brian torski, do, internal medicine pgy-1. overview of hepatorenal syndrome o pathophysiology o...
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Hepatorenal Syndrome Treatment
Brian Torski, DO, Internal Medicine PGY-1
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Outline Overview of Hepatorenal Syndrome
o Pathophysiologyo Diagnosiso Classificationo Prevention and Treatment
Octreotide/Midodrine Therapy Terlipressin Therapy Pooled Analysis of Vasoconstrictor Extracorporeal Albumin Dialysis Wrap Up
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Hepatorenal Syndrome (HRS)
First described in 1932 for post-op biliary tract Sx resulting in ATN
Found to be a cascade of events Kidney’s histologically normal Acute renal dysfunction occurs in 15% to 25% of
hopitalized pts w/ cirrhosis HRS an extension of prerenal therefore potentially
reversible Annual frequency of HRS 8% to 40%
o SBP or other infection then 30%o Severe alcoholic hepatitis 25%
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Pathophysiology Splanchnic & Systemic Arterial Vasodilatation
o Hallmarks of progression of portal HTN in cirrhosiso Mediated by numerous endogenous substanceso Early compensation includes increase in HR & CO
Cardiac dysfunctiono HRS developed in cirrhotic pt w/ more severe arterial
vasodilation and lower CO
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Pathophysiology
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Pathophysiology Renal Arterial Vasoconstriction
o Mediated by stimulation of SNS, activation of RAAS, nonosmotic release and activity of vasopressin
o Precise intrarenal mechanisms are speculativeo Balance between vasoconstrictive responses in kidney
and splanchnic vasodilation is lost
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Pathophysiology
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Diagnosis International Ascites Club Consensus Workshop
2007
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Diagnosis No prior evidence or history of renal impairment
criteria include inc creat by 50% above baseline to level > 1.5
Subset of pt w/ cirrhosis and ESLD profound decrease in muscle mass and urea synthesis
Many medications may influence intravascular volume status and renal perfusiono Diuretics, lactulose, ACE, ARBs, NSAIDs
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Classification Type 1 HRS: rapidly progressive form of renal
dysfunctiono Serum creat doubles to > 2.5 w/in 2 weekso Rapid decline in hemodynamic parameterso Bacterial infxn, GIB, Surgery, acute liver injury
Type 2 HRS: more slowly progressing entityo Severe ascites (diuretic resistant)o Serum creat < 2.5
Type 3 HRS?o Many pts w/ cirrhosis and portal hypertension also have
underlying CKD
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Prevention Intravascular volume depletion,
o Overdiuresis, diarrhea caused by lactulose, GIB (varices), large-volume paracentesis w/o colloid administration
Nephrotoxins Infection
o Prophylactic administration of Abx to pts at high risk of SBP
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Treatment Transjugular Intrahepatic Portosystemic Shunt
o Effective for treatment of diuretic-resistant ascities o 4 pilot studies have evaluated the use of TIPS in
nontransplant candidates with type 1 & 2o Limited by potential to accelerate liver function
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Treatment Liver Transplantation (OTL)
o ONLY therapy that has the potential to reverseo Should be considered in any pt found to have HRSo 35% of pts w/ HRS require long-term renal replacemento 3 yr survival is approximately 60%o Degree of renal dysfunction preoperatively may be
independent predictors of survival o Pts who responded to a vasopressin analog prior to OTL
had outcomes similar to those of pts who had OTL w/o HRS
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Treatment IV Albumin: Bolus 1g/kg/d on presentation (max
100 g/d)o Continue at 20 – 60 g/d to keep CVP @ 10-15
Terlipressin: 1 mg IV Q4hr & up to 2 mg if baseline serum creat does not improve by 25% at day 3
Midodrine & Octreotideo M: 2.5 – 5 mg PO TID up to 15 mg TID o O: 100 mcg SQ TID to 200 mcg TID or 25 mcg IV bolus +
25 mcg/hr Norepinehrine: 0.1 – 0.7 mcg/kg/min and inc by
0.05 Q4hr Duration of vasopressor treatment is generally a
max of 2 weeks until reversal of HRS or OTL
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Prognosis Prior to advent of newer therapies median
survival for pts w/ type 1 HRS was 1.7 weeks and 90% dead w/in 10 wks
Today treatments have allowed some increase in short-term prognosis
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References Sleisenger & Fordtran’s Gastrointestinal and Liver
Disease Pathphysiology/Diagnosis/Management . 9th edition. Ch 92
P.A. McCormick. Management of hepatorenal syndrome. Pharm & Therap. 119 (2008) 1-6.
T Restuccia. et al. Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study. Journ of Hepat. 40 (2004) 140-146.
P Gines. Renal Failure in Cirrhosis. N Engl J Med. 2009;361:1279-90
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Thanks For Coming Out