tomographic angiography or magnetic resonance angiography (d’Anjou et al., 2004; Sura et al., 2007; Berent and Tobias, 2009; Mai and Weisse, 2011; Nelson and Nelson, 2011). Liver biopsy is required for confirmation of parenchymal hepatic disease. MRI of the brain of dogs and cats with portosystemic shunts may reveal cerebral cortical atrophy characterized by widened sulci and hyperintensity of the lentiform nuclei on T1-weighted images (Torisu et al., 2005). In addition, bilateral diffuse hyperintensity predominately of the parietal and occipital cortex grey matter on T2-weighted MR images has been reported in a dog with portosystemic shunt. The authors suggested that the signal changes represented cerebral oedema associated with cortical laminar necrosis caused by acute hyperammonaemia (Moon et al., 2012).
Management
The management of HE depends on the underlying cause, the degree of hepatic dysfunction and the severity of clinical signs. The aims of HE treatment are: (i) stop seizure activity; (ii) reduce serum levels of neurotoxic agents; and (iii) treat the underlying aetiology.
Seizures should be controlled with AEMs that undergo minimal or no hepatic metabolism such as levetiracetam (LEV) (see Chapter 16). LEV can be administered in dogs and cats at 60 mg/kg intravenously or orally as an initial loading dose, which can be followed (8h later) by a maintenance dose of 20 mg/kg every 8 h. Alternatively or in addition to LEV, bromide can be administered at a loading dose in dogs (see Chapter 14). Intravenous propofol as boluses (1–2 mg/kg) or constant rate infusion (0.1–0.6 mg/kg/min titrated to effect or up to 6 mg/kg/h) may be required in animals with persistent seizure activity (see Chapter 24). Oro-tracheal intubation, ventilation, haemo-dynamic support and intensive care monitoring may be required.
The production of ammonia in the gastrointestinal tract can be reduced by administration of:
• Lactulose (1–3 ml/kg/day orally divided into two to three doses) to decrease intestinal transit time, prevent constipation, alter the intestinal flora, and create an acid environment in order to trap ammonia as ammonium;
Fig. 4.3. Doppler ultrasound images (a, b) of the cranial dorsal abdomen of a 5-month-old male bichon frise with a portocaval shunt resulting in hepatic encephalopathy. Two images (a, b) are shown of different segments of the shunt at the level of the lesser curvature of the stomach (S). The shunt (arrows) is a large tortuous vessel arising from the right gastric vein. The liver (L) is small. MR angiography of the same dog (c). Blood is shunted via a large sigmoidal, tortuous vessel arising at the level of the gastroduodenal vein. The vessel loops (arrows) cranially then across the midline dorsal to the lesser curvature of the stomach and medial to the body of the stomach and finally loops cranially again to enter the caudal vena cava just caudal to the diaphragm close to the confluence of the left hepatic veins. RK, right kidney; LK, left kidney; PV, portal vein; S, stomach; Ao, aorta; CVC, caudal vena cava. (Photo courtesy of Andrew Halloway)
• Antibiotics such as ampicillin (22 mg/kg orally every 8 h), metronidazole (7.5 mg/ kg orally every 12 h), or neomycin (20 mg/ kg orally every 8 h), to reduce the colonic bacterial flora producing ammonia;
• Low-level high-quality protein diet.
In animals unable to take oral medications (e.g. propofol infusion, severe post-ictal phase, stupor or coma) lactulose can be administered by retention enema (20 ml/kg, made of three parts of lactulose diluted in seven parts warm water, every 4–6 h) and the antibiotic can be administered parenterally. Feline liver steatosis (lipidosis) should not be treated by dietary protein reduction but instead by forced feeding of amino acid-rich nutrients (Rothuizen, 2009). Protein intake should not be restricted excessively in growing young animals. A balanced rather than excessively restricted protein intake is currently preferred in people with HE (Bismuth et al., 2011). Administration of high doses of probiotics containing urease negative bacteria (such as Lactobacillus acidophilus or Enterococcus faecium) may help to modify the intestinal flora and decrease ammonia production. In addition, it has been suggested that administration of L-carnitine may reduce ammonia level by increasing energy metabolism (Bismuth et al., 2011). Intravenous fluids should be administered to animals with fluid and electrolyte abnormalities. Conditions that aggravate HE (see Box 4.3) should be avoided. Proton pump inhibitors such as omeprazole should be administered to animals with proximal gastrointestinal haemorrhage. Supportive nutraceutical therapy such as S-adenosyol-L-methionine (SAMe) has been recommended for a variety of liver diseases; however, it is usually unnecessary in portovascular anomalies that can be treated surgically (Berent and Tobias, 2009). Congenital portosystemic shunts can be completely or partially ligated with nonabsorbable sutures or gradually attenuated with an ameroid constrictor, cellophane band, or hydraulic occluder. Gradual attenuation is preferred to reduce the risk of postoperative complications (Berent and Tobias, 2009). Acute complications of shunt attenuation include intraoperative haemorrhage, prolonged anaesthetic recovery, seizures and other forebrain neurological signs, portal hypertension and refractory hypoglycaemia. Severe persistent neurologic signs (including blindness and seizures) represent the most common cause of death after portosystemic shunts attenuation (Berent and Tobias, 2009). Central blindness has been reported in up to 44% of cats following portosystemic shunt surgery and usually resolves within 2 months after surgery (Kyles et al., 2002). Post-operative seizures have been reported in 3% to 7% of dogs and 8% to 22% of cats after shunt attenuation (Tisdall et al., 2000; Kyles et al., 2002; Frankel et al., 2006; Lee et al., 2006; Lipscomb et al., 2007). Seizures may occur up to 80 h after surgery, frequently progress to status epilepticus and may be difficult to control. These seizures are not associated with hypoglycaemia, hyperammonaemia, or attenuation technique (Berent and Tobias, 2009). Post-operative seizures can be treated with intravenous levetiracetam or propofol (see Chapters 16 and 24). Levetiracetam administered at 20 mg/kg orally every 8 h for a minimum of 24 h before surgery significantly decreased the risk of post-operative seizures and death in dogs undergoing surgical attenuation of extrahepatic congenital portosystemic shunts with ameroid ring constrictors (Fryer et al., 2011).
Renal-associated encephalopathy
Overview
Renal-associated encephalopathy can occur in animals with acute or end-stage chronic renal failure (uraemic encephalopathy), following haemodialysis (dialysis disequilibrium syndrome) or renal transplantation (post-renal transplantation encephalopathy). As for hepatic encephalopathy the pathogenesis of renal-associated encephalopathy is complex and incompletely understood. Neurological signs may result from accumulation of uraemic toxins, altered balance between excitatory and inhibitory neurotransmitters, as well as acid-base, fluid and electrolyte abnormalities. Parathyroid hormone (PTH) disturbance may also play a role in the pathogenesis of uraemic encephalopathy. In addition, hypertension secondary to renal disease may lead to intracranial cerebrovascular accidents (O’Brien, 1998). Dialysis disequilibrium syndrome is thought to be caused by an osmotic gradient between the brain cells and the extracellular fluid due to excessively rapid haemodialysis, which results in cellular swelling and cerebral oedema. Post-renal transplantation encephalopathy (resulting in seizures, stupor, ataxia and central blindness) has been reported in cats and it is most likely associated with uncontrolled hypertension (Kyles et al., 1999). Uraemic encephalopathy has been infrequently reported in dogs with renal failure (Wolf, 1980; Fenner, 1995).
