Chapter 23 Perioperative critical care in hepatopancreatobiliary patients
Overview
Patients with cirrhosis or decompensated liver disease (see Chapter 2, Chapter 70B, Chapter 72, Chapter 73, Chapter 74, Chapter 75A, Chapter 75B, Chapter 75C ) are at particularly high risk for perioperative morbidity and mortality after major surgery, often necessitating admission to the intensive care unit (ICU). Compared with noncirrhotic patients, patients with cirrhosis who are admitted to the ICU have higher rates of complications and hospital mortality, extended lengths of stay, and greater resource use (Aggarwal et al, 2001; Cholongitas et al, 2006). Combined respiratory and renal failure requiring the use of mechanical ventilation and renal replacement therapy carries a mortality rate ranging from 61% to 89% (Arabi et al, 2004; Cholongitas et al, 2009). Meticulous perioperative assessment, planning, and care are essential to minimize complications and decrease mortality rates in these patients. Although this chapter addresses the special perioperative concerns of cirrhotic patients, unless otherwise specified, the data are applicable to all types of chronic liver disease, including chronic infections with hepatitis B or C virus, chronic autoimmune hepatitis, biliary cirrhosis, sclerosing cholangitis, and hemochromatosis.
Preoperative Assessment and Care
Global Assessment
The loss of hepatic reserve capacity and the associated systemic derangements that result from liver dysfunction cause patients with chronic liver disease to have an inappropriate response to surgical stress. Increased surgical risk has been reported for various types of surgery in cirrhotic patients, including cardiac operations, open cholecystectomy, hysterectomy, nephrectomy, and transurethral resection of the prostate (Shaheen et al, 2009; Hayashida et al, 2004; Thulstrup & Sorensen, 2001; Lund et al, 2003; Nielsen et al, 2001, 2002). Emergency surgery and unscheduled laparotomy for trauma carry a high mortality rate (Pronovost et al, 1999; Carbonell et al, 2005; Wahlstrom et al, 2000; Demetriades et al, 2004). In contrast, patients with cirrhosis who undergo laparoscopic cholecystectomy have generally favorable outcomes (Morino et al, 2000; Pavlidis et al, 2009).
Two risk-stratification scoring systems have been developed to evaluate the preoperative severity of liver dysfunction and to predict postoperative outcome in cirrhotic patients. The Child score and its modification, the Child-Turcotte-Pugh (CTP) score, has been most commonly used. In the CTP score, a composite score of the degree of hepatic synthetic dysfunction (based on prothrombin time and serum levels of albumin and bilirubin), degree of ascites, and presence of hepatic encephalopathy yields a total score that ranges from well-compensated cirrhosis (class A, 5 to 6 points) to mild (class B, 7 to 9 points) and severe (class C, 10 to 15 points) decompensation. Cirrhotic patients undergoing elective or emergency extrahepatic surgery have a mortality rate ranging from 0% to 7.1% for class A to 84% to 100% for class C (Franzetta et al, 2003). Other risk factors for perioperative complications and mortality among cirrhotic patients undergoing surgery include male gender, preoperative infection or upper gastrointestinal bleeding, elevated creatinine concentration, and thrombocytopenia (Ziser et al, 1999).
In 2000, the Model for End-Stage Liver Disease (MELD) score was developed and proved to be superior to the CTP score in predicting the 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) (Malinchoc et al, 2000; Salerno et al, 2002). The MELD score is based on the prothrombin time–international normalized ratio (PT-INR) and serum bilirubin and creatinine levels, and it is calculated as follows:
The MELD score has been shown to correlate well with the CTP score in predicting postoperative mortality in cirrhotic patients undergoing elective and emergent surgery (Farnsworth et al, 2004). Other studies have shown that high MELD scores predict a poor outcome after hepatic resection for hepatocellular carcinoma (HCC) and following abdominal nonhepatic surgery in cirrhotic patients (Befeler et al, 2005; Teh et al, 2005). Finally, functional assays, such as the monoethylglycinexylidide (MEGX) test and indocyanine green clearance, may be used to assess hepatic functional reserve to predict postoperative morbidity and mortality prior to liver resection (Ercolani et al, 2000; Oellerich & Armstrong, 2001; Ravaioli et al, 2003; Lorf et al, 2008).
Risk Assessment (See Chapter 2)
Although surgical and anesthetic risks are largely related to the severity and not the cause of cirrhosis, determination of the etiology of the liver disease may be helpful in guiding the perioperative management and the timing of surgery (Table 23.1). A history of alcohol use should be obtained for all cirrhotic patients. Surgery should be deferred, if possible, in patients who are actively drinking alcohol because alcohol increases tolerance to narcotic and anesthetic agents, increases the risk of general anesthesia, and predisposes patients to alcohol withdrawal in the postoperative period (May et al, 2001; Spies et al, 2001). Prolonged alcohol abstinence (≥6 months) may lead to a significant reduction in the severity of portal hypertension and improvement in synthetic function in patients with alcoholic hepatitis. However, postponing surgery to allow alcohol abstinence is generally not practical in case of surgery for trauma or liver cancer.
Table 23.1 Risk Factors for Surgery and Preventive and Therapeutic Interventions
| Risk Factors | Detrimental Effects | Interventions |
|---|---|---|
| Active alcohol use | Acute alcohol hepatitis | Cancel elective surgery |
| Increased tolerance to sedatives and anesthetics | Prolonged alcohol abstinence | |
| Alcohol withdrawal and delirium | Use sedative and defer elective surgery | |
| Iron overload | Cardiomyopathy and arrhythmias | Therapeutic phlebotomies |
| Hepatitis B infection | Flare of hepatitis | Antiviral agents |
| Autoimmune hepatitis | Flare of hepatitis | Stress-dose steroids |
Similar to active alcohol use, chronic viral and autoimmune hepatitis increase the risk of perioperative complications. Among patients undergoing hepatectomy for hepatocellular carcinoma, the presence of high-grade inflammation of the remaining healthy liver is associated with postoperative hepatic dysfunction (Nanashima et al, 2003). Patients with cirrhosis as a result of chronic hepatitis B may benefit from antiviral and immunologic agents such as lamivudine, adefovir, entecavir, telbivudine, tenofovir, interferon alfa-2b, and peginterferon alfa-2a before surgery (Keeffe et al, 2008; Lau et al, 2005; Hadziyannis et al, 2005, 2006; Schalm et al, 2000; Chan et al, 2005). Patients with chronic autoimmune hepatitis who have been on long-term steroid therapy should receive stress-dose steroids in the perioperative period, and adjunctive immunomodulatory agents should be resumed as soon as possible (Czaja, 2009).
Portal Hypertension, Varices, and Ascites (See Chapter 70A, Chapter 70B, Chapter 74, Chapter 75A, Chapter 75B, Chapter 75C )
The severity of portal hypertension, as manifested by ascites and varices, is a major concern in the preoperative evaluation of cirrhotic patients. Preoperative endoscopy and measurement of hepatic venous pressures identify patients with severe portal hypertension who are at risk for variceal bleeding (Dittrich et al, 2003). Elevated hepatic venous pressures may portend the development of postoperative complications and higher hospital mortality in cirrhotic patients undergoing various surgical procedures including cholecystectomy, coronary artery bypass grafting, abdominal aortic aneurysm repair, and colorectal surgery (Csikesz et al, 2009; Nguyen et al, 2009). A platelet count of less than 100,000/µL is another useful surrogate marker of severe portal hypertension and of eventual hepatic decompensation (Zaman et al, 2001).
In patients with significant risk factors for variceal hemorrhage, nonselective β-blockers, such as propranolol or nadolol, are recommended to decrease the resting heart rate by 25% of pretreatment level or to approximately 50 to 60 beats/min. These agents, used either alone or in combination with nitrates, may reduce the variceal bleeding rate by half (Bureau et al, 2002; Patch et al, 2002). Alternatively, esophageal variceal band ligation or TIPS placement (see Chapter 76E) could be considered (Escorsell et al, 2002; Lo et al, 2002).
Ascites predisposes to bacterial peritonitis, respiratory compromise as a result of reduced lung expansion, and delayed wound healing. Adequate control and evaluation of ascites is important in cirrhotic patients scheduled to undergo abdominal surgery. In general, control of ascites may require several months and can be achieved with a low-sodium diet, diuretics, and/or large volume paracentesis (Table 23.2). In approximately two thirds of patients with ascites that is refractory or intolerant to diuretics, TIPS may be beneficial. Doppler ultrasound is advocated prior to TIPS procedure, as findings of abnormal blood flow in the portal venous system correlate well with increased mortality (Harrod-Kim & Waldman, 2005). Patients who undergo TIPS are also at increased risk for hepatic encephalopathy and should be monitored closely (Sahagun et al, 1997; Maleux et al, 2004). Patients with high MELD scores (>15) are at high risk for 30-day mortality and should not undergo TIPS for refractory ascites (Ferral et al, 2004; Schepke et al, 2003). In general, cirrhotic patients whose ascites is refractory to diuretics or TIPS should avoid abdominal surgery because of the high rates of postoperative morbidity and death. Finally, a high MELD score and use of a proton pump inhibitor are also associated with increased risks of spontaneous bacterial peritonitis (Bajaj et al, 2009; Obstein et al, 2007).
| Risk Factors | Evaluation and Management |
|---|---|
| Esophageal varices | Esophagogastroduodenoscopy |
| Nonselective β-blockers | |
| Band ligation | |
| Ascites | Abdominal ultrasound |
| Paracentesis to rule out spontaneous bacteral peritonitis | |
| Sodium restriction | |
| Diuretics | |
| Refractory ascites with low MELD score | TIPS |
| Hepatopulmonary syndrome | Arterial blood gas and bubble electrocardiogram |
| Quantitative tagged microaggregated lung perfusion scan | |
| Echocardiogram | |
| Right heart catheterization for confirmation |
MELD, Model for End-Stage Liver Disease; TIPS, transjugular intrahepatic portosystemic shunt
Avoiding preoperative intravascular volume depletion is important, as hypovolemia can lead to intraoperative and postoperative hypotension and shock, particularly in cases of surgery for emergent or life-threatening indications. Paracentesis and diuretics should be used judiciously, because they can trigger hypovolemic shock. Paracentesis may be performed with concomitant intravenous administration of selective colloid solutions. Albumin solutions are the preferred colloids used for resuscitation, as isotonic saline or dextran solutions may lead to ongoing accumulation of ascites (Garcia-Compean et al, 2002; Planas et al, 1990).
Nutrition (See Chapter 24)
Severe malnutrition affects up to 40% of cirrhotic patients and is associated with a high incidence of morbidity and mortality in patients with cirrhosis who are undergoing surgery (Kalaitzakis et al, 2007; Merli et al, 2002; Sam & Nguyen, 2009). In patients with advanced cirrhosis, several of the common parameters of nutritional status—such as body weight, body mass index, and albumin level—are not valid and reliable tools for assessment.
Perioperative interventions to enhance the nutritional status of cirrhotic patients may be associated with improved outcomes. Although special supplements with branched-chain amino acids are available and may reduce the risk of hepatic encephalopathy (Marchesini et al, 2003), in practice, their benefit is at most marginal. Nutrition via the enteral route is advocated, and nasogastric tubes can be employed safely in patients with esophageal varices. Total parenteral nutrition may be difficult to administer in cirrhotic patients because of concerns with fluid overload and infection.
Anemia
Bleeding, hemolysis, splenic sequestration, malnutrition, and underlying liver disease are among the multifactorial causes of anemia in cirrhotic patients. Longitudinal studies of patients with compensated cirrhosis without esophageal varices demonstrate that anemia may develop an average of 39 months after the onset of cirrhosis (Qamar et al, 2009). In 20% to 40% of patients with advanced cirrhosis of nonbiliary origin, a spur-cell hemolytic anemia associated with iron overload may become evident. Iron should be administered only in the presence of documented deficiency. In patients scheduled for partial hepatectomy for HCC, autologous blood transfusion and erythropoietin therapy have been used successfully to prevent the need for red blood cell transfusions (MacLaren et al, 2004; Shinozuka et al, 2000; Kajikawa et al, 1994).
Coagulopathy
Coagulation abnormalities are frequently found in cirrhotic patients undergoing surgery. Etiologies include decreased hepatic synthetic function, abnormal synthesis of coagulation factors, malnutrition, vitamin K deficiency, thrombocytopenia, and dysfibrinogenemia (Amitrano et al, 2002; Qamar et al, 2009; Richard et al, 2007). The degree of coagulopathy is proportional to the severity of cirrhosis. For patients with prolonged PT-INR and suspected vitamin K deficiency, a 3-day trial of vitamin K is recommended to determine whether the coagulopathy is correctable. Intravenous administration of vitamin K is the favored method in the ICU: subcutaneous administration has an inconsistent rate of absorption, and intramuscular injection carries the risk of hematoma formation. Oral menadiol, the water-soluble formulation of vitamin K, is effective for patients with cholestasis. If the PT-INR fails to correct with vitamin K, mixing studies may help identify possible inhibitors and guide therapy with fresh frozen plasma (FFP) or recombinant factors. Of note, the number of units of FFP commonly used in clinical practice infrequently corrects the coagulopathy (Youssef et al, 2003). In general, administration of cryoprecipitate is recommended when serum fibrinogen levels are less than 100 mg/dL, particularly in the presence of bleeding.
Excessive plasma transfusions can lead to volume overload and may exacerbate ascites. Human recombinant activated factor VIIa (rFVIIa) has been shown to be beneficial as an alternative to plasma. Rapid correction of the PT-INR has been documented within 15 minutes of a small, single intravenous dose of rFVIIa (Surudo et al, 2003), and rFVIIa has been used successfully in cirrhotic patients with coagulopathy to achieve hemostasis for colonic polypectomy, liver biopsy, dental extraction, and bleeding esophageal varices refractory to standard endoscopic therapy (Anantharaju et al, 2003; Berthier et al, 2002; Carvalho et al, 2002; Ejlersen et al, 2001; Romero-Castro et al, 2004). Transfusion of platelets is recommended before invasive procedures. A platelet count of less than 50,000/µL is the usual trigger for transfusion (Rebulla, 2001). Finally, desmopressin may be considered for refractory hemorrhage, particularly when azotemia is present.
Cardiorespiratory Evaluation
Patients with advanced cirrhosis typically have a hyperdynamic hemodynamic profile similar to the systemic inflammatory response syndrome: high cardiac output and vasodilatation of the pulmonary, splanchnic, and peripheral beds (Cazzaniga et al, 2009). Patients with alcoholic liver disease and iron overload are predisposed to cardiomyopathy and cardiac arrhythmias (Moller & Henriksen, 2008). Patients with cirrhosis also are at risk for coronary artery disease because of a high prevalence of cigarette smoking and diabetes mellitus (Hickman & Macdonald, 2007).
Hypocapnia is the most frequent gas-exchange abnormality in patients with cirrhosis (Aller et al, 1999), and pulmonary function can be compromised by tense ascites. Large-volume paracentesis may lead to improvement in the forced expiratory volume in 1 second (FEV1), functional residual capacity (FRC), and arterial oxygenation (Gupta et al, 2000).
Patients with cirrhosis are also at risk for the development of hepatopulmonary syndrome (HPS) (Gupta et al, 2001). Subclinical or overt HPS is often associated with portopulmonary hypertension and causes significant pulmonary abnormalities as a result of alterations in the pulmonary vasculature by various toxins that accumulate and bypass the cirrhotic liver. Patients with HPS are seen with hypoxemia, platypnea, orthodeoxia, clubbing, and spider angiomata. The predictive value of the alveolar-arterial oxygen gradient in identifying patients with HPS remains a matter of controversy (Schenk et al, 2002; Lima et al, 2004); however, transthoracic echocardiography can be performed to screen for HPS and portopulmonary hypertension; bubble contrast echocardiography identifies the presence of intrapulmonary shunts indicative of HPS (see Table 23.2).
The presence of HPS worsens the overall prognosis of patients with liver cirrhosis (Schenk et al, 2003). The severity of HPS can be quantified with a tagged, macroaggregated albumin lung perfusion scan and arterial blood gas analysis. Postoperative mortality from cardiorespiratory complications can be estimated by a preoperative Pao2 of 50 mm Hg or a macroaggregated albumin scan quantification shunt fraction of 20% or higher (Arguedas et al, 2003). General anesthesia for hepatic and extrahepatic procedures in patients with HPS is associated with increased perioperative risk (Mazzeo et al, 2004).
Portopulmonary hypertension, an integral component of HPS, is often asymptomatic and difficult to diagnose; however, this syndrome predisposes to intraoperative cardiac arrhythmias and cardiac arrest. Mortality of portopulmonary hypertension is high, with 1- and 5-year survival rates of 54% and 14%, respectively (Swanson et al, 2008). Although transthoracic echocardiogram may be the initial study performed, right heart catheterization is the best diagnostic tool for portopulmonary hypertension, and it helps discriminate this process from other causes of pulmonary hypertension (Krowka et al, 2006). Elective surgery under general anesthesia in patients with severe HPS-associated pulmonary hypertension should be deferred until the pulmonary hypertension is controlled with vasodilator agents.
Electrolytes
Hyponatremia is quite common in patients with cirrhosis because of their impaired ability to excrete free water, and it is associated with increased mortality (Borroni et al, 2000). Hyponatremia often occurs in the setting of severe ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome (Angeli et al, 2006). Hyponatremia and other electrolyte abnormalities, such as hypokalemia and hypomagnesemia, can result from the use of loop diuretics and as a consequence of the chronic respiratory alkalosis associated with cirrhosis. Patients with active alcohol use are also at increased risk of hypophosphatemia. Electrolyte imbalances should be evaluated and corrected before surgery to limit cardiac arrhythmias, peritonitis, and hepatic encephalopathy.
Infection
Spontaneous bacterial peritonitis (SBP) develops in 20% of hospitalized patients with cirrhosis. Risk factors for SBP include gastrointestinal hemorrhage, metabolic alkalosis, dehydration, hyponatremia, and a high MELD score (Obstein et al, 2007). SBP carries an increased mortality rate, which can be worsened by age, renal dysfunction, bacteremia, and elevated MELD score (Perdomo Coral & Alves de Mattos, 2003; Nobre et al, 2008; Cho et al, 2007). It is prudent to have a low threshold to perform a diagnostic paracentesis if SBP is suspected, especially in the setting of large-volume ascites (Kuiper et al, 2007). If SBP is present, elective surgery should be deferred until the infection has been adequately controlled. Prophylactic antimicrobial intestinal decontamination can prevent SBP in hospitalized patients with cirrhosis who have gastrointestinal hemorrhage or a low protein level in the ascitic fluid (Loomba et al, 2009; Terg et al, 2008).
Intraoperative Management
Anesthesia
The degree of impairment in hepatic synthetic function and other hepatic functions has to be strongly considered when selecting anesthetics, muscle relaxants, analgesics, and sedatives in the perioperative period. General anesthesia, which is required during hepatic surgery, decreases total hepatic blood flow. Inhalational agents such as isoflurane and sevoflurane, which undergo less hepatic metabolism, continue to be the preferred anesthetic agents in patients with liver disease Although significant increases in liver transaminases and alkaline phosphatase were observed when isoflurane was used compared with sevoflurane (Nishiyama et al, 2004), isoflurane continues to be favored because of its minimal effects on hepatic blood flow. Halothane is not used because of the high risk of hepatotoxicity (Golembiewski, 2004). Endotracheal intubation and induction are achieved in patients with liver disease similar to that in the general population. Atracurium and cisatracurium are the preferred neuromuscular blocking agents to facilitate intubation, because they are not metabolized through the hepatic or renal system.
Low doses of intravenous agents, such as fentanyl and midazolam, are generally used for induction and sedation. Midazolam may exacerbate hepatic encephalopathy, an adverse effect that is still evident several hours after surgery or an endoscopic procedure (Assy et al, 1999). Decreased protein binding and increased volume of distribution hinder the clearance of midazolam in cirrhotic patients, and significant delays in the elimination of midazolam and decreased psychomotor function have been shown in patients with severe alcohol-induced cirrhosis. Midazolam and meperidine are extensively metabolized by hepatocytes, and their half-life is altered in liver disease (Delco et al, 2005), therefore it is recommended that the doses of midazolam and meperidine be reduced by 50% in cirrhotic patients. Cirrhosis delays the elimination of alfentanil, whereas the metabolism of fentanyl, sufentanil, and remifentanil does not seem to be affected (Lentschener & Ozier, 2002). Nonetheless, opioids are avoided intraoperatively.
Hemodynamic Parameters
During surgery, the mean arterial blood pressure should be maintained above 70 mm Hg to avoid organ injury. Surgery may be complicated by excessive intraoperative hemorrhage resulting from the presence of portal hypertension and coagulopathy. As a result, it is often necessary to infuse large volumes of blood products or intravenous fluids during a limited time to maintain hemodynamic stability; this may result in exacerbation of portal hypertension and volume overload. To avoid excessive fluid overload, colloid solutions such as albumin should be administered. Permissive hypotension and ischemic conditioning are relatively contraindicated in cirrhotic patients (Clavien et al, 2003), and intraoperative blood transfusion is a significant factor related to morbidity and mortality in patients undergoing hepatic resections. Despite the lack of randomized trials, rFVIIa may limit bleeding and the need for red blood cells, plasma, and platelets transfusions (Franchini et al, 2008; Tsochatzis et al, 2007).
Postoperative Management
Admission to the ICU may become necessary for postoperative patients with underlying cirrhosis given the high risk of complications and mortality in these patients. Among the important critical care issues requiring careful postoperative assessment are fluid derangements, abdominal compartment syndrome, renal failure and hepatorenal syndrome, hepatic encephalopathy, venous thromboembolism, and bleeding as a result of coagulopathy and thrombocytopenia. Once a patient is admitted to the ICU, postoperative mortality rises with increasing length of stay (Povoski et al, 1999).
Fluid Management and Abdominal Compartment Syndrome
Postoperatively, cirrhotic patients are prone to transient hypotension, vasodilation, and fluid shifts. Oliguria also may occur because of reaccumulation of ascites at the expense of the intravascular space. Ascites may occur even in stable cirrhotic patients without documented preoperative ascites. Maintenance of normal renal function is paramount (Cholongitas et al, 2006). Colloid rather than crystalloid fluids should be administered (Garcia-Compean et al, 2002; Planas et al, 1990), and fluid replacement may be guided by the volume of peritoneal fluid drained intraoperatively. If hypotension develops that is refractory to the administration of colloids, vasopressor agents such as norepinephrine may be necessary (Saner et al, 2003). The goal is to limit ascites formation as much as possible. In general, oliguria should not be an indication for diuretic therapy in the setting of significant peritoneal fluid drainage, but rather an indication for fluid (colloids) and vasopressor support, especially if the patient is hemodynamically unstable (Moreau et al, 2002; Appenrodt et al, 2008).
The development of tense ascites may predispose to surgical wound dehiscence, renal failure, peritonitis, and abdominal compartment syndrome (ACS). ACS is characterized by an acute and progressive elevation of the intraabdominal pressure to more than 20 mm Hg in association with failure of one or more organs (Malbrain et al, 2007). The 24-hour fluid balance and peak airway pressure are two independent variables predictive of the development of ACS in nontrauma surgical patients (McNelis et al, 2002). Patients with ACS may have hypotension resulting from decreased venous return, hypoxemia from decreased FRC and ventilator dyssynchrony, and laboratory and radiologic abnormalities from renal failure and bowel ischemia. Measurement of intraabdominal pressure using the bladder is the current mainstay of diagnosis. Excessive fluid administration should be avoided by establishing appropriate endpoints of resuscitation (An & West, 2008). Paracentesis and, in extreme situations, surgical decompression may be necessary to prevent organ injury and wound dehiscence.
Acute Renal Failure and Hepatorenal Syndrome
Acute renal failure (ARF) after liver resection occurs in more than 15% of cases with an attributed mortality rate of 4.2% (Slankamenac et al, 2009). In contrast, ARF is uncommon after cardiac and noncardiac surgery with an overall incidence of 0.85 to 1.7% (Thakar et al, 2005; Kheterpal et al, 2007). A recent scoring system using four criteria—1) cardiovascular disease, 2) elevated alanine aminotransferase (ALT), 3) underlying renal disease, and 4) diabetes mellitus—demonstrated an increased risk of ARF after hepatic resection (Slankamenac et al, 2009). Postoperative ARF in patients with cirrhosis may be caused by parenchymal renal disease, administration of nephrotoxic drugs in the perioperative period, hypovolemia, and hepatorenal syndrome (HRS) (Gines & Schrier, 2009). Management of ARF varies with the etiology and ranges from providing fluid resuscitation in cases of hypovolemia-induced renal failure to renal replacement therapy (Table 23.3).
Table 23-3 Postoperative Issues and Management in Hepatobiliary Surgery
| Issues | Evaluation and Management |
|---|---|
| Fluid derangements |
HRS, hepatorenal syndrome; RBCs, red blood cells; rFVIIa, recombinant factor VIIa; NSAIDs, nonsteroidal antiinflammatory drugs; GPS, graduated pressure stockings; UFH, unfractionated heparin; LMWH, low-molecular-weight heparin
HRS represents the most dreadful postoperative renal complication in patients with underlying liver disease, and it develops in the setting of advanced cirrhosis, when splanchnic and peripheral vasodilation lead to decreased effective intravascular volume, impaired renal perfusion, and increased reabsorption of sodium (Kramer & Horl, 2002). HRS can be precipitated by infection or intravascular volume depletion as a result of perioperative peritoneal fluid drainage or diuretic administration. Subsequent renal ischemia and tubular injury can progress to renal failure. HRS is characterized by oliguria and a low urine sodium concentration.
Acute tubular necrosis (ATN) may be indistinguishable from HRS, as both conditions share similar clinical presentations and findings on urinalysis. The diagnosis of HRS can be established using the criteria of the International Ascites Club (Arroyo et al, 1996). When HRS is documented, the presence of infection, especially peritonitis, should be considered; empiric antibiotic therapy should also be considered, and peritoneal fluid cultures should be monitored (Fernandez et al, 2007). Administration of vasoconstrictors, such as vasopressin or terlipressin, has been shown to improve renal function and reverse HRS (Sanyal et al, 2008; Sharma et al, 2008; Alessandria et al, 2007; Gines et al, 2004). Randomized controlled studies are notably absent, but most reports indicate slow improvement of renal function in approximately two thirds of cases after several days of therapy with terlipressin (Halimi et al, 2002).
Anemia and Hemorrhage
Postoperative bleeding, variceal hemorrhage, and anemia are usually caused by cirrhosis-induced coagulopathy and thrombocytopenia. The risk of postoperative variceal rupture and bleeding is increased by large-volume ascites, excessive blood transfusion, increased portal pressure, and infection. Paracentesis may reduce the hepatic venous pressure gradient, the variceal pressure, and the wall tension in patients with ascites. Infection increases portal pressure, especially peritonitis, through endotoxin and cytokine-mediated responses (Bambha et al, 2008; Hou et al, 2004); this adversely affects coagulation in cirrhotic patients as a result of a heparin effect (Montalto et al, 2002; Zambruni et al, 2004). Octreotide alone or in combination with diuretics may prevent rebleeding by limiting portal hypertension (Morales et al, 2007; Kalambokis et al, 2006).
Anemia and the need for blood products may be prevented by the administration of recombinant erythropoietin if initiated on arrival in the ICU. Administration of FFP is commonly used to treat the coagulopathy; however, volume overload is a major limitation of FFP. Also, rFVIIa may be used to rapidly correct the coagulopathy of postoperative cirrhotic patients, who would need a large volume of FFP otherwise (Ejlersen et al, 2001; Romero-Castro et al, 2004; Bosch et al, 2004). In addition to blood transfusion, acute management of variceal hemorrhage and anemia includes administration of octreotide, vasopressin, and terlipressin (Morales et al, 2007; Abid et al, 2009; Escorsell et al, 2000; Feu et al, 1996; Ioannou et al, 2003).
Sedative and Pain Management and Hepatic Encephalopathy
Sedatives and pain medications should be used judiciously in postoperative patients with cirrhosis to prevent an exacerbation of hepatic encephalopathy. In cirrhotic patients, the pharmacokinetics and pharmacodynamics of sedative and narcotic agents are altered with prolongation of their elimination half-lives as a result of decreased clearance and increased volume of distribution (Delco et al, 2005; MacGilchrist et al, 1986). By impairing respiratory drive and delaying extubation, narcotics and sedatives may predispose to atelectasis, aspiration, and postoperative pneumonia. Among the narcotic agents available, remifentanil is preferred because of its limited hepatic metabolism. Propofol is a better choice than benzodiazepines for sedation because of its shorter recovery time, which may allow for more reliable serial neurologic assessment (Weston et al, 2003; Schilsky et al, 2009). Nonsteroidal agents should be avoided because of the potential for peptic ulceration, fluid retention from inhibition of renal prostaglandin synthesis, and precipitation of hepatorenal syndrome. Hepatic encephalopathy is commonly treated with lactulose orally or with lactitol enemas (Wright & Jahan, 2007). Side effects of lactulose include gaseous distension, abdominal cramps, and anorexia, which may result in higher narcotic requirements and a self-perpetuating cycle. To prevent these complications, simethicone and a polyethylene glycol laxative may be employed. Second-line agents for the treatment of hepatic encephalopathy include oral antibiotics such as neomycin, metronidazole, and rifaximin (Al Sibae & McGuire, 2009).
Prophylaxis against Venous Thromboembolism
The general guidelines for prophylaxis against venous thromboembolism (VTE) include early mobilization, use of intermittent pneumatic compression devices and/or graduated compression stockings, and pharmacologic thromboprophylaxis. Mechanical thromboprophylaxis should be used primarily in patients at high risk of bleeding. In postoperative cirrhotic patients, pharmacologic thromboprophylaxis with unfractionated heparin or low-molecular-weight heparins (LMWHs) must be applied judiciously, because these patients already are predisposed to bleeding (Geerts et al, 2008). The clinical advantages of LMWHs over unfractionated heparin include its once-daily administration and the lower risk of heparin-induced thrombocytopenia (Martel et al, 2005). When the high bleeding risk decreases postoperatively, pharmacologic thromboprophylaxis should be substituted for or added to the mechanical prophylaxis. Renal function must be considered when making decisions regarding the use of LMWHs, as these agents are cleared by the kidney.
Abid S, et al. Terlipressin vs. octreotide in bleeding esophageal varices as an adjuvant therapy with endoscopic band ligation: a randomized double-blind placebo-controlled trial. Am J Gastroenterol. 2009;104(3):617-623.
Aggarwal A, et al. Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU. Chest. 2001;119(5):1489-1497.
Al Sibae MR, McGuire BM. Current trends in the treatment of hepatic encephalopathy. Ther Clin Risk Manag. 2009;5(3):617-626.
Alessandria C, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007;47(4):499-505.
Aller R, et al. Etiology and frequency of gas exchange abnormalities in cirrhosis. Rev Esp Enferm Dig. 1999;91(8):559-568.
Amitrano L, et al. Coagulation disorders in liver disease. Semin Liver Dis. 2002;22(1):83-96.
An G, West MA. Abdominal compartment syndrome: a concise clinical review. Crit Care Med. 2008;36(4):1304-1310.
Anantharaju A, et al. Use of activated recombinant human factor VII (rhFVIIa) for colonic polypectomies in patients with cirrhosis and coagulopathy. Dig Dis Sci. 2003;48(7):1414-1424.
Angeli P, et al. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology. 2006;44(6):1535-1542.
Appenrodt B, et al. Prevention of paracentesis-induced circulatory dysfunction: midodrine vs. albumin: a randomized pilot study. Liver Int. 2008;28(7):1019-1025.
Arabi Y, et al. Outcome predictors of cirrhosis patients admitted to the intensive care unit. Eur J Gastroenterol Hepatol. 2004;16(3):333-339.
Arguedas MR, et al. Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation. Hepatology. 2003;37(1):192-197.
Arroyo V, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23(1):164-176.
Assy N, et al. Risk of sedation for upper GI endoscopy exacerbating subclinical hepatic encephalopathy in patients with cirrhosis. Gastrointest Endosc. 1999;49(6):690-694.
Bajaj JS, et al. Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol. 2009;104(5):1130-1134.
Bambha K, et al. Predictors of early re-bleeding and mortality after acute variceal hemorrhage in patients with cirrhosis. Gut. 2008;57(6):814-820.
Befeler AS, et al. The safety of intra-abdominal surgery in patients with cirrhosis: Model for End-stage Liver Disease score is superior to Child-Turcotte-Pugh classification in predicting outcome. Arch Surg. 2005;140(7):650-654.
Berthier AM, et al. Use of recombinant factor VIIa to treat persistent bleeding following dental extractions in two cirrhotic patients. Vox Sang. 2002;82(3):119-121.
Borroni G, et al. Clinical relevance of hyponatremia for the hospital outcome of cirrhotic patients. Dig Liver Dis. 2000;32(7):605-610.
Bosch J, et al. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology. 2004;127(4):1123-1130.
Bureau C, et al. “A La Carte” treatment of portal hypertension: adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology. 2002;36(6):1361-1366.
Carbonell AM, et al. Poor outcomes in cirrhosis-associated hernia repair: a nationwide cohort study of 32,033 patients. Hernia. 2005;9(4):353-357.
Carvalho A, et al. Small dose of recombinant factor VIIa (rFVIIa) to perform percutaneous liver biopsies in cirrhotic patients. Rev Esp Enferm Dig. 2002;94(5):280-285.
Cazzaniga M, et al. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol. 2009;51(3):475-482.
Chan HL, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med. 2005;142(4):240-250.
Cho JH, et al. Bacteremia is a prognostic factor for poor outcome in spontaneous bacterial peritonitis. Scand J Infect Dis. 2007;39(8):697-702.
Cholongitas E, et al. Risk factors, sequential organ failure assessment and Model for End-stage Liver Disease scores for predicting short-term mortality in cirrhotic patients admitted to intensive care unit. Aliment Pharmacol Ther. 2006;23(7):883-893.
Cholongitas E, et al. RIFLE classification as predictive factor of mortality in patients with cirrhosis admitted to intensive care unit. J Gastroenterol Hepatol. 2009;24(10):1639-1647.
Clavien PA, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003;238(6):843-850.
Csikesz NG, et al. Nationwide volume and mortality after elective surgery in cirrhotic patients. J Am Coll Surg. 2009;208(1):96-103.
Czaja AJ. Current and future treatments of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol. 2009;3(3):269-291.
Delco F, et al. Dose adjustment in patients with liver disease. Drug Saf. 2005;28(6):529-545.
Demetriades D, et al. Liver cirrhosis in patients undergoing laparotomy for trauma: effect on outcomes. J Am Coll Surg. 2004;199(4):538-542.
Dittrich S, et al. Role of hepatic hemodynamic study in the evaluation of patients with cirrhosis. Hepatogastroenterology. 2003;50(54):2052-2056.
Ejlersen E, et al. Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in patients with cirrhosis during bleeding from oesophageal varices. Scand J Gastroenterol. 2001;36(10):1081-1085.
Ercolani G, et al. The lidocaine (MEGX) test as an index of hepatic function: its clinical usefulness in liver surgery. Surgery. 2000;127(4):464-471.
Escorsell A, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000;32(3):471-476.
Escorsell A, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology. 2002;35(2):385-392.
Farnsworth N, et al. Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients. Am J Surg. 2004;188(5):580-583.
Fernandez J, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818-824.
Ferral H, et al. Survival after elective transjugular intrahepatic portosystemic shunt creation: prediction with Model for End-stage Liver Disease score. Radiology. 2004;231(1):231-236.
Feu F, et al. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group. Gastroenterology. 1996;111(5):1291-1299.
Franchini M, et al. The use of recombinant factor VIIa in liver diseases. Blood Coagul Fibrinolysis. 2008;19(5):341-348.
Franzetta M, et al. Prognostic factors of cirrhotic patients in extra-hepatic surgery. Minerva Chir. 2003;58(4):541-544.
Garcia-Compean D, et al. Treatment of cirrhotic tense ascites with Dextran-40 versus albumin associated with large volume paracentesis: a randomized controlled trial. Ann Hepatol. 2002;1(1):29-35.
Geerts WH, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(Suppl 6):381S-453S.
Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279-1290.
Gines P, et al. Review article: pharmacological treatment of hepatorenal syndrome. Aliment Pharmacol Ther. 2004;20(Suppl 3):57-62.
Golembiewski J. Considerations in selecting an inhaled anesthetic agent: case studies. Am J Health Syst Pharm. 2004;61(Suppl 4):S10-S17.
Gupta D, et al. Pulmonary function changes after large volume paracentesis. Trop Gastroenterol. 2000;21(2):68-70.
Gupta D, et al. Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction. Am J Gastroenterol. 2001;96(12):3395-3399.
Hadziyannis SJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005;352(26):2673-2681.
Hadziyannis SJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131(6):1743-1751.
Halimi C, et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002;14(2):153-158.
Harrod-Kim P, Waldman DL. Abnormal portal venous flow at sonography predicts reduced survival after transjugular intrahepatic portosystemic shunt creation. J Vasc Interv Radiol. 2005;16(11):1459-1464.
Hayashida N, et al. Clinical outcome after cardiac operations in patients with cirrhosis. Ann Thorac Surg. 2004;77(2):500-505.
Hickman IJ, Macdonald GA. Impact of diabetes on the severity of liver disease. Am J Med. 2007;120(10):829-834.
Hou MC, et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology. 2004;39(3):746-753.
Ioannou G, et al, 2003: Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev (1):CD002147.
Kajikawa M, et al. Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin. Surgery. 1994;115(6):727-734.
Kalaitzakis E, et al. Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis. Liver Int. 2007;27(9):1194-1201.
Kalambokis G, et al. The effects of treatment with octreotide, diuretics, or both on portal hemodynamics in nonazotemic cirrhotic patients with ascites. J Clin Gastroenterol. 2006;40(4):342-346.
Keeffe EB, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6(12):1315-1341.
Kheterpal S, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007;107(6):892-902.
Kramer L, Horl WH. Hepatorenal syndrome. Semin Nephrol. 2002;22(4):290-301.
Krowka MJ, et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502-1510.
Kuiper JJ, et al. Review article: management of ascites and associated complications in patients with cirrhosis. Aliment Pharmacol Ther. 2007;26(Suppl 2):183-193.
Lau GK, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352(26):2682-2695.
Lentschener C, Ozier Y. Anesthesia for elective liver resection: some points should be revisited. Eur J Anesthesiol. 2002;19(11):780-788.
Lima BL, et al. Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome. Mayo Clin Proc. 2004;79(1):42-48.
GH Lo, et al. Banding ligation versus nadolol and isosorbide mononitrate for the prevention of esophageal variceal rebleeding. Gastroenterology. 2002;123(3):728-734.
Loomba R, et al. Role of fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis: meta-analysis. Clin Gastroenterol Hepatol. 2009;7(4):487-493.
Lorf T, et al. Prognostic value of the monoethylglycinexylidide (MEGX) test prior to liver resection. Hepatogastroenterology. 2008;55(82-83):539-543.
Lund L, et al. Thirty-day case fatality after nephrectomy in patients with liver cirrhosis: a Danish population-based cohort study. Scand J Urol Nephrol. 2003;37(5):433-436.
MacGilchrist AJ, et al. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut. 1986;27(2):190-195.
MacLaren R, et al. Use of exogenous erythropoietin in critically ill patients. J Clin Pharm Ther. 2004;29(3):195-208.
Malbrain ML, et al. Consensus conference definitions and recommendations on intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS): the long road to the final publications, how did we get there? Acta Clin Belg Suppl. 2007;1:44-59.
Maleux G, et al. Early and long-term clinical and radiological follow-up results of expanded polytetrafluoroethylene-covered stent-grafts for transjugular intrahepatic portosystemic shunt procedures. Eur Radiol. 2004;14(10):1842-1850.
Malinchoc M, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31(4):864-871.
Marchesini G, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792-1801.
Martel N, et al. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710-2715.
May JA, et al. The patient recovering from alcohol or drug addiction: special issues for the anesthesiologist. Anesth Analg. 2001;92(6):1601-1608.
Mazzeo AT, et al. Hepatopulmonary syndrome: a concern for the anesthetist? Pre-operative evaluation of hypoxemic patients with liver disease. Acta Anesthesiol Scand. 2004;48(2):178-186.
McNelis J, et al. Predictive factors associated with the development of abdominal compartment syndrome in the surgical intensive care unit. Arch Surg. 2002;137(2):133-136.
Merli M, et al. Malnutrition is a risk factor in cirrhotic patients undergoing surgery. Nutrition. 2002;18(11-12):978-986.
Moller S, Henricksen JH. Cardiovascular complications of cirrhosis. Gut. 2008;57(2):268-278.
Montalto P, et al. Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study. J Hepatol. 2002;37(4):463-470.
Morales GF, et al. Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial. Hepatogastroenterology. 2007;54(73):195-200.
Moreau R, et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomized pilot study. Gut. 2002;50(1):90-94.
Morino M, et al. Laparoscopic cholecystectomy in cirrhosis: contraindication or privileged indication? Surg Laparosc Endosc Percutan Tech. 2000;10(6):360-363.
Nanashima A, et al. Fibrosis and inflammatory activity in noncancerous tissue and mitotic index of cancer tissue in patients with hepatocellular carcinoma: relationship to clinicopathological factors and prognosis after hepatic resection. Dig Dis Sci. 2003;48(8):1517-1522.
Nguyen GC, et al. The impact of cirrhosis and portal hypertension on mortality following colorectal surgery: a nationwide, population-based study. Dis Colon Rectum. 2009;52(8):1367-1374.
Nielsen IL, et al. Thirty-day postoperative mortality after hysterectomy in women with liver cirrhosis: a Danish population-based cohort study. Eur J Obstet Gynecol Reprod Biol. 2002;102(2):202-205.
Nielsen SS, et al. Postoperative mortality in patients with liver cirrhosis undergoing transurethral resection of the prostate: a Danish nationwide cohort study. BJU Int. 2001;87(3):183-186.
Nishiyama T, et al. A comparison of liver function after hepatectomy in cirrhotic patients between sevoflurane and isoflurane in anesthesia with nitrous oxide and epidural block. Anesth Analg. 2004;98(4):990-993.
Nobre SR, et al. In-hospital mortality in spontaneous bacterial peritonitis: a new predictive model. Eur J Gastroenterol Hepatol. 2008;20(12):1176-1181.
Obstein KL, et al. Association between Model for End-stage Liver Disease and spontaneous bacterial peritonitis. Am J Gastroenterol. 2007;102(12):2732-2736.
Oellerich M, Armstrong VW. The MEGX test: a tool for the real-time assessment of hepatic function. Ther Drug Monit. 2001;23(2):81-92.
Patch D, et al. A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis. Gastroenterology. 2002;123(4):1013-1019.
Pavlidis TE, et al. Laparoscopic cholecystectomy in patients with cirrhosis of the liver and symptomatic cholelithiasis. JSLS. 2009;13(3):342-345.
Perdomo Coral G, Alves de Mattos A. Renal impairment after spontaneous bacterial peritonitis: incidence and prognosis. Can J Gastroenterol. 2003;17(3):187-190.
Planas R, et al. Dextran-70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis: results of a randomized study. Gastroenterology. 1990;99(6):1736-1744.
Povoski SP, et al. The critically ill patient after hepatobiliary surgery. Crit Care. 1999;3(6):139-144.
Pronovost P, et al. The association between preoperative patient characteristics and both clinical and economic outcomes after abdominal aortic surgery. J Cardiothorac Vasc Anesth. 1999;13(5):549-554.
Qamar AA, et al. Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis. Clin Gastroenterol Hepatol. 2009;7(6):689-695.
Ravaioli M, et al. Operative risk by the lidocaine test (MEGX) in resected patients for HCC on cirrhosis. Hepatogastroenterology. 2003;50(53):1552-1555.
Rebulla P. Platelet transfusion trigger in difficult patients. Transfus Clin Biol. 2001;8(3):249-254.
Richard AW, et al. Synthetic function. In: Rodes, J, Benhamou, JP. Textbook of Hepatology from Basic Science to Clinical Practice. 3rd ed. Malden, MA: Blackwell; 2007:250-273.
Romero-Castro R, et al. Recombinant-activated factor VII as hemostatic therapy in eight cases of severe hemorrhage from esophageal varices. Clin Gastroenterol Hepatol. 2004;2(1):78-84.
Sahagun G, et al. Outcome of 100 patients after transjugular intrahepatic portosystemic shunt for variceal hemorrhage. Am J Gastroenterol. 1997;92(9):1444-1452.
Salerno F, et al. MELD score is better than Child–Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt. J Hepatol. 2002;36(4):494-500.
Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009;29(9):1396-1402.
Saner F, et al. Postoperative ICU management in liver transplant patients. Eur J Med Res. 2003;8(11):511-516.
Sanyal AJ, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134(5):1360-1368.
Schalm SW, et al. Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomized trial. Gut. 2000;46(4):562-568.
Schenk P, et al. Hepatopulmonary syndrome: prevalence and predictive value of various cutoffs for arterial oxygenation and their clinical consequences. Gut. 2002;51(6):853-859.
Schenk P, et al. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology. 2003;125(4):1042-1052.
Schepke M, et al. Comparison of MELD, Child–Pugh, and Emory model for the prediction of survival in patients undergoing transjugular intrahepatic portosystemic shunting. Am J Gastroenterol. 2003;98(5):1167-1174.
Schilsky ML, et al. ICU management of acute liver failure. Clin Chest Med. 2009;30(1):71-87. viii
Shaheen AA, et al. Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: a population-based study. Liver Int. 2009;29(8):1141-1151.
Sharma P, et al. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103(7):1689-1697.
Shinozuka N, et al. Autologous blood transfusion in patients with hepatocellular carcinoma undergoing hepatectomy. Am J Surg. 2000;179(1):42-45.
Slankamenac K, et al. Development and validation of a prediction score for postoperative acute renal failure following liver resection. Ann Surg. 2009;250(5):720-728.
Spies C, et al. Perioperative morbidity and mortality in chronic alcoholic patients. Alcohol Clin Exp Res. 2001;25(5 Suppl ISBRA):164S-170S.
Surudo T, et al. Rapid correction of prothrombin time after low-dose recombinant factor VIIa in patients undergoing orthotopic liver transplantation. Transplant Proc. 2003;35(6):2323-2325.
Swanson KL, et al. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Am J Transplant. 2008;8(11):2445-2453.
Teh SH, et al. Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of End-stage Liver Disease (MELD) score predicts perioperative mortality. J Gastrointest Surg. 2005;9(9):1207-1215.
Terg R, et al. Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. J Hepatol. 2008;48(5):774-779.
Thakar CV, et al. A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol. 2005;16(1):162-168.
Thulstrup AM, et al. Mortality after open cholecystectomy in patients with cirrhosis of the liver: a population-based study in Denmark. Eur J Surg. 2001;167(9):679-683.
Tsochatzis E, et al. Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment. Dig Liver Dis. 2007;39(5):490-494.
Wahlstrom K, et al. Trauma in cirrhotics: survival and hospital sequelae in patients requiring abdominal exploration. Am Surg. 2000;66(11):1071-1076.
Weston BR, et al. Nurse-administered propofol versus midazolam and meperidine for upper endoscopy in cirrhotic patients. Am J Gastroenterol. 2003;98(11):2440-2447.
Wright G, Jahan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95-110.
Youssef WI, et al. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol. 2003;98(6):1391-1394.
Zaman A, et al. Risk factors for the presence of varices in cirrhotic patients without a history of variceal hemorrhage. Arch Intern Med. 2001;161(21):2564-2570.
Zambruni A, et al. Endogenous heparin-like activity detected by anti-Xa assay in infected cirrhotic and non-cirrhotic patients. Scand J Gastroenterol. 2004;39(9):830-836.
Ziser A, et al. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology. 1999;90(1):42-53.
