Ethylene Glycol Ingestion

: Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of ethylene glycol ingestion. This case is also appropriate for senior medical students and advanced practice providers. The principles of crisis resource management, teamwork, and communication are incorporated into the case.


Linked objectives and methods:
Ethylene glycol is not commonly encountered, but emergency medicine providers must be familiar with its pathophysiology, presentation, potential complications, and treatment. Providers are expected to obtain a thorough toxicologic history to assess a patient's current and projected clinical course, as well as any cofounding co-ingestants (objective 1). Identifying nonspecific presenting signs and symptoms, as well as more specific presentations, may help obtain the proper diagnosis in an encephalopathic or otherwise uncooperative patient, and these signs and symptoms are reviewed in the debriefing (objective 2). Learners should identify an anion gap metabolic acidosis, osmolar gap, acute kidney injury, and hypocalcemia that are associated with toxicity, but clinically may present at different times and with varying severity, depending on amount ingested and timing of ingestion, which will be reviewed during debriefing (objective 3). Not only should learners administer fomepizole and discuss hemodialysis with nephrology, but also should continue aggressive intravenous (IV) fluid administration to mitigate the risk of worsening renal injury. Adjunctive therapies such as pyridoxine and thiamine should also be considered, and all treatments should be reviewed during debriefing (objective 4). Ultimately, the patient requires disposition to the intensive care unit due to tenuous status and requirement for close monitoring (objective 5), and management must be discussed during the case with nephrology, poison control, and the intensivist.

Recommended pre-reading for instructor:
We recommend that instructors review literature regarding toxic alcohol ingestion, including its diagnosis and management.

Results and tips for successful implementation:
This simulation was written to be performed as a high-fidelity simulation scenario, but also may be used with low-or moderate-fidelity or as a mock oral board case. Background and brief information: Emergency medical services (EMS) was called by wife from the patient's home. Paramedics bring patient to emergency department (ED).

Initial presentation:
Patient is a 47-year-old male with history of alcohol abuse who presents from home via EMS with altered mental status and vomiting. The patient is lying supine, mildly tachypneic, and able to converse but intoxicated.
How the scenario unfolds: Patient is a 47-year-old male who presents from home by EMS after being found altered by his wife in the garage, covered in vomit. Participants should obtain an ECG which shows prolonged QTc, bloodwork which reveals an elevated osmolar gap and metabolic acidosis and hypocalcemia, an undetectable ethanol level, and a urinalysis with calcium oxalate crystals that fluoresces under Wood's lamp (Wood's lamp and urine sample should be concealed within simulation bay until specifically requested), and a head CT which does not show an acute process. The team should administer IV fluids, initiate fomepizole therapy, discuss the case with poison control, notify nephrology to discuss emergent dialysis, and admit to the ICU. The patient will become more hypotensive and tachycardic until both intravenous fluid (IVF) bolus and fomepizole are administered. If the patient does not receive fomepizole by the 12-minute mark, he will go into a pulseless electrical activity (PEA) arrest requiring two rounds of CPR to attain ROSC.

History:
• History of present illness: Patient is a 47-year-old male who presents today from home, brought in by EMS after being found stuporous by his wife in the garage. He is arousable to loud voice and sternal rub, and he has been vomiting. The wife stated he was in a normal state of health earlier today, and she went to check on him after he had been in the garage for several hours. She found him confused and called 911.
Patient appears intoxicated, but can answer simple questions.
• Social history: History of alcohol abuse; no other known drug use. Drinks six beers per day on average. No tobacco use. • Family history: Noncontributory.

Secondary Survey/Physical Examination:
• General appearance: Lying supine in bed. He appears intoxicated and is drowsy but arousable to loud voice and to touch. He appears disheveled and is covered in vomit.  If they do not but team suspects toxic ingestion, nursing can prompt learners to call -"Is there anyone else we can call if you're worried that he took something?" If poison control is called for undifferentiated encephalopathy or unspecific toxic alcohol ingestion, the phone line will be busy Poison control will only be available once team voices specific concern for ethylene glycol ingestion. How helpful poison control will be is left to the discretion of the facilitator. If nephrology is called without the specific request to evaluate for hemodialysis, they will state they are busy and to call them back when you know what you want from them.
If nephrology is contacted to evaluate for hemodialysis, they will say they will be right down to evaluate the patient.
If the ICU is called but providers do not specifically state that the patient has ethylene glycol toxicity, the intensivist will tell them to call back when they figure out what's wrong with him, then hang up.
If ICU is contacted for ethylene glycol toxicity admission but nephrology was not yet called, the intensivist will tell them that they are busy and to call someone else to help them manage the patient in the meantime.
If ICU is called and the patient has been treated appropriately with IV fluids and fomepizole, nephrology has been contacted, and the team reports concern for ethylene glycol toxicity, the ICU will accept the patient.
If the patient arrested, ICU will ask why the patient arrested. They may provide further treatment guidance as felt appropriate per instructor. Then they will accept the patient.
Case ends.

Ingestions and Altered Mental Status
Do not forget to assess for co-ingestants and non-toxicologic causes of altered mental status, including but not limited to hypoglycemia, infections, seizures, stroke, and head trauma.

Ingestions and Suicide
All patients with a suspected overdose should be screened for suicidal intent.

Toxic Alcohols
The differential for an elevated anion gap after liquid ingestion should always include toxic alcohol ingestion, especially if the patient appears intoxicated but there is no clear history of ethanol ingestion or the patient does not smell of ethanol. Once discovered, clinicians should also order a lactate and calculate an osmolal gap. 2 Methanol is found in windshield-washer fluid, while ethylene glycol is present in antifreeze, engine coolant, and brake fluid. Isopropanol may be found in hand sanitizer and rubbing alcohol. Diethylene glycol may be found in automotive brake fluid, as a manufacturing solvent, or as a diluent in pediatric medications. Propylene glycol can be found in several consumer products, but toxicity may be seen in hospitalized patients, as high-dose infusions of medications which contain propylene glycol as a diluent (including phenobarbital, lorazepam, phenytoin, diazepam, esmolol, and nitroglycerin). Isopropanol is available as a 70% rubbing alcohol solution. 1 Toxic alcohols cause inebriating effects, but only isopropanol is directly toxic. Ethylene glycol and methanol are first metabolized by alcohol dehydrogenase and then subsequently by aldehyde dehydrogenase to their toxic metabolites. Methanol is metabolized to formic acid, while ethylene glycol is metabolized to glycolic acid, glyoxylic acid, and the nephrotoxic oxalic acid. Propylene glycol metabolizes to lactate, and isopropanol metabolizes into acetone. 2,3 Co-ingestion of ethanol delays production of the toxic alcohol metabolites because ethanol is a competitive substrate for alcohol dehydrogenase. 1 Methanol toxicity is most commonly associated with vision impairment, including the classically described "snowstorm vision," as well as abdominal pain, nausea, and vomiting. 2 Measured serum osmolality -calculated serum osmolality = osmolal gap. The normal osmolal gap is less than 10 mOsm/kg of water. 4 Initially, the osmolal gap is elevated from accumulation of the initial parent alcohol, but the gap decreases as the alcohols are metabolized. Co-ingestion of ethanol will prolong the anion gap because it impedes the metabolism of the toxic parent alcohols. 1 Conversely, the anion gap rises due to the increase in toxic metabolites. Therefore, early ingestions present with an elevated osmolal gap and a normal anion gap, while later ingestions may present with a normal osmolal gap and an elevated anion gap. 1 Some ethylene glycol metabolites, such as glycolate, are closely structurally similar to lactate, causing a factitious elevated lactic acid level and subsequently induce an even higher anion gap. 2 Lactic acidosis, ketoacidosis, and chronic kidney disease may also cause elevated osmolal and anion gaps. 2 Toxic alcohols are rapidly absorbed from the GI tract. Gastric decontamination is not effective for toxic alcohol ingestions. 2 Fomepizole inhibits alcohol dehydrogenase and has minimal side effects. If this is not readily available, ethanol may be given orally or intravenously to inhibit alcohol dehydrogenase. Fomepizole should not be given to patients with isolated isopropyl toxicity, however, because it will delay its metabolization and cause a prolonged intoxication. 5

DEBRIEFING AND EVALUATION PEARLS
Hemodialysis should be initiated for severe metabolic acidosis, methanol concentrations above 50mg/dl, ethylene glycol concentrations above 50mg/dl, isopropanol concentrations above 500 mg/dL, hemodynamic instability, visual disturbances after methanol ingestion, or acute kidney injury. 1 Treatment of propylene glycol is largely conservative with discontinuation of the offending agent, but hemodialysis may be indicated if otherwise unexplained lactic acidosis develops. 1 Folate may be used as an adjunctive therapy for methanol toxicity. Folate assists in the metabolism of the toxic formic acid metabolite to water and carbon monoxide. 5 Adjunctive therapies for ethylene glycol ingestions includes pyridoxine and thiamine. Pyridoxine 100mg IV encourages the metabolism of ethylene glycol to other substrates instead of downstream toxic metabolites, and thiamine 100 mg IV converts glyoxylic acid to alphahydroxy-beta-ketoadipic acid versus oxalic acid. 5