In most donor anesthesia protocols, maintenance of a CVP less than 5 cm H2O is utilized to reduce intraoperative blood loss. Adequate postoperative analgesia is required so that comfortable donor patients may be extubated at the end of the procedure. TAP blocks meet this need. Complications of this surgery for the donor patient include transient hepatic dysfunction, wound infection, postoperative bleeding, portal vein thrombosis, biliary leaks, and, rarely, death. An increased incidence of perioperative brachial plexus injury has been reported in donor patients.
CASE DISCUSSION Liver Transplantation
A 23-year-old woman develops fulminant hepatic failure after ingesting wild mushrooms. She is not expected to survive without a liver transplant. What are the indications for liver transplantation?
Orthotopic liver transplantation is usually performed in patients with end-stage liver disease who begin to experience life-threatening complications, especially when such complications become unresponsive to medical or nontransplant surgery. Transplantation is also carried out in patients with fulminant hepatic failure (from viral hepatitis or a hepatotoxin) when survival with medical management alone is judged unlikely. The MELD score is used to assess urgency for transplantation.
The most common indications for liver transplantation in children, in order of decreasing frequency, are biliary atresia, inborn errors of metabolism (usually α1-antitrypsin deficiency, Wilson disease, tyrosinemia, and Crigler–Najjar type I syndrome), and postnecrotic cirrhosis.
The most common indications in adults are postnecrotic (nonalcoholic) cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis, and, less commonly, primary malignant tumors in the liver. What factors have contributed to the recent success of liver transplantation?
One-year survival rates for liver transplantations exceed 80% to 85% in some centers. Currently, 5-year survival rates are 50% to 60%. The success of this procedure owes much to the use of cyclosporine and tacrolimus for immunosuppressant therapy. These drugs selectively suppress the activities of helper T cells (CD4 lymphocytes) by inhibiting production of interleukin-2 (IL-2) and other cytokines. IL-2 is required for the generation and proliferation of cytotoxic T cells responsible for graft rejection and for activating B cells responsible for T cell-dependent humoral responses. Cyclosporine is usually initially combined with corticosteroids and other agents (eg, mycophenolate and azathioprine). Tacrolimus has proved effective in cyclosporine-resistant rejection and is the preferred alternative to cyclosporine as the primary immunosuppressant agent. The use of anti-OKT-3, a monoclonal antibody directed against lymphocytes, has been extremely useful in treating steroid-resistant acute rejection.
Additional factors influencing the improvement in liver transplantation outcome include a greater understanding and experience with transplantation and improved assessment and monitoring with echocardiography. What are the phases of the transplantation surgical procedure?
These procedures can be divided into three phases: a dissection (preanhepatic) phase, an anhepatic phase, and a neohepatic phase.
What major problems complicate anesthesia for liver transplantation?
Dissection (preanhepatic) phase: Through a hockey stick incision, the liver is dissected so that it remains attached only by the inferior vena cava and portal vein. The hepatic artery, and common bile duct are ligated. Large abdominal varices may prolong the duration of, and increase the blood loss associated with, this phase.
Anhepatic phase: Once the donor liver graft is ready, the portal vein is clamped, followed by the inferior vena cava above and below the liver. The liver is then lifted out of the abdomen. Venovenous bypass maybe employed during this phase. The donor liver is then anastomosed to the supra- and infrahepatic inferior venae cavae and the portal vein.
Revascularization and biliary reconstruction (neohepatic or postanhepatic) phase: Following completion of the venous anastomoses, venous clamps are removed from the cava, allowing venous blood to return to the heart. Next, the portal vein is slowly opened, allowing blood to flush out preservation fluid and other substances accumulated in the liver during its ischemic time. This reperfusion may result in hypotension, arrhythmias, or cardiac arrest—a scenario termed the reperfusion syndrome. The circulation to the new liver is completed by anastomosing the hepatic artery. Lastly, the common bile duct of the donor liver is then usually anastomosed to the recipient using the recipient’s common bile duct or a Roux-en-Y choledochojejunostomy.
Potential problems include multiorgan dysfunction caused by cirrhosis, massive blood loss, hemodynamic instability from clamping and unclamping the inferior vena cava and portal vein, metabolic consequences of the anhepatic phase, and air embolism and hyperkalemia.
Preoperative coagulation defects, thrombocytopenia, and previous abdominal surgery greatly increase blood loss. Extensive venous collaterals between the portal and systemic venous circulations also contribute to increased bleeding from the abdominal wall. Potential complications of massive blood transfusion include hypothermia, coagulopathies, hyperkalemia, citrate intoxication (hypocalcemia), and the potential transmission of infectious agents. Blood salvaging techniques are useful in reducing donor red blood cell transfusion. What is adequate venous access for these procedures?
Bleeding is a recurring problem during each phase of liver transplantation. Adequate venous access is paramount in anesthetic management. Several large-bore (14-gauge or larger) intravenous catheters should be placed above the diaphragm. Specialized 8.5FR catheters can be placed in antecubital veins and used in conjunction with rapid infusion devices. Most centers place a large-bore central venous catheter. Efforts to minimize the risk of hypothermia should include the use of fluid warming and forced-air surface warming devices. What monitoring techniques are most useful during surgery?
All patients require direct intraarterial pressure monitoring. A central venous catheter should be available. Goal-directed hemodynamic and fluid management utilizing arterial pulse wave analysis, esophageal Doppler, PVI, or TEE is common. Urinary output should be monitored throughout surgery via an indwelling urinary catheter.
Laboratory measurements constitute an important part of intraoperative monitoring. Serial hematocrit measurements guide red blood cell replacement. Similarly, frequent measurements of arterial blood gases, serum electrolytes, serum ionized calcium, and serum glucose are necessary to detect and appropriately treat metabolic derangements. Coagulation can be monitored by measuring PT, activated partial thromboplastin time, fibrinogen level, and platelet counts, and by point-of-care viscoelastic coagulation analysis—TEG, ROTEM, or Sonoclot analysis. These latter modalities not only assess overall clotting and platelet function, but can also detect fibrinolysis. What anesthetic technique may be used for liver transplantation?
Most patients should be considered as having a “full stomach,” often because of marked abdominal distention or recent upper gastrointestinal bleeding. General anesthesia is usually induced via a rapid sequence induction. The semiupright (back up) position during induction prevents rapid oxygen desaturation and facilitates ventilation until the abdomen is open. Hyperventilation should be avoided unless there is increased intracranial pressure. Anesthesia is generally maintained with a volatile agent (usually isoflurane or sevoflurane), and an intravenous opioid (usually fentanyl or sufentanil). The concentration of the volatile agent should be limited to less than 1 minimum alveolar concentration in patients with severe encephalopathy. Nitrous oxide is usually avoided. Many patients are routinely transferred to the intensive care unit intubated and mechanically ventilated at the end of the operative procedure, although immediate postoperative extubation may be considered if the patient is comfortable, cooperative, physiologically stable, and not hemorrhaging significantly. What physiological derangements are associated with the anhepatic phase?
When the liver is removed, the large citrate load from blood products is no longer metabolized and results in hypocalcemia and secondary myocardial depression. Periodic calcium chloride administration (1 g) is necessary, but should be guided by ionized calcium concentration measurements to avoid hypercalcemia. Progressive acidosis is also encountered because acid metabolites from the intestines and lower body are not cleared by the liver. Sodium bicarbonate therapy may be necessary and should similarly be guided by arterial blood gas analysis. Excessive administration of sodium bicarbonate results in hypernatremia, hyperosmolality, and accentuation of the metabolic alkalosis that typically follows massive blood transfusions. Tromethamine should be considered when large amounts of alkali therapy are necessary. Although hypoglycemia can occur during the anhepatic phase, hyperglycemia is a more common occurrence following reperfusion.
Pulmonary and systemic (paradoxic) air embolism can occur when the circulation is fully reestablished to the donor liver because air often enters hepatic sinusoids after harvesting. Systemic air embolism probably reflects the fact that many of these patients have extensive arteriovenous communications. The anhepatic phase ends when the three venous clamps are removed and the donor liver is perfused. Thromboembolic phenomena are also possible following reperfusion. What problems may be anticipated during the revascularization phase?
Perfusion of the donor liver by the recipient’s blood often results in transiently increased serum potassium concentration of up to 1 to 2 mEq/L and increased systemic acidosis. Reperfusion releases potassium from any remaining preservative solution (115–120 mEq/L of potassium) still within the liver, as well as potassium released from tissues distal to venous clamps. Unclamping may also release a large acid load from ischemic tissue in the lower body (particularly without venovenous bypass); preemptive administration of sodium bicarbonate is advocated by some.
When the circulation to the new liver is established, the sudden increase in blood volume, acidosis, and hyperkalemia can produce tachyarrhythmias, or, more commonly, bradyarrhythmias. In addition to calcium chloride and sodium bicarbonate, inotropic support is also often required. Hyperfibrinolysis is commonly present and seems to be due to a marked increase in tissue plasminogen activator and a decrease in plasminogen activator inhibitor and α2-antiplasmin during the anhepatic phase. Fibrinolysis can be detected by point-of-care viscoelastic coagulation analysis. ε-Aminocaproic acid or tranexamic acid, which inhibit the formation of plasmin, may be indicated in those instances, but should not be used prophylactically. What problems are encountered postoperatively?
Patients often have an uncomplicated postoperative course and, after a sufficient period of observation in the intensive care unit, may be transferred directly to the nursing unit designed for liver transplant patients. Problems to anticipate include graft dysfunction or failure, persistent hemorrhage, fluid overload, metabolic abnormalities (particularly metabolic alkalosis and hypokalemia), respiratory failure, pleural effusions, acute kidney injury or failure, systemic infections, and surgical complications (eg, bile leaks or stricture, or thrombosis of the hepatic or portal vessels). The last two complications may become suspect during ultrasound examination and are confirmed by angiography. Neurological complications include seizures, intracranial hemorrhage, encephalopathy, osmotic demyelination syndrome from a sudden increase in serum sodium, and immunosuppressant-related neurotoxicity. Contributory factors for acute kidney injury or failure include periods of hypotension, impaired kidney perfusion when the inferior vena cava is clamped (resulting in high pressures in the renal veins), and cyclosporine or antibiotic nephropathy. Measurement of immunosuppressant levels may be helpful in avoiding toxicity.
Prophylactic antibiotics and antifungal agents are routinely given in many centers because of a high incidence of infections.
Graft function is usually monitored by the PT, serum bilirubin, aminotransferase activity, and serum lactate measurements. Diagnosis requires liver biopsy.