Keeping cats safe Nicola Bates has worked in human and veterinary toxicology for 25 years and has been with the Veterinary Poisons Informaon Service (VPIS) since it started. As well as providing emergency advice via the telephone she has wrien extensively on veterinary toxicology. In addion to service provision, she is involved in training of VPIS staff and veterinary professionals. She is currently the congress abstract editor for the European Associaon of Poisons Centres and Clinical Toxicologists (EAPCCT). Nicola Bates BSc (Brunel) BSc (Open) MSc MA Ethylene glycol poisoning Ethylene glycol poisoning is extremely serious in cats. A small dose can result in signs which are initally non-specific and may be easily missed. Ethanol is the antdote to ethylene glycol toxicity and works by preventng metabolism to toxic compounds. However, it is generally only worthwhile if started within a few hours of ingeston. Although a potentally lethal dose of ethylene glycol can be survived if treatment is prompt, many cats with ethylene glycol poisoning present late and as a result most cases have a fatal outcome. E thylene glycol (also known amongst other names as ethanediol) is a common ingredient of antifreeze; it is also found in some screenwashes or more rarely de-icers (Figure 1). Most antifreezes contain ethylene glycol (or occasionally methanol), and are liquids which are added to water in engine radiators to prevent freezing and improve cold weather performance. The usual final dilution is approximately 1:1. Exposure Cats may be exposed by drinking neat antifreeze from a spill, but are more commonly exposed after drinking the diluted fluid from drained vehicle radiators. Most exposures are not witnessed. Mechanisms of toxicity The major toxic agent in ethylene glycol poisoning is not the parent compound but the metabolites produced by the action of alcohol 1(11) feline focus 401 Key point As with many poisoning cases in cats, ingestion is rarely witnessed. Prevention by informing owners of the dangers of leaving antifreeze around is far preferable, as mortality from ingestion is high. Figure 1: Ethylene glycol is highly toxic to cats
Transcript
Keeping cats safe
Nicola Bates has worked in human andveterinary toxicology for 25 years and hasbeen with the Veterinary Poisons InformationService (VPIS) since it started. As well asproviding emergency advice via thetelephone she has written extensively onveterinary toxicology. In addition to serviceprovision, she is involved in training of VPISstaff and veterinary professionals. She iscurrently the congress abstract editor for theEuropean Association of Poisons Centres andClinical Toxicologists (EAPCCT).
Nicola Bates BSc (Brunel) BSc (Open) MSc MA
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 theantidote to ethylene glycol toxicity and works bypreventing metabolism to toxic compounds. However, itis generally only worthwhile if started within a fewhours of ingestion. Although a potentially lethal dose ofethylene glycol can be survived if treatment is prompt,many cats with ethylene glycol poisoning present lateand as a result most cases have a fatal outcome.
Ethylene glycol (also known amongst othernames as ethanediol) is a common
ingredient of antifreeze; it is also found insome screenwashes or more rarely de-icers(Figure 1). Most antifreezes contain ethyleneglycol (or occasionally methanol), and areliquids which are added to water in engineradiators to prevent freezing and improve coldweather performance. The usual final dilutionis approximately 1:1.
ExposureCats may be exposed by drinking neatantifreeze from a spill, but are morecommonly exposed after drinking the dilutedfluid from drained vehicle radiators. Mostexposures are not witnessed.
Mechanisms of toxicityThe major toxic agent in ethyleneglycol poisoning is not the parentcompound but the metabolitesproduced by the action of alcohol
1(11) feline focus 401
Key pointAs with manypoisoning cases incats, ingestion israrely witnessed.Prevention byinforming owners of the dangersof leaving antifreeze around is farpreferable, as mortality fromingestion is high.
dehydrogenase (Figure 2). Thisenzyme oxidises ethylene glycol toglycoaldehyde. This is thenmetabolised to glycolic acid whichappears to be the principle cause ofthe acidosis observed with ethyleneglycol toxicity. Further metabolitesof glycolic acid are glyoxylic acidand then oxalate; the latter causesrenal damage and hypocalcaemia bybinding to calcium to form calciumoxalate (crystals of which may bepresent in urine).
ToxicokineticsEthylene glycol is rapidly absorbedfrom the gastrointestinal tract; incats the peak plasma concentrationoccurs about 1 h after ingestion andthe urine concentration peaks about3 h after ingestion.1
Toxic doseCats are more susceptible toethylene glycol than dogs and signsprogress more rapidly, but it is notclear why. It may be that toxicmetabolites are eliminated moreslowly, or metabolites aremetabolised more rapidly to othermore toxic compounds.1
The lethal dose of ethylene glycol incats is commonly reported as 1.5 ml/kg.2 In another study 1 g/kg(where 1 ml is approximately 1 g)was fatal to cats within 48 h,whereas this dose did not affect rats,rabbits or guinea pigs.3 Undilutedethylene glycol-containingantifreezes generally contain 95% ormore, with ‘ready to use’ productsbeing approximately 50%.
How the antidotes workThe aim of antidotal therapy in themanagement of ethylene glycoltoxicosis is to prevent formation ofthe toxic metabolites (Figure 2).This is achieved throughadministration of ethanol orfomepizole (4-methylpyrazole, 4-MP), both of which are competitiveinhibitors of alcohol dehydrogenase,with a higher affinity for the enzymethan ethylene glycol. Fomepizole isthe more potent inhibitor. Inhibitionof ethylene glycol metabolism allowstime for renal excretion of theunchanged parent compound.
In the study by Connally et al,4 catsonly survived lethal doses ofethylene glycol if treated withfomepizole or ethanol at or before3 h. In an earlier study, of nine catsgiven lethal doses of ethylene glycol(4, 6 or 8 ml/kg) and treated withethanol at 4 h, five (55.5%) survivedcompared to only one (8%) survivorof 12 cats treated at 8 h.5 Thesestudies therefore suggest thatsurvival is most likely in cats iftreatment with ethanol orfomepizole is started within 3–4 h ofingestion.
Fomepizole is effective in cats butthe drug is expensive and the cost oftreatment is cats is increased furtherbecause they require a much higherdose (6 x dose) than dogs orhumans. In addition, this high dosecauses sedation, ataxia andhypothermia in cats.4 As a resultethanol is more commonly used andis much more readily available.
Clinical signsIn the early stages of ethylene glycolpoisoning, which occurs from 30minutes to 12 h, there are centralnervous system signs due tounmetabolised ethylene glycol.These include vomiting, ataxia,tachycardia and weakness. These
early signs may be easily missed,particularly in an outdoor cat.Polyuria, dehydration, tachypnoea,acidosis and hypothermia mayoccur. Polydipsia, although commonin dogs, is generally not seen in cats.Convulsions can occur at this stagein severe cases.
From 12–24 h cats remain depressedand develop cardiopulmonary signswith tachypnoea, tachycardia,acidosis, hyper- or hypotension,pulmonary oedema, arrhythmias,congestive heart failure andcirculatory shock. Cerebral oedemamay occur. Death can occur at thisstage in some cases.
Renal system signs includingoliguria, azotaemia and/or uraemiadevelop and the renal impairmentexacerbates acid/base andelectrolyte disturbances. Kidneysmay be swollen and painful andthere may be vomiting, anorexia,oral ulcers, severe depression,lethargy, coma and convulsions dueto uraemia.6
Laboratory changes There is raised urea and creatinine,which is generally seen from about 12 h in cats,7 low urine specific gravity(due to osmotic diuresis induced byethylene glycol), proteinuria,glucosuria, haematuria andalbuminuria. Calcium oxalate crystalscan appear in the urine within 3 h ofingestion (Figure 3),4 but theabsence of oxalate crystals does not
1(11) feline focus 403
Keeping cats safe
Key point
The longer the timebetween ingestion andtreatment, the poorerthe prognosis. If acutekidney injury hasoccurred then the prognosis is poor.
rule out ethylene glycol poisoning.There may also be hyperglycaemia,hypocalcaemia (due to binding ofcalcium to oxalate),hyperphosphataemia andhyperkalaemia (due to acute kidneyinjury and acidosis). Clinical signs ofhypocalcaemia generally do notoccur in ethylene glycol poisoningbecause of the shift to the active,ionised form of calcium whenmetabolic acidosis occurs.6,8
There is acidosis, typically with ablood pH of <7.3 and acidic urinewith a pH <6.5.9 The blood pH andplasma bicarbonate are decreased
by 3 h after ingestion, and markedlydecreased by 12 h.7 Neutrophilleukocytosis may also be observed.6
Prognosis Prognosis should be based on ananimal’s response to treatment,9 butthe longer the time to treatment theless favourable the prognosis.Recovery may take 3–5 days iftreated aggressively within a fewhours of ingestion,4 but in mostcases unless the ingestion waswitnessed, animals usually present inthe final stage of poisoning. Coma oracute renal injury indicates a poorprognosis.
In a study of 25 cases of ingestion ofethylene glycol in cats the mortalityrate was 96%.10 In another report of26 cats and 24 dogs with ethyleneglycol poisoning only six animals(12%) survived. Half of the survivorswere admitted within 12 h.6 In areview of all fatal cases of poisoningreported to the Veterinary PoisonsInformation Service (VPIS) the mostcommon agent to result in a fataloutcome in cats was presumed to be(few cases had laboratoryconfirmation) ethylene glycol. Of 213cats with suspected or confirmedethylene glycol poisoning withknown outcome, 38 died (17.8%) and159 were euthanased (74.6); this isan overall fatality rate of 92.5%.11
DiagnosisDiagnosis is generally based onhistory, clinical signs and laboratoryfindings. Ethylene glycol poisoningshould be suspected in any animalwith acute onset of signs, raisedurea, creatinine and low urinespecific gravity.9
Test kits are available for confirmingethylene glycol in blood but theyhave some limitations. Cats can bepoisoned at concentrations belowthat detected by the kits (usually
404 icatcare.org/felinefocus
Keeping cats safe
Key point
Cats with ethylene glycoltoxicity may have calciumoxalate monohydratecrystals in their urinebut the absence ofthese crystalsdoes not rule outpoisoning.
Figure 3: Calcium oxalate monohydratecrystals (x500 magnification, Kovastain): inthis image the crystals have a rounded ovoidappearance but they can be more hexagonal(picture courtesy of Kathleen Tennant)
500 mg/l) and some kits also givefalse positives in the presence ofalcohol (such as ethanol). These kitsonly detect ethylene glycol not itsmetabolites. Therefore, in latepresenting animals the test may benegative because the ethyleneglycol has been metabolised or isbelow the limit of detection.
Many antifreeze products containfluorescein (a green or red dyedepending on the pH of themedium), which fluoresces underultraviolet light. Sometimes the dyemay be detected in urine or vomitususing a Wood’s lamp andexamination of the paws, mouth andface may be useful.12 However, this isnot a reliable test,13 as it is difficult todetect fluorescence in a test samplewithout a positive and negativecontrol for comparison.14
TreatmentThe aim of therapy in ethylene glycolpoisoning is to prevent metabolismand the production of toxicmetabolites, reverse electrolyte andacid/base disturbances and maintainthe glomerular filtration rate. Adviceshould be sought from a poisonsinformation service and a specialistcentre to optimise treatment ofaffected cats.
Decontamination Treatment is recommended for anyquantity but gut decontamination isprobably only worthwhile within 1 h of ingestion. Adsorbents such asactivated charcoal are not useful. Inmost cases cats do not present untilthe onset of signs, hours afteringestion.
Monitoring, investigations and initial treatment In symptomatic cats the blood pH,electrolytes and renal functionshould be monitored. Intravenousfluids (2–3 times maintenance) are
essential to ensure adequatehydration and therefore renalperfusion and to promote diuresis. Ifpossible, the central venous pressureand urine output should bemonitored in cats with acute kidneyinjury because of the risk of fluidoverload and subsequent pulmonaryoedema. If there is oliguria or anuria,diuretics such as mannitol orfurosemide can be given if there isno response to fluid therapy alone.There is a significant risk of volumeoverload in cats with acute kidneyinjury and advice on treatmentshould be taken from a specialistand, ideally, the cat referred to aspecialist centre. Peritoneal dialysisor haemodialysis can be used inacidotic cats with oliguria, but arerarely available.
Other treatments may includetreatment of hyperkalaemia,management of nausea andvomiting and specific treatment ofsevere acidosis. Treatment ofhypocalcaemia is rarely required.
Antidotal treatment After ingestion of ethylene glycolthe sooner antidotal therapy isstarted the better the outcome. Apotentially lethal dose of ethyleneglycol can be survived if treatment isprompt. Survival is most likely iftreated within 3–4 h of ingestion.There is no point giving ethanol orfomepizole to block metabolism ifthe ethylene glycol has beenmetabolised. Unfortunately, cats
Tip
Antidotes must be givenwithin 3–4 h of ingestionand, unfortunately, thereis no point giving themto cats already sufferingacute kidney injury.
often present late by which time suchantidotal therapy is no longer of use.Management in these cases issupportive/palliative. Antidotes
should not be used in cats withacute kidney injury as antidotesincrease the half-life of ethyleneglycol and if renal damage hasalready occurred the kidneys maynot be able to effectively eliminateit.
Ethanol is the most readily availableand commonly used antidote forethylene glycol toxicity (Box 1). Itcan be given orally or intravenouslybut use of a constant rate infusion ispreferred as it will result in morestable blood ethanol concentration.4
The dose of ethanol required willcause significant central nervoussystem (CNS) depression andhypothermia. Nursing care for arecumbent patient will be required.Ethanol may also worsen acidosisand can cause hypoglycaemia. Theblood glucose should be monitoredevery 4–6 h, because of the risk ofhypoglycaemia.7 The airway shouldbe protected if there is significantCNS depression. If the cat survives itwill be depressed and lethargic (thatis, hung over) during recovery fromethanol therapy and require furthersupportive care (eg, nutritionalsupport and fluid therapy).
ConclusionsEthylene glycol ingestion iscommonly lethal in cats, but promptdiagnosis and treatment withethanol therapy can be life-saving.In many cases, however, the earlysigns may be missed or vague andnon-specific resulting in latepresentation. Clients should beeducated on avoiding exposing cats,for example, in the garage.
References1 Connally HE, Hamar DW and Thrall MA.
Inhibition of canine and feline alcoholdehydrogenase activity by fomepizole. Am JVet Res 2000; 61: 450–455.
2 Miles G. Ethylene glycol poisoning withsuggestions for its treatment as oxalatepoisoning. Arch Path 1946; 41: 631.
Intravenous dosage• 5% solution as a constant rate infusion
at a rate of 5 ml/kg/h for 48 h orlonger
OR• 5 ml/kg body weight 20% ethanol in
saline IV every 6 h for 5 doses thenevery 8 h for 4 doses.
Ideally, a pharmaceutical grade ofethanol should be used but if notavailable oral ethanol can be given or anIV solution made up using 40% vodka, asfollows:*
• To make a 5% solution: add 125 ml ofvodka to 875 ml of IV fluid lactatedRinger’s or saline, that is removeabout 125 ml from the bag and replacewith vodka. An in-line filter should beused for the IV.
To make a 20% solution: dilute anequal volume of vodka with IV fluidssuch as lactated Ringer’s or saline (eg,500 ml with 500 ml). An in-line filtershould be used for the IV.
Oral dosage• 2.4 ml/kg orally of a 40% solution (eg,
vodka, whisky, suitably diluted;equated to 750 mg/kg) over the firsthour, followed by 0.5 ml/kg/h(equates to 150 mg/kg/h).
This is best given via an indwellingnasogastric tube, periodically over thetreatment period (that is, not all at once,as it is irritant and could result invomiting).
Studies in detoxication. The metabolism of14C-labelled ethylene glycol. Biochem J 1961;79: 482.
4 Connally HE, Thrall MA and Hamar DW. Safetyand efficacy of high-dose fomepizolecompared with ethanol as therapy forethylene glycol intoxication in cats. J VetEmerg Crit Care 2010; 20: 191–206.
5 Penumarthy L and Oehme FW. Treatment ofethylene glycol toxicosis in cats. Am J Vet Res1975; 36: 209–212.
6 Thrall MA, Grauer GF and Mero KN.Clinicopathologic findings in dogs and catswith ethylene glycol intoxication. J Am VetMed Assoc 1984; 184: 37–41.
7 Osweiler GD, Hovda LR, Brutlag AG and Lee JA(eds). Blackwell’s five-minute veterinaryconsult clinical companion small animaltoxicology. Ames, Iowa, Wiley-Blackwell, 2011.
8 Winek CL, Shingleton DP and Shanor SP.Ethylene and diethylene glycol toxicity. ClinToxicol 1978; 13: 297–324.
9 Grauer GF and Thrall MA. Ethylene glycol(antifreeze) poisoning in the dog and cat.J Am Anim Hosp Assoc 1982; 18: 492–497.
10 Rowland J. Incidence of ethylene glycolintoxication in dogs and cats seen at ColoradoState University Veterinary Teaching Hospital.Vet Hum Toxicol 1987; 29: 41–44.
11 Bates N and Edwards N. Toxic deaths in catsand dogs reported to the Veterinary PoisonsInformation Service (VPIS) [abstract]. ClinToxicol 2015; 53: 273.
12 Winter ML, Ellis MD and Snodgrass WR. Urinefluorescence using a Wood's lamp to detectthe antifreeze additive sodium fluorescein: aqualitative adjunctive test in suspectedethylene glycol ingestions. Ann Emerg Med1990; 19: 663–667.
13 Parsa T, Cunningham SJ, Wall SP, Almo SC andCrain EF. The usefulness of urine fluorescencefor suspected antifreeze ingestion in children.Am J Emerg Med 2005; 23: 787–792. Erratumin: Am J Emerg Med 2006; 24: 396.
14 Wallace KL, Suchard JR, Curry SC and ReaganC. Diagnostic use of physicians' detection ofurine fluorescence in a simulated ingestion ofsodium fluorescein-containing antifreeze. AnnEmerg Med 2001; 38: 49–54.
Many cases of poisoning arepreventable by raising ownerawareness, one of the aims of theKeeping Cats Safe Campaign.The Campaign is run byInternational Cat Care inconjunction with the VeterinaryPoisons Information Service andAgria Pet Insurance.For more information see: http://icatcare.org/keeping-cats-safe
Feline NursingDistance Education Courses
ISFM Certificate in Feline Nursing
ISFM Diploma in Feline Nursing
ISFM is pleased to offer two qualifications in feline
veterinary nursing:
❖ Do you want to learn more about cats?
❖ Do you want to be a feline friendly nurse?
❖ Do you want to study from home?
www.icatcare.org/learn
The courses are online with workbooks tocomplete and marked by our experts.
