We present the case of an elderly male with altered mental status, acute kidney injury, elevated anion gap metabolic acidosis, and profound lactate and osmolal gaps. Ethylene glycol is an alcohol found in many household products such as antifreeze, deicing solutions and windshield wiper fluids [ 1 ].
Odorless, colorless, and sweet in taste, it is most commonly ingested by children, animals, and those seeking a substitute for ethanol but has also been reported in cases of homicide [ 2 ] and suicide. The toxicity of ethylene glycol is mediated by its metabolites, mainly glycolic acid and oxalate [ 4 ]. These metabolites are responsible for the pathogenesis of the symptoms with which patients present, which are classically those of profound acidosis altered sensorium and Kussmaul breathing and crystalluria consumptive hypocalcemia, oliguria, hematuria, and flank pain [ 5 ].
Diagnosis is made based on known or suspected ingestion in the appropriate clinical setting, with laboratory evaluation playing a key role.
While there are tests to specifically identify ethylene glycol in the serum, they may not be readily available and are not without their limitations. As such, clinicians often rely on clinical presentation and findings on blood tests, such as a severe and unexplained anion gap metabolic acidosis with an osmolar gap, to make the diagnosis.
Prevention of sequelae of ethylene glycol intoxication is dependent upon early identification and intervention in order to minimize the production of its toxic metabolites [ 6 ]. Early therapeutic intervention is important as most of the ethylene glycol is absorbed through the gastrointestinal tract within one hour of ingestion.
It should be noted that initial treatment with sodium bicarbonate, though necessary for correction of severe acidosis, may raise the urine pH and increase the likelihood of the precipitation of calcium oxalate crystals, furthering kidney injury and hypocalcemia. This highlights again the importance of early identification and effective intervention.
As patients are often critically ill, they frequently require monitoring in an intensive care unit to watch for secondary complications of altered mental status and cardiac arrhythmias. We herein present a case of an accidental ingestion of ethylene glycol in an elderly male that necessitated the above-mentioned therapeutic interventions.
A year-old male with a medical history significant for hypertension, dementia, and prior transient ischemic attack was brought into the hospital by his daughter for altered sensorium and gait disturbance. At baseline, the patient was capable of ambulating without assistance. He was last known well around one day prior to his emergency visit.
According to the daughter, around on the day of his admission, the patient was noted to have difficulty in standing and sitting upright unassisted. His speech was garbled and nearly unintelligible. Subsequently, the daughter brought the patient to the emergency room five hours later at around On presentation, the patient was afebrile, normotensive, tachycardic, and tachypneic. Physical exam findings were normal except for lethargy, disorientation, and response to deep pain by moving all extremities.
His blood profile showed an acute kidney injury with creatinine of 1. Lactic acid was 1. The venous lactic acid level was initially attributed to a laboratory error given the consistently profound low pH on repeated arterial blood gases.
A thorough investigation into the cause of this perceived severe lactic acidosis was undertaken and no clear etiology was identified. There was no evidence of sepsis or postictal symptoms, head CT was negative for stroke, and glucose and beta hydroxybutyrate were within normal limits. Furthermore, there were no signs of gangrenous tissue and surgical and radiological evaluations were negative for ischemic bowel or incarcerated hernia.
Additionally, the patient was hemodynamically stable with normal liver enzymes, making systemic hypoperfusion or decreased clearance of lactic acid highly unlikely. Despite several fluid boluses and sodium bicarbonate administration, the acidosis and lactate levels did not improve.
At this time, repeat lactic acid levels were sent from both venous blood and an arterial blood gas and demonstrated the same significant discrepancy 1. Subsequently, the patient was admitted to the intensive care unit and continued on intravenous sodium bicarbonate to correct the underlying acidosis and fomepizole to block conversion of ethylene glycol by alcohol dehydrogenase to toxic metabolites and initiated on emergent hemodialysis.
Thiamine and pyridoxine were also given to facilitate conversion of glycolate to less toxic metabolites. Serial labs were drawn to monitor acidosis and ethylene glycol levels. Initially, renal function was stable, with the patient making nearly 2 liters of urine in 24 hours; however, within 48 hours, the patient became oliguric and his renal function deteriorated.
Corrected serum calcium dropped from 9. He was discharged on long-term intermittent hemodialysis with uncertain potential for renal recovery. When patients present to the emergency room with altered mental status, the differential diagnosis is generally broad.
However, ethylene glycol intoxication is not uncommon. In their annual report, the American Association of Poison Control Centers reported a total of cases of ethylene glycol poisoning during alone, a steadily rising number over the years.
In , this number rose to a total of cases. In the report, ethylene glycol was the third most common chemical responsible for deaths by nonpharmaceutical poisoning, following ethanol and carbon monoxide [ 7 ]. It should be noted though that reporting of these cases to poison control depends solely on the discretion and initiative of the treating physician and, hence, the true number of cases is likely underestimated.
In the UK, the National Poisons Information Service reported a total of 91 cases of ethylene glycol poisoning ranking as the fourth most common after acetaminophen, drugs of misuse, and substance abuse. This number only rose to 92 in the following year [ 8 ]. This number is significantly smaller than that in the USA but authors will not speculate on the reason and there were no references exploring the differences.
Ethylene glycol is rapidly absorbed in the gastrointestinal tract within the first hour of ingestion. There have been no reported cases of toxicity after dermal or respiratory exposure [ 9 ]. Ingestion of ethylene glycol itself results in an inebriated state and central nervous system depression not unlike that seen in ethanol intoxication. The toxicity of ethylene glycol is mediated by its metabolites Figure 2 [ 4 ]. Ethylene glycol, like other alcohols, is metabolized in the liver.
Hepatic oxidation via alcohol dehydrogenase and aldehyde dehydrogenase generates glycolaldehyde and then glycolic acid, respectively. Further metabolism leads to glyoxylate, which may be converted to less toxic metabolites if thiamine and pyridoxine are available, and the final end product, oxalic acid.
Circulating glycolic acid in the blood leads to an elevated anion gap metabolic acidosis with resultant Kussmaul breathing and profound obtundation [ 4 ]. Direct renal tubular damage was traditionally attributed to glycolic acid, but there is evidence that glycolaldehyde and glyoxylate may be the principle ethylene glycol metabolites responsible for this mechanism of nephrotoxicity and the ensuing acute renal failure, oliguria, and hematuria Figure 2.
This particular damage was found to be independent of the calcium oxalate crystals formation [ 10 ]. As oxalate joins with calcium to form calcium oxalate, the resultant hypocalcemia may lead to nerve palsies and tetany. Seizures and arrhythmias may also develop. Calcium oxalate precipitates in urine and leads to further renal injury via crystal induced nephropathy with occasional flank pain [ 11 ]. Unfortunately, even if a clinician suspects ethylene glycol intoxication, definitive methods of detecting ethylene glycol in the serum have limitations which may significantly delay diagnosis and treatment in a situation where time is of the essence.
Solvent screens for alcohols may not include ethylene glycol and lead the clinician to incorrectly conclude that no ethylene glycol is present, while enzymatic assays have been known to give false positives in patients with elevated levels of lactate or lactate dehydrogenase [ 13 ]. Additionally, patients presenting late may have normal ethylene glycol levels but may be critically ill, having already metabolized ethylene glycol to its toxic metabolites. Outdoor Air: Ethylene glycol can release into outdoor air as a liquid spray aerosol , vapor, or mist.
Agricultural: If ethylene glycol releases as a liquid spray aerosol or mist, it may pollute agricultural products. If ethylene glycol releases as a vapor, it is unlikely to pollute agricultural products. Breathing ethylene glycol vapors may irritate eyes and lungs but is unlikely to cause systemic toxicity. Ethylene glycol does not absorb well through the skin so systemic toxicity is unlikely.
Eye exposure may lead to local adverse health effects but is unlikely to result in systemic toxicity. Personal Protective Equipment. Responders should wear these when entering an area with an unknown contaminant or when entering an area where the amount of the contaminant is unknown. Level A protection is necessary until monitoring results confirm the contaminant and the amount of the contaminant.
NOTE: Safe use of protective clothing and equipment requires specific skills from training and experience. Chemical-resistant gloves outer. Chemical-resistant gloves inner. Chemical-resistant boots with a steel toe and shank. It includes a non-encapsulating, splash-protective, chemical-resistant splash suit that provides Level A protection against liquids but is not airtight. A hooded chemical-resistant suit that protects against CBRN agents. Optional items: Coveralls, long underwear, a hard hat worn under the chemical-resistant suit, and chemical-resistant disposable boot-covers worn over the chemical-resistant suit.
Optional items: Escape mask, face shield, coveralls, long underwear, a hard hat worn under the chemical-resistant suit, and chemical-resistant disposable boot-covers worn over the chemical-resistant suit. Select when the amount is below the appropriate occupational exposure limit or less than AEGL-1 for the stated duration times. Limited to coveralls or other work clothes, boots, and gloves. Emergency Response. Upper explosive flammable limit in air UEL : Extinguish fires using an agent suitable for the type of surrounding fire.
Keep run-off water out of sewers and water sources. Also consider initial evacuation for 0. Immediately isolate an ethylene glycol spill or leak area for at least ft m in all directions. Hazardous amounts may develop quickly in enclosed, poorly ventilated, or low-lying areas. Keep out of these areas and upwind.
Ethylene glycol toxicity is categorized into three broad overlapping stages of adverse health effects. Stage 1 the neurological stage lasts from 30 minutes to 12 hours after ingestion. Stage 2 the cardiopulmonary stage occurs between 12 and 24 hours after ingestion.
Stage 3 the renal stage occurs between 24 and 72 hours after ingestion. The co-ingestion of alcohol can significantly delay adverse health effects. Initial adverse health effects caused by ethylene glycol intoxication include: central nervous system depression, intoxication, euphoria, stupor, and respiratory depression.
Nausea and vomiting may occur as a result of gastrointestinal irritation. Severe toxicity may result in coma, loss of reflexes, seizures uncommon , and irritation of the tissues lining the brain. Exposure to liquid ethylene glycol may result in swelling of the eyelid and cornea, swelling of the conjunctiva and iris, and conjunctival or corneal injury. Mild to moderate, Stage 2: Increased heart rate tachycardia ; abnormal or disordered heart rhythms dysrhythmia ; increased blood pressure hypertension ; and build-up of toxic breakdown products in the blood stream metabolic acidosis , resulting in increased rate and depth of breathing hyperventilation.
Mild to moderate, Stage 3: Effects are unusual following a mild to moderate exposure. Severe, Stage 1: Decreased reflex responses, seizures, loss of consciousness, and coma. Severe, Stage 2: More severe build-up of toxic breakdown products in the blood stream, resulting in increased rate and depth of breathing; heart damage, including congestive heart failure, resulting in buildup of fluid in the lungs pulmonary edema ; lung damage, including adult respiratory distress syndrome ARDS , resulting in a decreased oxygen supply to the body; multi-system organ failure; and death.
Severe, Stage 3: Reduced urine excretion; absence of urine excretion; and acute kidney failure, causing a build-up of toxic chemicals and chemical imbalances in the blood stream.
Exposure to levels of ethylene glycol concentrations higher than 80 ppm results in intolerable respiratory discomfort and cough. Decontaminate carefully because absorbed agent can release from clothing and skin as a gas. Your Incident Commander will provide you with decontaminants specific for the agent released or the agent believed to have been released.
The warm zone should include two decontamination corridors. One decontamination corridor is used to enter the warm zone and the other for exiting the warm zone into the cold zone. The decontamination zone for exiting should be upwind and uphill from the zone used to enter. Decontamination area workers should wear appropriate PPE. See the PPE section of this card for detailed information. A solution of detergent and water with a pH value of at least 8 but not higher than Fomepizole is a newer agent with a specific indication for the treatment of ethylene glycol poisoning.
Metabolic acidosis is resolved within three hours of initiating therapy. Initiation of fomepizole therapy before the serum creatinine concentration rises can minimize renal impairment.
Compared with nervous system and hypoglycemia, and easier maintenance of effective plasma levels. Family physicians are often the first health care professionals to see patients with undifferentiated complaints, including patients who have acute ingestion of poison.
The American Association of Poison Control Centers reported more than 4, and 6, exposures to ethylene glycol in 1 and , 2 respectively. Although the majority of these cases were unintentional, 21 in and 22 in were fatal. These reports are based on a surveillance system that underestimates the actual number of exposures. Ethylene glycol is a solvent found in products ranging from antifreeze fluid and de-icing solutions to carpet and fabric cleaners.
When treated appropriately, patients have survived much larger ingestions. While death and renal failure may occur with delayed diagnosis, death is uncommon in persons who receive prompt diagnosis and treatment. Toxicity results from the depressant effects of ethylene glycol on the central nervous system CNS. Metabolic acidosis and renal failure are caused by the conversion of ethylene glycol to noxious metabolites. Oxidative reactions convert ethylene glycol to glycoaldehyde, and then to glycolic acid, which is the major cause of metabolic acidosis.
Oxalic acid does not contribute to the metabolic acidosis, but it is deposited as calcium oxalate crystals in many tissues. Ethylene glycol is rapidly absorbed by the stomach and small intestine, and is quickly redistributed throughout the body. Metabolites of ethylene glycol remain in thebodyfor several days, with calcium oxalate present in tissues for much longer. However, presentation is highly variable and dependent on the amount ingested, the combined ingestion with ethanol, and the timing of medical intervention.
Ethylene glycol produces CNS depression similar to that of ethanol. Symptoms of ethylene glycol toxicity include confusion, ataxia, hallucinations, slurred speech, and comaSymptoms are most severe six to 12 hoursafter ingestion, when the acidic metabolites ofethylene glycol are at their maximal concentrationThe presentation may be similar toethanol intoxication, if the patient presentsearly or has consumed small amounts of ethyleneglycol.
However, an ethanol odor will beabsent, and serum or respiratory ethanol levelswill be too low to account for the degree ofCNS depression. The absence of a strong odorof alcohol in a patient who appears intoxicatedshould raise the suspicion of ethyleneglycol ingestion. Following a period of CNS depressionmetabolic acidosis and cardiopulmonary symptoms become prominent, although co-ingestion of ethanol will delay the metabolic acidosis.
The patient may experience nausea, vomiting, hyper ventilation, and hypocalcemia with muscle tetany and seizures. Hypertension, tachycardia, and cardiac failure may ensue. Pneumonitis, pulmonary edema, and adult respiratory distress syndrome have also been reported.
Renal involvement may become apparent within 24 to 72 hours after ingestion. Urinary crystal formation requires a sufficient amount of time for ethylene glycol to be metabolized into oxalate. Calcium oxalate formation depletes serum calcium levels and deposits in intestinal mucosa, liver, brain, heart, lung, and kidney. The excretion of calcium oxalate crystals in the urine is usually, but not always, present.
Oliguric or anuric renal failure is the result in the most severe cases and, although permanent renal failure is rare, recovery of renal function may take up to two months.
A year-old man who presented to the emergency department was completely unresponsive. His coworkers noted that he had a decreased level of function and had stumbled and fallen several times at work. The patient eventually became alert enough to admit that he had ingested three gallons of antifreeze within the past 48 hours. Physical examination while the patient wasminimally alert but disoriented revealed a rectal temperature of Neurologic examination was normal, lungs were clear to auscultation, and his extremities showed no cyanosis or edema.
The patient's blood chemistry data at admissionare shown in Table 1. Microscopic examination of the urine revealed more than redblood cells per high-power field, trace bacteria, and unidentifiable crystals. A urine toxicologyscreen was negative. A serum ethyleneglycol level of mg per dL Little correlation exists between blood levels of ethylene glycol and severity of poisoning, 4 making the diagnosis unclear at times.
Therefore, clinical or laboratory evidence is an indication for treatment even if toxic levels are not demonstrated. Calculation of the anion and osmolar gaps can facilitate an early diagnosis, and should be performed when the origin of metabolic acidosis is unknown. An increased anion gap with a normal chloride concentration indicates retention of nonvolatile organic acids such as glycolic acid.
If the serum osmolar gap is greater than 10 mOsm per kg of water, the presence of ethylene glycol poisoning is likely. If the patient presents soon after ingestion, ethylene glycol may not yet have been converted to its acid metabolites; late presentation may reveal no osmolar gap because the ethylene glycol has already been converted to toxic, but osmotically inactive, products.
High serum ethanol concentrations will cause an overestimation of the osmolar gap. The serum ethylene glycol test is specific for poisoning but is not commonly available. It requires a separate, dedicated gas chromatography column.
Although the test is not a good indicator of prognosis, a documented level above 20 mg per dL 3 mmol per L is an indication for treatment with fomepizole Antizol. The excretion of calcium oxalate crystals in the urine is a finding in approximately one half of patients and may be accompanied by red blood cells and myoglobin casts.
Unfortunately, the needle-shaped forms areoften confused with hippurate.
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