Version June 2024
INTRODUCTION — This topic will discuss preanesthetic consultation and preparations for patients undergoing liver transplantation.
Anesthetic management during the intraoperative and early postoperative periods is discussed separately. (See "Liver transplantation: Anesthetic management".)
Patient selection, evaluation, and pre- and postoperative medical management of liver transplant recipients are discussed in separate topics. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation" and "Liver transplantation in adults: Long-term management of transplant recipients".)
Donor selection after brain death and living donor liver transplantation are also addressed in separate topics. (See "Liver transplantation in adults: Deceased donor evaluation and selection" and "Living donor liver transplantation in adults".)
PREANESTHETIC CONSULTATION
Indications and timing for preanesthetic consultation — Transplant recipients may be assessed by an anesthesiology consultant at the time of listing for transplant, especially for planned living donor liver transplantation. However, in some liver transplantation centers, potential recipients are not seen by the anesthesiology team prior to the immediate preoperative period. Patients with high Model for End-stage Liver Disease (MELD) scores and patients admitted to the intensive care unit prior to transplantation are evaluated by the transplant anesthesiology team as early as possible to assess perioperative risk and participate in ensuring optimal clinical status before transplantation. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation" and "Model for End-stage Liver Disease (MELD)".)
Consultation with the surgeon in the immediate preoperative period is necessary to allow appropriate preparation for the specific surgical techniques planned for the anhepatic phase. Specifically, timing of transplant, donor quality and use of veno-venous bypass and/or continuous renal replacement therapy should be discussed. (See "Liver transplantation: Anesthetic management", section on 'Specific surgical techniques'.)
Notification of the transfusion medicine service or blood bank facilitates preparation for massive transfusion required during surgery. (See 'Availability of blood products' below.)
Liver pathophysiology: Anesthetic implications — Marked pathophysiologic changes occur with liver failure that directly affect anesthetic management. These are evaluated and documented during pretransplantation medical evaluations and are noted during the preanesthetic consultation. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation".)
Hematologic changes
Disorders of coagulation — Conventional preoperative coagulation tests (eg, prothrombin time, international normalized ratio) will be available in the preoperative period. However, the overall effect of various coagulation abnormalities varies in individual patients with end-stage liver disease [1-7]. Thrombin generation may be normal, abnormal with coagulopathy and bleeding, or exaggerated with hypercoagulability and thrombotic complications [3-6]. These forms of "rebalanced" hemostasis are not reflected in standard clotting tests. Furthermore, standard tests may be insensitive to moderate reductions in clotting factor levels, do not assess hyperfibrinolysis, and neglect the contribution of platelets to clot formation [1,2]. (See "Hemostatic abnormalities in patients with liver disease", section on 'Physiologic effects of hepatic dysfunction'.)
Viscoelastic testing provides in vivo assessment of clot formation and is often employed before and during liver transplantation to assess coagulopathy as well as likely hypercoagulability. (See "Liver transplantation: Anesthetic management", section on 'Blood and coagulation management'.)
●Coagulopathy can be present due to reduction in all liver-derived procoagulant factors (eg, factors V, VII, IX, X, and XI, fibrinogen, thrombin), with compensatory increases of extrahepatic factors [2,8]. Also, thrombocytopenia is common due to both decreased hepatic production of thrombopoietin and splenic sequestration of platelets in patients with portal hypertension [2,9] (see 'Cardiopulmonary changes' below). Furthermore, hyperfibrinolysis typically occurs during the transplantation procedure due to increased fibrinolytic activity and decreased hepatic clearance of tissue plasminogen activator (tPA) [10-13].
●Hypercoagulability with normal or exaggerated clot formation is present in some patients with end-stage liver disease, even those with thrombocytopenia. Anticoagulant factors (eg, antithrombin, protein S and protein C activity) and ADAMTS13 (a metalloprotease that cleaves high molecular weight von Willebrand factor [VWF]) are typically reduced in these patients, while VWF is elevated [14].
●Splenomegaly (ie, an enlarged spleen that is congested with blood) is common in patients with cirrhosis from nonalcoholic etiologies. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Splenomegaly'.)
Anemia — Anemia is often present, and its severity is noted, as this influences intraoperative decisions to transfuse salvaged or allogeneic blood during liver transplantation [15].
Anemia in liver disease is multifactorial. Causes may include:
●Bleeding (variceal or other)
●Chronic inflammation
●Iron deficiency
●Splenic pooling of blood in patients with portal hypertension and splenomegaly
●Hemodilution from fluid retention
●Vitamin deficiencies (folate, vitamin B12)
●Bone marrow suppression from medications
●Bone marrow suppression from alcohol in some individuals
●Hemolysis
Mechanisms are discussed in separate topics:
●(See "Anemia of chronic disease/anemia of inflammation".)
●(See "Hematologic complications of alcohol use", section on 'Anemia'.)
Cardiopulmonary changes — The pretransplantation cardiopulmonary evaluation performed by the liver transplant team assesses presence and severity of pulmonary hypertension, hepatopulmonary syndrome, restrictive or obstructive lung disease, right ventricular (RV) or left ventricular (LV) cardiomyopathy, coronary artery disease, or valvular heart disease. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation", section on 'Cardiopulmonary evaluation'.)
●Vasodilation and high cardiac output – A vasodilatory hyperdynamic state with low systemic vascular resistance (SVR) is typically present in patients with liver failure [16,17]. Notably, these patients respond to intraoperative administration of vasopressor agents (eg, vasopressin) in part because their endogenous arginine vasopressin levels may be inadequate [18].
Also, continuous low-level exposure to cytokines [19], as well as bacterial fragments [20,21], cause splanchnic hyperemia with pooling of blood in the splanchnic area. In addition, many patients have loss of intravascular volume due to ascites. Vasoconstrictors are activated via the sympathetic and renin-angiotensin-aldosterone systems as a compensatory mechanism to maintain blood pressure and organ perfusion by increasing intravascular volume, cardiac output (CO), and SVR in non-splanchnic organ beds [22-24].
●Pulmonary hypertension – A chronically high CO may cause pulmonary hypertension that is initially reversible, but some patients develop irreversible pulmonary hypertension (PH) and RV dysfunction [25]. Portopulmonary hypertension is defined as the presence of PH associated with portal hypertension [26]. Severity of PH is evaluated with echocardiography or by right heart catheterization to estimate RV systolic pressure during the transplant team's preoperative workup (see "Portopulmonary hypertension", section on 'Diagnostic evaluation'). Evaluation includes determining whether increases in pulmonary artery pressure (PAP) are primarily due to high CO with volume overload (which may improve with diuresis) or due to intrinsically increased pulmonary vascular resistance (PVR), and whether PH improves with pulmonary vasodilators (typically, inhaled nitric oxide). The anesthesiologist and all members of the transplant team are consulted when a patient with moderate or severe PH (ie, mean PAP >35 to 45 mmHg) is listed for liver transplantation. It is critically important to continue chronically administered medications throughout the perioperative period to ameliorate PH in such patients. Severe PH unresponsive to pulmonary vasodilators may preclude a patient from receiving a donor liver since perioperative mortality is high [26]. (See "Liver transplantation in adults: Patient selection and pretransplantation evaluation", section on 'Cardiopulmonary evaluation' and "Anesthesia for noncardiac surgery in patients with pulmonary hypertension or right heart failure", section on 'Management of chronic medications'.)
●Hepatopulmonary syndrome – Hepatopulmonary syndrome is characterized by portal hypertension and abnormal arterial oxygenation caused by intrapulmonary vascular dilatations and shunting [27]. Pretransplantation evaluation includes identification and assessment of transpulmonary shunts with transthoracic contrast echocardiography and a "bubble study" to determine whether hepatopulmonary syndrome is the primary cause of hypoxemia. (See "Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis".)
Intraoperative anesthetic management is not generally affected by mild-to-moderate symptoms of hepatopulmonary syndrome. Oxygenation typically improves when the patient is placed in the supine position or undergoes positive pressure ventilation. This occurs because increases in intrathoracic pressure cause compression of the intrapulmonary vasculature with decreases in abnormal transpulmonary shunting compared with the upright position and spontaneous ventilation [28]. However, severe hepatopulmonary syndrome may cause refractory hypoxia. (See "Extracorporeal life support in adults in the intensive care unit: Overview" and "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)".)
●Restrictive pulmonary defects – In some patients, marked ascites results in restrictive pulmonary defects. These may be exacerbated by pleural effusion (ie, hepatic hydrothorax) which is usually on the right side. Thoracentesis with drainage may be performed before transplantation for severe pleural effusion [29,30].
Hepatorenal syndrome — Some patients have hypoperfusion of the kidney resulting in renal insufficiency (ie, hepatorenal syndrome) due to the net effect of chronically low SVR, splanchnic hyperemia, and low intravascular volume (see 'Cardiopulmonary changes' above) [17,31,32]. Intraoperative exacerbation of renal insufficiency and acute kidney injury (AKI) can occur during liver transplantation [33]. (See "Hepatorenal syndrome".)
The use of the MELD score as an allocation tool for liver transplantation gives high preference to patients with renal dysfunction and as a consequence the number of combined liver kidney transplants has steadily increased over the last 15 to 20 years [34]. Continuous renal replacement therapy (CRRT) has been used for selected patients, as noted below (see "Hepatorenal syndrome", section on 'Kidney replacement therapy' and 'Use of continuous renal replacement therapy' below).
Some patients are candidates for simultaneous liver-kidney transplant surgery, as discussed in a separate topic [35,36]. (See "Kidney function and non-kidney solid organ transplantation", section on 'Approach in liver transplant candidates'.)
Esophageal pathology — Transesophageal echocardiography (TEE) is often used during liver transplantation [37]. (See "Liver transplantation: Anesthetic management", section on 'Monitoring considerations'.)
The presence of previously diagnosed gastric and esophageal varices is noted during the preanesthetic consultation [38]. Primary prophylaxis for esophageal variceal bleeding often includes the use of beta blockers, which may predispose patients to intraoperative hypotension (see "Primary prevention of bleeding from esophageal varices in patients with cirrhosis", section on 'Preventive strategies'). However, upper gastrointestinal (UGI) hemorrhage and other complications of TEE monitoring are rare in patients with end-stage liver disease, even among those with coagulopathy, thrombocytopenia, or esophageal varices [37,39-44]. Extra care with probe lubrication and insertion are appropriate to minimize this risk [45]. (See "Intraoperative transesophageal echocardiography for noncardiac surgery", section on 'Contraindications and precautions'.)
Obstructive sleep apnea — Patients who require liver transplantation due to non-alcoholic steatohepatitis (NASH) are likely to have metabolic syndrome and obstructive sleep apnea [46]. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults", section on 'Association with other disorders'.)
Planning for postoperative analgesia — Chronic opioid use is relatively frequent in patients waiting for liver transplantation [47]. In one study, postoperative opioid requirements were significantly higher in patients with preoperative opioid prescriptions in the first 24 hours (206 ± 319 versus 60 ± 34 mg) and at 7 postoperative days (57 ± 71 versus 19 ± 15 mg) compared with patients not using preoperative opioids [47]. Also, the incidence of chronic postsurgical pain was higher in those with preoperative opioid use (71 versus 46 percent).
Multimodal pain therapy has been suggested to decrease postoperative opioid requirements after liver transplantation; however, it is unclear whether such therapy also reduces chronic postsurgical pain [48,49].
Availability of blood products — Typing and crossmatching for an adequate number of blood products (eg, 10 units of red blood cells [RBCs], 10 units of fresh frozen plasma [FFP], 6 units of platelets [one platelet pack]) should be accomplished in the preoperative period as soon as the recipient is identified and arrives at the transplant center, especially if the patient has received prior transfusions or has been pregnant and may have developed alloantibodies.
TIMING FOR ANESTHETIC INDUCTION
Communication and coordination — Donor liver procurement (either cadaveric or living donor) is carefully coordinated to minimize the time from resection to implantation (ie, cold ischemic time). The recipient does not proceed to the operating room until the donor liver has been initially assessed to determine if its quality is adequate for transplantation. In some cases, timing of induction is influenced by whether the surgeon wants to visualize the graft or obtain a biopsy to ensure adequate graft quality prior to bringing the patient to the operating room.
During the preoperative period, regular communication between the anesthesiologist and the surgeon and/or transplant coordinator ensures optimal timing for induction of anesthesia. This is critically important because anesthetizing a patient with severe liver failure may precipitate deterioration of liver function and trigger acute-on-chronic liver failure from which the patient may not subsequently recover unless a high-quality donor liver has been implanted [50].
Cold preservation leads to liver injury over time. In general, cold ischemic times >12 hours may impact donor organ viability and graft survival, but some poor-quality donor organs (eg, donation after cardiac death [DCD]) may not tolerate cold ischemic times >6 to 10 hours. (See "Liver transplantation in adults: Deceased donor evaluation and selection", section on 'Cold ischemia time' and "Liver transplantation in adults: Deceased donor evaluation and selection", section on 'Donation after circulatory death'.)
Final checking of blood products — All blood products should be available at the time of the incision. (See 'Availability of blood products' above.)
Preoperative fasting status — Since liver transplant recipients receive notification of a potential matched donor liver within hours of receiving the organ, preoperative fasting may be inadequate to allow for stomach emptying.
A transplant is not elective and cannot be postponed. If there is inadequate time to adhere to fasting guidelines, or if the patient has moderate to severe ascites, rapid sequence induction of anesthesia is performed (table 1). (See "Liver transplantation: Anesthetic management", section on 'Induction of general anesthesia' and "Rapid sequence induction and intubation (RSII) for anesthesia".)
SPECIAL SITUATIONS
Considerations for patient testing positive for the COVID-19 — For patients who contract COVID-19 while waitlisted for liver transplantation, a reasonable approach is to become inactive on the waitlist until they become asymptomatic and one (or two for higher sensitivity) COVID-19 nucleic acid amplification test (NAAT) has been negative. (See "COVID-19: Issues related to solid organ transplantation".)
Acute liver failure with increased intracranial pressure — Patients with acute liver failure and increased intracranial pressure (ICP) are at high risk for complications and poor outcome. In one study of such patients undergoing liver transplantation, 11.3 percent suffered death by neurologic criteria (“brain death”) during or shortly after surgery [51,52].
The American Association for the Study of Liver Diseases (AASLD) recommends a target cerebral perfusion pressure (CPP) of 60 to 70 mmHg, where CPP = mean arterial pressure (MAP) – ICP [53]. Any therapies for elevated ICP that were initiated in the preoperative period should be continued throughout the perioperative period. If an ICP monitor is in place, monitoring is continued throughout the perioperative period to allow rapid identification and intervention for increases in ICP (eg, hyperventilation and/or administration of hypertonic saline) [54,55]. Other therapies may include administration of mannitol and/or hypertonic saline (eg, 2.7 to 3 percent solution) to achieve a blood sodium concentration of approximately 145 to 150 mEq/L. Some patients with acute liver failure and increased ICP undergo moderate cooling (32 to 33o C) in the preoperative period although effects on outcome are unclear [56-58]. If initiated in the preoperative period, moderate hypothermia should continue throughout the intraoperative period (and possibly postoperatively) to avoid rebound increases in ICP, even if coagulopathy is present. In selected patients, veno-venous (VV) bypass may be employed to avoid hemodynamic instability that may cause marked changes in CPP [59]. Furthermore, factors that may exacerbate neurologic injury (eg, hyperthermia, hyperglycemia) are carefully avoided. (See "Acute liver failure in adults: Management and prognosis", section on 'Intracranial pressure monitoring' and "Acute liver failure in adults: Management and prognosis", section on 'Induction of hypothermia'.)
Use of continuous renal replacement therapy — Chronic kidney disease is common in patients with liver disease. Recipient selection criteria for donor livers give strong preference to patients with severely impaired kidney function or kidney failure. Such patients may need either intermittent or continuous renal replacement therapy (CRRT) prior to transplantation.
Also, patients with severe kidney dysfunction who are not yet on dialysis may benefit from intraoperative CRRT. However, the volume of fluid removed is only approximately 300 mL/h, potassium clearance is inefficient and depends on effluent rate (dose), and lactate clearance is low during intraoperative CRRT because the technique corrects acidosis primarily by including bicarbonate in the dialysate [60-62]. In addition, sodium levels must be closely observed to avoid overly rapid correction in patients with severe hyponatremia [62]. (See "Kidney function and non-kidney solid organ transplantation", section on 'Approach in liver transplant candidates' and "Hepatorenal syndrome", section on 'Kidney replacement therapy'.)
CRRT is used in at least 35 percent of liver transplant centers in the United States [43,63]. Adequate dialysis access sites should be established before surgery commences if CRRT is planned.
Living donor transplantation — Anesthetic and surgical management for partial hepatic resection in a living liver donor and techniques for left or right liver lobe transplantation into the recipient are discussed separately. (See "Anesthesia for the patient with liver disease", section on 'Anesthesia for hepatic resection' and "Living donor liver transplantation in adults".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Liver transplantation".)
SUMMARY AND RECOMMENDATIONS
●Preanesthetic consultation – Includes assessment of pathophysiologic changes that occur with progressive liver failure and may directly affect anesthetic management:
•Hematologic – Coagulopathy with bleeding or hypercoagulability with thrombosis (or both) may be present, as well as anemia and splenomegaly. (See 'Hematologic changes' above.)
•Cardiopulmonary - Considerations include (see 'Cardiopulmonary changes' above):
-Cardiovascular changes produce a vasodilatory hyperdynamic state with likely requirements for intraoperative administration of vasoconstrictors such as vasopressin. (See 'Cardiopulmonary changes' above and "Liver transplantation: Anesthetic management", section on 'Hemodynamic and vasopressor management'.)
-Pulmonary hypertension (PH) with right ventricular dysfunction may be present. Severity and reversibility of pulmonary hypertension are noted, and chronically administered medications to ameliorate PH are continued throughout the perioperative period. (See 'Cardiopulmonary changes' above.)
-Patients with severe hepatopulmonary syndrome may have refractory hypoxia. Marked ascites results in restrictive pulmonary defects that are exacerbated by pleural effusion (ie, hepatic hydrothorax). Preoperative thoracentesis with drainage may be performed.
•Kidney disease – Chronic kidney disease (eg, hepatorenal syndrome) may be present due to the net effect of decreased renal blood flow due to chronically low systemic vascular resistance, splanchnic hyperemia, and low intravascular volume status. Intraoperative continuous renal replacement therapy (CRRT) is used by some centers to remove excess fluid, correct acid-base abnormalities, treat hyperkalemia, and correct severe hyponatremia. Adequate dialysis access sites are established before surgery commences if intraoperative CRRT is planned. (See 'Hepatorenal syndrome' above and 'Use of continuous renal replacement therapy' above.)
•Increased ICP – For patients with acute liver failure and increased intracranial pressure (ICP), therapies initiated in the preoperative period (eg, mannitol and/or hypertonic saline, hypothermia to 32 to 33°C) are continued during the perioperative period. If an ICP monitor is in place, monitoring is continued throughout the procedure to allow rapid identification and intervention for increases in ICP. (See 'Acute liver failure with increased intracranial pressure' above.)
•Varices – Esophageal or gastric varices are noted. Although not a contraindication to intraoperative use of transesophageal echocardiography (TEE) during liver transplantation, extra care with probe lubrication and insertion are appropriate. (See 'Esophageal pathology' above.)
●Timing– Donor liver procurement is carefully coordinated to minimize time from resection to implantation (cold ischemic time).
•Communication and coordination – Before transport of the patient to the operating room, preoperative communication with the surgeon and transfusion medicine service or blood bank is necessary to establish that the donor liver has been assessed and is of sufficient quality to be suitable for transplantation. (See 'Timing for anesthetic induction' above.)
•Availability of blood products – Typing and crossmatching for an adequate number of blood products (eg, 10 units of packed red blood cells [PRBCs], 10 units of fresh frozen plasma [FFP], 6 units of platelets [one platelet pack]) should be accomplished in the preoperative period. These products should be available in the operating room before surgical incision. (See 'Availability of blood products' above.)
•Fasting – Notification of a potential matched organ within hours of receiving the organ may not allow a preoperative fasting period adequate for stomach emptying (table 1); thus, rapid sequence induction is frequently necessary. (See 'Preoperative fasting status' above.)
●COVID-19 – For patients who contract COVID-19, a reasonable approach is to become inactive on the waitlist until they become asymptomatic and one (or two for higher sensitivity) COVID-19 nucleic acid amplification test (NAAT) has been negative. (See 'Considerations for patient testing positive for the COVID-19' above.)
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