Glycol Ingestion Research Articles

Treatment of Ethylene Glycol Poisoning-Reply

Our article 1 was not meant to be a complete review of the literature on the use of alcohol in treating ethylene glycol ingestion. Therefore, we do not feel that Wacker's article needed to be included, and we have no further comments on his letter at this time.

Complete recovery after massive ethylene glycol ingestion

Complete recovery after massive ethylene glycol ingestion

Complete Recovery After Massive Ethylene Glycol Ingestion

We treated a 64-year-old man who recovered completely from a massive antifreeze ingestion with ethylene glycol levels well above those of previously described survivors. Rapid and aggressive treatment of the patient with recognized methods, including hemodialysis, resulted in the favorable outcome.

Accidental and intentional poisonings with ethylene glycol in infancy

Ethylene glycol has long been recognized as a potentially lethal poison and remains available today as automotive antifreeze and windshield deicer fluids. Ethylene glycol is rapidly absorbed from the gastrointestinal tract, with peak levels measured one to four hours after ingestion. Metabolism of the parent compound and the production of several organic acids are responsible for the metabolic acidosis observed in ethylene glycol poisoning. Target organ cellular damage is seen in the kidney, brain, myocardium, pancreas, and blood vessel walls. Renal tubular deposition of calcium oxalate crystals is felt to be responsible for the development of the severe renal injury which may accompany ethylene glycol ingestion. The clinical course is quite varied and includes inebriation, hematuria, cardiorespiratory compromise, and neurologic effects. Prompt diagnosis and initiation of treatment, including ethanol therapy and hemodialysis, is necessary to ameliorate the effects of ethylene glycol ingestion. Two cases of ethylene glycol poisoning, one accidental and one intentional, are reviewed.

Multiple cranial nerve deficits after ethylene glycol poisoning

We report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt. Clinical findings included profound bilateral cranial nerve VII palsies and severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite treatment with hemodialysis. The dysphagia completely cleared within two weeks, but at six months a severe bilateral cranial nerve VII dysfunction persisted. A 22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a three-month follow-up, the patient demonstrated only moderate functional recovery. The etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol-induced pyridoxine dysfunction.

Excess serum osmolality gap after ingestion of methanol

Two cases of methanol ingestion and one case of combined methanol and ethylene glycol ingestion are presented to illustrate the large differences that exist between the serum osmolality gap and the measured methanol (plus ethylene glycol) concentration(s) before treatment of these poisonings. After treatment with intravenous ethanol and hemodialysis was initiated, the differences disappeared in all three cases. We speculate that one or more metabolites with osmotic activity are formed in cases of methanol intoxication where no ethanol has also been consumed. The possible identity of these compounds is discussed.

Erythrocyte Pathology and Mechanisms of Heinz Body-mediated Hemolysis in Cats

Despite the frequency of both oxidant drug-induced and spontaneous Heinz body formation in cats, the cellular and biochemical mechanisms by which Heinz bodies result in red blood cell (RBC) destruction and hemolytic anemia in this species remain unknown. Feline spleens are non-sinusoidal and inefficient at removing Heinz body-containing RBC from the circulation; therefore, alternative mechanisms must be involved in accelerated RBC destruction. Propylene glycol (PG) ingestion causes dose-dependent Heinz body formation and decreased RBC survival in cats. We investigated several aspects of Heinz body-containing RBC from three cats ingesting diets that provided 8.0 g PG/kg body weight for up to 3 weeks, in order to characterize cellular lesions that are associated with the presence of Heinz bodies and that might contribute to chronic, accelerated RBC destruction, as well as to gain insight into the mechanism by which PG induces Heinz body formation. Erythrocytes with PG-induced Heinz bodies had decreased levels of reduced glutathione and adenosine triphosphate and reduced deformability. There was no change in hemoglobin isoelectric focusing or membrane lipid peroxidation. Electrophoretic patterns of Heinz body-containing RBC membranes were significantly altered, and membrane surface charge distribution was disturbed. Progressively protruding Heinz bodies suggested that extrusion of Heinz bodies may be a means of cell healing and/or destruction in the absence of splenic pitting. When compared to results obtained using RBC from cats treated with the oxidant drug phenylhydrazine, significant differences were noted in packed cell volume, turbidity index, membrane heme, and morphologic appearance of Heinz bodies. Our results indicate that multiple cellular abnormalities develop in RBC with PG-induced Heinz bodies that do not cause acute hemolysis but that may shorten RBC survival. Propylene glycol-induced Heinz bodies provide an ideal model for studying the chronic effects of Heinz bodies on RBC structure and function and may be useful in understanding the mechanisms of formation and the consequences of endogenous Heinz bodies in cats.

Urine fluorescence using a wood's lamp to detect the antifreeze additive sodium fluorescein: A qualitative adjunctive test in suspected ethylene glycol ingestions

Antifreeze ingestions require rapid and accurate differential diagnosis to prevent fatal outcomes. Sodium fluorescein is added to some commercial antifreeze preparations (ethylene glycol) to a final concentration of approximately 20 micrograms/mL as a colorant to aid in detection of automobile cooling-system leaks. For an adult human being, a potentially toxic volume of antifreeze is 30 mL, which contains 0.4 to 0.6 mg sodium fluorescein. Six male volunteers were given a 0.6-mg oral bolus of sodium fluorescein on an empty stomach. Urine was collected at two-hour intervals. Using a Wood's lamp, visually detectable fluorescence was seen with 100% reliability for two hours and 60% reliability for four hours. A second group of male volunteers was given the same dose of sodium fluorescein, and fluorescence was measured with a fluorometer during a six-hour period. Detectable fluorescence was present in all samples except the zero time point, including those with no fluorescence present by visual examination. We conclude that exposing urine to a Wood's lamp may be a useful adjunctive diagnostic test for early evaluation of patients with suspected antifreeze ingestion while awaiting definitive quantitative analysis of serum ethylene glycol concentration. A prospective clinical trial is needed to evaluate the frequency of false-positives and false-negatives.

Ethylene glycol toxicity

Ingestion of ethylene glycol is a rare occurrence, but it is an attractive agent for intoxication and suicide. Treatment is aimed at rapid excretion of the EG, prevention of the formation of metabolites, and the prevention and treatment of renal failure. Prior to discharge, Mr K revealed that he had drunk the antifreeze because he was despondent about his work situation. He had a short, but intensive trajectory that followed the three-system-involvement classic to EG poisoning, with the renal system most severely affected. Mr K was discharged from the hospital one week after admission and referred to appropriate community resources for counseling. The critical care nurse plays a key role in alleviating the hazards of this complex disorder through complete and ongoing assessment of all systems.

Pyroglutamic acidemia in an adult patient.

Pyroglutamic acidemia, a rare metabolic disorder, usually appears in infancy. It is characterized by retardation, ataxia, hemolytic anemia, and chronic acidosis and is caused by a marked deficiency of glutathione synthetase (EC 6.3.2.3) activity. This disease is inherited as an autosomal recessive trait, but the clinical condition is also detected in heterozygotes. We report an unusual case of high-anion-gap metabolic acidosis in a 52-year-old woman who was admitted with neurological complaints and breathing problems but without the characteristic clinical features of congenital glutathione synthetase deficiency. The etiology of the acidosis could not be attributed to ketoacidosis, lactic acidosis, or ingestion of methanol, salicylate, or ethylene glycol. Analysis of the patient's plasma and urine for organic acids revealed the presence of high concentrations of pyroglutamate (5-oxoproline), which remained high throughout her hospitalization.

Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog

The purpose of this investigation was to compare the effects of ethanol and 4-methylpyrazole (4MP) on the toxicity and pharmacokinetics of ethylene glycol (EG) in the dog. All dogs received 173 mmol kg EG, p.o. Dogs were randomly assigned to 3 groups: EG-treated only, EG + ethanol (19.3 mmol kg , i.v. 3, 7, 14 and 24 h after EG) and EG + 4MP (0.24 mmol kg , i.v. 3 h after EG, 0.18 mmol kg at 24 h and 0.06 mmol kg at 36 h). EG produced a rapid onset of metabolic acidosis (within 3 h) and acute oliguric renal failure (after 48 h), whereas administration of ethanol or 4MP greatly attenuated acidosis and prevented renal toxicity. The administration of ethanol, however, severely increased the central nervous system (CNS) depression that existed after ingestion of EG. The half-life of EG in serum was 10.8 ± 0.7 h in the EG-only treatment group, 6.8 ± 0.7 ( P<0.05) in the EG + ethanol group and 9.8° 0.9 h in the EG + 4MP group. Approx. 10% and 48% of the dose of EG was excreted unchanged in the urine at the 0–3 and 3–72 h periods, respectively. Treatment with 4MP increased the amount of EG excreted in the urine (71% from 3–72 h), whereas ethanol did not (51%). However, both ethanol and 4MP increased the rate constant of EG excretion into urine approx. 70%. These data demonstrate the utility of 4MP over ethanol for the treatment of EG-induced toxicity in dogs and indicate that ethanol and 4MP cause an increase in the rate constant of EG excretion in the urine and not a prolongation in EG half-life.

Developmental phase-specific and dose-related teratogenic effects of ethylene glycol monomethyl ether in CD-1 mice

Several animal species have shown a teratogenic response to inhaled or ingested ethylene glycol monomethyl ether (EGME). The present study examined the developmental phase specificity and dose-response characteristics of EGME-induced embryotoxicity. Pregnant CD-1 mice (vaginal plug positive day = gestation Day [gd] 0) received multiple or single doses of EGME by gavage between gd 7 and 14. Fetuses were examined on gd 18 for external and skeletal malformations. EGME was not maternally toxic after multiple doses of 250 mg/kg or a single administration of up to 500 mg/kg. EGME induced embryotoxicity as manifested by reduced gd 18 fetal weights and increased resorptions. The observed malformations were specifically related to the developmental stage at the time of exposure. Exencephaly resulted after EGME exposure between gd 7 to 10 whereas paw anomalies (syndactyly, oligodactyly, and stunted digit No. 1) predominated during later stages of development. Paw anomalies were maximal after administration on gd 11, and forepaws exhibited greater susceptibility than hindpaws. The no observed effect dose for the induction of digit malformations after a single administration of EGME on gd 11 was 100 mg/kg. At 175 mg EGME/kg digit anomalies were induced without any concurrent reduction in fetal body weight while at 250 mg/kg and above, digit anomalies occurred concurrently with reduced fetal body weight.

Adult respiratory distress syndrome secondary to ethylene glycol ingestion

Presented is a case of ethylene glycol poisoning in a 24-year-old man who subsequently developed adult respiratory distress syndrome. The noncardiogenic nature of the patient's pulmonary edema was documented with hemodynamic monitoring, and a successful outcome was achieved with hemodialysis, ethanol, and intermittent mechanical ventilation with positive end-expiratory pressure.

8Drug and chemical-induced metabolic acidosis

Metabolic acidosis produced by drugs and/or chemicals can be conveniently divided into those with an increase in the anion gap (anion gap = Na- (Cl + HCO3)) and those with a normal anion gap. The increase in the anion gap is due to the accumulation of unmeasured organic anions, such as lactate or acetoacetate and beta-hydroxybutyrate, as occurs in ketoacidosis and lactic acidosis, or the accumulation of toxic anions such as formate or glycolate, as occurs with the ingestion of methanol or ethylene glycol. Increased concentrations of lactic acid may also be present in the toxic forms of metabolic acidosis. The most common drugs and chemicals that induce the anion gap type of acidosis are biguanides, alcohols, polyhydric sugars, salicylates, cyanide and carbon monoxide. In normal anion gap acidosis the reduction in bicarbonate is balanced by a reciprocal increase in the chloride concentration so that the sum of the two remains unchanged. Normal anion gap acidosis is caused by carbonic anhydrase inhibitors, hydrochloride salts of amino acids, toluene, amphotericin, spironolactone and non-steroidal anti-inflammatory drugs. The mechanism by which these substances produce metabolic acidosis and the therapy are discussed.

Ethylene Glycol Poisoning

<h3>To the Editor.—</h3> We read the recent case reports of massive ethylene glycol ingestion by Stokes and Aueron (1980;243:2065) and by Peterson et al.¹Our own experience in a recent ethylene glycol poisoning, where the diagnosis was not evident from the patient's history and made only post mortem, caused us to review the clinical indications and available methods for ethylene glycol determination. A metabolic acidosis value with a high anion gap and a substantial discrepancy between the measured and calculated osmolality is suggestive of ethylene glycol or methyl alcohol intoxication. In either case, one must often start therapy with the infusion of ethyl alcohol, correction of the acidosis with sodium bicarbonate, and preparation for dialysis before there is laboratory confirmation. If a gas chromatograph is available for volatile toxins, a change in the usual screening conditions will include ethylene glycol among the identifiable poisons. As usually performed, volatile screens

Carcinogenic epichlorohydrin: Laskin, S., Sellakumar, A. R., Kuschner, M., Nelson, N., La Mendola, S., Rusch, G. M., Katz, G. V., Dulak, N. C. & Albert, R. E. (1980). Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats. J. natn. Cancer Inst.65, 751

Several animal species have shown a teratogenic response to inhaled or ingested ethylene glycol monomethyl ether (EGME). The present study examined the developmental phase specificity and dose-response characteristics of EGME-induced embryotoxicity. Pregnant CD-1 mice (vaginal plug positive day = gestation Day [gd] 0) received multiple or single doses of EGME by gavage between gd 7 and 14. Fetuses were examined on gd 18 for external and skeletal malformations. EGME was not maternally toxic after multiple doses of 250 mg/kg or a single administration of up to 500 mg/kg. EGME induced embryotoxicity as manifested by reduced gd 18 fetal weights and increased resorptions. The observed malformations were specifically related to the developmental stage at the time of exposure. Exencephaly resulted after EGME exposure between gd 7 to 10 whereas paw anomalies (syndactyly, oligodactyly, and stunted digit No. 1) predominated during later stages of development. Paw anomalies were maximal after administration on gd 11, and forepaws exhibited greater susceptibility than hindpaws. The no observed effect dose for the induction of digit malformations after a single administration of EGME on gd 11 was 100 mg/kg. At 175 mg EGME/kg digit anomalies were induced without any concurrent reduction in fetal body weight while at 250 mg/kg and above, digit anomalies occurred concurrently with reduced fetal body weight.

Prevention of Organ Damage in Massive Ethylene Glycol Ingestion

ETHYLENE glycol is potentially lethal in adults when ingested in amounts greater than 100 mL.¹Even smaller amounts can be lethal in children and can produce renal, cardiac, and CNS toxic reactions. The patient in the case reported in this article ingested many times the lethal dose. Because therapy was instituted rapidly, she recovered without any of the sequelae classically ascribed to ethylene glycol poisoning. This case provides evidence that the principles of toxicity and its prevention derived from animal models are applicable to man. <h3>Report of a Case</h3> A 33-year-old woman was brought to the Parkland Hospital emergency room one hour after drinking 2 L of ethylene glycol. She had been unable to self-induce vomiting. She was taking thioridazine for chronic paranoid schizophrenia and had attempted suicide on at least one other occasion. On examination she appeared mildly intoxicated but was noncombative. The blood pressure was 105/90 mm

Prevention of organ damage in massive ethylene glycol ingestion

Prevention of organ damage in massive ethylene glycol ingestion

Effect of ethylene glycol toxicity on hepatic carbohydrate metabolism in rats

The effects of ethylene glycol (EG) ingestion on glucose tolerance, hepatic glycogen metabolism, anerobic glycolysis, pentose phosphate pathway, and Embden-Meyerhof-tricarboxylic acid (EM-TCA) cycle pathway were investigated in male albino rats. EG was administered po at a daily dose of 2 ml/kg for 6 days. The analyses were done on Day 7. An impaired glucose metabolism was seen from diminished glucose tolerance. Hepatic glycogen concentrations were low associated with decreased glycogen synthetase and increased phosphorylase activities. [U- 14C]Glucose incorporation into liver glycogen both in vivo and in vitro was decreased. Studies on the incorporation of 14C of [1- 14C]- and [6- 14C]glucose into respiratory CO 2 showed augmentation of the pentose phosphate pathway, while no significant alteration was observed in glucose oxidation through the EM-TCA cycle pathway. Anerobic glycolysis by liver slices was decreased. The increased NADPH made available by the enhanced pentose phosphate pathway activity following EG treatment may suggest possible oxidation of EG through the microsomal ethanol oxidizing system (MEOS) which is NADPH dependent, as well as through the alcohol dehydrogenase system.

Seizures: A significant side effect of chlorambucil therapy in children

Because the seizures in this patient occurred only during the period when propylene glycol was being ingested, the frequency of seizures increased in spite of anti-convulsant therapy, and a change in the medication was accompanied by complete relief from seizures which has lasted for over three years, the clinical course of this patient suggests a causal relationship between the seizures and the ingestion of propylene glycol. Propylene glycol is relatively safe because it enters the normal metabolic pathways of the body! It is partly excreted in the urine and partly metabolized to lactic and pyruvic acids and then to carbon dioxide and water. However, some patients seem to develop a reversible central nervous system effect associated with the ingestion of the compound. Martin and Finberg' described uncon­ sciousness, tachycardia, tachypnea, and diaphoresis in a 15-month-old child eight days after beginning the daily ingestion of 7.5 ml of propylene glycol. They refer to two instances of stupor associated with ingestion of 60 ml of propylene glycol. Seizure activity has not previously been ascribed to the ingestion of propylene glycol. The associa­ tion seen in this patientcould be related either to the long­ term ingestion of propylene glycol or to an idiosyncratic reaction peculiar to this patient. Another possibility is that the precipitation of seizures by propylene glycol was related to a lower than normal threshold for seizures. This mechanism is similar to the precipitation of seizures by ethyl alcohol, a substance chemically related to propyl­ ene glycol. Hypoglycemia has been suggested as a factor in the CNS symptoms related to propylene glycol ingestion, I an idea not supported by the findings in this case. The reversal of the symptoms suggests that the toxic manifes­ tations are related to the concentration of propylene glycol or one of its metabolites in the blood or tissues. The mechanism which caused the seizures in this patient can be only speculative in the absence of more specific metabolic data. The purpose of this report is to alert physicians to the possible relationship between ingestion of propylene glycol and CNS symptoms in some patients. It is a further reminder that toxic symptoms from medications can be caused not only by the primary medication but also by the vehicle used in preparation of it.