Patients with ESLD undergoing liver transplantation often present with hyperdynamic circulatory conditions, portal hypertension, portopulmonary hypertension, right heart failure, hepatopulmonary syndrome, cardiomyopathy, and pleural effusion. Systemic vasodilatation and formation of collateral veins (e.g., porto-systemic shunts) lead to hyperdynamic splanchnic and systemic circularity conditions. Persistent endotoxemia, caused by shunting through porto-systemic anastomoses and enhanced endotoxin absorption from the intestine as a result of bile salt deficiency, may contribute to the vasodilation by activation of cascades of secondary mediators. Portal hypertension results from hyperdynamic splanchnic circulation with increased afterload of the portal venous system with intrahepatic cirrhosis. This leads to ascites, splenomegaly, varicose vein formation in the esophagus, portal hypertensive gastropathy, and spontaneous bacterial peritonitis. Portopulmonary hypertension can be categorized as mild (mean pulmonary arterial pressure [MPAP] 25–44 mmHg), moderate (MPAP 45–59 mmHg), and severe (MPAP ≥ 60 mmHg). Moderate to severe portal hypertension is associated with high perioperative mortality in liver transplantation [3] and is considered a contraindication for isolated liver transplantation unless successfully medically managed pretransplant [4]. Right heart failure can be found in patients with pulmonary hypertension. Dilatation of the right ventricle, decreased wall motion of the right ventricle, tricuspid regurgitation, and dilatation of the right atrium are hallmarks of the condition. Hepatopulmonary syndrome (HPS) is characterized by microvascular alterations and dilatation in the pre-capillary and capillary pulmonary arterial circulation. HPS is defined as a widened alveolar-arterial oxygen gradient (AaPO ₂) on room air in the presence or absence of hypoxemia (AaPO ₂ = 15 mmHg, or 20 mmHg in patients more than 64 years old) as a result of intrapulmonary vasodilation. HPS can be graded on the basis of the degree of hypoxemia: mild (PaO ₂ ≥ 80 mmHg); moderate (PaO ₂ = 61–80 mmHg), severe (PaO ₂ = 50–60 mmHg), and very severe (PaO ₂ < 50 mmHg) [5]. Cirrhotic cardiomyopathy is a recently recognized condition and can be caused by any etiology of ESLD. It presents with systolic incompetence under hemodynamic stress, diastolic dysfunction related to altered diastolic relaxation and electrophysiological abnormalities in the absence of any known cardiac disease. The underlying pathogenetic mechanisms include abnormalities in the β-adrenergic signaling pathway, altered cardiomyocyte membrane fluidity, increased myocardial fibrosis, cardiomyocyte hypertrophy, and ion channel defects with widening of the QRS complex causing prolonged QT intervals. The clinical manifestations of this condition become relevant only in decompensated conditions or immediately after liver donor graft reperfusion with significant volume overload. Pleural effusion can be of a significant amount and may contribute to intraoperative hypoxemia due to atelectasis and decreased ventilation of the affected side of the lung.

Hepato-renal syndrome (HRS) [6] results from the cascade of events caused by ESLD with portal hypertension and mesenteric hyperemia; the two conditions cause relative renal hypo-perfusion, resulting in severe renal arterial vasoconstriction and progressive renal failure. Two types of HRS are observed in clinical practice [7]. Type 1 HRS is an aggressive form with a very poor prognosis, and type 2 HRS develops slowly over weeks; these patients usually have diuretic-resistant ascites and have a slightly better prognosis than those with type 1 HRS.

As a result, hyperkalemia and metabolic acidosis can be seen in patients with ESLD. Hyponatremia is also a common finding in ESLD patients. The pathogenesis is directly related to the vasodilatation and secondary neurohumoral adaptations that occur, including activation of endogenous vasoconstrictors such as antidiuretic hormone. This process leads to an impaired ability to excrete ingested water. Severity of the hyponatremia is related to the severity of ESLD.

Decreased synthetic function of the liver with ESLD leads to decreased production of procoagulant factors including vitamin K-dependent factors, factor V, and factor XI. Dysfibrinogenemia is caused both by the decreased production and by increased consumption of fibrinogen due to altered production of activators and inhibitors of fibrinolysis, activation of coagulation cascade by endotoxemia, and decreased clearance of fibrinolytic proteins. Of note, traditional laboratory-based coagulation tests, including prothrombin time, partial thromboplastin time, and fibrinogen level, do not necessarily reveal the entire picture of coagulation. This point is important as the coagulation status is a fine balance between these two opposing factors [8]: pro-coagulants and anti-coagulants. Therefore, aggressive correction of coagulation abnormalities measured by these laboratory tests with exogenous coagulation factors and blood products occasionally results in thromboembolic complications at liver transplantation [9]. Thrombocytopenia is a common feature in ESLD. This is primarily due to hypersplenism secondary to portal hypertension, but decreased production of hepatic thrombopoietin synthesis as well as direct bone marrow suppression with alcohol exposure or hepatitis C virus also play a role. Anemia is seen due to a combination of hemorrhage from the gastrointestinal tract, decreased production of red blood cells (bone marrow suppression and/or folate deficiency), and hemodilution due to water retention. Leucopenia can be seen due to bone marrow suppression with viral hepatitis B or C, and excessive alcohol consumption. Together with leukopenia and decreased production of the compliments, patients can be prone to infections including spontaneous bacterial peritonitis.

Esophageal varices and portal hypertensive gastropathy are primary abnormalities that occur due to ESLD. In general, varices can form at any portion of the alimentary tract from the esophagus to the rectum, but the distal esophagus is the most common site for varices in ESLD. Esophageal varices result from portal hypertension and often bleed. Child-Pugh score, variceal size, and presence of red wale markings can be used to calculate a prognostic index that quantifies the risk of variceal hemorrhage [10]. An endoscopic banding procedure is occasionally performed during the pretransplantation period either to therapeutically treat bleeding varices or for prophylactic purposes. The timing of this banding procedure and the severity of the varices are important to consider for intraoperative placement of transesophageal echocardiography (TEE) . Portal hypertensive gastropathy [11] has the characteristic endoscopic features of a mosaic pattern with or without red spots. It is most frequently located at the fundus and body of the stomach. Acute bleeding from portal hypertensive gastropathy is usually mild and seen in the presence of severe portal hypertension. Mucosal dysfunction of the intestine due to portal hypertension leads to malabsorption and bacterial translocation [12]. The former leads to malnutrition; the latter leads to bacteremia and spontaneous bacterial peritonitis as well as the main pathogenesis of hepatorenal syndrome due to splanchnic and systemic vasodilation.

Hepatic encephalopathy [13] indicates the spectrum of potentially reversible neuropsychiatric abnormalities observed in patients with liver dysfunction. There are three types of hepatic encephalopathy: Type A is associated with acute liver failure; Type B is associated with portal-systemic bypass and no intrinsic liver disease; and Type C is associated with ESLD. Therefore, hepatic encephalopathy of liver transplant patients are categorized as Type C, and are further subcategorized into those with episodic hepatic encephalopathy, persistent hepatic encephalopathy, and minimal hepatic encephalopathy. In terms of symptom severity, the West Haven criteria [14, 15] for semi-quantitative grading of mental status have been used to score the grade of clinical severity: mild (Grade 1), moderate (Grade 2—lethargy/minimal disorientation/subtle personality change), severe (Grade 3—somnolence/confusion/disorientation), or Grade 4 (coma). Several metabolic factors contribute to the development of hepatic encephalopathy, which include ammonia, inhibitory neurotransmission through gamma-aminobutyric acid receptors in the central nervous system, and changes in central neurotransmitters and circulating amino acids [16].

Diabetes mellitus is seen in 15–30 % of patients with cirrhosis [17]. Insulin resistance is present in many patients with nonalcoholic steatohepatitis and chronic hepatitis C. Cirrhosis has also been linked to abnormalities in the other endocrine glands, including abnormal sex hormone metabolism, thyroid disease (hypo- and hyperthyroidism), osteoporosis, and adrenocortical dysfunction.

The recipients’ preoperative condition is reviewed and examined for any further changes; any sign of deterioration of the condition compared to the pretransplantation workup should be investigated. Judicious use of anxiolytics is recommended to avoid oversedation prior to the induction of general anesthesia, as the bioavailability of benzodiazepine usually high due to low serum albumin. Given the urgency of the transplantation and possible delayed gastric emptying due to ESLD, the patient should be treated as if they have a full stomach and rapid sequence induction to secure the airway is warranted; however, routine use of succinylcholine in this scenario should be avoided due to a concern for acute hyperkalemia associated with this agent. Intravenous induction agents including propofol or etomidate can be safely used. When post induction hypotension is a concern, the latter agent may be preferred. Potential adrenal suppression with etomidate may be mitigated by the glucocorticoid administration for immunosuppression regimen. Maintenance of anesthesia can be easily achieved with the balanced technique using inhalational agents, nondepolarizing muscle relaxants, and opioids. If fast track anesthesia is planned to remove the endotracheal tube early in the postoperative period, the rapid offset agents can be selected, including sevoflurane or desflurane, rocuronium if sugammadex as a reversal agent is available, and remifentanil infusion.

Several inotropes of choice (epinephrine, dopamine, or norepinephrine) should be prepared for any unexpected hemodynamic changes. Vasopressin should also be available in case of refractory hypotension. A cell salvage device and a rapid infusion system should also be available in the operating room and ready for use if indicated. Prophylactic antibiotics (a third generation cephalosporin of choice) should be given prior to the skin incision and timely re-dosing during the operation. In case of massive bleeding, the timing of re-dosing should be shortened to maintain the effective plasma concentration of antibiotics. For intraoperative fluid maintenance, any isotonic-potassium and glucose-free crystalloids should be adequate. Excessive usage of normal saline solution should be avoided, since a sudden increase in serum sodium level may result in acute central pontine myelinolysis [36].

The degrees of cardiovascular and pulmonary system involvement in ESLD as well as the invasiveness of the surgical transplant method dictate selection of invasive hemodynamic monitoring. However, each transplantation institution has its own institutional guidelines based on its philosophy and historical practice [37]. These institutional practices can vary significantly from a minimalist approach (one arterial line, several large bore intravenous lines with or without central venous line) to a maximalist approach (two arterial lines, two central lines with a pulmonary arterial [PA] catheter with continuous cardiac output measurement and TEE). The advocates of two arterial lines (one radial arterial line and the other via a central arterial system: contralateral side of the brachial artery or the femoral artery) are based on observations that a central arterial line would better represent the central arterial pressure than a radial artery, especially under hypotensive conditions, would serve as a failsafe measure during the surgery, and would allow continuous monitoring during phlebotomy via the other arterial line. The two central lines may assure the two independent rapid infusion sites of blood and fluid at the time of hemodynamic disaster, while allowing placement of a PA catheter. A PA catheter provides direct measurement of right-sided pressures as well as pulmonary arterial pressure, which is crucial when the recipient has preexisting pulmonary arterial hypertension. The catheter can provide continuous monitoring of pulmonary arterial pressure postoperatively in the ICU. TEE can be especially useful to evaluate right ventricular function that demonstrates pulmonary hypertension to rapidly diagnose the potential cause of cardiac collapse (hypovolemia, myocardial depression, and clot/air embolism), and to evaluate the performance of VVB. If VVB placement using the axillary cut down technique is anticipated, a venous access on the ipsilateral side of the arm should be discouraged, since infusion via the distal site of the same side of the axillary cut down will be obliterated.