R1 orientation 蘇哲萱 2014/10/21

R1 orientation 蘇哲萱 2014/10/21

I. Decompensated liver cirrhosis & associated complications II. GI Bleeding

Liver cirrhosis Compensate liver cirrhosis Decompensate liver cirrhosis

Prognosis of Liver cirrhosis Child pugh classification

Prognosis of Liver cirrhosis Child pugh classification 1 2 3 HE None Gr 1~2 Gr 3~4 Ascites Absent slight Moderate Bilirubin <2 2~3 >3 mg/dl Albumin >3.5 2.8~3.5 <2.8 mg/dl PT prolong <4 s ( INR <1.7) 4~6 s( INR 1.7~2.3) >6 s (INR>2.3) Child A Child B Child C Total 5~6 7~9 10~15 1 year-survival 100 % 80 % 45 %

Complications of liver cirrhosis Variceal bleeding Ascites/ Spontaneous bacterial peritonitis Hepatic encephalopathy Hepatorenal syndrome Hepato-pulmonary syndrome / Hepatic hydrothorax

SPONTANEOUS BACTERIAL PERITONITIS

Spontaneous bacterial peritonitis Ascites fluid infection without an evident intra-abdominal surgically treatable source

Clinical manifestations Fever Abdominal pain Altered mental status Diarrhea/ paralytic ileus / Hypotension /Hypothermia

Diagnosis Paracentesis Ascites fluid PMN 250 Before any antibiotics What if traumatic paracentesis? Ascites routine: RBC 30 cells/mm3, WBC 500 cells/ mm3, 60 % Neutrophils ; monocyte 10 %, lymphocytes : 20 % SBP? RBC 60000 cells/mm3, WBC 500 cells/ mm3, 60 % Neutrophils ; monocyte 10 %, lymphocytes : 20 %, SBP?

In traumatic/bloody paracentesis Corrected neutrophil counts= Corrected PMN = PMN counts (RBC counts/250) RBC 60000 cells/mm3, WBC 500 cells/ mm3, 60 % Neutrophils ; monocyte 10 %, lymphocytes : 20 %, WBC: 500 * 0.6 = 300 Corrected PMN counts: 300 (60000/250) = 60 PMN/mm3

Diagnosis Paracentesis Routine Culture Gram stain Albumin Protein/Glucose/LDH Amylase Bilirubin

SAAG 1.1 g/dl Cirrhosis/ Heart failure, Portal hyperension SAAG < 1.1g/dL Peritoneal carcinomatosis, TB peritonitis, pancreatitis, nephrotic syndrome..

Diagnosis Protein/ LDH /Glucose Amylase (?) / Bilirubin (?) Runyon s criteria ( 2/3) Total protein > 1 gm/dl Glucose < 50 mg/dl (2.8 mmol/l) LDH > upper limit of serum

Treatment Antibiotics Tx Cefotaxime /3 rd cephalosporin Fluoroquinolone Discontinue non-selective beta-blocker

HEPATIC ENCEPHALOPATHY

Reversible syndrome of impaired brain function in advanced liver failure

Severity of HE Stage Mental status Asterixis EEG I Euphoria or depression, mild confusion, slurred speech, disordered sleep +/- Usually normal II Lethargy, moderate confusion + Abnormal III Marked confusion, incoherent speech, sleeping but arousable + Abnormal IV Coma; - Abnormal Delta activity

Finding precipitating causes GI bleeding Infection Electrolyte/ fluid status Sedative / transquilizer use Constipation Others

Common precipitants of Hepatic Encephalopathy Increase nitrogen load Gastrointestinal bleeding Excess dietary protein Azotemia Constipation Electrolyte and metabolic imbalance Hypokalemia Alkalosis Hypoxia Hyponatremia Hypovolemia Drugs Narcotics, tranquilizers, sedatives, Diuretics Miscellaneous Infection Surgery Superimposed acute liver disease Progressive liver disease Portal-systemic shunts

Treatment rationale Ammonia hypothesis Decrease ammoniagenic substrate Inhibition of ammonia production Metabolic ammonia removal False neurotransmitter hypothesis Branched chain amino acid supplementation Increased dopamine GABA hypothesis

Treament Control predisposing factors Decrease NH3 Lactulose / lactitol / rifaxim General supportive tx Fluid : adequate, avoid dehydration Electrolyte Pharmacologic restrain (haloperidol safer then BZD )

Lower Blood [NH3] Lactulose /lactitol / 30~45 ml BID ~ QID / day 2~3 stools / day Lactulose enemas Rifaximin (Gr 2C, 本院目前無藥 ) rifampin 400 mg TID / 550 mg BID in addition to lactulose Neomycin Ototoxicity / nephrotoxicity ; 500 mg TID / 1 gm BID ; metronidazole

Bar code HE IVF with D5W 1000 ml run 60ml/hr F/S stat CBC/DC Bun/Cr/Na/K/ Bil(T)/AST/ALT/NH3 CXR

HEPATORENAL SYNDROME

Diagnosis Renal failure in patient with advanced liver disease Type I Rapid decline renal function Cr elevated >2X (from baseline) to > 2.5 mg/dl <=2WKS Usually triggered by precipitating event with other organ dysfuction Type II Steady & progressive Characterized by refractory ascites & Na retension Average Cr around 2 mg/dl

Epidemiology Who is most affected With decompensated cirrhosis, precipitating as alcohol, hepatitis, or infection Incidence/Prevalence 4 % PT with decompensated cirrhosis 30 % PT with cirrhosis & SBP 45.8 % of PT with cirrhosis & renal failure

Pathogenesis Peripheral arterial vasodilation theory by cirrhosis/portal hypertension Splanchnic vasodilation, reduced arterial blood volume, decreased MAP RAA system activitaty renal vasoconstriction --< shift in renal autoregulatory curve Impaired CO due to cirrhosis cardiomyopathy Increased synthesis of vasoactive mediators affects renal blood flow or glomerular microcirculatory hemodynamics

Diagnosis Excluding other causes of AKD with advanced liver disease Major diagnositc criteria Cirrhosis with ascites Cr > 1.5 mg/dl No sustained improvement in Cr after 2 days of diuretic withdrawal and plasma volume expansion with albumin Absence of shock No current/recent use of nephrotoxic drugs No parenchymal renal disease (Proteinuria < 0.5g/d, no microhematuria, normal renal ultrasound

Tx Fluid restriction of 1L/day Prevent progression of dilutional hyponatremia in Type I hepatorenal dz Liver transplant / liver & renal transplant Tx prior to liver transplant Vasoconstriction + albumin Terlipressin level I» May increase CV events Large-volume paracentesis + albumin TIPS (transjugular intrahepatic portacaval shunts)

R1 orientation II GI Bleeding

UGIB

Definitions Upper GI bleeding; Above Ligament of Treitz s

Symptoms/signs Melena Black, tarry, foul-smelling stools Hematemesis Vomitus of red blood of coffee-ground Hematochezia Passage of bright red/maroon blood from rectum

Etiology UGIB Varices Non-varices Ulcer, mallory-weiss tear, erosive lesion, gastritis, dieulafoy lesion.etc

Etiology UGIB Mimic Mimics LGIB Extra-intestinal blood loss /Epistaxis / gingival bleeding/ hemoptysis False positive fecal OB test

Approach to the patient Symptoms /signs; Shock sign, volume status Conscious /Pale/Cold sweating/weakness Abdominal pain Dizziness, palpitation, faintness, syncope others?

Evaluation/ tx plan Support & Stability Finding the DZ & treat it Others

Evaluation/ tx plan - UGIB Support & Stability Restoring volume loss/blood loss Correct bleeding tendency Finding the bleeding area & stop bleeding Medications Endoscopy Image study Others Electrolyte, nutrition, associated comorbidities

ABC Volume status Initial assessment

ABC Volume status Initial assessment

Evaluation and Tx Resuscitation / survey Barcode( UGIB) ; Medications tx PPI/ Terlipressin. PES Angiography Surgery

Barcode --UGIB Recheck BP 30 mins later NPO CBC/ DC/ PT/ Sugar / Bun/Cr/ALT/ Na/K IVF with N/S 1000 ml run 500 ml stat then run 120 ml/hr On NG tube with saline irrigation CXR Panendoscopy

Acid suppression Proton pump inhibitor (PPI) High dose with IV form rebleeding rate, length of stay, rebleeding rate, need for B/T with highrisk ulcers tx with endoscopy Barcode: HI LOSEC, HI PANTO (for hi-dose PPI) H2 blocker not been shown to significantly lower the rate of ulcer rebleeding

Terlipressin Vasoconstrictor therapy splanchnic blood flow Terlipressin Only agents improving control of bleeding/ survival in RCT & meta-analysis Regimen 2mg stat, 1mg Q4h~Q6H

Somatostatin analog Somatostatin & analogue gastroduodenal mucosal blood flow Octreotide 20~50 mcg bolus, then 25~50 mcg/hr drip x 3 ~5 days Somatostatin 2 amp in 500ml; 20 ml loading 2~3 mins, then 3.5 mg/kg/hr for 24 hrs;

Antibiotics Bacterial infection occurs in 20~50 % of patient with cirrhosis & GI bleeding; Prophylatic antibiotics reduce incidence of bacterial infection Ceftriaxone 1 gm/ QD 5~7 days Norfloxacin 400 mg BID

Evaluation and Tx Resuscitation / survey Barcode( UGIB/LGIB) ; fluid ; X-ray Medications tx PPI/ Terlipressin. PES Angiography Surgery

Prokinetics before PES Erythromycin Metoclopramide Improve gastric visualization at time of endoscopy, 30~ 90 mins before PES Usually with large amounts of blood in the stomach

Forrest Classification High risk A: spurting (Gr IA) B: Oozing (IB) C: Non-bleedling visible vessels (IIA) D: Adherent clot (IIB)

Forrest Classification Low risk E: flat, pigmented spot (IIC) F: Clean base (III)

Risk of re-bleeding by Forrest grade Patients with endoscopic or clinical re-bleeding (%) 100 80 Forrest I* Forrest IIa Forrest IIb Forrest IIc Forrest III 60 55 40 43 20 22 0 10 5 *Patients did not receive endoscopic therapy Laine L & Peterson WL. N Engl J Med 1994;331:717 27

Variceal Bleeding Occurs in 1/3 of patients with cirrhosis 1/3 initial bleeding episodes are fatal Among survivors, 1/3 will rebleed within 6 weeks Only 1/3 will survive 1 year or more

Tx of GI bleeding Resuscitation / survey Barcode( UGIB/LGIB) ; fluid ; X-ray Medications tx PPI/ Terlipressin. PES Angiography Surgery

UGIB

LGIB

Definition Lower GI bleeding; Below Ligament of Treitz s

Symptoms/signs Melena Black, tarry, foul-smelling stools Hematemesis Vomitus of red blood of coffee-ground Hematochezia Passage of bright red/maroon blood from rectum

Common Etiology LGIB Colonic diverticular bleeding GI Angiodysplasia Hemorrhoid Intestinal dieulafoy Colitis (IBD/infection/ischemic ) Neoplasm Dieulafoy lesion

Approach to the patient Symptoms /signs; Shock sign, volume status Conscious /Pale/Cold sweating/weakness Dizziness, palpitation, faintness, syncope Abdominal pain / back pain Others : Hx, associated cormobidity..

Evaluation / Tx of LGIB ABC, stable vital sign;

Current Barcode - LGIB CBC / PT ; Cr/ ALT/ Na/ K On BP monitor & EKG monitor ; O2 N/C 5L/min Admission to GI ward IVF with N/S 1000 ml run stat then run 120 ml/hr Sigmoidscopy, flexible Fleet enema 2 PC before sigmoid

Evaluation & Tx of LGIB Sigmoidscopy Colonfiberscopy Need bowel preparation

Tx of LGIB Colonfiberscopy Angiography Surgery Others Hormone tx, angiogenesis inhibitors (thalidomide) Octreotide Long-acting form of octreotide (IM/month)

LGIB

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