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Critical Care Combined Conference: Hepatorenal syndrome

Critical Care Combined Conference: Hepatorenal syndrome. R4 翁林睿 /VS 吳允升. Consultation. A 67-year-old men with liver cirrhosis s/p liver transplantation with graft failure, for suspect hepatorenal syndrome. Patient Profile. Medical history

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Critical Care Combined Conference: Hepatorenal syndrome

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  1. Critical Care Combined Conference: Hepatorenal syndrome R4 翁林睿/VS 吳允升

  2. Consultation A 67-year-old men with liver cirrhosis s/p liver transplantation with graft failure, for suspect hepatorenal syndrome

  3. Patient Profile • Medical history • Liver cirrhosis, Child B, HBV and alcoholism related, with EVB s/p ligation(IV) • Hepatic tumor(1.3 cm over S#5), suspect HCC • HBV, under Telbivudine (2009/11-) • BPH • Surgical history: Nil

  4. Present illness Before OPD F/U with repeated EVB history 102/04 Hepatic tumor noted MRI (1)Liver cirrhosis with splenomegaly and mild ascites (2)One nodule(1.3cm) at S#5 of liver, suspect HCC CT (1)1.2 cm nodular lesion at S#5, faint enhancement in HA phase, HCC could not be excluded 102/06 EVB * 2 times 102/7/15 Admission for liver transplantation

  5. Living donor liver transplantation Treatment course T-bil elevated to 25 T-bil elevated to 40 AST/ALT 2263/1271 103 Alb 17 21 22 24 29 31 8/5 8 7/15 Fortum Claforen Tazocin Baktar Glypressin Rasitol Solu-medrol Predonine Solu-medrol Tacrolimus MMF BUN/Cre58.6/2.6 7/21 Abdominal CT Contrast(+) (1)Portal and splenic vein thrombosis (2)Heterogeneous density of liver 7/29 Abdominal CT Contrast(+) (1)Patent portal vein (2)Multiple infarction of graft liver Exploratory laparotomy Portal vein thrombosis Open thrombetomy with patent intra-OP echo

  6. Treatment course Shock 8/13 CT-guided drainage of hematoma GIB(1.5L) Fever HD Alb Alb Alb 10 12 13 14 18 19 21 22 25 26 8/8 Fortum Tazocin BUN/Cre64/1.9 BUN/Cre120/3.7 Rasitol U/A protein +/-, OB 3+, RBC 5-10 T-bil ↓to 25 Solu-medrol Predonine MMF Dopa. Acyclovir 8/8 Abdominal MRI (1)Multiple infarcts and atrophy of graft liver; patent prtal vein (2)Persisted peri-hepatic hematoma 8/19 EGD Spurting vessel, EG junction 8/19 Abdominal CT Contrast(+) No active contrast extra-vasation

  7. Treatment course Nephro. BUN/Cre98/3.0 T-bil 25~35 Fever HD Fever Shock Alb Alb 28 30 9/1 2 4 7 8 9 12 8/26 Tazocin Tazocin Tazocin GIB persisted BUN/Cre102/2.5 Anidulafungin Rasitol BUN/Cre95/2.4 BUN/Cre98/2.7 Rasitol Oliguria Predonine Solu-medrol MMF Acyclovir Dopa. Cyclsporin 9/9 Start regular HD at SICU

  8. Physical examination • General appearance • Consciousness clear; general malaise • Vital signs: T/P/R 36.3/91/24, BP 114/59 • HEENT: • Conjunctiva: mild pale; Sclera: icteric; • Pupils: isocoric; Light reflex: +/+; • Neck: supple, LAP (-), goiter(-) • Chest • Symmetric expansion • Breath sound: clear, no obvious basal crackles

  9. Physical examination • Heart • Regular heart beat, no obvious murmur • Abdomen • OP wound(+) • Bowel sound: normoacive • Extremities • Edema(+/-) • Rash(-), Ecchymosis(-)

  10. Laboratory results(9/4)

  11. Laboratory result

  12. Laboratory result(9/4)

  13. Nephrotoxic agents exposure till 9/4 • Baktar 7/18-28 • Tacrolimus 7/18-22 ■Renal: Acute renal failure, Hemolytic uremic syndrome, Nephrotoxicity (36% to 59% ) • Cyclosporin 8/4-5, 8/29-9/4 ■Renal: Hemolytic uremic syndrome, Nephrotoxicity (25% to 38% ) • Cellcept 8/6-9/4 ■Renal: Serum blood urea nitrogen raised (heart transplant, 34.6% ), Serum creatinine raised (heart transplant, 39.4% ), Urinary tract infectious disease (renal, 37% to 37.2% ) • Acyclovir 8/21-30 ■Renal: Renal failure • Contrast 7/21, 7/29, 8/19

  14. Tentative active diagnosis • Acute kidney injury, AKIN stage III, suspect shock and infection related, ruled out nephrotoxic agents (cyclosporin, cellcept, contrast) related, ruled out hepatorenal syndrome • Liver decompensation with hyperbilirubinemia and coagulopathy, graft liver infarction related, r/o rejection • Azotemia, suspect UGIB related, suspect pre-renal azotemia, suspect cellcept & steroid related, suspect catabolism state related • EG junction ulcer bleeding • Fever, suspect GI bacteria tranlocation

  15. Treatment course Anuria T-bil 25~35 Shock UGIB Shock Alb Alb Alb 19 20 21 22 23 24 25 9/12 Expired Tazocin Levo. Levo. Predonine MMF Cyclsporin 9/19 Failed pigtail for R’t sub-phrenic abscess drainage 9/21 Nerve block for right shoulder post-herpetic pain 9/23 Pigtail for R’t sub-phrenic abscess drainage

  16. Discussion • Hepatorenal syndrome

  17. AKI in liver cirrhosis • Actual prevalence unknown • 20~35% hospitalized P’ts • ↑ risk if ascites(+)50% AKI within 41+/- 3 months after developing ascites • HRS is not the most common cause • 7.6% of 129 liver cirrhosis P’ts with ascites & AKI • 423 P’ts with liver cirrhosis & AKI • ATN 35%; Pre-renal failure 32%; type I/II HRS 20%/6.6% • 463 P’ts with liver cirrhosis & AKI • Infection 46%; Pre-renal failure 32%; HRS 13%; Parenchyma kidney disease 9% ClinNephrol. Jan 2006 Clin Gastroenterol Hepatol. Jul 2010 Gastroenterology. 2002 Gastroenterology. 2011

  18. Semin Liver Dis. Feb 2008;28(1):81-95.

  19. Back to our P’t WBC, Na, AST, ALT, Bilirubin, Infection, GIB ClinNephrol. Jan 2006;65(1):28-33.

  20. 2010 South med.

  21. 2011 Expert Opin Pharmacotherapy

  22. 2011 Expert Opin Pharmacotherapy

  23. HRS in liver cirrhosis • Risk parallel progression of liver diseases • Minimal risk without ascites • In P’ts with liver cirrhosis & ascites, the probability of HRS in 1yr/5yr= 18%/39% • Advance liver diseases waiting for transplantation: 48% develop HRS Gastroenterology. July 1993 Kidney Int. Jul 2005

  24. Clin J Am SocNephrol. Sep 2006;1(5):1066-1079.

  25. Pathophysiology Nature review 2012

  26. Cardiac output Mean BP SVR Semin Liver Dis. Feb 2008;28(1):81-95. Hepatology. 2003;38(5)1210-1218

  27. Systemic involvement Semin Liver Dis. Feb 2008;28(1):81-95.

  28. How to diagnose HRS? • EXCLUDE other causes of renal failure • Absence of parenchymal kidney diseases • No proteinuria (>500mg/day), micro-hematuria (>50/HPF), abnormal renal echo • Tubular function preserved • UNa<10 meq/L • Establish diagnostics criteria Back to our P’t On diuretics, shock, nephrotoxic agents, infection Clin J Am SocNephrol. Sep 2006;1(5):1066-1079. Lancet. Nov 29 2003;362(9398):1819-1827

  29. Diagnostic criteria 1. Creatinine clearance no longer incorporated 2. Ongoing bacterial infection does not exclude HRS (provided septic shock not present) 3. Albumin is preferred to saline for plasma volume expansion 4. Nonessential minor diagnostic criteria including low urine sodium level have been omitted Back to our P’t No diuretics withdraw, shock, nephrotoxic agents Semin Liver Dis. Feb 2008;28(1):81-95.

  30. Type I & II HRS • Type 1 HRS • Doubling of the serum creatinine to a level >2.5 mg/dL in <2 weeks’ duration • Type 2 HRS • Gradual rise in serum creatinine to >1.5 mg/dL. 2 different clinical entities rather than stages of progression of the same disease Nature review 2012

  31. Precipitating factor • Bacteria infection • 20~30% patients with SBP develop HRS despite appropriate treatment • Large volume paracentesis without albumin infusion • ~15% develop HRS • Gastrointestinal bleeding • ATN or HRS? • Acute alcoholic hepatitis • 25% develop HRS • Others • Adrenal insufficiency in critically ills • Nephrotoxic agents N Engl J Med. Aug 1999 Gastroenterology. Jul 1993 Back to our P’t Bacteria infection, GIB, nephrotoxic agents Gastroenterology Dec 2000 Nephrol Dial Transplant (2012) 27: 34–41

  32. Advanced liver diseases correlated with renal failure after GIB Hepatology. Oct 2001;34(4 Pt 1):671-676

  33. Adrenal insufficiency Hepatology Apr 2006;43(4):673-681. Hepatology Nov 2006;44(5):1288-1295

  34. Nature history & prognosis • Potentially reversible • Type I HRS • Mortality 80% within 2 weeks; only 10% survive> 3 months • Median survival 1 month • Type II HRS • Median survival 6 months • MELD score >20/<20 1month/8months Hepatology. Jan 1996 Lancet. Nov 29 2003 Semin Liver Dis. Feb 2008;28(1):81-95.

  35. Survival of AKI in liver cirrhosis • 562 P’ts with AKI & liver cirrhosis • 3month survival • HRS: 15% • Infection induced AKI 31% • Hypovolemia induced AKI 46% • AKI associated with evidence of parenchymal renal disease 73% Gastroenterology. Sep 2007; 133(3):818-824.

  36. Prevention • Spntaneous bacteria peritonitis • Prophylactic abx in high risk P’ts • Albumin+ antibiotics rather than antibiotics alone if SBP occur • Acute alcoholic hepatitis • Pentoxyfylline use • Large volume paracentesis • Albumin for plasma expansion • Others • Avoid NSAID, aminoglycoside • Judicious use of diuretics Gastroenterology. Sep 2007 N Engl J Med. Aug 5 1999 Gastroenterology. Dec 2000 Hepatol. Jan-Mar 2002

  37. Gastroenterology. Sep 2007; 133(3):818-824.

  38. N Engl J Med. Aug 5 1999; 341(6):403-409

  39. Treatment • General measure • Pharmacological therapy • TIPS • RRT • Liver transplantation Lancet. Nov 29 2003;362(9398):1819-1827

  40. General measures • Care intensity • Type I/II HRS: ICU/OPD • Fluid status • Albumin infusion • DC diuretics • Treat precipitating factors • Access prognosis and determine further treatment plan • Others • Large volume paracentesis to ↓ intra-abdominal pressure • Treat adrenal insufficiency Back to our P’t No further treatment plan?

  41. • Cardiac index in cirrhotic patients with hepato-renal syndrome may be fluid-responsive despite normal CVP & GEDVI • Intra-abdominal hypertension, caused by ascites, can be reduced by paracentesis, resulting in a net increase in renal perfusion pressure Crit Care. 2008;12(1):R4.

  42. • After paracentesis, fluid substitution can be titrated to keep GEDVI constant, and creatinine clearance and fractional excretion of sodium may increase. • In cirrhotic intensive care patients with intra-abdominal hypertension caused by ascites resulting from fluid therapy, paracentesis is a safe procedure Crit Care. 2008;12(1):R4.

  43. Pharmacological therapy • Vasoconstrictor agents • Vasopressin analog: Terlipressin • α –agonists • Norepinephrine • Midodrine Lancet. Nov 29 2003;362(9398):1819-1827

  44. Abandoned vasoactive agents • Renal vasodilator agents: ineffective and associated with side effects • Dopamine, fenoldopam, prostaglandins • Ornipressin(Vasopressin analogue): effective, but high ischemic side effect(30%) Arch Intern Med. Jul 1975 J Hepatol. 1993 Gastroenterology. 1970 Hepatology. Oct 1999

  45. Terlipressin • Long-acting synthetic vasopressin analog • Acting through V1 receptor, which preferentially expressed within splanchnic circulation

  46. P=0.09 The mostimportant predictor of HRS reversal was a low serum creatinineat initiation of therapy P=0.839 Gastroenterology. 2008; 134(5):1360-1368.

  47. Response rate typeI/II HRS: 35%/67% Gastroenterology. 2008; 134(5):1352-1359

  48. Midodrine • Midodrine alone • Improved systemic hemodynamics but failed to improve renal function • Midodrine+Octreotide • Significant improvement in renal function Hepatology. Oct 1998 Hepatology. Jul 2003 Gastroenterology. 2008; 134(5):1352-1359

  49. Norepinephrine • 12 P’ts with type I HRS • Mean norepinephrine dose 0.8 mg/h for a mean duration of 10 days • Results • 10 (83%) achieved HRS reversal • 2 (17%) ischemic episodes In a recent meta-analysis, terlipressin and norepinephrine were equivalent in terms of side effect profile and probability of HRS reversal Some authority recommend norepinephrine rather than terlipressin in ICU admitted P’t Hepatology. Aug 2002;36(2):374-380

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