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Severe Poisoning After Accidental Pediatric Ingestion of Glycol Ethers

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Glycol Ethers

abstract

Human glycol ether poisonings are sparsely reported in the medical literature. We describe a healthy 22-month-old boy who accidentally drank up to 330 mL of brakefluid containing a 75% bleed of various glycol ethers (5%–50% polyethylene glycol monomethyl ether, 15%– 40% triethylene glycol monoethyl ether, 1%–30% triethylene glycol monomethyl ether, 1%–25% triethylene glycol monobutyl ether, 1%– 20% polyethylene glycol, monobutyl ether, 1%–20% triethylene glycol, and ,10% of other glycol ethers). Within 4 hours, he became som-nolent and developed a persistent metabolic acidosis. Thirty minutes later, he received 1 dose of fomepizole. Neither progression nor im-provement in clinical or metabolic status was noted after the fome-pizole. He received hemodialysis for 3 hours∼8 hours after ingestion, and his symptoms resolved resulting in an uneventfully recovery.

Pediatrics2012;130:e1026–e1029

AUTHORS:George S. Wang, MD,a,bShan Yin, MD,aBrian

Shear, MD,band Kennon Heard, MDa,c

aDenver Health and Hospitals, Rocky Mountain Poison and Drug

Center, Denver, Colorado;bSection of Emergency Medicine,

Department of Pediatrics, Children’s Hospital Colorado, Denver, Colorado; andcDepartment of Emergency Medicine, University of

Colorado School of Medicine, Denver, Colorado

KEY WORDS

toxicology, toxicity, pediatrics, emergency medicine, glycol ethers, toxic alcohols, fomepizole

ABBREVIATION

IV—intravenous

www.pediatrics.org/cgi/doi/10.1542/peds.2011-3849

doi:10.1542/peds.2011-3849

Accepted for publication May 4, 2012

Address correspondence to George S. Wang, MD, Rocky Mountain Poison and Drug Center, 777 Bannock St #0180, Denver, CO 80204. E-mail: george.wang@childrenscolorado.org

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE:The authors have indicated they have nofinancial relationships relevant to this article to disclose.

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The 2 most common nonethanol alcohol exposures reported to poison control centers are methanol and ethylene glycol.1 These alcohols cause severe metabolic acidosis, and the utility of alcohol dehydrogenase blockers and hemodialysis are well documented in adults and children. Glycol ethers are

less commonly encountered

non-ethanol alcohols, and although de-liberate ingestions by adults have caused mental status depression, hy-potension, and metabolic acidosis,2 significant toxicity after pediatric exposures are very rare. Furthermore, the effectiveness of alcohol dehy-drogenase blockers is unclear. We describe an accidental pediatric in-gestion of Valuecraft Blake Fluid, which contains a 75% blend of various glycol ethers (5%–50% polyethylene glycol monomethyl ether, 15%–40% tri-ethylene glycol monoethyl ether, 1%– 30% triethylene glycol monomethyl ether, 1%–25% triethylene glycol mon-obutyl ether, 1%–20% polyethylene glycol, monobutyl ether, 1%–20% tri-ethylene glycol, and ,10% of other glycol ethers), that rapidly developed a metabolic acidosis and mental status depression, who received fomepizole and a course of hemodialysis.

CASE REPORT

A healthy 22-month-old boy was trans-ported by ambulance to a children’s hospital with a chief complaint of al-tered mental status 1 hour after the father witnessed him drinking from an orange juice container found in the garage. Earlier that day, the fatherfi l-led the 360-mL orange juice container with an unknown amount of Valuecraft Brake Fluid for Drum and Disc Brakes. By the time the father stopped him, ,30 mL was remaining. The father immediately called the regional poison center for assistance. While on the phone, the patient was outside with other children, and he was noted to be

stumbling and fell onto the grass from standing position. He initially cried but became more sleepy and difficult to arouse over the next 20 to 30 minutes. The patient was transported to a children’s hospital. En route, he was reported to have depressed mental status and hypoventilation requiring bag mask ventilation.

Emergency Department Course

Upon arrival to the emergency de-partment, 1 hour after ingestion, the patient was crying with stimulation, but very sleepy. His heart rate was 173 beats per minute, respiratory rate was 36 breaths per minute, temperature 37.4°C, blood pressure was 96/38 mm Hg, and oxygen saturation of 90% to 93% on room air. His head was normocephalic, with a small hematoma to left frontal scalp. Pupils were equal, round, and re-active to light, conjugate gaze without nystagmus, and opening his eyes spon-taneously. His neck was placed in a c-collar, and no abnormalities were noted to palpation. He had normal respirations with clear examination and a normal cardiac examination. His abdomen was soft, nontender, nondistended, and with-out hepatosplenomegaly. Extremities were warm, well perfused, and without deformities or swelling noted. He was somnolent on examination but arousable to external stimulus and intermittently crying. He would withdraw and localize to pain, moving all extremities equally, and had normal reflexes and tone to his extremities.

Laboratory tests were ordered upon arrival and were remarkable for a met-abolic acidosis with an anion gap of 18 (Table 1) and normal renal function, normal serum transaminase, and a hemoglobin level of 12.6 g/dL. Acet-aminophen, salicylate, and serum eth-anol concentrations were undetectable. Urine toxicology screen was negative for cocaine, methadone, opioids, benzo-diazepines, barbiturates, amphetamines,

cannabinoids, and phencyclidine. A com-puted tomography scan of the brain was performed and revealed a normal brain and skull, without evidence of trauma. Cervical spine radiographs were also normal.

The patient was observed in the emergency department and received a 20 mL/kg normal saline intravenous (IV) bolus. Four hours after ingestion, he became more somnolent, difficult to arouse, with minimal response to ex-ternal stimuli and no gag reflex. Labo-ratory tests were repeated (Table 1) and revealed a worsening anion gap metabolic acidosis, mild renal in-sufficiency, normal lactate, and an os-molar gap of 29. Serum concentrations of various alcohols were sent at that time, and the patient was then intu-bated by using rocuronium, atropine, and etomidate for inability to protect his airway and worsening acidosis. A right femoral central venous line was placed. The local regional poison cen-ter was consulted and recommended starting fomepizole and hemodialysis. The patient was given 15 mg/kg fome-pizole IV 4.5 hours after ingestion, and he was admitted to the PICU.

PICU Course

The patient remained intubated upon arrival to the PICU. A right radial arterial line was placed. Six hours after in-gestion, his blood pressure decreased to 74/22 mm Hg despite 60 mL/kg of normal saline. Dopamine infusion was started and titrated to 10 mg/kg per minute to maintain normal blood pressures. He also received 2 mEq/kg of sodium bicarbonate IV bolus for persistent acidosis without improve-ment. Laboratory testing at this time revealed an anion gap metabolic acidosis and a respiratory acidosis (Table 1), stable renal function, normal serum transaminase, and a hemoglo-bin level of 10.5 g/dL without evidence for hemolysis.

CASE REPORT

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Later that night, 8 hours after ingestion, the patient received hemodialysis for 3 hours. Dialysis bath consisted of 3 mEq/ L potassium, 35 mEq/L bicarbonate, and 140 mEq/L sodium. Follow-up labora-tory results revealed resolution of the acidosis, a fall in serum urea nitrogen, creatinine, and osmolality (Table 1). The dopamine infusion was quickly weaned off shortly after dialysis; he was extu-bated the following day and discharged from the hospital on day 3 in normal health. Serum concentrations (mea-sured on samples from presentation) of isopropanol, methanol, and ethylene glycol were undetectable, and serum propylene glycol was 9 mg/dL.

DISCUSSION

Our patient rapidly developed mental status depression and persistent met-abolic acidosis after a witnessed in-gestion of brake fluid. The material safety data sheet of the product revealed the main ingredients as a 75% blend of various glycol ethers as pre-viously mentioned. The patient was given 1 dose of fomepizole 4.5 hours after ingestion, and he continued to have a persistent metabolic acidosis 8 hours after ingestion (Table 1). He then received a course of hemodialysis and recovered without complications. In this case, specific glycol ether serum concentrations were unavailable, es-pecially with the various percentages present in multiple types of glycol ethers. Thus, it is impossible to de-termine the specific concentrations of

glycol ethers in the exposure. However, it was a witnessed ingestion of a known product, there were no evidence of detectable concentrations of other nonethanol alcohols, and the patient developed symptoms and laboratory abnormalities consistent with pre-vious reports of glycol ether inges-tions in adults.2 Furthermore, the detectable propylene glycol level of 9 mg/dL is low and would not account for the osmolar gap (1 mmol/L) or clinical symptoms.

Case series suggest that pediatric in-gestion of ethylene glycol monobutyl ether, a common glycol ether, does not commonly cause severe toxicity.3 The reported lack of symptoms may have been reflective of small exposures or products of varying concentrations. In addition, there was no laboratory

con-firmation in this series. The authors of 1 previous report described a 16-month-old girl who ingested an un-known amount of a cleaning solution containing 10% to 30% 2-butoxyethanol and developed mental status de-pression and a moderate metabolic acidosis (serum bicarbonate 13 mmol/ L, anion gap 19) within 2 hours of in-gestion.4As with our patient, the rapid onset of symptoms suggests that the parent compound is responsible for the initial altered mental status. Fur-ther decline in clinical status and worsening metabolic acidosis could have been due to metabolites. Although pediatric toxicity is rare, there have been several reports of significant

toxicity after intentional adult inges-tions of glycol ethers by adults.5–9They report various adverse effects, in-cluding altered mental status, meta-bolic acidosis, hemolysis, and renal insufficiency.

The metabolism of glycol ethers has been described in animal models, and these models suggest the metabolite is responsible for at least some of the toxic effects, such as hemolysis.10,11It is well known that alcohol dehydrogenase in-hibition prevents metabolism of meth-anol and ethylene glycol to toxic metabolites. The role for alcohol de-hydrogenase inhibition for glycol ether ingestions remains unclear. It has been reported that patients who ingest gly-col ethers have recovered uneventfully after treatment with either an ethanol infusion or fomepizole.4–6 At least 1 case report reveals progression of acidosis after fomepizole; however, the patient was hypotensive and had sig-nificantly elevated serum lactate con-centrations.12 The authors of other reports describe patients only im-proving with hemodialysis.79,13,14 In the previously mentioned pediatric re-port,4 the patient received fomepizole soon after her ingestion, and her symptoms resolved within 2 hours of administration. Our patient had a met-abolic acidosis before the administra-tion of fomepizole, which persisted despite the fomepizole. The difference in response may be due to dose of glycol ether ingested (ie, higher volume and/or concentration), differences in

1 7.33/33/113/18/28 (arterial) 139 104 17 86 18 NA NA 0.25

4 7.11/47/116/15/214 (arterial) 143 107 15 87 21 327 29 0.31

4.5 Intubation, Fomepizole 15 mg/kg IV31

6 7.13/43/66/15/214 (venous) 149 115 14 94 20 320 12 0.35

8 Hemodialysis33 h

11 7.44/41/119/27/2.5 (arterial) 141 107 25 125 9 286 24 0.19

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the metabolism of 2-butoxyethanol as opposed to the other glycol ethers in the product our child ingested (pro-longed metabolism), or differences in timing (ie, our patient already had an acidosis, which may have been in-dicative that the toxic metabolites had already been formed). However, it is also possible that fomepizole is not effective for glycol ether poisonings and that the previously published re-port may have been the course of poisoning after a smaller exposure.12

Overall, there is limited data on the use of fomepizole in pediatric patients, and although the literature suggests it is efficacious in methanol and ethylene glycol poisonings, there is no clear evidence it is effective for other alco-hols.15 POISINDEX currently recom-mends fomepizole or ethanol for treatment of significant glycol ether poisoning.16 Because most pediatric ingestions of glycol ethers are acci-dental and small in amount, and do not develop clinical sequelae, very few

cases will require treatment. However, our case reveals that large ingestions of glycol ethers can have rapid and severe effects. The decision to use an alcohol dehydrogenase blocker or he-modialysis should be made in conjunc-tion with the timing of the ingesconjunc-tion and the significance or persistence of clini-cal and metabolic effects. If an alcohol dehydrogenase blocker is given, close observation for further deterioration is warranted because hemodialysis may still be indicated.

REFERENCES

1. Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 26th Annual Report.

Clin Toxicol. 2009;47(10):911–1084 2. Browning RG, Curry SC. Clinical toxicology

of ethylene glycol monoalkyl ethers.Hum Exp Toxicol. 1994;13(5):325–335

3. Dean BS, Krenzelok EP. Clinical evaluation of pediatric ethylene glycol monobutyl ether poisonings. J Toxicol Clin Toxicol. 1992;30(4):557–563

4. Osterhoudt KC. Fomepizole therapy for pe-diatric butoxyethanol intoxication.J Toxicol Clin Toxicol. 2002;40(7):929–930

5. Nitter-Hauge S. Poisoning with ethylene glycol monomethyl ether. Report of two cases.Acta Med Scand. 1970;188(4):277–280 6. McKenney PE, Palmer RB, Blackwell W, Benson BE. Butoxyethanol ingestion with

prolonged hyperchloremic metabolic aci-dosis treated with ethanol therapy.J Toxicol Clin Toxicol. 2000;38(7):787–793

7. Gijsenbergh FP, Jenco M, Veulemans H, Groeseneken D, Verberckmoes R, Delooz HH. Acute butylglycol intoxication: a case report.Hum Toxicol. 1989;8(3):243–245 8. Gualtieri JF, DeBoer L, Harris CR, Corley R.

Repeated ingestion of 2-butoxyethanol: case report and literature review.J Toxicol Clin Toxicol. 2003;41(1):57–62

9. Rambourg-Schepens MO, Buffet M, Bertault R, et al. Severe ethylene glycol butyl ether poisoning. Kinetics and metabolic pattern.

Hum Toxicol. 1988;7(2):187–189

10. Ghanayem BI, Burka LT, Sanders JM, Matthews HB. Metabolism and disposition of ethylene glycol monobutyl ether (2-butoxyethanol) in rats.Drug Metab Dispos. 1987;15(4):478–484 11. Ghanayem BI, Burka LT, Matthews HB.

Met-abolic basis of ethylene glycol monobutyl

ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases.

J Pharmacol Exp Ther. 1987;242(1):222–231 12. Hung T, Dewitt CR, Martz W, Schreiber W, Holmes DT. Fomepizole fails to prevent progression of acidosis in 2-butoxyethanol and ethanol coingestion. Clin Toxicol (Phila). 2010;48(6):569–571

13. Sharma N, Jain S. Toxicity of brake oil.

Emerg Med J. 2002;19(3):267–268 14. Burkhart KK, Donovan JW. Hemodialysis

following butoxyethanol ingestion.J Toxicol Clin Toxicol. 1998;36(7):723–725

15. Brent J. Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings.

Clin Toxicol (Phila). 2010;48(5):401–406 16. Rumack BH, Spoerke DG, eds. Glycol ethers

(management treatment protocol). In: POISINDEX Information System. Denver, CO: Micromedex, Inc; 2011

CASE REPORT

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DOI: 10.1542/peds.2011-3849 originally published online September 24, 2012;

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DOI: 10.1542/peds.2011-3849 originally published online September 24, 2012;

2012;130;e1026

Pediatrics

George S. Wang, Shan Yin, Brian Shear and Kennon Heard

Severe Poisoning After Accidental Pediatric Ingestion of Glycol Ethers

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Figure

TABLE 1 Time Frame of Significant Laboratory Values During Clinical Course

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