| System
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Considerations
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| Neurologic
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- Patients with liver disease are at risk for encephalopathy.
- Mental status may be further depressed by coexisting metabolic derangements, including hyponatremia and hypoglycemia.
- The failure of hepatic clearance of various toxins, such as ammonia, can lead to alterations in endogenous neurotransmitters and neuro-signaling pathways, largely involving y-aminobutyric acid (GABA), glutamate and nitric oxide.
- Anesthetic requirements for patients with end-stage liver disease will often be reduced, due to underlying cerebral disturbances.
- Acute fulminant hepatic failure may be accompanied by elevated intracranial pressure and varying degrees of coma.
- Preoperative placement of intracranial pressure monitors may guide peri-operative neuroprotective strategies, with the goal to maintain adequate cerebral perfusion pressure.
- Patients may be unable to consent for surgery, and may exhibit delayed emergence following anesthesia.
- A thorough baseline neurologic and mental status exam is necessary prior to surgery, to assist with assessment following transplantation and anesthetic exposure.
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| Cardiovascular
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- Systemic circulatory changes result in a hyperkinetic blood flow in most vascular beds, resulting in increased cardiac output and elevated circulating blood volume. Nitric oxide, cannabinoids, and cGMP have been implicated in the pathogenesis of this state. This is often further associated with lower PVR to accommodate this dynamic circulatory state.
- Systemic vasodilation results from circulation of vasoactive mediators and vasodilators, as well as low grade endotoxin, which are not cleared by the compromised liver.
- Due to high circulating blood volume, many patients will have elevated filling pressures, reflected as high CVP, PCWP and PADP. However, transpulmonary pressure gradients are often normal.
- Decompensated liver failure is often accompanied by some degree of diastolic dysfunction, chronotropic incompetence and catecholamine insensitivity.
- A subset of patients will manifest signs of cirrhotic cardiomyopathy, further characterized by conduction abnormalities/rhythm disturbances, alterations in calcium handling at the myocyte level and depressed myocardial performance.
- A very small subset of patients will have pulmonary hypertension, a pathological condition defined as a mean pulmonary artery pressure (mPAP) of greater than 25 mm Hg at rest, with a PCWP less than 15 mm Hg, and elevated pulmonary vascular resistance. Portopulmonary hypertension (PPHTN) further includes presence of portosystemic shunt. It is essential for portopulmonary hypertension (PPHTN) to be identified early, as significant perioperative mortality exists in patients with severe disease (mPAP>45, with associated elevation in PVR). There is a general consensus that there is a marked risk of intra and postoperative mortality in patients with mPAP> 45 mm Hg and PVR that exceeds 250 dynes/s/cm-5 .
- Early referral for initiation of pulmonary vasodilators (ie prostacyclin, PDE5 inhibitor, endothelin antagonist) is recommended, to evaluate response to therapy/disease reversibility and candidacy for future liver transplantation. Associated right ventricular dysfunction may recover, but correlates with severity of pressure overload.
- Echocardiography is routinely performed to evaluate RV function, LV systolic function, and measure RVSP. In the presence of elevated RVSP, right heart catheterization will be performed to assess RV function, measure cardiac output, and determine presence of elevation in pulmonary vascular resistance. If the diagnosis of PPHTN is made, treatment can be initiated and transplantation may be deferred. A favorable response to vasodilators is ideal, as this indicates presence of a reactive pulmonary bed and confers potential therapeutic options in the event of a precipitous rise in pulmonary artery pressures intraoperatively (application of inhaled nitric oxide or epoprostenol).
- Dobutamine stress echocardiography is an ideal preoperative screening assessment, as it can identify metabolic imbalance and ischemic risk, as well as underlying structural abnormalities. This test has a negative predictive value of 92-97%, with a negative test predicting good prognosis and low likelihood of major adverse cardiac events (Donovan et al, 1996; Cotton et al, 2002). If ischemic changes are present, a left heart catheterization should be performed to determine presence of severe coronary arteriopathy that may warrant intervention (angioplasty/stent v revascularization) prior to transplantation.
- The presence of coronary artery disease is associated with higher morbidity and mortality (Plotkin et al, 1996).
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| Pulmonary
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- Pulmonary abnormalities are common in patients with advanced liver disease. Presence of intrapulmonary shunt, ventilation-perfusion defects, and abnormalities in lung compliance are frequently encountered. Many transplant recipients are of advanced age, and thus have changes in FRC, closing capacity, and lung elasticity which may result in challenges with ventilation and gas exchange.
- Restrictive lung disease, largely secondary to presence of ascites and pleural effusions, may be noted during positive pressure ventilation. Careful attention is necessary during induction of anesthesia, to optimize patient position and pre-oxygenation, to mitigate ensuing hypoxemia that may occur during brief apnea.
- Lung protective ventilation with appropriately calculated tidal volume (6-8 cc/kg PBW) and application of PEEP should be employed during surgery, to minimize ventilator induced lung injury.
- Hypoxemia may be present secondary to hepatopulmonary syndrome (HPS) which, if severe, may persist for months following transplantation.
- HPS may present as asymptomatic cyanosis, though patients often endorse platypnea and orthodeoxia. Etiology is likely related to elaboration of vasoactive mediators (ie nitric oxide), which result in formation of abnormal pulmonary vascular communications, resulting in A-V shunt. This diagnosis can be confirmed by echocardiogram with “bubble” study, which will reveal presence of bubbles/agitated saline in the left atrium, 3-5 cycles after injection. Some correction of hypoxemia with 100% oxygen confers a favorable post-operative prognosis.
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| Gastrointestinal
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- Portal hypertension is present in the majority of patients receiving liver transplantation. This may manifest as severe GI bleed, gastric and esophageal varices, ascites, and previous portosystemic shunts. All patients with decompensated liver disease are at risk for delayed gastric emptying and, as such, rapid sequence intubation is strongly encouraged. Close attention to ascitic drainage during dissection is essential, and volume replacement with colloid rich solution is generally pursued to minimize hemodynamic changes associated with rapid fluid shifts. The presence of severe cirrhosis and portal hypertension often leads to engorgement of collateral vessels in the splanchnic and portal circulation, which may increase risk of massive bleeding during the dissection phase and vascular/hepatic mobilization. Ongoing GI bleed may continue intra-operatively. Some clinicians advocate management with octreotide to mitigate bleeding risk. Appropriate blood product transfusions and volume replacement is necessary in response to signs of ongoing bleeding and hypovolemia.
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| Hematologic
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- The predominant hematologic abnormality in patients awaiting liver transplantation is anemia. This results from occult or clinical bleeding, malnutrition/malabsorption, hemolysis, and reduced production red blood cells production, often exacerbated by co-existing renal disease.
- Thrombocytopenia secondary to thrombopoietin deficiency and splenic sequestration is common in patients with portal hypertension, and functional platelet defects may be exacerbated by uremia.
- Coagulation defects result from reduced production of clotting factors and inhibitors, vitamin K deficiency, abnormalities in fibrinolysis, and reduced clearance of activated factors (Amitrano et al, 2002; Kawasaki at al, 1999; Ingeberg et al 1985; Rubin et al, 1979).
- Associated trauma (secondary to surgery), sepsis, bleeding, or shock, may result in secondary fibrinolysis and disseminated intravascular coagulation (DIC).
- Deficiencies in inhibitors and serine proteases, such as plasminogen activator inhibitor, may increase risk for thrombosis in certain patients.
- Many individuals with biliary disease and associated autoimmune pathology, may have concomitant hypercoagulable conditions, increasing risk of vascular thrombosis after re-perfusion.
- Due to the complexity of hematologic derangements, it is imperative to approach transfusion strategies in a data-driven and clinically influenced manner. Interpretation of TEG, as well as clinical bleeding or hypercoagulability in the surgical field, should be primary variables used to impact decisions regarding transfusion with plasma, platelets, cryoprecipitate and administration of recombinant synthetic factors.
- Catastrophic consequences of inappropriate transfusion strategies include hepatic artery thrombosis with subsequent graft failure.
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| Renal
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- Many patients with end-stage liver disease will have associated renal insufficiency or renal failure.
- Generally patients with chronic renal failure will be listed for combined liver-kidney transplantation.
- Etiology of renal failure is often multifactorial, and related to relative hypoperfusion of the renal bed with acute kidney injury, acute tubular necrosis related to medication administration (contrast, etc), and possible acute interstitial nephritis.
- Patients may carry the diagnosis of hepatorenal syndrome (HRS), which occurs as a result of intense renal vasoconstriction prompted by renin-angiotensin activation in response to profound splanchnic vasodilation. HRS is often reversible with liver transplantation.
- Some patients will require acute hemodialysis in the period prior to transplantation.
- It is essential to determine associated anuria/oliguria, clinical response to diuretic therapy, associated metabolic derangements, and volume status in this patient population. Patients may require dialysis prior to commencement of transplant.
- It is rare to utilize intraoperative RRT, however, acute changes in potassium secondary to transfusion and reduced clearance, may warrant this therapy.
- Our strategy to manage this select patient population involves: limitation of exogenous potassium administration, red blood cell washing by perfusion prior to administration, gentle supplementation with bicarbonate containing fluids, possible diuretic challenge, and close monitoring of electrolytes.
- Crystalloid administration may be limited in this patient population in the presence of clinical hypervolemia with associated portal hypertension.
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| Endocrine
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- A myriad of metabolic perturbations may be present in the liver transplant recipient.
- Hypoglycemia is common in patients with advanced disease, due to impairment in gluconeogenesis.
- Patients may require supplementation with dextrose prior to surgery.
- A sign of graft function in the neohepatic phase, is hyperglycemia/insulin requirement in response to steroid administration.
- Patients often present with impaired temperature regulation resulting in hypothermia, prior to reperfusion of the new graft.
- As previously detailed, careful attention to application of external body warmers and warmed fluid administration, is essential to maintain normothermia and optimize hemostatic conditions.
- On occasion, patients with severe portal hypertension may also present with hyponatremia. This can occur as a result of altered renal free water handling/elimination and water retention resulting from activation of ADH in the setting of splanchnic vasodilation. These derangements may be exacerbated by concomitant sodium dietary restriction and use of diuretic therapy.
- Rapid correction of sodium intra-operatively should be avoided, to reduce clinical risk of CPM. This may involve supplementation of solute-rich colloid administration with hypotonic fluids intra-operatively, to maintain baseline sodium levels.
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| ID
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- Patients with end-stage liver disease are at high risk of infections. Altered hepatic clearance and dysregulation of Kupffer cell function, combined with poor underlying nutritional status, result in a functional immunocompromised state.
- Not uncommonly, these patients are treated, at the time of transplant, for biliary infections, spontaneous bacterial peritonitis (SBP), aspiration pneumonia, or cellulitis. Active septicemia or severe infection without treatment/source control, are contraindications to transplant.
- Appropriate selection of antimicrobials is necessary, and should be guided by infection source, probable or confirmed infectious pathogens, and patient history (previous infectious culprits/colonization). Standard antimicrobial prophylaxis is: cefazolin/metronidazole, or cefotetan.
- If there is concern for SBP at the time of transplantation, or if donor variables present concerns for possible infection/contamination, antimicrobial selection should be adjusted accordingly.
- Re-dosing of antibiotics should be guided by agent selection, blood loss, and recipient renal function.
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