Critical Care of the Liver and Intestinal Transplant Recipients
Ruy J. Cruz Jr
William D. Payne
Abhinav Humar
Introduction
The field of liver transplantation has undergone remarkable advances in the last two decades. From an essentially experimental procedure with poor results in the early 1980s, it has progressed to become the accepted treatment of choice for patients with acute and chronic end-stage liver disease. One-year survival rates have increased from 30% in the early 1980s, to more than 85% at present. The major reasons for this dramatic improvement in outcome include improved surgical and preservation techniques, better immunosuppressive regimens, more effective treatment of rejection and infection, and improved care during the critical perioperative period. The field of intestinal transplantation has also made tremendous strides in the last 20 years, though perhaps has not enjoyed the degree of success seen with liver transplantation. Nonetheless, results continue to improve and it is approaching success rates that are not dramatically inferior compared with liver transplantation.
Despite the improved results, both liver and intestinal transplantation remain major undertakings, with potential for complications affecting every major organ system. This chapter focuses on the critical care of these challenging and complicated patients, including preoperative selection and evaluation, intraoperative care, postoperative care, and management of potential complications.
Liver Transplantation
History
The origins of modern clinical liver transplantation date back to the late 1950s, when the surgical techniques were perfected in the dog model [1]. The first human liver transplant was performed by Starzl in 1963 [2], but not until 1967 was the first successful such transplant performed [3]. Little progress was made in the field over the next decade. It remained a dangerous procedure, reserved for terminal patients.
In the early 1980s, liver transplantation proliferated for a variety of reasons, the most important being the introduction of cyclosporine [4]. At that time, it was the most specific immunosuppressive agent and allowed for a dramatic rise in all organ transplants. Patient survival rates for liver recipients on cyclosporine more than doubled. In the late 1980s, the introduction of University of Wisconsin (UW) preservation solution extended the cold preservation time of the cadaver liver from 8 to 24 hours [5].
As the success of liver transplantation grew, so did the indications and the number of people awaiting a transplant. With each passing year, there was an ever increasing disparity between the number of transplants performed and the number of patients awaiting transplant. In 1988, there were approximately 1,500 transplants performed and 3,000 patients awaiting a transplant. In 2008, according to the UNOS Database, 6,319 liver transplants were performed in the United States, while 16,584 patients were listed waiting for an available/suitable organ (UNOS/OPTN, www.optn.transplant.hrsa.gov/, accessed August, 2009) [6].
Given this increasing disparity between the number of actual and potential recipients, recent attempts have been made to expand the donor pool. Some of this increase in donors has been achieved by the use of livers that are considered marginal and would not have been used for transplant a decade ago. Recently, the use of organs from donors after cardiac death (also referred as nonheart beating donors) has emerged as an important source of organs in response to the significant growth of the waiting list. Donation after cardiac death (DCD) involves those donors who present a severe neurological injury and/or irreversible brain damage but still have minimal brain function. In 2000, only 11 centers used DCD livers, increasing to 62 centers in 2007 [7,8,9].
Innovative surgical procedures have also been used in order to increase the donor pool. These procedures include, but are not limited to, living donor liver transplantation, split-liver transplantation, and dual liver transplantation. Living donor transplants involve transplanting a lobe or part of a lobe from a healthy donor into a potential recipient. Split-liver transplantation involves dividing a cadaver liver into two functional grafts, which can be transplanted into two recipients. Dual liver transplantation involves the use of two lobes (usually two left lobes) from two living donors that are implanted into one adult recipient. These procedures are helping expand the donor pool, but are also associated with unique problems.
Proper allocation of the scarce resource of a deceased donor liver graft has always been an important issue in the development of the field. Recent effects have focused on directing organs to individuals with the greatest need, rather than those with the longest waiting time. In the United States, this lead to the development and adaptation in 2002 of the MELD (Model for End-Stage Liver Disease) and PELD (Pediatric End-Stage Liver Disease) scoring systems [10].
Preoperative Evaluation
A liver transplant is indicated for liver failure, whether acute or chronic. Liver failure is signaled by a number of clinical symptoms (e.g., ascites, variceal bleeding, hepatic encephalopathy, malnutrition) and by biochemical liver test results that suggest impaired hepatic synthetic function (e.g., hypoalbuminemia, hyperbilirubinemia, coagulopathy). The cause of liver failure often influences its presentation. For example, patients with acute liver failure generally have hepatic encephalopathy and coagulopathy, whereas patients with chronic liver disease most commonly have ascites, gastrointestinal (GI) bleeding, and malnutrition.
A host of diseases are potentially treatable by a liver transplant. Broadly, they can be categorized as acute or chronic, and then subdivided by the cause of the liver disease (Table 187.1). Chronic liver diseases account for the majority of liver transplants today. The most common cause in North America is chronic hepatitis, usually due to hepatitis C, less commonly to hepatitis B. Chronic alcohol abuse accelerates the process, especially with hepatitis C. Progression from chronic infection to cirrhosis is generally slow, usually 10 to 20 years. Chronic hepatitis may also result from autoimmune causes, primarily in women; it can present either acutely over months or insidiously over years [11]. Alcohol often plays a role in end-stage liver disease (ESLD) secondary to hepatitis C, but it may also lead to liver failure in the absence of that viral infection. In fact, alcohol is the most common cause of ESLD in the United States. Such patients are generally suitable candidates for a transplant as long as an adequate period of sobriety can be documented. Most of the centers in the United States require a minimum of 6 months of demonstrated abstinence and an adequate evaluation and treatment period for alcohol addiction. In spite of this strict pretransplant screening the rate of alcohol use after transplant can reach 42% in the first 5 years after transplant [12]
Table 187.1 Diseases Potentially Treatable by a Liver Transplant | |
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Cholestatic disorders also account for a significant percentage of transplant candidates with chronic liver disease. In adults, the most common causes are primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). PBC, a destructive disorder of interlobular bile ducts, can progress to cirrhosis and liver failure over several decades. It most commonly affects middle-aged women. PSC, a disease characterized by inflammatory injury of the bile duct, occurs mostly in young men, 70% of whom have inflammatory bowel disease [13]. In children, biliary atresia is the most common cholestatic disorder. It is a destructive, inflammatory condition of the bile ducts; if untreated, it usually results in death within the first 1 to 2 years of life.
A variety of metabolic diseases can result in progressive, chronic liver injury and cirrhosis, including hereditary hemochromatosis (an autosomal recessive disorder characterized by chronic iron accumulation, which may result in cirrhosis, cardiomyopathy, and endocrine disorders including diabetes), α1-antitrypsin deficiency (which may result in cirrhosis at any age, most commonly in the first or second decade of life), and Wilson’s disease (an autosomal recessive disorder of
copper excretion, which may present as either fulminant hepatic failure or chronic hepatitis and cirrhosis) [14].
copper excretion, which may present as either fulminant hepatic failure or chronic hepatitis and cirrhosis) [14].
Hepatocellular carcinoma (HCC) may be a complication of cirrhosis from any cause, most commonly with hepatitis B, hepatitis C, hemochromatosis, and tyrosinemia. In 2007, almost 15% of all liver transplants in the United States were performed in patients with a diagnosis of HCC. HCC patients may have stable liver disease, but are not candidates for hepatic resection because of the underlying cirrhosis; they are best treated with a liver transplant. The best transplant candidates are those with a single lesion less than 5 cm in size or with no more than three lesions, the largest no greater than 3 cm in size (known as the Milan criteria). Transplantation outside of these criteria is usually associated with higher recurrence rates, though some centers have shown acceptable 5-year survival in patients that have tumors that slightly exceed the Milan criteria [15,16].
Currently, in the United States, only the patients within Milan criteria are eligible for priority listing for liver transplantation. The amount of waiting list time for patients with HCC remains a critical factor in the success of liver transplantation, as long waiting times may lead to disease progression. Recently downstaging treatment, with transarterial chemoembolization and radiofrequency ablation, has emerged as a possible option for those patients who slightly exceed Milan criteria [17].
A host of other diseases may lead to chronic liver failure and are potentially amenable to treatment with a transplant, including Budd–Chiari (obstruction of the hepatic veins secondary to thrombus, which leads to hepatic congestion, ascites, and eventually liver damage) and polycystic liver disease (in which a large number of cysts, depending on their size, can lead to debilitating symptoms).
Acute liver disease, more commonly termed fulminant hepatic failure (FHF), is defined as the development of hepatic encephalopathy and profound coagulopathy shortly after the onset of symptoms, such as jaundice, in patients without preexisting liver disease. The most common causes in the Western world include acetaminophen overdose, acute viral hepatitis, various drugs and hepatotoxins, and Wilson’s disease; often, however, no cause is identified [18]. Treatment consists of appropriate critical care support, giving patients time for spontaneous recovery. The prognosis for spontaneous recovery depends on the patient’s age (those younger than 10 and older than 40 years have a poor prognosis), the underlying cause, and the severity of liver injury (as indicated by degree of hepatic encephalopathy, coagulopathy, and kidney dysfunction) (Table 187.2) [19,20]. A subset of patients may have delayed onset of hepatic decompensation that occurs 8 weeks to 6 months after the onset of symptoms. This condition is often referred to as subacute hepatic failure; these patients rarely recover without a transplant.
Table 187.2 Adverse Prognostic Indicators for Patients with Acute Liver Failure | |
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Table 187.3 Indications for A Liver Transplant Evaluation in Patients with Chronic Liver Disease | |
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Indications for Transplant
Chronic Liver Disease
The simple presence of chronic liver disease with established cirrhosis is not an indication for a transplant (Table 187.3). Some patients have very well-compensated cirrhosis with a low expectant mortality. Patients with decompensated cirrhosis, however, have a poor prognosis without transplant. The signs and symptoms of decompensated cirrhosis include the following:
Hepatic Encephalopathy (HE): In its early stages, HE may begin with subtle sleep disturbances, depression, and emotional liability. Increasing severity of HE is indicated by increasing somnolence, altered speech, and at the extreme end, coma. Evaluation of the severity of HE is based on the West Haven criteria of altered mental status. A common finding on physical examination is asterixis, an ability to maintain position, which is most commonly tested by having the patients outstretch their arms and hold them in dorsiflexion. However, other simple tests (such as tongue protrusion, dorsiflexion of the foot, or asking the patient to grasp the examiner’s fingers) can also trigger the asterixis. Blood tests often reveal an elevated serum ammonia level. HE may occur spontaneously, but is more commonly triggered by a precipitating factor such as infections, GI bleeding, use of sedatives, constipation, diuretics, electrolyte imbalance, or excessive dietary protein intake. The purpose of treatment is to correct the precipitating factor in combination with pharmacological management including nonabsolvable disaccharides (i.e., lactulose), and antibiotics such as neomycin, rifaximin, and metronidazole.
Ascites: Ascites is generally associated with portal hypertension. The initial approach to the management of ascites is sodium restriction and diuretics. If this approach is not successful, patients may require repeated large-volume (4 to 6 L) paracentesis. A better option to diuretic-resistant ascites requiring frequent paracentesis is transjugular intrahepatic portosystemic shunting (TIPS). A potential complication of TIPS is progression of liver failure or disabling encephalopathy. Patients with signs of far-advanced liver disease such as hyperbilirubinemia, HE, and renal dysfunction are generally not good candidates for TIPS.
Spontaneous Bacterial Peritonitis (SBP): This complication of chronic liver failure generally signals advanced disease. Anaerobic Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae) account for 60% of the cultured organisms; Gram-positive cocci account for the remainder. Diagnosis is confirmed if a tap of the abdominal fluid shows
a polymorphonuclear neutrophil (PMN) count of > 250 per mL. If a traumatic tap is performed (red cells > 10,000 per mL), the PMN count should be corrected, subtracting 1 PMN for every 250 red cells. Treatment is generally with a third-generation cephalosporin. The recurrence rate of SBP at 1 year is up to 70%; therefore, prophylaxis with antibiotics (norfloxacin or ciprofloxacin) is highly recommended. The long-term prognosis of patients who develop SBP is extremely poor with mortality rates of 50% to 70% at 1-year follow-up [21].
Portal Hypertensive Bleeding: The likelihood of patients with cirrhosis developing varices ranges from 35% to 80%. About one-third of those with varices will experience bleeding. The risk of recurrent bleeding approaches 70% by 2 years after the index bleeding episode. Each episode of bleeding is associated with a 30% mortality rate. Thus, urgent treatment of the acute episode and steps to prevent rebleeding are essential. Endoscopy is indicated to diagnose and treat the acute bleed with either band ligation or sclerotherapy. Other therapies include vasoactive drugs such as octreotide or vasopressin, balloon tamponade, TIPS, and emergency surgical procedures (such as a portosystemic shunt or transection of the esophagus). Generally, patients whose endoscopic procedure fails should undergo emergency TIPS, if feasible, to control bleeding. Beta-blockers have been shown to be of value in preventing the first bleeding episode in patients with varices and in preventing rebleeding.
Hepatorenal Syndrome (HRS): In patients with advanced liver disease and ascites, HRS is characterized by oliguria (< 500 mL of urine per day) in association with low urine sodium (< 10 mEq per L). It is a functional disorder; the kidneys have no structural abnormalities, and the urine sediment is normal. The differential diagnosis includes acute tubular necrosis, drug nephrotoxicity, and chronic intrinsic renal disease. HRS may be precipitated by volume depletion from diuresis, SBP, or agents such as nonsteroidal anti-inflammatory drugs. Patients may require dialysis support, but the only effective treatment is a liver transplant.
Others: Other signs and symptoms of decompensated cirrhosis include severe weakness and fatigue, which may sometimes be the primary symptoms. Such weakness can be debilitating, leading to the inability to work or even to carry out day-to-day functions. It may be associated with malnutrition and muscle wasting, which at times may be quite severe. Biochemical abnormalities and loss of synthetic function in advanced ESLD are associated with a low-serum albumin, a high-serum bilirubin, and a rise in the serum international normalized ratio (INR).
The severity of illness and prognosis of patients with chronic liver disease can be estimated by a number of different scoring models including the Childs–Pugh–Turcotte score and the MELD score. The latter is now widely used in the United States for the allocation of organs. It is based on a predicted 3-month mortality for patients awaiting a liver transplant, and uses 3 laboratory values to generate a score which determines priority. The three laboratory values used are serum bilirubin, serum creatinine, and INR. The format is as follows:
For pediatric patients, the scoring system is somewhat different. The PELD (pediatric end-stage liver disease) score is calculated using the following factors: serum bilirubin, albumin, and INR, the age of the patient (additional points if < 1 year old), and if the patient has growth failure [22].
Acute Liver Disease
Patients with FHF should be considered for transplant if they have any one of a number of poor prognostic indicators that predict a low likelihood for spontaneous recovery of liver function (Table 187.2). Generally, FHF patients are more acutely ill than chronic liver failure patients, and thus require more intensive care pretransplant. FHF patients have more severe hepatic parenchymal dysfunction, as manifested by coagulopathy, hypoglycemia, and lactic acidosis. Infectious complications are more common, as is their incidence of kidney failure and neurologic complications, especially cerebral edema.
Coagulopathy is usually secondary to the impaired hepatic synthesis of clotting factors. A component of consumption, as a result of disseminated intravascular coagulation (DIC), may also be associated with FHF. Close attention should be given to the serum glucose level, which is more likely to be decreased in FHF patients. Intravenous (IV) glucose should be administered at a sufficient rate to maintain euglycemia.
The prevalence of bacterial infection in FHF patients is very high, a reflection of the loss of the liver’s immunologic functions. The respiratory and urinary systems are the most common sources. In addition, almost one-third of FHF patients develop some form of fungal infection, usually secondary to Candida species [23]. Sepsis is generally a contraindication to a transplant; if it is unrecognized pretransplant, the outcome posttransplant is poor.
Multiple organ dysfunction syndrome, characterized by respiratory distress, kidney failure, increased cardiac output, and decreased systemic vascular resistance, is a well-described complication of FHF. It may be due to impaired clearance of vasoactive substances by the liver. Mechanical ventilation and dialysis support may become necessary pretransplant. Hemodynamic abnormalities may manifest as hypotension and worsening tissue oxygenation.
Cerebral edema is substantially more common in FHF patients. As many as 80% of patients dying secondary to FHF have evidence of cerebral edema. The pathogenesis is unclear, but it may be due to potential neurotoxins that are normally cleared by the liver. Diagnosis may be problematic; patients are often sedated and ventilated, making clinical examination difficult. Radiologic imaging is neither sensitive nor specific. Several centers have tried intracranial pressure (ICP) monitoring; therapy (e.g., mannitol, hyperventilation, thiopental) can then be directed to achieve an adequate cerebral perfusion pressure. ICP monitoring also helps predict the likelihood of neurologic recovery posttransplant. Sustained cerebral perfusion pressures of less than 40 mm Hg have been associated with postoperative neurologic death. Disadvantages of ICP monitoring include the risks of performing it in patients with severe coagulopathy; it is also a possible source of infection and may precipitate an intracranial hemorrhage.
Contraindications for Transplant
The indications for a liver transplant are numerous (and are increasing), but the numbers of absolute contraindications are few (and have decreased with time). There are no specific age limits for recipients; their mean age is steadily increasing. Patients must have adequate cardiac and pulmonary function. Other contraindications, as with other types of transplants, include uncontrolled systemic infection and malignancy. HCC patients with metastatic disease, obvious vascular invasion, or significant tumor burden are not good transplant candidates. Patients with other types of extrahepatic malignancy should be deferred for at least 2 years after completing curative therapy before a transplant is attempted.
Currently, the most common contraindication in the United States to a liver transplant is ongoing substance abuse. Before considering patients for a transplant, most centers require a documented period of abstinence, demonstration of compliant behavior, and willingness to pursue a chemical dependency program.
Unique to patients with chronic liver disease, a transplant may be contraindicated in the presence of severe hepatopulmonary syndrome or pulmonary hypertension. Hepatopulmonary syndrome is characterized by impaired gas exchange, resulting from intrapulmonary arteriovenous shunts. These shunts may lead to severe hypoxemia, especially when patients are in the upright position (orthodeoxia). A transplant may be contraindicated if intrapulmonary shunting is severe, as manifested by hypoxemia that is only partially improved with high inspired oxygen concentrations. Pulmonary hypertension (mean pulmonary artery pressure > 25 mm Hg in the setting of portal hypertension) is seen in a small proportion of patients with established cirrhosis. Its exact cause is unknown [24]. Diagnosing pulmonary hypertension pretransplant is critical, because major surgical procedures in the presence of nonreversible pulmonary hypertension are associated with a very high risk of mortality. The initial screening is usually performed with transthoracic Doppler echocardiography (TTE) which can estimate pulmonary arterial systolic pressure when tricuspid regurgitation is present. TTE presents a sensitivity of 97% and specificity of 77% in diagnosing pulmonary hypertension in the setting of liver failure. In patients with elevated pulmonary arterial systolic pressure (> 50 mm Hg), a more invasive assessment (right heart catheterization) is recommended. It has been shown that perioperative mortality is directly proportional to the mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. For these reasons, most transplant centers consider a mPAP greater than 35 mm Hg to be an absolute contraindication for transplant. If the mPAP can be lowered below that value using medications (epoprostenol, sildenafil), the patient can still be considered for transplant [24].
Another absolute contraindication for liver transplantation, in case of acute liver failure, is a presence of unresponsive cerebral edema with sustained elevation of intracranial pressure (> 50 mm Hg) and a persistent decrease in cerebral perfusion pressure (< 40 mm Hg).
Intraoperative Care
A detailed description of the operative procedure and anesthetic management is beyond the scope of this chapter. A basic understanding of the intraoperative course is necessary, however, to aid in postoperative care and monitoring for possible complications.
The operation itself may be divided into three phases: preanhepatic, anhepatic, and postanhepatic. The preanhepatic phase involves mobilizing of the recipient’s diseased liver in preparation for its removal. The basic steps include isolating the supra- and infrahepatic vena cava, portal vein, and hepatic artery, and then dividing the bile duct. Given existing coagulopathy and portal hypertension, the recipient hepatectomy may be the most difficult aspect of the procedure. The anesthesia team must be prepared to deal with excessive blood loss during this time.
Once the above-named structures have been isolated, vascular clamps are applied. The recipient’s liver is removed, thus beginning the anhepatic phase. This phase is characterized by decreased venous return to the heart because of occlusion of the inferior vena cava and portal vein. Many centers routinely employ a venous bypass system during this time: blood is drawn from the lower body and bowels via a cannula in the common femoral vein and portal vein, and returned through a central venous cannula in the upper body. Potential advantages of bypass include improved hemodynamic stability, reduction of bleeding from an engorged portal system, and avoidance of elevated venous pressures in the renal veins. However, many centers do not routinely use venovenous bypass (VVB). Very few randomized trials have measured specific clinical outcomes with or without VVB. In one randomized trial, postoperative renal function and the need for hemodialysis or hemofiltration were no different between liver recipients with versus without VVB [25]. This, combined with the potential complications of VVB (air embolism, thromboembolism, hypothermia, hemodilution, cannula and incision-related morbidity, trauma to vessels, and incremental costs), have led some centers to adopt a selective use for VVB—reserving it for patients without portal hypertension or for those patients who demonstrate hemodynamic instability with a trial of caval clamping [26].
 Figure 187.1. Illustration of standard liver transplant procedure with replacement of the recipient’s inferior vena cava. Typical vascular and biliary anastomoses are shown. |
With the recipient liver removed, the donor liver is anastomosed to the appropriate structures to place the new liver in an orthotopic position (Fig. 187.1). The suprahepatic caval anastomosis is performed first, followed by the infrahepatic cava and the portal vein. The portal and caval clamps may be removed at this time, allowing reperfusion of the new liver. Either before or after this step, the hepatic artery may be anastomosed.
With the clamps removed and the new organ reperfused, the postanhepatic phase begins, often characterized by marked changes in the patient’s status. The most dramatic changes in hemodynamic parameters usually occur upon reperfusion, with hypotension and the potential for serious arrhythmia. Severe coagulopathy may also develop because of the release of natural anticoagulants from the ischemic liver or active fibrinolysis. Both epsilon aminocaproic acid and aprotinin have been used prophylactically to prevent fibrinolysis and decrease transfusion requirements [27]. Electrolyte abnormalities, most commonly hyperkalemia and hypercalcemia, are often seen after reperfusion; they are usually transient and respond well to treatment with calcium chloride and sodium bicarbonate. After reperfusion of the liver, the final anastomosis is performed, establishing biliary drainage. The recipient’s remaining common
bile duct (choledochoduodenostomy) or a loop of bowel (choledochojejunostomy) may be used.
bile duct (choledochoduodenostomy) or a loop of bowel (choledochojejunostomy) may be used.
 Figure 187.2. Illustration of “piggyback” liver transplant procedure with preservation of the recipient’s inferior vena cava. |
Several variations of the standard operation have been described, including the “piggyback technique.” Here the recipient’s inferior vena cava is preserved, the infrahepatic donor cava is oversewn, and the suprahepatic cava is anastomosed to the confluence of the recipient hepatic veins (Fig. 187.2). With this technique, the recipient’s cava does not have to be completely crossclamped during anastomosis—thus allowing blood from the lower body to return to the heart uninterrupted, without the need for VVB. In spite of the potential advantages of the “piggyback technique,” this procedure is precluded, for obvious reasons, in patients with tumors involving retrohepatic vena cava or main hepatic veins.
The surgical procedure for children does not differ significantly from that for adults. However, the size of the recipient is a significantly more important variable and has an impact on both the donor and the recipient operations.
For pediatric patients (especially infants and small children), the chance of finding a size-matched cadaver graft may be very small: the vast majority of cadaver donors are adults. Accordingly, pretransplant mortality used to be very high in pediatric patients. As a result, three procedures evolved from the principle that a liver is made up of several self-contained segments, each with its own vascular inflow, vascular outflow, and biliary drainage. As a result of these three procedures (namely, reduced-size liver transplants, living related liver transplants, and split-liver transplants), pediatric waiting list mortality rate is now very low.
Reduced-Size Liver Transplants
The earliest efforts involved tailoring a whole-cadaver graft on the back table to fit the recipient. A portion of the liver, such as the right lobe or extended right lobe, was resected and discarded. The remaining left lateral segment was then used for transplant. Reduced-size liver transplant (RSLT) significantly reduced waiting times for children, but negatively affected the adult recipient pool.
Living Donor Liver Transplant
Living donor liver transplant (LDLT) is a natural extension of RSLT. Usually, the left lateral segment from an adult is used (Fig. 187.2), providing sufficient liver tissue for children up to 25 kg. Advantages include the ability to perform the transplant before the recipient deteriorates clinically and the ability to select an ideal donor. The main disadvantage, obviously, is the risk to the donor.
Split-Liver Transplants
With this technique, an adult cadaver liver is divided into two functional grafts: the left lateral segment (which can be transplanted into a child) and the remaining right trisegment (which can be transplanted into an adult). Most split-liver transplants (SLTs) are now performed in vivo: the liver is divided in the cadaver, in a similar fashion to the LDLT procedure. SLT overcomes the disadvantages of both LDLT and RSLT while increasing the donor pool.
Because the severe shortage of organs, partial transplants, either a living donor transplant or a deceased donor split-liver transplant, are being increasingly used for adult recipients also. Usually, in LDLTs for pediatric recipients, the left lateral segment is used; for adult recipients, however, this would be inadequate liver mass and so usually the right lobe is used. Split-liver transplants from deceased donors involve dividing the donor liver into two segments, each of which is subsequently transplanted.
The greatest advantage of a LDLT is that it avoids the waiting time seen with deceased donor organs. In the United States, over 16,500 people are now waiting for liver transplants, but only 6,000 transplants are performed every year (UNOS/OPTN, www.optn.transplant.hrsa.gov/, accessed August, 2009) [6]. Approximately, 15% to 25% of the candidates will die of their liver disease before having the chance to undergo a transplant. For those who do end up receiving a transplant from a deceased donor, the waiting time can be significant, resulting in severe debilitation. With a LDLT, this waiting time can be bypassed, allowing the transplant to be performed before the recipient’s health deteriorates further. In 2007, 266 LDLTs were performed in the United States, accounting for 4% of the total liver transplants performed that year.
A partial hepatectomy in an otherwise healthy donor is a significant undertaking, so all potential donors must be very carefully evaluated. Detailed medical screening must ensure that the donor is medically healthy; radiologic evaluation must ensure that the anatomy of the donor’s liver is suitable; and a psychosocial evaluation must be done to ensure that the donor is mentally fit and not being coerced. The decision to donate should be made entirely by the potential donor after careful consideration of the risks and of the potential complications, with no coercion from anyone.
The overall incidence of donor complications after living donor liver donation ranges from 5% to 10%. There is also a small risk (< 0.5%) of death [28,29]. Of note, mortality is higher for adult-to-adult donation (0.24% to 0.4%) compared with adult-to-child donation (0.09% to 0.2%). This is explained by the fact that adult-to-child donation usually removal of a smaller portion of the liver. Bile duct problems are the most worrisome complication after donor surgery. Bile may leak from the cut surface of the liver or from the site where the bile duct is divided. That site may later become strictured. Generally, bile leaks resolve spontaneously with simple drainage. Strictures and sometimes bile leaks may require an ERCP and stenting. If the above measures fail, a reoperation may be required. Intra-abdominal infections developing in donors are usually related to a biliary problem. Other complications after donor surgery may include incisional problems such as infections and hernias. The risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is the same as for other major abdominal procedures.
The recipient operation with LDLTs is not greatly different from whole-organ deceased donor liver transplants. The hepatectomy is performed in a similar fashion—the cava should be preserved in all such cases, because the graft will generally only have a single hepatic vein for outflow. This is then anastomosed directly to the recipient’s preserved vena cava. Outflow problems tend to be more common with partial versus whole transplants, especially with right lobe transplants (which, again, are usually used for adult recipients). Various methods have been described to improve the outflow of the graft, such as including the middle hepatic vein with the graft, reimplanting accessory hepatic veins, and reimplanting large tributaries that drain the right lobe into the middle hepatic vein [30,31,32]. Inflow to the graft can be reestablished by anastomosing the donor’s hepatic artery and portal vein branch to the corresponding structures in the recipient.
Another method to increase the number of liver transplants is to split the liver from a deceased donor into two grafts, which are then transplanted into two recipients [33]. Thus, a whole adult liver from such a donor can be divided into two functioning grafts. The vast majority of split-liver transplants have been between one adult donor and two pediatric recipients. Splitting one adult liver for two pediatric recipients has no negative impact on the adult donor pool, but it does not increase it either. Adults now account for the majority of patients awaiting a transplant—and the majority of patients dying on the waiting list. Therefore, if split-liver transplants are to have a significant impact on waiting list time and mortality, they must be performed so that the resulting two grafts can also be used in two adult recipients [34]. The worry is that the smaller of the two pieces would not be sufficient to sustain life in a normal-sized adult. However, with appropriate donor and recipient selection criteria, a small percentage of livers from deceased donors could be split and transplanted into two adult recipients.
Recently, the use of organs from donors after cardiac death (also referred as non-heart–beating donors) has emerged as an important source of organs in response to the significant growth of the waiting list. DCD involves those donors who present a severe neurological injury and/or irreversible brain damage but still have minimal brain function. Therefore, DCD offers the patient and the family the opportunity to donate when criteria for brain death will not have been met [7,8,9]. Two different types of DCD are described. Controlled DCD involves planned withdrawal of ventilatory and organ-perfusion support, most often in the operating room with a surgical team readily available (Maastricht III). In contrast, uncontrolled DCD sustains an unexpected cardiopulmonary arrest and either fails to respond to resuscitation or is declared dead on arrival to the hospital (Maastricht I, II, and IV). The number of DCD liver allografts has gradually increased, and now represents approximately 5% of all liver transplants performed in the United States. In 2000, only 11 centers used DCD livers, increasing to 62 centers in 2007 [8].
Because of the constant imbalance between the number of available organs and the number of candidates for liver transplant, organs that were previously thought to be associated with an unacceptably high risk of initial poor function have been used to increase the donor pool. These organs obtained from the so-called expanded criteria donors have been used with an increase rate of primary nonfunction (PNF).
In 2006, a retrospective study using characteristics of more than 20,000 donors identified several factors that were associated with an increase risk of graft loss. These factors were used to generate a “donor risk index,” which is directly related to a predicted rate of graft survival. Six donor/graft characteristics are as follows: (1) donor age over 40 (particularly over 60), (2) donation after cardiac death, (3) African American race, (4) shorter in height, (5) cerebrovascular accident as cause of death and (6) use of partial grafts, were significantly associated with graft failure. In parallel to the recipient risk score (i.e. MELD score) the donor risk index may help to optimize the donor/recipient matching. However, the potential benefit of utilization of this score in organ allocation remains to be determined [35].
Postoperative Care
The postoperative course can range from smooth to extremely complicated, depending mainly on the patient’s preoperative status and the development of any complications. The care of all such patients involves (1) stabilization and recovery of the major organ systems (e.g., cardiovascular, pulmonary, renal); (2) evaluation of graft function and achievement of adequate immunosuppression; and (3) monitoring and treatment of complications directly and indirectly related to the transplant.
Initial Stabilization
The initial care immediately posttransplant should be performed in an intensive care unit (ICU) setting. Recipients generally require mechanical ventilatory support for the first 24 to 48 hours. The goal is to maintain adequate oxygen saturation, acid base equilibrium, and stable hemodynamics. Guidelines for extubation are no different from the standard postoperative patient: a level of consciousness sufficient to protect the airway and the ability to maintain adequate oxygenation and ventilation. As well, there should be some indication of function of the new graft prior to attempting extubation. After extubation, it is crucial to continue with aggressive physiotherapy, deep breathing exercises, and ambulation to reduce the typically high incidence of respiratory complications.
Continuous hemodynamic monitoring should be maintained via an arterial line and pulmonary artery catheter. Information obtained should be used to ensure adequate perfusion of the graft and vital organs. The preoperative hyperdynamic circulatory state will often persist into the postoperative period. Later, as hepatic function improves, the cardiac index progressively declines and the SVR increases toward normal values. However, the myocardial dysfunction that is often seen early in the reperfusion phase may persist, with decreased compliance and contractility of the ventricles. The cause of this myocardial depression is unclear, but may be related to the release of vasoactive substances after reperfusion of the ischemic liver and decompression of the portal circulation. The usual treatment is to optimize preload and afterload, and inotropic agents such as dopamine or dobutamine.
To assess for possible bleeding, serial hematocrits should be measured initially every 4 to 6 hours. Coagulation parameters
(prothrombin time, partial thromboplastin time, thrombin time) need to be carefully monitored because of frequent coagulopathy, most likely related to intraoperative blood loss and temporary ischemic damage in the revascularized new liver. Other laboratory values to monitor include serum transaminases and serum bilirubin. Normalization of these values, along with improvement in mental status and renal function, are valuable indicators of good graft function.
(prothrombin time, partial thromboplastin time, thrombin time) need to be carefully monitored because of frequent coagulopathy, most likely related to intraoperative blood loss and temporary ischemic damage in the revascularized new liver. Other laboratory values to monitor include serum transaminases and serum bilirubin. Normalization of these values, along with improvement in mental status and renal function, are valuable indicators of good graft function.
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