Annual performance of multiorgan transplantation including the liver. (a) Annual incidence of heart–liver (HLT) and lung–liver transplantation (LULT) in the United States. (b) Annual incidence of liver–kidney (LKT) transplantation in the United States. (Data from United Network for Organ Sharing .)
Multiorgan transplantation is a unique challenge to the anesthesiologist due to the complex physiology of multiple impaired organ systems and potential conflicting management goals for each transplanted allograft. This chapter will discuss anesthetic considerations of combined organ transplantation including liver–kidney transplantation (LKT), heart–liver transplantation (HLT), and lung–liver transplantation (LULT).
Combined Liver–Kidney Transplantation (LKT)
The adoption of the model for end-stage liver disease (MELD) score in 2002 as the basis for liver allograft allocation has resulted in an increase in the annual incidence of LKT (Fig. 30.1) [1–3]. Renal insufficiency is common, occurring in approximately 30 % of patients awaiting OLT [4, 5]. Renal insufficiency in the setting of end-stage liver disease can be broadly categorized as: (a) acute kidney injury (AKI) secondary to prerenal azotemia, hepatorenal syndrome, or acute tubular necrosis, and (b) chronic kidney disease (CKD) secondary to glomerulonephritis, polycystic kidney disease, and primary hyperoxaluria .
The duration and degree of renal insufficiency prior to OLT correlate with posttransplant renal dysfunction [5, 7, 8]. Northup et al. analyzed a large cohort of OLT recipients who received renal replacement therapy while waiting for transplantation between 2002 and 2007 to identify predictors of spontaneous recovery of renal function following transplantation . Pretransplant variables independently associated with recovery of renal function included short duration of therapy, lower recipient age, absence of diabetes, and younger donor age. Of these, pretransplant duration of hemodialysis was the most predictive of spontaneous renal recovery as recipients requiring <30 days of renal replacement therapy were likely to experience spontaneous recovery while those requiring >90 days were unlikely to recover . Unfortunately, the vast majority of patients fall between these two extremes with few data available to support evidence-based recommendations.
Post-OLT renal dysfunction, particularly the need for hemodialysis, significantly increases morbidity and mortality [4, 9]. An SRTR analysis of cirrhotics with renal failure who received either OLT or LKT between 2002 and 2008, demonstrated significantly greater graft and patient survival among LKT recipients; particularly LKT for renal failure secondary to hepatorenal syndrome . However, LKT remains controversial because of insufficient data to formulate consistent guidelines on identification of candidates who will derive benefit.
The International Liver Transplantation Society hosted a consensus conference on renal insufficiency among OLT candidates that proposed specific criteria for LKT (Table 30.1) . Despite these recommendations, variability continues among centers with respect to the length of time AKI is tolerated prior to listing for LKT.
Criteria for simultaneous liver–kidney transplantation 
1. End-stage renal disease and dialysis
2. No dialysis with a glomerular filtration rate <30 mL/min and proteinuria >3 g/day with a 24-h urine protein/creatinine ratio >3
3. Acute kidney injury and a requirement for dialysis at least 2 times per week for more than 6 weeks
The decision to list a patient for LKT who has previously been an isolated OLT candidate is a clinical dilemma with significant ramifications. Avoiding chronic hemodialysis is obviously beneficial as hemodialysis, either pre or posttransplant, are each independent predictors of post-OLT mortality [4, 9, 11]. However, the addition of a renal allograft for LKT reduces the available donor pool, increases wait-list mortality, and denies renal transplant candidates an opportunity.
Detailed preoperative evaluation focusing upon the etiology of hepatic and renal failure is prerequisite to accurate prediction of the need for LKT. In these complex patients, clinical investigation of renal function should focus upon the last documentation of adequate glomerular filtration rate, abdominal imaging of the kidneys, and evidence of proteinuria as a renal biopsy is often precluded by the patient’s underlying coagulopathy. Deterioration of renal function in a candidate with a history of renal insufficiency, ultrasound evidence of abnormal renal anatomy, or significant proteinuria prompts earlier consideration of LKT. As these patients demonstrate dual organ system failure with a significantly higher probability of wait-list mortality, the astute practitioner should perform thorough surveys of additional organ involvement including neurologic, cardiac, pulmonary, and hematologic pathology.
Vascular access may be difficult due to previous or preexisting central venous catheters, arteriovenous fistulas, or lack of venous access. Preoperative venous mapping utilizing magnetic resonance imaging is superior to computed tomography and ultrasound for the evaluation of venous patency, anatomy, and the presence of stenoses. Ultrasound guidance at central venous cannulation is recommended, particularly in the presence of a coagulopathy or atypical vascular anatomy. For the liver transplant procedure, femoral arterial cannulation for monitoring and femoral venous access for veno-venous bypass (VVB) or continuous renal replacement therapy (CRRT) may be necessary. Prior to any catheter placement involving the femoral vessels, the intended site for renal allograft implantation should be verified and protected .
Pretransplant hemodialysis to optimize electrolyte concentrations prior to the large-volume resuscitation, blood transfusions, and electrolyte shifts expected during OLT is recommended. Electrolyte stability during OLT is enhanced further by intraoperative CRRT and packed red blood cell mass washing prior to transfusion [13, 14].
The operative sequence is determined by the allograft with the lowest tolerance to cold ischemia. In LKT, implantation of the liver precedes the kidney. In general, the anesthetic considerations of LKT are similar to OLT but LKT recipients can be expected to display greater variation in volume status and electrolyte imbalance. Long-standing renal failure also portends a higher incidence of cardiac and peripheral vascular disease.
Patient preparation for LKT is similar to OLT. Patient positioning should be meticulous with special attention to avoiding compression of an arteriovenous fistula or hemodialysis access graft . Verification of the incision and location for renal transplantation prior to performing the operation by anesthesiologists, surgeons, and nursing is prerequisite to avoid unwanted skin incisions, drain placements, or venous catheter insertions that may compromise the renal transplant procedure.
Rapid sequence induction is recommended due to the increased risk of aspiration from uremia and ascites. Hypotension during anesthetic induction may result from intravascular volume depletion secondary to hemodialysis or chronic diuretic therapy for the management of ascites. Judicious volume loading prior to induction, principally through the administration of blood products to offset the recipient’s coagulopathy, improves hemodynamics while optimizing the recipient for intraoperative monitor placement. Typical intraoperative monitoring and access include a radial arterial catheter, a femoral arterial catheter, two large bore peripheral veins, and a central venous high flow conduit. In addition, the patient should have a pulmonary artery catheter (PAC) or intraoperative transesophageal echocardiogram (TEE) for evaluation of volume status and assessment of cardiac function. Early establishment of adequate monitoring is essential to optimize these patients’ precarious physiology.
Fluid management is challenging in the setting of renal failure as large-volume blood replacement and rapid electrolyte shifts occur during OLT. Crystalloid administration should be tempered as targeted blood and blood product administration form the mainstay of infusion therapy. Observation of the surgical field, as well as communication with the surgeon as to the amount of ascitic drainage and the formation of thrombus avert acute hypovolemia and facilitate resuscitation. Fluid management is further guided by acid-base data from arterial blood gases, lactate levels, PAC pressures, or TEE data.
Electrolyte abnormalities are inevitable in the performance of major surgery and the ability of the anesthesiologist to address issues other than the short-term correction of hyperkalemia, hypocalcemia, and hypomagnesemia is limited. Frequent laboratory analysis and monitoring of serum sodium is critical as crystalloid and colloid solutions utilized in resuscitation contain significant amount of sodium, and acute increases in sodium may result in central pontine myelinolysis . Sodium bicarbonate may be required intraoperatively to treat acidosis and hyperkalemia during liver allograft reperfusion; however, these ampules may contain as much as 1000 mEq/L of sodium that can accelerate hypernatremia. Hyperkalemia is frequent in the setting of renal insufficiency and may be problematic during liver transplantation as a result of large-volume blood transfusion and ischemia/reperfusion injury. In our center, the perfusionist is able to “wash” blood products to minimize the amount of potassium administered during blood transfusion. Intraoperative CRRT is useful in promoting electrolyte stability during LKT [13, 14].
During renal transplantation, fluid resuscitation is the mainstay for the treatment of hypotension as the use of vasopressors potentiates renal allograft vasoconstriction. However, overzealous fluid infusion may precipitate hepatic venous congestion and parenchymal dysfunction. Isotonic crystalloid solutions are the first choice for volume restoration in renal transplantation, but in the setting of severe hypovolemia, colloid solutions are ideal in restoring intravascular volume and tissue perfusion . Hypotension refractory to adequate fluid therapy and blood transfusion may respond to dopamine . Diuretics such as mannitol and furosemide are frequently administered during renal allograft reperfusion; however, their use in LKT should be tempered to avoid overdiuresis that can promote portal vein thrombosis.
Postponing kidney transplantation to promote stabilization and resuscitation of the patient in the intensive care unit following liver transplantation can be a distinct advantage in scenarios where the patient is profoundly coagulopathic, hemodynamically unstable, or requires excessive vasopressor support upon completion of liver transplantation. In these situations, a 6–12 h delay to optimize the recipient’s physiology through improved hemostasis and reduced vasopressor requirements is unlikely to affect long-term renal function.
The postoperative course for the LKT recipient is dependent upon the duration of surgery as well as early allograft function. Communication among the various teams is essential as the management and goals of care for each specific organ-system may not be parallel. Hepatic allograft dysfunction manifests as refractory acidemia, coagulopathy, hypoglycemia, and encephalopathy with subsequent acute kidney injury. Renal allograft dysfunction manifests as oliguria with subsequent electrolyte imbalance. Doppler ultrasound evaluation of the transplanted allografts in the setting of early dysfunction may demonstrate vascular abnormalities that could trigger reexploration .
Hypotension in the postoperative period is typically the result of hypovolemia or hemorrhage but may be secondary to arrhythmias from electrolyte imbalance, acidemia, or vasodilatory shock. Frequent assessment of abdominal drains and laboratory analyses are essential. In the setting of refractory hypotension, an echocardiogram to supplement PAC data can guide treatment. In general, maintaining a target urine output may not be appropriate in the setting of LKT as the practice of large-volume crystalloid boluses to enhance renal perfusion followed by high dose diuretic administration to promote urine production can be harmful to the hepatic allograft as high central venous pressures precipitate hepatic congestion with subsequent hepatocyte dysfunction. Conversely, overdiuresis results in hypotension, reduced portal venous flow, and a potentially hypercoagulable state that may precipitate portal venous thrombosis. LKT recipients may require a brief period of hemodialysis until the transplanted kidney assumes sufficient function.
Immunosuppression will vary according to the recipient’s indication for LKT and any previous history of a preexisting solid-organ transplant. In general, immunosuppressive regimens are guided by the liver allograft and typically avoid the antibody induction regimens commonly employed in renal transplantation.
Combined Heart–Liver Transplantation
Combined heart and liver transplantation (HLT), originally described by Thomas Starzl in 1984, has been increasingly accepted as a therapeutic option for patients suffering from concomitant cardiac and hepatic failure as well as certain metabolic disorders . While HLT remains an infrequent procedure, its incidence has steadily risen with excellent outcomes reported (Fig. 30.1) [19–23]. In fact, HLT recipient 1- and 5-year survival are comparable to recipients of isolated cardiac or liver transplantation, reflecting precise identification of appropriate HLT candidates and restriction of the procedure to centers with robust cardiac and hepatic transplantation programs .
HLT candidates can be fundamentally divided into two categories: those candidates where the liver is being replaced to support cardiac function and those candidates who demonstrate true dual organ failure  (Table 30.2). Metabolic diseases, such as familial amyloidosis and familial hypercholesterolemia, involve a genetic defect of the liver that results in cardiac failure . For these indications, the role of the hepatic allograft in HLT is to provide a gene product to support the newly transplanted cardiac allograft. Explanted livers from metabolic disease candidates appear normal and these candidates do not exhibit manifestations of end-stage liver disease. The absence of coagulopathy, thrombocytopenia, or portal hypertension simplifies the liver transplant procedure and facilitates recovery. These candidates are distinctly different from the true dual organ failure population where portal hypertension and its complications are present, resulting in a patient who is significantly more debilitated at the time of HLT.
Indications for combined heart liver transplantation
I. Metabolic diseases
II. Dual-organ failure
Congenital heart disease
Idiopathic dilated cardiomyopathy
Ischemic dilated cardiomyopathy
HLT candidates are currently underserved by United Network for Organ Sharing (UNOS) allocation policy that prohibits cardiac and liver allografts from allocation as a single unit [24, 25]. As a result, HLT waitlist mortality is greater than predicted by the sum of MELD and cardiac status scores with fewer than 30 % of patients listed nationally for HLT receiving transplantation .
Meticulous preoperative preparation for HLT is essential as time is limited when organs are available. Ideally, this occurs among the cardiac and liver transplant teams at the time of listing with periodic review. The preoperative evaluation should include extra-cardiac and extra-hepatic organ system assessment, recent laboratories, vasoactive medications including infusions, the presence of an implantable cardioverter-defibrillator or an intra-aortic balloon pump. A thorough understanding of the indications for HLT provides guidance in candidate assessment with respect to the operative strategy and anticipated difficulty.
Patients with coexisting cardiac and hepatic disease are predisposed to pulmonary hypertension which may manifest as a result of ischemic, idiopathic, or cirrhotic cardiomyopathy, hepatopulmonary syndrome, or portopulmonary hypertension. In assessing cardiac function, recent testing, including an echocardiogram and cardiac catheterization to determine pulmonary vascular resistance and reversibility of pulmonary hypertension, is critical. Irreversible or “fixed” pulmonary hypertension is a contraindication to HLT because of the high risk of right heart failure and early morbidity .
The physiology of cirrhosis and cardiac failure complicates the anesthetic management of HLT . Catheter derived pressures supplemented by TEE are useful in guiding therapy. Standard patient monitoring includes: arterial catheter, PAC, and TEE. Rapid sequence induction is indicated for a variety of reasons including inadequate NPO status, gastroparesis, dysmotility, and ascites. Hypotension at induction may result from a preexisting cardiomyopathy or decreased systemic vascular resistance that is characteristic of the hyperdynamic cardiac physiology observed in cirrhotics . Balanced anesthesia utilizing opioids, muscle relaxants, and low dose volatile anesthetics minimizes vasopressor requirements.
HLT begins with implantation of the cardiac allograft as the heart demonstrates the least tolerance to cold ischemia and improved cardiac function supports early hepatic allograft function. Numerous HLT operative strategies have been reported and range widely from complete cardiac transplantation with sternal closure before proceeding with abdominal dissection to maximal abdominal dissection before initiating cardiopulmonary bypass (CPB) [29, 30]. The key to evaluating an operative strategy is recognition of the two fundamentally different HLT patient populations as the aim should be to minimize the duration of extracorporeal circulation with its associated complications of coagulopathy, hypothermia, and metabolic abnormalities .
The most reported surgical approach is cardiac transplantation performed first followed by interruption of extracorporeal circulation and heparin neutralization [20, 21, 23]. With the mediastinum open, liver transplantation is performed by caval sparing hepatectomy (piggyback technique) or caval excision with or without veno-venous bypass (VVB) [20, 21, 23, 30, 32]. Sternotomy closure is delayed until the risk of tamponade is minimal. Advantages of this technique include short periods of cardiac allograft ischemia and a decreased length of CPB, thereby reducing blood loss and transfusion requirements. While this technique reduces the period of anticoagulation, it increases hepatic allograft cold ischemia.
Alternatively, the performance of both cardiac and hepatic transplantation while on CPB has been advocated . In this technique, the cardiac and hepatic dissections are concomitantly performed with exposure of the hepatic vasculature. CPB is initiated and the cardiac transplant completed. With the newly transplanted heart beating and CPB maintained, the liver transplant procedure is performed. The patient is then weaned from CPB and the chest is closed. The procedure concludes with the biliary anastomosis and abdominal closure. The authors noted decreased blood transfusion requirements despite CPB but required high doses of anti-fibrinolytic therapy. Potential advantages of this approach include decreased hepatic cold ischemia and improved hemodynamic stability by avoidance of hepatic reperfusion upon the transplanted heart .