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Ethylene Glycol Poisoning in Three Dogs: Importance of Early Diagnosis and Role of Hemodialysis As a Treatment Option

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Ethylene Glycol Poisoning in Three Dogs: Importance of Early Diagnosis and Role of Hemodialysis As a Treatment Option Fallberichte | Case reports Ethylene glycol poisoning in three dogs: Importance of early diagnosis and role of hemodialysis as a treatment option A. Schweighauser, T. Francey Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland Summary Intoxikation mit Ethylenglykol bei drei DOI 10.17236/sat00051 Hunden: Bedeutung der frühzeitigen Received: 10.07.2015 Poisoning with ethylene glycol as contained in anti- Diagnosestellung und Rolle der Accepted: 09.09.2015 freeze can rapidly lead to irreversible acute renal failure Hämodialyse bei der Behandlung and other organ damage. It carries a grave prognosis unless diagnosed early and adequate treatment is initi- Frostschutzmittelintoxikation mittels Ethylenglykol ated within 8 hours of ingestion. Toxicity of ethylene kann in kurzer Zeit zu irreversiblem akuten Nierenver- glycol is related to the production of toxic metabolites sagen und anderen Organschäden führen. Die Progno- by the enzyme alcohol dehydrogenase (ADH), leading se ist schlecht, falls die Diagnose nicht sehr früh gestellt to early signs of severe polyuria (PU) and polydipsia und die korrekte Therapie innerhalb der ersten 8 Stun- (PD), gastritis, ataxia and central nervous depression, den nach Toxinaufnahme eingeleitet wird. Die Toxizität followed by progressive dehydration, and ultimately von Ethylenglykol beruht auf der Produktion von gifti- oligoanuric renal failure. In addition to general support- gen Metaboliten durch das Enzym Alkoholdehydro- ive care, therapeutic interventions must include either genase (ADH), was in der Frühphase zu hochgradiger antidotes blocking ADH-mediated metabolism or blood Polyurie/Polydipsie, Gastritis, Ataxie und Depression purification techniques to remove both the parent com- des Zentralnervensystems führt, gefolgt von progressi- pound and the toxic metabolites. The goal of this case ver Dehydratation und schlussendlich oligoanurischem report is to describe three cases of acute antifreeze in- Nierenversagen. Zusätzlich zu einer allgemein unter- toxication in dogs, and to discuss treatment options stützenden Therapie, können Antidote genutzt werden, available for this poisoning. die den ADH-übertragenen Metabolismus blockieren, sowie Blutreinigungsverfahren, um die Ursprungssub- Keywords: ethylene glycol, antifreeze, acute kidney injury, hemodialysis, intoxication stanz sowie die toxischen Metaboliten zu entfernen. Das Ziel dieses Fallberichtes ist die Beschreibung von drei Hunden mit akuter Frostschutzmittelvergiftung sowie die Diskussion möglicher Therapieansätze. Schlüsselwörter: Ethylenglykol, Frostschutzmittel, akute Nierenschädigung, Hämodialyse, Intoxikation Introduction have been regularly reported in the United States (Mueller, 1982; Rowland, 1987; Adams et al., 1991; Ethylene glycol based antifreeze is a toxic agent report- Connally et al., 1996; Khan et al., 1999). 510 cases of ed to cause irreversible damage to the kidneys, and to ethylene glycol exposures in animals, 98% being dogs affect the hepatic, cardiovascular and central nervous and cats, were compiled by the ASPCA National Animal system (CNS) (Doty et al., 2006). It is odorless, and is Poison Control Center in Illinois, USA, from 1995–1997 commonly reported to be ingested for its sweet taste (Khan et al., 1999). Individual case reports on ethylene (Keller and Goddard, 2005). If appropriate treatment is toxicity have also been published in other geographical not started within a few hours, prognosis is grave with locations including Switzerland (Kupper et al., 2011), progression from acute kidney injury to acute renal fail- South Africa (Keller and Goddard, 2005) and Spain ure. Cases of ethylene glycol toxicity in dogs and cats (Goicoa et al., 2003). Band 158, Heft 2, Februar 2016, 109–114, © GST | SVS SAT | ASMV 2 | 2016 109 109_114_Schweighauser.indd 109 25.01.16 12:32 Fallberichte | Case reports Ethylene glycol poisoning Antifreeze solutions usually contain approximately 95% The goal of this case report is to highlight the fact that in three dogs: Importance ethylene glycol (Thrall et al., 1998). In Switzerland, the acute ethylene glycol poisoning also occurs in Switzer- of early diagnosis and role of hemodialysis as law of the EU applies where products containing more land, to describe the clinical picture in dogs, as well as a treatment option than 25% ethylene glycol must be labeled as such as well the possible treatment options. as for being dangerous for health with an advice to con- A. Schweighauser, T. Francey tact a physician in case of ingestion (Ethylenglykol in Frostschutz und Enteisern. Federal Office of Public Case histories Health June 2007). While most of the commercially available antifreeze solutions in Switzerland contain Case 1 propylene glycol, more than 3000 different products A 2–year-old male intact German Shepherd, BW 30.4 kg, registered in our country contain ethylene glycol in var- was presented to the Small Animal Teaching Hospital iable amounts (personal communication Federal Office in Bern with a history of witnessed ingestion of ethylene of Public Health). The minimum lethal dose of undi- glycol-containing antifreeze (Agrola Frostschutz II luted ethylene glycol is 6.6 ml/kg in the dog and xl 50/50) in an estimated amount of several deciliters 1.5 ml/kg in the cat (Thrall et al., 1998). Propylene gly- approximately 3 hours prior to presentation. Clinical col, on the other hand, seems to be less of a risk, al- signs reported by the owners included ataxia, disorien- though Claus et al. (2011) reported a dog with clinical tation and acute onset of severe PU/PD shortly after signs similar to early stage ethylene glycol toxicity. ingestion. On initial clinical examination, the dog showed moderate depression, severe generalized ataxia, Ethylene glycol toxicosis is potentially lethal, and early disorientation and limited responsiveness. Cardiovas- diagnosis and treatment are crucial. After ingestion, it cular parameters were normal except for a bradycardia is rapidly absorbed from the gastrointestinal tract with of 52 bpm with a sinus rhythm on ECG. Blood pressure peak plasma concentrations in dogs 2–3 hours post-in- measured with an oscillometric device (Cardell Veteri- gestion. It is subsequently metabolized primarily by the nary monitor 9403, Midmark Animal Health, USA) was liver (Grauer et al., 1984; Grauer et al., 1987). Its toxic- systolic 112, diastolic 63, and mean arterial pressure ity is not related to the parent compound, but to the 86 mmHg on average of 3 consecutive measurements. production of toxic metabolites by the enzyme ADH. Serum creatinine and urea were within normal limits At the end of the cascade, oxalic acid chelates calcium, (Tab. 1). Treatment goals at this time included preven- leading to the formation of insoluble calcium oxalate tion of ethylene glycol metabolism and enhancement complexes. These are freely filtered by the kidneys and of its elimination. Ethanol 5% (Ethanol 20%, Chris- will ultimately deposit in the renal tubules causing acute toffel Apotheke Bern, diluted in a 5% glucose solution, kidney injury and to a lesser extent, in the vasculature Glucosum 5% “Bichsel”, Laboratorium Dr. G. Bichsel of the brain, heart and other organs (Gaynor and AG) was infused at 22 ml/kg iv over 30 minutes. Addi- Dhupa, 1999a; Rietjens et al., 2014). tionally, high-clearance hemodialysis was initiated to rapidly remove the small molecular weight ethylene Table 1: Selected laboratory data of 3 dogs with ethylene glycol toxicity Hct, hematocrit; iCa2+, ionized calcium; AG, anion gap; p.i., post ingestion of ethylene glycol; a, pre dialysis; b, post dialysis Hct Creatinine Urea Total Ca iCa2+ K+ AG % µmol/l mmol/l mmol/l mmol/l mmol/l mmol/l Dog #1 3h p.i.a 40 78 4.8 2.28 1.20 3.4 15.9 11h p.i. b 15 0.8 2.06 n/a 3.4 n/a 24h p.i. 83 5.4 2.36 n/a 3.9 n/a 15d p.i. 95 5.3 n/a n/a n/a n/a Dog #2 9h p.i. 47 70 2.7 2.88 n/a 4.7 n/a 30h p.i. 36 433 23.9 n/a 0.91 6.6 35.2 Dog #3 24h p.i. 45 324 10.3 2.42 n/a 4.8 n/a 48h p.i. n/a 742 22.6 2.17 n/a 5.0 n/a 54h p.i. 26 n/a n/a n/a 1.15 n/a 24.6 Ref. range 39–57 53–120 3.5 –11.1 2.50–2.93 1.09–1.38 4.1–5.3 14.8–19.0 110 SAT | ASMV 2 | 2016 Band 158, Heft 2, Februar 2016, 109–114, © GST | SVS 109_114_Schweighauser.indd 110 25.01.16 12:32 Fallberichte | Case reports glycol and its metabolites. For this purpose, a 12-French ataxic. Treatment for cardiovascular stabilization was Ethylene glycol poisoning 20 cm double lumen central venous catheter (Arrow initiated with iv crystalloid infusion. Due to progression in three dogs: Importance of early diagnosis and Swiss GmbH, Baar, Switzerland) was placed in the right of obtundation to stupor, oliguria, and development of role of hemodialysis as jugular vein under deep sedation with butorphanol azotemia, the dog was then referred to the clinic approx- a treatment option (Morphasol, Dr. E. Gräub AG, 0.3 mg/kg iv) and propo- imately 30 hours post suspected ingestion. On presenta- A. Schweighauser, fol (Propofol 1% MCT, Fresenius Kabi Schweiz AG, iv tion, the dog was in severely reduced general condition, T. Francey to effect after an initial bolus of 3 mg/kg). Dialysis ther- stuporous with intermittent signs of mental disorienta- apy was performed on a Gambro AK 200R Ultra S ma- tion and vocalization. Perfusion and hydration were chine using a PolyfluxR 140H filter and Gambro considered adequate and results of emergency blood- BL200BD blood tubings with a total extracorporeal work are summarized in Table 1. The dog showed mod- volume of 240 ml. Bicarbonate based dialysate was used erate azotemia (creatinine 433 µmol/l, reference range: (A Component 283 and BiCartR, Gambro Lundia AB, 53–120) and severe high anion gap metabolic acidosis Sweden) and systemic heparinization (Heparin Bichsel with venous pH 7.064 (7.320–7.517), HCO3- 8 mmol/l 1000 IU/ml, Laboratorium Dr.
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