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Inpatient Management of the Cirrhotic Patient Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery Hepatocentric View “In the beginning, there was nothing……… Then God created the liver and gave it internal viscera and appendages to provide sustenance and mobility.” A bit about me… Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery What is Cirrhosis? The end stage of any chronic liver disease HCV and EtOH are main causes in USA Results in two major syndromes – Portal hypertension – Hepatic insufficiency Associated with hyperdynamic circulatory state due to – Peripheral vasodilation – Splanchnic vasodilation Manifestations of Decompensation Jaundice: hepatic insufficiency GEV: portal HTN and hyperdynamic circulation Ascites: sinusoidal HTN and sodium retention due to vasodilation and neurohumoral systems HRS: peripheral dilation->renal vasoconstriction HE: shunting through portosystemic collaterals, brain edema, and hepatic insufficiency “Status of the Liver” 1964 – Child and Turcotte publish a system to predict mortality related to portocaval shunt surgery in cirrhosis* 1973 – Pugh modified C-T scoring system to predict mortality related to esophageal surgery for bleeding varices (replaced ‘nutritional status” with PT)** Child’s score = C-P score = CTP score *Child, CG, Turcotte, JG. Surgery and portal hypertension. In: The Liver and Portal Hypertension, Child, CG (Ed), Saunders, Philadelphia 1964. p.50. **Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC and Williams R. Transection of the esophagus for bleeding esophageal varices. Brit. J. Surg. 60: 646-654, 1973 Child’s Classification Points* Presentation: 1 2 3 Albumin (g/dl) > 3.5 2.8 - 3.5 < 2.8 Prothrombin time (INR) < 1.7 1.7 - 2.3 > 2.3 Bilirubin (mg/dl) <2 2-3 >3 Ascites Absent Mild/Moderate Severe (diuretic responsive) (diuretic refractory) Encephalopathy None Gr. I – II Gr. III – IV (precipitated) (chronic) *Class A = 5-6 points, B = 7-9 points, C = 10-15 points Interpreting Child’s Score These grades correlate with one- and two-year patient survival: – Class A - 100 and 85 % – Class B - 80 and 60 % – Class C - 45 and 35 % Child’s class A are compensated – Median survival ~9-12 years – Management goals: Treat underlying liver disease Prevention/early diagnosis of complications Child’s class B&C are decompensated Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has renal insufficiency - If patient has portosystemic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery If The Patient Has Ascites Development of ascites in cirrhosis is common (60% over 10yrs); once ascites develops mortality can reach 50% over the next 2yrs. Ascites formation is very common in postoperative setting in patients with cirrhosis/portal HTN due to liberal use of saline IVF (this can often be the initial presentation of cirrhosis - - missed pre-op!) If The Patient Has Ascites Clues: – Exam: palpable left/small right lobe, splenomegaly, caput medusa – Labs: Platelets < 175,000 Hepatic insufficiency: albumin <3.8, INR >1.3 – Imaging: nodular liver, splenomegaly If The Patient Has Ascites Diagnostic paracentesis: – No coagulopathy cutoff, need for “reversal”, etc – Cell count and differential, albumin, and total protein – If first presentation, concern over infection, or atypical presentation Glucose Bedside culture Flow cytometry Simultaneous blood cultures (more later) LDH Triglycerides – Don’t forget serum albumin to determine SAAG If The Patient Has Ascites - - Make the diagnosis (i.e. recognize it, then analyze the fluid - - diagnostic paracentesis) Turn off the NS IV infusion! Think about carrier solutions for each of the patient’s IV infusions Sodium restriction: 2gm/day (88mEq) Oral diuretics: spironolactone alone or spironolactone/furosemide (100/40 ratio) Goal: 300-500 ml/d (no edema) vs. 1000 ml/d (w/ edema) Tense ascites: perform a large volume paracentesis (don’t forget the albumin - - 6-8 gm per liter ascites removed) High risk patients with ascites should be placed on SBP prophylaxis (TP<1 and advanced liver failure) If The Patient Has Ascites - Do NOT use furosemide alone - Sodium not taken up in LoH absorbed in DCT/CT due to hyperaldosteronism - Do NOT use IV diuretics No evidence that other diuretics (metolazone, thiazides, torsemide) offer advantage of spironolactone +/- furosemide Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery If The Patient Has SBP - - - Most common infection in cirrhosis Occurs in 10-20% of hospitalized patients with cirrhosis and ascites Mortality 10-20% (was 80% when first described) Early diagnosis is KEY to management and reduction of complications Diagnostic paracentesis in any patient with cirrhosis and ascites: - Upon hospital admission - Who develops S/Sx compatible with SBP (abd pain, F/C) - With worsening renal or liver function If The Patient Has SBP - Diagnosis established: - Ascites PMN cell count >250 - Ensure bedside cultures collected - Simultaneous BCx should also be drawn (>50% SBP also have bacteremia) - Traumatic tap if >10,000 RBC - Subtract 1 PMN for every 250 RBC If The Patient Has SBP - Do not wait on culture results to start Abx - Cefotaxime most studied (2g q12hr) - 3rd generation cephalosporine (ceftriaxone 1-2g q12hr) - “Quinolone” ok if community-acquired, uncomplicated - Extended spectrum Abx (carbapenems, piperacillin/tazobactam) if nosocomial SBP Can change to PO in 48hrs if improving - 5 day course of Tx minimum, 8 days preferred, thus 7 days reasonable - Repeat paracentesis/broaden coverage if not improving in 48hrs (expect at least 25% PMN decrease) - If The Patient Has SBP - Albumin to prevent renal dysfunction (10% vs. 3%) and 3 month mortality (41% vs. 22%) - 1.5g/kg on day #1 within 6 hours of Dx - 1.0g/kg on day #3 (reasonable to tailor to renal fx) - What NOT to do: - Avoid aminoglycosides - No large volume paracentesis - Avoid diuretics (stop them if Pt is taking them) Cuban Rock Iguana Cuban Rock Iguana Cuban Rock Iguana Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery If The Patient Acute Kidney Injury (AKI) AKI occurs in ~19% hospitalized patients with cirrhosis – Pre-renal ~68% of these – Intra-renal next most common (ATN vs. GN) – Post-renal <1% Hepatorenal syndrome (HRS) is a form of pre-renal failure: systemic/splanchnic vasodilation and reduced EAV->renal vasoconstriction HRS ~33% of pre-renal AKI (1/5 of cirrhotics hospitalized with AKI) Development of HRS-1 median survival ~2wks Dec. Effective Arterial Pressure (inc. CO/CI, dec. SVR, splanchnic vasodilation) Endotoxemia Nitric Oxide Carotid/Renal Baroreceptors Sense Dec. Perfusion Activation of Endogenous Vasoconstrictors Dec. renal PG’s synthesis and effect Non-Osmotic R.A.A.S S.N.S AgII Dec. PGE2 Aldo Na+/H2O Retention Loss of local renal vasodilators ADH V2 Receptor Inc. Renal Vascular Tone H2O Retention Abnml Renal Hemodynamics If The Patient Has AKI Definition of HRS shifting target – Consensus conferences: Cr double to >2.5 – Suggested that Tx initiated earlier, with only 1.5-fold increase in Cr from baseline Key to success is the early recognition and Tx of this condition If The Patient Has AKI D/C medications that decrease blood volume – Diuretics – Lactulose – Vasodilators Expand intravascular volume – Albumin 1g/kg up to max 100g – NS if over-diuresis is suspected If The Patient Has AKI Search for and Tx AKI precipitants – Infection – Fluid loss – Blood loss If no improvement or continued worsening – Renal U/S to R/O post-renal AKI – Urinary sediment to R/O intrinsic AKI Proteinuria/hematuria suggests GN Granular/epithelial casts suggests ATN – Historical clues such as sepsis, hypovolemia, recent nephrotoxins, contrast dye help sort out ATN vs. HRS If The Patient Has AKI OLT is only definitive Tx that provides long-term survival Arteriolar vasoconstrictors bridge to OLT – Terlipressin most studied but not available in USA – Midodrine plus octreotide most common in USA Midodrine: start 5-7.5mg PO TID and increase to 12.5-15mg TID Octreotide 100mcg SQ TID and increase to 200mcg SQ TID (continues infusion or used as sole therapy->no benefit) – Should be coupled with albumin infusions Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery If The Patient Has Hepatic Encephalopathy (HE) HE (or portosystemic encephalopathy: PSE) is a clinical spectrum of reversible abnormalities in neuropsychiatric function of patients with advanced liver disease Continuum of neuropsychiatric alteration: – Episodic (acute): either precipitated or spontaneous – Recurrent : 2 or more acute episodes per year – Persistent (chronic): persistent deficits negatively affect social/occupational function – Minimal (subclinical): only found with careful testing If The Patient Has HE Precipitating Factors: – – – – – – – – – – – – Infection Recent TIPS placement Non-compliance HCC HV/PV thrombosis Hypovolemia GI bleeding Hypokalemia Metabolic alkalosis (diarrhea) Hypoxia Sedatives Hypoglycemia Asterixis If The Patient Has HE Grade Mental Status Neuro. Findings 0 No alterations No alterations 1 Trivial lack of awareness, euphoria or anxiety, short attention span Tremor, uncoordinated, poor handwriting, early asterixis 2 Lethargy, disorientation, personality changes, inappropriate behavior Asterixis, slurred speech, ataxia, hypoactive reflexes 3 Somnolence to semi stupor, confusion, response to noxious stimuli Hyperactive reflexes, Babinski, clonus 4 Coma, no response to noxious stimuli Dilated pupils, coma, decerebrate posturing (transient) If The Patient Has HE Psycodynamic or “Trail test” If The Patient Has HE Therapy: 1) Fix/Remove the precipitating factors 2) Lactulose: 30-50ml q2h initially, then TID (goal 3-5 soft BM/d); can use 300ml retention enemas also 3) Antibiotics: rifaximin 200-600mg TID 4) 5) 6) No evidence that combo with lactulose is better Use in patients who can’t tolerate or don’t respond to lactulose Flumazenil: 0.4-2.0 mg IV (lasts 2-4 hrs only) Don’t restrict protein (1.0 -1.2 g/kg/day) If recent TIPS may need reduction/occlusion Hutia a.k.a “Banana Rat” “Banana Rat: The Other White Meat” Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery Acute Gastrointestinal Bleeding Liver involved in all 3 systems (coagulation, fibrinolysis and protein C dep. pathway) Nearly all proteins involved in hemostasis are produced in the liver (exceptions: Factor VIII, vWF, thrombomodulin) Impaired production and clearance effect fibrinolytic system (dec. clearance t-PA, PAI-1) Clinical importance of PLT dysfxn in cirrhosis unclear; thrombocytopenia is due to splenic sequestration Acute Gastrointestinal Bleeding Overall have impaired thrombin generation and less stable fibrin structure with increased fibrinolysis (“defective hemostatic plug”) Hemostatic disturbances in cirrhosis are similar to those described for DIC Acute Variceal Hemorrhage Acute variceal hemorrhage mortality 15-20% Acute Variceal Hemorrhage Volume expansion: colloids over crystalloids – SBP 90-100mm Hg – HR<100 bpm Transfusion of blood products to maintain – Hgb ~8g/dl (higher increases re-bleeding/mortality) – Platelets ~50,000 – INR to 1.3 Consider prophylactic intubation if massive bleeding and decreased LOC Acute Variceal Hemorrhage Initiate somatostatin analog (octreotide) as soon as diagnosis suspected – 50 mcg IV bolus followed by 50 mcg/hr infusion – Continued for 5 days Antibiotic prophylaxis for 3-7 days with cipro vs. ceftriaxone (ascites, PSE, bilirubin >3, malnutrition) Endoscopic evaluation within 12 hours Acute Variceal Hemorrhage Sengstaken Blakemore tube: 2 balloons Linton tube: large gastric balloon Control hemorrhage in >80% Mortality is 20% due to complications – Aspiration – Migration – Perforation Re-bleeding after deflation almost universal Only used in patients in whom shunt planned within 24 hours Intubation strongly recommended Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery Pain Management Short-acting analgesics (and sedatives) are always preferred in cirrhotics Opiods are metabolized via hepatic glucuronidation (and oxidation); thus clearance is impaired (potential for toxic metab. accum.) NSAIDs impair renal fxn in cirrhosis, as well as decreasing natriuresis (effect on ascites therapy) NSAIDs increase risk for variceal bleeding (in addition to standard risk for GI toxicity/PUD) Pain Management Recommendations: 1) Do not use NSAIDs (even COX-2’s) !! 2) Fentanyl is the opiod of choice in cirrhosis (long acting methadone is safe as well) 3) If using morphine, oxycodone or demerol decrease the dose by 50% and increase dosing interval 2-fold 4) Acetaminophen is the analgesic of choice ! (maximum dose 2 gm/day); but use caution in cirrhotics who are actively drinking EtOH 5) Don’t forget about analgesic combinations containing acetaminophen Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated cirrhosis Admission Evaluation: - If patient has ascites - If the patient has SBP - If patient has acute kidney injury - If patient has hepatic encephalopathy - If patient has gastrointestinal bleeding - Pain management Preoperative Evaluation: - Risk Factors for morbidity/mortality - “Status” of the Liver - Type of Surgery - Contraindications to Surgery Preoperative Evaluation: Risk Factors for M&M in Cirrhotics Characteristics of the Patient: - Child’s classification (C>B>A) - Presence of ascites or encephalopathy - Presence of jaundice, hypoalbuminemia and/or prolonged PT (>2.5-3 sec above normal, not correctable w/ Vit. K) - Presence of portal hypertension - On-going infection (i.e. SBP, cellulitis) - Anemia, hypoxemia or malnutrion Type of Surgery: - Emergent - Abdominal (esp. gastrectomy, colectomy, chole) - Any cardiac surgery - Hepatic resection Perioperative Mortality and CPT 1984 – periop. mortality (non-shunt, abd. surgery); Child’s A = 10%, B = 31%, C = 76% 1997 – periop. mortality (non-shunt, abd. surgery); Child’s A = 10%, B = 30%, C = 82% 2003 – periop. mortality (non-shunt, abd. surgery); Child’s A = 7.1%, B = 23%, C = 84% MELD For Pre-operative Risk Stratification Retrospective 1980-2004, N=773 (675 MELD<15), ave. age 61 Primary Endpoint: MELD as a predictor of peri-op mortality in non-transplant surgery Secondary Endpoint: Does the type of surgery matter? ’93-’04 vs. ’80-’92 showed a trend toward better outcomes, but NS overall “Other” vs. “Foregut” (hepatobiliary, pancreatic,UGI) surgery trended to better overall outcomes Multivariate Analysis: Age (in increments of 10yr) increased risk 1.5x (30d) and MELD (increments of 5pts) increased mortality risk 2.2x (1.9-2.5) at 30days MELD FOR PRE-OP RISK STRATIFICATION MELD <10 11-15 16-20 21-25 7 Day Mortality 0.8% 6% 8% 15% 30 Day Mortality 4% 15% 32% 58% *MELD >25 had >60% mortality at 30d and >80 mortality at 90d Model for End-Stage Liver Disease (MELD) Website: www.mayoclinic.org/gi-rst/mayomodel6.html Types of Surgery Hepatic resection: - operative mortality ‘92-’98 = 3-16% (approaching 0% in “centers of excellence” ’99-’03) Partial colectomy (open): (typically for diverticulitis) - periop. mortality for Child’s A = 12.8%, Child’s C = 53% Laparoscopic Surgery: (’05) – chole,spleen,colon,hernia,RY - 0% mortality, 16% morbidity; 39/50 pts. Child’s A Open cholecystectomy (for obstructive jaundice): - mortality down from 25-28% (’82) to 8% (’97) Cardiothoracic surgery: (‘04) - morbidity: Child’s A = 60%, B = 72%, C = 100% - mortality: Child’s A = 0%, B = 50%, C = 100% Contraindications to Elective Surgery Acute viral hepatitis (especially icteric hepatitis) Acute alcoholic hepatitis Fulminant hepatic failure (unless OLT) Child’s class C cirrhosis/ ? MELD > 20-25 Severe coagulopathy (PT > 3 sec out after Vit. K, platelet count < 50k) - - relative contraindication Severe extrahepatic complications: - Hypoxemia (PaO2 < 50) (consider HPS) - Cardiomyopathy/CHF - Acute renal failure (consider HRS) Summary Algorithm Navy…it’s more than just a job… QUESTIONS ?