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  1. Planning the anesthetic must take into account the surgical procedure, type and severity of liver disease, and alterations to hepatic blood flow due to anesthetics. Meticulous attention must be paid to maintaining adequate hepatic perfusion and oxygen delivery. Both general and regional anesthesia techniques can decrease total hepatic blood flow. Episodes of perioperative hepatic ischemia (due to surgical manipulation or anesthetics) can exacerbate preexisting liver disease. Hypotension, hemorrhage, and vasopressors can compromise hepatic oxygenation delivery, resulting in increased postoperative hepatic dysfunction. Surgical traction and patient positioning can compromise hepatic blood flow. Positive-pressure ventilation and positive end-expiratory pressure may cause deleterious effects in hepatic venous pressure, resulting in decreased cardiac output and total hepatic blood flow. Hyperventilation should be avoided because hypocarbia can independently reduce hepatic blood flow.
  2. Many factors must be considered when choosing an anesthetic agent in the setting of liver failure such as drug distribution and metabolism, protein binding, and often concurrent renal insufficiency. Benzodiazepines should be avoided to avoid oversedation. Propofol is the preferred induction agent because of its redistribution, but can cause hypotension and vasodilation that may reduce hepatic perfusion. Maintenance with volatile agents is preferred because they are mainly eliminated via the respiratory system. Older halogenated compounds are absorbed more readily because of their lipophilicity and require more hepatic metabolism than newer agents such as sevoflurane and desflurane. Processed EEG monitoring should be considered as duration of action of various agents may be affected to altered liver metabolism and renal impairment.
  3. Neuromuscular blockade consideration is important given the different metabolism of various drugs noted earlier. Cisatracurium and atracurium are safe as they undergo Hoffman elimination. Considerations for renal dysfunction when must be assessed when using vecuronium and rocuronium. Mean time of recovery of TOF (train-of-four) ratio >0.9 in patients with liver dysfunction is not significantly different compared to patients with normal liver function with use of sugammadex reversal for rocuronium. Due to reduction of pseudocholinesterases, the action of succinylcholine may be prolonged in patients with liver disease. Patients with cirrhosis may exhibit a significantly elevated cardiac output, which will shorten the onset time of neuromuscular blockade agents; however, this is variable and should not change decision-making around choice of agents for rapid sequence intubation.
  4. Caution must be exercised when regional anesthesia is considered in a patient with liver disease. Coagulopathy and thrombocytopenia put these patients at a higher risk for epidural bleeding and hematoma formation. However, in a patient with well-compensated liver disease and a reasonably normal coagulation profile and platelet count, regional anesthesia may be appropriate and may even be beneficial, but this must be considered on a case-by-case basis. Particularly with epidural placement, postoperative transfusion of FFP or administration of vitamin K may be necessary to remove the epidural catheter, and this risk should be discussed with the surgical team. Additionally, there is also a theoretical concern of hypotension with epidural anesthesia; more recent studies have demonstrated no difference in postoperative fluid administration, vasopressor support, and end-organ dysfunction with use of epidural anesthesia in liver resection.
  5. Analgesia in patients with liver disease can be challenging due to altered drug metabolism and alterations in mental status. Acetaminophen is deemed safe; however, the dose must be reduced in patients with chronic liver disease. (Total daily dose less than 2000 mg is considered safe.) Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided due to increased risk of renal injury and gastrointestinal bleeding. Additionally, NSAIDs may exacerbate coagulopathies associated with liver disease. Long-acting opiates should be avoided if possible. Measured doses of shorter-acting opiates such as fentanyl are tolerated in cirrhotic patients. Opioid-induced constipation may exacerbate encephalopathy in patients with liver disease. Coadministration of laxatives is imperative.
  6. Sufficient venous access is of paramount importance, especially in surgery involving the liver parenchyma. Large-bore peripheral intravenous cannulas are inserted before or after the induction of anesthesia for major surgery (often 14 gauge or larger). In patients with insufficient peripheral access, large-bore central venous catheters (ie, 8.5F single-lumen or 12F double-lumen catheters) may be inserted. Universal precautions are mandatory given the high risk of infection in this patient population.
  7. Invasive monitoring is also an important component of anesthetic planning. An arterial catheter facilitates blood sampling for monitoring serial blood gases, glucose, and electrolytes and is needed for measuring arterial blood pressure. It is considered routine in major surgery for patients with end-stage liver disease. Central venous catheterization is indicated for pressure monitoring and rapid drug administration into the central circulation. Pulmonary artery catheters may help guide fluid and vasopressor therapy in some patients. Skillful line placement is important in coagulopathic patients. Ultrasonographic visualization of the vein before or during cannulation will reduce the incidence of carotid arterial puncture and the number of needle passes needed to cannulate the jugular vein.
  8. Transesophageal echocardiography (TEE) may be safely performed if clinically indicated in patients with liver disease with a low risk of bleeding provided that any varicies are grade II or better. Risk/benefit of a TEE must certainly be considered in this patient population but may be beneficial in patients who are at a high likelihood of hemodynamic deterioration (such as liver transplant or emergent surgery in a cirrhotic patient).
  9. A low threshold for performing a rapid sequence induction should exist for these patients given their elevated intra-abdominal pressure and increased risk of aspiration.
  10. Other physiologic variables that should be taken into consideration include urine output, body temperature, blood sugar levels, electrolyte disturbances, and coagulation status.
  11. Proper postoperative care and the timing of extubation for patients presenting with severe comorbidities should also be considered.
  12. Surgical considerations for the anesthesiologist during procedures on the liver. Excessive bleeding and transfusion requirements have been correlated with increased postoperative morbidity. Management must focus on the balance between reducing blood loss while maintaining adequate liver perfusion. Surgical techniques for hepatic resection and other procedures on the liver have been developed to decrease blood loss. Total hepatic vascular exclusion (TVE), the Pringle maneuver (PM), low central venous pressure (CVP) anesthesia, and venovenous bypass are four such techniques.
    1. TVE consists of clamping the hepatic inflow vessels (portal vein and hepatic artery) to the liver as well as the outflow vessels (inferior vena cava and suprahepatic inferior vena cava). This can have profound deleterious effects on venous return and the hemodynamics of the patient. This also results in a significant amount of warm ischemic time to the liver and may increase postoperative hepatic dysfunction.
    2. The PM consists of intermittent clamping of the hepatic inflow vessels (portal vein and hepatic artery) causing intermittent hepatic ischemia. There can be significant back bleeding through the hepatic veins and vena cava. A recent meta-analysis did not demonstrate a difference in blood loss using PM in patients undergoing liver resection; however, previous older studies have shown a reduction in blood loss. This difference is thought to be attributed to newer surgical techniques that limit blood loss without occluding the hepatic inflow vessels.
    3. A low CVP (generally referred to as a CVP lower than 5 mm Hg) facilitates control of bleeding from hepatic veins and the inferior vena cava during parenchymal dissection. Low CVP anesthesia reduces the pressure gradient that promotes bleeding through inadvertent extrahepatic venous injuries as well as hepatic venous bleeding during parenchymal dissection. Low CVP anesthesia has been demonstrated to reduce blood loss; however, it has not been demonstrated to reduce postoperative morbidity. Caveats for CVP monitoring with liver resection include increased risk of AKI with hypoperfusion and limitations of CVP monitoring with structural cardiac disease and with surgical compression of the liver-associated hepatic inflow and outflow vessels.
    4. Venovenous bypass consists of the placement of large-bore cannulas in the common femoral vein and potentially the portal vein to drain venous blood and then return the blood to the cannula in either the internal jugular or axillary vein. This allows for caval interruption of the liver during surgery for control of hemorrhage without a significant drop in preload. There is risk to placement of these cannulas, and this should only be performed by an experienced team but may allow for safer surgical manipulation particularly in patients with limited cardiac reserve. To date, no study has shown a benefit to this technique and clinical judgment, and surgical needs must be considered on a case-by-case basis.
  13. Enhanced Recovery after Surgery (ERAS) for liver resection has been adopted in many respects as ERAS protocols have been shown to decrease morbidity and duration of postoperative admissions. In 2016, the ERAS society published guidelines for liver resection. Preoperative considerations specific for liver resection highlight ensuring adequate preoperative nutritional status and avoiding long-acting anxiolytics. The guidelines also recommend using abdominal wound catheters and intrathecal opioids instead of epidural anesthesia and maintaining low-CVP anesthesia with balanced crystalloids. Minimally invasive surgery is recommended when appropriate. Postoperative considerations are similar to other ERAS strategies with early oral intake, mobilization, and a strong recommendation for multimodal analgesia. While there is strong evidence for many of the ERAS recommendations for perioperative nutrition and early mobilizations, the data for some of the other recommendations are equivocal particularly for low CVP anesthesia and epidural analgesia as discussed above.