low CO states in the ICU after LT are caused by volume loss usually from bleeding, third spacing, and/or a stunned myocardium due to SIRS or sepsis. Dynamic left ventricular outflow tract obstruction due to decreased LV preload in the setting of inotropes is also a potential cause of low CO post-LT. Rarely, low CO may be caused by an acute myocardial infarction. Other causes of low CO after LT include cirrhotic cardiomyopathy or cardiomyopathies associated with alcohol, hepatitis, or hemochromatosis, although these should have been screened out during the preoperative work up.
Management of hemodynamic instability includes treatment of the causative factors. Central venous pressure measurement is a poor guide for intravascular volume and adequate resuscitation both in the ICU and in the operating room. No relationship between CVP and liver graft outcome has been demonstrated subsequent to an uncontrolled observational study to the contrary. The use of CO trending and mixed venous blood gases via a pulmonary artery catheter (often present in the immediate postoperative period after intraoperative placement), and or serial echocardiography, coupled with lactate trends are helpful to guide hemodynamic management. Although there are no randomized control trials to support the use of colloids over crystalloids after LT, albumin 5% is preferred for volume resuscitation after LT due to hypoalbuminemia and to limit positive fluid balance.
Hypertension may develop posttransplant and is more common in patients with preexisting hypertension. Hypertension can be caused or exacerbated by immunosuppressive drugs such as tacrolimus, cyclosporine, and steroids. The treatment may include diuresis in the setting of fluid overload or the addition of antihypertensive agents.
Renal Dysfunction—The incidence of acute renal failure after LT varies widely in the literature, ranging between 27% and 67%. The most important risk factor for postoperative renal dysfunction is pretransplant renal dysfunction (ie, hepatorenal syndrome or ATN). Most kidneys recover with time and only a small percentage of patients develop chronic kidney failure. Management of renal failure in the posttransplant period includes renal replacement therapy and judicious use of immunosuppressants, particularly, nephrotoxic calcineurin inhibitors (ie, tacrolimus or cyclosporine) or a calcineurin inhibitor-sparing protocol (eg, mycophenolate mofetil, steroids, monoclonal antilymphocyte antibodies) at the discretion of the transplant team. In hemodynamically unstable patients and particularly those with primary nonfunction or poor early graft function, continuous veno-venous hemofiltration is the preferred modality for renal replacement and should be started as early as feasible to maintain metabolic homeostasis during this critical time of multiorgan dysfunction.
Neuropsychiatric Complications—Neuropsychiatric complications occur in up to 30% of liver transplant patients and often require prolonged management in the ICU. Complications include encephalopathy (delirium), tremors, myoclonus and less commonly seizures (including nonconvulsive status epilepticus), meningitis, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
Delirium is common after LT. Treatment with antipsychotic medications may be required (eg, haloperidol or risperidone). It may be due to preexisting hepatic encephalopathy, postoperative liver graft dysfunction, renal failure, sepsis, or side effects of immunosuppressive medications such as steroids and calcineurin inhibitors (see later under Immunosuppressive Drugs). If there are no focal deficits and the patient is hemodynamically and or respiratory unstable, computed tomography (CT) imaging may be postponed or avoided. However, if the patient exhibits focality or seizures, emergent CT should be performed. Ischemic stroke, subarachnoid, and subdural hemorrhages are uncommon but possible. Central nervous system infections such as meningitis and brain abscess are unusual but possible in these immunocompromised patients.
HAT occurs in less than 2% to 3% of patients after LT. Thirty percent develop signs of acute hepatic necrosis with high transaminases, sepsis, mental status changes, and coagulopathy, but may the presentation be more subacute with progressive biliary infections and hepatic dysfunction. Suspicion of HAT should be immediately investigated with DUS and potentially confirmed by an arteriogram or exploratory laparotomy depending on the level of surgical concern. HAT within the first week after OLT is an indication for relisting for retransplantation. Portal vein thrombosis is also diagnosed by DUS. If the diagnosis is made during the ICU stay, the patient may undergo thrombectomy depending on the degree of occlusion and collateral circulation.
Biliary complications remain frequent after LT varying between 1.6% and 18% and include bile leaks, bilomas, and strictures. Early bile leaks should be suspected in any patient with constant abdominal pain, or unexplained fever or sepsis after liver transplant. Most leaks occur from the biliary anastomosis and present early. Many require abdominal washout and surgical repair, although endoscopic stenting may be successful. Late bile leaks (after 30 days) are rare, however late strictures are the most frequent cause of biliary complications after LT and are often associated with recurrent cholangitis. Treatment of anastomotic strictures usually requires endoscopic stenting; intrahepatic strictures are more complex and may lead to retransplantation.
In uncomplicated liver transplants an oral diet can be started within the first 1 to 2 days after surgery. A protein-rich diet is recommended, as the liver patient needs 1.5 to 2 g protein per kg body weight per day. If oral intake is not sufficient, postpyloric feeding through a tube should be considered. Parenteral nutrition should be initiated only if tube feeding is not possible due to intestinal complications and prolonged nothing by mouth (NPO) (eg, > 3-7 days) is anticipated. Both steroids and calcineurin inhibitors may cause hyperglycemia and this will be even more pronounced in patients with preexisting diabetes mellitus. Hypoglycemia may be a sign of liver graft dysfunction or excess insulin dosing.