Glycol Elimination Research Articles

Ethylene glycol intoxication following brake fluid ingestion complicated with unilateral facial nerve palsy: a case report

BackgroundBrake oil is an automobile transmission fluid composed of a mixture of toxic alcohols such as ethylene glycols and glycol ethers. Both accidental and intentional ingestion cases have been reported and they can present with multisystem involvement. Life-threatening complications evolve from deleterious effects on cardiopulmonary and renal systems. Effects on neurological and gastrointestinal systems give rise to a multitude of complications although non-fatal in nature. The biochemical panel consists of a high concentration of ethylene glycol with severe metabolic acidosis, high anion gap, high osmolar gap, oxaluria, and hypocalcemia. The mainstay of treatment is enhanced elimination of ethylene glycol and its metabolites by hemodialysis, together with general supportive care, gastric decontamination, and vitamins such as thiamine and pyridoxine to minimize the adverse effects of intoxication.Case presentationA 26-year-old Sinhalese woman presented with reduced urine output, shortness of breath, reduced level of consciousness, abdominal pain, and vomiting with mild degree fever of 2 days’ duration. She had bilateral lower limb edema, crepitations over bilateral lower lung fields, and right-sided lower motor type facial nerve palsy. Investigations showed severe metabolic acidosis with high anion gap and high osmolar gap. With regular hemodialysis she made a complete recovery after 3 months.ConclusionEven without a clear history of poisoning, the presence of a high anion, high osmolar gap metabolic acidosis should prompt one to search for ethylene glycol ingestion. Uncommon manifestations like cranial neuropathies need to be examined and considered. Timely aggressive treatment leads to a better prognosis.

Ethylene glycol elimination in amine loop for more efficient gas conditioning

The gas sweetening unit of phase 2 and 3 in South Pars Gas Field (Asalouyeh, Iran) was first simulated to investigate the effect of mono ethylene glycol (MEG) in the amine loop. MEG is commonly injected into the system to avoid hydrate formation while a few amounts of MEG is usually transferred to amine gas sweetening plant. This paper aims to address the points where MEG has negative effects on gas sweetening process and what the practical ways to reduce its effect are. The results showed that in the presence of 25% of MEG in amine loop, H2S absorption from the sour gas was increased from 1.09 to 3.78 ppm. Also, the reboiler temperature of the regenerator (from 129 to 135 °C), amine degradation and required steam and consequently corrosion (1.10 to 17.20 mpy) were increased. The energy consumption and the amount of amine make-up increase with increasing MEG loading in amine loop. In addition, due to increasing benzene, toluene, ethylbenzene and xylene (BTEX) and heavy hydrocarbon solubility in amine solution, foaming problems were observed. Furthermore, side effects of MEG presence in sulfur recovery unit (SRU) such as more transferring BTEX to SRU and catalyst deactivation were also investigated. The use of total and/or partial fresh MDEA, install insulation and coating on the area with the high potential of corrosion, optimization of operational parameters and reduction of MEG from the source were carried out to solve the problem. The simulated results were in good agreement with industrial findings. From the simulation, it was found that the problem issued by MEG has less effect when MEG concentration in lean amine loop was kept less than 15% (as such observed in the industrial plant). Furthermore, the allowable limit, source and effects of each contaminant in amine gas sweetening were illustrated.

Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning

Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15mg/kg b.w. after 2h, followed by 10mg/kg b.w. every 12h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney’s lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.

Prediction and validation of the duration of hemodialysis sessions for the treatment of acute ethylene glycol poisoning

The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD formore than 14 days, and two died. In 19 cases, the meanethylene glycol elimination half-life during high-efficiency HD was 165 minutes (95% confidence interval of151-180 minutes). In a training set of 12 patients with acute ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model was then validated in a set of seven acute ethylene glycol poisonings. Thus, the HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.

Plotting of Ethylene Glycol Blood Concentrations Using Linear Regression before and during Hemodialysis in a Case of Intoxication and Pharmacokinetic Review.

Introduction. As blood concentration measurement of commonly abused alcohol is readily available, the equation was proposed in previous publication to predict the change of their concentration. The change of ethylene glycol (EG) concentrations was studied in a case of intoxication to estimate required time for hemodialysis (HD) using linear regression. Case Report. A 55-year-old female with past medical history of seizure disorder, bipolar disorder, and chronic pain was admitted due to severe agitation. The patient was noted to have metabolic acidosis with elevated anion gap and acute kidney injury, which prompted blood concentration measurement of commonly abused alcohol. Her initial EG concentration was 26.45 mmol/L. Fomepizole therapy was initiated, soon followed by HD to enhance clearance. Discussion. Plotting of natural logarithm of EG concentrations over time showed that EG elimination follows first-order kinetics and predicts the change of its concentration well. Pharmacokinetic review revealed minimal elimination of EG by alcohol dehydrogenase (ADH) which could be related to genetic predisposition for ADH activity and home medications as well as presence of propylene glycol. Pharmacokinetics of EG is relatively well studied with published parameters. Consideration and application of pharmacokinetics could assist in management of EG intoxication including HD planning.

Ethylene Glycol Elimination Kinetics and Outcomes in Patients Managed Without Hemodialysis

Ethylene glycol remains an important toxic cause of metabolic acidosis and acute renal failure. Traditionally, inhibition of alcohol dehydrogenase along with hemodialysis has been used for treatment. Because of reported long elimination half-life of ethylene glycol during alcohol dehydrogenase inhibition, hemodialysis has been used in patients who are otherwise doing well to clear ethylene glycol. We study ethylene glycol elimination kinetics in patients treated with fomepizole, but without hemodialysis. This was a retrospective, multicenter cohort study of patients older than 15 years who were treated at one of 3 medical centers during an 8-year period. Inclusion criteria were peak serum ethylene glycol concentration greater than 20 mg/dL, lack of renal failure on admission, treatment with fomepizole but without hemodialysis, and availability of serial serum ethylene glycol concentrations, allowing calculation of elimination half-life. The primary outcome variable was ethylene glycol elimination half-life; mortality and onset of renal failure were secondary outcome variables. During the study period, 85 patients were treated for ethylene glycol toxicity, of whom 40 met inclusion criteria. The mean serum ethylene glycol elimination half-life was 14.2 hours (SD=3.7 hours; 95% confidence interval 13.1 to 15.3 hours). One patient presented with metabolic acidosis on admission and developed mild transient renal insufficiency but did not require hemodialysis. No patient died. The mean elimination half-life of ethylene glycol in this population was shorter than previously reported without hemodialysis, and this select group of patients did well without enhanced elimination by hemodialysis.

Ethylene Glycol Intoxication: Case Report and Pharmacokinetic Perspectives

A 42-year-old man was brought to the emergency department with ethylene glycol intoxication. He was hemodynamically stable and had normal renal function. His serum ethylene glycol concentration was 284 mg/dl approximately 1 hour after ethylene glycol consumption. The patient was treated with fomepizole and forced diuresis. Elimination of ethylene glycol in this patient followed first-order pharmacokinetics. Elimination pharmacokinetics in this patient were compared with that in a patient who received fomepizole and hemodialysis. Fomepizole monotherapy can be given in patients without renal failure or metabolic acidosis even with serum ethylene glycol concentrations greater than 50 mg/dl. However, cost estimates based on this case suggest that if the patient is treated adequately with a single hemodialysis session and 24-hour hospitalization, then fomepizole monotherapy may be more expensive than the combination regimen of fomepizole and hemodialysis.

In vivo biocompatibility and biodegradation of poly(ethylene carbonate)

Biodegradation and biocompatibility of poly(ethylene carbonate) (PEC) was examined using an in vivo cage implant system. Exudate analysis showed that PEC and PEC degradation products were biocompatible and induced minimal inflammatory and wound healing responses. Adherent foreign body giant cells (FBGCs) caused pitting on the PEC surface, which led to extensive degradation over time. Data obtained from molecular weight and examination of film cross-sections in the scanning electron microscope (SEM) indicated that PEC underwent surface erosion with no change to the remaining bulk. Attenuated total reflectance infrared (ATR-FTIR) spectroscopy was used to characterize the chemical degradation. Superoxide anion released from inflammatory cells appeared to initiate an “unzipping” mechanism of degradation by deprotonation of PEC hydroxyl end groups. The resulting alkoxide ion participated in a concerted mechanism involving water and the carbonate carbonyl, leading to elimination of ethylene glycol. Carbonate ions decomposed further with release of carbon dioxide to regenerate alkoxide ion.

Mechanistic study of stereoselective gas-phase reactions of phosphenium ions with cis- and trans-1,2-diaminocyclohexanes.

The 1,3-dioxolane-2-phosphenium ion, 1,3-benzodioxole-2-phosphenium ion, and o-biphenylenephosphenium ion are reported to react in a stereoselective manner with cis- and trans-1,2-diaminocyclohexanes in the gas phase in a Fourier transform ion cyclotron resonance mass spectrometer. Elimination of NH3 from an addition product was observed only for the trans isomer. Several reaction mechanisms were experimentally and computationally examined (B3LYP/6-31G(d)//HF/6-31G(d) + ZPVE level of theory). The most plausible mechanism is initiated by addition of one of the amino groups to the electrophilic phosphorus atom followed by proton transfer between the amino groups. A change to a diaxial conformation for the trans isomer facilitates anchimeric assistance by the now nucleophilic phosphorus atom as the C-N bond breaks to release NH3. Intramolecular proton transfer competes with the conformational change and ultimately leads to ethylene glycol elimination. The transition states for the critical steps of these two reactions are calculated to be nearly equal in magnitude, which rationalizes the observation of both reactions for the trans-diamine. In contrast, the adduct of the cis isomer can eliminate NH3 via a concerted 1,2-hydride shift without a need for a conformational change. However, the barrier associated with this reaction was found to be substantially greater than for proton transfer between the N- and O-atoms. The latter reaction dominates and ultimately leads to ethylene glycol elimination.

Propylene Glycol Toxicity Associated with Lorazepam Infusion in a Patient Receiving Continuous Veno-Venous Hemofiltration with Dialysis

Propylene Glycol Toxicity Associated with Lorazepam Infusion in a Patient Receiving Continuous Veno-Venous Hemofiltration with Dialysis

Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management

Study Objective: The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize elimination pathways. Methods: Drug concentration data from patients enrolled in the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open-label trial of fomepizole, were analyzed and compared with published estimates. Results: In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), elimination was first order during fomepizole monotherapy (half-life of 19.7±1.3 hours) and was not affected by the presence of ethanol. The elimination rate was significantly faster (half-life of <8.6±1.1 hours, P <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys was directly proportional to remaining renal function as estimated by creatinine clearance, with a fractional excretion of 25.5%±9.4%. Renal elimination and hemodialysis were the only significant routes of EG elimination as long as fomepizole concentrations were maintained well above 10 μmol/L (EG/fomepizole molar ratio, <100:1). All patients with normal serum creatinine concentrations at the initiation of fomepizole treatment had rapid rates of renal elimination (half-life of 16.8±0.8 hours). Conclusion: At doses used, fomepizole effectively inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at presentation and creatinine clearance can be used to predict EG elimination during fomepizole therapy and can help determine which patients will require hemodialysis to expedite EG elimination. An absolute EG concentration above 50 mg/dL should no longer be used as an independent criterion for hemodialysis in patients treated with fomepizole. [Sivilotti MLA, Burns MJ, McMartin KE, Brent J, for the Methylpyrazole for Toxic Alcohols Study Group. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. Ann Emerg Med. August 2000;36:114-125.]

Kinetics of propylene glycol elimination and metabolism in rat

The kinetics of 1,2-propanediol (PD) metabolism in vivo have been determined by employing the Michaelis-Menten rate equation; it was found that maximum metabolizing capacity was 8.33 mmole PD/kg/hr in the rat, which is equivalent to 1.06 kg/day for an average 70-kg human. The rate equation could be suitably used for optimizing the dosage schedule of a drug from the linear elimination pattern; in the present case this gave a K m value of 17.86 mmole/kg on the basis of the elimination rate of PD. The competitive inhibition of PD elimination by preadministration of pyrazole ( K i = 44 μmole/kg) demonstrated that the first step of the biotransformation of PD catalyzed by the NAD-dependent dehydrogenase might be the rate-limiting step for its in vivo metabolism. The low threshold level of the compound and significant rate of metabolism suggested that the CNS toxicity reported in clinical studies might be due to some of its metabolites such as lactaldehyde and other oxo compounds. Thus, PD could not be considered as an inert and innocuous substance.

Field desorption mass spectral fragmentation of monosaccharide isomers

AbstractField desorption ionization of selected monosaccharide isomers by potassium ion attachment in high fields is described. The ionization is obtained with a tungsten wire activated with carbon needles and covered with KH2PO4 salt. In addition to the potassium cationized molecular ions, reproducible fragmentation was obtained at 10 mA and 20 mA typical of the various monosaccharides. For instance, D‐glucose tends to lose a water molecule, whereas D‐fructose loses primarily methanol under similar conditions. Methanol elimination is suggested to be characteristic of furanoidal ketoses and water elimination for pyranoidal aldoses, whereas glycol elimination occurs for furanoidal aldoses.

New method for preparing saturated and unsaturated aliphatic polyurethanes

AbstractSaturated and unsaturated aliphatic polyurethane were obtained from three different routes. In route 1, 1,4‐dichloro‐2‐butene, sodium cyanate, and methanol were reacted to give dimethyl 2‐butene‐1,4‐dicarbamate. This is hydrogenated easily to give dimethyl butane‐1,4‐dicarbamate. Ester exchange reaction of this compound with glycol gave saturated aliphatic polyurethane. In another procedure, route 2, 1,4‐dichloro‐2‐butene, sodium cyanate and excess glycol were reacted to give bis(ω‐hydroxyalkyl)‐2‐butene‐1,4‐dicarbamate. This was hydrogenated to give bis(ω‐hydroxyalkyl)‐butane‐1,4‐dicarbamate. A glycol elimination reaction gave poly(polymethylene tetramethyl‐enedicarbamate). By route 3, 1,4‐dichloro‐2‐butene, sodium cyanate, and glycol were reacted to give poly(polymethylene 2‐butene‐1,4‐dicarbamate), a new unsaturated aliphatic polyurethane.