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Background & Aims: Whether the effect of beta-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of beta-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. Methods: Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting beta-blockers and again after 1 to 3 months of treatment (short-term). Results: Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under -blockers, decompensated patients had lower portal pressure decrease (10 +/- 18% vs. 15 +/- 12%; p

Anesthetic management of the patient with major burn injuries presents numerous challenges. During the acute resuscitation phase, massive crystalloid infusions may be required. Anatomical distortions make airway management and vascular access difficult. With time, pathophysiological changes in cardiovascular function range from initial hypovolemia and impaired perfusion to a hyperdynamic circulation and hypermetabolic state. Pharmacological support of the circulation may be needed. These and other changes profoundly alter response to anesthetic drugs. Effective anesthetic management will depend on knowledge of the continuum of pathophysiological changes, technical skills, proper planning, and availability of proper resources. A team approach is necessary, keeping in mind that perioperative management not only depends on the surgical plan, but also should be compatible with ICU management and goals. This requires close communication with other members of the burn care team, which is one of the most important principles of effective anesthetic management of these challenging patients.

BackgroundLiver cirrhosis is often accompanied by portal-systemic collateral formation with hemorrhage and encephalopathy. Prostacyclin participates in hyperdynamic circulation and vascular hyporeactiveness to vasoconstrictors in cirrhosis. It has been shown that arginine vasopressin (AVP) induces direct collateral vasoconstriction in portal hypertensive rats, which is potentiated by indomethacin preincubation. However, the influence of chronic indomethacin administration in cirrhosis remains unexplored.MethodsThis study was performed on male Sprague-Dawley rats with liver cirrhosis induced by common bile duct ligation. They received subcutaneous indomethacin (5 mg/kg/day) or distilled water (control) injection from the 36th to 42nd day after operation. On the 43rd day, systemic and portal hemodynamics were evaluated and the following experiments were performed with an in situ collateral perfusion model: in the first series, concentration-response curves to AVP (10−10−10−7 M) were obtained; in the second series, flow-pressure curves were plotted (Krebs solution, 6–18 mL/min), where the slope represents an index of collateral vascular resistance (the higher the resistance, the smaller the amount of shunting vessels, that is, the lower the degree of shunting).ResultsThe mean arterial pressure and portal pressure were similar between indomethacin and control groups (p > 0.05). Indomethacin elevated the collateral perfusion pressure to AVP (3 × 10−9, 10−8 M, p < 0.05) but did not influence the slope of the flow-pressure curve (p > 0.05).ConclusionIn bile duct-ligated cirrhotic rats, indomethacin improves the portal-systemic collateral vascular responsiveness to AVP without alleviating the severity of shunting.

Liver cirrhosis is associated with a wide range of cardiovascular abnormalities. These abnormalities include hyperdynamic circulation characterized by an increase in cardiac output and a decrease in peripheral vascular resistance. Despite the increased cardiac output, impaired ventricular contractility in response to both physiological and pharmacological stimuli has been described. Other cardiac abnormalities include structural changes including enlargement or hypertrophy of different cardiac chambers and electrophysiological changes such as QT prolongation. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. The pathogenic mechanisms of cirrhotic cardiomyopathy are multifactorial and include cardiomyocyte plasma membrane physico-chemical changes, attenuated stimulatory pathways, and enhanced activity of inhibitory systems. Accumulating evidence suggests that cirrhotic cardiomyopathy plays a major role in the pathogenesis of cardiac dysfunction following liver transplantation or transjugular intrahepatic portosystemic shunt placement. Recent research also strongly suggests that cirrhotic cardiomyopathy contributes to the pathogenesis of hepatorenal syndrome, especially following infections such as spontaneous bacterial peritonitis. Treatment of this syndrome remains largely empirical. Successful liver transplantation is thought to improve all the organ-related hemodynamic dysfunctions, including hepatopulmonary syndrome, cerebral hypoperfusion, hepatorenal syndrome, and cirrhotic cardiomyopathy. The prolonged QT interval normalizes following liver transplantation. Thus, liver transplantation appears to be the ultimate treatment for the cardiovascular complications of cirrhosis.

During the course of cirrhosis, a progressive reduction of splanchnic vascular resistance takes place in parallel with a deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a fall in cardiac output. This compromises arterial pressure and determines a homeostatic activation of endogenous vasoconstrictor systems. Cirrhotic patients are prone to developing renal vasoconstriction, decreased renal perfusion and renal failure in response to insults that impairs the effective arterial blood volume such as severe bacterial infections or other clinical events that produce hypovolemia. Although circulatory dysfunction in cirrhosis predominantly affects the kidney, it has also effects on other organs and systems: brain edema and encephalopathy, increased portal pressure and decreased intestinal motility. Albumin infusion is effective in the prevention of circulatory dysfunction after therapeutic paracentesis or acute bacterial infections and in in the treatment of hepatorenal syndrome. This effectiveness may be related to the dual effect of albumin on the cardio-circulatory function, the increase in the cardiac output and in the systemic vascular resistance. The administration of intravenous albumin not only expands the plasma volume and increases cardiac preload and cardiac output but also induces arterial vasoconstriction at the level of splanchnic microcirculation. Moreover, albumin is a powerful antioxidant as well as plays a crucial role in the transport of physiologic substances and disposal of toxic substances. Impairment of albumin function is one of the most characteristic traits of cirrhosis. Administration of exogenous albumin could be beneficial because of its positive effects on microcirculation.

Publisher Summary This chapter describes the occurrence of cytopathic hypoxia in septic shock. The term “sepsis” refers to the systemic response of an organism to infection. Septic shock refers to overwhelming sepsis resulting in organ hypoperfusion and decreased blood pressure. The incidence of human sepsis is gradually rising as a result of an aging population and the increasing severity of acquired forms of immunodeficiency. The de-energization in sepsis may contribute directly or indirectly to dysfunction and to apoptosis and necrosis. Because most adenosine triphosphate (ATP) is synthesized aerobically, coupled to the reduction of cellular O 2 to H 2 O, the role of O 2 kinetics in sepsis is a major focus. Although evidence for diffuse tissue hypoxia in sepsis is lacking, regional hypoxia is hypothesized to play a substantial role in the cause of multiple organ dysfunction. Low cardiac output, anemia, and arterial hypoxia might occur singly or in combination in sepsis. Human sepsis is characterized by a hyperdynamic circulation with elevated mixed-venous oxygen content in the setting of regional or systemic metabolic acidosis and hyperlactatemia that are the markers of increased anaerobic respiration.