Inpatient Management of the Cirrhotic Patient. Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated

Inpatient Management of theInpatient Management of the

CirrhoticCirrhotic PatientPatient

Things You Will LearnThings You Will Learn

Background Information:-What is cirrhosis- What is compensated versus decompensated cirrhosis

Admission Evaluation:- If patient has ascites- If the patient has SBP- If patient has acute kidney injury- If patient has hepatic encephalopathy- If patient has gastrointestinal bleeding- Pain management

Preoperative Evaluation:- Risk Factors for morbidity/mortality- “Status” of the Liver- Type of Surgery- Contraindications to Surgery

Hepatocentric ViewHepatocentric View

““In the beginning, there was nothing………In the beginning, there was nothing………

Then God created the liver and gave it Then God created the liver and gave it internal viscera and appendages to provide internal viscera and appendages to provide sustenance and mobility.”sustenance and mobility.”

A bit about me…A bit about me…





What is Cirrhosis?What is Cirrhosis?

The end stage of any chronic liver disease HCV and EtOH are main causes in USA Results in two major syndromes

– Portal hypertension– Hepatic insufficiency

Associated with hyperdynamic circulatory state due to– Peripheral vasodilation– Splanchnic vasodilation

Manifestations of DecompensationManifestations of Decompensation

Jaundice: hepatic insufficiency GEV: portal HTN and hyperdynamic circulation Ascites: sinusoidal HTN and sodium retention due

to vasodilation and neurohumoral systems HRS: peripheral dilation->renal vasoconstriction HE: shunting through portosystemic collaterals,

brain edema, and hepatic insufficiency

““Status of the LiverStatus of the Liver””

1964 – Child and Turcotte publish a system to predict mortality related to portocaval shunt surgery in cirrhosis*

1973 – Pugh modified C-T scoring system to predict mortality related to esophageal surgery for bleeding varices (replaced ‘nutritional status” with PT)**

Child’s score = C-P score = CTP score

**Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC and Williams R. Transection of the esophagus for bleeding esophageal varices. Brit. J. Surg. 60: 646-654, 1973

*Child, CG, Turcotte, JG. Surgery and portal hypertension. In: The Liver and Portal Hypertension, Child, CG (Ed), Saunders, Philadelphia 1964. p.50.

Child’s ClassificationChild’s Classification

Presentation: 1 2 3Albumin (g/dl) > 3.5 2.8 - 3.5 < 2.8

Prothrombin time (INR)

< 1.7 1.7 - 2.3 > 2.3

Bilirubin (mg/dl) < 2 2 - 3 > 3

Ascites Absent Mild/Moderate(diureti

c responsive)

Severe(diuretic refractory)

Encephalopathy None Gr. I – II(precipitated)

Gr. III – IV(chronic)

*Class A = 5-6 points, B = 7-9 points, C = 10-15 points*Class A = 5-6 points, B = 7-9 points, C = 10-15 points

Points*

Interpreting Child’s ScoreInterpreting Child’s Score

These grades correlate with one- and two-year patient survival: – Class A - 100 and 85 %– Class B - 80 and 60 %– Class C - 45 and 35 %

Child’s class A are compensated– Median survival ~9-12 years– Management goals:

Treat underlying liver disease Prevention/early diagnosis of complications

Child’s class B&C are decompensated



Admission Evaluation:- If patient has ascites- If the patient has SBP- If patient has renal insufficiency- If patient has portosystemic encephalopathy- If patient has gastrointestinal bleeding- Pain management


If The Patient Has AscitesIf The Patient Has Ascites

Development of ascites in cirrhosis is common (60% over 10yrs); once ascites develops mortality can reach 50% over the next 2yrs.

Ascites formation is very common in postoperative setting in patients with cirrhosis/portal HTN due to liberal use of saline IVF (this can often be the initial presentation of cirrhosis - - missed pre-op!)


Clues:– Exam: palpable left/small right lobe,

splenomegaly, caput medusa– Labs:

Platelets < 175,000 Hepatic insufficiency: albumin <3.8, INR >1.3

– Imaging: nodular liver, splenomegaly


Diagnostic paracentesis:– No coagulopathy cutoff, need for “reversal”, etc– Cell count and differential, albumin, and total protein– If first presentation, concern over infection, or atypical

presentation Glucose Bedside culture Flow cytometry Simultaneous blood cultures (more later) LDH Triglycerides

– Don’t forget serum albumin to determine SAAG


- Make the diagnosis (i.e. recognize it, then analyze the fluid - - diagnostic paracentesis)

- Turn off the NS IV infusion! Think about carrier solutions for each of the patient’s IV infusions

- Sodium restriction: 2gm/day (88mEq)- Oral diuretics: spironolactone alone or

spironolactone/furosemide (100/40 ratio)- Goal: 300-500 ml/d (no edema) vs. 1000 ml/d (w/ edema)- Tense ascites: perform a large volume paracentesis (don’t

forget the albumin - - 6-8 gm per liter ascites removed)- High risk patients with ascites should be placed on SBP

prophylaxis (TP<1 and advanced liver failure)


- Do NOT use furosemide alone- Sodium not taken up in LoH absorbed in DCT/CT due

to hyperaldosteronism

- Do NOT use IV diuretics- No evidence that other diuretics (metolazone,

thiazides, torsemide) offer advantage of spironolactone +/- furosemide





If The Patient Has SBPIf The Patient Has SBP

- Most common infection in cirrhosis- Occurs in 10-20% of hospitalized patients with cirrhosis

and ascites- Mortality 10-20% (was 80% when first described)- Early diagnosis is KEY to management and reduction of

complications- Diagnostic paracentesis in any patient with cirrhosis and

ascites:- Upon hospital admission- Who develops S/Sx compatible with SBP (abd pain, F/C)- With worsening renal or liver function


- Diagnosis established:- Ascites PMN cell count >250 - Ensure bedside cultures collected- Simultaneous BCx should also be drawn (>50% SBP

also have bacteremia)- Traumatic tap if >10,000 RBC

- Subtract 1 PMN for every 250 RBC


- Do not wait on culture results to start Abx- Cefotaxime most studied (2g q12hr)- 3rd generation cephalosporine (ceftriaxone 1-2g q12hr)- “Quinolone” ok if community-acquired, uncomplicated- Extended spectrum Abx (carbapenems,

piperacillin/tazobactam) if nosocomial SBP

- Can change to PO in 48hrs if improving- 5 day course of Tx minimum, 8 days preferred, thus 7

days reasonable - Repeat paracentesis/broaden coverage if not improving in

48hrs (expect at least 25% PMN decrease)


- Albumin to prevent renal dysfunction (10% vs. 3%) and 3 month mortality (41% vs. 22%)- 1.5g/kg on day #1 within 6 hours of Dx- 1.0g/kg on day #3 (reasonable to tailor to renal fx)

- What NOT to do:- Avoid aminoglycosides- No large volume paracentesis- Avoid diuretics (stop them if Pt is taking them)

Cuban Rock IguanaCuban Rock Iguana

Cuban Rock Iguana

Cuban Rock Iguana





If The Patient Acute Kidney If The Patient Acute Kidney Injury (AKI)Injury (AKI)

AKI occurs in ~19% hospitalized patients with cirrhosis– Pre-renal ~68% of these– Intra-renal next most common (ATN vs. GN)– Post-renal <1%

Hepatorenal syndrome (HRS) is a form of pre-renal failure: systemic/splanchnic vasodilation and reduced EAV->renal vasoconstriction

HRS ~33% of pre-renal AKI (1/5 of cirrhotics hospitalized with AKI)

Development of HRS-1 median survival ~2wks

Carotid/Renal Baroreceptors Sense Dec. Perfusion

Activation of Endogenous Vasoconstrictors

R.A.A.SR.A.A.S S.N.SS.N.S ADHADH Loss of local Loss of local renal vasodilatorsrenal vasodilators

AgII

Aldo

Na+/H2O Na+/H2O RetentionRetention

Inc. Renal Inc. Renal Vascular ToneVascular Tone

H2O H2O RetentionRetention

Abnml Renal Abnml Renal HemodynamicsHemodynamics

Dec. Effective Arterial PressureDec. Effective Arterial Pressure(inc. CO/CI, dec. SVR, splanchnic vasodilation)(inc. CO/CI, dec. SVR, splanchnic vasodilation)

V2 Receptor

Dec. PGE2

Dec. renal PG’s synthesis and effect

Nitric OxideNitric OxideEndotoxemiaEndotoxemia

Non-Osmotic

If The Patient Has AKIIf The Patient Has AKI

Definition of HRS shifting target– Consensus conferences: Cr double to >2.5– Suggested that Tx initiated earlier, with only

1.5-fold increase in Cr from baseline

Key to success is the early recognition and Tx of this condition


D/C medications that decrease blood volume– Diuretics– Lactulose– Vasodilators

Expand intravascular volume– Albumin 1g/kg up to max 100g– NS if over-diuresis is suspected


Search for and Tx AKI precipitants– Infection– Fluid loss– Blood loss

If no improvement or continued worsening– Renal U/S to R/O post-renal AKI– Urinary sediment to R/O intrinsic AKI

Proteinuria/hematuria suggests GN Granular/epithelial casts suggests ATN

– Historical clues such as sepsis, hypovolemia, recent nephrotoxins, contrast dye help sort out ATN vs. HRS


OLT is only definitive Tx that provides long-term survival

Arteriolar vasoconstrictors bridge to OLT– Terlipressin most studied but not available in USA– Midodrine plus octreotide most common in USA

Midodrine: start 5-7.5mg PO TID and increase to 12.5-15mg TID

Octreotide 100mcg SQ TID and increase to 200mcg SQ TID(continues infusion or used as sole therapy->no benefit)

– Should be coupled with albumin infusions





If The Patient Has Hepatic If The Patient Has Hepatic Encephalopathy (HE)Encephalopathy (HE)

HE (or portosystemic encephalopathy: PSE) is a clinical spectrum of reversible abnormalities in neuropsychiatric function of patients with advanced liver disease

Continuum of neuropsychiatric alteration:– Episodic (acute): either precipitated or spontaneous– Recurrent : 2 or more acute episodes per year– Persistent (chronic): persistent deficits negatively affect

social/occupational function– Minimal (subclinical): only found with careful testing

If The Patient Has HEIf The Patient Has HE

Precipitating Factors: – Infection– Recent TIPS placement– Non-compliance– HCC– HV/PV thrombosis– Hypovolemia– GI bleeding– Hypokalemia– Metabolic alkalosis (diarrhea)– Hypoxia– Sedatives– Hypoglycemia

AsterixisAsterixis


GradeGrade Mental StatusMental Status Neuro. FindingsNeuro. Findings

00 No alterations No alterations

11 Trivial lack of awareness, euphoria or anxiety, short

attention span

Tremor, uncoordinated, poor handwriting, early asterixis

22 Lethargy, disorientation, personality changes,

inappropriate behavior

Asterixis, slurred speech, ataxia, hypoactive reflexes

33 Somnolence to semi stupor, confusion, response to noxious

stimuli

Hyperactive reflexes, Babinski, clonus

44 Coma, no response to noxious stimuli

Dilated pupils, coma, decerebrate posturing (transient)


Psycodynamic or “Trail test”Psycodynamic or “Trail test”


Therapy:

1) Fix/Remove the precipitating factors

2) Lactulose: 30-50ml q2h initially, then TID (goal 3-5 soft BM/d); can use 300ml retention enemas also

3) Antibiotics: rifaximin 200-600mg TID No evidence that combo with lactulose is better Use in patients who can’t tolerate or don’t respond to lactulose

4) Flumazenil: 0.4-2.0 mg IV (lasts 2-4 hrs only)

5) Don’t restrict protein (1.0 -1.2 g/kg/day)

6) If recent TIPS may need reduction/occlusion

Hutia a.k.a “Banana Rat”

“Banana Rat: The Other White Meat”





Acute Gastrointestinal BleedingAcute Gastrointestinal Bleeding

Liver involved in all 3 systems (coagulation, fibrinolysis and protein C dep. pathway)

Nearly all proteins involved in hemostasis are produced in the liver (exceptions: Factor VIII, vWF, thrombomodulin)

Impaired production and clearance effect fibrinolytic system (dec. clearance t-PA, PAI-1)

Clinical importance of PLT dysfxn in cirrhosis unclear; thrombocytopenia is due to splenic sequestration

Acute Gastrointestinal BleedingAcute Gastrointestinal Bleeding

Overall have impaired thrombin generation and less stable fibrin structure with increased fibrinolysis (“defective hemostatic plug”)

Hemostatic disturbances in cirrhosis are similar to those described for DIC

Acute Variceal HemorrhageAcute Variceal Hemorrhage

Acute variceal hemorrhage mortality 15-20%


Volume expansion: colloids over crystalloids– SBP 90-100mm Hg– HR<100 bpm

Transfusion of blood products to maintain– Hgb ~8g/dl (higher increases re-bleeding/mortality)– Platelets ~50,000– INR to 1.3

Consider prophylactic intubation if massive bleeding and decreased LOC


Initiate somatostatin analog (octreotide) as soon as diagnosis suspected– 50 mcg IV bolus followed by 50 mcg/hr infusion– Continued for 5 days

Antibiotic prophylaxis for 3-7 days with cipro vs. ceftriaxone (ascites, PSE, bilirubin >3, malnutrition)

Endoscopic evaluation within 12 hours


Sengstaken Blakemore tube: 2 balloons Linton tube: large gastric balloon Control hemorrhage in >80% Mortality is 20% due to complications

– Aspiration– Migration– Perforation

Re-bleeding after deflation almost universal Only used in patients in whom shunt planned within 24

hours Intubation strongly recommended





Pain ManagementPain Management

Short-acting analgesics (and sedatives) are always preferred in cirrhotics

Opiods are metabolized via hepatic glucuronidation (and oxidation); thus clearance is impaired (potential for toxic metab. accum.)

NSAIDs impair renal fxn in cirrhosis, as well as decreasing natriuresis (effect on ascites therapy)

NSAIDs increase risk for variceal bleeding (in addition to standard risk for GI toxicity/PUD)

Pain ManagementPain Management

Recommendations:1) Do not use NSAIDs (even COX-2’s) !!2) Fentanyl is the opiod of choice in cirrhosis (long

acting methadone is safe as well)3) If using morphine, oxycodone or demerol decrease

the dose by 50% and increase dosing interval 2-fold4) Acetaminophen is the analgesic of choice !

(maximum dose 2 gm/day); but use caution in cirrhotics who are actively drinking EtOH

5) Don’t forget about analgesic combinations containing acetaminophen





Preoperative Evaluation:Preoperative Evaluation:Risk Factors for M&M in CirrhoticsRisk Factors for M&M in Cirrhotics

Characteristics of the Patient:- Child’s classification (C>B>A)- Presence of ascites or encephalopathy- Presence of jaundice, hypoalbuminemia and/or prolonged PT

(>2.5-3 sec above normal, not correctable w/ Vit. K)- Presence of portal hypertension- On-going infection (i.e. SBP, cellulitis)- Anemia, hypoxemia or malnutrionType of Surgery:- Emergent- Abdominal (esp. gastrectomy, colectomy, chole)- Any cardiac surgery- Hepatic resection

Perioperative Mortality and CPT Perioperative Mortality and CPT

1984 – periop. mortality (non-shunt, abd. surgery); Child’s A = 10%, B = 31%, C = 76%

1997 – periop. mortality (non-shunt, abd. surgery); Child’s A = 10%, B = 30%, C = 82%

2003 – periop. mortality (non-shunt, abd. surgery); Child’s A = 7.1%, B = 23%, C = 84%

MELD For Pre-operative Risk StratificationMELD For Pre-operative Risk Stratification

Retrospective 1980-2004, N=773 (675 MELD<15), ave. age 61 Primary EndpointPrimary Endpoint: MELD as a predictor of peri-op mortality in

non-transplant surgery Secondary EndpointSecondary Endpoint: Does the type of surgery matter? ’93-’04 vs. ’80-’92 showed a trend toward better outcomes, but

NS overall “Other” vs. “Foregut” (hepatobiliary, pancreatic,UGI) surgery

trended to better overall outcomes Multivariate Analysis:Multivariate Analysis: AgeAge (in increments of 10yr) increased

risk 1.5x (30d) and MELDMELD (increments of 5pts) increased mortality risk 2.2x (1.9-2.5) at 30days

MELD FOR PRE-OP RISK STRATIFICATIONMELD FOR PRE-OP RISK STRATIFICATION

MELD <10 11-15 16-20 21-25

7 Day Mortality

0.8% 6% 8% 15%

30 Day Mortality

4% 15% 32% 58%

*MELD >25 had >60% mortality at 30d and >80 mortality at 90d

Model for End-Stage Liver Disease (MELD)Model for End-Stage Liver Disease (MELD)

Website: www.mayoclinic.org/gi-rst/mayomodel6.htmlWebsite: www.mayoclinic.org/gi-rst/mayomodel6.html

Types of SurgeryTypes of Surgery

Hepatic resection:- operative mortality ‘92-’98 = 3-16% (approaching 0% in

“centers of excellence” ’99-’03)

Partial colectomy (open): (typically for diverticulitis)- periop. mortality for Child’s A = 12.8%, Child’s C = 53%

Laparoscopic Surgery: (’05) – chole,spleen,colon,hernia,RY- 0% mortality, 16% morbidity; 39/50 pts. Child’s A

Open cholecystectomy (for obstructive jaundice):- mortality down from 25-28% (’82) to 8% (’97)

Cardiothoracic surgery: (‘04)- morbidity: Child’s A = 60%, B = 72%, C = 100%- mortality: Child’s A = 0%, B = 50%, C = 100%

Contraindications to Elective SurgeryContraindications to Elective Surgery

Acute viral hepatitis (especially icteric hepatitis) Acute alcoholic hepatitis Fulminant hepatic failure (unless OLT) Child’s class C cirrhosis/ ? MELD > 20-25 Severe coagulopathy (PT > 3 sec out after Vit. K,

platelet count < 50k) - - relative contraindication Severe extrahepatic complications:

- Hypoxemia (PaO2 < 50) (consider HPS)

- Cardiomyopathy/CHF

- Acute renal failure (consider HRS)

Summary AlgorithmSummary Algorithm

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QUESTIONS ?QUESTIONS ?

Documents

Inpatient Management of the Cirrhotic Patient. Things You Will Learn Background Information: -What is cirrhosis - What is compensated versus decompensated