Anda di halaman 1dari 43


Morning Report
Gautam Balakrishnan PGY-3
April 5th 2016

Chief complaint: Shortness of Breath

56 year old female presents to the ER with three days of

persistent non-productive cough with increasing shortness
of breath. Her symptoms worsened and her cough
became productive with yellow-green sputum, developed
orthopnea, watery non-melanotic non-bloody diarrhea,
and shortness of breath at rest and elicits orthopnea.

So she sought care in the Clark County ED. There she was
found to have bilateral pleural effusion with left sided
loculated in appearance. She was also found to have
lactic acidosis of 5.1, fluids and blood cultures were
obtained and was transferred to IMMC.

No chest pain, fevers, recent travel, sick contact

Medical History:
Hepatitis C
Surgical History:
Social History:
35 year history of smoking and
drinking alcohol quit 2 years



Vitals: BP 100/60, pulse 100, Temp 36.7C RR 24, spo2 94%
General: mild distress
HEENT: icteric +, PEERL, no erythema
CV: S1S2 +, no rubs/gallops
LUNGS: decreased breath sounds at the bases
ABD: distended +, no peritoneal signs, no HSM palpable
SKIN: palmar erythema, telangectasias on torso
EXT: clubbing + warm extremities, no edema
NEURO: asterexis +, no focal deficits
Pych: AOx3

Summary Statement

56 year old female with cirrhosis, hep C, HTN admitted with 3 days
of progressively increasing SOB, productive cough associated with
nausea and diarrhea.


Lactic acid 5.1

Differential Diagnosis

Heart failure

Pulmonary embolism




Kidney disease

Inflammatory disease

What do you want to do next?

More info

1.7 L removed in total

8 Hours later

UOP 50ml so far..


Hepatorenal syndrome

Assessing kidney function in pts

with cirrhosis
Cr assays are subject to interference by
chromogens, bilirubin being the major one
There is decreased hepatic production of
The edematous state that complicates endstage liver disease leads to large distribution of
Cr in the body and lower serum Cr concentration
Complications such as variceal bleeding,
spontaneous bacterial peritonitis or sepsis lead
to increased Cr tubular excretion

Proulx et al. Nephrology Dialysis Transplantation 2005

HRS is a form of acute or subacute renal failure
characterized by severe renal vasoconstriction,
which develops in decompensated cirrhosis or
Nearly half of patients die within 2 weeks of this
The annual incidence of HRS ranges between
8% and 40% in cirrhosis depending on the MELD
The frequency of HRS in severe acute alcoholic
hepatitis and in fulminant liver failure is about
30% and 55%, respectively
Munoz S. Medical Clinics of North America July 2008

Munoz S. Medical Clinics of North America July 2008

Classification of the hepatorenal

Type 1: cirrhosis with rapidly progressive
acute renal failure
Type 2: cirrhosis with subacute renal failure

Causes of AKI in pts with cirrhosis

Acute tubular necrosis (41.7%)

Pre-renal failure (38%)

Hepatorenal syndrome (20%)

Post-renal failure (0.3%)

Moreau et al. Hepatology 2003

Major diagnostic criteria for

hepatorenal syndrome
Cirrhosis with ascites
Serum creatinine > 1.5mg/dL
No improvement in serum creatinine (decrease to a level
of <1.5mg/dL) after at least 2 days with diuretic
withdrawal and volume expansion with albumin. The
recommended dose of albumin is 1g/kg of body weight
per day up to a maximum of 100g/day
Absence of shock
No current or recent treatment with nephrotoxic drugs
Absence of parenchymal kidney disease as indicated by
proteinuria >500mg/day, microhematuria (<50 RBC/high
power field) and/or abnormal renal ultrasonography
Angeli et al. Journal of Hepatology February 2008

Minor diagnostic criteria for

hepatorenal syndrome

Urine volume < 500 mL/24 h

Urine sodium <10 mEq/L

Urine osmolality greater than plasma osmolality

Urine red blood cells < 50 per high power field

Serum sodium <130 mEq/L

Angeli et al. Journal of Hepatology February 2008

Type 1 hepatorenal syndrome

The serum creatinine level doubles to greater than 2.5

mg/dL within 2 weeks

It is characterized by its rapid progression and high

mortality, with a median survival of only 1 to 2 weeks

Associated with SBP (20%) or large volume paracentesis

w/o albumin (15%)

In some cases acute hepatic injury, superimposed on

cirrhosis, may lead to liver failure and HRS

Munoz S. Medical Clinics of North America July 2008

Type 2 hepatorenal syndrome

Serum creatinine increases slowly and gradually during

several weeks or months

Many patients with type 2 HRS eventually progress to

type 1 HRS because of a precipitating factor

The median survival of type 2 HRS is about 6 months

Diuretic resistant or refractory ascites

Munoz S. Medical Clinics of North America July 2008

7-10% in hospitalized cirrhotics with ascites
20% at 1 year, 40% at 5 years

Risk Factors
Advanced ascites (diuretic resistant)
Large volume paracentesis w/o albumin (15%)
SBP (20%)

Worst prognosis of all complications of cirrhosis
Type 1 median survival: <2 weeks
Type 2 median survival: ~6 months

Lack of specific testing
Diagnosis of exclusion
Differential Diagnosis of renal failure in cirrhosis

Hypovolaemia (GI hemorrhage, shock)

Nephrotoxins (drugs, contrast)
Glomerulonephritis (Hep B and C)
Acute Tubular Necrosis

Munoz S. Medical Clinics of North America July 2008

Nitric oxide and L-Arginine

The imbalance between NO and vasoconstrictors
such as endothelin-1 in the renal microcirculation
has been proposed to be responsible for the
progressive deterioration in kidney function in these
both metabolites of NO are excreted predominantly
by the kidney, decreased renal clearance rather
than overproduction could account for the elevated
level of NOx in decompensated cirrhosis
L-Arginine (L-Arg), a nonessential amino acid, is the
precursor for NO production by nitric oxide synthase

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

After adjusting for all demographics and variables, HRS was

the only disease state predicting high levels of NOx in the
peripheral circulation (P<0.001)
Multivariate analysis also revealed that HRS was an
independent factor predicting high levels of L-Arg (P=0.03)
Chronic renal failure and stages of progressive renal
dysfunction in decompensated cirrhosis were not
independently associated with peripheral levels of NOx or LArg
Peripheral levels of NOx reliably reflect NOx levels in the
splanchnic circulation, suggesting that peripheral levels of
NOx can be used diagnostically as a marker for disease state

Kayali et al. Journal of Gastroenterology and Hepatology February 2009


Angeli et al. Journal of Hepatology February 2008

Combination therapy with midodrine (a
selective alpha-1 adrenergic agonist) and
octreotide (a somatostatin analog) may be
effective and safe
Midodrine is a systemic vasoconstrictor and
octreotide is an inhibitor of endogenous
vasodilator release, combined therapy would
improve renal and systemic hemodynamics

Initial study, five patients received 1020 g

intravenous albumin per day for 20 days, plus
octreotide with a target dose of 200 g
subcutaneously three times per day, and midodrine
titrated up to a maximum of 12.5 mg orally three
times per day to achieve an increase in mean blood
pressure of 15 mm Hg. (Angeli P HEPATOLOGY 1999; 29: 1690

Results were superior to those of eight patients

treated with dopamine and albumin.
This regimen can be administered outside of an
intensive care unit and can even be given at home.

A retrospective study from the United States

involving 60 patients treated with
octreotide/midodrine/albumin and 21 concurrent
nonrandomized albumin-treated controls reported
reduced mortality in the treatment group (43% versus
71%, P < 0.05). (Esrailian E et al. Dig Dis Sci 2007; 52: 742748.)

Terlipressin, an agonist of the V1
vasopressin receptors, is inactive in its
native form, but is transformed into the
biologically active form, lysine-vasopressin
through enzymatic cleavage of glycyl
residues by tissue peptidases
Because of this modification, terlipressin
has a prolonged biological half-life
compared with other vasopressin analogues

Terlipressin: Meta Analysis

Five studies involving 243 patients with HRS were
Pooling of study results showed a significant increase in
HRS reversal among patients who received terlipressin
versus those who received placebo (the pooled odd ratio
OR of HRS reversal was 8.09 p=0.0001)
The rate of severe ischemic events was higher in study
than control patients, (pooled OR=2.907 p=0.032)
Terlipressin use had no significant impact upon survival
(pooled OR for survival rate, 2.064 p=0.07)
Fabrizi et al. The International Journal of Artificial organs March 2009


Pentoxifylline has been shown in a randomized trial to be

superior to placebo in preventing hepatorenal syndrome in
patients with cirrhosis, ascites, and creatinine clearances
between 41 and 80 mL/min

This drug has also been shown to prevent hepatorenal

syndrome and improve survival in patients with severe alcoholic

Tyagi et al. Eur J Gastro Hep 2011;23:210-217.

Renal Replacement

no comparative studies have been reported between renal

replacement therapy and other methods of treatment, such as
vasoconstrictor drugs

Both HD and CVVHD have been used in HRS

MARS - molecular adsorbents recirculating system; isolated reports

Significant suppression of the endogenous vasoconstrictor systems
Decrease in creatinine levels
More easily controllable ascites

Reduce portal hypertension

Increase effective arterial volume

Reverse splanchnic vasodilatation

Shunt stenosis

Liver Transplantation
Treatment of choice for HRS
Limited by organ availability and mortality of HRS
Higher rate of complications:
Higher post operative mortality
More days in the ICU
Increased need for post-op RRT (35% vs. 5% w/o HRS)

Improvement in renal function

Increased GFR post-op vs. decline in non-HRS pts
Lower overall GFR compared to non HRS pts

Key Points
Cirrhosis + renal failure = poor prognosis.
Survival is 50% at one month, and just 20% at
6 months.
Don't forget to discuss this along with
introducing code status and goals of care in
these patients, and make sure you know
where they stand from a liver transplant
Albumin infusion in patients with spontaneous
bacterial peritonitis - prevents hepatorenal
syndrome (N Engl J Med 1999;341:403-409.)

cascade of pathophysiology from portal

hypertension (portal hypertension-->splanchnic
vasodilation-->reduced effective (arterial) blood
volume + increase in renal vasoconstrictors
including the renin-angiotensin system-->kidney
dysfunction) plays a primary role in the disease
Differentiating HRS from ATN is difficult, but it's
worth the effort since HRS has specific therapies.
FENA, Urine Na.

1. Urinary biomarkers such as neutrophil gelatinase
associated lipocalin may assist in the differential diagnosis
of azotemia in patients with cirrhosis. (Class IIa, Level B)
2. Albumin infusion plus administration of vasoactive drugs
such as octreotide and midodrine should be considered in
the treatment of type I hepatorenal syndrome. (Class IIa,
Level B)

3. Albumin infusion plus administration of norepinephrine

should also be considered in the treatment of type I
hepatorenal syndrome, when the patient is in the
intensive care unit. (Class IIa, Level A)

Patients with cirrhosis, ascites, and type I or type II

hepatorenal syndrome should have an expedited referral
for liver transplantation. (Class I, Level B)

Big picture

Types I rapidly progressive

1. acute deterioration (doubling of creatinine or halving of CrCl
over 2 weeks)
2. absent renal parenchymal disease
3. absent proteinuria
4. no shock
5. no history of nephrotoxic drugs
Type 2 renal failure in the context of end-stage liver disease that
does not meet the criteria of type I


In which scenarios would you give IV fluids along with diuretics?

Crystal induced nephropathy hyperuricemia
Obstructive uropathy
Heart failure (albumin) intravascular volume