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.
46 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.
Vol 55: january • janvier 2009 Canadian Family Physician • Le Médecin de famille canadien 47
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.
✶✶✶
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
Vol 55: january • janvier 2009 Canadian Family Physician • Le Médecin de famille canadien 49