**3.3.2 Gastroesophageal varices**

Hemorrhage due to gastroesophageal variceal bleeding can be imminently fatal, and requires emergent therapy. Airway protection with endotracheal intubation reduces the risk of aspiration during massive hematemesis. Intravenous volume resuscitation or blood products should be administered carefully, as excess volume can increase portal pressures and exacerbate bleeding. An appropriate post-transfusion hemoglobin goal is 8 g/dL.

Infusion of the somatostatin analogue octreotide reduces portal pressure and can induce splanchnic vasoconstriction and facilitate hemostasis during variceal bleeding. Terlipressin, a vasopressin analogue, has been used with success in Europe to help control variceal bleeding. All patients should receive prophylactic antibiotics with either ceftriaxone or a fluoroquinolone, which have been shown to reduce infections, reduce the risk of rebleeding, and improve survival (*Bernard et al., 1999*).

Following initiation of pharmacologic therapy, definitive therapy for gastroesophageal varices requires upper endoscopy with endoscopic band ligation or sclerotherapy. If these measures fail, or if gastric varices are detected, urgent TIPS can be used to achieve hemostasis and prevent the development of new varices. For severe uncontrolled bleeding, esophageal balloon tamponade may be necessary for temporary stabilization until definitive TIPS therapy is undertaken.

### **3.3.3 Cardiovascular impairments**

*Cardiovascular system derangements* frequently complicate the hemodynamic picture of decompensated cirrhosis. Circulatory changes resemble those of septic shock, including increased cardiac output, reduced systemic vascular resistance, wide pulse pressure, and decreased mean arterial pressure. Patients are susceptible to sepsis-induced hypotension and septic shock. Norepinephrine is the preferred vasoactive agent in such patients, as it preserves cardiac output while increasing vascular resistance. Hypotension can also occur by decreased venous return if severe ascites produces compression of the inferior vena cava. Finally, the phenomenon of cirrhotic cardiomyopathy with impaired systolic and diastolic dysfunction, and reduced response to inotropic therapy has been described (*Zardi et al., 2010*). Several mechanisms for cirrhotic cardiomyopathy have been proposed, including myocardial apoptosis, involvement of circulating carbon monoxide and nitric oxide, and cardiomyocyte receptor impairments. If overt heart failure develops, consultation with a cardiologist is advisable.

#### **3.3.4 Pulmonary complications**

326 Liver Transplantation – Basic Issues

supportive and focuses on patient safety and avoidance of complications. As in ALF, patients with grade III or IV encephalopathy warrant elective intubation for airway protection. Causative factors of hepatic encephalopathy include dehydration, overdiuresis, infection, use of benzodiazepines and narcotics, gastrointestinal bleeding, constipation, electrolyte or acid-base imbalances, or recent transjugular intrahepatic portosystemic shunt (TIPS) procedure. Progression of underlying liver disease may be the only identifiable precipitant; when reversible causes are identified, they should be

Medical treatment of hepatic encephalopathy consists of oral agents to assist in toxin elimination. Lactulose and other nonabsorbable disaccharides improve intestinal excretion of nitrogen and reduce production of ammonia by enteric bacteria. Intestinal decontamination with oral antibiotics such as rifaximin or metronidazole reduces the burden of ammonia-

Hemorrhage due to gastroesophageal variceal bleeding can be imminently fatal, and requires emergent therapy. Airway protection with endotracheal intubation reduces the risk of aspiration during massive hematemesis. Intravenous volume resuscitation or blood products should be administered carefully, as excess volume can increase portal pressures and exacerbate bleeding. An appropriate post-transfusion hemoglobin goal is

Infusion of the somatostatin analogue octreotide reduces portal pressure and can induce splanchnic vasoconstriction and facilitate hemostasis during variceal bleeding. Terlipressin, a vasopressin analogue, has been used with success in Europe to help control variceal bleeding. All patients should receive prophylactic antibiotics with either ceftriaxone or a fluoroquinolone, which have been shown to reduce infections, reduce the risk of rebleeding,

Following initiation of pharmacologic therapy, definitive therapy for gastroesophageal varices requires upper endoscopy with endoscopic band ligation or sclerotherapy. If these measures fail, or if gastric varices are detected, urgent TIPS can be used to achieve hemostasis and prevent the development of new varices. For severe uncontrolled bleeding, esophageal balloon tamponade may be necessary for temporary stabilization until definitive

*Cardiovascular system derangements* frequently complicate the hemodynamic picture of decompensated cirrhosis. Circulatory changes resemble those of septic shock, including increased cardiac output, reduced systemic vascular resistance, wide pulse pressure, and decreased mean arterial pressure. Patients are susceptible to sepsis-induced hypotension and septic shock. Norepinephrine is the preferred vasoactive agent in such patients, as it preserves cardiac output while increasing vascular resistance. Hypotension can also occur by decreased venous return if severe ascites produces compression of the inferior vena cava.

treated.

8 g/dL.

producing bacteria.

**3.3.2 Gastroesophageal varices** 

and improve survival (*Bernard et al., 1999*).

TIPS therapy is undertaken.

**3.3.3 Cardiovascular impairments** 

*The pulmonary system derangements* in decompensated cirrhosis are characterized by distinct disorders of varying severity. In the *hepatopulmonary syndrome* (HPS), excess vasodilation of the pulmonary vasculature system limits oxygen diffusion across the alveolar-capillary membrane. Vasodilation may occur through nitric oxide and other circulating vasodilators, or through arteriovenous malformations resulting in intrapulmonary shunts; the difference in these two mechanisms distinguish type I and type II HPS, respectively. Presenting symptoms include dyspnea, platypnea, orthodeoxia, cyanosis, and hypoxemia. Arterial blood gas and transthoracic double bubble echocardiogram or lung perfusion scans can help establish the diagnosis. Supplemental oxygen improves hypoxemia in type I HPS, whereas embolization of arteriovenous malformations can be performed in type II syndrome. In both forms, liver transplantation is the definitive treatment, and the presence of either form facilitates priority listing for transplantation.

*Portopulmonary hypertension* (PPH) is a form of pulmonary arterial hypertension occurring in the presence of portal hypertension, and portends a poor prognosis. The mechanism of the adverse effects of portal hypertension on the pulmonary vasculature remains unclear. Proposed explanations include endothelial remodeling in response to a hyperdynamic circulation, as well as inflammatory cascades related to cytokines. Patients present with exertional dyspnea, fatigue, chest pain, and signs of volume overload. Diagnosis is confirmed by right heart catheterization, which demonstrates a pulmonary artery pressure (PAP) of 25 mmHg or greater with a normal pulmonary capillary wedge pressure. The degree of PAP elevation correlates with mortality during liver transplant, and patients with moderate or severely elevated pressures generally are not candidates for transplantation. Continuous infusion of vasodilatory prostaglandins such as epoprostenol may improve hemodynamics and reduce PAP to allow patients improved likelihood of tolerating transplantation.

*Hepatic hydrothorax* refers to pleural effusions that occur when diaphragmatic defects allow the transudation of ascitic fluid into the pleural space. Dyspnea, cough, chest discomfort, and respiratory collapse can occur. Diagnostic and therapeutic thoracentesis should be performed to exclude infection, malignancy, and cardiopulmonary etiologies of pleural effusions. Diuretics such as furosemide and spironolactone can be administered, but patients with respiratory compromise should undergo therapeutic thoracentesis. Chest tubes are contraindicated in hepatic hydrothorax, as re-expansion pulmonary edema and hypovolemic shock can occur and are poorly tolerated in the cirrhotic patient. If hepatic

hydrothorax is refractory to diuresis and thoracentesis, TIPS is indicated to help prevent the formation of ascites and subsequent transudation.
