Ethylene glycol poisoning: A case report and review of the literature

Abstract

BACKGROUND

Ethylene glycol (EG) poisoning is often caused by the accidental ingestion of antifreeze. EG is metabolized into glycolate and oxalate and may cause metabolic acidaemia, neurotoxicity, acute kidney injury, and death. A variety of EG poisoning case reports have been published, and we wrote this case report and literature review to summarize the clinical experience of patients who survived EG poisoning.

CASE SUMMARY

In this case report, a 55-year-old man developed EG poisoning after ingesting antifreeze by accident and experienced acute kidney injury, nervous system dysfunction and inhalation pneumonia. The timely use of ethanol for detoxification, initiation of haemodialysis, and protection of organ function are effective treatment methods for patients with antifreeze poisoning. The patient was discharged in the 3rd week after admission. When discharged, the patient did not report any discomfort, had stable vital signs, did not have fever or diarrhoea, and had improved liver and kidney functions.

CONCLUSION

A timely diagnosis, haemodialysis, and organ protection are the keys to the successful treatment of poisoned patients.

Core Tip: Ethylene glycol (EG) poisoning causes harmful clinical outcomes. Although published EG poisoning case reports are not rare, summative literature reviews are lacking. We shared a case about how we rescued an EG poisoning patient and summarized the case reports of EG poisoning from the PubMed database in the decade. We found out the rough hospital stay time for EG poisoning patients and the potential quick test to determine EG poisoning. This article aims to provide a more systematic clinical strategy for diagnosing and treating EG patients.

INTRODUCTION

Ethylene glycol (EG) is the main component of antifreeze. People suffer from EG poisoning every year. In 2020, United States poison control centers reported 5277 calls related to EG poisoning, 13 of which resulted in death[1]. EG is metabolized into oxalic acid, formic acid, and hippuric acid in the body, which can lead to acute kidney injury and nervous system inhibition[2]. We present a case report detailing the successful treatment of high-dose antifreeze ingestion (the timeline of events and findings are shown in Figure 1) to improve the treatment success rate for EG poisoning. Additionally, we searched for case reports of EG poisoning published in the PubMed database from 2014 to August 2024, aiming to consolidate clinical treatment insights.

Figure 1.

Timeline of events and findings.

CASE PRESENTATION

Chief complaints

A 55-year-old man was admitted on August 2, 2018, due to dizziness, fatigue, irritability, and unclear speech for 16 hours after ingesting antifreeze.

History of present illness

The patient mistakenly ingested approximately 250 mL of antifreeze, after which he experienced dizziness and mild irritability. After learning that the patient had mistakenly taken antifreeze for 2 hours, the family helped the patient induce vomiting (the patient’s family had forgotten the specific situation). Nevertheless, the patient's dizziness and irritability worsened, and the patient developed an unsteady gait and unclear speech. Sixteen hours after the patient mistakenly ingested antifreeze, the family sent the patient to the Emergency Department of Chengdu Integrated TCM and Western Medicine Hospital for treatment. After gastric lavage, the emergency department physicians immediately sent the patient to the intensive care unit (ICU) for advanced treatment.

History of past illness

The patient was in good health in the past.

Personal and family history

The patient denied any family history of genetic diseases.

Physical examination

At admission, the patient was delirious, exhibited unclear speech, and was short of breath. The physical examination revealed a temperature of 36.5 °C, heart rate of 93 bpm, respiratory rate of 34 breaths/min, and blood pressure of 22.4/12 kPa. The patient had an acute appearance, no yellow skin or sclera, and no palpable swelling of superficial lymph nodes throughout the body. His heart rate was synchronized, and no murmurs were heard in any valve. No abnormalities were found in the chest, and the percussion of both lungs revealed clear sounds. No clear dry or wet rales were heard. The whole abdomen was soft, without tenderness or rebound pain. The Babinski sign was negative.

Laboratory examinations

Point-of-care tests in the emergency department revealed the following: PH of 7.18; carbon dioxide partial pressure of 1.03 kPa; oxygen partial pressure of 16.67 kPa; bicarbonate concentration of 2.90 mmol/L; K⁺ concentration of 4.40 mmol/L; anion gap of 26.0 mmol/L; serum osmolality of 315.58 mmol/L; creatinine concentration of 0.97 mg/dL; and blood urea nitrogen concentration of 6.78 mmol/L.

An auxiliary blood gas examination in the ICU revealed the following: PH of 7.315; carbon dioxide partial pressure of 4.21 kPa; oxygen partial pressure of 8.22 kPa (during oxygen inhalation); bicarbonate concentration of 15.7 mmol/L; anion gap of 16.5 mmol/L; serum osmolality of 275 mmol/L; and K⁺ concentration of 3.92 mmol/L. A routine blood examination revealed the following: Haemoglobin level of 166 g/L; white blood cell count of 11.35 × 10⁹ cells/L; neutrophil percentage of 73.7%; and platelet count of 213 × 10⁹/L. The coagulation test results were as follows: Prothrombin time, 11.1 sec; activated partial thromboplastin time, 26.8 sec; and fibrinogen concentration, 2.747 g/L. The biochemical test results were as follows: Total bilirubin concentration, 8.2 μmol/L; direct bilirubin concentration, 1.4 μmol/L; alanine aminotransferase level, 28 IU/L; aspartate aminotransferase level, 29 IU/L; creatine kinase level, 154 IU/L; albumin level, 48.9 g/L; creatinine level, 1.93 mg/dL; and blood urea nitrogen level, 7.0 mmol/L.

Imaging examinations

A bedside chest X-ray revealed scattered exudation in both lower lung fields (Figure 2).

Figure 2.

Patient’s bedside chest X-ray on the second day after admission to the intensive care unit. A bedside chest X-ray revealed scattered exudation in both lower lungs.

FINAL DIAGNOSIS

On the basis of the aforementioned findings, the diagnosis at admission was as follows: (1) Chemical poisoning (antifreeze/ EG); (2) Inhalation pneumonia; (3) Respiratory failure, and (4) Acute kidney injury.

TREATMENT

After admission, the patient’s airway was immediately checked for any obstructions, and he was placed on inhaled oxygen and administered 21.5 g of glucose in aqueous solution + 52.5 g of ethanol via a gastric tube (29.6 g/h). Ethanol was administered for four days. At the same time, continuous replacement renal treatment was started immediately after admission to the ICU. Vitamins B1 and B6 were administered to reduce the production of calcium oxalate, a toxic EG metabolite. Medicinal charcoal tablets were administered to adsorb toxins, and cathartics were administered to accelerate the elimination of toxins. Other treatments, such as dexamethasone, were administered to reduce inflammation, protect the stomach, and provide parenteral nutrition support.

On the 2^nd day after admission to the ICU, the patient developed disordered consciousness, and his blood oxygen saturation level decreased to 70%. A physical examination revealed dry and wet rales in both lungs. A bedside chest X-ray revealed scattered exudation in both lower lungs (Figure 2). We diagnosed the patient with aspiration pneumonia and respiratory failure. The airway was cleared immediately, and tracheal intubation was performed after the induction of anaesthesia. The patient was provided mechanical ventilation and appropriate analgesia and sedation. Ceftazidime was administered as an anti-infective agent, and sputum culture was performed. On the 4th day in the ICU, the sputum culture results revealed the presence of Klebsiella pneumoniae [ESBL (-)], and the antibiotic was adjusted to moxifloxacin based on drug sensitivity results. On the 6^th day after admission, the patient presented with fever and an elevated procalcitonin level, indicating that the pulmonary infection was exacerbated. Combined with the presence of fungal spores on the patient's sputum smear and the high-risk factors for an invasive fungal infection, we determined that the patient was suffering from a pulmonary fungal infection, and fluconazole was added to the regimen. On the 7^th day after admission, an electronic bronchoscope was used to enhance sputum drainage. On the 8th day after admission, the patient was successfully weaned from mechanical ventilation and subsequently extubated.

The patient was administered haemodialysis with continuous veno-venous haemofiltration filtration (CVVHDF) because he experienced acute kidney injury. From 16:30 on August 2^nd to 20:00 on August 8^th, the patient underwent continuous renal replacement treatment (in CVVHDF mode), during which low-molecular-weight heparin was administered for anticoagulation, and one filter was replaced approximately every 24 hours. On the 7^th day after admission, the patient's urine output remained stable at above 1000 mL/day (Table 1), and haemodialysis was discontinued. The patient was successfully transferred from the ICU to the Nephrology Department on the 12^th day after admission for further treatment. Because the patient's creatinine level was greater than 2.26 mg/dL, he received intermittent hemodialysis treatment twice in the nephrology department.

Table 1.

Patient’s urine volume in the intensive care unit

Days in ICU/day	1	2	3	4	5	6	7	8	9	10	11	12
Urine volume/mL	500	455	1000	850	850	1000	970	1600	1650	1650	1450	1850

ICU: Intensive care unit.

OUTCOME AND FOLLOW-UP

After a sequence of effective treatments, the patient was discharged on August 23. The patient had stable vital signs, no fever or diarrhoea, and improved liver and kidney functions at the time of discharge. The patient still received intermittent hemodialysis treatment 7–8 times within one month until his kidney function completely recovered. The patient’s son informed us that his father was in good health without kidney failure or nervous system inhibition by telephone.

DISCUSSION

Antifreeze usually contains EG, rust inhibitors, fungicides, pH regulators, and pour point depressants. EG is a colorless and sweet liquid with low toxicity, but its metabolites are highly toxic. The lethal dose of EG for adults is 80–100 mL[3]. In this case report, the patient ingested antifreeze by accident, and the amount ingested significantly exceeded the lethal dose. EG is quickly absorbed by the gastrointestinal tract and then diffuses into the blood and interstitial fluid because of its high water solubility. EG is metabolized to ethanol aldehyde by ethanol dehydrogenase and then to glycolic acid by aldehyde dehydrogenase; then, it is oxidized to glyoxylate by glycolate oxidase in the liver[3]. The main final metabolite of EG is oxalic acid, whereas other metabolites include formic acid and hippuric acid[3]. Due to the formation of a large amount of organic acids, metabolic acidosis and hyperkalaemia can occur. In addition, the presence of oxalate and calcium can lead to hypocalcaemia, and the deposition of oxalate calcium crystals in renal tubules can cause acute kidney injury[4]. Patients with severe EG poisoning may die quickly because of severe hyperkalaemia or metabolic acidosis, whereas others may die a few days later because of acute kidney injury or central nervous system injury[5].

The clinical manifestations of acute EG poisoning are generally divided into three stages: Central nervous system inhibition (0.5–12 hours after ingestion), circulatory and respiratory dysfunction (12–24 hours after ingestion), and renal dysfunction (24–72 hours after ingestion)[3]. However, in practical clinical work, organ dysfunction does not always follow the order of the above stages.

The diagnosis and assessment of the severity of EG poisoning depend mostly on the medical history. However, an inaccurate medical history obtained for patients with EG poisoning could be an obstacle to timely diagnosis and treatment. Therefore, gas chromatography is a key alternative method for diagnosing EG poisoning[6,7]. An increasing number of case reports have shown that the anion gap[8], osmolar gap[9], urinary calcium oxalate level[8,9] or urine fluorescence test[10] may help diagnose EG poisoning. In addition, Zhou et al[11] reported that bile acids may serve as biomarkers that could reflect the severity of renal function damage in EG poisoning model mice with acute kidney injury. However, in this case report, the patient's bile acid level was within the normal range. Therefore, more related in vivo and in vitro experiments need to be conducted.

Detoxifying agents and blood purification are crucial for treating patients with EG poisoning. Ethanol and fomepizole are specific antidotes to EG. Ethanol rapidly oxidizes in the body and competes with EG in the liver for the ethanol dehydrogenase necessary for the oxidation of the latter, inhibiting the production of more toxic oxygen-containing EG metabolites[12]. Fomepizole is an inhibitor of EG[5,12]. Both of these antidotes can cause EG to be excreted from urine in its primary form. Fomepizole has been approved by the United States Food and Drug Administration as an antidote to EG. Compared with ethanol, the pharmacokinetics of fomepizole are clearer, and its dosage is easier to control. Moreover, fomepizole does not require blood drug concentration monitoring and cannot cause central nervous system inhibition, thus reducing adverse drug events[3]. If doctors have no experience in choosing antidotes to EG, the selection of fomepizole may be safer, especially when treating pediatric patients with EG poisoning[3]. However, fomepizole has not been approved as a treatment for EG poisoning in China. Thus, ethanol remains the preferred antidote to EG in China. Injecting 0.7 g of ethanol per liter of blood can inhibit the metabolism of most of the EG in the body[13]. According to previous case reports, fomepizole can be replaced by an intravenous infusion of 10% ethanol[3].

The use of ethanol for detoxification alone does not achieve good therapeutic effects, especially in patients with acute kidney injury. Therefore, extracorporeal treatments (ECTRs), such as haemodialysis, haemofiltration and haemoperfusion, must be used[2,14]. The function of ECTRs is to remove EG and its toxic metabolites, which can shorten the duration of the administration of antidotes and hospitalization[2,14]. Intermittent haemodialysis is the preferred method for rapidly removing EG[14]. Roberts et al[15] indicated that measuring the concentration of EG in plasma supported the accurate establishment of a haemodialysis prescription in patients with EG poisoning. On the other hand, the selection of ECTRs for patients with EG poisoning needs to be tailored to the individual circumstances[2,16].

We selected case reports of EG poisoning published from January 2014 to August 2024 in PubMed (Table 2 and Table 3). The full-text reports of 19 cases[3,6,8-10,12,17-29] were available in English for our review. Sixteen patients[3,12,18-20] recovered. Information was provided on the duration of hospitalization for 11 patients[3,6,8,10,17,18,20,21,24-26], with a median hospitalization duration of 21 (7,30) days. The patient in our study had a hospital stay of 22 days, which is compatible with the numbers in published case reports. Three patients[6,21,24] died: One[21] ingested more than 1000 mL of antifreeze agent, one[24] ingested EG more than once, and the other[6] died because his incomplete medical history led to an unclear diagnosis. Haemodialysis was not used in only one[10] of the 19 patients, and the patient did not suffer severe organ dysfunction, which was due to the quick bedside analysis of the patient’s urine with ultraviolet fluorescence. These findings highlight that the timely diagnosis of EG poisoning is essential. In addition, 12 patients[6,9,17,19,20,21,23-28] received invasive mechanical ventilation to protect their airways and provide respiratory support, and one patient[25] received extracorporeal membrane oxygenation for circulatory and respiratory support. Therefore, early organ function support should be instituted for patients with antifreeze poisoning. Three patients[3,6,28] did not receive antidotes: The specific reason was not described for one patient[3]; in another patient[6], EG poisoning was initially misdiagnosed as ethanol poisoning due to a lack of clarity in the patient’s medical history, and the patient unfortunately died; in the third patient from South Africa[28], ethanol was not used because the patient had severe epilepsy, and fomepizole was not used because it was not available in South Africa.

Table 2.

Literature review and our case of ethylene glycol poisoning

Ref.	Age	Sex	Location	Volume of antifreeze	Time after taking antifreeze	Hospital stay duration	Main treatment			Pulmonary infection	Outcome
							Detoxifying agents	Hemodialysis	Mechanical ventilation
Wu et al[3]	35	M	China	About 200 mL	About 19 hours	30 days	Did not use	Y	N	Y	Recovered
Judea-Pusta et al[6]	36	M	Romania	UK	UK	7 days	Did not use	Y	Y	Y	Died
Ukita et al[8]	71	FM	Japan	UK	UK	29 days	Fomepizole and ethanol	Y	N	N	Recovered
Gaddam et al[9]	60	M	United States	UK	3 hours	UK	Fomepizole	Y	Y	N	Recovered
Varshavsky et al[10]	70	M	United States	UK	UK	7 days	Fomepizole	N	N	N	Recovered
Drick et al[12]	60	M	Turkey	About 500 mL	12 hours	UK	Fomepizole and ethanol	Y	N	N	Recovered
Lulić et al[17]	35	FM	Croatia	500 mL	8 hours	28 days	Ethanol	Y	Y	N	Recovered
Basnayake et al[18]	26	FM	Sri Lanka	UK	48 hours	10 days	Fomepizole	Y	N	N	Recovered
Tang[19]	61	M	United States	UK	12 hours	UK	Fomepizole	Y	Y	N	Recovered
Ahmed et al[20]	64	FM	United States	UK	UK	30 days	Fomepizole	Y	Y	N	Recovered

M: Male; FM: Female; Y: Yes; N: No; UK: Unknown.

Table 3.

Literature review and our case of ethylene glycol poisoning

Ref.	Age	Sex	Location	Volume of antifreeze	Time after taking antifreeze	Hospital stay duration	Main treatment			Pulmonary infection	Outcome
							Detoxifying agents	Hemodialysis	Mechanical ventilation
Erickson[21]	37	M	United States	About 1000 mL	12 hours	22 hours	Fomepizole	Y	Y	N	Died
Kim[22]	55	FM	United States	UK	UK	UK	Fomepizole	Y	N	N	Recovered
Kolosionek et al[23]	62	M	United States	About 400 mL	5 hours	UK	Fomepizole	Y	Y	N	Recovered
Loriaux et al[24]	38	FM	United States	UK	12 hours	3 days	Fomepizole	Y	Y	UK	Died
Orlando et al[25]	60	M	Italy	UK	UK	21 days	Fomepizole	Y	Y	N	Recovered
Owen et al[26]	17	M	United States	UK	2 days	38 days	Fomepizole	Y	Y	N	Recovered
Sheta et al[27]	57	M	Denmark	UK	UK	UK	Ethanol	Y	Y	N	Recovered
Smit et al[28]	29	M	South Africa	UK	UK	UK	Did not use	Y	Y	N	Recovered
Zuckerman and Vo[29]	39	M	United States	UK	UK	UK	Fomepizole	Y	N	N	Recovered
Our case	55	M	China	About 250 mL	16 hours	22 days	Ethanol	Y	Y	Y	Recovered

M: Male; FM: Female; Y: Yes; N: No; UK: Unknown.

Compared with other published studies on the successful rescue of EG poisoning, our case report has some shortcomings in terms of the diagnosis and subsequent disease assessment because we could not detect the blood concentration of EG at our hospital. However, owing to the relatively accurate illness history, blood gas analysis, and renal function tests, the diagnosis and treatment of the patient were not delayed. In addition, the treatment strategy we adopted was almost identical to that used for successful rescue cases. The patient's length of hospital stay is similar to the median length of hospital stay in the literature we searched, which can indirectly suggest the effectiveness of the treatment.

CONCLUSION

In summary, this case report describes the successful treatment of a 55-year-old male with multiple organ dysfunction due to poisoning caused by the ingestion of a large amount of antifreeze. The timely use of ethanol for detoxification, implementation of an individualized haemodialysis plan, and protection of organ function are effective treatment methods for patients with antifreeze poisoning. Finally, based on reports in the literature, a timely diagnosis and prompt initiation of organ function support are clearly essential for patients with EG poisoning.