Toxic Alcohol Ingestion: Prompt Recognition and Management in the Emergency Department (Critical Care Topic and Pharmacology CME)

Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Differential Diagnosis
6. Prehospital Care
7. Emergency Department Evaluation
   1. History
   2. Physical Examination
8. Diagnostic Studies
9. Ethylene Glycol Poisoning
   1. Etiology And Pathophysiology
   2. Emergency Department Evaluation Of Ethylene Glycol Ingestion
   3. Treatment For Ethylene Glycol Ingestion
      1. Fomepizole
      2. Ethanol
      3. Hemodialysis
      4. Adjunctive Therapies
10. Methanol Poisoning
    1. Etiology And Pathophysiology
    2. Emergency Department Evaluation Of Methanol Ingestion
    3. Treatment For Methanol Ingestion
       1. Fomepizole
       2. Ethanol
       3. Hemodialysis
       4. Adjunctive Therapies
11. Diethylene Glycol Poisoning
    1. Etiology And Pathophysiology
    2. Emergency Department Evaluation Of Diethylene Glycol Ingestion
    3. Treatment For Diethylene Glycol Ingestion
12. Propylene Glycol Toxicity
    1. Etiology And Pathophysiology
    2. Emergency Department Evaluation Of Propylene Glycol Toxicity
    3. Treatment For Propylene Glycol Toxicity
13. Isopropanol Poisoning
    1. Etiology And Pathophysiology
    2. Emergency Department Evaluation Of Isopropanol Ingestion
    3. Treatment For Isopropanol Ingestion
14. Special Circumstances And Special Populations
    1. Toxic Alcohol Ingestion In Pediatric Patients
    2. Toxic Alcohol Ingestion In Pregnant Patients
    3. Patients With Poor Nutritional Status
15. Controversies In The Management Of Toxic Alcohol Exposure
16. Disposition
17. Summary
18. Risk Management Pitfalls In Management Of Toxic Alcohol Ingestion
19. Time- And Cost-Effective Strategies
20. Case Conclusions
21. Clinical Pathway For Management Of Patients With Toxic Alcohol Ingestion
22. Tables and Figures
    1. Table 1. Differential Diagnosis For Patients With Possible Toxic Alcohol Ingestion
    2. Figure 1. Pathways Of Ethylene Glycol Metabolism
    3. Figure 2. The Reciprocal Relationship Of The Anion Gap And The Osmol Gap Over Time
    4. Figure 3. Major Pathway Of Methanol Metabolism
    5. Figure 4. Isopropanol Metabolism
23. References

Abstract

Identifying patients with potential toxic alcohol exposure and initiating appropriate management is critical to avoid significant patient morbidity. Sources of toxic alcohol exposure include ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropanol. Treatment considerations include the antidotes fomepizole and ethanol, and hemodialysis for removal of the parent compound and its toxic metabolites. Additional interventions include adjunctive therapies that may improve acidosis and enhance clearance of the toxic alcohol or metabolites. This issue reviews common sources of alcohol exposure, basic mechanisms of toxicity, physical examination and laboratory findings that may guide rapid assessment and management, and indications for treatment.

Case Presentations

A 27-year-old man with a history of depression presents after a reported ingestion of “about 8 ounces” of a workplace industrial solvent that has been identified by a shift supervisor as diethylene glycol. You are familiar with ethylene glycol and wonder if diethylene glycol poisoning results in similar toxicity. The patient has normal vital signs and a normal examination. What laboratory testing is warranted in this patient? Is it possible to obtain a diethylene glycol level? Based on this reported ingestion, what treatment is warranted?

A 54-year-old man you admitted on your last shift for severe alcohol withdrawal remains on a lorazepam infusion that you started 24 hours ago in the ED. When following up his case, you note that the patient has developed a worsening lactic acidosis since his admission. You discuss the case with the intensivist who is caring for the patient in the ICU. His infectious workup has been normal, and the rest of his laboratory testing has been within normal limits. What is the etiology of his lactic acidosis?

A 67-year-old man with a history of alcohol abuse is brought in by EMS after he was found unconscious outside a grocery store. EMS notes that the patient is responding to painful stimuli only and had an episode of blood-tinged emesis on the scene. He arrives to the ED receiving oxygen via nonrebreather mask. An empty bottle of rubbing alcohol is found in his coat pocket. What are your concerns in a patient with likely isopropanol exposure? What laboratory workup is warranted?

Introduction

The term toxic alcohol refers to a group of hydrocarbons that contain a hydroxyl group (-OH group) and are not intended for ingestion. This group includes ethylene glycol, methanol, propylene glycol, and isopropanol.¹ Diethylene glycol belongs to a class of glycol ethers that contain hydroxyl groups. It is also discussed here, as it may present in a clinically similar fashion to the toxic alcohols.²

Ethylene glycol is used primarily as an engine coolant, antifreeze, or brake fluid, and it may be unintentionally consumed by children or animals because of its sweet taste.^1,3 Methanol, most commonly in the form of windshield-washer fluid, has been implicated in several poisoning epidemics resulting from tainted beverages.^1,4-7 Outbreaks have been reported in undeveloped countries as a result of the adulteration of ethanol with methanol. Diethylene glycol, used as an antifreeze and as a solvent in industry and manufacturing, is responsible for multiple mass poisoning events due to its unsafe use as a diluent in medications and as a sweetener in wines, and it has also been used in self-harm attempts.^2,8-14 In 1937, 107 deaths followed ingestion of diethylene glycol that was used as a diluent for an elixir of the antibiotic sulfanilamide. This incident led to passage of the 1938 Food, Drug, and Cosmetic Act, which made the declaration that pharmaceutical products must be shown to be safe prior to public marketing.¹⁵ Propylene glycol, present in many foods, beverages, and cosmetics, is used as a diluent in many pharmaceuticals and also as an alternative to ethylene glycol in some antifreeze products.¹⁶ Isopropanol, or isopropyl alcohol, is typically available as a 70% rubbing alcohol solution and may be abused as an ethanol substitute. It is also a solvent used in household and pharmaceutical products.¹

All of the toxic alcohols may cause altered mental status, due to both increased inhibitory gamma-aminobutyric acid (GABA) tone and inhibition of the excitatory N-Methyl-D-aspartic acid (NMDA) glutamate receptors.¹ The metabolism of toxic alcohols to their metabolites may result in acidosis or ketosis. Specific end-organ toxicity from toxic alcohol metabolites is possible, including glycolic acid in ethylene glycol exposure, formic acid in methanol exposure, (2-hydroxyethoxy)acetic acid (HEAA) in diethylene glycol exposure, lactate in propylene glycol exposure, and acetone in isopropanol exposure.^1,2

The presence of a metabolic acidosis should also prompt consideration of other causes, including poisoning by xenobiotics such as metformin, which can cause a lactic acidosis; cellular poisoning by salicylate, iron, or cyanide; diabetic, alcoholic, or starvation ketosis; renal failure; and multiorgan failure from critical systemic illness such as sepsis.

A large difference in measured osmolarity and calculated osmolality (the osmol gap) should prompt consideration of a toxic alcohol exposure; however, this finding is neither sensitive nor specific and cannot be used to definitively rule in or rule out this exposure.

Disposition of the critically ill patient with toxic alcohol exposure requires consideration of patient needs, including access to antidotal therapies (such as fomepizole or ethanol), the availability of hemodialysis services, if needed, and an inpatient unit capable of providing critical care and resuscitation.

Critical Appraisal Of The Literature

To identify primary relevant literature, standard search strategies were used, including querying MEDLINE^® with the search terms toxic alcohol, ethylene glycol, methanol, diethylene glycol, propylene glycol, isopropyl alcohol, isopropanol, and fomepizole. Results were reviewed for clinical and practical relevance. Clinical studies, animal studies, review articles, editorials, commentaries, case reports, and case series were identified for review. The Cochrane Database of Systematic Reviews and the National Guideline Clearinghouse (www.guideline.gov) were also queried. Additional information was obtained from book chapters and Internet material.

Risk Management Pitfalls In Management Of Toxic Alcohol Ingestion

1. “The patient was found unconscious at home next to an empty container of windshield-washer fluid. I began fomepizole therapy and admitted him. I don’t know why he started to posture.”
   Patients who are found unconscious or who present with significant intoxication may need a head CT scan to evaluate for underlying traumatic injury. Patients intoxicated with a toxic alcohol who receive antidotal therapy will remain intoxicated for a prolonged period of time due to ADH blockade, and emergency clinicians should have a low threshold to assess for traumatic intracranial abnormality early, given that the patient’s neurological examination is compromised by the presence of intoxication.
2. “The patient had a normal anion gap, so I knew he couldn’t have ingested a toxic alcohol.”
   Failure to understand the reciprocal relationship between the osmol gap and the anion gap in toxic alcohol poisoning may lead to a misdiagnosis. Patients with toxic alcohol exposure may have a normal or elevated osmol gap early after the ingestion. However, after just a few hours, the parent toxic alcohol compound will be metabolized to toxic metabolites that cause an anion gap acidosis, and any elevation in the osmol gap may resolve. Early assessment of a patient with exposure to a toxic alcohol may reveal normal osmol and anion gaps, and this may be misleading if the emergency clinician uses these results alone to rule out a toxic alcohol exposure.
3. “I used a Wood's Lamp to test the patient's urine sample for fluorescence. Since I didn't see any, I know he didn't ingest any ethylene glycol.”
   The use of urine fluorescence to determine whether the patient has ingested a toxic alcohol (such as ethylene glycol) is unreliable and should not be used to rule out ingestion.
4. “The patient was very intoxicated and admitted to drinking rubbing alcohol, so I started fomepizole right away to prevent any further toxicity.”
   Patients with isolated isopropanol intoxication do not need fomepizole therapy, as blocking ADH is not needed to prevent toxic metabolite formation. Fomepizole therapy will prolong the patient’s severe intoxication by preventing the appropriate metabolism of the isopropanol.
5. “The patient drank antifreeze in a self-harm attempt, so I treated him with fomepizole and admitted him. I reviewed his chart, and I don’t understand why he developed delayed fulminant hepatic failure.”
   Neglecting assessment for other ingestions in the suicidal patient (such as acetaminophen and salicylate) may lead to significant morbidity or mortality. Obtain acetaminophen and salicylate concentrations in patients with suicidal ingestion and laboratory abnormalities concerning for an additional toxic ingestion. Patients may take multiple substances in self-harm attempts.
6. “I discussed the patient with the consulting nephrologist and recommended continuing the standard dose of fomepizole during dialysis.”
   Neglecting to adjust fomepizole dosing during hemodialysis will result in decreased effectiveness of antidotal therapy. During dialysis, fomepizole is given every 4 hours instead of every 12 hours. When discussing the patient with any inpatient clinicians, it is important for the emergency clinician to encourage dosing for fomepizole that is appropriate for hemodialysis.
7. “The patient reported ethylene glycol exposure, but I knew this was untrue because his ethylene glycol level came back negative.”
   Failure to provide appropriate therapy in patients reporting toxic alcohol exposure but who have negative toxic alcohol concentrations and a normal osmol gap can result in a missed diagnosis of toxic alcohol exposure. Patients who present in a delayed manner following toxic alcohol exposure may have negative or very low concentrations of toxic alcohols because the parent compound has already been metabolized to the toxic metabolites that cause a metabolic acidosis and end-organ damage.
8. “The patient is a known alcoholic, so I assumed he would sober up and be able to go home.”
   Individuals with a history of alcohol abuse are at risk for toxic alcohol ingestions. Ensure that a comprehensive history and laboratory workup are performed, as appropriate, in patients with altered mental status, anion gap metabolic acidosis, elevated osmol gap, renal failure, or vision loss.
9. “I waited for the methanol and ethylene glycol levels to come back from the laboratory to make sure the patient really needed to be treated with fomepizole.”
   Neglecting to start antidotal and adjunctive therapy while waiting for laboratory assessment for toxic alcohol exposure can result in worsening metabolic acidosis and the development of end-organ damage, such as renal failure or vision loss. In patients with a history suspicious for toxic alcohol exposure, antidotal therapy should be initiated while laboratory tests are processing.
10. “The patient had a severe anion gap metabolic acidosis after drinking antifreeze, so I started treatment with fomepizole to reverse his toxicity.”
    Neglecting to consider the potential need for hemodialysis in patients who present with end-organ damage after toxic alcohol exposure will delay definitive management of these patients. Once toxic alcohols have been metabolized to toxic metabolites and a severe anion gap metabolic acidosis has occurred, hemodialysis is indicated, and a nephrologist should be involved in the patient’s care. While fomepizole therapy should be initiated, this will not reverse toxicity from toxic alcohol exposure. Hemodialysis is needed to remove the toxic metabolites.

Tables And Figures

References

Evidence-based medicine requires a critical ap¬praisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study are included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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