Page 475 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

442 SECTION | V Metals and Micronutrients

VetBooks.ir targets lead in the soft tissue (e.g., British Anti-Lewisite experimental work, succimer given to experimentally lead-
poisoned calves IV at 25 mg/kg/day for 4 days was more
or BAL) has been recommended but is difficult to accom-
effective than CaEDTA at decreasing lead concentrations in
plish in most practice settings. CaEDTA can be nephro-
toxic, especially in situations where the animal is the liver and kidney (Meldrum and Ko, 2003).
dehydrated. Recommended treatment with CaEDTA for In an recent experimental study, Pachauri et al. (2009)
large animals is 73 mg/kg/day, divided into two or three provide evidence of the efficacy of combinational therapy
doses given over the course of a day by slow IV. For using an antioxidant with a thiol chelator in reversing neuro-
example, a 6.6% solution of CaEDTA (in normal saline logical dystrophy caused by chronic lead exposure in rats.
or 5% dextrose) can be given IV at a rate of 1 mL per 2
pounds (0.9 kg) of body weight per day in divided doses. CONCLUDING REMARKS AND FUTURE
Treatment should continue for 3 5 days. If additional DIRECTIONS
treatment is needed, a rest period of 2 days with contin-
ued supported care is suggested before the additional While cases of lead toxicosis in animals have been decreas-
3 5-day second treatment period. An alternative treat- ing, it should remain on the clinician’s list of rule-outs for
ment regimen is to administer CaEDTA at 110 mg/kg IV seizure-like activity, blindness, and vague neurological and
twice daily for 2 days. If additional treatment is needed, GI disorders. At a minimum, the environment of the ani-
first apply the 2-day rest period of supportive care before mal should be reviewed for possible lead sources.
initiating the second treatment period of 2 days at
110 mg/kg twice daily. Thiamine has been shown to be a REFERENCES
valuable adjunct to the treatment of lead poisoning in
ruminants (Bratton et al., 1981) and is recommended for Aronson, A.L., 1972. Lead poisoning in cattle and horses following
other species as well. A dose of 2 mg/kg/day for calves long-term exposure to lead. Am. J. Vet. Res. 33, 627.
and 250 2000 mg/day for adult cattle has been recom- Bratton, G.R., Zmudzki, J., Kincaid, N., et al., 1981. Thiamine as treat-
mended. A 2-day withdrawal period for both meat and ment of lead poisoning in ruminants. Mod. Vet. Pract. 62, 441 446.
milk is recommended (Haskell et al., 2005). Bressler, J.P., Goldstein, G.W., 1991. Mechanisms of lead neurotoxicity.
If commercial CaEDTA is unavailable, a stock solution Biochem. Pharmacol. 41, 479 484.
Clasen, R.A., Hartmann, J.F., Starr, A.J., et al., 1973. Electron micro-
can be formulated for emergency antidotal usage. A 10%
scopic and chemical studies of the vascular changes and edema of
stock solution can be made by dissolving 101.1 g of tetra-
lead encephalopathy. Am. J. Pathol. 74, 215 240.
sodium EDTA (Na 4 EDTA) plus 30 g of anhydrous calcium
FDA-CVM, 2011. Target animal safety review memorandum. https://
chloride (CaCl 2 ) in distilled water to a final volume of
www.fda.gov/downloads/aboutfda/centersoffices/officeoffoods/cvm/
1000 mL. From the stock solution, a working 2.22% cvmfoiaelectronicreadingroom/ucm274327.pdf. (accessed 01.03.17.).
solution can be made by mixing 220 mL of the 10% stock Flora, S.J.S., Agrawal, S., 2017. Arsenic, cadmium and lead. In: Gupta,
solution with 780 mL distilled water. Using the 2.22% solu- R.C. (Ed.), Reproductive and Developmental Toxicology, second ed.
tion, the daily dosage of 73 mg/kg/day is equal to approxi- Academic Press/Elsevier, Amsterdam, pp. 537 566.
mately 3.5 mL/kg of body weight. This should be divided Goldstein, G.W., Asbury, A.K., Diamond, I., 1974. Pathogenesis of lead
into two or three separate administrations (Thompson, encephalopathy. Uptake of lead and reaction of brain capillaries.
1992). Tetrasodium EDTA should never be administered Arch. Neurol. 31, 382 389.
Gwaltney-Brant, S., 2004. Lead. In: Plumlee, K.H. (Ed.), Clinical
by itself as it may cause hypocalcemia.
Veterinary Toxicology. Mosby, St. Louis, MO, pp. 204 210.
Recommended treatment with CaEDTA for dogs is
Hamir, A.N., Sullivan, N.D., Handson, P.D., 1988. Tissue lead distribu-
100 mg/kg/day in four divided doses. Treatment should
tion and pathological findings in lead exposed dogs maintained on
continue for 2 5 days, and a second round of treatment is
fat and calcium modified diets. Br. Vet. J. 144, 240 245.
rarely needed. A 5-day rest period is recommended before Haskell, S.R., Payne, M., Webb, A., et al., 2005. Antidotes in food ani-
applying additional treatment. CaEDTA concentration mal practice. J. Am. Vet. Med. Assoc. 226 (6), 884 887.
should be 10 mg/mL and may be administered by slow IV Kelman, B.J., Walter, B.K., 1980. Transplacental movements of inorganic
or by SQ route. Cats can be treated with 27.5 mg in lead from mother to fetus. Proc. Soc. Exp. Biol. Med. 163, 278 282.
15 mL normal saline or 5% dextrose SQ every 6 h for 5 King, J.B., 2016. Proximal tubular nephropathy in two dogs diagnosed
days or the same dose as a slow IV infusion. with lead toxicity. Aust. Vet. J. 94, 280 284.
Succimer (meso-2,3-dimercaptosuccinic or DMSA) is an Kowalczyk, D.F., 1984. Clinical management of lead poisoning. J. Am.
Vet. Med. Assoc. 184, 858 860.
orally administered chelating agent that is less likely to have
Meldrum, J.B., Ko, K.W., 2003. Effects of calcium disodium EDTA and
adverse side effects associated with CaEDTA. The recom-
meso-2,3-dimercaptosuccinic acid on tissue concentrations of lead
mended treatment in dogs is an oral dose of succimer at
for use in treatment of calves with experimentally induced lead toxi-
10 mg/kg, repeated three times daily for 10 days (Ramsey
cosis. Am. J. Vet. Res. 64, 672 676.
et al., 1996). Succimer has also been used orally in caged O’Hara, T.M., Bennett, L., McCoy, P.C., et al., 1995. Lead poisoning
birds at a dose of 25 35 mg/kg twice daily for 5 days. and toxicokinetics in a heifer and fetus treated with CaNa 2 EDTA
Several weeks of therapy may be needed in avians. In initial and thiamine. J. Vet. Diag. Investig. 7, 531 537.