How would liver failure affect pulmonary function? What evaluation of pulmonary function would be helpful for this case? Would bronchodilator therapy be indicated preoperatively?

What cardiovascular abnormalities would you expect in this patient?

Is this patient exhibiting hepatic encephalopathy? Does she have raised ICP? What treatments should be given for each of these problems?

What is the relationship between ESLD and impaired renal function? Is the hepatorenal syndrome present?

Is this patient at risk for gastrointestinal hemorrhage? Would the presence of a portosystemic shunt affect the pre-op evaluation?

What disorders of the hematologic system would be expected in their patient?

How should she be evaluated for metabolic abnormalities?

Children with liver disease severe enough to be candidates for transplantation nearly always have abnormal pulmonary function [1–3]. Restrictive lung disease is caused by ascites in these children. In addition to the peritoneal space, there may be abnormal transudation of fluid in the pleural space. Pleural effusions will also compromise pulmonary function. Abdominal distention also decreases the functional residual capacity (FRC). These children are often malnourished, and the muscles of respiration, the diaphragm, and intercostal muscles are weakened, leading to a further decrease in the FRC. In addition to restrictive pulmonary pathophysiology, these children have other reasons for hypoxemia. The hepatopulmonary syndrome of hypoxemia and intrapulmonary shunts in these patients contributes to pulmonary morbidity. Intrapulmonary shunting of blood and impaired hypoxic pulmonary vasoconstriction lead to lower hemoglobin saturation. Pulmonary hypertension with increased pulmonary vascular resistance (PVR) can affect right ventricular performance. A small subset of patients with severe liver disease will manifest pulmonary hypertension.

Children with end-stage liver disease (ESLD) presenting for transplantation have significant derangements of cardiovascular function [4, 5]. These children have an increased cardiac output, increased ejection fraction, and lowered systemic vascular resistance (SVR). Peripheral vasodilatation and arteriovenous shunts account for the lower SVR. The circulating plasma volume is increased. The etiology of the hyperdynamic state of the circulatory system is unclear. Although children with liver failure generally have preserved cardiac function, those with severely advanced disease can exhibit impaired left ventricular performance. S_vO₂ is often elevated, probably due to the A–V shunts and to decreased oxygen delivery to the tissues. The RBCs in these patients are depleted of 2, 3-DPG and deliver less oxygen to the periphery. These children nearly always have a low albumin as part of ESLD. The Child–Pugh classification system includes serum albumin (along with bilirubin, prothrombin time (PT), and degree of encephalopathy) as one of the factors in determining the severity of liver insufficiency.

Patients with severe liver disease often have CNS changes. The cause for hepatic encephalopathy is not known, but the severity of the CNS dysfunction does parallel the severity of the liver disease. Possible causes for hepatic encephalopathy are the elevated levels of ammonia and other products of metabolism that accumulate as the liver fails, or the appearance of false neurotransmitters derived from amino acids that had not undergone degradation. The encephalopathy usually improves when appropriate therapy for the liver failure is started. Acute worsening of hepatic encephalopathy is usually an indication that the underlying liver disease has also worsened. In situations where more is demanded of the liver such as GI hemorrhage or increased protein intake, hepatic encephalopathy will worsen. Infections or dehydration will also worsen hepatic encephalopathy. Treatment of hepatic encephalopathy includes restriction of protein intake, enteral lactulose, and neomycin and maintenance of as normal a metabolic state as possible [6–9]. If the patient is in fulminant hepatic failure, raised ICP is likely to be present. The exact etiology of the cerebral edema is not known, but vasogenic and cytotoxic mechanisms are thought to contribute. As the cerebral edema worsens, the ICP increases and the patient becomes more and more encephalopathic. Treatment is supportive and includes the usual measures used in the treatment of raised ICP [10]. These include intubation, sedation, and ventilation to modest hypocarbia, mild hypothermia, and treatment of blood pressure to maintain adequate cerebral perfusion pressure (CPP = MAP – ICP or CVP). Placement of an intracranial pressure monitor is necessary to have an accurate measurement of ICP.

Patients with ESLD often also have impaired renal function, secondary to lowered GFR resulting either from dehydration or from having developed the hepatorenal syndrome. Urine sodium concentration is generally low (<10 mEq/L) in both conditions, but in patients with prerenal azotemia, urine output increases, and serum BUN and Cr levels decrease following expansion of the intravascular volume. Patients with hepatorenal syndrome have oliguria and increased BUN levels that are generally not responsive to volume administration. Affected individuals also have ascites, and overly aggressive treatment of the ascites with diuretics may play a role in the development of the syndrome. Often dialysis is needed to reverse the pathophysiologic alterations of the hepatorenal syndrome until liver transplantation, which reverses the syndrome, can be accomplished [11, 12].

Portal hypertension is often part of liver failure [13]. Bleeding from esophageal and gastric varices are major consequences of portal hypertension. A moderately severe episode of GI hemorrhage may tip a patient in tenuous condition into fulminant hepatic failure. Even if the bleeding is controlled, as the blood in the GI tract is metabolized and absorbed, the encephalopathy will worsen, and the episode of hypotension associated with the bleeding episode will worsen the renal ischemia, with the possible development of hepatorenal syndrome. Breakdown of liver glycogen is an important mechanism in the maintenance of normoglycemia. In liver failure, there is diminished breakdown of liver glycogen, making these patients susceptible to episodes of hypoglycemia.

Coagulation abnormalities are quite likely in patients with severe liver insufficiency or failure. In addition, these patients usually are anemic and thrombocytopenic. Fibrinogen, prothrombin, plasminogen, and many other coagulation factors synthesized by the liver are greatly diminished in patients with liver dysfunction/failure. Many patients with liver failure produce an abnormal fibrinogen molecule. In addition, bile salts are needed for absorption of fat-soluble vitamins that includes vitamin K, a cofactor in the production of many coagulation factors. Many interventions by anesthesiologists, such as NG tube placement, intubation, and cannulation of vessels, have the potential to cause bleeding so that correction of coagulation abnormalities often is undertaken prior to the induction of anesthesia. Treatment of the coagulopathy seen in patients with liver failure may require replacement of factors and vitamin K. If platelet dysfunction is evident, DDAVP may be needed.

Patients with liver failure have derangements of many serum electrolytes. Common abnormalities are hypoglycemia and hyponatremia. Elevated BUN and Cr as a result of renal dysfunction are present, and elevated levels of ammonia are thought to be responsible for the encephalopathy [12].

What are the effects of liver disease on pharmacokinetics and dynamics of medications?

What preparations should be made with the blood bank and laboratory support for this case? How will rapid transfusion be accomplished?

Describe special consideration for monitoring and vascular access for this patient and procedure.

How will induction be performed? Does this patient have a full stomach? How does ascites affect the induction plan?

Describe the conduct of maintenance during the procedure.

What problems are expected during the preanhepatic phase?

What is important for the anesthesiologist during the anhepatic phase?

What problems are likely to occur during reperfusion?

What problems are expected during the neo-hepatic/biliary reconstruction phase?

There is a complex set of effects on the action and distribution of medications in patients with liver failure. These patients have a decreased serum albumin, which would lead to an enhanced effect of IV medications given at the usual dose on a mg/kg basis. These patients also have impaired hepatic metabolic function as well as impaired renal function. As a result of these abnormalities, the serum levels of medications will remain high for longer periods of time and will be less bound to protein. In addition, these patients may have depressed cardiovascular and pulmonary function prior to the induction of anesthesia.

Preparation of the OR should be for a long case in which massive blood loss is expected, temperature maintenance will be problematic, invasive hemodynamic monitoring will be needed, and many metabolic derangements will occur [14]. The OR table should be particularly well padded since these cases may last for many hours. Devices for rapid transfusion should be, at the very least, available or fully prepared. In the past, in larger patients, venovenous bypass was used, with the expectation that bowel edema and bleeding would be decreased compared with cases in which the vena cava was simply clamped. This practice is generally no longer used, however, simplifying the intraoperative management of liver transplant patients. The blood bank should be given as much notice as possible in order that the proper amounts and types of blood products are available. As a general guideline, ten units of PRBCs, ten units of FFP, and six to ten units of pooled platelets should be immediately available, with the expectation that more may be needed. Of course, these amounts should be adjusted upward or downward based upon the size and condition of the patient. Throughout the case, many ABGs, sets of electrolytes, coagulation profiles, CBCs, etc. will be sent. It may be necessary to have additional laboratory personnel to run these frequent and multiple tests.

In addition to routine monitors, temperature should be measured in more than one location. Rectal or bladder probes can be used in addition to esophageal probes. Several large IVs are needed, preferably in the upper extremities. During the anhepatic phase of the procedure, when the inferior vena cava (IVC) is clamped, lower extremity venous return will be limited to collateral veins or the venovenous bypass if it is used. Similar considerations apply to the arterial catheter. In some cases, the aorta will be clamped during the arterial anastomosis. Some centers use two arterial catheters. The direct arterial pressure tracing is unavailable during the frequent sampling, and if, because of frequent use, one arterial line fails, the second line will be available. A large, sheath-type central line is used in these cases for monitoring of central venous pressure, administration of vasoactive medications, and also administration of fluids and/or blood products. In general, pediatric patients need not be monitored with a pulmonary artery catheter. On occasions when peripheral IV access is difficult, two central lines may be used.