Emergency Files - Canadian Family Physician

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at the outset of the poisoning, as these alcohols are all osmotically ... erable amounts of this poison. .... presence of folate, the formic acid is reduced to carbon.

Emergency Files Should I stay or should I go? Toxic alcohol case in the emergency department Constance LeBlanc

MD MAEd CCFP(EM) FCFP 

Nancy Murphy

MD CM CCFP(EM) ABMT

An upset mother calls the emergency department while you are working. She found her 3-year-old son chewing on a Bingo marker approximately 30 minutes ago. She is worried and wants advice on whether to consult a physician or stay at home. He appears well and has continued to play after crying briefly when she took the marker from him. The boy is developmentally normal and has no medical illnesses. They live 40 km from the hospital, and she is alone at home with her son and 4-year-old daughter. She has no vehicle. The triage nurse who has taken the call asks you what, if any, action is appropriate in this case.

The 3 most common toxic alcohol ingestions include ethylene glycol, methanol, and isopropanol. None of these parent compounds is very toxic; they cause inebriation and a serum osmolar gap soon after ingestion. As they are metabolized, however, the osmolar gap decreases and a metabolic acidosis develops. This acidosis is the cause of the end-organ damage we recognize as the specific pattern of injury associated with each of these toxins.1 Fortunately, all 3 of these toxic alcohols follow a common metabolic pathway via the enzyme alcohol dehydrogenase (ADH) (Figure 1). This provides physicians the opportunity to block this enzyme with enzyme blocking agents or substrate substitution using ethanol, preventing

the development of acidosis and toxic metabolites. The fact that ADH has a greater affinity for ethanol than for any of the other 3 toxic alcohols makes administration of ethanol a feasible treatment strategy. This can be especially important in the treatment of these ingestions in the prehospital phase of care. A common “urban myth” asserts that the anion gap and serum osmolality are not useful in the management of toxic alcohols. We suggest that better understanding allows the osmolality and anion gap metabolic acidosis, if present, to be interpreted in light of clinical findings. Figure 2 shows that serum osmolality is elevated at the outset of the poisoning, as these alcohols are all osmotically active. As the ADH enzyme metabolizes the toxin, a metabolic acidosis develops. The time of ingestion and the half-life of the alcohol ingested will direct us to the segment of the graph we should use for individual cases. Often, more than 1 set of laboratory values obtained several hours apart are required to determine the degree of toxicity in an individual patient (Figure 3).

Ethylene glycol Ethylene glycol is found mostly in coolant mixtures, such as radiator antifreeze. As it has a sweet taste, animals and young children might consume considerable amounts of this poison. It has a short half-life

Figure 1. Metabolic pathway for alcohols via the enzyme ADH

Ethylene glycol

Glyoxylic acid

oxalate

Methanol

Formaldehyde

formate*

Ethanol

ADH

Isopropanol

ADH—alcohol dehydrogenase. * Folic acid dependent.

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Canadian Family Physician • Le Médecin de famille canadien  Vol 55:  january • janvier 2009

Acetaldehyde Acetone

Emergency Files Figure 2. Osmolar and anion gaps graphed over time of post-toxic alcohol ingestion: Note that early in presentation, osmolar gap can be elevated with a normal anion gap. Late presenters might have an elevated anion gap with a normal osmolar gap. 100 90 80

RANGE

70 60

Anion gap (mEq/L)

50

Osmolar gap (mmol/L)

40 30 Normal

20 10 0

1

2

3

4

5

6

TIME* * Units of time vary, depending on the half-life of the alcohol ingested.

Figure 3. Anion gap and osmolar gap calculations, including correction of ethanol

Anion gap: AG = Na - (Cl + HCO3)



An increased anion gap in toxic alcohol poisoning implies the following: - toxic metabolites already accumulated and - delayed presentation

Calculated osmolality: 2(Na) + BUN + GLUC + 1.25(EtOH level)



Ethylene glycol, isopropanol, and methanol are all osmotically active (many other things are as well)



Normal gap = [-10 to +10] or [-2 to +6]



A “normal” osmolar gap does not exclude toxic alcohol



A very high osmolar gap can be helpful (>50 to 70 mOsm)

Osmolar gap: Measured - calculated

AG—anion gap, BUN—blood urea nitrogen, Cl—chloride, EtOH—ethyl alcohol, GLUC—glucose, HCO3—bicarbonate, Na—sodium.

of approximately 3 hours, so initial and 6-hour serum electrolytes and serum osmolality are sufficient to rule out serious toxicity. Alcohol dehydrogenase metabolizes ethylene glycol to glycoaldehyde, then aldehyde dehydrogenase further metabolizes glycoaldehyde into glycolic acid. The glycolic acid is then further metabolized into glyoxylic acid and finally into either

glutamate or α-ketoadipic acid or very toxic oxalate metabolites. The proportion of each can be affected by administering a vitamin such as folic acid, as it reduces the production of oxalate. If oxalate is formed, calcium oxalate is then also formed and deposited in the renal cortex and other tissues—the result is endorgan damage.

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Emergency Files Clinically, toxicity follows a 3-phased pattern: • In the first 12 hours postingestion, the patient will be inebriated, have some nausea and vomiting, and be somnolent. A few patients will be comatose. • In the second phase, between 12 and 24 hours postingestion, symptoms include tachycardia, pulmonary edema, and hypocalcemia. • The third and last phase consists of acute tubular necrosis and renal failure, and begins 24 hours postingestion.2,3 Ancillary evaluations specific to ethylene glycol include a urinalysis to see if calcium oxalate crystals are present and a Wood lamp (UV light) examination of the urine, as almost all radiator fluids have fluorescein added to facilitate the detection of leaks. Fluorescein in the urine is contributory; however, a negative UV light test does not rule out ethylene glycol ingestion. Management can include supportive care, ADH blockade with ethanol or fomepizole, and dialysis.4-7

Methanol Methanol is found in industrial solvents, paints and varnishes, windshield-washer fluid, Sterno fuel, and,

Assessment of patient History As with other poisonings, history is key and must include the following details: •

route of ingestion and source (physicians should make every attempt to obtain container in order to have access to accurate information about the contents of the ingestant), • circumstances and intent, • quantity ingested, and • known or possible co-ingestants, most specifically ethanol.

Physical examination The physical examination should be a complete toxicologic examination, which should include the following: • skin, • neurologic, • cardiorespiratory, and • abdominal examinations. Initial ancillary evaluation Initial ancillary evaluations should include the following: • complete blood count, • serum electrolytes, • serum osmolality, • acetaminophen and acetylsalicylic acid levels, • ethanol level, and • a β-human chorionic gonadotropin test in female patients of childbearing age. 48 

sometimes, moonshine. It can be ingested unintentionally in alcoholic beverages or intentionally in solvent form. Intentional methanol ingestions are cause for serious concern. Methanol has a much longer half-life than the other toxic alcohols, approximately 8 hours, so serum electrolytes and levels must be repeated at far wider intervals than for ethylene glycol. Methanol is rapidly absorbed after ingestion and metabolized to formaldehyde by ADH. Methanol levels peak at 30 to 90 minutes postingestion. These correlate poorly with the degree of toxicity and we recommend formic acid levels. Then aldehyde dehydrogenase rapidly metabolizes the formaldehyde into formic acid, a very toxic metabolite. The formate accumulates in the body resulting in a metabolic acidosis, in addition to neurologic and ophthalmologic manifestations. In the presence of folate, the formic acid is reduced to carbon dioxide and water.8 Clinically, methanol toxicity also consists of 3 phases: • Initially, there is inebriation. • After a 12- to 24-hour lag postingestion, toxic manifestations begin to develop. • Following the second phase, severe metabolic acidosis, visual disturbance, including the appearance of blurred vision and flashing lights, and neurologic manifestations, such as Parkinson-like syndrome, might be present. Management can include supportive care, ADH blockade with ethanol or fomepizole, and dialysis.

Isopropanol Isopropanol is found in rubbing alcohol (70%), some cleaning products, and many personal hygiene products. This alcohol produces an intense inebriation and more severe respiratory and neurologic depression than the other 2 toxic alcohols. Gastritis is also a frequent clinical finding in isopropanol poisonings. Isopropanol is readily absorbed through the gastro­ intestinal tract and, unlike the other alcohols, toxicity can result from excessive dermal exposure. Approximately 30% of isopropanol is excreted unchanged through the kidney, while ADH metabolizes the other 70% into acetone, which is excreted through the lungs or the kidneys. Management includes supportive care. Special attention should be given to airway management owing to the degree of coma and respiratory depression coupled with severe gastritis. In severely symptomatic patients with cardiac manifestations, ADH blockade with ethanol or fomepizole or dialysis should be considered. In this case, as with any toxin, you must make every attempt to ascertain the nature, concentration, and timing of the ingestion. Here, the brand of marker contained between 3% and 90% methanol—a toxin of concern, especially in a small child. The volume and exact concentration are unavailable to you in this

Canadian Family Physician • Le Médecin de famille canadien  Vol 55:  january • janvier 2009

Emergency Files BOTTOM LINE

Take a detailed history in order to rule out coingestants. • Calculate and carefully interpret anion and osmolar gaps. • Two sets of blood tests taken several hours apart are required. • Use alcohol dehydrogenase blockade with fomepizole or ethanol for management. • Dialysis is indicated if a patient is comatose, has severe metabolic acidosis, or has large intentional ingestion. •

6. Megarbane B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med 2005;31(2):189-95. Epub 2004 Dec 31. 7. Mycyk MB, Leikin JB. Antidote review: fomepizole for methanol poisoning. Am J Ther 2003;10(1):68-70. 8. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA; American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002;40(4):415-46.

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POINTS SAILLANTS •

Faites une anamnèse détaillée pour écarter la possibilité de co-ingestion. • Calculez et interprétez attentivement les trous anionique et osmolaire. • Il faut deux séries d’analyses de spécimens sanguins prélevés à quelques heures d’intervalle. • Pour la prise en charge, utilisez le fomepizole ou l’éthanol comme inhibiteur de l’alcool déshydrogénase. • La dialyse est indiquée si le patient est comateux, s’il a une acidose métabolique grave ou s’il y a eu une importante ingestion intentionnelle. poisoning, making clinical assessment and ancillary evaluation imperative. Despite the seemingly innocuous nature of this poisoning at first glance, it requires further assessment and possibly treatment. All ingestions should be taken seriously to avoid undertriage. Despite the inconvenience of bringing a child to the emergency department, long-term sequelae far outweigh this inconvenience over time. This child must come in to the emergency department.  Dr LeBlanc is an Associate Professor and Dr Murphy is an Assistant Professor in the Department of Emergency Medicine at Dalhousie University in Halifax, NS. Competing interests None declared References 1. Levine MD, Barker TD. Toxicity, alcohols. [eMedicine website]. Available from: www.emedicine.com/emerg/topic19.htm. Accessed 2008 Nov 4. 2. Korabathina K, Benbadis SR, Likosky D. Methanol [eMedicine website]. Available from: www.emedicine.com/neuro/topic217.htm. Accessed 2008 Nov 4. 3. Keyes D. Toxicity. Ethylene glycol [eMedicine website]. Available from: www. emedicine.com/emerg/topic177.htm. Accessed 2008 Nov 4. 4. Caravati EM, Erdman AR, Christianson G, Manoguerra AS, Booze LL, Woolf AD, et al. Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 2005;43(5):327-45. 5. Ries NL, Dart RC. New developments in antidotes. Med Clin North Am 2005;89(6):1379-97.



Emergency Files is a new quarterly series in Canadian Family Physician coordinated by the members of the Emergency Medicine Committee of the College of Family Physicians of Canada. The series explores common situations experienced by family physicians doing emergency medicine as part of their primary care practice. Please send any ideas for future articles to Dr Robert Primavesi, Emergency Files Coordinator, at [email protected] FOR PRESCRIBING INFORMATION SEE PAGE 101

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