1. Anesthetic Implications of End-Stage Liver Disease and Liver Transplantation
Todd M. Oravitz, MD
Associate Professor
Department of Anesthesiology
University of Pittsburgh School of Medicine
Chief, Liver Transplantation Anesthesia
VA Pittsburgh Healthcare System

2. Lecture objectives
1) Discuss the pathophysiology of end-stage liver disease 2) Discuss the management of anesthesia in patients with end-stage liver disease 3) Discuss the perioperative management of patients undergoing liver transplantation 4) Discuss the perioperative management of patients undergoing procedures after liver transplantation

3. Normal Hepatic Function
Liver plays a role in
Carbohydrate metabolism
Produces/stores glycogen, which can be depleted after hours of fasting
Site of gluconeogenesis, with amino acids, glycerol and lactate as substrates

4. 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

5. 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

6. 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
Other phase I rxns – deamination, sulfoxidation, dealkylation and/or methylation.
Phase II – substances conjugated w/glucuronide, sulfate, taurine and/or glycine.

7. 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
Induction – more enzyme to metabolize drugs = tolerance.
Inhibition – less enzyme to metabolize drugs = exaggerated effect.

8. 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

9. 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

10. 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
Normal function may be present in patients that have had up to 80% of their liver resected!

11. End-Stage Liver Disease (ESLD)
Common symptoms
Anorexia
Weakness
Nausea/vomiting
Abdominal pain
Common signs
Hepatosplenomegaly
Ascites
Jaundice
Spider angiomas
Encephalopathy

12. 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

13. Pathophysiology of ESLD
Portal hypertension leads or contributes to
Ascites
Esophageal varices
Gastric and other intra-abdominal varices
Splenomegaly

14. 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
Remember, varices can occur in the stomach and/or small intestines as well.
Portal system pressure is high 2/2 intrinsic hepatic disease and the resultant increased resistance to blood flow through the liver.

15. 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)

16. 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

17. T I P S

18. 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

19. 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

20. 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%

21. 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

22. 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
Azotemia = excess urea and other nitrogenous waste in the blood that are normally excreted in urine via the kidneys.

23. 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

24. 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

25. 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)
Protein S levels also decreased in ESLD (all 3 – antithrombin III, protein C and S – made by liver); the potential (and actual) occurrence of thrombosis (portal vein, DVT/PE) usually overshadowed by the bleeding tendencies in these patients.

26. 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
Standard lab assessment of coagulation – PT/INR/PTT – will be normal as long as patients have at least 30% functioning hepatocytes.
Poor nutrition 2/2 ESLD or from one of the causes of ESLD (EtOH, for example).

27. 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
Folate (and other vitamin) deficiency and EtOH can suppress bone marrow thrombopoiesis, leading to and/or aggravating thrombocytopenia.

28. 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

29. 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

30. 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
Glucagon and VIP can induce peripheral vasodilation, decrease SVR and increase AV shunting.

31. 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

32. 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

33. 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
TTE/TEE – bubble study will show evidence of early crossover from the R to the L side of the heart.

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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
Octretide – inhibits release of glucagon and vasoactive intestinal peptide (VIP); mimics somatostatin.
Midodrine – alpha agonist and vasoconstrictor that works in this instance by splanchnic constriction and renal vasodilation.

41. 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

42. Pathophysiology of ESLD
Ascites
Common complication of ESLD; in fact, nearly 50% of patients develop ascites within 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

43. 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

44. 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
ESLD pts tend to be whole body fluid overloaded but intravascularly volume depleted.
Some of these interventions may be time-sensitive (i.e. need time to improve nutritional status).

45. 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

46. 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
Hepatic perfusion pressure and/or splanchnic vascular resistance decrease 20-30% in the absence of surgical stimulation in pts having inhalational or regional anesthesia.

47. Child-Pugh Classification System

48. 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

49. 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%
Again, 30 day mortality from the previous slide was 10, 30 and 80% for classes A, B and 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

51. 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
Time on the waiting list was a major determinant prior to MELD as there were only 3 categories of patients – status 2A, 2B and 3. A pt w/severe disease who happened to be listed late in their disease course was at a disadvantage before MELD.
Many other factors play into mortality after OLTx – donor organ quality, intraop complications or lack thereof, etc.

52. MELD Score

53. Anesthesia and ESLD Perioperative mortality calculator
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

54. 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?

55. Anesthesia and ESLD YES!!! 7 day mortality 2.719%
1 year mortality %
5 year mortality %

56. 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”

57. 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

58. 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

59. 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

60. 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

61. 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

62. 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
I have NOT seen pts w/prolonged sux (or mivacurium) duration, even those w/severe ESLD.
Conversely, I have NOT noticed the need for increased dosing of NDMRs, even those w/significant ascites.

63. 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)

64. 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
Audience question – who still uses halothane? Or even has it available in their hospital?

65. 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

66. 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

67. 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

68. 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

69. Thromboelastography (TEG)

70. 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

71. 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

72. 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

73. 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

74. OLTx at VAPHS Common ESLD etiologies Uncommon etiologies Hepatitis C
Alcoholic cirrhosis
Hepatocellular carcinoma (HCC)
Some combination of the three
Primary sclerosing cholangitis
Primary biliary cirrhosis
Non-alcoholic steato-hepatitis (NASH)
Autoimmune hepatitis
PSC – autoimmune induced bile duct obstruction leading to ESLD; more than 80% of pts w/PSC have ulcerative colitis.
PBC – autoimmune destruction of bile ducts leading to ESLD; 9:1 female:male ratio.

75. 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

76. 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

77. 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

78. 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
Muscle relaxant – pancuronium (80% renal unchanged, 10% hepatic bdown, 10% biliary excretion unchanged); vec (15-25, 20-30, 40-75%); roc (10-25, 10-20, 50-70%). If the new liver isn’t working, you won’t be worried about suitability for extubation anyway!

79. 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

80. 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

81. 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

82. 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

83. 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

84. 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

85. Anhepatic Phase
Portal hypertension does NOT protect against hemodynamic instability
Anastomotic order
Supra-hepatic IVC
Infra-hepatic IVC
Portal vein
Hepatic artery
Portal HTN – the associated collateral circulation offers some, but usually only mild, buffering against hypotension.

86. 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
This is why VAPHS places external pacing/defib pads on all patients – we pace if there is extreme bradycardia/asystole.

87. 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

88. 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

89. 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

90. OLTx at VAPHS End of case management Post-op day #1, etc
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

91. 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

92. 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

93. 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

94. 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

95. 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
Infection remains a lifelong concern 2/2 immunosuppression – must use strict aseptic technique!

96. 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.

97. 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:

98. References
Follo A, et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: Incidence, clinical course, predictive factors and prognosis. Hepatology 1994; 20: 1495.
Wadei HM, et al. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol 2006; 1: 1066.
Kujovich JL. Hemostatic defects in end stage liver disease. Crit Care Clin 2005; 21:
Senzolo M, et al. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 2006; 12(48):

99. References
Tripodi A and Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365:
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:

100. 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:
Albeldawi M, et al. Cumulative risk of cardiovascular events after orthotopic liver transplantation. Liver Transplant 2012; 18:
McGuire BM, et al. Long-term management of the liver transplant patient: recommendations for the primary care doctor. Am J Transplant 2009; 9: