Critical Care Aspects of Chronic Critical Care Aspects of Chronic Hepatic FailureHepatic Failure

Aditya N. Dubey, MDAditya N. Dubey, MD

Peter K. Linden, MDPeter K. Linden, MDUniversity of Pittsburgh Medical Center

Department Critical Care Medicine

Learning ObjectivesLearning Objectives

Be familiar with the complications of chronic liver failure requiring critical care support

Pathophysiology and clinical sequelae of portal hypertension

Urgent treatments for variceal hemorrhage

Strategies to treat diuretic refractory ascites

Diagnosis, treatment, and prevention of SBP

Management of hepatorenal syndrome

Causes and treatment of hepatic encephalopathy

Indications for referral for liver transplantation

Hepatic FailureHepatic Failure

Major Reasons for ICU Admission

Variceal hemorrhage

Encephalopathy

Refractory ascites

Spontaneous bacterial peritonitis

Hepatorenal syndrome

Portal HypertensionPortal Hypertension

Terminology

Portal pressure = PV inflow x outflow resistance

The trans-hepatic gradient (THG) can be measured by the difference between the free hepatic vein to a wedge pressure in the hepatic vein (estimated PV pressure)

THG = free HVP – wedged HVP

Normal gradient < 5 mm Hg

Increased risk of bleeding > 12 mm Hg

Portal hypertension may be elevated without intrinsic liver disease due to pre- and post-sinusoidal pathology (see next slide).

Causes of Portal HypertensionCauses of Portal Hypertension

LIVER

Pre-sinusoidal PV thrombosis PV extrinsic comp. Schistosomiasis Sarcoidosis PBC

Sinusoidal Cirrhosis Alcoholic hepatitis

Post Sinusoidal Budd – Chiari Veno-occlusive dis. Severe CHF Restrictive heart dis.

BLOOD FLOW

Variceal HemorrhageVariceal Hemorrhage

Incidence and Outcome

Gastroesophageal varices in 40 - 60% cirrhotics

Variceal hemorrhage occurs in 25 - 35% cirrhotics

30% of the initial bleeding episodes are fatal

70% have recurrent bleeding with a one-year survival ranging from 30 - 80%

Non-variceal pathology (ulcers, gastritis, mucosal tear) may cause bleeding in patients with known liver disease and portal hypertension.

Sharara and Rockey. N Engl J Med. 2001;345 (9); 669.

Variceal HemorrhageVariceal Hemorrhage

Initial evaluation and stabilization

Assessment of intravascular volume status• Blood pressure is unreliable indicator of volume status• Hematocrit does not reflect acute blood losses

Fluid resuscitation• Place twp large bore i.v.’s and/or a central venous catheter• Colloid or crystalloid titrated to parameters of perfusion• Cross-matched or O negative blood can be used

Endotracheal intubation prior to endoscopy for: • Uncontrolled bleeding• Altered mental status, severe agitation• Respiratory distress or depression

Hierarchal Treatment for Hierarchal Treatment for Variceal Bleeding Variceal Bleeding

Pharmacologic

Endoscopic

Radiologic shuntTIPSS

Surgical Shunt

Balloon Tamponade

Pharmacologic and endoscopic therapyare the usual 1st and

2nd interventions

Acute Variceal Hemorrhage: Acute Variceal Hemorrhage: PharmacotherapyPharmacotherapy

Octreotide• Synthetic analogue of somatostatin

• Decreases portal pressure and azygos blood flow

• Stops variceal bleed in 80% of the cases

• Efficacy is similar to endoscopic sclerotherapy and better than vasopressin

• 5-day course reduces bleeding after endoscopic therapy

• Can cause mild hyperglycemia and abdominal cramping

Vasopressin• Reduces portal pressure but causes myocardial and mesenteric ischemia

Terlipressin• Efficacy similar to endoscopic sclerotherapy and as effective as balloon

tamponade when used with nitroglycerin

• Not approved for use in U.S.

Corley DA. Gastroenterology. 2001;120(4):946-54; Harry R. Curr Opin Crit Care. 2002;8:164-170; Sharara and Rockey. N Engl J

Med. 2001;345(9):669.

Possible Targets for Therapeutic Possible Targets for Therapeutic Intervention in Variceal HemorrhageIntervention in Variceal Hemorrhage

1. Reduction of cardiac output by beta-1 blockade to prevent bleeding (NOT for acute bleeding!!)

2. Reduction of splanchnic blood flow by beta-2 blockade or vasoconstrictors such as alpha-adrenergic agonists or vasopressin analogues

3. Reduction of intrahepatic resistance by vasodilators

4. Reduction of variceal or collateral flow by beta-2 blockade, balloon tamponade, or endoscopic therapy

Esophageal vs. Gastric VaricesEsophageal vs. Gastric Varices

Esophageal varices• Primary approach is endoscopic

banding or sclerotherapy

• TIPSS, surgical shunts are

alternatives

Gastric varices• Diffuse, deep submucosal

anatomy

• Endoscopic tx difficult, dangerous

• Primary approach are TIPSS or surgery

Variceal Hemorrhage: Endoscopic TherapyVariceal Hemorrhage: Endoscopic Therapy

Endoscopic Band Ligation (see next slide)• Controls bleeding in 80 - 90% of cases

• Lower complication rates than sclerotherapy

Endoscopic Sclerotherapy• Intravariceal or paravariceal injection of a sclerosing agent

• Stops bleeding in 80 to 90% of the cases

• Complications include perforation, ulceration and stricture

Cyanoacrylate Injection• Used to control bleeding from gastric varices

• Superior to EBL for treatment of bleeding gastric varices

• Not available in U.S.

Laine L. Ann Intern Med. 1995;123(4):280-7.

Lo GH. Hepatology. 2001;33:421-427.

Banding of Esophageal VarixBanding of Esophageal Varix

Post endoscopy problems include…Post endoscopy problems include…

Abdominal distension: From endoscopic air insufflation, retained luminal blood, and increased ascites from resuscitation. This can even progress to abdominal compartment syndrome with associated respiratory compromise, hypotension, oliguria, and acidosis. Nasogastric decompression may partially

alleviate this problem.

Worsening encephalopathy: This may occur due to gastrointestinal passage of blood, hepatic hypoperfusion (“shock liver), and accumulation of sedative medication.

Recurrent bleeding: More likely to recur in advanced cirrhosis. Incidence can be reduced with a 5-day course of octreotide post banding and long term use of a

non-selective beta blocker (propanol, naldolol).

Infection: Spontaneous bacterial peritonitis is 3-5x higher following variceal hemorrhage due to occult bacteremia and ascites seeding. Antimicrobial

prophylaxis (quinolone, beta-lactam) reduces the incidence of SBP significantly.

Acute Variceal HemorrhageAcute Variceal HemorrhageBalloon TamponadeBalloon Tamponade

Effectively controls bleeding in 90% of the patients but is only a temporizing measure in massive uncontrolled variceal hemorrhage when initial endoscopic treatment is delayed or unsuccessful. • Can cause aspiration, esophageal ulceration, perforation with

mediastinitis

• Balloon-related mortality is 3 - 5%

• Gastric balloon inflation is usually sufficient

• Esophageal balloon inflation should only be used when gastric balloon is unsuccessful as it is associated with higher morbidity.

Sengstaken – Blakemore TubeSengstaken – Blakemore Tube

Gastric balloon

Esophageal balloon

Gastric aspiration port

Minnesota TubeMinnesota Tube

Gastric balloon

Esophageal balloon

Gastric aspiration port

Esophageal aspirationport

Tube Positioning and Gastric Balloon InflationTube Positioning and Gastric Balloon Inflation

1. Tube inserted to 50 cm

2. Auscultate in stomach

3. Inflate gastric balloon with 50 cc

4. Stat portable film

1. Re-confirm proximal position

2. Inflate GB 300-400 cc air

3. Pull to insure anchorage

4. Recheck film

5. 1-2 lbs of pully traction

Gastric and Esophageal Balloon InflationGastric and Esophageal Balloon Inflation

Esophageal Balloon inflated to 30 mmHg

1. Last resort

2. Deflate periodically

3. Use minimum effective pressure

4. Complication

- ulcer

- perforation

- stricture

Malposition of the Gastric Balloon of a Malposition of the Gastric Balloon of a Minnesota Tube Retroverted in the Distal Minnesota Tube Retroverted in the Distal

EsophagusEsophagus

Transjugular Intrahepatic Portosystemic Transjugular Intrahepatic Portosystemic Shunt (TIPSS)Shunt (TIPSS)

Major Indications

• Refractory variceal bleeding

• Refractory ascites, hydrothorax

• Radiologic insertion of a metallic shunt (8 -

12 mm diameter) which joins the hepatic and portal veins

• Target gradient (HV-PV) < 12 mmHg

• Restores hepatopedal flow

• Decompression of varices

Summary of Trials Comparing TIPSS to Summary of Trials Comparing TIPSS to Endoscopic Therapy for Variceal BleedingEndoscopic Therapy for Variceal Bleeding

Stanley. Lancet. 1997;350(9086):1235-1239.

Generally, higher rates of rebleeding were more common after Endoscopy treatment, while encephalopathy rates were higher in the

TIPSS groups

Complications of TIPSSComplications of TIPSS

Peri-procedure mortality of 1 - 2%• Intraperitoneal bleeding due to perforation of the hepatic capsule, hepatic,

or portal veins

• TIPSS embolization

• Acute right heart failure due to increased venous return to right heart

Later complications include recurrent bleeding due to TIPSS stenosis or thrombosis, infection, and hepatic encephalopathy.

Conditions Which May Contraindicate TIPSSConditions Which May Contraindicate TIPSS

This venogram shows an occlusive thrombus of the portal vein, which may make safe TIPSS placement

impossible.

This abdominal CT demonstrates a large hypodense hepatic lesion due to hepatocellular carcinoma in a very shrunken cirrhotic liver. Other contraindications include hepatic vein occlusion, heart failure or pulmonary hypertension, biliary obstruction, and

poorly controlled systemic infection.

TIPSS Thrombosis/StenosisTIPSS Thrombosis/Stenosis

Incidence 12 - 74%

Most likely within the first month

Symptoms - recurrent bleeding, ascites

Detection - Doppler ultrasound angiography (shows velocity gradient)

Treatment • Balloon dilatation

• Placement of TIPS shunt

Trans-TIPSS Embolization of Persistent VaricesTrans-TIPSS Embolization of Persistent Varices

Persistent variceal bleeding due to high flow collaterals despite a patent TIPS shunt may be coil-embolized radiologically via the TIPS shunt itself.

Acute Variceal Hemorrhage: SurgeryAcute Variceal Hemorrhage: Surgery

The distal splenorenal shunt (Warren shunt) procedure is generally reserved for Child’s A or B cirrhotics.

Consider in patients with bleeding refractory to pharmacologic, endoscopic, and radiologic treatment.

Complications include shunt thrombosis, infection, and worsening encephalopathy.

30-day mortality is close to 80% in Child’s C patients requiring emergency shunt surgery.

Relative Effectiveness of Available Therapies for Relative Effectiveness of Available Therapies for

the Prevention of Recurrent Variceal Bleedingthe Prevention of Recurrent Variceal Bleeding

Beta-blockers are the single most effective and safest strategy to prevent the recurrence of variceal Bleeding.

More aggressive strategies such as banding, TIPSS, or shunt surgery may decrease bleeding but are associatedwith higher risks and costs.

Sharara A, et al. N Engl J Med. 2001.

Hepatic EncephalopathyHepatic Encephalopathy

Hepatic encephalopathy reflects a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease.

Hepatic Encephalopathy – West Haven Hepatic Encephalopathy – West Haven Criteria for Grading Mental StateCriteria for Grading Mental State

Grade 1• Trivial lack of awareness• Euphoria or anxiety• Shortened attention span• Impaired performance of addition

Grade 2• Lethargy or apathy• Minimal disorientation for time or place• Subtle personality change• Inappropriate behavior• Impaired performance of subtraction

Grade 3• Somnolence to semi-stupor but responsive to verbal stimuli• Confusion • Gross disorientation

Grade 4• Coma, unresponsive to verbal or noxious stimuli

Hepatic Encephalopathy: Differential Hepatic Encephalopathy: Differential DiagnosisDiagnosis

Metabolic encephalopathies• Hypoglycemia• Hypoxia• Uremia• Electrolyte abnormalities

Toxic encephalopathies• Alcohol• Barbiturates, other CNS depressants• Heavy metals

Intracranial lesions• Subarachnoid, subdural, or intracerebral hemorrhage• Stroke• Intracranial tumor• Intracranial abscess• Epilepsy

Neuropsychiatric disorders

Hepatic Encephalopathy: Hepatic Encephalopathy: Precipitating FactorsPrecipitating Factors

Increased ammonia production• Gastrointestinal hemorrhage• Excess dietary protein• Azotemia• Infection including SBP• Blood transfusion• Hypokalemia• Systemic alkalosis• Constipation

Reduced metabolism of toxins because of hepatic hypoxia• Dehydration• Arterial hypotension• Anemia

Portosystemic shunts• Spontaneous

• TIPSS

• Surgical

Progressive hepatic

parenchymal damage

Hepatoma

Use of benzodiazepines or other psychoactive drugs

Riordan. N Engl J Med. 1997; 337(7):473-479.

Why does the ammonia level correlate Why does the ammonia level correlate poorly with encephalopathy?poorly with encephalopathy?

Venous ammonia levels < arterial

Time lag from ↑NH3 and CNS

Blood-brain permeability is variable

Balance of NH3 / NH4+

Processing (must be on ice, < 20 min)

Management of Hepatic EncephalopathyManagement of Hepatic Encephalopathy

First and foremost control the underlying precipitant(s).

Medical therapy - optimal agent is controversial (see meta-analysis)

Lactulose - has multiple actions including cathartic, acidification of the colon to

“ion-trap” ammonia as NH4+, and reduces inoculum of urea-splitting bacteria.

Drawbacks include osmotic diarrhea with hypernatremia due to free water loss

and gaseous bowel distension.

Neomycin - non-absorbed aminoglycoside which reduces colon bacterial

burden. Dosed at 2-6 grams orally per day. Small incidence of ototoxicity and

nephrotoxicity with prolonged usage.

Metronidazole - oral dosing at 800 mg/day. No large scale reported

experience. Is associated with neurotoxicity in hepatic failure due to

accumulation.

Flumazenil - benzodiazepine receptor (GABA) antagonist.

Flumazenil in Hepatic EncephalopathyFlumazenil in Hepatic Encephalopathy

In this double-blind, placebo-controlled, randomized trial,

flumazenil showed transient benefit in higher grades of

encephalopathy. The role of flumazenil for all degrees of encephalopathy or as a longer term agent in critically ill patients has not been determined.

Flumazenil

N = 265

Placebo

N = 262

Neurologic

improvement17.5% (Gr3)

14.7% (Gr4)

3.8% (Gr3)

2.7% (Gr4)

EEG

improvement27.8% (Gr3)

21.5% (Gr4)

5.0% (Gr3)

3.3% (Gr4)

Barbaro G, et al. Hepatology. 1998

Ascites - Critical Care AspectsAscites - Critical Care Aspects

Complicated ascites may be the principal reason for care admission but is frequently co-associated with intensive hemorrhage, renal failure, and/or hepatic encephalopathy.

Common complications of ascites include: • Diuretic-refractory ascites - defined as unresponsiveness to sodium

restriction and high-dose diuretics (400 mg/day spironolactone and 160 mg/day furosemide) OR rapid recurrence after therapeutic paracentesis

• Tense ascites - this may result in the development of:- Abdominal compartment syndrome with impaired venous return causing

hypotension, impaired renal perfusion causing oliguria and reduced hepatosplanchic perfusion

- Respiratory compromise may occur due to impaired diagphagmatic contractility and/or hydrothorax due to the passage of ascites into the pleural space

• Infection - (spontaneous bacterial peritonitis)

Runyon BA. Hepatology March 2004

ParacentesisParacentesis

Abdominal paracentesis is the most rapid and cost-effective technique to diagnose the cause of ascites. • An area of percussion dullness in the left lower quadrant (2 cm cephalad

and anterior to the anterior superior iliac spine) has a greater likelihood of ascites present than the midline.

• Ultrasound guidance should be utilized if ascites is difficult to localize and to avoid venous collaterals, intestine.

• Since bleeding is sufficiently uncommon, the prophylactic use of plasma or platelets before paracentesis is not recommended.

• An indwelling drainage catheter can be left for 3 - 5 days if therapeutic drainage is required.

Runyon BA. Hepatology. 2004.

Ascites - ClassificationAscites - Classification

High SAAG 1.1g/dl

Cirrhosis (75% cases)

Alcoholic hepatitis

Portal vein thrombosis

Budd-Chiari syndrome

Cardiac failure

Veno-occlusive disease

Low SAAG Low SAAG 1.1g/dl 1.1g/dl

Peritoneal carcinomatosis

Pancreatic ascites

Biliary ascites

Nephrotic syndrome

Tuberculous peritonitis

Krige J, et al. BMJ. 2001;322.

Spontaneous Bacterial PeritonitisSpontaneous Bacterial Peritonitis

Spontaneous infection of ascitic fluid in the absence of a secondary intra-abdominal source of infection

Translocation of intestinal bacteria or hematogenous seeding of ascites

Mainly a complication of cirrhotic ascites

Incidence is 15 - 20% of cirrhotics with the highest incidence in Child’s Class C cirrhosis and following upper gastrointestinal bleeding

E. coli, Klebsiella sp., S. pneumoniae most common

Clinical manifestations include fever, abdominal pain, unexplained encephalopathy, although asymptomatic presentations are not uncommon

Mortality per episode = 20 - 30%

One year follow-up mortality = 50%

Spontaneous Bacterial PeritonitisSpontaneous Bacterial PeritonitisDiagnosisDiagnosis

Ascites should be processed for the following:• Total cell count and differential

• Bacterial cultures in blood culture bottles

• Other tests (protein, albumin, LDH, glucose, special cultures) may be indicated based upon clinical judgment

A diagnosis of SBP is established by any one of the following:• > 250 polymorphonuclear cells per cubic mm of ascitic fluid and a

positive ascitic fluid culture is diagnostic.

• Patients with 250 PMN’s/mm3 but negative cultures (neutrocytic ascites)

• Positive ascites cultures and < 250 PMNs/mm3 (monomicrobial non-neutrocytic ascites)

Runyon BA. Hepatology. 2004.

Spontaneous Bacterial PeritonitisSpontaneous Bacterial PeritonitisTreatmentTreatment

Intravenous albumin 1.5g/kg at the time of diagnosis followed by 1g/kg on day 3 helps in preventing hepatorenal syndrome and decreases mortality (Sort P, et al. N Engl J Med. 1999;341:403-409)

Secondary bacterial peritonitis• PMN count 250 cells/mm3

• Multiple organisms on Gram’s stain and culture

• Two of the following ascites criteria:- Total protein > 1g/dl

- LDH > upper limit of normal for serum

- Glucose < 50mg/dl

• Treatment – Third generation cephalosporin and laparotomy

Spontaneous Bacterial PeritonitisSpontaneous Bacterial PeritonitisAASLD GuidelinesAASLD Guidelines

Patients with ascitic fliud PMN 250/mm should receive empiric antibiotic therapy e.g., cefotaxime, 2 g every 8 hours (I).

Patients with ascitic fliud PMN < 250/mm with signs or symptoms of infection should receive empiric antibiotics pending culture results (II-B).

Oral ofloxacin can be considered in patients without vomiting, shock, grade 2 hepatic encephalopathy, or serum creatinine > 3mg/dl.

Prevention of SBP:• Short-term (7 days) inpatient norfloxacin or bactrim prophylaxis in patients

with gastrointestinal hemorrhage

• Patients with prior SBP should receive long term prophylaxis with daily norfloxacin or bactrim (SBP recurs in up to 70% of cases within one year).

Refractory Ascites: ManagementRefractory Ascites: Management

Serial paracentesis every 2 to 4 weeks and/or transjugular intrahepatic portosystemic shunts:• Post-paracentesis volume expansion is controversial but may be

considered when 5 l or more of fluid is removed. Albumin (6-8 g per l of fluid removed), dextran 70 or hemacecel may be used.

A recent meta-analyses comparing TIPS vs. Paracentesis showed: • 30-day mortality - no difference, OR 1.0 (CI 0.1-10.06)

• 24-month mortality - no difference, OR 1.17 (CI 0.52-2.66)

• 12-month ascitic fluid reaccumulation - less in TIPS, OR 0.14 (CI 0.06-0.28)

• Hepatic encephalopathy - more with TIPS, OR 2.11 (CI 1.22-3.66)

• No difference in the incidence of GI bleed, infections, or acute renal failure.

Sheagren JN, et al. J Clin Gast. 1996; Saab S. Cochrane Hepato-Biliary Group. 2005.

Tc Labeled Sulfur Colloid Showing Fluid Tc Labeled Sulfur Colloid Showing Fluid Passage From Peritoneal to Pleural SpacePassage From Peritoneal to Pleural Space

9999

Bhattacharya, et al.J Gastroenterol Hepatol. 2001.

Right Hydrothorax Managed with Plerual Right Hydrothorax Managed with Plerual Catheter DrainageCatheter Drainage

Before After

Hepatorenal SyndromeHepatorenal Syndrome

• Type 1 HRS:

Acute impairment in renal function defined by doubling of initial serum creatinine above 2.5 mg/dl or a 50% reduction of the initial 24-hour creatinine clearance to a level lower than 20 ml/min in less than two weeks. Mortality is as high as 90% after 2 - 4 weeks

• Type 2 HRS:

Stable or slowly progressive impairment in renal function not meeting the above criteria. Associated with better survival than Type 1 HRS.

Hepatorenal SyndromeHepatorenal Syndrome

Pere Ginès, et al. N Engl J Med. 2004;350:1646-1654.

Hepatorenal SyndromeHepatorenal Syndrome

Criteria for Diagnosis of HRS:• Serum creatinine >1.5 mg/dl or 24-hr creatinine clearance < 40ml/min

• Absence of shock, ongoing bacterial infection or fluid loss, and no current treatment with nephrotoxic drugs

• Absence of sustained improvement in renal function (decrease in serum creatinine to 1.5mg/dl) after discontinuation of diuretics and trial of plasma expansion

• Absence of proteinuria (< 500 mg/d) or hematuria (< 50 RBCs per HPF)

• Absence of ultrasonographic evidence of obstructive uropathy or parenchymal renal disease

• Urinary sodium concentration < 10 mmol/L

Hepatorenal Syndrome: TreatmentHepatorenal Syndrome: Treatment

Administration of one of the following drugs or drug combinations can be considered:• Norepinephrine 0.5 - 3.0mg/h intravenously

• Midodrine 7.5 mg three times daily increased to 12.5 mg three times daily if needed in combination with octreotride 100 g subcutaneously three times daily, increased to 200 g three times daily if needed

Concomitant adminstration of albumin 1 g/kg intravenously on day one, followed by 20 - 40 g daily

This treatment is given for 5 to 15 days.

End point of the treatment is reduction of serum creatinine to < 1.5 mg/dl

Vasoconstrictor Studies in HRSVasoconstrictor Studies in HRS

STUDY Treatment # Pts HRS Reversal Survival Liver Tx

Guevara Or + A 8 4 5 -

Uriz Te + A 9 7 5 3

Gulberg Or, D, A 7 4 4 2

Mulkay Te + A 12 7 4 2

Ortega Te ± A 13 10 9 5

Angeli Mi,Oc,A 5 4 4 2

Duvoux NE + A 12 10 6 3

Moreau Te ± A 99 58 36 13

TOTAL 165 104 (63%) 73 (44%) 30 (18%)Or – orlipressin NE – norepinephrineTe - terlipressin OC - octreotide Mi - midodrine A - albumin

These results, although encouraging, need to be validated by a large, prospective randomized trial.

Hepatorenal Syndrome: TreatmentHepatorenal Syndrome: Treatment

Hemodialysis or continuous venovenous hemofiltration may be required as a bridge to liver transplant.

Liver transplantation offers the best survival rate of 70% at two years.

Kidney function may return to normal post successful

liver transplant.

Other Pulmonary Complications of Chronic Other Pulmonary Complications of Chronic Liver DiseaseLiver Disease

Hoeper MM, et al. Lancet. 2004;363(9419):1461-8.

Hepatopulmonary syndrome• Incidence of 4 - 29%• Diagnosis requires demonstration of hypoexmia due to abnormal intrapulmonary vascular dilatations

causing shunting or severe ventilation:perfusion mismatching. • Vascular dilatations demonstrable by either agitated saline echocardiography or macro-aggregated albumin

scanning. • Orthodeoxia (desaturation with upright posture) and platypnea (dyspnea with upright posture) may be seen.• Management include supplemental oxygen to maintain SaO2.• Mortality rate of 41% at 2.5 years reported. • Severe HPS may slowly remit after successful liver transplantation although supplemental oxygen required.

Portopulmonary hypertension• Incidence of 2 - 10% (as high as 16% in those referred for liver transplant)• Mean PA pressure > 25 mmHg, PVR > 250 dyne s-1 cm-5, PA occlusion (wedge) < 15 mmHg• Pathogenesis unclear but may include pulmonary arterial plexopathy in medium pulmonary arteries due to

shear stress or high output state or humoral influences.• Suspect in patients with progressive dyspnea and signs of right heart failure.• Continuous prostacyclin (PGI2) infusion has shown benefit in non-randomized, open label experience but

may not improve long term survival without liver transplantation. • Severe cases (mean PA > 45) or poor right heart function contraindicates liver transplantation.

Pathophysiology of Hypoxemia in Pathophysiology of Hypoxemia in Hepatopulmonary SyndromeHepatopulmonary Syndrome

Hoeper MM, et al. Lancet.2004;363(9419):1461-8.

Considerations for Liver Transplantation in Considerations for Liver Transplantation in Critically IllCritically Ill

Liver transplantation is the most effective treatment for chronic liver failure with an overall, one-year, 88% patient survival.

Patients with cirrhosis should be referred for transplantation when evidence of hepatic dysfunction or major complications develop.

Patients with type I HRS should have an expedited referral for liver transplantation.

The prognostic model for end stage liver disease (MELD score) predicts liver-related mortality based upon the serum Cr, serum bilirubin, and INR.

Murray K, Carithers R. AASLD Practice Guidelines: evaluation of the patient for liver transplantation. Hepatology. 2005.

Liver Transplantation