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Major Physiologic Functions of the Liver

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Blood reservoir Endocrine organ Moderate immune/inflammatory responses - Kupher cells Metabolic functions - carb, lipid, gluconeogenesis, protein synthesis Regulator of blood coagulation - Vit K dependent clotting factors, fibrinokysis Bilirubin excretion Drug metabolism

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Splanchnic Circulation

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- Hepatic artery supplies 25% of blood - Portal vein supplies 75% of blood - Oxygenated blood is 50/50 because of the high O2 content in the hepatic artery - Pressure is about 8 mmHg in the portal vein

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Hepatic Disease

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- Acute vs Chronic Hepatic Disease - Acute - drug toxicity/infection, ETOH, nonacetaminophen drug toxicity, pregnancy related hepatic diseases - Chronic - chronic viral hepatitis (HEPB/C), alcoholic liver disease, nonalcoholic fatty liver diseases (NAFLD) - Acute either resolves or progresses to chronic disease/ALF

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Acute Liver Failure

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- Previously termed fulminant hepatic failure - no previous hx of liver disease, illness LESS THAN 26 WEEKS, with encephalopathy and coagulopathy (INR greater than 1.5) - 2000 cases a year - half are drug related toxicity, recovery in 45%, liver tx in 25%, death without tx in 30%

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ALF Manifestations

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- Acute cerebral edema and intracrainal HTN - cerebral edema corresponds to degree of encephalopathy - Stage I and II - no edema - Stage III - 25-35% - Stage IV - 75% - Coagulopathy - Circulatory dysfunction and hypotension - AKI - Metabolic derangements

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History Regarding Liver Disease

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- AImed at potential infectious or toxic exposures and detailed hx of recent medications/ingestions - Prior episodes of jaundice - r/t surgical procedures - Transfusion history - Pharmacy - prescribed/OTC/Recreational - Tylenol Toxicity - Lifestyle - Travel/tatoos

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Physical Findings of Liver Disease

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Jaundice Palmar erythema Spider angiomas Gynecomastia Ascites Peripheral edema

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Physical Findings of Biliary Disease

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Fatigue Anorexia N/V Biliary colic Pruritis Fever Dark-colored urine

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T/F - You will only have findings of just biliary disease or hepatic disease, never both

answer

FALSE - Almost always both

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Labs that look at Hepatocellular Injury

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AST - Aspartate aminotransferase ALT - Alanine aminotransferase LDH - Lactate dehydrogenase GST - Glutathione S-transferase

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Labs that look at Cholestasis

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- AP - Alkaline phosphatase - 5′-Nucleotidase (5′NT) - GGT - γ-glutamyltransferase - Bilirubin

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Labs that look at excretory capacity

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- Serum bilirubin - Conjugated

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Labs that look at Protein synthesis

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- Albumin - Coagulation factors

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T/F - AST is not liver specific but ALT is

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TRUE - ALT IS SPECIFIC

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Normal AST/ALT

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AST - 6-40 IU/L ALT - 20-35 IU/L

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Normal TBili/Conjugated Bili

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Total - 0.3 - 1.2 mg/dL Conjugated - 0-0.3 mg/dL

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Normal Albumin

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3.5-5.5 g/dL

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Normal PT

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9.5-13.5 seconds

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Normal INR

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0.8-1.2

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Imaging

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- Utrasound - screening for hepatic/parynchymal disease and extrahepatic biliary disease - used frequently for gallstones, ascites, and portal/hepatic vein thrombosis - CT scan - supplements ultrasounds for liver texture, gallbladder disease, bile duct dilation, and liver/pancreatic masses - provides more resolution than ultrasounds

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MRIs

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Evaluate disease durther

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Percutaneous transhepatic cholangiography

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- AKA THC - Percutaneous injection of contrast into the bile ducts with fluro - Determines the site of biliary obstruction, evaluates cholangiocarcinoma, can be used for balloon dilation and or placement of stents/drains (ERCP)

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Perioperative Risk

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- Acute vs chronic - acute is less than 6 months, chronic more than 6 months - Extent/duration/location of surgery - Advanced age (greater than 70) - Presence of coexisting diseases - Degree of liver dysfunction

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Surgical procedures that Increase Risk

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- Procedures near the liver reduce HBF up to 60% due to sympathetic activation, local reflexes, and direct compression of the portal/hepatic vessels/structures - Neuroendocrine stress response - increased level of catacholamines, glucagon, and cortisol - May cause increased liver enzymes

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Other Procedures that increase risk

answer

- Abdominal Surgery - manipulation of sphlanic bed - Hepatic resection for HCC - Cardiothoracic surgery - exacerbated by CPB - Non-cardiac thoracic surgery

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Child-Turcotte-Pugh Scoring System

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Looks at: - Albumin - Prothrombin time - International normalized ratio (INR) - Bilirubin - Ascites - Encephalopathy - Critique is that acities and encephalopathy are both subjective things so it can be altered to make a persons score higher

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Model of End Stage Liver Disease (MELD)

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MELD score looks at: - Creatinine - Bilirubin - INR - Na+ (Sodium) - MELD of 25-30 has a 50% 30 day mortality post abdominal surgery - proceed with surgery - 11-15 --> caution with elective surgery - 15+ --> postpone any elective surgery

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Effects of Anesthetics On the Liver

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- Hepatocellular injury occurs whenever O2 demand exceeds supply - Perioperative risk depends more on operative site and degree of liver impairment than anesthetic technique - Hepatic blood flow (HBF) usually decreases during anesthesia, related to: - direct and indirect effects of agents - type of ventilation

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Volatile Agents

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- Reduce MAP - Decrease CO - most decrease PBF due to decreased CO, but HABF may increase - Alter portal venous and hepatic arterial vascular resistance

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T/F - Isoflurance and sevoflurane have no net effect on the hepatic artery buffer response

answer

TRUE

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T/F - All volatile anesthetics decrease hepatic artery blood flow, portal blood flow, and total hepatic blood flow

answer

TRUE

question

T/F - Sevoflurane has no toxic metabolites in liver disease

answer

TRUE - Iso and Des have small amounts

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Intravenous Agents

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- Modest negative impact on HBF - No meaningful adverse effects when MAP is maintained - OK for short durations - etomidate, propofol, versed, ketamine - all OK for induction dosages - Infusions - propofol infusion syndrome more likely with prolonged use (hypotension and metabolic acidosis)

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Opioids and Liver disease

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DURING ERCP THEY CAUSE SPASM - tx with glucagon

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Regional Anesthesia

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- High (T-5+) SABs and epidural anesthesia reduce HBF - Conflicting data on effective tx with pressors vs IVF - Consider usual contraindications to neuraxial blockade - Nerve blocks when neuraxial blocks are contraindicated

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Additional agents

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- Adrenergic blockers, a1 agonists, H2 receptor blockers, vasopressin - may reduce HBF - low dose dopamine may increase HBF

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T/F - Anesthetic agents decrease cardiac output, reducing HBF, causing reflex sympathetic activation

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TRUE

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Ventilation in Liver Pts

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- Controlled positive-pressure (pressure control) ventilation - increases hepatic venous pressure - High mean airway pressures - reduces venous return & cardiac output and reduces blood pressure and increases sympathetic tone - Both compromise hepatic blood flow - PEEP further accentuates these effects

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Portal HTN

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- Caused by impaired blood flow to the liver - Causes local production of vasodilators - NP, VIP, endotoxin, glucagon, NO - Increases blood flow to PV with no where to go causing collateralizations (spider angiomas, eso varicies, hemorrhoids) --> acities formation and decreased responsiveness to sympathetic stimulation

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Transjugular Intrahepatic Portosystemic Shunt (TIPS)

answer

- A connection is made between the portal and systemic circulations - Indications - to decompress protal HTN in the setting of eso varicies or intractable acities - Can be MAC vs General - Increased risk for peritonitis and encephalopathy due to the bypassing of the liver (metabolites floating around in the blood)

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CV considerations

answer

Hyperdynamic circulation - Cirrhotic cardiomyopathy - increased CO and decreased PVR --> systolic and diastolic dysfunction with down regulation of B-adrenergic recetpors - can cause conduciton disturbances - Reduced cardiac contractile response to stress --> severe hypotension with stress

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Respiratory Considerations

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- Hyperventilation from respiratory alkalosis - Hypoxemia due to right-to-left shunting - Pulmonary arteriovenous communications (hepatopulmonary syndrome) and entilation/perfusion mismatching - Elevation of the diaphragm from ascites decreases lung volume - Ascites cause restrictive ventilatory defect that increases work of breathing - Assess respiratory status pre op - physical exam, CXR, ABGs - Consider paracentesis with massive ascites & pulmonary compromise - perform with caution b/c excessive fluid removal can lead to circulatory collapse (can be dependent upon the acities)

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T/F - Someone with intrapulmonary vascular dilations (part of hepatopulmonary syndrome will have orthodeoxia

answer

TRUE - means that when they lay flat their sat is better than when they sit up

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Hematologic Considerations

answer

- Anemia - blood loss, increased red blood cell destruction, bone marrow suppression, & nutritional deficiencies - Thrombocytopenia - congestive splenomegaly 2nd to portal hypertension - Coagulopathy - deceased clotting factors with enhanced fibrinolysis 2nd to decreased clearance of activators

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Preoperative Heme Considerations

answer

- Preoperative blood transfusions should carefully considered - protein breakdown from transfusions can precipitate encephalopathy - Clotting factors - replaced with specific products, such as fresh frozen plasma and cryoprecipitate. - Platelet transfusions - for counts less than 75,000/μL, immediately before surgery

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Renal Considerations

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- Reduced renal perfusion and decreased GFR - F/E imbalances manifest as ascites & edema die tp portal hypertension, hypoalbuminemia, & sodium and water retention - Also electrolyte disturbances due to hyponatremia (dilutional) & hypokalemia (diuretic effect)

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T/F - Those in liver failure have dilutional hyponatremia and a rebound diuretic hypokalemia

answer

TRUE

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Hepatorenal Syndrome (HRS)

answer

- Functional renal defect that usually follows GI bleeding, aggressive diuresis, sepsis, or major surgery - Characterized by progressive oliguria, sodium retention, azotemia (nitrogen in blood), intractable ascites - Associated with very high mortality rate

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CNS Considerations: Hepatic Encephalopahty

answer

- Alterations in mental status with fluctuating neurological signs - Due to (1) hepatocellular damage and (2) shunting of portal blood (toxins) away from the liver and directly into systemic circulation - May have elevated intracranial pressure - Precipitating factors: GI bleeding, increased protein intake, hypokalemic alkalosis from vomiting or diuresis, infections, and worsening liver function

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Other CNS Considerations

answer

- Aggressively treat preoperatively - Precipitating causes corrected - Treat to inhibit ammonia production & absorption - Oral lactulose 30-50 mL every 8 hr, Neomycin 500 mg every 6 hr - Sedatives should be avoided

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Hepatic Clearance is based on...

answer

- Blood flow to the liver - drugs with high hepatic extraction are dependent upon blood flow - Fraction of bound/unbound drug - drugs with low extraction ratios are dependent upon protein binding - Intrinsic clearance

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Opioids and Hepatic Dysfunction

answer

- Reduced metabolism --> prolonged half life - Reduced protein binding --> Exaggerated sedative and respiratory depressant effects - Dosing recommendations: smaller doses, longer increments, single bolus - NO INFUSIONS - Fent/Sufent - mostly hepatic metbaolized - Remi- hydrolysis by plasma esterases

question

Benzos and Hepatic Dysfunction

answer

- Low extraction ration - Prolonged elimination half-life - Reduced protein binding --> enhanced sedative effect - Avoid in HE - Smaller doses, avoid multiple doses and infusions

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IV anesthetics (Thiopental, prop, etc)

answer

- Thiopental - low extraction ratio, reliable clearance - Ketamine, Propofol, Etomidate - High extraction ratio, highly lipid soluble, metabolized by the liver - reliable clearance after single doses - Precedex - metabolized by the liver, decreased clearance and prolonged half life - increased sedation

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Neuromuscular Blockage in Liver Failure

answer

- Rocuronium/vecuronium/pancuronium - hepatic metabolism/biliary elimination - decreased cclearance and increased block duration - Atracurium - ester hydrolysis - Cis-atracurium - Hoffman elimination - Mivacurium & succinylcholine - plasma cholinesterase (produced by the liver) --> prolonged effect

question

Monitors

answer

Invasive Lines - based on hemodynamics, anticipated blood loss, and need for intraoperative labs - Alive, CVP - depends on case - PACs - known or suspected PAHtn, low EF - TEE - sensitive for preload, contractility, ejection fraction, regional wall abnormalities, and emboli

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