Page 689 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

654 SECTION | IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir of dogs and cats (Thrall et al., 1984b; Connally et al., 1989; Connally et al., 1996) and cats (Thrall et al., 2006;
Connally et al., 2010). Fomepizole is an ADH inhibitor,
1996) and is attributed to inhibition of glucose metabolism
not a competitive substrate, and it does not induce CNS
by aldehydes, increased epinephrine and endogenous corti-
costeroids, and uremia. Animals presenting with late EG depression (in dogs), diuresis, or hyperosmolality at the
poisoning are likely to have little or no osmole gap recommended dosage. The recommended dose of fomepi-
increase but will have an increased osmolality (whether zole for dogs is 20 mg/kg body weight i.v. initially, fol-
calculated or measured) because of the azotemia and lowed by 15 mg/kg i.v. at 12 and 24 h and 5 mg/kg i.v. at
hyperglycemia. Animals remain isosthenuric in the later 36 h (Grauer et al., 1987; Connally et al., 1996; Thrall
stages of toxicosis due to renal dysfunction and impaired et al., 2006). Cats must be given a much higher dose of
ability to concentrate urine. Calcium oxalate crystalluria fomepizole than dogs because feline ADH is less effec-
persists for as long as animals are producing urine. Urine tively inhibited by fomepizole than is canine ADH
abnormalities associated with renal damage may include (Connally et al., 2000, 2010). Cats are initially treated
hematuria, proteinuria, and glucosuria. Granular and cellu- with 125 mg/kg fomepizole i.v. followed by 31.25 mg/kg
lar casts, white blood cells, red blood cells, and renal epi- i.v. fomepizole at 12, 24, and 36 h. The only adverse clin-
thelial cells may be observed in the urine sediment of ical sign that the authors have observed is CNS depres-
some patients (Thrall et al., 1984b; Connally et al., 1996). sion that appears to be fomepizole related (Connally
et al., 2010). If ingestion of a large dose of EG is sus-
pected, repeating serum quantification tests can be per-
Treatment formed to determine whether continuation of therapy
Therapy for EG poisoning is aimed at preventing absorp- beyond 36 h is necessary. Alternatively, additional doses
tion, increasing excretion, and preventing metabolism of of fomepizole can be administered empirically.
EG. Supportive care to correct fluid, acid base, and elec- Appropriate therapy also consists of i.v. fluids to correct
trolyte imbalances is also helpful. Although therapeutic dehydration, increase tissue perfusion, and promote diure-
recommendations have traditionally included induction of sis. The fluid volume administered should be based on the
vomiting, gastric lavage, and administration of activated maintenance, deficit, and continuing loss needs of the
charcoal (Thrall et al., 1995, 1998), it is likely that these patient. Frequent measurement of urine production, serum
procedures are not beneficial because of the rapidity with urea nitrogen and creatinine, and blood pH, bicarbonate,
which EG is absorbed (Davis et al., 1997). The most criti- ionized calcium, and electrolytes daily or twice daily will
cal aspect of therapy is based on prevention of EG oxida- help guide fluid and electrolyte therapy (Grauer, 1998).
tion by ADH, the enzyme responsible for the initial Bicarbonate should be given slowly i.v. to correct the
reaction in the EG metabolic pathway (Parry and metabolic acidosis. Hypothermia can be controlled with
Wallach, 1974). Typically, dogs must be treated within blankets or the use of a pad with circulating warm water.
8 h following ingestion and cats must be treated within In animals that are azotemic and in oliguric renal fail-
3 h for treatment to be successful (Dial et al., 1994a,b). ure on presentation, almost all of the EG has been metabo-
However, this is somewhat dependent on the amount of lized, and treatment to inhibit ADH is likely to be of little
EG ingested. Historically, treating EG toxicosis has been benefit. However, ADH inhibitors should be given up to
directed toward inhibiting EG metabolism with ethanol, a 36 h following ingestion to prevent the metabolism of any
competitive substrate that has a higher affinity for ADH residual EG. Fluid, electrolyte, and acid base disorders
than EG (Penumarthy and Oehme, 1975; Bostrom and Li, should be corrected and diuresis established, if possible.
1980). Ethanol has numerous disadvantages because it Diuretics, particularly mannitol, may be helpful. The tubu-
enhances many of the metabolic effects of EG. Both etha- lar damage caused by EG may be reversible, but tubular
nol and EG are CNS depressants, and it is the com- repair can take weeks to months. Animals may take up to
pounded CNS depression that most limits the usefulness 1 year following EG toxicosis to regain concentrating abil-
of ethanol as an antidote. Additional disadvantages of eth- ity, and some remain isosthenuric. Supportive care to main-
anol treatment include its metabolism to acetaldehyde, tain the patient during the period of renal tubular
which impairs glucose metabolism and is a cerebral irri- regeneration is necessary, and peritoneal dialysis may be
tant. Ethanol also contributes to metabolic acidosis by useful (Shahar and Holmberg, 1985; Fox et al., 1987; Crisp
enhancing the formation of lactic acid from pyruvate and et al., 1989). Hemodialysis has been attempted in dogs
may potentiate hypocalcemia (Money et al., 1989). with EG-induced renal failure (DiBartola et al., 1985)and
Moreover, ethanol compounds the effects of EG-induced has been shown to have a relatively good success rate in
osmotic diuresis and serum hyperosmolality (Kruse and cats with acute renal failure (Langston et al., 1997). Renal
Cadnapaphornchai, 1994). transplantation has also been used with variable success in
4-Methylpyrazole (fomepizole) has become the pre- cats with renal failure (Mathews and Gregory, 1997)and
ferred antidote in dogs (Grauer et al., 1987; Dial et al., has been described in dogs (Nemeth et al., 1997).