Presentation on theme: "Todd M. Oravitz, MD Associate Professor Department of Anesthesiology"— Presentation transcript:
1Anesthetic Implications of End-Stage Liver Disease and Liver Transplantation Todd M. Oravitz, MDAssociate ProfessorDepartment of AnesthesiologyUniversity of Pittsburgh School of MedicineChief, Liver Transplantation AnesthesiaVA Pittsburgh Healthcare System
2Lecture objectives1) 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
3Normal Hepatic Function Liver plays a role inCarbohydrate metabolismProduces/stores glycogen, which can be depleted after hours of fastingSite of gluconeogenesis, with amino acids, glycerol and lactate as substrates
4Normal Hepatic Function Liver plays a role inProtein metabolismAll plasma proteins, except for immunoglobulins, made in the liverAlbumin helps maintain plasma oncotic pressure and is the primary binding/transport protein for many anesthetic drugsAll coagulation factors, except for factor VIII and von Willebrand factor, made in the liver
5Normal Hepatic Function Liver plays a role inDrug metabolismMost medications undergo at least some hepatic degradation or biotransformation, or bothEnd products either metabolically inactive or more water-soluble for biliary or urinary excretion
6Normal Hepatic Function Drug metabolismPhase I reactionsInclude oxidation/reduction (redox)Cytochrome p450Benzodiazepines and barbiturates degraded via phase IPhase II reactionsMay or may not follow phase IInvolve conjugation to facilitate elimination via bile or urineOther phase I rxns – deamination, sulfoxidation, dealkylation and/or methylation.Phase II – substances conjugated w/glucuronide, sulfate, taurine and/or glycine.
7Normal Hepatic Function Drug metabolismCytochrome p450Ethanol, ketamine capable of enzyme induction, resulting in tolerance to the drugs’ effectsCimetidine, chloramphenicol can cause prolongation of drug effects by enzyme inhibitionInduction – more enzyme to metabolize drugs = tolerance.Inhibition – less enzyme to metabolize drugs = exaggerated effect.
8Normal Hepatic Function Anatomy/physiologyLargest organ in the body, weighing about 1.5kgRight upper quadrant locationDual blood supplyLiver blood flow ~1.5L/minHepatic arteryPortal vein
9Normal Hepatic Function Dual blood supplyHepatic arteryAccounts for 25% of blood flow and 50% of O2 deliveryFlow is auto-regulatedPortal veinAccounts for 75% of blood flow and 50% of O2 deliveryFlow depends on GI and splenic blood flow
10End-Stage Liver Disease (ESLD) The liver has a remarkable capacity for regenerationThe liver has tremendous physiologic reserveHepatic disease can develop insidiously and a large proportion of function can be lost before problems become apparentNormal function may be present in patients that have had up to 80% of their liver resected!
11End-Stage Liver Disease (ESLD) Common symptomsAnorexiaWeaknessNausea/vomitingAbdominal painCommon signsHepatosplenomegalyAscitesJaundiceSpider angiomasEncephalopathy
12Pathophysiology of ESLD Hepatic changesPortal hypertension – high resistance to blood flow through the liver – hallmark of ESLDLeads to accumulation of blood and increased venous pressure in the vascular beds “upstream” to the liverEsophagusSpleenStomach and intestines
13Pathophysiology of ESLD Portal hypertension leads or contributes toAscitesEsophageal varicesGastric and other intra-abdominal varicesSplenomegaly
14Pathophysiology of ESLD Esophageal varicesPortal-systemic collaterals that allow splanchnic venous blood to flow from the high-pressure portal system to the low-pressure azygos and hemi-azygous systemNot all patients with ESLD develop varices and not all patients with varices have bleedingPatients that do bleed have significant morbidity and mortality – up to 30% of initial episodes of bleeding are fatalRemember, 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.
15Variceal Disease Treatment Chronic Propranolol is a non-selective beta-blocker that decreases portal venous pressureReduces risk of primary bleedingReduces risk of re-bleedBanding, ligation, sclerotherapyTransjugular intrahepatic portosystemic shunt (TIPS)
16Pathophysiology of ESLD TIPSImproves blood flow through the liverPercutaneous approach to create a shunt between the portal and hepatic veinsDecreases activity of the sodium-retaining pathwaysImproves renal response to diuretics
18Variceal Disease Treatment Acute Aggressive fluid resuscitation; ± bloodCorrect coagulation defects, if presentAirway protection – intubationOctreotide – reduces portal pressureEndoscopy with possible intervention – bandingBalloon tamponade – Blakemore tube
19Pathophysiology of ESLD Hepatic changesSpontaneous bacterial peritonitis (SBP)Spontaneous infection of ascitic fluid without an intra-abdominal sourceIncreased intestinal wall permeability allows translocation of bacterial into the conducive media of ascitic fluid
20Pathophysiology of ESLD Hepatic changesSpontaneous 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 pneumococcusQuinolone (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 survivalTwo year survival after SBP is less than 50%
21Pathophysiology of ESLD Hepatic changesHepatic encephalopathy (HE)Occurs when substances normally metabolized by the liver accumulate due to its dysfunctionAmmonia felt to be most important in HE patientsIncreased activity of inhibitory neurotransmitters also may play a roleIncreased GABAergic toneAdministration of the benzodiazepine antagonist flumazenil often results in an improvement in the mental status of HE patients
22Hepatic Encephalopathy Often occurs after a precipitating eventIncreased ammonia levelLarge dietary protein loadGI bleedingAzotemiaDecreased hepatic perfusionAnesthesia and surgery with resultant hypotension, hypoxemia and/or hypovolemiaDiuretic administration, paracentesis or GI disturbance such as diarrhea or vomitingAzotemia = excess urea and other nitrogenous waste in the blood that are normally excreted in urine via the kidneys.
23Hepatic Encephalopathy Other possible precipitating eventsSepsisIncreased ammonia levels due to protein catabolismDecreased hepatic perfusionCreation of portal-systemic shuntTIPSResults in decreased hepatic metabolism
24Hepatic Encephalopathy TreatmentRemove/minimize, to the extent possible, any/all underlying causesDecrease blood ammonia levelsReduce productionLower dietary protein intakeNeomycin – targets urease-producing bacteriaReduce GI absorptionLactulose – non-absorbable disaccharide that decreases large intestinal absorption of ammonia and also promotes growth of non-urease producing bacteria
25Pathophysiology of ESLD Coagulation/hematologic changesCoagulopathy results mostly from two factorsImpaired synthesis of clotting factorsThrombocytopeniaDecreased levels of anticoagulants, most notably antithrombin III and protein C, can lead to thrombotic complicationsPortal vein thrombosisDeep 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.
26Coagulation/Hematologic Changes CoagulopathyImpaired synthesis of coagulation cascade proteinsAll clotting factors, except von Willebrand factor, made in the liverVitamin K dependent factors – II, VII, IX and X – at additional riskBile salts needed for intestinal absorption of vitamin K and may be decreased by ESLDOverall poor nutritional status in many ESLD patientsStandard 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).
27Coagulation/Hematologic Changes CoagulopathyThrombocytopeniaPortal hypertension-induced splenomegalyOccurs in 30-60% of ESLD patientsUp to 90% of platelets can be sequestered in the enlarged spleenPlatelet count usually >30K and spontaneous bleeding is fairly uncommonAssociated disease processes can contributePoor nutrition – folate deficiencyChronic alcohol intakeFolate (and other vitamin) deficiency and EtOH can suppress bone marrow thrombopoiesis, leading to and/or aggravating thrombocytopenia.
28Pathophysiology of ESLD Cardiovascular changesHyperdynamic circulationIncreased cardiac outputDecreased systemic vascular resistanceNormal to decreased blood pressureIncreased heart rateNormal to increased stroke volume
29Pathophysiology of ESLD blood pressure=cardiac output x systemic vascular resistance↔/↓BP = ↑CO X ↓SVR↓−−−−−−−−−−−−−−−−−↓ ↓↑HR X ↔/↑SVcardiac output = heart rate x stroke volume
30Pathophysiology of ESLD Cardiovascular changesResult from development of vasodilation and abnormal shuntingBlood passes from the arterial to the venous circulation without crossing a capillary bed; an anatomic example of this is a spider angiomaThought to result from increased plasma levels of glucagon and vasoactive intestinal polypeptideGlucagon and VIP can induce peripheral vasodilation, decrease SVR and increase AV shunting.
31Pathophysiology of ESLD Pulmonary changesHypoxemia, with PaO2 values of 60-70mmHg, is commonly seen in ESLD patientsCauses includeUnderlying cardiopulmonary diseaseIntrapulmonary shuntingV/Q mismatchDecreased diffusion capacity
32Pulmonary Changes - Hypoxemia Underlying cardiopulmonary diseaseCongestive heart failure, interstitial lung disease, chronic obstructive pulmonary diseaseIntrapulmonary shuntingPre-capillary or larger arteriovenous communications are the result of intrapulmonary vascular dilatationHepatopulmonary syndrome
33Hepatopulmonary Syndrome (HPS) Defined by the clinical triad ofChronic liver diseaseIncreased A-a gradientEvidence of intrapulmonary vascular dilatationIncreased pulmonary nitric oxide production is the likely causeUsually diagnosed by echocardiographyTTE/TEE – bubble study will show evidence of early crossover from the R to the L side of the heart.
34Hepatopulmonary Syndrome (HPS) Incidence 5-30%Decreased survival compared to patients with similar degree of liver disease who do not have HPSHPS patients with severe preoperative hypoxemia (PaO2 <50mmHg) have increased mortality after liver transplantationHPS often resolves completely after transplant
35Pathophysiology of ESLD Pulmonary changesHepatic hydrothoraxSeen in 5-10% of ESLD patientsPleural effusion from transfer of ascitic fluid through diaphragmatic defectsTreated by sodium restriction, diuretics and/or thoracentesis
36Pathophysiology of ESLD Pulmonary changesPulmonary hypertensionSeen in <5% of ESLD patientsDefined as mean pulmonary artery pressure (MPAP) >25mmHg and increased pulmonary vascular resistancePatients with MPAP >35mmHg have increased perioperative morbidity/mortalityPatients with MPAP >50mmHg, at VAPHS, are not transplant candidates secondary to greatly increased mortalityEtiology not well understood
37Pulmonary Hypertension Avoid physiologic conditions that increase pulmonary vascular resistance, as acute right-sided heart failure can resultHypoxemiaHypercapniaAcidosisImportant to remember during monitored anesthesia care (MAC) cases
38Pathophysiology of ESLD Renal changesImpaired free water and sodium excretionDecreased 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
39Pathophysiology of ESLD Renal changes lead to development ofEdemaAscitesLong term decrease in renal perfusion and GFR can lead to hepatorenal syndrome (HRS)HRS occurs in up to 10% of patients with ESLDFunctionally HRS is a pre-renal phenomenon whose hallmark is intense renal vasoconstriction
40Hepatorenal Syndrome (HRS) Type IProgressive oliguria with rapidly rising creatinineOften follows an episode of spontaneous bacterial peritonitis (SBP)Poor outcome – median survival < 1 month without interventionTreatment with albumin, octreotide, and midodrine has shown some promiseOctretide – 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.
41Hepatorenal Syndrome (HRS) Type IIUsually seen in patients with refractory ascitesRenal impairment is usually more mild than type IClinical course is far less progressive than type I
42Pathophysiology of ESLD AscitesCommon complication of ESLD; in fact, nearly 50% of patients develop ascites within years of initial diagnosisSignificant associated mortality – nearly 50% of patients die within 3 years of onset of ascitesEtiology complex, multifactorial and not completely understoodPortal hypertensionSodium, water retention
43Pathophysiology of ESLD AscitesTreatmentSodium restriction and diuretics (spironolactone)Refractory cases treated with repeated large-volume paracentesis and volume expanders, usually albuminTransjugular intrahepatic portosystemic shunt (TIPS) also can be used for refractory ascites, but it has not been shown to improve survival compared to repeat paracentesis
44Anesthesia and ESLDPreoperative preparation should focus on optimizing liver-related pathology (if possible)Volume statusCoagulation – parenteral vitamin K if INR elevatedRenal functionElectrolyte imbalanceNutritional statusESLD 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).
45Anesthesia and ESLDMedications should be scrutinized in the preoperative period, as there are a large number that can cause or worsen underlying hepatic dysfunctionAcetaminophenIsoniazidMethyldopaPhenytoinIndomethacin
46Anesthesia and ESLDAdministration of anesthesia decreases liver blood flow via changes in hepatic perfusion pressure and/or splanchnic vascular resistancePhysiologic reserve is decreased patients with ESLDPerioperative morbidity and mortality in patients undergoing all but minor procedures is increasedHepatic perfusion pressure and/or splanchnic vascular resistance decrease 20-30% in the absence of surgical stimulation in pts having inhalational or regional anesthesia.
48Child-Pugh Class and Mortality Thirty day mortality in patients undergoing either cholecystectomy, hernia repair, GI or miscellaneous surgery; 25% were emergenciesClass A – 10%Class B – 30%Class C – 80%Highest mortality in GI and emergent procedures
49Child-Pugh Class and Mortality Three month mortality for patients hospitalized with liver complications, but not undergoing surgeryClass 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.
50Model for End-Stage Liver Disease (MELD) Score Originally developed to predict survival in patients with portal hypertension undergoing elective TIPS proceduresFound to be an accurate predictor of survival in patients with a variety of liver diseasesAdopted in 2002 as the rank list criteria for liver transplantation by the United Network of Organ Sharing (UNOS), replacing Child-Pugh
51Model for End-Stage Liver Disease (MELD) Score Resulted in an almost 15% reduction in mortality on the waiting listMedian waiting time also decreased, about 35%, from 656 to 416 daysWhile it accurately estimates mortality on the waiting list, MELD does not correlate well with mortality following liver transplantationTime 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.
53Anesthesia 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
54Anesthesia and ESLD52 year male presenting for R total knee arthroplastyPMHx HTN, DM, hep C, CKD, COPD, GERD, PTSDLab data – HgB 11, platelets 95K, K 4, BUN/Cr 20/1.4, total bili 1.5, PT/INR 15.7/1.3Does this patient have a significant degree of morbidity/mortality in the perioperative period?
55Anesthesia and ESLD YES!!! 7 day mortality 2.719% 1 year mortality %5 year mortality %
56Anesthesia and ESLD Pharmacokinetic and pharmacodynamic considerations Multiple aspects possibly affectedHepatic metabolismRenal metabolismVolume of distributionProtein bindingAll medications should be titrated to effect“You can always give more”
57Anesthesia and ESLD Intraoperative management Anesthetic technique No one medication, technique or approach has proven superior in patients with ESLDMAC and regional are appropriate, but need to be considered on a case-by-case basisAll medications should be titrated to effect
58Intraoperative Management Overall hepatic blood flow is decreased due to portal hypertensionHepatic oxygenation, therefore, is more dependent on hepatic artery blood flow than normalVolatile anesthetics blunt the ability of the hepatic artery to vasodilate in the face of decreased portal vein blood flow
59Intraoperative Management Overall hepatic blood flow is decreased due to portal hypertensionAny decrease in systemic blood pressure, for example from volatile anesthetic-induced peripheral vasodilation, can decrease hepatic artery blood flowProbably best to avoid delivering high concentrations of volatile agents to patients with ESLD
60Intraoperative Management Monitoring and vascular accessStandard American Society of Anesthesiology (ASA) monitorsAdditional invasive monitors as dictated byDegree of liver diseasePresence/absence of other underlying diseaseNature of surgical procedure
62Intraoperative Management Induction of general anesthesia (GA)Rapid sequence vs routine inductionDoes the presence of ascites = full stomach?Succinylcholine may have a prolonged duration of action due to decreased plasma cholinesterase activityTheoretically may need larger initial dose of non-depolarizing muscle relaxants due to increased volume of distribution, especially in those patients with significant ascitesI 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.
63Intraoperative Management Maintenance of GAThe golden rule – maintain homeostasisAvoid hypotensionAvoid low cardiac outputAvoid bradycardiaAvoid myocardial depressionAvoid peripheral vasodilationRemember, pressure = flow X resistance(BP = CO X SVR)
64Intraoperative Management Maintenance of GAHalothane hepatitisDiagnosis of exclusionAutoimmune vs hepato-toxic metabolites~1:35,000 incidence of fatal hepatic necrosisRisk factorsMiddle ageObesityFemale genderRepeated exposure, especially within 28 daysAudience question – who still uses halothane? Or even has it available in their hospital?
65Intraoperative Management Maintenance of GAMuscle relaxantsMetabolism of both rocuronium and vecuronium is 60-90% dependent on hepatic degradation and biliary excretionPancuronium relies mostly on renal excretion (80%) but about 20% of metabolism occurs via the liverCisatracurium, by nature of its organ-independent clearance via Hofmann degradation, is ideal to use in patients with ESLD
66Intraoperative Management Maintenance of GAFluid therapyNo prospective data exist showing a benefit to crystalloid vs colloidMaintenance of adequate filling pressure is more important than the choice of fluidBlood transfusionCommunication with blood bank is crucialRBCs, FFP, platelets, cryoprecipitate
67Intraoperative Management Vasoactive medicationsESLD patients typically are in a hyperdynamic, vasodilated stateAnesthetic-induced increases in peripheral vasodilation can lead to profound hypotensionAdministration of vasoconstricting agents – phenylephrine, norepinephrine, vasopressin – is common and dosing is often higher than normally required
68Intraoperative Management Blood transfusionLab turnover time may render traditional coagulation testing (i.e. PT/INR, PTT, platelet count) irrelevant during high-volume blood loss cases in ESLD patientsThromboelastography (TEG)Allows real-time assessment of all aspects of the coagulation cascadeUsed in cardiac surgery, trauma and liver transplantation
70Thromboelastography (TEG) ComponentsR, reaction time: time until initial clot formationK, clot formation time: period after R to achieve clot width of 20mmα, alpha angle: measures speed of clot formationMA, maximum amplitude: measure of the strength of the fully formed clotA60/MA ratio: compares maximum clot size to that 60 minutes later
71Thromboelastography (TEG) Treatment decisionsProlongation of R and/or K, or a decrease in α, treated with fresh frozen plasma (FFP)Decrease in MA treated with plateletsA60/MA < 0.85 indicates fibrinolysis and is treated with epsilon-aminocaproic acidUse of TEG during liver transplantation has been shown to reduce the amounts of RBCs and FFP transfused
72Orthotopic Liver Transplantation (OLTx) VA Pittsburgh Healthcare System experienceStarted doing liver transplants in the mid-1980sDedicated VA transplant surgeon since Jan 2004One year survival 84.6%; national average 90.2%Latest data per UNOSPeriod ending December 31, 2012
73OLTx at VAPHS Cases are always emergent All adult patients Frequently occur after hours or on weekendsSeparate, dedicated call teamAnesthesiologistCRNAAnesthesia technician
74OLTx at VAPHS Common ESLD etiologies Uncommon etiologies Hepatitis C Alcoholic cirrhosisHepatocellular carcinoma (HCC)Some combination of the threePrimary sclerosing cholangitisPrimary biliary cirrhosisNon-alcoholic steato-hepatitis (NASH)Autoimmune hepatitisPSC – 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.
75OLTx at VAPHS Preoperative considerations All patients undergoing multi-disciplinary evaluation, including surgery, anesthesiology and psychiatry consultationWorkup includes a full battery of lab tests, ECG, CXR and PFTs
76Preoperative Considerations Cardiopulmonary workup includesStress testingLow threshold for cardiac catheterizationCase-by-case decision, but generally any patient with more than mild CAD is not a surgical candidateTransthoracic echocardiographyPulmonary artery pressure (PAP) estimationMean PAP >35mmHg associated with increased perioperative morbidity/mortality; patients with MPAP >50mmHg are not surgical candidates
77OLTx at VAPHS Intraoperative considerations Standard ASA monitors plus BISArterial line – right femoralLarge-bore iv access – “double stick”Right internal jugular (RIJ) 9Fr double-lumen introducer with pulmonary artery catheter (PAC)RIJ veno-venobypass (VVB) cannula, 18FrUltrasound guidancePacing/defibrillator pads
78OLTx at VAPHS Intraoperative considerations Emergency case – “full stomach” managementAnesthetic maintenanceUsually a balanced techniqueMy preference is more toward a cardiac anestheticHigh dose benzodiazepine/opioid dosingLow, steady state dose of volatile anestheticMuscle relaxant – dealer’s choiceMuscle 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!
79Intraoperative Considerations Coagulation managementArterial blood gas (ABG) and TEG done hourlyPT/INR/PTT/platelets done every 2 or 3 hoursReperfusion resets the lab timelineAdditional labs as needed
80Intraoperative Considerations Rapid infusion system (RIS)In OR and primed for every caseDecision to use made on a case-by-case basisCell-saver blood salvage systemSet up for every caseNot employed until after reperfusion in VAPHS patients with hepatocellular CA
81Intraoperative Considerations OLTx procedure can be broken down into 3 phasesPre-anhepaticAnhepaticPost-anhepatic or neohepaticAverage operative time at VAPHS ~8 hours
82Pre-anhepatic PhaseLasts from skin incision to the point when the native liver is freed to its vascular pedicleNative liver is mobilizedHilum locatedHepatic artery (HA) ligatedBile duct transectedInfra- and supra-hepatic inferior vena cava (IVC) and portal vein (PV) encircled
83Pre-anhepatic Phase May involve veno-venobypass (VVB) Venous outflow via 2 cannulas – L common iliac vein and portal veinVenous return via 1 cannula – R internal jugular (may use the L axillary vein via cutdown)VVB complications includeHypothermiaAir or thromboembolismBrachial plexus and/or vessel trauma
84Anhepatic PhaseLasts from clamping of the infra- and supra-hepatic IVC, PV and hepatic artery and ends when the IVC and PV anastomoses are completeUsually see decreased cardiac output/index from decreased venous returnUse of VVB can lead to profound hypothermia, especially if a heat exchanger is not used
85Anhepatic PhasePortal hypertension does NOT protect against hemodynamic instabilityAnastomotic orderSupra-hepatic IVCInfra-hepatic IVCPortal veinHepatic arteryPortal HTN – the associated collateral circulation offers some, but usually only mild, buffering against hypotension.
86Anhepatic Phase Reperfusion Occurs when PV (inflow) and IVC (outflow) anastomoses are completeOften associated with hemodynamic instabilityBradycardia, asystoleHypotensionHyperkalemia, despite donor organ flush, may result from preservation solution with high K+ concentrationAir or thromboembolismPulmonary hypertension, often with acute right heart failure, is rare but may occurThis is why VAPHS places external pacing/defib pads on all patients – we pace if there is extreme bradycardia/asystole.
87Anhepatic Phase Reperfusion Post-reperfusion syndrome Decrease in mean arterial pressure of at least 30% for at least 1 minute within 5 minutes of reperfusionUsually see bradycardia, high filling pressures and peripheral vasodilation (↓ SVR)Washout of “evil humors” from the donor organ – kinins, cytokines, free radicalsUsually responds to vasoconstrictors – phenylephrine, norepi or vasopressin
88Anhepatic Phase Reperfusion Preparation should include Ventilation with 100% FiO2Priming/filling of the RIS, if in useVasoactive meds/infusions in lineEpinephrineCalciumPhenylephrine, norepi, vasopressinPacer connected, turned on
89Post-anhepatic (Neohepatic) Phase Begins with PV and HA unclampingBiliary drainage is reconstructedEnd-to-end anastomosis, often with T-tubeRoux-en-Y choledochojejunostomyFibrinolysis may occur – epsilon-aminocaproic acid 500mg-1g iv if present on TEGUnclamping order – PV, infra-hepatic IVC, supra-hepatic IVC, HA and lastly the bile duct
90OLTx at VAPHS End of case management Post-op day #1, etc VVB cannula removal – needs purse-string sutureETT, arterial line and introducer/PAC stay inTransport with full monitors and 100% FiO2 via ambu to intensive carePost-op day #1, etcExtubation and invasive monitor removal depend on graft function, co-existing disease & patient status preoperatively
91Anesthetic Management of Patients after OLTx Following successful OLTx, liver synthetic function and metabolic activity return to normalLab values normalizeNormal hepatic drug clearanceCirculation no longer hyperdynamicOxygenation generally improves, although some anatomic V-Q mismatch may persist
92Anesthesia after OLTxNo routine lab work (PT/INR/platelets/LFTs) needed for patients with normally functioning graftsProblems arise from adverse effects (anemia, thrombocytopenia) of and/or drug interactions with chronic immunosuppressive therapy
93Anesthesia after OLTx Short-term complications Technical considerationsHepatic artery thrombosis (HAT)Portal vein thrombosis – less commonBile duct leakPrimary graft non-functionInfectionIn these situations refer to previous slides as patients will physiologically once again have ESLD
94Anesthesia after OLTx Long-term complications Chronic kidney disease occurs more frequently in patients withDiabetesHepatitis CDiabetes occurs more commonly in patients with hep CInfection
95Anesthesia after OLTx Long-term complications Coronary artery disease Risk factors – older age at transplant, male sex, post-transplant diabetes or hypertensionInfectionThese long-term problems are managed in the usual fashion, irrespective of the OLTx historyInfection remains a lifelong concern 2/2 immunosuppression – must use strict aseptic technique!
96ReferencesBarash, 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.
97ReferencesMurray 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:
98ReferencesFollo 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):
99ReferencesTripodi 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:
100ReferencesMansour 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: