Page 915 - Equine Clinical Medicine, Surgery and Reproduction, 2nd Edition

890 CHAPTER 5

VetBooks.ir hyperammonaemia deriving from the GI tract glutamine from ammonia. Efficacy or safety have
not been established in horses. Sodium benzoate and
leading to increased cerebral ammonia, and subse-
quently glutamine, leading to oedema. Sedation is
purported benefits on ammonia detoxification, as
usually required in subjects manifesting moderate to zinc supplementation have also been used for their
severe signs of HE. This should not pose any par- have several other drugs including the dopamine
ticular problems in mature horses in which slightly receptor agonist bromocriptine, the benzodiazepine
reduced doses of commonly-used sedatives and tran- receptor antagonist flumazenil, glutamate receptor
quillisers (e.g. xylazine 0.5 mg/kg i/v; detomidine 10 antagonists, NSAIDs and antihistamines.
μg/kg i/v; acepromazine 25 μg/kg i/v) are suitable.
Diazepam or midazolam may be best avoided due to Antifibrotic therapy
the implication of benzodiazepine-like substances Hepatic fibrosis is a common histopathological find-
in the pathophysiology of HE. Acute management ing in liver biopsies and the single histopathological
of severe HE is best approached with i/v boluses of feature with the strongest association with a poor
hypertonic (7.2%) saline (6 ml/kg). This can have an outcome for the affected horse. It is, however, poten-
acute and dramatic effect in resolving or improv- tially reversible (depending on stage and duration)
ing the neurological signs in many cases. Mannitol and persists only as a dynamic balance between the
boluses (0.5–1.0 g/kg 20% solution) might also be activities of degradative matrix metalloproteinases
used but tend to be less effective in this author’s (MMPs) and tissue inhibitors of metalloproteinases
experience. (TIMPs) controlled by hepatic stellate cells (HSCs).
Oral administration of lactulose (0.3 ml/kg q4–12 Activated HSCs tend to promote fibrosis, with qui-
h), a non-absorbable disaccharide, is useful for con- escent cells favouring fibrolysis. Although many
tinued treatment of signs of HE. The unabsorbed proposed antifibrotic therapies that target HSCs
lactulose arrives in the colon where it is metabo- are likely to be cost-prohibitive, several drugs used
lised by bacteria to acetic and lactic acids, lower- in humans may be acceptable in horses, although
ing the intraluminal pH. This has several beneficial none have been subject to well-controlled trials and
effects including decreased absorption of proton- lack an evidence basis. Anti-inflammatory drugs
ated ammonium ions, increased incorporation of are suggested to moderate the fibroplastic activi-
ammonia into bacteria and inhibition of luminal ties of HSCs and include glucocorticoids such as
urease and proteases. In the author’s experience, oral prednisolone (1–2 mg/kg q24 h) and dexametha-
lactulose administration generally has a beneficial sone (0.05 mg/kg alternate days to 0.1 mg/kg q24 h).
effect on the clinical signs of HE in horses and this Other drugs such as pentoxyfylline (10 mg/kg q12 h)
product also remains the most popular substance and azathioprine (3 mg/kg q24 h) might be preferred
for decreasing intestinal ammonia production in in laminitis-prone individuals or may be used along-
human HE patients, despite a lack of strong scien- side glucocorticoids when more aggressive therapy is
tific evidence. Oral antimicrobials including metro- deemed appropriate.
nidazole (15–25 mg/kg q12 h) or neomycin (15 mg/ Angiotensin II has been shown to promote activa-
kg q6 h) may also be used as a means of reducing tion of HSCs and to stimulate transforming growth
intestinal bacterial ammoniagenesis. In addition to factor-β1 synthesis, which is the major profibrotic
decreasing systemic absorption of ammonia, another cytokine. Consequently angiotensin-converting
strategy used in human patients is promotion of enzyme inhibitors have been shown in other species
peripheral ammonia detoxification, although this is to disrupt hepatic fibrosis and have further beneficial
not yet reported in horses. L-ornithine-L-aspartate actions including enhancing hepatic regeneration
(LOLA) is the product with the best evidence basis due to promoting hepatocyte growth factor syn-
and can be administered orally or as an i/v infusion thesis. No equine reports exist concerning the use
to human HE patients. LOLA effectively reduces of such drugs and there are bioavailability concerns
serum ammonia concentration by providing essen- about some. Good efficacy of benazepril (0.25–0.5
tial substrates for peripheral synthesis of urea and mg/kg p/o q24 h) is reported in cases of equine