Liver transplantation & its anaesthetic management


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  • afflicted liver may recover,iforginal liver recovers donor liver atrophies
  • The best survival has been shown to occuramong patients who undergo liver transplantation for chronic cholestaticliver diseases, including primary biliary cirrhosis and primary sclerosingcholangitis; the worst survival occurred in patients who underwenttransplantation for hepatic malignancy.
  • In the past Childs-Turcotte-Pugh (CTP) score.
  • (Growth failure is calculated based on age and gender using thecurrent WHO growth chart)
  • patient and graft survival is superior with compatible
  • Proper planning
  • One must have sound knowledge of these changes which dictate planning of anaesthetic management during the entire peri-operative period
  • Patients are more prone to hypoxia ,ventilation-perfusion mismatch,diffusionderfects however liver transplantation is not contraindicated
  • Thiscondition has been attributed to sympathetic nervous system overactivity,inadequate clearance of vasoactive substances (bypassing the liver anddecreased hepatic function)
  • Test myocardial function Ischaemic heart disease
  • need for dialysis hyperdynamic circulation
  • NormalGrade I Altered spatial orientation, sleep patterns and affectGrade II Drowsy but arousable, slurred speech, confusion, asterixisGrade III Stuporous, responsive only to painful stimuliGrade IV Unresponsive, with decorticate or decerebrate posturing
  • Intractable ICP is a contraindication for surgery.
  • Upper GI Endoscopy to stop active bleeding
  • Anemia is common secondary to blood loss, haemolysis from hypersplensim, anaemia of chronicillness, bone marrow depression or nutritional deficiency
  • MEASURE VISCOELASTIC PROPERTIES Of blood & predicts its tendenct to thrombousformation
  • Aspiration prophylaxis – H2 receptor blockerProkinetic agent PARTICULATE FREE ANTACIDS
  • Invasive arterial blood pressure monitoring is essential forProvides continuous monitoring of intra-arterial BP to see frequent hemodynamic changes usually secondaryto surgical manipulations such as caval clamping, sudden blood loss, hepatic reperfusionand providing access for blood sampling for ABG & coagulationtests.
  • duration of action are prolonged
  • Muscle relaxantsvecuronium bromide and rocuronium as neuromuscular blocking agents provide optimalConditions. Musclerelaxants have been used as a probe to evaluate the function ofthe newly implanted liverThe new liver graft may be evaluated by vecuronium since the time for thereturn of a train-of-four (TOF) with a nerve stimulator correlates with the function of thenew liver (Lukin et al, 1995)
  • Desflurane has the advantage of being least hepatic metabolism and providing rapid emergence
  • 37 C at a rate of 1.5L/min
  • Complexity of surgery cause rapid fluid shift, blood loss. HaemodMANAGEMENT VARIES IN ALL THE PHASES & MUST BE VIGIL
  • There is no ideal crystalloid solution and all have limitations; normal saline (0.9% NS) causes hyperchloremic acidosis while the lactate in Ringers Lactate (RL) requires liver metabolism for its elimination. Hydroxyl ethyl starches (modern low-molecular weight) and Gelatins in liver transplant has not been supported by convincing evidence. Furthermore, these may affect the coagulation profile
  • Red blood cells aretransfused to maintain a haematocrit around 30%. FFP is given tomaintain the prothrombin time below 1.2-1.5 times normal andplatelets are kept above 50X109 L-1.
  • Diminished hepatic glycogen stores as well asimpaired gluconeogenesis in patients with liver disease may result insevere hypoglycaemia. Hence high dose IV glucose infusions mustbe continued during patient transport as well as intraoperatively, andblood glucose concentrations should be measured frequently duringsurgery.
  • Decompensation occurs with fall in MAPMAP is usuallymaintained for up to 1 h because of increased heart rate and acompensatory increase in SVR
  • Diminished hepatic glycogen stores as well asimpaired gluconeogenesis in patients with liver disease may result insevere hypoglycaemia. Hence high dose IV glucose infusions mustbe continued during patient transport as well as intraoperatively, andblood glucose concentrations should be measured frequently duringsurgery.
  • changes related toreperfusion may be decreased by using the piggy back technique contributing to a side-biteof IVC allowing the venous return to continue
  • Prostaglandin E1 is administered at a rate of 0.3-0.6 mg/kg/h inthe post anhepatic portion of the surgery as a hepatic and renalcytoprotectiveagent,improving blood flow.
  • Fast-tracking’ defined as tracheal extubation at theconclusion of surgery before leaving the operating roomEarlyextubation in selected patients has shown toimprove early graft function and reduce duration of stayin the Intensive Care Unit and nosocomial infections
  • The requirements for blood transfusion continues also in the postoperativeperiod.
  • Liver transplantation & its anaesthetic management

    1. 1. Liver Transplantation & its Anaesthetic Management Dr. Swadheen kumar Rout 2nd year P.G Dept. of Anaesthesiology M.K.C.G College & hospital
    2. 2. Introduction:-  Liver transplantation is the only life saving procedure in pts. with end – stage liver disease & some cases of acute liver failure. Orthotopic Heterotopic  First orthotopic liver transplant was performed by Dr Thomas Starzl in 1963.  Patient was a 3 year old child with biliary atresia, who died in the operating room from massive haemorrhage caused by venous collaterals & uncontrollable coagulopathy.  However with continued improvements in Organ preservation technique, Surgical technique, Immunosuppressive agents, Management of  Has become highly successful in prolonging survival & improving coagulopathy,in affected patients. quality of life Treatment of
    3. 3.  Data from the United Network for Organ Sharing (UNOS) on 24,900 ad patients undergoing liver transplantation in a 10 year study showed tha yr, 4-yr, and 10-yr patient survival rates were 85%, 76%, and 61%, respectively,  Survival (%) after adult liver transplantation by thus confirming that liver transplantation results in prolongation of life. diagnosis* Diagnosis 1-yr 4-yr 10-yr Primary sclerosing cholangitis 91 84 78 Primary biliary cirrhosis 89 84 79 Autoimmune hepatitis 86 81 78 Chronic hepatitis C 86 75 67 Alcoholic liver disease 85 76 63 Cryptogenic cirrhosis 84 76 67 Chronic hepatitis B 83 71 63 Malignancy 72 43 34  Liver transplantation can be performed in patients of all ages. Paediatric liver transplantation has a better survival rate (10-yr = 80–
    4. 4. Indications for liver transplantation: Acute liver failure Acute hepatitis A,B,C infection Drug/toxin hepato-toxicity  Cirrhosis from chronic liver diseases Chronic hepatitis B virus and chronic hepatitis C virus infection Alcoholic liver disease Autoimmune hepatitis Cryptogenic liver disease Primary biliary cirrhosis and primary sclerosing cholangitis  Metabolic Disorders Alpha-1 antitrypsin deficiency Hereditary haemochromatosis Wilson‟s disease Glycogen-storage disorders Type 1 hyperoxaluria Familial homozygous hypercholesterolemia  Malignancy Primary hepatic cancer: hepatocellular carcinoma and cholangiocarcinoma Metastatic: carcinoid tumors and islet cell tumours  Miscellaneous Polycystic liver disease Budd-Chiari syndrome
    5. 5.  The decision to list a patient for transplantation is based more on the severity of hepatic dysfunction than the underlying aetiology.  Determining the need for liver transplantation must take into account the natural history of the patient‟s disease and carefully compare it to the anticipated survival after liver transplantation.  Priority is based on specific prognostic criteria using a number of scoring systems devised by United Network for Organ Sharing (UNOS) for optimal use of the limited number of available organs.  In the past Childs-Turcotte-Pugh (CTP) score plus the amount of time on the waiting list.  For listing purposes, a patient must have at least 7 points (i.e, be at least a Child‟s class B),
    6. 6.  However this did not always ensure that organs were allocated to the sickest patients with the greatest risk of mortality.  In 2002, model for end-stage liver disease (MELD) , based on the patient‟s risk of dying while awaiting transplantation.  The MELD risk score is a mathematical formula based on the following factors: 1) Creatinine 2) Bilirubin (mg/dL) 3) International normalized ratio  Most patients on the liver transplant waiting list have a MELD score between 11 & 20.
    7. 7.  Pediatric End-Stage Liver Disease (PELD) scoring system incorporates the following criteria(<12 yr) 1) Albumin: 2) Total bilirubin (Growth failure is calculated based on 3) INR age 4) Growth failure and gender using the current WHO growth chart) PELD score = 0.436 (age) – 0.687 x Log e (albumin g/dL) + 0.480 x Log e (total bilirubin mg/dL) + 1.857 x Log e (INR) + 0.667 (growth failure)
    8. 8. Contraindications to Liver Transplantation: Absolute contraindications Brain death Extrahepatic malignancy Active uncontrolled infection Active alcoholism and substance abuse AIDS Severe cardiopulmonary disease Uncontrolled sepsis Anatomic abnormalities precluding liver transplantation Compensated cirrhosis without complications  Relative contraindications Cholangiocarcinoma Portal vein thrombosis Psychologic instability
    9. 9. Anaesthetic importance: According to (UNOS) most deaths occurred within the first week following OLTX, and the most common causes of death during that interval were cardiovascular disease (28.2%), operative mortality (14.6%), primary graft failure (13.5%), and haemorrhage (13.0%).  The disease process causes major patho-physiological changes in all other organ systems,hence requiring a thorough examination of the recipient and a carefully scheduled anaesthesia to reduce morbidity & mortality during & after the procedure. Anaesthetic management Living donors Recipients
    10. 10. Anesthetic management of the living donors:Careful selection of donors (physically & psychologicaly stable) Organ Matching (ABO compatible)  For successful transplantation of the liver, it is necessary to provide excellent conditions for the donor especially during harvesting (i.e removal) while preserving optimal hemodynamic parameters.  By maintaining sufficient organ perfusion, adequate cardiac output, avoiding excessive bleeding, keeping hematocrit at about 30% and preventing coagulopathies.  Invasive monitoring is obligatory to ensure sufficient organ perfusion. Many protocols suggest a central venous pressure (CVP) below 5 cm H20 reduce blood loss & graft oedema.  Harvesting is only half the job done & anaesthesiologist plays a vital role both in successful recovery of the living donor and the donor liver.
    11. 11. Anaesthetic management of the recipients: Preoperative evaluation:-selection of appropriate and perfectly The prepared recipient is the gold standard for the success of liver Multi-disciplinary approach transplantation. Tests to Exclude Contraindications: Prior assessment Infectious disorders : HIV, syphilis, EBV, & tests cytomegalovirus, toxoplasmosis Malignancy : Colonoscopy, ERCP Anaesthesist role (cholangiocarcinoma) In HCC: bone scan, lung CT (metastatic work-up) Screening (colon, breast,cervical, prostate cancer) Complexity of the operationDisturbed patho-physiology of all major organ systems Decides recipient fit Requires medical manageme Proper planning Successful transplantation
    12. 12. Patho-physiological changes & its evaluation: Most of the recipients have End stage liver disease, Secondary dysfunction of virtually all other organ system(CNS,CVS) Metabolic derangement Anaesthetic Complications  One must have sound knowledge of these changes which dictate planning of anaesthetic management during the entire peri-operative period
    13. 13. Respiratory system:- Pulmonary complications associated with liver disease include: results a) Restrictive Lung Disease: from ascites or pleural effusion and management involves removal of this fluid. Triad of b) Hepatopulmonary syndrome (HPS): liver disease, hypoxaemia, (Pao2 <70 mm Hg) and right to left shunt due to Intrapulmonary Vasodilation. Patients are more prone to hypoxia ,ventilation-perfusion mismatch, diffusion derfects however liver transplantation is not contraindicated. c) Portopulmonary hypertension(POPH):  Best defined as pulmonary artery hypertension (PAH) associated with portal hypertension whether or not that portal hypertension is secondary to underlying liver disease. The diagnosis of POPH is defined as a mean pulmonary artery pressure >25 mm Hg in the presence of a normal pulmonary capillary wedge pressure. progress rapidly and carries high  Portopulmonary hypertension may perioperative morbidity and mortality when significant. Pulmonary hypertension responding to
    14. 14. Assessment of the patient`s pulmonary system:1) Chest radiography 2) Lung function tests 3) Arterialial blood gas analysis(ABG) 4) Occasionally MAA( microaggregated albumin) scan - quantify intrapumonary shunting
    15. 15. Cardiovascular system: Patients with end-stage liver disease develop a hyperdynamic circulation characterized by increased cardiac output and arteriolar vasodilatation, systemic vascular resistance(SVR) is low.  This condition has been attributed to sympathetic nervous system overactivity, inadequate clearance of vasoactive substances (bypassing the liver due to ventricular dysfunction may occur secondary to  Right decreased hepatic function). portopulmonary hypertension(POPH).  Another important consideration in adults undergoing transplant is the preoperative evaluation for ischaemic heart disease .  Cirrhotic cardiomyopathy characterized by abnormal or blunted cardiovascular response to stress, is present in as many as 50% of the patients undergoing liver transplant.
    16. 16. Assessment of the patient`s cardiovascular system:Routinely, 1) Electrocardiogram (ECG ) & 2) Echocardiography (ECHO) useful in identifying ventricular dysfunction, valvular pathology, pulmonary Hypertension Special tests like 3) Pharmacologic stress tests: dobutamine stress echocardiography (DSE) / myocardial perfusion scan. 4) Coronary angiography: Test myocardial function (Ischaemic heart disease)
    17. 17. Renal System: Renal function is an important predictor of survival with chronic liver failure and liver transplantation.  Diagnosing HRS requires the absence of primary renal disease, proteinuria, ↑ levels of endogenous vasodilators nephrotoxins, hypovolemia, or hemodynamic causes of renal peripheral vasodilatation + hypoperfusion. low blood pressure  A urinary sodium level <10 mEq/L or a hyperdynamic fractional excretion of sodium <1% ,with a circulation ctivation of the sympathetic creatinine level of more than 1.5 mg/dL & a nervous system & RAAS urine volume of less than 500 mL/day is Routinely Vasoconstriction required for diagnosis. ,BUN & Serum urea, creatinine End stage liver disease Renal hypo-perfusion electrolytes Hepatorenal syndrome(HRS)
    18. 18. Central nervous system: Any organic disease, that contributes to the changes in cerebral functions is a contraindication for liver transplantation.  Hepatic Encephalopathy -hepatic clearance failure leads to accumulation of toxins such as ammonia, GABA & other neuroactive substances. exclude a pre-existing organic disease mimicing hepatic  In order to encephalopathy, EEG, stimulated potential tests & CT Scan are recommended. Grade 0 Normal Grade 1 Altered spatial orientation, sleep patterns and affect Grade 2 Drowsy but arousable, slurred speech, confusion, asterixis Grade 3 Stuporous, responsive only to painful stimuli Grade 4 Unresponsive, with decorticate or decerebrate posturing
    19. 19.  Patients with grade IV encephalopathy may develop cytotoxic and vasogenic cerebral oedema with associated increase in intracranial pressure (ICP).  In such patients, intracranial pressure monitoring and first line therapy with mannitol should be instated when ICP is greater than 25 mm refractory to mannitol, the following may be considered in the  If Hg. following order based upon ease and safety of administration, and efficacy based upon the available literature. 1) hypertonic saline, 2) induced moderate hypothermia 3) barbiturate coma 4) indomethacin  A cerebral perfusion pressure >60 mmHg must be maintained. Intractable ICP is a contraindication for surgery.  In pre-encephalopathic patients benzodiazepines can precipitate encephalopathy & should be avoided.
    20. 20. Gastrointestinal System:Portal hypertension Upper GI Endoscopy Oesophageal Varices. Blood in stomach Ascites Delayed gastric emptying Patient considered full stomach Aspiration prophylaxis pre-medication
    21. 21. Haematological system: Anaemia is common secondary to blood loss, haemolysis from hypersplenism, anaemia of chronic illness or nutritional deficiency  Thrombocytopenia due to portal hypertension-induced splenic sequestration and alcohol or sepsis induced bone marrow suppression isIn ESLD balance between prohaemostatic & antihaemostatic  common. mechanisms is impaired.  Levels of procoagulant factors (II, V, VII, IX, X) and anticoagulant factors (protein C and S, antithrombin III) are frequently decreased.  There is a correlation between the severity of preoperative coagulopathy and Intra-operative requirement for blood and blood products; as the severity increases, requirements are increased.
    22. 22. Tests for haemostatic status:1) Bleeding time (BT) 2) Prothrombin time (PT) 3) Activated partial thromboplastin time (APTT) 4) Platelets count 5) Thmromboelastogram (TEG)  Administration of fresh frozen plasma (FFP), vitamin K, platelets and other blood products before the surgery should be considered. However no special preoperative coagulation management is necessary in the absence of bleeding.  Optimisation of electrolytes, intravascular volume status, coagulation, nutritional and infection status of recipient preoperatively is essential to decrease the risk of peri-operative complications or death.
    23. 23. Preoperative Preparation: Blood bank services should have sufficient packed cells/whole blood/platelets/cryoprecipitate and FFP`s in stock. Some centres recommend up to 24 units of each be available per transplant case with a minimum of 2-10 units immediately available in theatre.  Lab services should be immediately available for blood sampling of ABG`s and coagulation studies including platelet count, PT, APTT, TEG ,etc.  Preparation of the operating theatre includes the following 1) Warm room to 21-26 °C 2) Fluid warming devices 3) Forced air warming device 4) Rapid fluid infusion systems 5) Blood salvaging devices (eg cell saver) 6) Antibiotics prepared: Tazocin 4gm + Flagyl 500mg 7) Syringe pumps 8) Emergency Drugs: norepinephrine , epinephrine, atropine, calcium, dextrose, insulin, lignocaine
    24. 24. Premedication: One large bore peripheral venous access secured for premedications & induction  Aspiration prophylaxis – H2 receptor blocker Prokinetic agent Particulate free ANTACIDS  Intramuscular injections should be avoided in patients with coagulopathy.  Sedative premedication can be given as long as pt. does not have encephalopathy.
    25. 25. Intra-operative Management:Haemodynamic monitoring is essential for successful Monitoring: liver transplantation  Routine monitoring should be established pre-induction. • • • • • ECG Pulse Oximetry Capnography Temperature Urine output  Invasive monitoring can be established post-induction. • Arterial Catheter • Central Venous Catheter • Pulmonary Artery Catheter • Transesophageal Echocardiography
    26. 26.  Invasive arterial catheter is essential to provide continuous monitoring of intra-arterial BP to see frequent hemodynamic changes usually secondary to surgical manipulations such as caval clamping, blood loss, hepatic reperfusion.Provides access for blood sampling for ABG & coagulation tests.  Central Venous Catheter(CVC) / Pulmonary Artery Catheter(PAC) provide information to aid the maintenance of intravascular volume and the need for vasopressors to maintain adequate perfusion pressures. PAC is considered gold-standard but has its own limitations. (invasive & induced ventricular arrythmia)  Transoesophageal echocardiography (TEE) is non invasive , hence preferred nowadays. It provides real time monitoring of ventricular filling and contractile function. This information may guide the administration of i.v. fluids as well as inotropic drugs. In addition, intracardiac microthrombi/air emboli may be observed during dissection or hepatic reperfusion. Contraindication - varices.
    27. 27. Induction of Anaesthesia:  A routine rapid sequence induction with cricoid pressure should be performed because of the risk of aspiration.  All ETT should be placed orally. Nasotracheal intubation is contraindicated as it may cause bleeding, especially in the presence of coagulopathy and thrombocytopenia. Choice of anaesthetic agents:
    28. 28. Drug metabolism:  Drug elimination half-life is a function of clearance and volume of distribution.  Decrease in albumin levels results in intra and extravascular volume changes, leading to an increase in distribution volume of drugs (e.g. neuromuscular blocking agents(highly ionised)-duration of action prolonged).  There may be a prolonged duration of action for succinylcholine as a result of reduced levels of pseudocholinesterase, but it is rarely of clinical consequence.  End stage liver disease results in diminished hepatic drug clearance due to reduced hepatic blood flow and hepatic extraction ratio.  Clearance of drugs with a high hepatic extraction ratio (morphine, pethidine ) is diminished when hepatic blood flow is compromised. Hence these drugs should have a dosage decreased but not a decrease in frequency of dosing.  One must have sound knowledge of drugs pharmacokinetics & pharmacodynamics with respect to liver disease.
    29. 29. Induction of Anaesthesia:  A routine rapid sequence induction with cricoid pressure should be performed because of the risk of aspiration.  All ETT should be placed orally. Nasotracheal intubation is contraindicated as it may cause bleeding, especially in the presence of coagulopathy and thrombocytopenia. Choice of anaesthetic agents:  Propofol - An excellent choice - short half-life even in patients with decompensated cirrhosi (considerable extra-hepatic metabolism). - It should be remembered that sensitivity to the sedative & cardio respiratory effects of propofol are increased in liver failure & so the dose should be reduced.
    30. 30.  Thiopentone - A reduced dose is again needed, as reduction in plasma proteins causes an increased unbound fraction of the drug. The distribution half life and duration of action are also prolonged.  Ketamine - is highly extracted by the liver and not significantly bound to albumin leading to a variable clearance depending on the degree of synthetic liver function.  Etomidate can also be used. Muscle relaxants:  All non-depolarizing agents have been used successfully in liver transplantation as long as appropriate neuromuscular monitoring is performed.  Atracurium and cisatracurium are metabolized independent of the liver and are therefore preferred in patients with liver disease.  Vecuronium and rocuronium also provide optimal conditions, (increase requirement of first dose of nondepolarizing muscle relaxants & prolong duration of their action).
    31. 31. Maintenance of anaesthesia: A balanced anaesthetic is used which consists of a volatile agent in low to moderate concentrations (0.5–1 MAC) in an air-oxygen mixture to ensure unconsciousness, while an opioid, is chosen to blunt the sympathetic response to stimulation.  Nitrous oxide should be avoided, in order to minimize gaseous distension of the bowel & to avoid its effect on expansion of venous air emboli which may occur during the procedure Maintenance of blood flow to the liver is crucial once Volatile agentthe new allograft has been transplanted.  Nearly all volatile anaesthetic agents reduce cardiac output and MAP, hence reduce hepatic blood flow.  Isoflurane has been the volatile agent to be preferred because of its vasodilation effect on hepatic circulation, preserving splanchnic blood flow better than the others;(advantageous for the reperfused graft)  Different studies give conflicting reports on desflurane & sevoflurane effect on hepatic blood flow.
    32. 32. Opioids:-  Elimination of morphine is delayed in cirrhotic patients due to reduced hepatic blood flow and extraction ratio.(accumulation of the active metabolite morphine-6-glucuronide occurs).Morphine may therefore precipitate encephalopathy and possibly best avoided in severe liver dysfunction.  Fentanyl, Sufentanil & Remifentanil are commonly used as their clearance is unaffected.  Following induction - Invasive monitoring  Positioning & Padding.  Orogastric tube insertion.  Multiple venous access.  Antibiotic adminstration.
    33. 33. Haemodynamic management: Complexity of surgery cause rapid fluid shift, blood loss. Haemodynamic stability is essential intra-op to maintain perfusion to vital organs & successful transplantation.  The transplant operation can be conceptualized as consisting of three phases: 1). hepatectomy (liver removal, Pre-anhepatic) phase, 2). Anhepatic (no liver) phase, and 3). post implantation(Post anhepatic) phase.
    34. 34. Pre-anhepatic phase: Begins with surgical incision and ends with cross-clamping of the portal vein, the suprahepatic inferior vena cava(IVC), the infrahepatic IVC, and the hepatic artery. This phase involves dissection and mobilization of the liver. Drainage of ascitic fluid Hemodynamic instability Transection of large varices Surgical manipulation obstructing venous return  Hypotension is initially due to drainage of ascites, resulting in hypovolemia. Hypovolemia should be treated in an anticipated fashion with colloid containing fluid to minimize changes in preload . (Ringer acetate solution + Albumin is on the vasopressor of choice in maintaining the  No evidence to date administered routinely at 10 mL/ kg/ h.) blood pressure during OTLX. Epinephrine, norepinephrine & dopamine have all been Used.
    35. 35.  In this period of liver transplantation the primary issue is surgical bleeding. Degree of pre-existing coagulop Severity of portal hypertension Complexity of the surgical proc  Several approaches have been applied to manage this problem: 1) Pre-operative autologous blood donation, 2) Erythropoietin administration, 3) Intra-op isovolemic hemodilution, 4) Blood salvage techniques 5) Maintenance of low intra-op central venous pressure(CVP < 5 cm H2O)  6) Preventing hypothermia-induced coagulation abnormalities and Monitoring coagulation parameters by PT, APTT, fibrinogen platelet counts & thromboelastography(TEG).  The administration of FFP, RBCs, platelets, & cryoprecipitate remains the mainstay of therapy .  Excessive treatment of coagulopathy is not usually recommended at this phase unless bleeding is extreme .Aggressive correction of the coagulation status may lead to hypervolaemia & diilutional coagulopathy.
    36. 36.  Red blood cells are transfused to maintain a haematocrit around 30%. FFP is given to maintain the prothrombin time below 1.2-1.5 times normal and platelets are kept above 50X109 L-1.  Diuretics can be used to maintain euvolemic conditions and reduce transfusion requirements.  Mannitol 20% IV bolus (0.3–0.5 g/kg) prior to venous clamping, with its potential for free radical scavenging and antioxidant properties, helps to remove free water in the abdominal organs & provides renal protection.  Overall use of blood products during liver transplantation has been significantly reduced in recent years because of improved surgical technique, intra-op management, and patient selection.
    37. 37. Anhepatic phase: Starts with the occlusion of blood inflow to the liver and ends with graft reperfusion, when the IVC and portal vein clamps are removed with or without unclamping of the hepatic artery.(interpositional anastomosis) cava is occluded Inferior vena VENOVENOUS BYPASS (VVB) overcomes the pro  If VVBP is not used, volume loading with a target CVP of 10 to 20 mm Hg & small doses of vasopressors are ↓ CO and hypotension needed before the infrahepatic and ↑ Distal venous pressure suprahepatic venacaval clamps are placed to prepare for the anhepatic phase. Increase bleeding, Loss of venous return Renal hypoperfusion The majority of patients will tolerate IVC clamping for a period of about one hour. MAP is usually maintained for up to 1 h because of increased heart rate and a compensatory increase in SVR.
    38. 38. Venovenous Bypass (VVB): This involves the extracorporeal divertion of blood from the venous system below the caval clamps (inferiormesenteric and femoral veins) to the central veins (axillary or internal jugular veins) via a centrifugal pump and heparin bonded tubing.  In the past, a greater than 50% reduction in cardiac output after vena cava clamping was considered an indication for VVBP. The decision of using VVB depends on medical team experiences, preferences Disadvantages:Advantages:- and judgement. 1) Improved hemodynamic stability, 2) Improved perfusion of organs during anhepatic phase, 3) Decreased RBCs and fluid requirements 4) Renal protection, 5) Reduced incidence of pulmonary edema. 1) No evidence that it improves outcome 2) Vascular access related complications - pneumothorax, - lymphoceles, - hematoma formation, - air embolism, - major vascular/ nerve injury, - vessel thrombosis
    39. 39.  Close observation of serum electrolytes (Sodium, pottasium & ionised ca & ABG is essential and should be kept within normal limits.  Calcium chloride administration during the absence of hepatic functions avoids citrate intoxication related hypocalcemia associated with infusion of citrate rich blood products.  Acid metabolites originating from intestine cannot be cleared in the absence of liver, resulting in progressive acidosis. Sodium bicarbonate therapy should be guided by ABG analysis, because excessive administration may result in hypernatremia, hyperosmolality and metabolic alkalosis.  Due to absence of a liver produced plasminogen activator inhibitor, fibrinolysis may begin during this phase. During this phase platelets and coagulation factors continue to decrease.  Antifibrinolytic strategies differs among centers, used if there is evidence of fibrinolysis and there are no contraindications for its use. . Epsilon aminocaproic acid Tranexamic acid
    40. 40. Post Anhepatic Phase:-(Reperfusion phase)  The onset of this phase is heralded by the unclamping of the portal vein and IVC , with reperfusion of the new liver.  The most critical part of the reperfusion phase is the period immediately after the vascular clamps are removed from the liver graft. Significant hemodynamic instability like bradycardia, ventricular dysrhythmias and cardiac arrestmajor anaestheticseconds to minutes of unclamping.  The can occur within issue during this phase is that of “postreperfusion syndrome.” The hallmark of the postreperfusion syndrome (PRS) is systemic hypotension(at least 30% decrease) for more than 1 min with or without pulmonary hypertension occurring within the first 5 minutes after reperfusion of the graft and anesthetic management is directed at maintaining or recovering cardiovascular stability.  These changes are provoked by the rapid infusion of effluent from the transplanted liver, which is high in potassium and low in pH & temperature.
    41. 41. Some steps to manage the cardiovascular instability 1- Continuous Monitoring of BP. 2- Norepinephrine infusion to be started. 3- Blood and colloid infusion by rapid infusion system. Retrograde flushing with the recipient's blood by the surgeon prior to reperfusion(`blood flush') reduces the potassium concentration and acid content of the effluent(Flushing has been shown to decrease the incidence of post reperfusion cardiac arrest). 4- Epinephrine and atropine should be at hand for treatment of bradycardia. 5- Calcium chloride should also be continued. 6- Sodium bicarbonate, dextrose 25% and insulin should be readily available to rapidly treat acidaemia and hyperkalaemia. 7- After complete revascularization of the allograft, methylprednisolone (10mg/Kg) is administered as immunoinduction. 8- Maintenance of temperature is important because it plays a vital role in optimizing the function of the coagulation system.
    42. 42.  Prostaglandin E1 is administered at a rate of 0.3-0.6 mg/kg/h in the post anhepatic portion of the surgery as a hepatic and renal cytoprotective agent, improving blood flow to the graft..  This reperfusion of the graft is associated with restoration of electrolyte and acid base balance.  Signs of liver function which may be seen in the operating room are decreased calcium requirements, improvement in acidosis, increased urine output, rising core temperature and biliary output from the graft.  As the graft begins functioning the coagulopathy gradually improves. Fibrinolysis and heparin effect ceases within 2 hours, coagulation factors and platelets begin to increase toward baseline levels; PT and APTT reach their baseline values within a few days.
    43. 43. EXTUBATION: Postoperative tracheal intubation is no longer mandatory as long as significant respiratory compromise or concern for airway protection is absent, and established criteria for extubation are fulfilled.  „Fast-tracking‟ defined as extubation at the conclusion of surgery before leaving the operating room in selected patients has shown to improve early graft function and reduce duration of stay in the ICU and nosocomial infectio  Selection of patients for early extubation depends on duration of the surgery, coagulation profile, amount of blood and products transfused, patients‟ pre-operative status (MELD score), and status of the graft.  Regardless of whether the patient is extubated in the operating room, most centers admit patients to the ICU for close monitoring purposes.
    44. 44. Postoperative Care: Frequent assessment of cardiac and pulmonary function, serum glucose and electrolytes, renal and liver functions , coagulation status and the blood count is crucial.  Adequate Pain control , prevention of shivering & hypothermia to avoid excessive sympathetic nervous system stimulation.  The requirements for blood transfusion continues also in the postoperative Period. If ongoing bleeding, despite correction of coagulopathy & rewarming of the patient especially if hemodynamic instability & oliguria are present, the patient should undergo immediate reoperation to identify and stop the ongoing Liver Function-Favourable signs regarding hepatic function in the immediate bleeding. Haematocrit maintained between following: postoperative period include the 0.26 & 0.32. . 1. Hemodynamic stability 2. Clearance of lactate 3. Resolution of hypoglycaemia 4. Normalization of coagulation profile 5. Resolution of elevated liver enzymes. 6. Good renal function