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Ethylene Glycol Poisoning

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Ethylene Glycol Poisoning 401-408Bates-ethylenegylcol.qxp_FF Layout1 28/10/2015 09:31 Page 1 Keeping cats safe Ethylene glycol poisoning Ethylene glycol poisoning is extremely serious in cats. A small dose can result in signs which are initially non-specific and may be easily missed. Ethanol is the antidote to ethylene glycol toxicity and works by preventing metabolism to toxic compounds. However, it is generally only worthwhile if started within a few hours of ingestion. Although a potentially lethal dose of ethylene glycol can be survived if treatment is prompt, Nicola Bates many cats with ethylene glycol poisoning present late BSc (Brunel) BSc (Open) MSc MA and as a result most cases have a fatal outcome. Nicola Bates has worked in human and veterinary toxicology for 25 years and has thylene glycol (also known amongst other been with the Veterinary Poisons Information Enames as ethanediol) is a common Service (VPIS) since it started. As well as ingredient of antifreeze; it is also found in providing emergency advice via the some screenwashes or more rarely de-icers telephone she has written extensively on (Figure 1). Most antifreezes contain ethylene veterinary toxicology. In addition to service glycol (or occasionally methanol), and are provision, she is involved in training of VPIS liquids which are added to water in engine staff and veterinary professionals. She is radiators to prevent freezing and improve cold currently the congress abstract editor for the weather performance. The usual final dilution European Association of Poisons Centres and is approximately 1:1. Clinical Toxicologists (EAPCCT). Exposure Cats may be exposed by drinking neat Key point antifreeze from a spill, but are more As with many commonly exposed after drinking the diluted poisoning cases in fluid from drained vehicle radiators. Most cats, ingestion is exposures are not witnessed. rarely witnessed. Prevention by informing owners of the dangers of leaving antifreeze around is far preferable, as mortality from ingestion is high. Mechanisms of toxicity The major toxic agent in ethylene Figure 1: glycol poisoning is not the parent Ethylene glycol is highly toxic compound but the metabolites to cats produced by the action of alcohol 1(11) feline focus 401 401-408Bates-ethylenegylcol.qxp_FF Layout1 28/10/2015 09:31 Page 2 Keeping cats safe dehydrogenase (Figure 2). This Toxic dose enzyme oxidises ethylene glycol to Cats are more susceptible to glycoaldehyde. This is then ethylene glycol than dogs and signs metabolised to glycolic acid which progress more rapidly, but it is not appears to be the principle cause of clear why. It may be that toxic the acidosis observed with ethylene metabolites are eliminated more glycol toxicity. Further metabolites slowly, or metabolites are of glycolic acid are glyoxylic acid metabolised more rapidly to other and then oxalate; the latter causes more toxic compounds. 1 renal damage and hypocalcaemia by binding to calcium to form calcium The lethal dose of ethylene glycol in oxalate (crystals of which may be cats is commonly reported as present in urine). 1.5 ml/kg. 2 In another study 1 g/kg (where 1 ml is approximately 1 g) Toxicokinetics was fatal to cats within 48 h, Ethylene glycol is rapidly absorbed whereas this dose did not affect rats, from the gastrointestinal tract; in rabbits or guinea pigs. 3 Undiluted cats the peak plasma concentration ethylene glycol-containing occurs about 1 h after ingestion and antifreezes generally contain 95% or the urine concentration peaks about more, with ‘ready to use’ products 3 h after ingestion. 1 being approximately 50%. Figure 2: Mechanism of ethylene glycol toxicity 402 icatcare.org/felinefocus 401-408Bates-ethylenegylcol.qxp_FF Layout1 28/10/2015 09:31 Page 3 Keeping cats safe How the antidotes work Key point The aim of antidotal therapy in the management of ethylene glycol The longer the time toxicosis is to prevent formation of between ingestion and the toxic metabolites (Figure 2). treatment, the poorer This is achieved through the prognosis. If acute administration of ethanol or kidney injury has fomepizole (4-methylpyrazole, 4- occurred then the prognosis is poor. MP), both of which are competitive inhibitors of alcohol dehydrogenase, with a higher affinity for the enzyme than ethylene glycol. Fomepizole is early signs may be easily missed, the more potent inhibitor. Inhibition particularly in an outdoor cat. of ethylene glycol metabolism allows Polyuria, dehydration, tachypnoea, time for renal excretion of the acidosis and hypothermia may unchanged parent compound. occur. Polydipsia, although common in dogs, is generally not seen in cats. In the study by Connally et al, 4 cats Convulsions can occur at this stage only survived lethal doses of in severe cases. ethylene glycol if treated with fomepizole or ethanol at or before From 12 –24 h cats remain depressed 3 h. In an earlier study, of nine cats and develop cardiopulmonary signs given lethal doses of ethylene glycol with tachypnoea, tachycardia, (4, 6 or 8 ml/kg) and treated with acidosis, hyper- or hypotension, ethanol at 4 h, five (55.5%) survived pulmonary oedema, arrhythmias, compared to only one (8%) survivor congestive heart failure and of 12 cats treated at 8 h. 5 These circulatory shock. Cerebral oedema studies therefore suggest that may occur. Death can occur at this survival is most likely in cats if stage in some cases. treatment with ethanol or fomepizole is started within 3 –4 h of Renal system signs including ingestion. oliguria, azotaemia and/or uraemia develop and the renal impairment Fomepizole is effective in cats but exacerbates acid/base and the drug is expensive and the cost of electrolyte disturbances. Kidneys treatment is cats is increased further may be swollen and painful and because they require a much higher there may be vomiting, anorexia, dose (6 x dose) than dogs or oral ulcers, severe depression, humans. In addition, this high dose lethargy, coma and convulsions due causes sedation, ataxia and to uraemia. 6 hypothermia in cats. 4 As a result ethanol is more commonly used and Laboratory changes is much more readily available. There is raised urea and creatinine, which is generally seen from about Clinical signs 12 h in cats, 7 low urine specific gravity In the early stages of ethylene glycol (due to osmotic diuresis induced by poisoning, which occurs from 30 ethylene glycol), proteinuria, minutes to 12 h, there are central glucosuria, haematuria and nervous system signs due to albuminuria. Calcium oxalate crystals unmetabolised ethylene glycol. can appear in the urine within 3 h of These include vomiting, ataxia, ingestion (Figure 3), 4 but the tachycardia and weakness. These absence of oxalate crystals does not 1(11) feline focus 403 401-408Bates-ethylenegylcol.qxp_FF Layout1 28/10/2015 09:31 Page 4 Keeping cats safe by 3 h after ingestion, and markedly decreased by 12 h. 7 Neutrophil leukocytosis may also be observed. 6 Prognosis Prognosis should be based on an animal’s response to treatment, 9 but the longer the time to treatment the less favourable the prognosis. Recovery may take 3 –5 days if treated aggressively within a few hours of ingestion, 4 but in most cases unless the ingestion was witnessed, animals usually present in the final stage of poisoning. Coma or Figure 3: Calcium oxalate monohydrate crystals (x500 magnification, Kovastain): in acute renal injury indicates a poor this image the crystals have a rounded ovoid prognosis. appearance but they can be more hexagonal (picture courtesy of Kathleen Tennant ) In a study of 25 cases of ingestion of ethylene glycol in cats the mortality rate was 96%. 10 In another report of Key point 26 cats and 24 dogs with ethylene glycol poisoning only six animals Cats with ethylene glycol (12%) survived. Half of the survivors toxicity may have calcium were admitted within 12 h. 6 In a oxalate monohydrate review of all fatal cases of poisoning crystals in their urine reported to the Veterinary Poisons but the absence of Information Service (VPIS) the most these crystals common agent to result in a fatal does not rule out outcome in cats was presumed to be poisoning. (few cases had laboratory confirmation) ethylene glycol. Of 213 cats with suspected or confirmed ethylene glycol poisoning with known outcome, 38 died (17.8%) and rule out ethylene glycol poisoning. 159 were euthanased (74.6); this is There may also be hyperglycaemia, an overall fatality rate of 92.5%. 11 hypocalcaemia (due to binding of calcium to oxalate), Diagnosis hyperphosphataemia and Diagnosis is generally based on hyperkalaemia (due to acute kidney history, clinical signs and laboratory injury and acidosis). Clinical signs of findings. Ethylene glycol poisoning hypocalcaemia generally do not should be suspected in any animal occur in ethylene glycol poisoning with acute onset of signs, raised because of the shift to the active, urea, creatinine and low urine ionised form of calcium when specific gravity. 9 metabolic acidosis occurs. 6,8 Test kits are available for confirming There is acidosis, typically with a ethylene glycol in blood but they blood pH of <7.3 and acidic urine have some limitations. Cats can be with a pH <6.5. 9 The blood pH and poisoned at concentrations below plasma bicarbonate are decreased that detected by the kits (usually 404 icatcare.org/felinefocus 401-408Bates-ethylenegylcol.qxp_FF Layout1 28/10/2015 09:31 Page 5 Keeping cats safe 500 mg/l) and some kits also give essential to ensure adequate false positives in the presence of hydration and therefore renal alcohol (such as ethanol). These kits perfusion and to promote diuresis. If only detect ethylene glycol not its possible, the central venous pressure metabolites. Therefore, in late and urine output should be presenting animals the test may be monitored in cats with acute kidney negative because the ethylene injury because of the risk of fluid glycol has been metabolised or is overload and subsequent pulmonary below the limit of detection.
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