anesthetic implications of end-stage liver disease and liver transplantation todd m. oravitz, md...

Anesthetic Implications of End-Stage Liver Disease and

Liver Transplantation

Todd M. Oravitz, MDAssociate Professor

Department of AnesthesiologyUniversity of Pittsburgh School of Medicine

Chief, Liver Transplantation AnesthesiaVA Pittsburgh Healthcare System

Lecture objectives

1) Discuss the pathophysiology of end-stage liver disease2) Discuss the management of anesthesia in patients with end-stage liver disease3) Discuss the perioperative management of patients undergoing liver transplantation4) Discuss the perioperative management of patients undergoing procedures after liver transplantation

Normal Hepatic Function

• Liver plays a role in–Carbohydrate metabolism• Produces/stores glycogen, which can be

depleted after 24-48 hours of fasting• Site of gluconeogenesis, with amino acids,

glycerol and lactate as substrates

Normal Hepatic Function

• Liver plays a role in–Protein metabolism• All plasma proteins, except for

immunoglobulins, made in the liver– Albumin helps maintain plasma oncotic

pressure and is the primary binding/transport protein for many anesthetic drugs

• All coagulation factors, except for factor VIII and von Willebrand factor, made in the liver

Normal Hepatic Function

• Liver plays a role in–Drug metabolism• Most medications undergo at least some hepatic

degradation or biotransformation, or both• End products either metabolically inactive or more

water-soluble for biliary or urinary excretion

Normal Hepatic Function

• Drug metabolism– Phase I reactions• Include oxidation/reduction (redox)• Cytochrome p450• Benzodiazepines and barbiturates degraded via phase I

– Phase II reactions• May or may not follow phase I• Involve conjugation to facilitate elimination

via bile or urine

Normal Hepatic Function

• Drug metabolism– Cytochrome p450• Ethanol, ketamine capable of enzyme induction,

resulting in tolerance to the drugs’ effects• Cimetidine, chloramphenicol can cause prolongation

of drug effects by enzyme inhibition

Normal Hepatic Function

• Anatomy/physiology– Largest organ in the body, weighing about 1.5kg– Right upper quadrant location– Dual blood supply• Liver blood flow ~1.5L/min• Hepatic artery• Portal vein

Normal Hepatic Function

• Dual blood supply– Hepatic artery• Accounts for 25% of blood flow and 50% of O2 delivery• Flow is auto-regulated

– Portal vein• Accounts for 75% of blood flow and 50% of O2 delivery• Flow depends on GI and splenic blood flow

End-Stage Liver Disease (ESLD)

• The liver has a remarkable capacity for regeneration

• The liver has tremendous physiologic reserve• Hepatic disease can develop insidiously and

a large proportion of function can be lost before problems become apparent

End-Stage Liver Disease (ESLD)

• Common symptoms– Anorexia– Weakness– Nausea/vomiting– Abdominal pain

• Common signs– Hepatosplenomegaly– Ascites– Jaundice– Spider angiomas– Encephalopathy

Pathophysiology of ESLD

• Hepatic changes– Portal hypertension – high resistance to blood

flow through the liver – hallmark of ESLD– Leads to accumulation of blood and increased

venous pressure in the vascular beds “upstream” to the liver• Esophagus• Spleen• Stomach and intestines

Pathophysiology of ESLD

• Portal hypertension leads or contributes to– Ascites– Esophageal varices– Gastric and other intra-abdominal varices– Splenomegaly

Pathophysiology of ESLD

• Esophageal varices– Portal-systemic collaterals that allow splanchnic

venous blood to flow from the high-pressure portal system to the low-pressure azygos and hemi-azygous system

– Not all patients with ESLD develop varices and not all patients with varices have bleeding

– Patients that do bleed have significant morbidity and mortality – up to 30% of initial episodes of bleeding are fatal

Variceal Disease

• Treatment– Chronic• Propranolol is a non-selective beta-blocker

that decreases portal venous pressure– Reduces risk of primary bleeding– Reduces risk of re-bleed

• Banding, ligation, sclerotherapy• Transjugular intrahepatic portosystemic shunt (TIPS)

Pathophysiology of ESLD

• TIPS– Improves blood flow through the liver– Percutaneous approach to create a shunt

between the portal and hepatic veins– Decreases activity of the sodium-retaining

pathways– Improves renal response to diuretics

T I P S

Variceal Disease

• Treatment– Acute• Aggressive fluid resuscitation; ± blood• Correct coagulation defects, if present• Airway protection – intubation• Octreotide – reduces portal pressure• Endoscopy with possible intervention – banding• Balloon tamponade – Blakemore tube

Pathophysiology of ESLD

• Hepatic changes– Spontaneous bacterial peritonitis (SBP)• Spontaneous infection of ascitic fluid without

an intra-abdominal source• Increased intestinal wall permeability allows

translocation of bacterial into the conducive media of ascitic fluid

Pathophysiology of ESLD

• Hepatic changes– Spontaneous bacterial peritonitis (SBP)• Cefotaxime is the antibiotic of choice for treatment as

it covers 95% of the offending flora, including the 3 most common – E coli, Klebsiella and pneumococcus• Quinolone (e.g. ciprofloxacin) prophylaxis is indicated

after an initial episode as there is a 70% recurrence rate in the 1st year and it has a beneficial effect on patient survival• Two year survival after SBP is less than 50%

Pathophysiology of ESLD

• Hepatic changes– Hepatic encephalopathy (HE)• Occurs when substances normally metabolized

by the liver accumulate due to its dysfunction– Ammonia felt to be most important in HE patients

• Increased activity of inhibitory neurotransmitters also may play a role– Increased GABAergic tone– Administration of the benzodiazepine antagonist

flumazenil often results in an improvement in the mental status of HE patients

Hepatic Encephalopathy

• Often occurs after a precipitating event– Increased ammonia level• Large dietary protein load• GI bleeding• Azotemia

– Decreased hepatic perfusion• Anesthesia and surgery with resultant hypotension,

hypoxemia and/or hypovolemia• Diuretic administration, paracentesis or GI

disturbance such as diarrhea or vomiting

Hepatic Encephalopathy

• Other possible precipitating events– Sepsis• Increased ammonia levels due to protein catabolism• Decreased hepatic perfusion

– Creation of portal-systemic shunt• TIPS• Results in decreased hepatic metabolism

Hepatic Encephalopathy

• Treatment– Remove/minimize, to the extent possible, any/all

underlying causes– Decrease blood ammonia levels

• Reduce production– Lower dietary protein intake– Neomycin – targets urease-producing bacteria

• Reduce GI absorption– Lactulose – non-absorbable disaccharide that decreases

large intestinal absorption of ammonia and also promotes growth of non-urease producing bacteria

Pathophysiology of ESLD

• Coagulation/hematologic changes– Coagulopathy results mostly from two factors• Impaired synthesis of clotting factors• Thrombocytopenia

– Decreased levels of anticoagulants, most notably antithrombin III and protein C, can lead to thrombotic complications• Portal vein thrombosis• Deep venous thrombosis (DVT)• Pulmonary embolism (PE)

Coagulation/Hematologic Changes

• Coagulopathy– Impaired synthesis of coagulation cascade

proteins• All clotting factors, except von Willebrand factor,

made in the liver• Vitamin K dependent factors – II, VII, IX and X –

at additional risk– Bile salts needed for intestinal absorption of vitamin K

and may be decreased by ESLD– Overall poor nutritional status in many

ESLD patients

Coagulation/Hematologic Changes

• Coagulopathy– Thrombocytopenia• Portal hypertension-induced splenomegaly

– Occurs in 30-60% of ESLD patients– Up to 90% of platelets can be sequestered

in the enlarged spleen– Platelet count usually >30K and spontaneous bleeding

is fairly uncommon

• Associated disease processes can contribute– Poor nutrition – folate deficiency– Chronic alcohol intake

Pathophysiology of ESLD

• Cardiovascular changes– Hyperdynamic circulation• Increased cardiac output• Decreased systemic vascular resistance• Normal to decreased blood pressure• Increased heart rate• Normal to increased stroke volume

Pathophysiology of ESLD

blood pressure=cardiac output x systemic vascular resistance

↔/↓BP = ↑CO X ↓SVR ↓ −−−−−−−−−−−−−−−−− ↓ ↓

↑HR X ↔/↑SV

cardiac output = heart rate x stroke volume

Pathophysiology of ESLD

• Cardiovascular changes– Result from development of vasodilation

and abnormal shunting• Blood passes from the arterial to the venous

circulation without crossing a capillary bed; an anatomic example of this is a spider angioma• Thought to result from increased plasma levels of

glucagon and vasoactive intestinal polypeptide

Pathophysiology of ESLD

• Pulmonary changes– Hypoxemia, with PaO2 values of 60-70mmHg,

is commonly seen in ESLD patients– Causes include• Underlying cardiopulmonary disease• Intrapulmonary shunting• V/Q mismatch• Decreased diffusion capacity

Pulmonary Changes - Hypoxemia

• Underlying cardiopulmonary disease– Congestive heart failure, interstitial lung disease,

chronic obstructive pulmonary disease• Intrapulmonary shunting– Pre-capillary or larger arteriovenous

communications are the result of intrapulmonary vascular dilatation

– Hepatopulmonary syndrome

Hepatopulmonary Syndrome (HPS)

• Defined by the clinical triad of– Chronic liver disease– Increased A-a gradient– Evidence of intrapulmonary vascular dilatation

• Increased pulmonary nitric oxide production is the likely cause

• Usually diagnosed by echocardiography

Hepatopulmonary Syndrome (HPS)

• Incidence 5-30%• Decreased survival compared to patients with

similar degree of liver disease who do not have HPS

• HPS patients with severe preoperative hypoxemia (PaO2 <50mmHg) have increased mortality after liver transplantation

• HPS often resolves completely after transplant

Pathophysiology of ESLD

• Pulmonary changes– Hepatic hydrothorax• Seen in 5-10% of ESLD patients• Pleural effusion from transfer of ascitic fluid

through diaphragmatic defects• Treated by sodium restriction, diuretics

and/or thoracentesis

Pathophysiology of ESLD

• Pulmonary changes– Pulmonary hypertension• Seen in <5% of ESLD patients• Defined as mean pulmonary artery pressure (MPAP)

>25mmHg and increased pulmonary vascular resistance– Patients with MPAP >35mmHg have increased

perioperative morbidity/mortality– Patients with MPAP >50mmHg, at VAPHS, are not transplant

candidates secondary to greatly increased mortality

• Etiology not well understood

Pulmonary Hypertension

• Avoid physiologic conditions that increase pulmonary vascular resistance, as acute right-sided heart failure can result– Hypoxemia– Hypercapnia– Acidosis

• Important to remember during monitored anesthesia care (MAC) cases

Pathophysiology of ESLD

• Renal changes– Impaired free water and sodium excretion– Decreased renal perfusion and glomerular

filtration rate (GFR)– Vasodilation, which effectively reduces plasma

volume, leads to sympathetic nervous system activation of the renin-angiotension-aldosterone pathway, resulting in enhanced sodium and free water resorption

Pathophysiology of ESLD

• Renal changes lead to development of– Edema– Ascites

• Long term decrease in renal perfusion and GFR can lead to hepatorenal syndrome (HRS)– HRS occurs in up to 10% of patients with ESLD– Functionally HRS is a pre-renal phenomenon

whose hallmark is intense renal vasoconstriction

Hepatorenal Syndrome (HRS)

• Type I– Progressive oliguria with rapidly rising creatinine– Often follows an episode of spontaneous bacterial

peritonitis (SBP)– Poor outcome – median survival < 1 month

without intervention– Treatment with albumin, octreotide, and

midodrine has shown some promise

Hepatorenal Syndrome (HRS)

• Type II– Usually seen in patients with refractory ascites– Renal impairment is usually more mild than type I– Clinical course is far less progressive than type I

Pathophysiology of ESLD

• Ascites– Common complication of ESLD; in fact, nearly

50% of patients develop ascites within 10 years of initial diagnosis

– Significant associated mortality – nearly 50% of patients die within 3 years of onset of ascites

– Etiology complex, multifactorial and not completely understood• Portal hypertension• Sodium, water retention

Pathophysiology of ESLD

• Ascites– Treatment• Sodium restriction and diuretics (spironolactone)• Refractory cases treated with repeated large-volume

paracentesis and volume expanders, usually albumin• Transjugular intrahepatic portosystemic shunt (TIPS)

also can be used for refractory ascites, but it has not been shown to improve survival compared to repeat paracentesis

Anesthesia and ESLD

• Preoperative preparation should focus on optimizing liver-related pathology (if possible)– Volume status– Coagulation – parenteral vitamin K if INR elevated– Renal function– Electrolyte imbalance– Nutritional status

Anesthesia and ESLD

• Medications should be scrutinized in the preoperative period, as there are a large number that can cause or worsen underlying hepatic dysfunction– Acetaminophen– Isoniazid– Methyldopa– Phenytoin– Indomethacin

Anesthesia and ESLD

• Administration of anesthesia decreases liver blood flow via changes in hepatic perfusion pressure and/or splanchnic vascular resistance

• Physiologic reserve is decreased patients with ESLD

• Perioperative morbidity and mortality in patients undergoing all but minor procedures is increased

Child-Pugh Classification System

Child-Pugh Class and Mortality

• Thirty day mortality in patients undergoing either cholecystectomy, hernia repair, GI or miscellaneous surgery; 25% were emergencies– Class A – 10%– Class B – 30%– Class C – 80%

• Highest mortality in GI and emergent procedures

Child-Pugh Class and Mortality

• Three month mortality for patients hospitalized with liver complications, but not undergoing surgery– Class A – 4%– Class B – 14%– Class C – 50%

Model for End-Stage Liver Disease (MELD) Score

• Originally developed to predict survival in patients with portal hypertension undergoing elective TIPS procedures

• Found to be an accurate predictor of survival in patients with a variety of liver diseases

• Adopted in 2002 as the rank list criteria for liver transplantation by the United Network of Organ Sharing (UNOS), replacing Child-Pugh

Model for End-Stage Liver Disease (MELD) Score

• Resulted in an almost 15% reduction in mortality on the waiting list

• Median waiting time also decreased, about 35%, from 656 to 416 days

• While it accurately estimates mortality on the waiting list, MELD does not correlate well with mortality following liver transplantation

MELD Score

Anesthesia and ESLD

• Perioperative mortality calculator– http://www.mayoclinic.org/medical-

professionals/model-end-stage-liver-disease/post-operative-mortality-risk-patients-cirrhosis

– Input patient age, ASA physical status, bilirubin, creatinine, INR and cirrhosis etiology (alcoholic/cholestatic vs viral/other)

– Calculates mortality at 7, 30 and 90 days, as well as 1 and 5 years

Anesthesia and ESLD

• 52 year male presenting for R total knee arthroplasty– PMHx HTN, DM, hep C, CKD, COPD, GERD, PTSD– Lab data – HgB 11, platelets 95K, K 4, BUN/Cr

20/1.4, total bili 1.5, PT/INR 15.7/1.3• Does this patient have a significant degree

of morbidity/mortality in the perioperative period?

Anesthesia and ESLD

• YES!!!– 7 day mortality 2.719%– 30 day mortality 10.696%– 90 day mortality 16.698%– 1 year mortality 29.079%– 5 year mortality 61.382%

Anesthesia and ESLD

• Pharmacokinetic and pharmacodynamic considerations– Multiple aspects possibly affected• Hepatic metabolism• Renal metabolism• Volume of distribution• Protein binding

– All medications should be titrated to effect• “You can always give more”

Anesthesia and ESLD

• Intraoperative management– Anesthetic technique• No one medication, technique or approach has

proven superior in patients with ESLD• MAC and regional are appropriate, but need to be

considered on a case-by-case basis

– All medications should be titrated to effect

Intraoperative Management

• Overall hepatic blood flow is decreased due to portal hypertension– Hepatic oxygenation, therefore, is more

dependent on hepatic artery blood flow than normal

– Volatile anesthetics blunt the ability of the hepatic artery to vasodilate in the face of decreased portal vein blood flow

Intraoperative Management

• Overall hepatic blood flow is decreased due to portal hypertension– Any decrease in systemic blood pressure,

for example from volatile anesthetic-induced peripheral vasodilation, can decrease hepatic artery blood flow

• Probably best to avoid delivering high concentrations of volatile agents to patients with ESLD

Intraoperative Management

• Monitoring and vascular access– Standard American Society of Anesthesiology

(ASA) monitors– Additional invasive monitors as dictated by • Degree of liver disease• Presence/absence of other underlying disease• Nature of surgical procedure

Intraoperative Management

• Monitoring and vascular access– Other considerations• Urine output• “Gentle” esophageal manipulation – varices• Bispectral index (BIS)• Real-time coagulation assessment –

thromboelastography (TEG)

– Vascular access• Large bore catheter(s) recommended

Intraoperative Management

• Induction of general anesthesia (GA)– Rapid sequence vs routine induction– Does the presence of ascites = full stomach?– Succinylcholine may have a prolonged

duration of action due to decreased plasma cholinesterase activity

– Theoretically may need larger initial dose of non-depolarizing muscle relaxants due to increased volume of distribution, especially in those patients with significant ascites

Intraoperative Management

• Maintenance of GA– The golden rule – maintain homeostasis• Avoid hypotension• Avoid low cardiac output• Avoid bradycardia• Avoid myocardial depression• Avoid peripheral vasodilation

– Remember, pressure = flow X resistance (BP = CO X SVR)

Intraoperative Management

• Maintenance of GA– Halothane hepatitis• Diagnosis of exclusion• Autoimmune vs hepato-toxic metabolites• ~1:35,000 incidence of fatal hepatic necrosis• Risk factors

– Middle age– Obesity– Female gender– Repeated exposure, especially within 28 days

Intraoperative Management

• Maintenance of GA– Muscle relaxants• Metabolism of both rocuronium and vecuronium

is 60-90% dependent on hepatic degradation and biliary excretion• Pancuronium relies mostly on renal excretion (80%)

but about 20% of metabolism occurs via the liver• Cisatracurium, by nature of its organ-independent

clearance via Hofmann degradation, is ideal to use in patients with ESLD

Intraoperative Management

• Maintenance of GA– Fluid therapy• No prospective data exist showing a benefit

to crystalloid vs colloid• Maintenance of adequate filling pressure is more

important than the choice of fluid

– Blood transfusion• Communication with blood bank is crucial• RBCs, FFP, platelets, cryoprecipitate

Intraoperative Management

• Vasoactive medications– ESLD patients typically are in a hyperdynamic,

vasodilated state– Anesthetic-induced increases in peripheral

vasodilation can lead to profound hypotension– Administration of vasoconstricting agents –

phenylephrine, norepinephrine, vasopressin – is common and dosing is often higher than normally required

Intraoperative Management

• Blood transfusion– Lab turnover time may render traditional

coagulation testing (i.e. PT/INR, PTT, platelet count) irrelevant during high-volume blood loss cases in ESLD patients

– Thromboelastography (TEG)• Allows real-time assessment of all aspects of

the coagulation cascade• Used in cardiac surgery, trauma and liver

transplantation

Thromboelastography (TEG)

Thromboelastography (TEG)

• Components– R, reaction time: time until initial clot formation– K, clot formation time: period after R to achieve

clot width of 20mm– α, alpha angle: measures speed of clot formation– MA, maximum amplitude: measure of the

strength of the fully formed clot– A60/MA ratio: compares maximum clot

size to that 60 minutes later

Thromboelastography (TEG)

• Treatment decisions– Prolongation of R and/or K, or a decrease in α,

treated with fresh frozen plasma (FFP)– Decrease in MA treated with platelets– A60/MA < 0.85 indicates fibrinolysis and is

treated with epsilon-aminocaproic acid• Use of TEG during liver transplantation has

been shown to reduce the amounts of RBCs and FFP transfused

Orthotopic Liver Transplantation (OLTx)

• VA Pittsburgh Healthcare System experience– Started doing liver transplants in the mid-1980s– Dedicated VA transplant surgeon since Jan 2004– One year survival 84.6%; national average 90.2%• Latest data per UNOS• Period ending December 31, 2012

OLTx at VAPHS

• Cases are always emergent• All adult patients• Frequently occur after hours or on weekends• Separate, dedicated call team– Anesthesiologist– CRNA– Anesthesia technician

OLTx at VAPHS

Common ESLD etiologies• Hepatitis C• Alcoholic cirrhosis• Hepatocellular carcinoma

(HCC)• Some combination of the

three

Uncommon etiologies• Primary sclerosing

cholangitis• Primary biliary cirrhosis• Non-alcoholic steato-

hepatitis (NASH)• Autoimmune hepatitis

OLTx at VAPHS

• Preoperative considerations– All patients undergoing multi-disciplinary

evaluation, including surgery, anesthesiology and psychiatry consultation

– Workup includes a full battery of lab tests, ECG, CXR and PFTs

Preoperative Considerations

• Cardiopulmonary workup includes– Stress testing

• Low threshold for cardiac catheterization• Case-by-case decision, but generally any patient with

more than mild CAD is not a surgical candidate

– Transthoracic echocardiography• Pulmonary artery pressure (PAP) estimation• Mean PAP >35mmHg associated with increased

perioperative morbidity/mortality; patients with MPAP >50mmHg are not surgical candidates

OLTx at VAPHS

• Intraoperative considerations– Standard ASA monitors plus• BIS• Arterial line – right femoral• Large-bore iv access – “double stick”

– Right internal jugular (RIJ) 9Fr double-lumen introducer with pulmonary artery catheter (PAC)

– RIJ veno-venobypass (VVB) cannula, 18Fr– Ultrasound guidance

• Pacing/defibrillator pads

OLTx at VAPHS

• Intraoperative considerations– Emergency case – “full stomach” management– Anesthetic maintenance• Usually a balanced technique• My preference is more toward a cardiac anesthetic

– High dose benzodiazepine/opioid dosing– Low, steady state dose of volatile anesthetic– Muscle relaxant – dealer’s choice

Intraoperative Considerations

• Coagulation management– Arterial blood gas (ABG) and TEG done hourly– PT/INR/PTT/platelets done every 2 or 3 hours– Reperfusion resets the lab timeline– Additional labs as needed

Intraoperative Considerations

• Rapid infusion system (RIS)– In OR and primed for every case– Decision to use made on a case-by-case basis

• Cell-saver blood salvage system– Set up for every case– Not employed until after reperfusion in VAPHS

patients with hepatocellular CA

Intraoperative Considerations

• OLTx procedure can be broken down into 3 phases– Pre-anhepatic– Anhepatic– Post-anhepatic or neohepatic

• Average operative time at VAPHS ~8 hours

Pre-anhepatic Phase

• Lasts from skin incision to the point when the native liver is freed to its vascular pedicle

• Native liver is mobilized– Hilum located– Hepatic artery (HA) ligated– Bile duct transected– Infra- and supra-hepatic inferior vena cava (IVC)

and portal vein (PV) encircled

Pre-anhepatic Phase

• May involve veno-venobypass (VVB)– Venous outflow via 2 cannulas – L common iliac

vein and portal vein– Venous return via 1 cannula – R internal jugular

(may use the L axillary vein via cutdown)• VVB complications include– Hypothermia– Air or thromboembolism– Brachial plexus and/or vessel trauma

Anhepatic Phase

• Lasts from clamping of the infra- and supra-hepatic IVC, PV and hepatic artery and ends when the IVC and PV anastomoses are complete

• Usually see decreased cardiac output/index from decreased venous return

• Use of VVB can lead to profound hypothermia, especially if a heat exchanger is not used

Anhepatic Phase

• Portal hypertension does NOT protect against hemodynamic instability

• Anastomotic order– Supra-hepatic IVC– Infra-hepatic IVC– Portal vein– Hepatic artery

Anhepatic Phase

• Reperfusion– Occurs when PV (inflow) and IVC (outflow)

anastomoses are complete– Often associated with hemodynamic instability

• Bradycardia, asystole• Hypotension• Hyperkalemia, despite donor organ flush, may result from

preservation solution with high K+ concentration• Air or thromboembolism• Pulmonary hypertension, often with acute right

heart failure, is rare but may occur

Anhepatic Phase

• Reperfusion– Post-reperfusion syndrome• Decrease in mean arterial pressure of at least 30% for

at least 1 minute within 5 minutes of reperfusion• Usually see bradycardia, high filling pressures and

peripheral vasodilation (↓ SVR)• Washout of “evil humors” from the donor organ –

kinins, cytokines, free radicals• Usually responds to vasoconstrictors –

phenylephrine, norepi or vasopressin

Anhepatic Phase

• Reperfusion– Preparation should include• Ventilation with 100% FiO2• Priming/filling of the RIS, if in use• Vasoactive meds/infusions in line

– Epinephrine– Calcium– Phenylephrine, norepi, vasopressin

• Pacer connected, turned on

Post-anhepatic (Neohepatic) Phase

• Begins with PV and HA unclamping• Biliary drainage is reconstructed– End-to-end anastomosis, often with T-tube– Roux-en-Y choledochojejunostomy

• Fibrinolysis may occur – epsilon-aminocaproic acid 500mg-1g iv if present on TEG

• Unclamping order – PV, infra-hepatic IVC, supra-hepatic IVC, HA and lastly the bile duct

OLTx at VAPHS

• End of case management– VVB cannula removal – needs purse-string suture– ETT, arterial line and introducer/PAC stay in– Transport with full monitors and 100% FiO2 via

ambu to intensive care• Post-op day #1, etc– Extubation and invasive monitor removal

depend on graft function, co-existing disease & patient status preoperatively

Anesthetic Management of Patients after OLTx

• Following successful OLTx, liver synthetic function and metabolic activity return to normal– Lab values normalize– Normal hepatic drug clearance

• Circulation no longer hyperdynamic• Oxygenation generally improves,

although some anatomic V-Q mismatch may persist

Anesthesia after OLTx

• No routine lab work (PT/INR/platelets/LFTs) needed for patients with normally functioning grafts

• Problems arise from adverse effects (anemia, thrombocytopenia) of and/or drug interactions with chronic immunosuppressive therapy

Anesthesia after OLTx

• Short-term complications– Technical considerations

• Hepatic artery thrombosis (HAT)• Portal vein thrombosis – less common• Bile duct leak

– Primary graft non-function– Infection

• In these situations refer to previous slides as patients will physiologically once again have ESLD

Anesthesia after OLTx

• Long-term complications– Chronic kidney disease occurs more

frequently in patients with• Diabetes• Hepatitis C

– Diabetes occurs more commonly in patients with hep C

– Infection

Anesthesia after OLTx

• Long-term complications– Coronary artery disease• Risk factors – older age at transplant, male sex,

post-transplant diabetes or hypertension

– Infection– These long-term problems are managed in the

usual fashion, irrespective of the OLTx history

References

• Barash, Paul G, et al. Clinical Anesthesia. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2009.

• Miller, Ronald D, et al. Miller’s Anesthesia. 7th ed. Philadelphia: Churchill Livingstone, 2010.

• Jaffe, Richard A, et al. Anesthesiologist’s Manual of Surgical Procedures. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2009.

• Winter, Peter M., and Yoo Goo Kang. Hepatic Transplantation. New York: Praeger, 1986.

References

• Murray JF, et al. Circulatory changes in chronic liver disease. Am J Med 1958; 24: 358.

• Sharara AI and Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001; 345: 669.

• Salerno F, et al. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology 2007; 133: 825.

• Rodriguez-Roisin R and Krowka MJ. Hepatopulmonary syndrome – a liver-induced lung vascular disorder. N Engl J Med 2008; 358: 2378-87.

References

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• Wadei HM, et al. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol 2006; 1: 1066.

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• Senzolo M, et al. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 2006; 12(48): 7725-36.

References

• Tripodi A and Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365: 147-56.

• Pugh RNH, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646.

• Kamath PS, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464.

• Kamath PS and Kim WR. A model for end-stage liver disease (MELD). Hepatology 2007; 45: 797-805.

References

• Mansour A, et al. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery 1997; 122: 730.

• Kang YG, et al. Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation. Anesthesiology 1987; 66: 766-773.

• Albeldawi M, et al. Cumulative risk of cardiovascular events after orthotopic liver transplantation. Liver Transplant 2012; 18: 370-5.

• McGuire BM, et al. Long-term management of the liver transplant patient: recommendations for the primary care doctor. Am J Transplant 2009; 9: 1988-2003.