Initial approach to ascites

Transcription

1 Ascites: Filling and Draining the Water Balloon Common Pathogenesis in Refractory Ascites, Hyponatremia, and Cirrhosis intrahepatic resistance sinusoidal portal hypertension Splanchnic vasodilation (effective hypovolemia) Activation of renin, angiotensin, aldo, vasopressin cardiac output Arun J M.D. Charles Caravati Professor of Medicine Virginia Commonwealth University Richmond, Virginia DISCLOSURES: Consultant to Sanofi-Aventis, Exhalenz, Na retention ASCITES hyponatremia Renal adaptation failure (vasoconstriction) REFRACTORY ASCITES H2 retention Pfizer, Salix, Orphan Therapeutics, Gilead, Astellas Natural history of cirrhosis with ascites Initial approach to ascites Pre-ascitic cirrhosis Na retention Ascites Refractory ascites Hepatorenal syndrome Na restriction + diuretics: Na (88 meq/day) use combination of loop-acting and distal acting diuretics when feasible Slow Does not affect survival Large volume paracentesis (LVP): > liters Fast High rate of recurrence Does not affect survival Requires albumin infusion to prevent post paracentesis circulatory dysfunction Treatment of ascites Refractory Ascites International Ascites Club Criteria Remove ascites and maintain an ascites free state Prevent and treat infection Prevent and treat renal failure Diuretic Resistant: failure to lose at least. Kg/wk on: 4 mg Spironolactone 6 mg furesemide Diuretic intractable: failure to lose weight due to inability to use effective doses because of diuretic side effects.

2 TIPS vs Taps (impact on recurrence of ascites) (Impact on encephalopathy) All studies showed similar trend Lebrec Rossle Salerno TIPS is better than taps TIPS used in addition to taps Standardized Na restriction not uniformly provided in all studies Lebrec Rossle Salerno Not powered to test for this endpoint Overall increased PSE after TIPS - Age - Shunt size - liver function Odds ratio: Lower with TIPS Albillos et al, J Hepatol 2. Favors TIPS Favors TAPS (impact on rates of complications related to cirrhosis) (impact on survival) No significant differences in the 2 largest studies Specifically, infection and sepsis rates were similar Favors TIPS Favors TAPS et al, Gastroenterology, 23 et al, Gastroenterology, 22 Saab et al, Cochrane review, Oct 26 (impact on renal failure) No significant differences in the 2 largest studies Specifically, rates of were not different Role of TIPS in refractory ascites TIPS resolves ascites in > 7% of cases Liver function and nutrition improved in some cases and worsened in others Optimal candidate: refractory ascites + relatively preserved liver function + creatinine <. mg/dl Contraindication: Bili > 3 mg/dl, P.T.> 2 secs, creatinine > 2 mg, severe encephalopathy, pulmonary hypertension Favors TIPS Favors TAPS et al, Gastroenterology, 23 et al, Gastroenterology, 22 2

3 Prevalence of hyponatremia in subjects with cirrhosis Once hyponatremia develops, outcomes are bad % 4 3, ,9 2 2,8,,3 4, 4,4 </= >4 serum sodium (meq/l) Angeli et al, Hepatology, 26 Hackworth et al, Liver International, 2, 29:7-77 Hyponatremia (impact on survival) Treatment of ascites Probability Mortality Serum sodium p=. <3 meq/l 3-3 meq/l Probability month survival Remove ascites and maintain an ascites free state Prevent and treat infection Prevent and treat renal failure.2 >3 meq/l.2. 2 Months Serum sodium (meq/l) Londoño et al; Gut 27 Effect of tolvaptan on refractory ascites Primary prophylaxis of SBP N= 3 vs 33 CPT 9 Bili 3 Creatinine.2 Na 3 meq/l % * * * norfloxacin placebo * p<. SBP endpoints survival Okita et al, J Clin Gastroenterol, 2, April EPub Fernandez et al, Gastroenterology, 27; 33:

4 PPI: too much of a good thing!! (increased risk of SBP with PPI) N= 44 SBP (case) vs 88 cirrhosis admissions without SBP (controls) Parameter SBP No SBP P value Age (yrs ± S.D) 4 ± 2 4 ± 2.9 CTP C (%) SBP proph (%) On PPI Inappropriate use of PPI Type and Frequency of Injury in Acute Renal Failure in Cirrhosis Type ATN (ischemic) Prerenal failure Decreased volume Drugs Obstruction Intrinsic Frequency Common Very common Relatively common Relatively common Uncommon Uncommon Bajaj et al, Am J Gastroenterol, 29 Use of albumin during Spontaneous bacterial peritonitis % Sepsis recovery N= 63 vs 63 renal failure deaths cefotaxime cef + albumin Hepatorenal syndrome Salerno et al, Gut, 27, epub March 27 Cirrhosis with ascites Serum creatinine >. mg/dl No improvement after at least 2 days of diuretic withdrawal and volume replacement with albumin No nephrotoxic drugs used Absence of intrinsic renal disease Sort et al, NEJM, 34:43-9, 999 Treatment of ascites Reversal of 4 Remove ascites and maintain an ascites free state Prevent and treat infection Prevent and treat renal failure Reversal (%) Day et al, Gastroenterol, 28 Terlipressin Placebo 4

5 Impact of Reversal of on Transplant-Free Survival Impact of octreotide + midodrine followed by TIPS in..9.8 Initial cohort (n=4) 4 Survival Distribution Function Death Nonresponders Alive TIPS 4 Responders Liver transplantation No TIPS 2 3 Death P-value: (.) (.4) (.3) (.) Survival (Days) = Censored = Reversal = No Reversal Wong et al, Hepatology,24 Factors associated with failure to respond to terlipressin Effect of Liver Transplant on Glomerular Filtration Rate Baseline creatinine > 6 mg/dl Duration of therapy < 48 hrs Ventilator support due to multi-organ dysfunction Glomerular filtration rate (ml/min) No Pretransplant 3 days 9 days year Gonwa TA, et al. Transplantation. 99;: Utility of vasoconstrictors for A rational basis for treating ascites Midodrine Terlipressin Norepinephrine Cirrhosis Transplant Rationale: Sinusoidal portal hypertension TIPS Route: Oral + octreotide i.v. slow bolus i.v. infusion Splanchnic arterial vasodilation vasoconstrictors Clinical effectiveness: Level of monitoring: Uncontrolled no special needs Phase III RCT + phase II RCT Monitored bed Phase II RCTs ICU bed LVP/TP Decreased effective circulating volume Activation of Na/H2O retention (ascites) Renal vasoconstriction Safety: Cost: GI, piloerection GI, ischemia? Ischemia, GI, ARDS Diuretics Yes compensated Renal adaptation No Refractory ascites aquaretics

6 THANK YOU FOR YOUR ATTENTION 6