The liver is important for metabolism and clearance of drugs. Proper drug choice and dosage can help prevent anesthetic complications. Phenothiazines, benzodiazepines, and alpha-2 adrenergics should be avoided or used sparingly in patients with moderate to severe liver disease. A main concern with phenothiazine tranquilizers is the dose-dependent hypotension that is potentiated due to these drugs. Additionally phenothiazine tranquilizers (acepromazine) have been linked to thrombocytopenia (Tranquilli et al. 2007). These drugs should be avoided in the hepatic patient where clotting factors are a concern. The liver metabolizes phenothiazines (Plumb 2005).
|CBC/Chem||Why It’s Important||Normal Values|
|ALT||Elevations are specific to liver disease. Possible to see no increase if hepatobiliary disease is present.||K9 0–77 IU Fel 0–100 IU|
|Alk phos||It has a short half life and increased levels are seen with cholestasis or bonelysis, or if injections of corticosteroids are present. Increased levels also seen with muscle trauma. Increased levels in cats should be taken seriously. Its half life is 6 hours; a cat’s total liver content is 50% less than dogs.||K9 0–400 IU Fel 0–193 IU|
|Glucose||Decreased levels can cause seizures, lethargy, PU/PD, ataxia. Decreased levels can also be associated with portosystemic shunts. Supplement fluids with dextrose.||K9 59–121 mg/dL Fel 54–145 mg/dL|
|Cholesterol||Is required for the production of bile acids.||K9 135–281 mg/dL Fel 69–225 mg/dL|
|Bilirubin||If levels are increased, prehepatic, hepatic, and posthepatic causes should be considered. Elevated levels are indicative of certain diseases. During red blood cell metabolism, hemoglobin is phagocytized and bilirubin is produced. If plasma levels reach 1–2 mg/dL, plasma will appear icteric.||K9 0–0.7 mg/dL Fel 0–0.5 mg/dL|
|GGT||Similar to alkaline phosphatase. Important in amino acid membrane transport. If serum levels are increased, it can be due to cholestatic liver disease. Anticonvulsants and corticosteroids will also elevate GGT, but only in dogs.||K9 1–12 μ/L Fel 1–10 μ/L|
|PCV||Determines patient overall blood status. Important aspect of the CBC. Determines hydration and protein levels. Indicator of anemia.||K9 36–55% Fel 29–48%|
|BUN||Increased levels can indicate dehydration in patients with hepatobiliary disease. Decreased levels are seen with the reduction of converting of ammonia to urea.||K9 5–23 mg/dL Fel 14–36 mg/dL|
|Albumin||Produced entirely in the liver. Maintains oncotic pressure. Half life is 7–10 days, so a severe decrease doesn’t correlate to acute liver disease. Decreased levels can cause pulmonary edema. If the liver is diseased, the ability to produce albumin is maintained. Production is decreased only if severe liver disease is present.||K9 2.7–3.8 g/dL Fel 2.9–3.9 g/dL|
|PT/PTT||Associated with liver disease, DIC, sensitive to vitamin K deficiency. Important test to run prior to anesthetizing a patient with neoplasias or biopsies. PT is measured in the extrinsic pathway and PTT is measured in the intrinsic pathway.||K9 12–17 sec Fel 15–23 sec|
|Bile acids||Formed in the liver and excreted in the bile. Most specific test to determine liver function. There will be no increase in bile acids in a patient with a normal liver; a normal liver can clear bile acids by “first-pass extraction.”||K9 < 25 mmol/L Fel < 15 mmol/L|
Benzodiazepines can cause prolonged effects in patients with elevated liver enzymes. The prolonged effects are due to diminished biotransformation occurring in the liver (Tranquilli et al. 2007). Diazepam (valium) can cause profound sedation in patients with elevated liver enzymes. Lower doses of diazepam should therefore be used to achieve desired effects. Flumazenil is a reversal agent that antagonizes the effects of benzodiazepines by competitively blocking the receptors in the CNS.
Cats may be especially susceptible to the effects of benzodiazepines. There are reports of cats presenting with liver failure after the administration of oral diazepam. It was reported that these cats presented with anorexia, increased liver values, and hyperbilirubinemia (Plumb 2005).
Alpha-2 adrenergics cause rapid sedation and provide analgesia. They have profound effects on blood pressure and the cardiovascular system. The hepatic effects of alpha-2 agonists are seen more with xylazine versus medetomidine. The administration of xylazine has been shown to augment plasma glucose concentrations by decreasing insulin (Tranquilli et al. 2007). Xylazine activates the alpha-1 receptor, thus stimulating hepatic glucose production by decreasing insulin, which indirectly causes hyper-glycemia (Tranquilli et al. 2007). Medetomidine is a more selective drug and has an affinity for the alpha-2 receptor, which causes it to have less hepatic effects. The advantage of these drugs is that any unwanted effects can be reversed with an alpha-2 antagonist. Xylazine is antagonized with yohimbine or tolazoline, and medetomidine is antagonized with atipamezole.
The opioids can be used in patients with hepatic disease. Ideally, doses should be titrated to effect to help control the degree of untoward side effects. Bradycardia can be treated with an anticholinergic in an effort to maintain cardiac output. Opioid-induced respiratory depression may cause reduced oxygenation of the liver and other tissues. Of the mu opioids, morphine and meperidine have been shown to cause histamine release. The release of histamine can cause hypotension, thus causing a reduction in hepatic blood flow. Similar to alpha-2 agonists, unwanted side effects of opioids can be reversed or antagonized. The reversal agent for opioids is naloxone, which can be titrated to effect so as to retain some of the analgesia and sedation provided by the opioid (Tranquilli et al. 2007).
Barbiturates are detoxified by the liver and should be avoided or used sparingly in hepatic patients. A single dose of a thiobarbiturate to facilitate intubation is not necessarily contraindicated due to redistribution. If hypoalbuminemia is present, the length of the anesthesia may be prolonged by these highly protein-bound drugs (Tranquilli et al. 2007). Maintaining a surgical plane by the redosing of barbiturates should never be done in hepatic patients.
Propofol is a nonbarbiturate emulsion, lecithin-based hypnotic that is used for inducing anesthesia and providing maintenance anesthesia as a constant rate infusion. Propofol provides a rapid induction and recovery. Its rapid recovery is due to metabolism in the liver as well as extra-hepatic metabolism elsewhere in the body and possibly in the lungs and kidneys (Tranquilli et al. 2007). The metabolites are then excreted in the urine. The rate of hepatic flow is slower than the disappearance of propofol from the plasma making it an ideal drug for hepatic patients (Tranquilli et al. 2007). Cats may experience longer recovery times due to slower metabolism (Plumb 2005). Propofol does cause dose-dependent vasodilation and hypotension. Crystalloid or colloid fluid therapy should be strongly considered.
Etomidate can be a good choice for induction of anesthesia. An advantage of etomidate is that it doesn’t cause a decrease in hepatic perfusion (Tranquilli et al. 2007). Metabolism of etomidate is rapid and done by the liver. The metabolism process is done by hydrolysis or glucuronidation, and the metabolites are inactive (Plumb 2005). Etomidate will suppress the adrenal gland, rendering the patient unable to mount a stress response to surgery and so it should not be used in patients with decreased adrenal gland function (Addisonian patients) (Plumb 2005). The main benefit of etomidate is that it does not negatively affect the cardiovascular system. Overall, this can help maintain perfusion to the liver.
Dissociative anesthetics can be used in the hepatic patient. This drug class includes ketamine (Ketaset) and tiletamine (Telazol). The additional component of Telazol is zolazepam, a benzodiazepine. The use of ketamine in a clinical sense has not been shown to cause hepatic dysfunction. The liver metabolizes dissociative anesthetics, which are mostly excreted by the kidneys in cats. Norketamine is a metabolite formed by the liver during metabolism in cats. It is about 1/10 as active as ketamine (Tranquilli et al. 2007).
If hepatic function is impaired, the use of Telazol could cause a longer recovery time due to the benzodiazepine component zolazepam (Tranquilli et al. 2007). As with other benzodiazepines, flumazenil can be used to antagonize any unwanted effects.
The use of inhalant anesthetics has been regarded as “the best choice for maintenance of anesthesia in patients with severe liver disease” (Tranquilli et al. 2007). One caveat is the use of halothane. Halothane will cause a reduction in blood flow to the liver. Roughly 12–20% of metabolism of halothane is done by the liver (Tranquilli et al. 2007; Plumb 2005). The common gas anesthetics used in veterinary medicine today are isoflurane and sevoflurane. Very little of either inhalant is metabolized. Inhalants cause a change in perfusion through vasodilation. Hepatic blood flow and oxygenation appear to be well maintained when inhalants are used to maintain a surgical plane of anesthesia. (Tranquilli et al. 2007).
If severe liver disease is present, the use of local anesthetics should be considered as part of a balanced anesthesia protocol. Drugs from the ester class are preferred because they are hydrolyzed in plasma (Tranquilli et al. 2007). Drugs from the amide class are metabolized in the liver. Lidocaine and bupivicaine are in the amide class, and, although very versatile, drugs are metabolized up to 90% in the liver. The toxic dose of lidocaine may be more apparent in a patient with a severely compromised liver, so doses should be monitored carefully.
Nonsteroidal antiinflammatories (NSAIDs) are a group of drugs that are widely used alone or in combination with opioids to help relieve pain. NSAIDs work by preventing the activity of COX enzymes that function in the production of prostaglandins (Tranquilli et al. 2007). The main disadvantage to NSAID therapy is the effect they can have on the kidneys and gastrointestinal tract. NSAIDs should be used judiciously in patients with hepatic dysfunction because it has been shown that all NSAIDs have the potential to cause harm to the liver (Boothe 2005). Of the six NSAIDs in use, no one drug has been shown to be less hepatotoxic over the others. Risks should be weighed. If the patient could benefit from the NSAID therapy and mild hepatic disease is present, it is possible that the patient can tolerate the drug. Frequent monitoring of liver values should be performed to detect any abnormal change (Boothe 2005).
Conditions That Affect the Liver
Portosystemic shunts are defined as “vessels that allow normal portal blood draining from the stomach, intestines, pancreas and spleen to pass directly into the systemic circulation without first passing through the liver” (Fossum and Duprey 2002). Essentially, toxins that would normally be filtered in the liver are allowed to circulate back through the body. Portosystemic shunts can be intraheptic or extrahepatic. Intrahepatic shunts are within the liver parenchyma and account for roughly 30% of all diagnosed shunts (Leib and Monroe 1997). These shunts are seen more commonly in large-breed dogs. Extrahepatic shunts, occurring outside the parenchyma, occur more commonly in smaller-breed dogs (Fig. 25.2).
The liver can atrophy due to the lack of nutrients from the pancreas and intestines. This atrophy can potentiate liver failure and hepatic encephalopathy (Leib and Monroe 1997).
Hepatic encephalopathy is the inability of the liver to metabolize any nutrients and toxins (Bonagura and Kirk 2000). Because the liver is unable to filter these toxins, they are able to circulate throughout the body and enter the central nervous system. Once the central nervous system is affected, the toxins inhibit neural function and neurotransmission (Leib and Monroe 1997). The effects of hepatic encephalopathy can be reversed; this is done surgically by fixing or attenuating the shunt that is present. Although not completely understood, the main toxin associated with hepatic encephalopathy is ammonia (Bonagura and Kirk 2000). Ammonia is produced by a protein that is broken down by the intestinal tract (Leib and Monroe 1997). Because of the shunt, ammonia — a neurotoxin — causes encephalopathy.