A simple description of a less understood topic in Intensive Care Medicine. Aim to make understanding and management easy for the residents and prevention steps for all ICU workers.

1. Muhammad Asim Rana
BSc, MBBS, MRCP, MRCPS, FCCP, EDIC, SF-CCM
Critical Care Department
King Saud Medical City

2. Outline
1- Definition and type.
2- Etiology.
3- Diagnosis.
4- Differential Diagnosis.
5- Treatment.
6- Conclusion.

3. Introduction
• HRS is the development of renal failure in Pts
with advanced chronic liver disease(eg. portal
HTN due to cirrhosis, severe alcoholic
hepatitis, or (less often) metastatic tumors
• HRS occasionally happened with fulminant
hepatitis, who have portal HTN & ascites.

4. Pathogenesis
Progression of liver failure
&
portal hypertension
↑Arterial
vasodilatation
↓Effective arterial BP
Moderate Na
retention
Severe water
retention & ↓ Na
Central Hypovolemia
↓Cardiac
output
↑Chronotropic
function
Extreme Hepato-renal Syndrome

5. Types
• Type 1:
• Increase in serum creatinine >2.5mg/dl
(221 micromol/L) or 50% decrease in Cr. Clearance
<20ml/min. during a periods of less than 2 weeks.
– Rapidly progressive and very poor short term outcome.
• Type 2:
• Increase in serum creatinine>1.5 mg/dl, without
meeting criteria of type 1.
– refractory ascites is usually present.
– Slower I progress but prognosis is not bad as type 1.

6. Prognosis
• Worst of all complications
of cirrhosis.
• Median survival in type
1 to 2 weeks
• Median survival in type 2:
up to 6 months

7. Risk Factors
It may happen spontaneously, but there are
many triggers include:
- diuretic resistance ascites
- large volume paracentesis without
albumin replacement (15%).
- SBP (20%).

8. Major Criteria
– Advanced chronic hepatic failure and portal hypertension
– Serum Creatinin > 1.5 mg/dl or 24 hours urine creatinin
clearance < 40 ml/min
– Absence of shock, massive GI or renal fluid losses,
exposure to nephrotoxic drugs, hypovolemia & ongoing
sepsis
– No sustained improvement in renal function following
diuretic withdrawal & volume expansion with 1.5 litres of
isotonic saline
– Proteinuria < 500 mg/dl
– No evidence of obstructive uropathy or parenchymal renal
disease

9. Minor Criteria
• Urine volume < 500 ml/day
• Urine sodium < 10 m eq/L
• Urine osmolality > plasma osmolality
• Urine RBCs < 50 per HPF
• Serum sodium < 130 mEq/L

10. Differential Diagnosis
• Glomerulonephritis and vasculitis:
– IgA nephropathy, renal disease associated with hepatitis B & C.
• Obesity with DM
– Who have NASH and diabetic nephropathy.
• ATN:
– 10-20% of patients with AKI in the setting of cirrhosis have ATN.
ATN with FENa ……
• SBP in absence of septic shock can be associated with HRS
(expert opinion).
• Pre-renal azotemia:
– In cirrhotics induced by GI fluid losses, bleeding, or therapy with
a diuretic or NSAIDs.

11. Factors playing role in the management of HRS
• Is the recovery expected in short term?
• Is the pt. admitted to the ICU?
• Which drugs are available for HRS?
• National and regional variability.
• Is the pt. a candidate for liver transplantation?

12. Treatment
• Patient in ICU:
Initially, we have to start:
o norepinephrine(0.5 – 3 mg/kg) with the goal of raising MAP:10
mmHg.
o albumin for @ least 2 days (1 g/kg per day or 100 gm
maximum).
o IV vasopressin may also be effective, starting at rate of
0.01 units/min & titrating upward as needed.
• Patient not in ICU: (terlipressin + albumin)
o Terlipressin:1 to 2 mg / 4 to 6 hrs).
o albumin: for 2 days (1 g/kg per day [100 g maximum]), followed
by 25 to 50 grs / day until terlipressin therapy is discontinued.

13. Treatment
• If terlipressin is not available:
(midodrine + octeriotide + albumin)
o Midodrine orally (starting @ 7.5 and increasing
the dose /8 hr. up to a maximum of 15 mg t.d.s).
o Octreotide is either given intravenous infusion
(50 mcg/hr) or S/Q (100 to 200 mcg t.d.s)
o Albumin is given for 2 days as an IV bolus
(1 g/kg /day [100 g maximum]), followed by 25 to
50 grs /day until midodrine & octreotide therapy
is discontinued.

14. Treatment
• In highly selected Pt. who fail to responds to
medical therapy:
• Transjugular intrahepatic porto-systemic shunt
is some times successful.
o TIPS: has numerous complication.
o TIPs: needs contrast so CRRT should be considered
particularly if serum creatinine >1.5 mg/dL.
o TIPS should be considered only as a last resort in
selected patients.

15. Treatment
• In patients who fail to
– respond to the above therapies,
– develop severely impaired renal function
– are candidates for liver transplantation
– have a reversible form of liver injury
– are expected to survive
• The recommendation is
– to start dialysis as a bridge to liver transplantation
or liver recovery.

16. Treatment
• Other therapies:
Misoprostol
N-acetylcysteine
ACE inhibitors
None of these approaches are consistently
associated with benefit.
Peritoneovenous shunt:
no more recommended because of lack of long term
benefit and high rate of complication.

17. Prevention
• As the HRS regularly developed in Pt. with systemic
bacterial infection and/or alcoholic hepatitis, so the
following intervention can help to prevent HRS:
o IV albumin in Pt. with SBP 1.5g/kg in the 1st day and
1g/kg in the 3rd day of antibiotic.
o It will reduce the incidence of renal impairment and mortality.
o Norfloxacin:
A randomized trial reported significant benefits with the
oral administration of norfloxacin at 400 mg/day.
Norfloxacin was associated with the following significant
benefits:
- decreased one-year probability of SBP (7 versus 61 percent) and
hepatorenal syndrome (28 versus 41 percent), and
- improved survival at three months (94 versus 62 percent) and
one year (60 percent versus 48 percent).

18. Conclusion:
• HRS can happen with advanced CLD and also with fulminant
hepatitis.
• Diuretics will cause azotemia but not HRS.
• HRS diagnosis needs good history and clinical diagnosis after
exclusion of other DD.
• Starting medical therapy depends on drug availability and Pt.
Position (ICU VS. medical ward).
• TIPS: should be considered as a last resort because of most Pt.
are not suitable for operation, numerous complication related
to the procedure, and needs for CRRT before and after the
procedure.
• CRRT should be started for Pt. expected to responds to
medical therapy or as a bridging to liver transplant.

19. Thank you