Ethylene Glycol Ingestion Resulting in Brainstem and Midbrain Dysfunction

Introduction: Ethylene glycol toxicity has produced central nervous system abnormalities including coma, cerebral edema, and cranial nerve dysfunction. Case Report: A 26-year-old male developed widespread brainstem and midbrain dysfunction with corresponding cranial computed tomography findings after ingesting ethylene glycol. The computed tomography scan which was obtained 3 days after ethylene glycol ingestion showed low density areas in the basal ganglia, thalami, midbrain, and upper pons. The neurologic findings in our patient reflected dysfunction of all the areas of hypodensity on the cranial computed tomography scan. A magnetic resonance imaging of the brain obtained 24 days after ingestion revealed bilateral putamen necrosis. The patient's neurologic sequelae resolved over the following 4 months.     

Massive Ethylene Glycol Poisoning Triggers Osmotic Demyelination Syndrome

Background

Ethylene glycol is a toxic organic solvent implicated in thousands of accidental and intentional poisonings each year. Osmotic demyelination syndrome (ODS) is traditionally known as a complication of the rapid correction of hyponatremia.

Objective

Our aim was to describe how patients with ethylene glycol toxicity may be at risk for developing ODS in the absence of hyponatremia.

Case Report

A 64-year old female patient was comatose upon presentation and laboratory results revealed an anion gap of 39, a plasma sodium of 150 mEq/L, a plasma potassium of 3.5 mEq/L, an osmolal gap of 218, an arterial blood gas pH of 7.02, whole blood lactate of 32 mEq/L, no measurable blood ethanol, and a plasma ethylene glycol concentration of 1055.5 mg/dL. The patient was treated for ethylene glycol poisoning with fomepizole and hemodialysis. Despite having elevated serum sodium levels, the patient's hospital course was complicated by ODS.

Conclusions

Rapid changes in serum osmolality from ethylene glycol toxicity or its subsequent treatment can cause ODS independent of serum sodium levels.     

Ethylene Glycol Poisoning: Resolution of Cranial Nerve Deficit

Ethylene glycol poisoning is a major contributor to the development of idiopathic metabolic acidosis, which may lead to renal failure. Ethylene glycol poisoning should be among suspected differentials when assessing a seemingly intoxicated patient with hypocalcemia, anion gap acidosis, and nontoxic blood alcohol levels. Glycol intoxication may lead to delayed neurologic manifestations, which may lead to an inaccurate diagnosis. No clear clinical guidelines exist to recommend treatment for this late effect. This is a case of the complete resolution of facial nerve deficit secondary to glycol poisoning after the completion of a steroid therapy course on an inpatient psychiatric unit.     

Treatment of Severe Pediatric Ethylene Glycol Intoxication Without Hemodialysis

Background: There is limited experience treating severe ethylene glycol poisoning in children without hemodialysis. The objective of this study was to describe the clinical course and outcome of severe pediatric ethylene glycol poisoning treated without hemodialysis. Methods: Patient records were identified retrospectively by hospital discharge diagnosis (ICD‐9 code) of ethylene glycol poisoning from 1999 through 2002 at a pediatric medial center. Patients with initial serum ethylene glycol concentrations less than 50 mg/dL or those who received hemodialysis were excluded. Results: Six patients with an age range of 22 months to 14 years were admitted for treatment of ethylene glycol poisoning over a four‐year period. Initial serum ethylene glycol concentrations ranged from 62 to 304 mg/dL (mean 174.0 mg/dL). The lowest‐measured individual serum bicarbonates ranged from 4 to 17 mEq/L. All patients were initially admitted to intensive care. One patient received ethanol only, two patients received fomepizole only, and three patients received a loading dose of ethanol and then were converted to fomepizole therapy. None of the patients received hemodialysis. Treatment was continued until the serum ethylene glycol was less than 10 mg/dL. Metabolic acidosis resolved with intravenous fluid and supplemental bicarbonate within 24h. All patients had a normal creatinine upon presentation and at discharge. The mean length of stay in intensive care was 21h and on the ward was 33.7h. One episode of hypoglycemia occurred in a 22‐month‐old. All patients recovered without evidence of renal insufficiency or other major complications at discharge. Conclusion: Six pediatric patients with severe ethylene glycol intoxication and normal renal function were successfully treated without hemodialysis.     

Clinical Evaluation of Pediatric Ethylene Glycol Monobutyl Ether Poisonings

Ethylene glycol butyl ether, CAS 111-76-2, an ingredient in many popular commercial window/glass cleaners, is known to produce equal if not greater toxicity than ethylene glycol when administered to animals. Treatment recommendations for human poisonings are based upon animal data and include the use of ethanol therapy to inhibit the production of toxic metabolites. No human experiential data exist to accurately assess human toxicity or to verify treatment modalities. A 5 month retrospective review of all glass cleaner ingestions reported to a regional poison information center disclosed 24 pediatric patients, ages 7 mo to 9y, who ingested 5-300 mL of a liquid glass cleaning product containing ethylene glycol butyl ether. All ingestions were reported within 5 min of ingestion, and all 24 children were asymptomatic at that time and subsequently. The product concentrations of ethylene glycol butyl ether ranged from 0.5% to 9.9%. Two of the 24 children ingested > 15 mL and were treated by gastric emptying and 24?h hospital observation. Neither hospitalized child suffered symptoms consistent with hemolysis, nervous system depression, acidosis, or renal compromise. Dilution with oral fluids at home is considered appropriate treatment of pediatric ingestions of <10 mL of a commercial liquid glass/window cleaners containing <10% ethylene glycol butyl ether.     

A Rapid Qualitative Test for Suspected Ethylene Glycol Poisoning

Objectives:  Many hospitals must send out ethylene glycol (EG) samples to a reference laboratory, and delays in diagnosis and treatment may occur. A qualitative colorimetric test (ethylene glycol test [EGT] kit), already in use by veterinarians, gives results in 30 minutes with little expertise or cost. The EGT reliably detects the presence of EG in spiked human serum samples. The objective of this study was to prospectively assess the sensitivity and specificity of the EGT kit in actual clinical samples submitted for EG testing by the criterion standard gas chromatography (GC).
Methods:  Blood samples from patients with suspected toxic alcohol poisoning submitted to a reference laboratory were tested by GC. An investigator blinded to the GC results tested the same sample with the EGT kit following the manufacturer's instructions and using the internal control. Three physicians also blinded to the GC results categorized the sample as positive for EG, negative, or inconclusive. Interrater reliability was assessed with a kappa statistic (κ). Results of the EGT kit testing were then compared to those from GC testing.
Results:  Data are reported on 24 samples submitted. By GC, 15 samples were confirmed for EG (range 27–281 mg/dL), 5 were confirmed for methanol (ME; range 64–101 mg/dL), and 4 were negative for both alcohols. The EGT was unanimously positive in all confirmed EG samples and negative in all ME samples. In one of the negative samples, an ambiguous result occurred and was counted as a false-positive. Interobserver agreement with the EGT was high (κ = 0.909; 95% confidence interval [CI] = 0.735 to 1.0). Sensitivity and specificity were 100% (95% CI = 70% to 100%) and 88.8% (95% CI = 52% to 100%), respectively.
Conclusions:  The EGT appears to be a reliable qualitative test in cases of suspected human EG poisoning.     

Accelerated Clearance of Ultrasound Contrast Agents Containing Polyethylene Glycol is Associated with the Generation of Anti-Polyethylene Glycol Antibodies

Emerging evidence suggests that the immune system can recognize polyethylene glycol (PEG), leading to the accelerated blood clearance (ABC) of PEGylated particles. Our aim here was to study the generation of anti-PEG immunity and changes in PEGylated microbubble pharmacokinetics during repeated contrast-enhanced ultrasound imaging in rats. We administered homemade PEGylated microbubbles multiple times over a 28-d period and observed dramatically accelerated clearance (4.2?×?reduction in half-life), which was associated with robust anti-PEG IgM and anti-PEG IgG antibody production. Dosing animals with free PEG as a competition agent before homemade PEGylated microbubble administration significantly prolonged microbubble circulation, suggesting that ABC was largely driven by circulating anti-PEG antibodies. Experiments with U.S. Food and Drug Administration-approved Definity microbubbles similarly resulted in ABC and the generation of anti-PEG antibodies. Experiments repeated with non-PEGylated Optison microbubbles revealed a slight shift in clearance, indicating that immunologic factors beyond anti-PEG immunity may play a role in ABC, especially of non-PEGylated agents.     

Ethylene Glycol Exposure: an Evidence-Based Consensus Guideline for Out-of-Hospital Management

In 2002, poison centers in the US reported 5816 human exposures to ethylene glycol. A guideline that effectively determines the threshold dose for emergency department referral and need for pre-hospital decontamination could potentially avoid unnecessary emergency department visits, reduce health care costs, optimize patient outcome, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the primary author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with a suspected exposure to ethylene glycol by 1) describing the process by which the exposure might be evaluated, 2) identifying the key decision elements in managing the case, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care, considering all of the circumstances involved. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) A patient with exposure due to suspected self-harm, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the dose reported (Grade D). 2) Patients with inhalation exposures will not develop systemic toxicity and can be managed out-of-hospital if asymptomatic (Grade B). Patients with clinically significant mucous membrane irritation should be referred for evaluation (Grade D). 3) Decontamination of dermal exposures should include routine cleansing with mild soap and water. Removal of contact lenses and immediate irrigation with room temperature tap water is recommended for ocular exposures. All patients with symptoms of eye injury should be referred for an ophthalmologic exam (Grade D). 4) Patients with symptoms of ethylene glycol poisoning should be referred immediately for evaluation regardless of the reported dose (Grade C). 5) The absence of symptoms shortly after ingestion does not exclude a potentially toxic dose and should not be used as a triage criterion (Grade C). 6) Adults who ingest a “swallow” (10–30 mL), children who ingest more than a witnessed taste or lick, or if the amount is unknown of most ethylene glycol products should be referred immediately for evaluation. The potential toxic volume of dilute solutions (e.g., concentration < 20%) is larger and can be estimated by a formula in the text (Grade C). 7) A witnessed taste or lick only by a child, or an adult who unintentionally drinks and then expectorates the product without swallowing, does not need referral (Grade C). 8) Referral is not needed if it has been > 24 hours since a potentially toxic unintentional exposure, the patient has been asymptomatic, and no alcohol was co-ingested (Grade D). 9) Gastrointestinal decontamination with ipecac syrup, gastric lavage or activated charcoal is not recommended. Transportation to an emergency department should not be delayed for any decontamination procedures (Grade D). 10) Patients meeting referral criteria should be evaluated at a hospital emergency department rather than a clinic. A facility that can quickly obtain an ethylene glycol serum concentration and has alcohol or fomepizole therapy available is preferred. This referral should be guided by local poison center procedures and community resources (Grade D). 11) The administration of alcohol, fomepizole, thiamine, or pyridoxine is not recommended in the out-of-hospital setting (Grade D).     

Ethylene Glycol Toxicity: The Role of Serum Glycolic Acid In Hemodialysis

Objective: To correlate serum glycolic acid levels with clinical severity and outcome in ethylene glycol poisoning and to determine if glycolic acid levels are predictive of renal failure and the need for hemodialysis. Methods: We measured serum ethylene glycol and glycolic acid levels by gas chromatography/mass spectrometry for 41 admissions (39 patients) for ethylene glycol ingestion and performed retrospective chart reviews. Results: Eight patients died, all of whom developed acute renal failure. Of the survivors, 15 also developed acute renal failure, whereas 18 did not. Of those with normal renal function, 8 had glycolic acid levels below detection limits (<0.13 mmol/L) despite ethylene glycol levels as high as 710 mg/dL; 7 of these patients coingested ethanol. Pertinent initial laboratory data for each group are as follows (mean; range): Deceased: pH 6.99 (6.82–7.22); bicarbonate, 4.8 mmol/L (2–9); anion gap, 28.6 mmol/L (24–40); glycolic acid, 23.5 mmol/L (13.8–38.0); ethylene glycol, 136.5 mg/dL (6–272). Survived/acute renal failure: pH 7.07 (6.75–7.32); bicarbonate, 5.6 mmol/L (1–12); anion gap, 28.7 mmol/L (18–41); glycolic acid, 20.2 mmol/L (10.0–30.0); ethylene glycol, 238.8 mg/dL (12–810). No acute renal failure with glycolic acid >1.0 mmol/L: pH 7.29 (7.12–7.46); bicarbonate, 14.7 mmol/L (4–23); anion gap, 16.5 mmol/L (10–26); glycolic acid, 6.8 mmol/L (2.6–17.0); ethylene glycol, 269.1 mg/dL (6–675). No acute renal failure with glycolic acid <1.0 mmol/L: pH 7.41 (7.38–7.47); bicarbonate, 23.4 mmol/L (17–25); anion gap, 11.8 mmol/L (8–18); glycolic acid, 0.1 mmol/L (0–0.66); ethylene glycol, 211 mg/dL (8–710). The mean time postingestion to admission generally correlated with severity as follows: deceased, ≥10.4 h; survived/acute renal failure, ≥9.9 h; no acute renal failure with glycolic acid >1.0 mmol/L, ≥6.2 h; no acute renal failure with glycolic acid <1.0 mmol/L, ≥3.7 h. Hematuria was more prevalent than oxaluria (86% and 41%, respectively), but neither was individually predictive of acute renal failure. Good correlations were found between glycolic acid levels and anion gap (r² = 0.7724), pH (r² = 0.7921), and bicarbonate (r² = 0.6579); poor correlations (r² <0.0023) occurred between ethylene glycol levels and glycolic acid, pH, anion gap, and bicarbonate. Measured ethylene glycol values were highly correlated with ethylene glycol values calculated from the osmolal gap (r² = 0.9339), but the latter overestimates the true value by about 7%, on average. An initial glycolic acid level ≥10 mmol/L predicts acute renal failure with a sensitivity of 100%, a specificity of 94.4%, and an efficiency of 97.6%. Ethylene glycol levels are not predictive of acute renal failure or central nervous system manifestations of toxicity. If only ethylene glycol values are available (measured or calculated), an initial anion gap >20 mmol/L is 95.6% sensitive and 94.4% specific for acute renal failure when ethylene glycol is present. Likewise, initial pH <7.30 is 100% sensitive and 88.5% specific for acute renal failure. Conclusion: We propose glycolic acid <8 mmol/L as a criterion for the initiation of hemodialysis in ethylene glycol ingestion. Patients with glycolic acid <8 mmol/L probably do not need dialysis, regardless of the ethylene glycol concentration, when metabolism of ethylene glycol is therapeutically inhibited. In the absence of glycolic acid values, an anion gap >20 mmol/L or pH <7.30 predicts acute renal failure.     

Ethylene Glycol Poisoning. The Value of Glycolic Acid Determinations for Diagnosis and Treatment

Abstract

Glycolic acid is the ethylene glycol (EG) metabolite that accumulates in the highest concentrations in the blood and may be the major contributing factor to the acute toxicity of EG. Serum and urine levels of glycolic acid have been found to correlate directly with clinical symptoms and mortality in poisoning cases, making it a valuable diagnostic tool. A high pressure liquid chromatographic (HPLC) method for quantitation of glycolic acid in serum was used in several cases of EG ingestion presented to the Louisiana Regional Poison Control Center. The data collected in this study support the value of glycolic acid determination for diagnosis and evaluation of patients poisoned by EG.     

Recurrent Ethylene Glycol Poisoning with Elevated Lactate Levels to Obtain Opioid Medications

Background

Malingering is when a patient feigns illness for secondary gain. While most patients with malingering manufacture or exaggerate symptoms, some patients may induce illness. Previous reports of malingering patients inducing illness include sepsis, kidney pain, migraine, and chest pain. However, acute poisoning as a manifestation of malingering appears to be rare.

American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning

Fomepizole (4-methylpyrazole, 4-MP, Antizol?) is a potent inhibitor of alcohol dehydrogenase that was approved recently by the US Food and Drug Administration (FDA) for the treatment of ethylene glycol poisoning. Although ethanol is the traditional antidote for ethylene glycol poisoning, it has not been studied prospectively. Furthermore, the FDA has not approved the use of ethanol for this purpose. Case reports and a prospective case series indicate that the intravenous (IV) administration of fomepizole every 12 hours prevents renal damage and metabolic abnormalities associated with the conversion of ethylene glycol to toxic metabolites. Currently, there are insufficient data to define the relative role of fomepizole and ethanol in the treatment of ethylene glycol poisoning. Fomepizole has clear advantages over ethanol in terms of validated efficacy, predictable pharmacokinetics, ease of administration, and lack of adverse effects, whereas ethanol has clear advantages over fomepizole in terms of long-term clinical experience and acquisition cost. The overall comparative cost of medical treatment using each antidote requires further study.     

An Activated Charcoal Hemoperfusion System for the Treatment of Barbital or Ethylene Glycol Poisoning in Dogs

Abstract

The efficacy of activated charcoal (AC) hemoperfusion therapy was studied in dogs acutely poisoned with lethal doses of barbital or ethylene glycol (EG). Two of three barbital-poisoned dogs treated with AC hemoperfusion survived; the dog that died was only hemoperfused for 1.5?h. Although AC hemo'perfusion of EG-poisoned dogs reduced the blood level of the toxicant considerably, this was not enough to effect survival. The use of AC hemoperfusion was an effective therapeutic measure for dogs poisoned with lethal doses of barbital. The use of the AC hemoperfusion system with existing drugs of therapy for EG poisoning may be beneficial.     

Clearance of lidocaine by hemodialysis

Because little has been known regarding the dialyzability of lidocaine, we studied the clearance of this drug by hemodialysis. The dialysance of lidocaine was found to range between 10.6 to 21.3 ml/min. Lidocaine-urea extraction ratio averaged 11%. Because of the low therapeutic and even toxic plasma levels, the amount of drug removed by dialysis is negligible. Therefore, dose adjustment is unnecessary during dialysis, and dialysis appears to be of little help in the treatment of lidocaine toxicity.     

Kidneys and MR urography

Clinically useful images of the kidneys, ureters, and bladder can be generated routinely on a 3T MR scanner. Although little has been published directly comparing 3.0-T MR imaging of the urinary tract with 1.5T imaging, the same benefits and limitations that apply to other areas of the body apply to urinary tract imaging at 3T. The potential benefits of improved signal-to-noise ratio and conspicuity of gadolinium enhancement and the potential for functional MR imaging of the kidneys at 3T are compelling, but need to be investigated further.     

Synthesis of Immunoglobulins and 15 Other Proteins by Diseased Human Kidneys

Summary. In an effort to determine the synthetic capacity of human kidneys for serum proteins, pieces of both kidneys removed at operation prior to transplantation were placed in organ culture. Incubation with ¹⁴C labelled amino acids and subsequent radioimmunoelectrophoresis with antisera to all five classes of immunoglobulins showed synthesis of IgG by all 5 pairs of kidneys of IgA and IgE by 4, and of IgM by 2. None synthesized IgD. Radioimmunoelectrophoresis with specific antisera to 15 non-immunoglobulin proteins revealed synthesis of lactoferrin and uromucoid while several other serum proteins, such as al antitrypsin and α2 macroglobulin, known for their binding properties, showed apparent synthesis. No evidence for secretory component synthesis was seen despite positive immunofluorescent localization in the tubular cells. Further, Zn α2 and β₂GP I also showed positive immunofluorescence but negative synthesis. It seems possible that these latter proteins may not be synthesized by the tubular cells but rather may be actively excreted or reabsorbed by them.