T. Αnagnostou1, P. Κaramichali2
11DVM, PhD, Companion Animal Clinic, School of Veterinary Medicine, Faculty of Health Sciences, A.U.Th.
2DVM, MSc, Companion Animal Clinic, School of Veterinary Medicine, Faculty of Health Sciences, A.U.Th.
Keywords:
anaesthesia, cat, liver diseases, dog
Αbstract
Veterinarians sometimes face cases of animals with liver disease that they should anaesthetise to perform surgery unrelated to the liver disease. This can also occur in surgeries that is considered necessary to establish a diagnosis for the liver disease (e.g. liver biopsy) or surgery to treat the liver disease (e.g. partial hepatectomy, ligation of portosystemic shunt).
After performance of surgery on an animal with liver disease has been decided, every effort must be made to stabilise the condition of the animal pre-operatively. Special attention must be paid to pathology stemming from the liver disease and potentially adversely affecting anaesthesia and surgery.
With regard to the pre-anaesthetic medication and the anaesthetic protocol, use of drugs largely dependent on hepatic metabolism and elimination should be avoided. Furthermore, the fact that all central nervous system depressant drugs have an exaggerated effect, when administered to animals with hepatic dysfunction, should be taken into consideration.
Almost all injectable anaesthetics are subject to hepatic metabolism and/or elimination, while the novel inhalant anaesthetics are not extensively metabolised by the liver. In high risk cases of animals with liver disease, the anaesthetic goal is to minimise the use of injectable anaesthetics, which are subject to hepatic metabolism, and to use inhalational anaesthetics for induction and maintenance of anaesthesia instead.
Peri-operative analgesia for animals with liver disease undergoing surgery can be accomplished via the administration of opioids (a constant rate infusion of remifentanil is an excellent choice) or via the epidural administration of local anaesthetics and/ or preservative-free morphine. An epidural injection should be attempted only if potential bleeding disorders have been ruled out or treated.
Veterinarians often face cases of dogs or cats with liver disease, in which anaesthesia is required for surgery unrelated to the liver disease itself. This can also occur in surgeries that is considered necessary for diagnostic (e.g. liver biopsy) or treatment purposes intended for the liver disease (e.g. partial hepatectomy, ligation of portosystemic shunt).
The proper anaesthetic management of such cases requires comprehension of normal hepatic function. The role of the liver is central in the production (gluconeogenesis), storage (glucogenesis) and catabolism (glycolysis) of glucose. The liver is the primary organ in which plasma proteins are composed, except for γ-globulins and coagulation factor VIII. Reduced plasma levels of albumin can be used as a rough, non-specific indicator of advanced hepatic dysfunction. The reduced protein production affects the plasma protein binding of drugs, the blood coagulation cascade and the colloid osmotic pressure of plasma, which is mostly generated by albumin.3,5,15,28,37
The liver is also the organ responsible for drug and hormone metabolism (and/or elimination), as well as bilirubin metabolism and clearance (binding to glycuronic acid). Hepatic Kupffer cells are charged with the removal of bacteria and endotoxins from the portal circulation. Finally, the liver is integral to the absorption of fat and fat-soluble vitamins, through release of bile acids and phospholipids in the lumen of the duodenum.3,5,15,28
Clinical signs in animals with hepatic dysfunction may include neurological signs due to hepatic encephalopathy, vomiting, diarrhoea, anorexia, ascites and icterus. Dogs with congenital portosystemic shunts may have reduced weight gain compared to what is normal for their age group. Serum biochemistry results may reveal hypoalbuminaemia, hypoglycaemia, reduced blood urea nitrogen (BUN), increased bile acids (measured after fasting and repeated measuring 2 hours post feeding), hyperammonaemia and hypokalaemia, whereas liver enzyme activities may be normal or increased. In dogs and cats which require anaesthesia and surgery and in which there is a suspicion of underlying liver disease, it is necessary to perform a diagnostic evaluation in order to estimate the efficiency and competence of the clotting factors (prothrombin time PT, partial thromboplastin time PTT). Anaemia may be noted after a complete blood count.28
After liver disease of some degree has been diagnosed and surgery has been deemed necessary, the clinician may elect to cancel the surgery, to continue with the procedure under local anaesthesia, to administer medical therapy until the liver disease is managed or to proceed with the surgery under general anaesthesia taking into account the hepatic dysfunction. The procedure may be cancelled if it has been scheduled due to the owner’s preference or for reasons unrelated to the animal’s health. Using local anaesthesia is a particularly tempting solution; however, it is often impractical and difficult to apply. The prescription of medical treatment until the hepatic disorder is managed should be the clinician’s first choice whenever it is possible to stabilise the disorder and surgery can be postponed. In contrast, when liver disease cannot be controlled or when an emergency situation is present and surgery is necessary for the survival of the patient, the veterinarian should perform the surgery even though liver disease is present.5
Prior to selecting the anaesthetic protocol, it is important to determine if the case in question is a high risk case which necessitates a properly modified anaesthetic protocol for severe liver disease or if it is not a high risk case. Dogs and cats admitted due to trauma could have elevated liver enzymes due to hepatic contusions, however, liver function is usually normal. This patient category is not usually considered to be high risk regarding liver function, especially if liver enzyme activity has increased less than sevenfold or tenfold above the normal range. In aged animals, mild increase of liver enzyme activity may be noted in the absence of clinical signs, however, these cases do not belong in the high risk category either. Animals belonging in the high risk category from an anaesthetic perspective are those that present with clinical signs and indications of liver dysfunction in the serum biochemistry results, especially the bile acid assays which are the most representative of liver function. In non-emergency cases, the administration of general anaesthesia is postponed until the disorder can be controlled with medical treatment, whereas in emergency cases, the anaesthetic protocol is properly modified.25
Dogs and cats with biliary tract disease are considered to be high-risk patients. Surgery is postponed, if possible, until the remission of the underlying disorder. If surgery cannot be postponed, a modified anaesthetic protocol is used. Vascular anomalies are represented by portal vein shunts, and these are particularly high-risk cases. Liver function is compromised, due to the abnormal formation of blood vessels and liver hypoplasia.25
In human medicine, the presence of: 1) hypoalbuminemia, 2) clinical signs of hepatic encephalopathy, 3) ascites and 4) icterus, is considered to be a compromising parameter which, when present, results in classifying a case into the high risk category.27 It is clear that proper preparations are vital prior to anaesthesia in a case with severe liver disease. Therefore, during the preanaesthetic period, every effort must be made so that any underlying disorders stemming from the hepatic dysfunction may be controlled, because they could negatively affect the outcome of anaesthesia and surgery.28
Such disorders include:
Hepatic encephalopathy (ΗΕ). It is common in dogs with portosystemic shunts. Severity of clinical signs may vary from mild depression to a nearly comatose state. In normal animals, ammonia produced by bacterial breakdown of aminoacids and toxins which are absorbed by the intestine are both retained in the liver and, therefore, they do not enter the systemic circulation. In animals with severe hepatic dysfunction, however, the liver no longer performs this function correctly, thus exposing the brain to these toxins resulting in HE. In the aetiopathogenesis of HE, γ-aminobutyric acid (GABA), as well as substances with an effect similar to GABA also play a role.2,3,5,15,17,24,28 In cases with chronic liver disease, the effect of small amounts of GABA, which can normally be found in the brain as neurotransmitters, is amplified by agents with an effect similar to GABA, which originate from the intestine and portal blood, resulting in the disruption of normal balance of excitatory and inhibitory neurotransmitters. In dogs and cats with hepatic disease, there is an increase in the number of GABA receptors in the central nervous system (CNS). Benzodiazepines and barbiturates potentiate GABA-receptors, and this is the reason why animals with severe liver disease usually manifest an increased sensitivity to these drugs. In animals with HE, general anaesthesia should be avoided, if possible. However, in dogs with portosystemic shunts (which usually present with clinical signs of HE), general anaesthesia is required as part of surgical treatment.2,3,5,11,15,24,28
Animals with HE should receive proper medical treatment prior to surgery: low protein diet, lactulose, enemas and antibiotics effective against Gram (–) enteric bacteria. The purpose of the treatment is controlling clinical signs through a reduction in ammonia and other toxin production. It is likely that antiepileptic medications might be needed, such as levetiracetam, in order to manage epileptic activity prior to as well as post-surgery.3,5,24,28
Hypoalbuminemia (reduced production by the liver, loss due to coagulation disorders). It results in increased plasma levels of non-protein bound (therefore active) anaesthetic agent. This is particularly important for drugs with high plasma protein binding, such as barbiturates, diazepam, and opioids, and it can lead to side effects, if standard doses, intended for animals without liver disease, are used. If such agents are used, their dose must be reduced.
Any possible fluid losses and electrolyte disorders due to vomiting and/or diarrhoea should be managed prior to surgery by fluid administration. Often fluids may be required in order to increase blood volume during surgery. Because animals with liver disease are usually hypoalbuminemic, particular care should be given to the infusion of crystalloids, because large volumes may exacerbate hypoalbuminemia. When albumin concentration is reduced to values under 1.5 g dl-1, the colloid osmotic pressure of plasma is expected to decrease as well. The use of colloids (blood, plasma, starch solutions, gelatin or dextran) (5 ml kg-1 h-1) combined with crystalloids may be the indicated solution in such cases. Concerns expressed in the past regarding the increase of lactate after Lactated Ringer’s infusion due to inability to metabolise lactate to bicarbonate in animals with liver disorders, seem not to have clinical substantiation.28 Colloids increase plasma volume, support colloid osmotic pressure and make up for any deficiency in coagulation factors in cases where blood, fresh plasma or fresh-frozen plasma are used. In cases where blood transfusion is needed (e.g. due to anaemia), relatively fresh blood should be used (no more than one week old), because the levels of ammonia increase during storage in preserved blood.3,5,11,14
Ascites. If copious amounts of abdominal fluid are noted, it should be removed prior to surgery via abdominocentesis. Enough fluid should be drained to facilitate lung expansion and respiratory function.5,11
Electrolyte disorders. Hypokalaemia may be observed (losses with vomiting, diarrhoea, urination). In such cases, potassium should be infused at a rate no higher than 0.5 mEq kg-1 h-1.5,11
Coagulation disorders. Coagulation factors (other than VIII) are produced in the liver, therefore in dogs and cats with liver disease, it is likely that coagulation factor synthesis is reduced. Moreover, coagulation factors II, VII, ΙΧ, Χ become functional after activation in the liver with the contribution of vitamin Κ. In cases of cholostatic liver disease, however, the absorption of fat-soluble vitamins, such as vitamin K may be inadequate. For this reason, prothrombin time should be evaluated prior to surgery. Some clinicians choose to inject vitamin K for 24-48 hours. In case of emergency surgery, plasma or fresh-frozen plasma can be infused, because these supplement most of the coagulation factors.3,5,15
Regarding the selected anaesthetic protocol for dogs or cats with hepatic dysfunction, every effort must be made to avoid drugs mostly dependent on hepatic metabolism and elimination. If this is not possible, then the dose must be properly modified, because CNS depressants that are used in the peri-anaesthetic setting have an exaggerated effect when administered to animals with hepatic dysfunction. The latter occurs due to hypoalbuminemia, reduced hepatic perfusion and reduced hepatic metabolism of the anaesthetic agent, as well as the increased number of central GABA-receptors.
Ηypoalbuminaemia affects plasma protein binding of most anaesthetic agents, resulting in increasing amounts of free or active drug (relative overdose). Hepatic perfusion is usually reduced in animals with liver disease due to e.g. portal vein hypertension or portosystemic shunt, and this inevitably results in reduced drug absorption by the liver. However, other than reduced drug retention, hepatic metabolism and elimination of drugs that manage to reach the organ can also be reduced. Finally, in animals with liver disease an increase in central GABA- receptors has been observed, resulting in exaggerated sensitivity to agents like benzodiazepines and barbiturates, which potentiate such receptors.3,5,15
The selection of agents to be included in the anaesthetic protocol should be meticulous and based on their pharmacological properties, side effects and pharmacokinetics. In particular, the preferred drugs should have a short half-life, the termination of their anaesthetic effect should rely on a mechanism other than hepatic metabolism, and they should be reversible by antagonist drugs.37
More specifically, phenothiazines can result in hypotension, have a prolonged duration of action and their effect is expected to be even more prolonged in dogs and cats with liver disease. It is best to avoid these agents entirely.28,37 Also, the use of a2-agonists is not recommended due to severe circulatory depression and likely compromise of blood flow and oxygen provision in various organs.37 If they need to be used, small doses are preferred; in case of severe circulatory side effects, their effect can be reversed with atipamezole.28 Regarding benzodiazepines, because substances with an effect similar to benzodiazepines have been implicated in the aetiopathogenesis of HE, most authors consider that they can exacerbate HE and therefore they do not recommend benzodiazepine use.2,3,15,28,37
Even though opioids undergo hepatic metabolism, they are considered a good choice for animal patients with liver disease, because they seem to have minimal or no side effects to the liver. Their effect can be exaggerated or prolonged in animals with liver disease, however the option of reversing their effect with naloxone (0.04 mg kg-1), if deemed necessary, is an advantage. The circulatory sequelae are minimal and potential bradycardia can be easily managed with anticholinergic drugs. Agonist/antagonists such as butorphanol (0.2 mg kg-1) apparently cause less severe respiratory depression than pure μ-agonists. Satisfactory options, though, also include morphine (0.1-0.2 mg kg-1), and pethidine (3-4 mg kg-1). The safety of these drugs, the availability of antagonists, the mild sedation and powerful analgesia render them very useful in animals with hepatic disease.3,5,11,15,28,37
Remifentanil is a noteworthy option for perioperative (and postoperative) constant rate infusion.28 This is a potent short-acting opioid which does not depend on hepatic function for the termination of its effect, as it is metabolised by esterase enzymes in the blood and tissues.19 This agent can be used in patients with end-stage liver disease (e.g. for liver transplantation) 23 and it has been used without problems in dogs with liver disease as well.1
The use of thiobarbiturates in order to anaesthetise animals with liver disorders should be avoided. Nevertheless, a single bolus of thiopentone for intubation is not absolutely contraindicated, because the redistribution of the agent from the brain to less perfused tissues terminates its anaesthetic effect. However, repeated doses of thiobarbiturates should not be used for the maintenance of anaesthesia, under any circumstances, considering that liver disease affects the depth and duration of anaesthesia with thiobarbiturates due to increased sensitivity of the CNS and reduced plasma protein binding (hypoalbuminemia) in such cases.3,5,11,15,37 The use of thiopentone, even for induction purposes only, can be avoided nowadays, because there are safer options available for anaesthetic induction in patients with liver disease, such as propofol and isoflurane.
The main advantage of propofol is its swift hepatic metabolism, which is based on conjugation to glucuronic acid (biotransformation). This pathway seems not to be severely affected (compared to other metabolic processes) in dogs with liver disease and it remains functional until end-stage liver disease. Therefore, it is likely that agents with metabolism dependent on this pathway, such as propofol, are safer.15 Furthermore, there may be extrahepatic sites for propofol elimination (lung, kidney),10,28 because it has been proven that propofol clearance from plasma exceeds hepatic perfusion. Special consideration should be given to cats with liver disease, however, due to slower propofol clearance in this species due to the relative lack of enzymes that are necessary for glucuronide conjugation. If intravenous anaesthetics are deemed necessary for the induction of anaesthesia, propofol is a reasonable option.3,5,11,15
The use of etomidate for induction ensures remarkable stability of standard haemodynamic monitoring parameters, consequently preserving hepatic perfusion. Potential side effects (suppression of corticosteroid release, haemolysis due to propylene glycol), do not seem to be of clinical significance when etomidate is used only for induction. Etomidate is suggested as an option for induction of anaesthesia in animals with liver disease.3,5,11,15,37
Ketamine should be avoided in patients with HE, because it can induce seizures. It is often combined with benzodiazepines in order to prevent the manifestation of side effects, however, use of these drugs also in cats with liver disease can be a considerable risk. Ketamine, like other injectable anaesthetics, is eliminated by the liver, therefore it should not be used for anaesthetic maintenance. If it is used during induction, the intravenous route is preferable, so that the minimal dose can be injected.3,5,11,15
Another option for induction of anaesthesia is alphaxalone. Propofol, however, seems to be a better alternative, due to the advantage of the biotransformation metabolic pathway of glucuronide conjugation and also due to its potential extrahepatic metabolism.28
Regarding the effect of inhalational anaesthetics on hepatic function, it should be noted that the hepatic blood supply stems from the hepatic artery and portal vein. The hepatic artery provides 25% and the portal vein 75% of hepatic blood flow, however, oxygen is supplied by 45-50% through the hepatic artery blood and by 50-55% through portal blood.15 Control of blood flow through the hepatic artery is obtained through mechanisms that counteract changes in blood flow in the portal vein. Therefore, hepatic perfusion can be maintained with limited changes. This protective mechanism is suppressed during deep general anaesthesia. All of the inhalational anaesthetics may cause dose-dependent hypotension and reduced hepatic perfusion to varying extent. This may lead to a reduction in oxygen supply and hepatic cell necrosis. Any other factor that may result in a reduction in cardiac output or hypotension can also cause a reduction in hepatic perfusion, with the expected consequences. Among the inhalational anaesthetics, isoflurane (and the newer sevoflurane and desflurane) seems to least affect hepatic perfusion, whereas halothane results in the most severe reduction.3,5,7,9,11,15,16
Halothane has been implicated in hepatopathy (halothane-induced hepatitis), due to an immune-mediated response after the halothane metabolite, trifluroacetylchloride, binds with hepatic proteins. In humans, this condition is rare (1 in every 6000-10000 anaesthesia cases). In dogs there have been reports of halothane-induced hepatitis.8 For that reason, it is preferable to avoid halothane in animals with hepatic disorders, replacing it with isoflurane, sevoflurane or desflurane.3,5,11,15
Almost every injectable anaesthetic undergoes hepatic metabolism and/or elimination. In contrast, inhalational anaesthetics do not depend on the liver for elimination for the most part, except for halothane and methoxyflurane. When general anaesthesia is necessary in high risk animals with liver disease, the clinician’s goal should be to avoid injectable anaesthetics and use inhalational agents for induction and maintenance of anaesthesia.25
Perioperative analgesia in dogs and cats with liver disease can be attained with opioids (which can be included in the preanaesthetic medication) or with the epidural injection of local anaesthetics or morphine (preservative-free). An epidural injection should be attempted only in cases in which coagulation disorders have been excluded or treated. Even though the surgical approach to the liver is via upper midline laparotomy, epidural anaesthesia may provide sufficient pain relief. It has been proven that epidural injection of morphine in dogs provides analgesia also for surgery or painful conditions in the front limbs or thorax. In cases of animals with liver disease in which surgery is necessary but unrelated to the liver disease, if possible the procedure should be performed under local anaesthesia. Sedatives are usually required for this purpose. However, animals with hepatic disorders may have a reduced level of consciousness therefore high doses of sedatives are usually not required.3,11,15
In cases in which muscular relaxation is needed, atracurium or cis-atracurium are preferable, considering that these drugs do not undergo hepatic metabolism. Instead, they are broken down in plasma based on Hofmann elimination, which depends only on plasma pH and temperature. Between the two, cis-atracurium is preferable because of the production of smaller amounts of the metabolite laudanosine, which is considered to be epileptogenic.28
The monitoring of vital signs of an animal with liver disease under general anaesthesia should be particularly meticulous. Ideally, it should be performed with the use of electronic multimodal monitoring equipment. The following factors should be monitored: electrocardiogram, pulse oximetry, capnogram, central venous pressure, arterial pressure (direct or indirect), temperature, blood gas analysis, urine production, haematocrit, total protein, blood glucose, and electrolyte levels.3,15 Nevertheless, the standard monitoring of vital signs performed by a clinician during general anaesthesia can severely reduce the complication rate and prevent negative sequelae. Furthermore, the following are considered to be particularly useful:
It is important to monitor arterial blood pressure during general anaesthesia, because inhalational anaesthetics, as well as other anaesthetic agents, cause a reduction in cardiac output, and therefore a reduction in hepatic perfusion. Mean arterial pressure should be maintained above 60 mmHg, with appropriate titration of anaesthetic depth and infusion of crystalloids and/or colloid solutions [5-10 ml kg h-1, intravenously (IV)].3,11
Glucose homeostasis may not be affected even after 80% loss of hepatic function; therefore, glucose concentration could be maintained within normal levels even in such cases. Nevertheless, animals with liver disease which undergo the stress of anaesthesia and surgery may manifest hypoglycaemia. The levels of blood glucose should be monitored after the induction of anaesthesia and in case of hypoglycaemia, the latter should be managed with bolus infusions of dextrose 35% or with constant rate infusion of dextrose 5%.3,11
Blood loss is more extensive in cases of surgery intended to correct intrahepatic portal vein shunts. In such cases, blood obtained from an appropriate donor should be available for transfusion.3
Care should be given to avoid or manage hypothermia by use of proper heat-providing means, due to consequent reduced anaesthetic agent metabolism, among other issues.5
Regarding support of the respiratory function, hyperventilation and hypocapnia must be avoided (ideal partial pressure of carbon dioxide in arterial blood, PaCO2, should be 40-42 mmHg). If artificial ventilation is necessary, the fact that the increased intrathoracic pressure is likely to reduce venous return, cardiac preload, cardiac output and, finally, hepatic perfusion, should be taken into consideration. Furthermore, hypercapnia results in reduced blood flow in the portal vein, whereas hypocapnia and consequent alkalosis favour the conversion of nitrate into ammonia, which is aggravating for animals with hepatic encephalopathy.5,15
Suggested anaesthetic protocol for animals with liver disease
- Preanaesthetic medication: opioids (morphine 0.1-0.2 mg kg-1, intramuscularly (IM), pethidine 2-3 mg kg-1 IM, butorphanol 0.1-0.2 mg kg-1 IM, methadone 0.2-0.5 mg kg-1 IM in mild hepatopathies) or no premedication. Benzodiazepines, phenothiazines and a2- agonists are best avoided.
- Lactated Ringer’s or 0.9% NaCl IV are infused at a rate of 5-10 ml kg-1 h-1.
- Pre-oxygenation with 100% oxygen for 5 minutes via face mask and induction of anaesthesia with isoflurane via face mask (4-5%) in oxygen with or without small doses of propofol.
- Analgesia with epidural injection of morphine and/ or local anaesthetic (provided that coagulation disorders have been excluded or treated).
- Maintenance of anaesthesia with isoflurane (1.5- 2%) with oxygen.
- Meticulous monitoring of vital signs.
- Factors with negative effects on liver perfusion should be avoided: hypovolaemia and hypotension should be managed with fluids, anaesthetic depth should be properly adjusted and hyperventilation should be avoided.3,15,25
Extensive monitoring of the animal with hepatic disease that undergoes surgery should continue during the immediate postoperative period. The risk is that reduced liver metabolism of agents that require liver metabolism will probably prolong the recovery period. Even though this prolongation is often unavoidable, the patient should be supported (οxygen, IV fluids, warming) until recovery is complete. During the recovery period, administration of glucose may be necessary.5
Specific aspects of anaesthesia in dogs with portosystemic shunts
The patients are usually young dogs (congenital shunt) with hepatic hypoplasia. In such dogs increased ammonia levels are usually observed, as well as reduced protein synthesis, coagulation disorders, acid-base disorders, and blood glucose level abnormalities. Cases with such disorders should be classified as high risk patients.15,25,26 In dogs with portosystemic shunts the proper preanaesthetic preparation is of utmost importance (management of HE, coagulation disorders, ascites). Everything that has been already discussed for dogs with severe liver disease also applies in such cases. Furthermore, medical treatment including a diet with reduced protein content should be administered with lactulose, enemas, and antibiotics (in order to reduce the production of ΝΗ3 and other toxins), and possibly levetiracetam in order to prevent any epileptic activity. Medical and dietary treatment administered to these animals prior to surgery should be continued post-operatively. Specifically, if there is a history of seizures, it has been shown that levetiracetam (20 mg kg-1 per os q8h beginning 24 h prior to surgery) continued post-operatively, results in control of the epileptic activity and reduced mortality.8
Because abdominal bleeding is common in cases of ligation of intrahepatic shunts, blood for transfusion should be available (obtained no longer than one week prior to surgery).3
In the immediate postoperative period following portosystemic shunt ligation, portal hypertension may ensue, which manifests with abdominal pain, ascites, vomiting and diarrhoea. In dogs, the normal portal vein pressure is 8-13 cmH2O, whereas in animals with portosystemic shunts it is usually lower. After surgical ligation of the shunt, portal pressure should not increase by more than 9-10 cmH2O, compared to the pressure measured prior to ligation and it should not be above 20-23 cmH2O as an absolute number. Perioperative measurement of central venous pressure may assist in predicting postoperative portal hypertension. More specifically, central venous pressure measured 3 minutes post ligation should not be lower by more than 1 cmH2O compared to its value prior to ligation in order to avoid portal hypertension.35,36
Liver biopsy
In order to perform an ultrasound-guided liver biopsy, short-acting drugs which ensure analgesia and anaesthesia can be used, so that the procedure can be completed unimpeded. A combination often used for this purpose is fentanyl (5 μg kg-1 IV) with propofol (1-2 mg kg-1 IV). In stabilised cases even dexmedetomidine can be used (2-3 μg kg-1 IV), followed by the administration of propofol. The effect of dexmedetomidine is reversed at the end of the procedure by administration of atipamezole. The animals should be monitored postoperatively for bleeding in the abdominal cavity.28
If liver biopsy is performed via laparotomy, the appropriately modified anaesthetic protocol is selected according to what has already been previously discussed for animals with liver disease.
Feline hepatic lipidosis
In cats with hepatic lipidosis anaesthesia may be required to insert a feeding tube (e.g. oesophagostomy). In such cases, short-acting drugs are selected (e.g. propofol), but induction of anaesthesia can also be accomplished via inhalational anaesthetic (isoflurane) in an induction chamber/oxygen cage. Anaesthesia is maintained by isoflurane administration via an endotracheal tube. The concern that has been raised over the lipids contained in the propofol solution seems to be only theoretical in nature and no sequelae have been observed in the clinical setting.28
Biliary tract disease
In people, fentanyl, remifentanil, and also morphine increases the tone of the sphincter of Oddi, resulting in increased pressure in the biliary tract. In contrast, tramadol and buprenorphine are considered to have a minimal effect on the latter. The frequency, however, of problems being observed due to increased pressure in the biliary tract is very low, even when μ-agonists such as fentanyl are used. In dogs, the pancreatic duct and the biliary duct sphincters function independently. Even though it was suggested in the past, nowadays it is not considered good practice to withhold administration of μ-agonists for the risk of precipitating cholangitis or pancreatitis.28
In conclusion, animals with hepatic disorders may be submitted to general anaesthesia relatively safely nowadays and without increased complication rates, if the sequelae of the underlying liver disease are taken into consideration, and the proper anaesthetic drugs are selected, which depend as little as possible on hepatic metabolism for the termination of their anaesthetic effect, and if close monitoring and proper support are offered during the postoperative period.
References
1. Anagnostou TL, Kazakos GM, Savvas I, Papazoglou LG, Rallis TS, Raptopoulos D. Remifentanil/isoflurane anesthesia in five dogs with liver disease undergoing liver biopsy. J Am Anim Hosp Assoc 2011, 47:103-109.
2. Aronson LR, Gacad RC, Kaminsky-Russ K, Gregory CR, Mullen KD. Endogenous Benzodiazepine Activity in the Peripheral and Portal Blood of Dogs with Congenital Portosystemic Shunts. Vet Surg 1997, 26:189-194.
3. Bennett RC and Pascoe PJ. Gastrointestinal and Hepatic Disease. In: Manual of Small Animal Anaesthesia and Analgesia. Seymour C, Gleed R (eds). BSAVA: Cheltenham, 1999, pp.197-209. 4. Benson GJ and Thurmon JC (1987) Special Anesthetic Considerations for Caesarean Section. In: Principles & Practice of Veterinary Anesthesia. Short CE (ed). Williams & Wilkins: Baltimore, 1987, pp.337-348.
5. Dodman NH and Engelking LR. Pathophysiological changes of the hepatic system. In: Principles & Practice of Veterinary Anesthesia. Short CE (ed). Williams & Wilkins: Baltimore, 1987, pp.221-237.
6. Downing JW, Buley RJR, Brock-Utne JG, Houlton PC. Etomidate for induction of anaesthesia at caesarean section: comparison with thiopentone. Br J Anaesth 1979, 51:135-140.
7. Frink EJ, Morgan SE, Coetzee A, Conzen PF, Brown BR. The Effects of Sevoflurane, Halothane, Enflurane, and Isoflurane on Hepatic Blood Flow and Oxygenation in Chronically Instrumented Greyhound Dogs. Anesthesiology 1992, 76:85-90.
8. Fryer KJ, Levine JM, Peycke LE, Thompson JA, Cohen ND. Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. J Vet Intern Med 2011, 25:1379-1384.
9. Gaunt PS, Meuten DJ, Pecquet-Goad ME. Hepatic necrosis associated with use of halothane in a dog. J Am Vet Med Assoc 1984, 184:478- 480.
10. Gelman S, Fowler KC, Smith LR. Liver Circulation and Function during Isoflurane and Halothane Anesthesia. Anesthesiology 1984, 61:726-730.
11. Greene SA. Gastrointestinal Disease. In: Lumb & Jones’ Veterinary Anesthesia. 3rd edn. Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins: Baltimore, 1996, pp.798-803.
12. Greene SA. Hepatic Disease. In: Lumb & Jones’ Veterinary Anesthesia. 3rd edn. Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins: Baltimore, 1996, pp.791-797.
13. Greene SA and Benson GJ. Pregnancy. In: Veterinary anesthesia and pain management secrets. Greene SA (eds). Hanley & Belfus: Philadelphia, 2002, pp.229-231.
14. Hall LW, Clarke KW, Trim CM, Veterinary Anaesthesia. 10th edn. W.B. Saunders: London, 2001. 15. Hedlund J. Surgery of the Reproductive and Genital Systems. In: Small Animal Surgery. Fossum TW (ed). Mosby-Year Book: St. Louis, Missouri. 1997.
16. Jones JL. Perioperative management of patients with liver disease. In: Veterinary anesthesia and pain management secrets. Greene SA (ed). Hanley & Belfus: Philadelphia, 2002, pp.179-185.
17. Merin RG, Bernard J, Doursout M, Cohen M, Chelly JE. Comparison of the Effects of Isoflurane and Desflurane on Cardiovascular Dynamics and Regional Blood Flow in the Chronically Instrumented Dog. Anesthesiology 1991, 74:568-574.
18. Meyer HP, Legemate DA, Van den Brom W, Rothuizen J. Improvement of Chronic Hepatic Encephalopathy in Dogs by the Benzodiazepine- Receptor Partial Inverse Agonist Sarmazenil, but Not by the Antagonist Flumazenil. Met Brain Dis 1998, 13(3):241-251.
19. Michelsen LG1, Salmenperä M, Hug CC Jr, Szlam F, VanderMeer D. Anesthetic potency of remifentanil in dogs. Anesthesiology 1996, 84:865-72.
20. Muir WW. Acid-Base and electrolyte disturbances in dogs with gastric dilatation-volvulus. J Am Vet Med Assoc 1982, 181:229-231.
21. Muir WW. Gastric dilatation-volvulus in the dog, with emphasis on cardiac arrhythmias. J Am Vet Med Assoc 1982, 180:739-742.
22. Muir WW and Mason DE. Side effects of etomidate in dogs. J Am Vet Med Assoc 1989, 194:1430-1434.
23. Navapurkar VU, Archer S, Gupta SK, Muir KT, Frazer N, Park GR. Metabolism of remifentanil during liver transplantation. Br J Anaesth 1998, 81:881-886.
24. Paddleford RR. Anesthesia for Cesarean Section in the Dog. Vet Clin North Am Small Anim Pract 1992, 22:481-484.
25. Rallis T. Canine and Feline Gastroenterology. 2nd edn. University Studio Press: Thessaloniki, 2000.
26. Raffe MR. Anesthesia for Severe Liver Dysfunction. Vet Clin North Am Small Anim Pract 1992, 22:478-480.
27. Rahimzadeh P, Safari S, Hamid Reza Faiz S, Moayed Alavian S. Anesthesia for Patients With Liver Disease, Hepat Mon 2014, 14:e19881.
28. Self I. Gastrointestinal, laparoscopic and liver procedures, BSAVA Manual of canine and feline Anesthesia and analgesia. 3rd edn. 2017, 24:342-355.
29. Seymour C. Caesarian Section. In: Manual of Small Animal Anaesthesia and Analgesia. Seymour C, Gleed R (eds). BSAVA: Cheltenham, 1999, pp.217-222.
30. Swalec KM, Smeak DD. Partial versus complete attenuation of single portosystemic shunts. Vet Surg 1990, 19:406-411.
31. Swalec KM, Smeak DD, Brown J. Effects of mechanical and pharmacologic manipulations on portal pressure, central venous pressure, and heart rate in dogs. Am J Vet Res 1991, 52:1327-1335.
32. Thurmon JC, Tranquilli WJ, Benson GJ. Cesarean Section Patients. In: Lumb & Jones’ Veterinary Anesthesia. 3rd edn. Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins: Baltimore, 1996, pp.818-828.
33. Tranquilli WJ. Anesthesia for Cesarean Section in the Cat. Vet Clin North Am Small Anim Pract 1992, 22:484-486.
34. Trim CM. Anesthetic Considerations of the Gastrointestinal Tract. In: Principles & Practice of Veterinary Anesthesia. Short CE (ed). Williams & Wilkins: Baltimore, 1987, pp.261-270.
35. Waterman-Pearson AE. Περιεγχειρητική θεραπεία με υγρά και ηλεκτρολύτες. Πρακτικά ημερίδας αναισθησιολογίας και εντατικής θεραπείας μικρών ζώων, Χαλκιδική, 1997, σελ.31-45.
36. Waterman-Pearson AE. Urogenital Disease. In: Manual of Small Animal Anaesthesia and Analgesia. Seymour C, Gleed R (eds). BSAVA: Cheltenham, 1999, pp.211-215.
37. Weil AB. Anesthesia for Patients with Renal-Hepatic Disease, Top Companion Anim Med 2010, 2:87-91.
38. Wong PL. Anesthesia for Gastric Dilatation/Volvulus. Vet Clin North Am Small Anim Pract 1992, 22:471-478.
Corresponding author:
Αnagnostou Tilemachos
Companion Animal Clinic
School of Veterinary Medicine, A.U.Th.
11 Stavrou Voutyra str., 546 27 Thessaloniki
Τel: +30 2310 994420
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