What the Anesthesiologist Should Know before the Operative Procedure

Hepatic tumors can either be primary tumors of the liver or be the result of metastatic extrahepatic malignancies. Because of the absence of pathognomonic symptoms and the large functional reserve of the liver, lesions are either discovered as an incidental finding on a scan or the patients present late in the course of the disease.

The presentation of the disease and the type of surgery planned is going to define your anesthetic management. For simple fine needle aspirations or liver biopsies, a simple deep MAC or general anesthetic will suffice but special lines and monitors will be needed for the liver resections or transplants. Benign lesions include hepatic adenomas, focal nodular hyperplasia, small cysts, hemangiomas, or biliary hamartomas. Malignant lesions are most commonly metastatic in origin and the source should be identified but hepatocellular carcinomas are common. These carcinomas most often occur in patients with chronic liver disease like viral hepatitis, hemochromatosis, and alcohol abuse. The median survival following the diagnosis of a hepatocellular carcinoma is approximately 8 to 20 months with large tumor size, vascular invasion, poor functional status and nodal metastases being associated with a poor outcome.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

General consideration that might affect the timing of the surgery are 1) whether the surgery might be curative or not, 2) the severity of hepatic dysfunction as well as other comorbid conditions on presentation, 3) the type of surgery planned, or 4) the availability of a donor.

In general these operations are elective or urgent. Patients should have had extensive workups in the diagnosis of the lesion or the staging of the tumor. Preoperative blood work and scans should allow you to adequately plan your anesthetic.

Emergent surgery might be needed under a few circumstances:

Tumor rupture: Intraperitoneal bleeding secondary to the tumor rupturing will present with sudden onset of severe abdominal pain with distension, an acute drop in the hematocrit and hypotension. This is a life-threatening complication, and control of bleeding may require emergent angiography and embolization of the bleeding vessel, or even surgery.

Liver transplantation: When liver transplantation is considered curative the availability of the donor liver would make surgery emergent.

Variceal bleed: A life-threatening variceal bleed might require an emergent surgical procedure.

2. Preoperative evaluation

A careful history should be taken to identify risk factors for chronic liver disease and metastatic disease. Specifically, a history of viral hepatitis, metabolic liver diseases and alcohol abuse. Physical examination should be directed toward identifying peripheral stigmata of cirrhosis or decompensated liver disease. Special examinations should focus on the size and extent of the tumor and the current liver function.

Adenoma: Associated with premenopausal woman using oral contraceptives and type1 glycogen storage diseases. They often present with abdominal pain andare scheduled for elective surgery but they may present with a ruptureand life threatening bleeding.
Carcinoma: Patients often have no symptoms or may present as patients with previously compensated cirrhosis now with ascites, encephalopathy, jaundice or variceal bleeding. Laboratory examinations are usually nonspecific and reflect the underlying liver disease and may include thrombocytopenia, hypoalbuminemia, hyperbilirubinemia, and hypoprothrombinemia. Mild anemia and electrolyte disturbances (e.g., hyponatremia, hypokalemia, metabolic alkalosis) are also common and are associated with the abnormal fluid status associated with chronic liver disease or with diuretic use. Hypovolemia should be suspected.
Paraneoplastic syndromes: Can manifest with hypoglycemia, erythrocytosis, hypercalcemia, and severe diarrhea.

Medically unstable conditions warranting further evaluation shall be discussed below under coexisting disease implications on perioperative care. They include hepatic encephalopathy, anemia and coagulopathy, hypovolemia, intrapulmonary ateriovenous shunting, dyspnea, pleural and or pericardial effusions, paraneoplastic syndromes, hepatorenal syndrome, malnutrition, electrolyte disturbances, and decreased metabolism of medications.

3. What are the implications of co-existing disease on perioperative care?

b. Cardiovascular system:

Acute/unstable conditions: Those with end stage liver disease have hyperdynamic circulations characterized by a low systemic vascular resistance (SVR) and high cardiac output (CO) state. The twice normal cardiac output, tachycardia and decreased peripheral vascular resistance will exacerbate any pre-existing cardiac disease. In advanced disease they ultimately progress to a low cardiac output state.

In addition, these patients present with increased mixed venous oxygen tension due to extensive arteriovenous malformations and portosystemic shunting.

Baseline coronary artery disease or cardiac dysfunction will be severely affected by the low SVR and high CO state. Before inducing a patient with preexisitng cardiac disease, an arterial line should be placed and appropriate vasoactive medications should be immediately available.

Despite increased total body fluid volume, the effective intravascular volume is diminished. This hypovolemia will further complicate the hemodynamic affects of a general anesthetic.

Frequent use of diuretics, leads to further intravascular depletion and electrolyte abnormalities

c. Pulmonary:

There is a generalized reduction in lung function that leads to hyperventilation, hypoxemia, and dyspnea. Restrictive lung physiology is predominant. Decreased diaphragmatic movement may result from a large liver mass or severe ascites. Pulmonary effusions further decrease functional residual capacity and encourage atelectasis. Intrapulmonary shunts result in a functional right to left physiology and hypoxia. Diminished hypoxic pulmonary vasoconstriction leads to increased V/Q mismatching. Airway protection is important in patients with altered mental status and because of ascites and potential full stomach, a rapid sequence induction and intubation should be considered.

d. Renal- GI:

Hepatorenal syndrome is characterized by an increased renal vascular resistance that results in decreased renal cortex blood flow, oliguria, and renal failure. Hemodynamic changes that occur during surgery from blood loss or clamping of major blood vessels may exacerbate renal perfusion and lead to further deterioration of renal function. The cause is most likely associated with abnormal prostaglandin metabolism and this may explain the increased non-steroidal drug induced renal failure incidence seen in these patients.

Decreased bile acids production by the liver results in deficient fat-soluble vitamin absorption. These deficiencies may cause a host of other comorbid diseases including night blindness and keratomalacia (vitamin A), rickets and osteomalacia (vitamin D), and bleeding diathesis (vitamin K).

Watery diarrhea is common and is thought to result from various peptide secretions leading to intestinal secretion and may lead to significant hypovolemia.

e. Hepatic:

Impaired synthetic and metabolic liver functions may be present. Deficient coagulation factors increase the risk of bleeding perioperatively. Hypoalbuminemia results in decreased oncotic pressure and increased extravasation of fluid from blood vessels into tissue. The metabolism of drugs is negatively affected by the decreased hepatic blood flow, decreased hepatic function, and decreased protein binding. Hypoglycemia is common thus, close monitoring of blood glucose levels as well as infusion of glucose solutions may be considered.

f. Endocrine:

Paraneoplastic syndromes can manifest with hypoglycemia, erythrocytosis, hypercalcemia, and severe diarrhea.
Hypoglycemia, results from the tumor’s high metabolic needs and is usually mild, however some tumors secrete insulin-like growth factor-II, which can cause severe symptomatic hypoglycemia.
In severe liver disease glycogen stores are diminished and gluconeogensis is impaired, both of which will further increase the risk of hypoglycemia.
Erythrocytosis is probably due to tumor secretion of erythropoietin, however elevations in the hematocrit is uncommon as most patients are anemic at diagnosis because of other effects of the tumor.
Although hypercalcemia is mostly associated with osteolytic metastases, it may occur due to secretion of a parathyroid hormone like protein by the tumor.
Watery diarrhea is common and is thought to result from various peptide secretions leading to intestinal secretion and may lead to significant hypovolemia.

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthestic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

Hematology

Coagulation deficiencies are common among patients with liver disease. Most commonly affected variables include INR, PTT, and platelet count. Platelets are produced abnormally small and functionally deficient. Disseminated intravascular coagulopathy is not uncommon in patients with chronic liver disease.

Neurologic

Hepatic encephalopathy is a major risk in patients with liver disease. Baseline mental status should be evaluated and documented. New changes in neurological function should not be immediately attributed to hepatic dysfunction but thoroughly evaluated, due to the risk of occult intracranial hemorrhages.

Decreased clearance of certain anesthetic drugs may lead to prolonged sedation and respiratory depression. Caution should be used with the use of premedications. Airway protection is important in patients with altered mental status.

4. What are the patient's medications and how should they be managed in the perioperative period?

In general, there are no specific medications that are taken for hepatic tumors. However, the patient might be on multiple medications for liver dysfunction. All supportive medications should be continued until surgery (e.g., vitamin K). Consider holding the scheduled dose of diuretic on the day of surgery to decrease the risk of the patient being in a significant hypovolemic state on arrival in the operating room.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

While surgical treatments are regarded as the mainstay of treatment, cytotoxic chemotherapy agents like doxorubicin may be tried. In addition to their immunosuppresive effects, you should consider the effects these various agents might have on cardiac or lung function. Depending on the dose and duration of administration, a cardiac echocardiogram may be warranted.

i. What should be recommended with regard to continuation of medications taken chronically?

Cardiac: Propanolol is used to maintain lower portal venous pressures and reduce the risk of variceal bleeding. It should be continued perioperatively but care should be taken to prevent hypotension.
Renal: Spironolactone and other diuretics are given for treatment of ascites and excess total body water. These lead to intravascular hypovolemia and electrolyte abnormalities. Hold diuretics on the day of surgery.

j. How to modify care for patients with known allergies –

N/A

k. Latex allergy – If the patient has a sensitivity to latex (eg. rash fromg loves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

N/A

l. Does the patient have any anti-biotic allergies-

N/A

m. Does the patient have a history of allergy to anesthesia?

N/A

5. What laboratory and special tests should be obtained and has everything been reviewed?

We will approach this section from a systems based approach. Patients will present in such extremes of the disease that a one size fits all approach will not suffice. Each patient will need to be evaluated according to the planned surgical procedure and the stage of the disease. The special examinations results will guide you in your type of anesthetic (GA plus minus regional) and the type of monitoring you will use (arterial line, central venous catheter plus/minus a pulmonary artery catheter or even an intraoperative echocardiogram).

Cardiovascular: For major tumor resection, an electrocardiogram, chest x-ray and depending on the condition of the patient, an echocardiogram should be ordered to evaluate the cardiac function and to look pericardial effusion. If indicated, more invasive cardiac testing may be required in patients with known history of heart disease with angiography or cardiac catheterization.

Respiratory: A chest x-ray should be sufficient in most cases to evaluate for pulmonary edema and pleural effusions. In sicker patients, an arterial blood gas analysis would help determine a baseline level of function and guide further perioperative anesthetic management

Renal:Preoperative serum electrolytes, urea nitrogen, and creatinine results will serve as a baseline and provide important information as to the current renal function and whether any electrolyte abnormalities need to be addressed prior to the operation.

Hepatic/coagulation: Liver function tests, ammonia levels, and coagulation blood work should be reviewed. Appropriate blood transfusion samples should be sent and blood products ordered. If available, a thromboelastogram should be done. Preoperative correction of clotting abnormalities with fresh frozen plasma and vitamin K may be necessary. The viral hepatitis status should be clearly known.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

There is no one technique that could be suggested that would cover all potential scenarios. The surgical approach in general is one of surgical resection of the tumor but the patient might be needing anesthesia services for other treatment modalities such as radio frequency ablation, cryoablation, radiation therapy, percutaneous ethanol ablation, and transarterial chemoembolization. Each of these circumstances would require a different level of sedation and special monitoring devices depending on the treatment’s invasiveness.

For the surgical resection in the operating room, a general anesthetic will be required with sufficient venous access for the anticipated blood loss, central venous access for pressure monitoring and vasoactive medication administration, and an arterial line for systemic blood pressure measurements and blood sampling. A regional technique, thoracic epidural, or paravertebral catheters should be considered if the pre-operative coagulation profile is normal and the hepatic function is expected to be reasonable in the post operative period.

Regional anesthesia

Neuraxial: thoracic epidural

Benefits: Opioid sparing in the postoperative period; early extubation.

Drawbacks:Significant concern for the risk of a neuraxial hematoma secondary to abnormal coagulation in the post operative period.

Issues

Coagulation might be normal preoperatively for the placement of the epidural but it should be expected that they will be abnormal in the post operative period which might complicate the continued use and removal of the catheter.
Relative hypotension requiring increased blood transfusions.
Urinary retention.

Peripheral nerve block

Bilateral or right side paravertebral catheters.

Benefits:

Opioid sparing in the post operative period; Early extubation.
Minimal concern for neuraxial hematoma formation.

Drawbacks: Risk of bleeding and infection in the paravertebral space.

General anesthesia

Benefits

Provide optimal conditions for surgery.
Does not have the concerns of neuraxial or paravertebral hematoma formation.

Drawbacks:Will require the use of significant opioids.

Airway concerns

Induction: Ascites and decreased bowel motility create a significant risk for aspiration. A rapid sequences induction and intubation should be considered.
Postoperative: Prolonged surgery, poor liver function, likely slow awakening and residual respiratory depression make it likely that the patient will remain intubated.

Monitored anesthesia care

Benefits:Reserved only for the simplest non-invasive procedures in patients with good liver function.

Drawbacks:

Patients with decreased liver function will be extremely sensitive to the sedatives used.
Patients with significant disease are an aspiration risk.

6. What is the author's preferred method of anesthesia technique and why?

What prophylactic antibiotics should be administered?

Current SCIP recommendations suggest the single drug use of cefotetan, cefoxitin, ampicillin/sulbactam OR a combination of cefazolin or cefuroxime plus metronidazole. If allergic to β-lactam antibiotics then clindamycin plus an aminoglycoside or clindamycin plus aztreonam.

What do I need to know about the surgical technique to optimize my anesthetic care?

The surgical approach in the operating room will either be a laparoscopic or an open abdominal procedure. A balanced general anesthetic with appropriate muscle relaxation will provide optimal surgical conditions.
Ensure an empty stomach with either an orogastric or nasogastric tube.
Avoid ventilating with large tidal volumes to minimize surgical field motion.
Avoid nitrous oxide to prevent bowel distention.

What can I do intraoperatively to assist the surgeon and optimize patient care?

Keep the patient normotensive and prevent the surgical stress response with adequate opioid administration and/or the use of a regional technique.
Use muscle relaxants to facilitate surgical exposure.
Use non-lactate containing fluids for maintenance.
Due to the potential decreased liver function, use medications that require minimal liver metabolism e.g., cisatracurium, remifentanil and fentanyl, desflurane, although sevoflurane and isoflurane have been shown to be safe.
Decrease doses of highly protein bound medication (e.g., midazolam) due to hypoalbuminemia but increase dosage of water soluble medications (muscle relaxants) because of their increased volume of distribution.
Avoid and prevent factors that decrease hepatic blood flow such as hypotension, excessive sympathetic activation, hypocarbia, and high mean airway pressures.
Use appropriate blood products to prevent excessive bleeding due to abnormal coagulation and transfuse packed red blood cells to maintain an appropriate hematocrit.
Maintain an adequate CVP and systemic blood pressure to encourage and protect renal function.
Upper and lower body warming devices should be used. Hypothermia will exacerbate the coagulation concerns.
Monitor for hypoglycemia.
Cell Saver should not be used in the presence of a malignancy.

What are the most common intraoperative complications and how can they be avoided/treated?

Blood loss from surgical field: Keep the patient normotensive, normothermic, and treat existing and developing coagulopathies with vitamin K and blood products.
Coagulopathies: as above.
Pulmonary compromise caused by retractors, laparoscopic technique, Trendelenburg positioning: Prevent by using PEEP and good communication with surgeons.
Hypothermia:Prevent by using body warming devices, warming all fluids and the operating room.
Electrolyte derangements: Do frequent blood gases/electrolyte test to monitor and then treat any abnormalities.
Hepatic dysfunction: Avoid hypotension, excessive sympathetic activation, hypocarbia, and high mean airway pressures.
Renal dysfunction: Prevent by maintaining an adequate CVP and systemic blood pressure and if necessary use diuretics.
Pneumothorax: Monitor for increasing airway pressure and treat with placement of an intercostal drain if it occurs.
Abrupt drainage of ascites fluid my cause hypotension.
Prolonged post operative sedation and the need to remain intubated to protect the airway: Avoid by using shorter acting medications and medications not heavily reliant on hepatic metabolism.
Air embolism: Should be suspected if there is a sudden loss of end tidal CO2 or a pulseless electrical arrest occurs.

b. If the patient is intubated, are there any special criteria for extubation?

N/A

c. Postoperative management

What analgesic modalities can I implement?

Regional: Thoracic epidural or right sided or bilateral paravertebral blocks. These can be performed prior to incision or at the end of the procedure.
Opioids: Either as continuous infusions, or if the patient is awake as a patient controlled analgesia plan.
NSAIDs are generally avoided because of preexisting coagulopathies and the risk of hepatorenal syndrome.

What level bed acuity is appropriate?

For any hepatic resection the ICU will be required for potential post operative ventilation and management of major fluid shifts and coagulopathies.
For less invasive procedures like liver biopsies, the regular floor or a step down unit will suffice depending on the patients condition.

What are common postoperative complications, and ways to prevent and treat them?

Bleeding: Maintain normothermia and transfuse appropriate blood products.
Delirium: Minimize using long acting sedative medications and dose conservatively.
Pain: Use regional techniques if coagulation status allows.
Hepatic and renal dysfunction: Keep hemodynamic parameters as normal as possible.

What's the Evidence?

Barash, PG. Clinical anesthesia. 2009. pp. 569-597.

Stoelting, RK, Hines, RL, Marschall, KE, Hines, Roberta L., Marschall, Katherine E. Stoelting's anesthesia and co-existing disease. 2008. pp. 259-278.

Bruix, J, Llovet, JM. “Prognostic prediction and treatment strategy in hepatocellular carcinoma”. Hepatology. vol. 35. 2002. pp. 519-24.

Hanje, AJ, Patel, T. “Preoperative evaluation of patients with liver disease”. Nat Clin Pract Gastroenterol Hepatol. vol. 4. 2007. pp. 266-76.

“Continuing education in anaesthesia, critical care & pain. Anaesthesia for hepatic resection”. Contin Educ Anaesth Crit Care Pain. vol. 9. 2009. pp. 1-5.

Shontz, R, Karuparthy, V, Temple, R, Brennan, TJ. “Prevalence and risk factors predisposing to coagulopathy in patients receiving epidural analgesia for hepatic surgery”. Reg Anesth Pain Med. vol. 34. 2009. pp. 308-11.

Weinberg, L, Scurrah, N, Gunning, K, McNicol, L. “Postoperative changes in prothrombin time following hepatic resection: implications for perioperative analgesia”. Anaesth Intensive Care. vol. 34. 2006. pp. 438-43.

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