Hepatic Failure


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Hepatic Failure

  1. 1. Critical Care Aspects of Chronic Hepatic Failure Aditya N. Dubey, MD Peter K. Linden, MD University of Pittsburgh Medical Center Department Critical Care Medicine
  2. 2. Learning Objectives <ul><li>Be familiar with the complications of chronic liver failure requiring critical care support </li></ul><ul><li>Pathophysiology and clinical sequelae of portal hypertension </li></ul><ul><li>Urgent treatments for variceal hemorrhage </li></ul><ul><li>Strategies to treat diuretic refractory ascites </li></ul><ul><li>Diagnosis, treatment, and prevention of SBP </li></ul><ul><li>Management of hepatorenal syndrome </li></ul><ul><li>Causes and treatment of hepatic encephalopathy </li></ul><ul><li>Indications for referral for liver transplantation </li></ul>
  3. 3. Hepatic Failure <ul><li>Major Reasons for ICU Admission </li></ul><ul><li>Variceal hemorrhage </li></ul><ul><li>Encephalopathy </li></ul><ul><li>Refractory ascites </li></ul><ul><li>Spontaneous bacterial peritonitis </li></ul><ul><li>Hepatorenal syndrome </li></ul>
  4. 4. Portal Hypertension <ul><li>Terminology </li></ul><ul><li>Portal pressure = PV inflow x outflow resistance </li></ul><ul><li>The trans-hepatic gradient (THG) can be measured by the difference between the free hepatic vein to a wedge pressure in the hepatic vein (estimated PV pressure) </li></ul><ul><li>THG = free HVP – wedged HVP </li></ul><ul><li>Normal gradient < 5 mm Hg </li></ul><ul><li>Increased risk of bleeding > 12 mm Hg </li></ul><ul><li>Portal hypertension may be elevated without intrinsic liver disease due to pre- and post-sinusoidal pathology (see next slide). </li></ul>
  5. 5. Causes of Portal Hypertension LIVER Pre-sinusoidal PV thrombosis PV extrinsic comp. Schistosomiasis Sarcoidosis PBC Sinusoidal Cirrhosis Alcoholic hepatitis Post Sinusoidal Budd – Chiari Veno-occlusive dis. Severe CHF Restrictive heart dis. BLOOD FLOW
  6. 6. Variceal Hemorrhage <ul><li>Incidence and Outcome </li></ul><ul><li>Gastroesophageal varices in 40 - 60% cirrhotics </li></ul><ul><li>Variceal hemorrhage occurs in 25 - 35% cirrhotics </li></ul><ul><li>30% of the initial bleeding episodes are fatal </li></ul><ul><li>70% have recurrent bleeding with a one-year survival ranging from 30 - 80% </li></ul><ul><li>Non-variceal pathology (ulcers, gastritis, mucosal tear) may cause bleeding in patients with known liver disease and portal hypertension. </li></ul>Sharara and Rockey. N Engl J Med. 2001;345 (9); 669.
  7. 7. Variceal Hemorrhage <ul><li>Initial evaluation and stabilization </li></ul><ul><li>Assessment of intravascular volume status </li></ul><ul><ul><li>Blood pressure is unreliable indicator of volume status </li></ul></ul><ul><ul><li>Hematocrit does not reflect acute blood losses </li></ul></ul><ul><li>Fluid resuscitation </li></ul><ul><ul><li>Place twp large bore i.v.’s and/or a central venous catheter </li></ul></ul><ul><ul><li>Colloid or crystalloid titrated to parameters of perfusion </li></ul></ul><ul><ul><li>Cross-matched or O negative blood can be used </li></ul></ul><ul><li>Endotracheal intubation prior to endoscopy for: </li></ul><ul><ul><li>Uncontrolled bleeding </li></ul></ul><ul><ul><li>Altered mental status, severe agitation </li></ul></ul><ul><ul><li>Respiratory distress or depression </li></ul></ul>
  8. 8. Hierarchal Treatment for Variceal Bleeding Pharmacologic Endoscopic Radiologic shunt TIPSS Surgical Shunt Balloon Tamponade Pharmacologic and endoscopic therapy are the usual 1 st and 2 nd interventions
  9. 9. Acute Variceal Hemorrhage: Pharmacotherapy <ul><li>Octreotide </li></ul><ul><ul><li>Synthetic analogue of somatostatin </li></ul></ul><ul><ul><li>Decreases portal pressure and azygos blood flow </li></ul></ul><ul><ul><li>Stops variceal bleed in 80% of the cases </li></ul></ul><ul><ul><li>Efficacy is similar to endoscopic sclerotherapy and better than vasopressin </li></ul></ul><ul><ul><li>5-day course reduces bleeding after endoscopic therapy </li></ul></ul><ul><ul><li>Can cause mild hyperglycemia and abdominal cramping </li></ul></ul><ul><li>Vasopressin </li></ul><ul><ul><li>Reduces portal pressure but causes myocardial and mesenteric ischemia </li></ul></ul><ul><li>Terlipressin </li></ul><ul><ul><li>Efficacy similar to endoscopic sclerotherapy and as effective as balloon tamponade when used with nitroglycerin </li></ul></ul><ul><ul><li>Not approved for use in U.S. </li></ul></ul>Corley DA. Gastroenterology. 2001;120(4):946-54; Harry R. Curr Opin Crit Care. 2002;8:164-170; Sharara and Rockey. N Engl J Med. 2001;345(9):669.
  10. 10. Possible Targets for Therapeutic Intervention in Variceal Hemorrhage <ul><li>Reduction of cardiac output by beta-1 blockade to prevent bleeding (NOT for acute bleeding!!) </li></ul><ul><li>Reduction of splanchnic blood flow by beta-2 blockade or vasoconstrictors such as alpha-adrenergic agonists or vasopressin analogues </li></ul><ul><li>Reduction of intrahepatic resistance by vasodilators </li></ul><ul><li>Reduction of variceal or collateral flow by beta-2 blockade, balloon tamponade, or endoscopic therapy </li></ul>
  11. 11. Esophageal vs. Gastric Varices <ul><li>Esophageal varices </li></ul><ul><li>Primary approach is endoscopic banding or sclerotherapy </li></ul><ul><li>TIPSS, surgical shunts are alternatives </li></ul><ul><li>Gastric varices </li></ul><ul><li>Diffuse, deep submucosal anatomy </li></ul><ul><li>Endoscopic tx difficult, dangerous </li></ul><ul><li>Primary approach are TIPSS or surgery </li></ul>
  12. 12. Variceal Hemorrhage: Endoscopic Therapy <ul><li>Endoscopic Band Ligation (see next slide) </li></ul><ul><ul><li>Controls bleeding in 80 - 90% of cases </li></ul></ul><ul><ul><li>Lower complication rates than sclerotherapy </li></ul></ul><ul><li>Endoscopic Sclerotherapy </li></ul><ul><ul><li>Intravariceal or paravariceal injection of a sclerosing agent </li></ul></ul><ul><ul><li>Stops bleeding in 80 to 90% of the cases </li></ul></ul><ul><ul><li>Complications include perforation, ulceration and stricture </li></ul></ul><ul><li>Cyanoacrylate Injection </li></ul><ul><ul><li>Used to control bleeding from gastric varices </li></ul></ul><ul><ul><li>Superior to EBL for treatment of bleeding gastric varices </li></ul></ul><ul><ul><li>Not available in U.S. </li></ul></ul>Laine L. Ann Intern Med. 1995;123(4):280-7. Lo GH. Hepatology. 2001;33:421-427.
  13. 13. Banding of Esophageal Varix
  14. 14. Post endoscopy problems include… <ul><li>Abdominal distension : From endoscopic air insufflation, retained luminal blood, and increased ascites from resuscitation. This can even progress to abdominal compartment syndrome with associated respiratory compromise, hypotension, oliguria, and acidosis. Nasogastric decompression may partially alleviate this problem . </li></ul><ul><li>Worsening encephalopathy : This may occur due to gastrointestinal passage of blood, hepatic hypoperfusion (“shock liver), and accumulation of sedative medication. </li></ul><ul><li>Recurrent bleeding : More likely to recur in advanced cirrhosis. Incidence can be reduced with a 5-day course of octreotide post banding and long term use of a non-selective beta blocker (propanol, naldolol). </li></ul><ul><li>Infection : Spontaneous bacterial peritonitis is 3-5x higher following variceal hemorrhage due to occult bacteremia and ascites seeding. Antimicrobial prophylaxis (quinolone, beta-lactam) reduces the incidence of SBP significantly. </li></ul>
  15. 15. Acute Variceal Hemorrhage Balloon Tamponade <ul><li>Effectively controls bleeding in 90% of the patients but is only a temporizing measure in massive uncontrolled variceal hemorrhage when initial endoscopic treatment is delayed or unsuccessful. </li></ul><ul><ul><li>Can cause aspiration, esophageal ulceration, perforation with mediastinitis </li></ul></ul><ul><ul><li>Balloon-related mortality is 3 - 5% </li></ul></ul><ul><ul><li>Gastric balloon inflation is usually sufficient </li></ul></ul><ul><ul><li>Esophageal balloon inflation should only be used when gastric balloon is unsuccessful as it is associated with higher morbidity. </li></ul></ul>
  16. 16. Sengstaken – Blakemore Tube <ul><li>Gastric balloon </li></ul><ul><li>Esophageal balloon </li></ul><ul><li>Gastric aspiration port </li></ul>
  17. 17. Minnesota Tube <ul><li>Gastric balloon </li></ul><ul><li>Esophageal balloon </li></ul><ul><li>Gastric aspiration port </li></ul><ul><li>Esophageal aspirationport </li></ul>
  18. 18. Tube Positioning and Gastric Balloon Inflation <ul><ul><li>1. Tube inserted to 50 cm </li></ul></ul><ul><ul><li>2. Auscultate in stomach </li></ul></ul><ul><ul><li>3. Inflate gastric balloon with 50 cc </li></ul></ul><ul><ul><li>4. Stat portable film </li></ul></ul><ul><li>Re-confirm proximal position </li></ul><ul><li>Inflate GB 300-400 cc air </li></ul><ul><li>Pull to insure anchorage </li></ul><ul><li>Recheck film </li></ul><ul><li>1-2 lbs of pully traction </li></ul>
  19. 19. Gastric and Esophageal Balloon Inflation <ul><li>Esophageal Balloon inflated to 30 mmHg </li></ul><ul><li>Last resort </li></ul><ul><li>Deflate periodically </li></ul><ul><li>Use minimum effective pressure </li></ul><ul><li>Complication </li></ul><ul><li>- ulcer </li></ul><ul><li>- perforation </li></ul><ul><li>- stricture </li></ul>
  20. 20. Malposition of the Gastric Balloon of a Minnesota Tube Retroverted in the Distal Esophagus
  21. 21. Transjugular Intrahepatic Portosystemic Shunt (TIPSS) <ul><li>Major Indications </li></ul><ul><li>Refractory variceal bleeding </li></ul><ul><li>Refractory ascites, hydrothorax </li></ul><ul><li>Radiologic insertion of a metallic shunt (8 - </li></ul><ul><li>12 mm diameter) which joins the hepatic and portal veins </li></ul><ul><li>Target gradient (HV-PV) < 12 mmHg </li></ul><ul><li>Restores hepatopedal flow </li></ul><ul><li>Decompression of varices </li></ul>
  22. 22. Summary of Trials Comparing TIPSS to Endoscopic Therapy for Variceal Bleeding Stanley. Lancet. 1997;350(9086):1235-1239. Generally, higher rates of rebleeding were more common after Endoscopy treatment, while encephalopathy rates were higher in the TIPSS groups
  23. 23. Complications of TIPSS <ul><li>Peri-procedure mortality of 1 - 2% </li></ul><ul><ul><li>Intraperitoneal bleeding due to perforation of the hepatic capsule, hepatic, or portal veins </li></ul></ul><ul><ul><li>TIPSS embolization </li></ul></ul><ul><ul><li>Acute right heart failure due to increased venous return to right heart </li></ul></ul><ul><li>Later complications include recurrent bleeding due to TIPSS stenosis or thrombosis, infection, and hepatic encephalopathy. </li></ul>
  24. 24. Conditions Which May Contraindicate TIPSS This venogram shows an occlusive thrombus of the portal vein, which may make safe TIPSS placement impossible. This abdominal CT demonstrates a large hypodense hepatic lesion due to hepatocellular carcinoma in a very shrunken cirrhotic liver. Other contraindications include hepatic vein occlusion, heart failure or pulmonary hypertension, biliary obstruction, and poorly controlled systemic infection.
  25. 25. TIPSS Thrombosis/Stenosis <ul><li>Incidence 12 - 74% </li></ul><ul><li>Most likely within the first month </li></ul><ul><li>Symptoms - recurrent bleeding, ascites </li></ul><ul><li>Detection - Doppler ultrasound angiography (shows velocity gradient) </li></ul><ul><li>Treatment </li></ul><ul><ul><li>Balloon dilatation </li></ul></ul><ul><ul><li>Placement of TIPS shunt </li></ul></ul>
  26. 26. Trans-TIPSS Embolization of Persistent Varices Persistent variceal bleeding due to high flow collaterals despite a patent TIPS shunt may be coil-embolized radiologically via the TIPS shunt itself.
  27. 27. Acute Variceal Hemorrhage: Surgery <ul><li>The distal splenorenal shunt (Warren shunt) procedure is generally reserved for Child’s A or B cirrhotics. </li></ul><ul><li>Consider in patients with bleeding refractory to pharmacologic, endoscopic, and radiologic treatment. </li></ul><ul><li>Complications include shunt thrombosis, infection, and worsening encephalopathy. </li></ul><ul><li>30-day mortality is close to 80% in Child’s C patients requiring emergency shunt surgery. </li></ul>
  28. 28. Relative Effectiveness of Available Therapies for the Prevention of Recurrent Variceal Bleeding Beta-blockers are the single most effective and safest strategy to prevent the recurrence of variceal Bleeding. More aggressive strategies such as banding, TIPSS, or shunt surgery may decrease bleeding but are associated with higher risks and costs. Sharara A, et al. N Engl J Med. 2001.
  29. 29. Hepatic Encephalopathy <ul><li>Hepatic encephalopathy reflects a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease. </li></ul>
  30. 30. Hepatic Encephalopathy – West Haven Criteria for Grading Mental State <ul><li>Grade 1 </li></ul><ul><ul><li>Trivial lack of awareness </li></ul></ul><ul><ul><li>Euphoria or anxiety </li></ul></ul><ul><ul><li>Shortened attention span </li></ul></ul><ul><ul><li>Impaired performance of addition </li></ul></ul><ul><li>Grade 2 </li></ul><ul><ul><li>Lethargy or apathy </li></ul></ul><ul><ul><li>Minimal disorientation for time or place </li></ul></ul><ul><ul><li>Subtle personality change </li></ul></ul><ul><ul><li>Inappropriate behavior </li></ul></ul><ul><ul><li>Impaired performance of subtraction </li></ul></ul><ul><li>Grade 3 </li></ul><ul><ul><li>Somnolence to semi-stupor but responsive to verbal stimuli </li></ul></ul><ul><ul><li>Confusion </li></ul></ul><ul><ul><li>Gross disorientation </li></ul></ul><ul><li>Grade 4 </li></ul><ul><ul><li>Coma, unresponsive to verbal or noxious stimuli </li></ul></ul>
  31. 31. Hepatic Encephalopathy: Differential Diagnosis <ul><li>Metabolic encephalopathies </li></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Hypoxia </li></ul></ul><ul><ul><li>Uremia </li></ul></ul><ul><ul><li>Electrolyte abnormalities </li></ul></ul><ul><li>Toxic encephalopathies </li></ul><ul><ul><li>Alcohol </li></ul></ul><ul><ul><li>Barbiturates, other CNS depressants </li></ul></ul><ul><ul><li>Heavy metals </li></ul></ul><ul><li>Intracranial lesions </li></ul><ul><ul><li>Subarachnoid, subdural, or intracerebral hemorrhage </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Intracranial tumor </li></ul></ul><ul><ul><li>Intracranial abscess </li></ul></ul><ul><ul><li>Epilepsy </li></ul></ul><ul><li>Neuropsychiatric disorders </li></ul>
  32. 32. Hepatic Encephalopathy: Precipitating Factors <ul><li>Increased ammonia production </li></ul><ul><ul><li>Gastrointestinal hemorrhage </li></ul></ul><ul><ul><li>Excess dietary protein </li></ul></ul><ul><ul><li>Azotemia </li></ul></ul><ul><ul><li>Infection including SBP </li></ul></ul><ul><ul><li>Blood transfusion </li></ul></ul><ul><ul><li>Hypokalemia </li></ul></ul><ul><ul><li>Systemic alkalosis </li></ul></ul><ul><ul><li>Constipation </li></ul></ul><ul><li>Reduced metabolism of toxins because of hepatic hypoxia </li></ul><ul><ul><li>Dehydration </li></ul></ul><ul><ul><li>Arterial hypotension </li></ul></ul><ul><ul><li>Anemia </li></ul></ul><ul><li>Portosystemic shunts </li></ul><ul><ul><li>Spontaneous </li></ul></ul><ul><ul><li>TIPSS </li></ul></ul><ul><ul><li>Surgical </li></ul></ul><ul><li>Progressive hepatic </li></ul><ul><li>parenchymal damage </li></ul><ul><li>Hepatoma </li></ul><ul><li>Use of benzodiazepines or other psychoactive drugs </li></ul>Riordan. N Engl J Med. 1997; 337(7):473-479.
  33. 33. Why does the ammonia level correlate poorly with encephalopathy? <ul><li>Venous ammonia levels < arterial </li></ul><ul><li>Time lag from ↑NH3 and CNS </li></ul><ul><li>Blood-brain permeability is variable </li></ul><ul><li>Balance of NH3 / NH4 + </li></ul><ul><li>Processing (must be on ice, < 20 min) </li></ul>
  34. 34. Management of Hepatic Encephalopathy <ul><li>First and foremost control the underlying precipitant(s). </li></ul><ul><li>Medical therapy - optimal agent is controversial (see meta-analysis) </li></ul><ul><li>Lactulose - has multiple actions including cathartic, acidification of the colon to </li></ul><ul><li>“ ion-trap” ammonia as NH 4 + , and reduces inoculum of urea-splitting bacteria. </li></ul><ul><li>Drawbacks include osmotic diarrhea with hypernatremia due to free water loss </li></ul><ul><li>and gaseous bowel distension. </li></ul><ul><li>Neomycin - non-absorbed aminoglycoside which reduces colon bacterial </li></ul><ul><li>burden. Dosed at 2-6 grams orally per day. Small incidence of ototoxicity and </li></ul><ul><li>nephrotoxicity with prolonged usage. </li></ul><ul><li>Metronidazole - oral dosing at 800 mg/day. No large scale reported </li></ul><ul><li>experience. Is associated with neurotoxicity in hepatic failure due to </li></ul><ul><li>accumulation. </li></ul><ul><li>Flumazenil - benzodiazepine receptor (GABA) antagonist. </li></ul>
  35. 35. Flumazenil in Hepatic Encephalopathy <ul><li>In this double-blind, placebo-controlled, randomized trial, </li></ul><ul><li>flumazenil showed transient benefit in higher grades of </li></ul><ul><li>encephalopathy. The role of flumazenil for all degrees of encephalopathy or as a longer term agent in critically ill patients has not been determined. </li></ul>Barbaro G, et al. Hepatology. 1998 5.0% (Gr3) 3.3% (Gr4) 27.8% (Gr3) 21.5% (Gr4) EEG improvement 3.8% (Gr3) 2.7% (Gr4) 17.5% (Gr3) 14.7% (Gr4) Neurologic improvement Placebo N = 262 Flumazenil N = 265
  36. 36. Ascites - Critical Care Aspects <ul><li>Complicated ascites may be the principal reason for care admission but is frequently co-associated with intensive hemorrhage, renal failure, and/or hepatic encephalopathy. </li></ul><ul><li>Common complications of ascites include: </li></ul><ul><ul><li>Diuretic-refractory ascites - defined as unresponsiveness to sodium restriction and high-dose diuretics (400 mg/day spironolactone and 160 mg/day furosemide) OR rapid recurrence after therapeutic paracentesis </li></ul></ul><ul><ul><li>Tense ascites - this may result in the development of: </li></ul></ul><ul><ul><ul><li>- Abdominal compartment syndrome with impaired venous return causing hypotension, impaired renal perfusion causing oliguria and reduced hepatosplanchic perfusion </li></ul></ul></ul><ul><ul><ul><li>- Respiratory compromise may occur due to impaired diagphagmatic contractility and/or hydrothorax due to the passage of ascites into the pleural space </li></ul></ul></ul><ul><ul><li>Infection - (spontaneous bacterial peritonitis) </li></ul></ul>Runyon BA. Hepatology March 2004
  37. 37. Paracentesis <ul><li>Abdominal paracentesis is the most rapid and cost-effective technique to diagnose the cause of ascites. </li></ul><ul><ul><li>An area of percussion dullness in the left lower quadrant (2 cm cephalad and anterior to the anterior superior iliac spine) has a greater likelihood of ascites present than the midline. </li></ul></ul><ul><ul><li>Ultrasound guidance should be utilized if ascites is difficult to localize and to avoid venous collaterals, intestine. </li></ul></ul><ul><ul><li>Since bleeding is sufficiently uncommon, the prophylactic use of plasma or platelets before paracentesis is not recommended. </li></ul></ul><ul><ul><li>An indwelling drainage catheter can be left for 3 - 5 days if therapeutic drainage is required. </li></ul></ul>Runyon BA. Hepatology. 2004.
  38. 38. Ascites - Classification <ul><li>High SAAG  1.1g/dl </li></ul><ul><li>Cirrhosis (75% cases) </li></ul><ul><li>Alcoholic hepatitis </li></ul><ul><li>Portal vein thrombosis </li></ul><ul><li>Budd-Chiari syndrome </li></ul><ul><li>Cardiac failure </li></ul><ul><li>Veno-occlusive disease </li></ul><ul><li>Low SAAG  1.1g/dl </li></ul><ul><li>Peritoneal carcinomatosis </li></ul><ul><li>Pancreatic ascites </li></ul><ul><li>Biliary ascites </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Tuberculous peritonitis </li></ul>Krige J, et al. BMJ. 2001;322.
  39. 39. Spontaneous Bacterial Peritonitis <ul><li>Spontaneous infection of ascitic fluid in the absence of a secondary intra-abdominal source of infection </li></ul><ul><li>Translocation of intestinal bacteria or hematogenous seeding of ascites </li></ul><ul><li>Mainly a complication of cirrhotic ascites </li></ul><ul><li>Incidence is 15 - 20% of cirrhotics with the highest incidence in Child’s Class C cirrhosis and following upper gastrointestinal bleeding </li></ul><ul><li>E. coli, Klebsiella sp., S. pneumoniae most common </li></ul><ul><li>Clinical manifestations include fever, abdominal pain, unexplained encephalopathy, although asymptomatic presentations are not uncommon </li></ul><ul><li>Mortality per episode = 20 - 30% </li></ul><ul><li>One year follow-up mortality = 50% </li></ul>
  40. 40. Spontaneous Bacterial Peritonitis Diagnosis <ul><li>Ascites should be processed for the following: </li></ul><ul><ul><li>Total cell count and differential </li></ul></ul><ul><ul><li>Bacterial cultures in blood culture bottles </li></ul></ul><ul><ul><li>Other tests (protein, albumin, LDH, glucose, special cultures) may be indicated based upon clinical judgment </li></ul></ul><ul><li>A diagnosis of SBP is established by any one of the following: </li></ul><ul><ul><li>> 250 polymorphonuclear cells per cubic mm of ascitic fluid and a positive ascitic fluid culture is diagnostic. </li></ul></ul><ul><ul><li>Patients with  250 PMN’s/mm 3 but negative cultures (neutrocytic ascites) </li></ul></ul><ul><ul><li>Positive ascites cultures and < 250 PMNs/mm 3 (monomicrobial non-neutrocytic ascites) </li></ul></ul>Runyon BA. Hepatology. 2004.
  41. 41. Spontaneous Bacterial Peritonitis Treatment <ul><li>Intravenous albumin 1.5g/kg at the time of diagnosis followed by 1g/kg on day 3 helps in preventing hepatorenal syndrome and decreases mortality </li></ul><ul><li>(Sort P, et al. N Engl J Med. 1999;341:403-409) </li></ul><ul><li>Secondary bacterial peritonitis </li></ul><ul><ul><li>PMN count  250 cells/mm3 </li></ul></ul><ul><ul><li>Multiple organisms on Gram’s stain and culture </li></ul></ul><ul><ul><li>Two of the following ascites criteria: </li></ul></ul><ul><ul><ul><li>- Total protein > 1g/dl </li></ul></ul></ul><ul><ul><ul><li>- LDH > upper limit of normal for serum </li></ul></ul></ul><ul><ul><ul><li>- Glucose < 50mg/dl </li></ul></ul></ul><ul><ul><li>Treatment – Third generation cephalosporin and laparotomy </li></ul></ul>
  42. 42. Spontaneous Bacterial Peritonitis AASLD Guidelines <ul><li>Patients with ascitic fliud PMN  250/mm should receive empiric antibiotic therapy e.g., cefotaxime, 2 g every 8 hours (I). </li></ul><ul><li>Patients with ascitic fliud PMN < 250/mm with signs or symptoms of infection should receive empiric antibiotics pending culture results (II-B). </li></ul><ul><li>Oral ofloxacin can be considered in patients without vomiting, shock, grade 2 hepatic encephalopathy, or serum creatinine > 3mg/dl. </li></ul><ul><li>Prevention of SBP: </li></ul><ul><ul><li>Short-term (7 days) inpatient norfloxacin or bactrim prophylaxis in patients with gastrointestinal hemorrhage </li></ul></ul><ul><ul><li>Patients with prior SBP should receive long term prophylaxis with daily norfloxacin or bactrim (SBP recurs in up to 70% of cases within one year). </li></ul></ul>
  43. 43. Refractory Ascites: Management <ul><li>Serial paracentesis every 2 to 4 weeks and/or transjugular intrahepatic portosystemic shunts: </li></ul><ul><ul><li>Post-paracentesis volume expansion is controversial but may be considered when 5 l or more of fluid is removed. Albumin (6-8 g per l of fluid removed), dextran 70 or hemacecel may be used. </li></ul></ul><ul><li>A recent meta-analyses comparing TIPS vs. Paracentesis showed: </li></ul><ul><ul><li>30-day mortality - no difference, OR 1.0 (CI 0.1-10.06) </li></ul></ul><ul><ul><li>24-month mortality - no difference, OR 1.17 (CI 0.52-2.66) </li></ul></ul><ul><ul><li>12-month ascitic fluid reaccumulation - less in TIPS, OR 0.14 (CI 0.06-0.28) </li></ul></ul><ul><ul><li>Hepatic encephalopathy - more with TIPS, OR 2.11 (CI 1.22-3.66) </li></ul></ul><ul><ul><li>No difference in the incidence of GI bleed, infections, or acute renal failure. </li></ul></ul>Sheagren JN, et al. J Clin Gast. 1996; Saab S. Cochrane Hepato-Biliary Group. 2005.
  44. 44. Tc Labeled Sulfur Colloid Showing Fluid Passage From Peritoneal to Pleural Space 99 Bhattacharya, et al. J Gastroenterol Hepatol. 2001.
  45. 45. Right Hydrothorax Managed with Plerual Catheter Drainage Before After
  46. 46. Hepatorenal Syndrome <ul><li>Type 1 HRS: </li></ul><ul><li>Acute impairment in renal function defined by doubling of initial serum creatinine above 2.5 mg/dl or a 50% reduction of the initial 24-hour creatinine clearance to a level lower than 20 ml/min in less than two weeks. Mortality is as high as 90% after 2 - 4 weeks </li></ul><ul><li>Type 2 HRS: </li></ul><ul><li>Stable or slowly progressive impairment in renal function not meeting the above criteria. Associated with better survival than Type 1 HRS. </li></ul>
  47. 47. Hepatorenal Syndrome Pere Ginès, et al. N Engl J Med. 2004;350:1646-1654.
  48. 48. Hepatorenal Syndrome <ul><li>Criteria for Diagnosis of HRS: </li></ul><ul><ul><li>Serum creatinine >1.5 mg/dl or 24-hr creatinine clearance < 40ml/min </li></ul></ul><ul><ul><li>Absence of shock, ongoing bacterial infection or fluid loss, and no current treatment with nephrotoxic drugs </li></ul></ul><ul><ul><li>Absence of sustained improvement in renal function (decrease in serum creatinine to  1.5mg/dl) after discontinuation of diuretics and trial of plasma expansion </li></ul></ul><ul><ul><li>Absence of proteinuria (< 500 mg/d) or hematuria (< 50 RBCs per HPF) </li></ul></ul><ul><ul><li>Absence of ultrasonographic evidence of obstructive uropathy or parenchymal renal disease </li></ul></ul><ul><ul><li>Urinary sodium concentration < 10 mmol/L </li></ul></ul>
  49. 49. Hepatorenal Syndrome: Treatment <ul><li>Administration of one of the following drugs or drug combinations can be considered: </li></ul><ul><ul><li>Norepinephrine 0.5 - 3.0mg/h intravenously </li></ul></ul><ul><ul><li>Midodrine 7.5 mg three times daily increased to 12.5 mg three times daily if needed in combination with octreotride 100  g subcutaneously three times daily, increased to 200  g three times daily if needed </li></ul></ul><ul><li>Concomitant adminstration of albumin 1 g/kg intravenously on day one, followed by 20 - 40 g daily </li></ul><ul><li>This treatment is given for 5 to 15 days. </li></ul><ul><li>End point of the treatment is reduction of serum creatinine to < 1.5 mg/dl </li></ul>
  50. 50. Vasoconstrictor Studies in HRS Or – orlipressin NE – norepinephrine Te - terlipressin OC - octreotide Mi - midodrine A - albumin These results, although encouraging, need to be validated by a large, prospective randomized trial. 30 (18%) 73 (44%) 104 (63%) 165 TOTAL 13 36 58 99 Te ± A Moreau 3 6 10 12 NE + A Duvoux 2 4 4 5 Mi,Oc,A Angeli 5 9 10 13 Te ± A Ortega 2 4 7 12 Te + A Mulkay 2 4 4 7 Or, D, A Gulberg 3 5 7 9 Te + A Uriz - 5 4 8 Or + A Guevara Liver Tx Survival HRS Reversal # Pts Treatment STUDY
  51. 51. Hepatorenal Syndrome: Treatment <ul><li>Hemodialysis or continuous venovenous hemofiltration may be required as a bridge to liver transplant. </li></ul><ul><li>Liver transplantation offers the best survival rate of 70% at two years. </li></ul><ul><li>Kidney function may return to normal post successful liver transplant. </li></ul>
  52. 52. Other Pulmonary Complications of Chronic Liver Disease <ul><li>Hepatopulmonary syndrome </li></ul><ul><ul><li>Incidence of 4 - 29% </li></ul></ul><ul><ul><li>Diagnosis requires demonstration of hypoexmia due to abnormal intrapulmonary vascular dilatations causing shunting or severe ventilation:perfusion mismatching. </li></ul></ul><ul><ul><li>Vascular dilatations demonstrable by either agitated saline echocardiography or macro-aggregated albumin scanning. </li></ul></ul><ul><ul><li>Orthodeoxia (desaturation with upright posture) and platypnea (dyspnea with upright posture) may be seen. </li></ul></ul><ul><ul><li>Management include supplemental oxygen to maintain SaO2. </li></ul></ul><ul><ul><li>Mortality rate of 41% at 2.5 years reported. </li></ul></ul><ul><ul><li>Severe HPS may slowly remit after successful liver transplantation although supplemental oxygen required. </li></ul></ul><ul><li>Portopulmonary hypertension </li></ul><ul><ul><li>Incidence of 2 - 10% (as high as 16% in those referred for liver transplant) </li></ul></ul><ul><ul><li>Mean PA pressure > 25 mmHg, PVR > 250 dyne s -1 cm -5 , PA occlusion (wedge) < 15 mmHg </li></ul></ul><ul><ul><li>Pathogenesis unclear but may include pulmonary arterial plexopathy in medium pulmonary arteries due to shear stress or high output state or humoral influences. </li></ul></ul><ul><ul><li>Suspect in patients with progressive dyspnea and signs of right heart failure. </li></ul></ul><ul><ul><li>Continuous prostacyclin (PGI2) infusion has shown benefit in non-randomized, open label experience but may not improve long term survival without liver transplantation. </li></ul></ul><ul><ul><li>Severe cases (mean PA > 45) or poor right heart function contraindicates liver transplantation. </li></ul></ul>Hoeper MM, et al. Lancet. 2004;363(9419):1461-8.
  53. 53. Pathophysiology of Hypoxemia in Hepatopulmonary Syndrome Hoeper MM, et al. Lancet.2004;363(9419):1461-8.
  54. 54. Considerations for Liver Transplantation in Critically Ill <ul><li>Liver transplantation is the most effective treatment for chronic liver failure with an overall, one-year, 88% patient survival. </li></ul><ul><li>Patients with cirrhosis should be referred for transplantation when evidence of hepatic dysfunction or major complications develop. </li></ul><ul><li>Patients with type I HRS should have an expedited referral for liver transplantation. </li></ul><ul><li>The prognostic model for end stage liver disease (MELD score) predicts liver-related mortality based upon the serum Cr, serum bilirubin, and INR. </li></ul>Murray K, Carithers R. AASLD Practice Guidelines: evaluation of the patient for liver transplantation. Hepatology. 2005.
  55. 55. Liver Transplantation