Hepatic Artery

25% of blood supply

50% Oxygen supply

Portal Vein

75% of blood supply

50% of Oxygen supply

Hepatic artery - at mean aortic pressure

Portal vein - at 6-10mmHg

What are the tributaries of the Portal Vein?

T/F Portal HTN causes all of these tributaries to back up/become engorged.

Inferior Mesenteric Vein

Superior Mesenteric Vein

Splenic Vein (supplied by pancreatic veins)

Gastric Vein

Esophageal Vein

True; this causes things like esophageal varices

Supply adequate oxygen and substrate for the livers intrinsic needs

To allow the liver to serve its purposes for the rest of the body (supplies blood to be "cleaned")

Intrinsic Regulation controls _______ in the liver itself and includes 2 mechanisms; List them:

Extrinsic regulation of liver blood flow is controlled by 2 mechanisms:

Intrinsic regulation controls regional microvasculature in the liver itself

 hepatic buffer system

 metabolic regulation

neural (mostly SNS)

humoral (epi, glucagon etc)

Is there any intrinsic regulation of portal venous flow?

What does the body do if there is a decrease in blood flow to the liver from portal vein (75% of normal bld supply)?

What is max response?

What is this mechanism called?

Metabolic Regulation of liver blood flow

Decrease portal blood ___ & ___ content or increased ____ cause & increase in ______ flow.

This type of regulation is most active in the _______ state, much less so in the ____ state.

Metabolic Regulation

Decrease portal blood pH & O2 content or increased PCO2 cause & increase in hepatic artery flow.

This type of regulation is most active in the postprandial state, much less so in the fasted state.

Hepatic Buffer Response

What is secreted all of the time in the sinusoids and as portal flow decreases then less of this substance is washed out of the liver and thus hepatic arterioles dilate and this increases blood flow to liver.

In the Postprandial state

Less active in the fasted state

Extrinsic Regulation - Neural

What is Portal Venous pressure dependent on?

Dependent on the diff in pressures across the:

Splanchnic arteriolar tone

Portal venules

Post-sinusoidal tone (Hepatic Veins)

[image]

T/F Dopamine also has a large effect in the liver.

False it is insignificant here

What does glucagon do to the vasculature of the liver?

 It accomplishes this effect by?

Glucagon produces long-lasting arteriolar dilation.

 Antagonizing arterial constriction from other responses

Marked constriction of arterial & portal vasculature

 Reduced mesenteric outflow

Reduced total hepatic blood flow

Intense vasoconstriction of splanchnic arterial vessels while decreasing portal venous resistance,

= Marked decrease in Portal Vein blood flow

Esophageal Variceal bleeding can be treated by high doses of __________ to reduce portal hypertension & bleeding?

What is the more common treatment for esophageal varicies?

Vasopressin

More common tx is Octreotide/sandostatin

(inhibits glucagon's vasodilation effect)

Hepatic vascular resistance increases

Hepatic blood volume decreases

Blood glucose increases

(increased gluconeogenesis, increased glycogenolysis)

Blood glucose decreases

(increases glycogen synthesis, increases glucoses uptake)

III - tissue thromboplastin (vascular wall)

IV - Ca++ (diet)

VIII:vWF (vascular endothelial cells)

II - prothrombin

VII -Proconvertin

IX - Christmas factor

X - Stuart-Prower factor

Protien C

Protien S

What are modultors of fibrinolysis and clotting produced by the liver? (3)

Antithrombin III

Protein C and S

Fibrinolytic Factors (TPA and urokinase)

----------The liver is therefore important not only in production of clotting factors, but in modulating their consumption by producing fibrinolysis factors.

T/F all liver derived coagulation factors have short T1/2 lives? 

Which coagulation factor has the shortest half life and what is its 1/2 life?

True 

Factor VII (Proconvertin)

T1/2 of 4 hours

The liver synthesizes and secretes 3 endocrine substances: 

It biotransforms: 

It also inactivates 5 substances:

Synthesis and secretion of:

IGF - 1

Angiotensinogen

Thrombopoietin 

Biotransformation of:

conversion of T4 to T3 

Inactivation of:
Corticosteroids

Aldosterone

Estrogen, androgens

Insulin

Anti-diuretic hormone

Bilirubin is the end product of _________?

 What % is derived from Hgb breakdown.

Heme degradation

75% derived from hemoglobin breakdown

KNOW What are the steps of bilirubin excretion? (5)

___% of conjugated bilirubin is absorbed in intestine & returns to liver via ______, where it is sent back through bile to small intestine.

1. Bilirubin binds to albumin & is transported to liver
2. In liver, Albumin is removed from unconjugated bilirubin
3. Then bilirubin is conjugated primarily with glucuronic acid
4. Conjugated bilirubin is excreted into bile
5. Passes into intestine, where it is converted to urobiliongen and excreted

10% of conjugated bilirubin is absorbed in intestine & returns to liver via portal vein, where it is sent back through bile to small intestine.

The Portal Vein

(makes sense b/c this receives blood from gut)

How much glucose can the liver store? How long could this supply the body with glucose in the fasted state? 

Glucose is converted to glycogen ----- the Liver can store about 75 gms of glycogen ---- 24hrs 

Initially glucagon mediated glycogen breakdown

Then muscle & fat catabolism & gluconeogenesis

Portosystemic shunting

(glucose is not taken into the liver to be stored because of portal system congestion and instead it goes straight back into the systemic circulation via a shunt per lecture)

What causes the hypoglycemia that is more common then hyperglycemia in advanced liver disease? (3)

What other liver condition may cause hypoglycemia?

Impaired glycogen storage

Impaired glycogenolysis

Impaired gluconeogenesis

Lg hepatocelllular CA d/t glucose uptake by tumor

Carbs

Protein

Lipids

Esterfies FFA to form

Triglycerides

Cholesterol

Phospholipids

Glucose production (gluconeogenesis)

Lipid metabolism (lipoproteins)

Further deaminated to keto-acids, glutamine, or ammonia

urea 

kidneys

20 days (thus not a good marker to determine acute liver function)

16hrs = exogenous albumin

In the liver

Psuedocholinesterase is required for the degradation of what four drugs used in anesthesia?

Is it okay to use Suc with liver disease?

Succinylcholine

Mivacurium

Ester local anesthetics

Esmolol

YES - just may last a bit longer, but shouldnt be a big deal

Tissue macrophages which filter toxins, bacteria, debris from GI tract (an immune tissue)

10% of hepatic mass

The impairment of Kupffer cell function is often a precursor to ______ and _______.

Hepatic Biotransformation is metabolism of drug by hepatocytes into _____, _________ substances for excretion in _____ or _____.

render drugs more polar for excretion by...

 Oxidation

Reduction

N-dealkylation

 Most involve cytochrome P450 enzymes

What occurs during phase II reactions?

 What enzymes are required?

Water solubility of the compound is enhanced

 Requires transferase enzymes

The fraction of drug metabolized or extracted during a single pass through the liver

What is the basis of classification of drugs as having low to high hepatic extraction ratios?

 What is clearance determined by with a high hepatic extraction ratio drug?

 the drug's Intrinsic Clearance; is it high or low

 Hepatic Blood Flow

(as BF increases the rate of clearance increases linearly...low hepatic extraction ratio drugs are not affected much by liver BF per graph in handout)

Clearance relatively independent of hepatic BF

Clearance much more effected by increased free fraction/fraction unbound to proteins

(i.e. hypoalbuminemia)

(they have a linear relationship with free fraction; more free fraction = increase effect of drug and more extraction by the liver per graph and lec.)

Reduced hepatic blood flow prolongs the T1/2 and increases the effects of which drugs?

 Give an example of anesthetic that decreases liver blood flow and thus may prolong extraction and metabolism of some drugs.

Those with High Hepatic Extraction Ratios

 *linear relationship* 

IAs

Increased drug effect (more free drug)

More rapid clearance of low HER drugs 

*linear relationship*

Portosystemic shunting allows orally administred drugs to partially bypass the liver. What is the result?

What is the bottom line with administering drugs with liver dysfunction?

Increased systemic effect

Prolonged duration of action

titrate carefully

List examples of

Low hepatic extraction ratio drugs (3)

Intermediate (2)

High (9)

Low hepatic extraction ratio drugs (3)

Alfentanyl

Diazepam

Thiopental

Intermediate (2)

Midazolam

Vecuronium

High (9)

Bupivacaine

Lidocaine

Etomidate

Propofol

Ketamine

Labetalol

Fentanyl

Morphine

Sufentanyl

They can identify a category of dysfunction

1. Hepatocellular
2. Hepatobiliary
3. Hepatic synthesis

What are tests that will indicate hepatocellular damage?

Transaminases

AST (SGOT)

ALT (SGPT)

AST is located...? 

ALT is located...?

AST is in many tissues

*less specific

Heart

Muscle

Kidney

Brain

ALT is primarily in liver

Fatty liver

Nonalcoholic steatohepatitis

Drug toxicity

Chronic viral hepatitis

Acute Hepatitis

Exacerbation of chronic hepatitis

Drug or toxin-induced hepatocellular necrosis

Severe viral hepatitis

Ischemic hepatitis secondary to shock

Nope - decreasing levels may indicate recovery from injury or few surviving hepatocytes left

 Note: These enzymes increase in circulation with damage to the hepatocytes b/c they leak out of the damaged cells

What is GST?

 Where is GST found?

Glutathione S-Transferase - a phase II enzyme

Many tissues, but isoenzyme B specific to liver

Where is GST found in the highest concentration? 

What is significant about this area?

In Centrolobular (zone 3) hepatocytes 

These are most susceptible hypatocytes to ischemic injury and toxic drug metabolites

Obstruction to bile flow

May be elevated during normal pregnancy

What is the most sensitive test for biliary tract disease?

 BUT what makes it un-useful?

GGT (Gamma glutamyl transpeptidase)

 un-useful b/c found in so many tissues it lacks specificity

Severity of jaundice

 *we look at conjugated and unconjugated levels*

1-4mg/dl  

Excessive production (hemolysis) or Defective conjugation

>5mg/dl

Liver disease

Conjugated Bilirubin elevation indicate? (2)

Conjugated bilirubin levels of ___ or greater can cause renal damage & compound situation.

impaired hepatic excretion

extrahepatic obstruction (ie bile duct)

 liver is conjugated as it should but it cant get it out

>35mg/dl

Serum Albumin

PT/INR

Worsening of chronic liver disease 

burns

nephrotic syndrome

poor nutrition

fluid retention

T/F Albumin (endogenous) is only a long term measurement of function b/c half life is 20 days.

True

What are useful markers in acute hepatocellular injury?

May not see a change in above markers with mild or even moderate liver injury b/c?

PT/INR

(d/t short 4 hr 1/2 life of Factor VII)

b/c the body has excess factors floating around and it takes awhile to deplete them per Anderson

What screening test is ultrasound used for?

Hepatic disease

Cholelithiasis (gallstones)

Biliary Tract disease

CT

but $$$$$

Endoscopic Retrograde CholangioPancreatography

Endoscopic guidance of a catheter through the ampulla of Vater (sphincter of Oddi) to inject contrast into the pancreatic duct & common bile duct (both which empty from sphincter of Oddi into sm intestine)

Technique of choice when choledocholithiasis (stone in common bile duct) is suspected b/c a sphincterotomy can be done at the same time & the stone can be removed.

What type of bilirubin would be elevated with a common bile duct obstruction?

Tx sphincter of Oddi spasms with ____ per lec.

What is the only way to know the specific nature of hepatic damage?

Conjugated (liver is still doing its job, the bilirubin is just not getting into GI tract for elimination d/t obstruction)

Glucagon

Liver Biopsy

ampulla of Vater

common hepatic duct and cystic duct

pancreatic duct

What biopsy technique is safer when the coags are out of whack?

 T/F Liver biopsies can also be done open?

Platlets less than 60,000

PT more than 3 secs greater than control

Transjugular 

True

10-15%

Acute viral hepatitis reported in the US

HAV?

HBV?

HCV?

HDV and HEV?

HAV - 20%

HBV - 50%

HCV - 30% 

 HDV and HEV - seen more in 3rd world countries along with HAV

What is the most common blood-borne infection in the U.S?

This accounts for ___% of chronic liver disease?

 Chronic liver disease will develop in __% of Hep B positive pts & __% of Hep C positive pts.

HCV

This accounts for 40% of chronic liver disease

 Chronic liver disease will develop in 1-5% of Hep B positive pts & 75% of Hep C positive pts.

Acetaminophen

Carbon tetrachloride (dry cleaner)

Amanita Phalloides (mushroom)

NSAIDS

Volatile Anesthetics

Antibiotics

Antihypertensives

Anticonvulsants

Halothane 

1/35000 - Kind of alot 

*Note only 1/3000 were nonfatal

What is the biggest risk factor for Hepatitis associated with Halothane?

List 4 other risk factors:

Prior exposure to Halothane (10x more frequent in those with multiple exposures)

female

obesity

Hispanic

Adulthood

(most over 50, children resistant)

Fever

Chills

Anorexia

Nausea

Myalgias

Rash

Jaundice 3-6 days later

Overt Jaundice

Age over 40

Obesity

Affects only a very small percentage of those exposed

Incidence & severity unrelated to dose

What are the clues to the mechanism of halothane hepatitis? 

What do we think is the mechanism?

Idiosyncratic

Prior exposure common

Delayed onset

Antibody production

Eosinophilia

Circulating immune complexes

Antibodies that bind to antigens from halothane treated rabbits 

Occupational exposure (Pediatric anesthesiologists have higher serum autoantibodies than controls. Levels are higher w female pedi anesthetists.)

Allergic or immunologic

T/F there are currently no reports of halothane hepatitis from occupational exposure.

 Why is there a risk for hepatitis with IAs exposure?

List the IAs in order from most to least metabolized with metabolite:

True 

metabolism & production of fluoroacetyl metabolites 

H>E>I>D>S (0 fluoroacetyl metabolites for S)

Volatile Anesthetics and Hepatic Blood Flow

Volatile Anesthetics and Hepatic Blood Flow

 Which other IAs has a marked reduction (30%) in hepatic blood flow?

Volatile Anesthetics and Hepatic Blood Flow

 Hepatic blood flow and oxygenation are well preserved with which IAs?

Which IAs is best for preserving blood flow & O2 to liver?

List 2 other benefits of this IA for the liver:

When is this IA NOT best? Then which one is?

Sevo best preserves blood flow & oxygen delivery to liver

1.Hepatic arterial buffer system remains intact
2.Less reactive metabolic products produced

At very high MAC level (2.0MAC)

Iso is better at these high levels *per graph slide 53-54

Sympathomimetic vs direct hepatotoxicity

Altered hepatic metabolism

When might Thiopental cause some hepatic dysfunction?

T/F Other induction agents appear to be safe?

At doses greater than 750mg

True

Opiods produce no significant effect on liver T/F?

 What is a SE of opioids that could cause liver issues?

How do you treat this SE?

True as long as blood flow & oxygenation remain normal

  Spincter of Oddi Spasm

(equal risk with all narcotics)

 glucagon, nitroglycerin, narcan

Sepsis and Inflammation

(hypovolemia & splanichnic hypoperfusion/ lg bacterial toxin load/ impairment of of hepatic arterial buffer response)

Hypoxia and Ischemia

(Liver is extremely sensitive to hypoxic insult; remember 25% of CO goes to liver normally and w/o that ischemic hepatitis can result)

Sympathetic nervous system stimulation

Release of vasopressin (ADH)

Activation of renin-angioensin-aldosterone sys.

all equal less liver blood flow

Bad

Low flow, non-pulsatile perfusion

Catacholamine usage 

Good

Hypothermia

Hepatic arterial buffer response helps maintain blood flow

Chronic Hepatitis implies hepatic inflammation & ______ for greater than _____ months. Classified based on: (3)

Hepatic inflammation and necrosis for >6 months

Classified based on:

Cause (based on serologic testing)

Grade (degree of necrosis & inflammation)

Stage (degree of fibrosis)

What % of acute HCV progresses to chronic HCV

 1.8 million of US population has HCV and it is the most common indicator for __________.

85% of acute HCV progresses to chronic HCV

 Most common indication for liver transplantation

*also cirrhosis per Anderson

Fatty liver disease (non alcohol)

 Up to 24% of Americans have NAFLD

What are the risk factors for NAFLD? (2)

 Are these pts symptomatic?

Do they develop cirrhosis?

Obesity (70%)

DM II (75%)

 Most asymptomatic

Some develop cirrhosis (<5% per Anderson)

Fatty liver (steatosis)

Alcoholic hepatitis

Cirrhosis

Alcoholic hepatitis is a precursor of ______. 

It has up to a ____ fold increase in aminotransferase. 

Describe the AST/ALT ratio with Alcoholic hepatitis.

Alcoholic hepatitis is a precursor of cirrhosis

up to 10-fold increase in aminotransferases (ie GST)

AST typically higher than ALT (>2 ratio)

Abstinence

Bedrest

Adequate nutrition

2-3x increase

What are the most frequent etiologies of Cirrhosis?(2)

Hep C

Alcoholic Hepatitis

  Cirrhosis is the 12th leading cause of death in US and affects 3 million people

Anorexia

Weakness

N/V

Abdominal pain

Jaundice

Encephalopathy

Spider Nevi

Hepatosplenomegaly

Ascites

JES HA 

Hyperdynamic circulation

Decreased PVR

Normal to increased stroke volume

Normal filling pressures

Mildly increased heart rate

Low to normal arterial blood pressure

Total blood volume increased

↑vascular resistance to portal BF (from liver) + ↑portal venous inflow from dilated splanchnic arterioles

↓

↑portal venous pressure & subsequent development of portosystemic collaterals & shunting

↓

Majority of portal venous blood bypassing the liver

How is hepatic oxygenation and BF maintained with Cirrhosis & Portal HTN?

Hepatic arterial buffer response 

(remember 75% of liver BF normally comes from portal vein & 50% of oxygen)

Esophageal varices

(back up in esophageal vein)

Hepatic encephalopathy 

Altered drug metabolism

(many drugs bypass liver via shunts)

Susceptibility of bacterial infection

(liver not cleaning normally, & most GI absorption going systemic before going to liver) 

Ascites

Splenomegaly

How many gastroesophageal varices will bleed? 

___% that are fatal? 

T/F most will not rebleed if controlled with medications.

1/3

30% are fatal 

False, most will rebleed

What is the management of Gastroesophageal Varices? (5)

Fluid resuscitation/blood replacement

Airway protection

Octreotide (synthetic somatostatin - blocks glucagon's vasodilatory effects) 

Endoscopic band ligation or sclerotherapy

TIPS

Interstitial and airway edema

(dec albumin production = increased edema)

Mechanical effects of ascites

(dec FRC)

Pleural effusions

Hepatopulmonary Syndrome

(dyspnea & hypoxia with liver disease; worse when upright)

1. Chronic liver disease 

2. Intrapulmonary Vascular Dilations

      Vascular dilations result in arteriovenous communications & hypoxia

3. Increased alveolar-arterial oxygen gradient

      d/t pulm edema from vascular congestion

What is the most common major complication in cirrhosis?

Na+ and H2O

hypoalbuminemia

Na restriction & gentle diuresis

(if you diuresis too fast may cause RAS activation and subsequent renal issues; plus these pts don't tolerate losses in BV very well d/t lack of liver reservoir fx)

Paracentesis

Peritoneal-venous shut

TIPS

Transplant

Cefotaxime (3rd generation cephalosporin)

Long term antibiotic prophylaxis

Spontaneous Bacterial Peritonitis

1/3 of cases develop what other organ dysfunction?

Spontaneous Bacterial Peritonitis

Mortality? With and without renal dysfunction?

54% with renal dysfunction

9% without renal dysfunction

↓Renal perfusion & GFR seen with cirrhosis

Intense renal vasoconstriction

Low GFR = hypoperfusion

Preserved renal tubular function

Normal renal histology

(no injury to kidney tissue at first it is just a perfusion issue per lec)

Describe the pathophysiology of hepatorenal syndrome

(5 steps)

Decreased portal vein blood flow to liver 

↓

Prostacyclin, nitric oxide, glucagon, adenosine

↓

Splanchnic arterial vasodilation (metabolic/buffer system)

↓

Reduced effective blood volume

(d/t pooling in portal system -- also d/t acities fluid shifts)

↓

Activation of renin-angiotensin-aldosterone system and sympathetic stimulation

↓

Intense renal vasoconstriction

1. The livers role as a blood reservoir is impaired so even modest blood loss can produce severe hypotension and lead to acute ischemic injury 

2. Obstructive Jaundice & elevated levels of conjugated bilirubin contribute to renal toxicity (>35mg/dl).

*so diuresis gently and stay on top of fluid needs*

What are the 2 major coagultion disorders with cirrhosis?

What is the specific cause of each?

Disorders of clotting factors & vit k (decreased synthesis)

 Thrombocytopenia (backed up in spleen and incr destruction)

Portal hypertension-induced splenomegaly with seqestration of up to 90% of circulating platletes in spleen

1. Increased destruction by immune mechanisms

2. Low-grade DIC

3. Sepsis

4. Bone marrow suppression by ehtanol, folate deficiency

1. Glycogen depletion (d/t poor nutritional state) &

    interference with gluconeogenesis (by ETOH)

2. Impaired conversion of lactic acid to lactate & then to

   glucose

Oligomenorrhea

Amenorrhea 

"men become women and women become men per Dr. Anderson"

Reversible, metabolic encephalopathy

Ranging from minimal personality changes or sleep disturbances to confusion, lethargy, coma

30-60% of cirrhotics

Large dietary protein load = inc ammonia

GI Bleed

Constipation

Diuretics

Azotemia

(dec renal perfusion = incr. nitrogen waste products ie BUN and urea)

Surgery & anesthesia

Increased availability of agonist ligands of GABA receptors, so called natural benzodiazipines

(Improvement in mental status with flumazenil)

Disruption of blood-brain barrier

Neurotoxic compounds

Impaired cerebral energy metabolism

Prevention

Lactulose

Neomycin

Zinc

Liver Transplant

Not broken down in the intestine

Produces mvmt of ammonia from blood to bowel

Cathartic (cleansing/purging)

Primary Hepatocellular Carcinoma

2.4/100,000 in U.S.

When does primary hepatocellular carcionoma occur?

Usually follows cirrhosis

Worldwide - large majority follow viral hepatitis

U.S. - 30-40% after viral hepatitis

Liver transplant 

Few patients have a surgically resectable tumor at the time of presentation

When does pregnancy-related liver disease present? 

What is this type of liver disease called?

What syndrome is commonly seen with it?

3rd trimester or immediately post-partum

 Actue Fatty Liver of Pregnancy

 HELLP

Characteristics of Acute Fatty Liver of Pregnancy

Severe?

Recovery?

Tx?

Rarely severe

Most recover fully

Treatment: Expedite delivery

(without delivery pt will go into acute liver failure and die without transplant per Stolting)

What is HELLP?

 When may this be seen?

 What is tx?

Hemolysis

Elevated Liver Enzymes

Low Platelets 

Liver disease of Pregnancy

(caused by ischemic hepatocellular necrosis that will continue until baby is delivered)

Expedite delivery

Nause/Malaise

↓

Rapid onset of jaundice

↓

Altered mental status

List exam findings that would make you suspicious of hepatic disease (9)

1. Icterus (jaundiced sclera)
2. jaundice
3. ascites
4. spider angiomata
5. petechiae
6. asterixis (push hand back and if it flutters = liver issues)
7. gynecomastia
8. splenomegaly
9. palpable enlarged liver

What should we do if we have abnormal labs in the absence of history or physical exam findings?

 (previously healthy non-liver diseased pt)

T/F Acute hepatic disease, regardless of the etiology, increases perioperative morbidity and mortality

True by 2-3X

acute hepatic disease

When do you investigate and elevated AST/ALT? 

If greater than 2X normal what should you do? 

If second test still >2X norm then if ALT>AST consider _____ and if AST>ALT consider ______. 

T/F a formal evaluation with these pts will be required before surgery can proceed?

When it is greater than 2X normal 

(if less than 2X then proceed with surgery)

Repeat test

ALT>AST (ratio <1) = viral hepatitis

AST>ALT (ratio >2) = ETOH/drug abuse

True

If pt with elevated AST/ALT and abnormal INR then consider ______ dysfunction and ____ surgery. 

Biliary disease is indicated with what abnormal labs?

When is it ok to proceed with surgery?

hepatobiliary dysfuction

delay (needs workup) 

If Alkaline phosphatase elevated >2X norm with abnormal GGT and bilirubin 

If AP up <2X and normal GGT and Bilirubin then you can 

If a pt has 7-8 of these risk factors they have a ____% risk for complications. 

1. Child-Pugh factors
2. Ascites
3. Cirrhosis (other than primary biliary)
4. Serum creatinine
5. COPD
6. Preop infection
7. Preop upper GI bleed
8. Higher ASA physical status
9. Intraop hypotension
10. Higher surgical severity score

100%

Serum Albumin

Serum Bilirubin

Ascites

Encephalopathy

PT/INR

Extent of liver disease

Age

Coexisting disease

Type, location, duration of surgery

There is increased cerebral uptake of benzodiazipines

Consider decreased doses

Careful titration

Creatinine

bilirubin

INR

prioritization of liver transplants

meld score = 0.957 x log (creatinine mg/dl) + 0.378 x log (bilirubin mg/dl) + 1.12 x log (INR) + 0.643

No it is a low HER drug

Elimination T1/2 unchanged in cirrhosis

Elimination profile unchanged from control 

May see slight increase in recovery time/duration following infusion b/c it is a HHER drug (not significant per Ron)

Etomidate - high or low HER?

Clearance

Elimination

Duration/Recovery

High HER

Clearance unchanged in cirrhosis 

Increased Vd may result in prolonged elimination of T1/2 and unpredictable recovery

Ketamine

high HER

 prolly not the best d/t SNS stimulation but "do what you need to do"

Increased free fraction (less albumin) 

Decreased clearance

(clearance would be increased with increase in free fraction of drug but, d/t liver disease & its effect on the CYP450 system, the overall clearance is decreased--remember low HER drugs are much more dependant on CYP450 syst)

Fentanyl

 Volume of distribution

Elimination T1/2

No change in volume of distribution

Increased Elimination T1/2 d/t decreased clearance

Sufentanyl

No significant pharmacokinetic change from control

May have slightly prolonged effect following multiple doses

Dexmedetomidine (precedex) with liver disease

Clearance

Elimination T1/2

Significantly decreased clearance

prolonged half-lives

Avoid direct drug-related toxicity

Maintain adequate hepatic perfusion and oxygenation 

How are we going to avoid drug-related toxicty and maintain adequate hepatic perfusion and oxygenation?????!!!!!!! 

Most important is simply....b/c blood reservoir is gone.

Maintain adequate:

Cardiac output

Blood volume

Perfusion pressure

Oxygenation 

Prompt replacement of fluid & blood

Decreased plasma cholinesterase

but likely not an issue

Hofman elimination 

Essentially independent of hepatic & renal disease

Other NDPMR and hepatic disease...?

 Dose?

Length of blockade?

Clearance?

Increase Vd so increased inital dose?

(Ron says yes, then can titrate subsequent doses with info gained with 1st dose & PNS)

Anticipate prolonged blockade

(recall all aminosteroidals are metabolized in liver/kidneys)

Markedly decreased clearance

Titrate to effect

Overall there is an increased concentration of vasodilatory substances such as _______ with liver disease, resutling in markedly reduced response to ___________.

So what should you do to treat hypotension?

May need increased doses of catecholamines

or

give a non-adrenergic vasoconstrictor like vasopressin

May encounter coagulopathy and excessive bleeding

Will not tolerate hypovolemia well

Adequate fluid loading

Absence of coagulopathy

What do large increases in serum transaminases post op reflect? 

Postop liver dysfunction is ____ but rarely _____ in a previously healthy pt?

Extensive hepatocellular necrosis 

Postop liver dysfunction is common but rarely severe previously healthy pt.

Fulminant Hepatic Failure = A term used to describe acute liver failure in a previously healthy pt with the following criteria:

Encephalopathy within 2 weeks of developement of juandice

or

Encephalopathy within 8 weeks of initial manifestation of hepatic disease.

new onset of hepatic dysfunction

surgery should be delayed

full workup should be done

Child-Pugh Score 

Class A, B, C, how many points and % surgical mortality?

Class A = 5-6 pts = 10% surgical mortality

Class B = 7-9 points = 30% surgical mortality

Class C = 10-15 points = 82% surgical mortality

AST = 10-40 units/L

ALT = 7-56 units/L

- unconjugated bilirubin levels will be elevated

- AST/ALT levels will be normal

- AP levels will be normal

- Causes: hemolysis, hematoma resorbtion, bilirubin overdose in blood transfusion

- increased conjugated fraction

- increased AST/ALT, GST

- normal or slightly increased AP

- Causes: viruses, drugs, cirrhosis, sepsis, hypoxemia

- conjugated bilirubin is increased

- AST/ALT, GST are normal 

- markely increased AP

- Cause: biliary tract stones or sepsis