AscitesAscites andand RelatedRelated DisordersDisorders LuisLuis S.S. Marsano,Marsano, MDMD ProfessorProfessor ofof MedicineMedicine DirectorDirector ofof HepatologyHepatology UniversityUniversity ofof LouisvilleLouisville CausesCauses ofof AscitesAscites Malignant Neoplasia 10% Cardiac Insufficiency 3% Tuberculous Peritonitis Chronic hepatic 2% disease Nephrogenic 81% a scite s (dia lysis) 1% Pancreatic ascites 1% Biliary ascites 1% Others 1% PathophysiologyPathophysiology ofof CirrhoticCirrhotic AscitesAscites Hepatic sinusoidal pressure Activation of hepatic baroreceptors Compensated Peripheral arterial vasodilation with hypervolemia, (normal renin, aldosterone, vasopressin, or norepinephrine) Peripheral arterial vasodilation (“underfilling”) Decompensated Neurally mediated Na+ retention, (with elevated renin, aldosterone, vasopressin, or norepinephrine) ClassificationClassification ofof AscitesAscites SerumSerum--ascitesascites albuminalbumin gradientgradient (SAAG)(SAAG) SAAGSAAG (g/dl)(g/dl) == albuminalbumins –– albuminalbumina GradientGradient >>1.11.1 g/dlg/dl == portalportal hypertensionhypertension Serum globulin > 5 g/dl:: – SAAG correction = (SAAG mean)(0.21+0.208 serum globulin g/dl) AscitesAscites withwith HighHigh SAAGSAAG >>1.11.1 g/dlg/dl == portalportal hypertensionhypertension Cirrhosis Alcoholic Hepatitis Cardiac ascites Massive hepatic metastasis Fulminant hepatic failure Budd-Chiari syndrome Portal vein thrombosis Veno-occlusive disease Acute fatty liver of pregnancy Myxedema Mixed ascites LowLow SAAGSAAG <1.1<1.1 g/dlg/dl Peritoneal carcinomatosis Tuberculous peritonitis (without cirrhosis) Biliary ascites (without cirrhosis) Pancreatic ascites (without cirrhosis) Nephrotic ascites Connective tissue disease Intestinal obstruction/infarction Ovarian Hyperstimulation Syndrome POEMS Syndrome Chylous Ascites Urine ascites SurvivalSurvival ofof CirrhoticsCirrhotics withwith AscitesAscites Survival in cirrhotic ascites 1 0.8 0.6 Probability 0.4 Survival 0.2 0 012345 YEARS CharacteristicsCharacteristics ofof UncomplicatedUncomplicated CirrhoticCirrhotic AscitesAscites Polymorphonucleocytes < 250/mm3 SAAG > 1.1 g/dl Ascites/plasma LDH < 0.6 Protein < 2.5 g/dl 0 20 40 60 80 100 % Ascites/plasma amylase ~0.5 Leucocytes < 300/mm3; intense diuresis 1100/mm3 TreatmentTreatment ofof AscitesAscites withwith HighHigh SAAGSAAG ((>> 1.11.1 mg/dl)mg/dl) TreatTreat primaryprimary diseasedisease (alcoholism,(alcoholism, WilsonWilson’’s,s, autoimmuneautoimmune hepatitis,hepatitis, cardiaccardiac insufficiency,insufficiency, ……)) Na+Na+ restrictionrestriction:: –– Inpatient:Inpatient: 250250--10001000 mgmg (11(11--4444 mEmEq)q) dependingdepending onon urinaryurinary lossloss –– Outpatient:Outpatient: 11--22 gg (44(44--8888 mEq)mEq) ofof Na/dayNa/day withwith diureticsdiuretics forfor 00 oror slightlyslightly negativenegative balancebalance TreatmentTreatment ofof AscitesAscites DiureticsDiuretics – General therapeutic goal Without edema : 1 lb/d weight loss With edema : 1-2 lb/d weight loss If urine Na/K ratio 24 h after diuretics is >1, then 90% of patients will loose at least 88 mEq Na/day. any Random spot urine Na/K > 0.97 has similar value (PPV 84%; NPV 90%) and if Na/K >/= 3.5, PPV is 100% (Liver Int. 2012;32(1):172-3), – Spironolactone: more effective than loop diuretics. Can produce hyperK and acidosis Dose: 100, 200, or 400 mg QD TreatmentTreatment ofof AscitesAscites ––FurosemideFurosemide:: producesproduces hypoKhypoK andand alkalosisalkalosis Dose:Dose: 40,40, 80,80, oror 160160 mgmg QDQD ––MetolazoneMetolazone:: addedadded whenwhen maximalmaximal spironolactonespironolactone 400400 ++ FurosemideFurosemide 160160 isis notnot controllingcontrolling ascites.ascites. CausesCauses severesevere hypoKhypoK DoseDose 2.52.5--1010 mgmg QDQD TreatmentTreatment ofof AscitesAscites withwith HighHigh SAAGSAAG WaterWater restrictionrestriction – If serum Na < 126-130 mEq/L – Restrict to 0.8-1.5 liters/day – If water restriction fails: Tolvaptan (Samsca) 15 mg po q day; increase to 30 mg po qd if serum Na fails to increase by 5 mMol in 24 h, and to 60 mg po qd if Na fail to increase by 5 mMol after 30 mg x 1 day. Goal: correct Na by 8 mMol/d (never > 12 mMol/d) Correct hypothyroidism and adrenal insufficiency. Contraindications: MI, ventricular arrhythmia, PCWP < 5 mmHg, BPs < 90 mmHg, severe pulm. HTN, Creat > 3.5, Serum Na < 120 with neuro impairment, uncontrolled DM. AggressivelyAggressively correctcorrect malnutritionmalnutrition TreatmentTreatment ofof AscitesAscites TherapeuticTherapeutic paracentesis:paracentesis: done in patients with stable cirrhosis with or without edema – Single large volume paracentesis (4-6 L): with or without colloid infusion – Serial LVP (4-6 L/Day): Colloid infusion (40 g albumin) need is controversial – Total paracentesis (6-22 L over 1 hr) with IV albumin (6-8 g/L removed), or Dextran 70 (8 g/L removed), or Midodrine 5-10 mg p.o. TID with goal to increase baseline MAP by 10 mmHg x 72 hours (Am J Gastroenterol 2008;103:1399-1405) TreatmentTreatment ofof RefractoryRefractory AscitesAscites DefinitionDefinition:: AscitesAscites thatthat cancan notnot bebe controlledcontrolled onon aa 22 gg NaNa dietdiet withwith SpironolactoneSpironolactone 400400 mgmg ++ FurosemideFurosemide 160160 mg,mg, withoutwithout causingcausing azotemia.azotemia. TreatTreat asas HRSHRS:: AlbuminAlbumin ++ MidodrineMidodrine ++ OctreotideOctreotide TIPSSTIPSS NonNon--selectiveselective surgicalsurgical ShuntShunt SpontaneousSpontaneous BacterialBacterial PeritonitisPeritonitis (SBP)(SBP) andand CultureCulture NegativeNegative NeutrocyticNeutrocytic AscitesAscites (CNNA)(CNNA) PrevalencePrevalence 1010--27%27% inin hospitalizedhospitalized patientspatients withwith cirrhoticcirrhotic ascitesascites PathogenesisPathogenesis:: distantdistant bacteremiabacteremia (UTI,(UTI, URI,URI, etc.)etc.) oror translocationtranslocation ofof bacteriabacteria fromfrom intestinalintestinal lumenlumen SignsSigns andand SymptomsSymptoms ofof SBPSBP Abdominal pain Encephalopathy Abdominal tenderness Leucocytosis Bacteremia Fever Hypotension Rebound 0 20 40 60 80 100 % DiagnosisDiagnosis ofof SBPSBP andand CNNACNNA SBPSBP == PMNPMN >250/mm>250/mm3 withwith (+)(+) cultureculture (>(> 90%90% monobacterial)monobacterial) – Other predictors: ascites WBC > 1000/uL; ascites pH < 7.35; blood-ascites pH gradient =/> 0.1 CNNACNNA == PMNPMN >250/mm>250/mm3 withwith ((--)) cultureculture (without(without previousprevious antibioticsantibiotics nornor otherother causescauses ofof increasedincreased PMNPMN [bleeding,[bleeding, cancer,cancer, TB,TB, pancreatitis]pancreatitis] )) BacteriologyBacteriology ofof SBPSBP GramGram--NegativeNegative BacilliBacilli 70%70% Escherichia coli Klebsiella spp. GramGram--PositivePositive CocciCocci 20%20% Streptococcus pneumonia Enterococcus spp Staphylococcus spp Anaerobes,Anaerobes, MicroaerophilsMicroaerophils && othersothers 10%10% AscitesAscites CultureCulture 100 80 60 % 40 20 0 Blood culture bottle Culture in plate SBPSBP andand CNNACNNA MorbidityMorbidity andand MortalityMortality – Mortality without treatment: 78-100% – Mortality w. Cefotaxime: 30% (HRS= 33%) – Mortality w. Cefotaxim+albumin: 10% (HRS=10%) – Recurrent SBP in 69% TreatmentTreatment – Cefotaxime 2g TID x 5 days + Albumin 1.5 gm/Kg @ day 1 & 1 gm/Kg @ day 4 – Re-paracentesis at 48hrs (50% reduction in WBCs) SBPSBP && CNNACNNA ProphylaxisProphylaxis –– CirrhoticCirrhotic withwith totaltotal proteinprotein << 1.51.5 g/dl;g/dl; NorfloxacinNorfloxacin 400400 mg/dmg/d popo oror BactrimBactrim DSDS 55 days/weekdays/week duringduring hospitalizationhospitalization –– CirrhoticCirrhotic withwith GIGI bleedbleed NorfloxacinNorfloxacin 400400 mgmg popo BIDBID xx 77 daysdays MonomicrobialMonomicrobial BacterascitesBacterascites DiagnosisDiagnosis ––(+)(+) ascitesascites cultureculture withwith PMNPMN << 250/mm250/mm33 andand withoutwithout surgicallysurgically treatabletreatable intraintra-- abdominalabdominal sourcesource ofof infectioninfection SignsSigns andand SymptomsSymptoms ofof MonomicrobialMonomicrobial BacterascitesBacterascites Rebound Abdominal pain Abdominal tenderness Encephalopathy Fever 0 20 40 60 80 100 % MonomicrobialMonomicrobial BacterascitesBacterascites Mortality:Mortality: 40%40% TreatmentTreatment –– CefotaximeCefotaxime 22 gg TIDTID asas perper antibioticantibiotic susceptibilitysusceptibility –– RepeatRepeat paracentesisparacentesis inin 4848 hrhr AscitesAscites ManagementManagement EVALUATE:EVALUATE: TREAT:TREAT: ParacentesisParacentesis postpost-- NaNa restrictrestrict ++ LVPLVP ++ adm, PSE, Azotemia, adm, PSE, Azotemia, diureticsdiuretics FeverFever PMN>250: Cefotaxim Check:Check: Prot,Prot, Alb,Alb, PMN>250: Cefotaxim WBC,WBC, Glu,Glu, LDHLDH inin ++ AlbuminAlbumin serumserum && ascitesascites ProtProt << 1.5g:1.5g: NorfloxacNorfloxac BedsideBedside CultureCulture inin GIGI Bleed:Bleed: NorfloxacinNorfloxacin BloodBlood CultureCulture bottlebottle HepaticHepatic HydrothoraxHydrothorax In 10% of patients with ascites Usually right sided T. protein in hydrothorax > ascites by 0.75-1 g/dl Protein ratio (s/h) > 0.5 LDH, ratio s/h > 2/3 upper limit in serum “Transudate” Glucose > 60 mg/dl LDH ratio (s/h) > 0.6 0 102030405060708090100 % SignsSigns andand Symptoms:Symptoms: SpontaneousSpontaneous BacterialBacterial EmpyemaEmpyema Cough Shock Thoracic pain Abdominal pain Dyspnea Chills Fever SBP 0 102030405060708090100 % SpontaneousSpontaneous bacterialbacterial empyemaempyema Diagnosis: – A) culture (+) (in blood culture bottle), or