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Kenneth E. Mcmartin - One of the best experts on this subject based on the ideXlab platform.
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are calcium oxalate crystals involved in the mechanism of acute renal failure in Ethylene Glycol Poisoning
Clinical Toxicology, 2009Co-Authors: Kenneth E. McmartinAbstract:Introduction. Ethylene Glycol (EG) Poisoning often results in acute renal failure, particularly if treatment with fomepizole or ethanol is delayed because of late presentation or diagnosis. The mechanism has not been established but is thought to result from the production of a toxic metabolite. Methods. A literature review utilizing PubMed identified papers dealing with renal toxicity and EG or oxalate. The list of papers was culled to those relevant to the mechanism and treatment of the renal toxicity associated with either compound. Role of metabolites. Although the “aldehyde” metabolites of EG, Glycolaldehyde, and glyoxalate, have been suggested as the metabolites responsible, recent studies have shown definitively that the accumulation of calcium oxalate monohydrate (COM) crystals in kidney tissue produces renal tubular necrosis that leads to kidney failure. In vivo studies in EG-dosed rats have correlated the severity of renal damage with the total accumulation of COM crystals in kidney tissue. Stud...
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relationship between serum Glycolate and falsely elevated lactate in severe Ethylene Glycol Poisoning
Journal of Analytical Toxicology, 2009Co-Authors: Alex F. Manini, Kenneth E. Mcmartin, Robert S. Hoffman, Lewis S NelsonAbstract:In the setting of Ethylene Glycol (EG) Poisoning, a falsely elevated serum lactate concentration is suggested to be an assay cross-reaction with Glycolate, but a concentration-dependent relationship has never been identified. We correlate serum lactate and Glycolate concentrations in a case of severe EG Poisoning. Serial EG [by gas chromatography (GC)], Glycolate (derivatized to methyl Glycolate, analysis by GC), and lactate (both enzymatic spectrophotometry and GC) concentrations were correlated at five time points. False-positive lactate was confirmed by absence of lactate on GC analysis. The correlation coefficient (Pearson's r) between lactate (by enzymatic spectrophotometry) and Glycolate was 0.984 and was statistically significant (p < 0.01). The mean lactate/Glycolate conversion factor was 2.58 ± 0.95. We demonstrate the linear correlation between falsely elevated serum lactate and Glycolate concentrations in a case of severe EG Poisoning. Our data provide further support to the belief that the lactate assay may cross-react with Glycolate in EG Poisoning.
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Calcium Oxalate Monohydrate, a Metabolite of Ethylene Glycol, Is Toxic for Rat Renal Mitochondrial Function
2004Co-Authors: Kenneth E. Mcmartin, Kendall B. WallaceAbstract:Ethylene Glycol Poisoning can produce acute renal failure, requiring long-term hemodialysis to restore function. The mechan-ism of the renal failure is unknown, but is associated with tubular cell necrosis and Ethylene Glycol metabolism. The end metabolite of Ethylene Glycol is oxalic acid, the precipitation of which as calcium oxalate monohydrate (COM) crystals in the tubular lumen has been linkedwith the renal toxicity.Our recent studies suggest thatCOMis an intracellular toxicant to normal human proximal tubule cells in culture. The present studies were designed to assess whether COM or ionic oxalate alters mitochondrial function so as to lead to renal cell death. In isolated rat kidney mitochondria, COM produced a dose-dependent decrease in State 3 respiration (40 % decrease at 0.05 mM COM with either succinate or glutamate/malate as sub-strate), without affecting either State 4 respiration or the ADP/O ratio. COM, from 0.01–0.05 mM also dose-dependently increase
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Fomepizole for the Treatment of Ethylene Glycol Poisoning
The New England Journal of Medicine, 1999Co-Authors: Jeffrey Brent, Kenneth E. Mcmartin, Scott E. Phillips, Wells M, Kenneth W. KuligAbstract:Background Ethylene Glycol Poisoning causes metabolic acidosis and renal failure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of Ethylene Glycol Poisoning. Methods We administered intravenous fomepizole to 19 patients with Ethylene Glycol Poisoning (plasma Ethylene Glycol concentration, ≥20 mg per deciliter [3.2 mmol per liter]). Patients who met specific criteria also underwent hemodialysis. Treatment was continued until plasma Ethylene Glycol concentrations were less than 20 mg per deciliter. Acid–base status, renal function, the kinetics of fomepizole, and Ethylene Glycol metabolism were assessed at predetermined intervals. Results Fifteen of the patients initially had acidosis (mean serum bicarbonate concentration, 12.9 mmol per liter). Acid–base status tended to normalize within hours after the i...
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Glycolate kinetics and hemodialysis clearance in Ethylene Glycol Poisoning meta study group
Clinical Toxicology, 1998Co-Authors: C L Moreau, William Kerns, Christian Tomaszewski, Susan R Rose, Marsha Ford, Kenneth E. Mcmartin, Jeffrey BrentAbstract:AbstractObjective: Toxic manifestations following Ethylene Glycol exposure are due to accumulation of metabolites, particularly Glycolate. We characterized Glycolate elimination kinetics and dialysis properties in a series of Ethylene Glycol Poisonings. Methods: Patients who ingested Ethylene Glycol and received fomepizole (4-methylpyrazole; 4-MP) ± hemodialysis were prospectively evaluated. Serial blood samples for Ethylene Glycol, Glycolate, pH, and bicarbonate were drawn to determine Glycolate elimination rate, t½, and correlations between initial Glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis Glycolate clearance. Plasma Ethylene Glycol and Glycolate were determined by gas chromatography. Results: Ten patients, mean age 49 years (range 28–73 years), presented a mean of 10.5 hours (range 3.5–21.5 hours) after Ethylene Glycol ingestion. Mean initial Ethylene Glycol was 18.5 mmol/L (range 0.8–62.2 mmol/L) (115 mg/dL; range 5–386 mg/dL) an...
Ziad N Kazzi - One of the best experts on this subject based on the ideXlab platform.
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intentional Ethylene Glycol Poisoning increase after media coverage of antifreeze murders
Western Journal of Emergency Medicine, 2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of malicious EG Poisonings also increased during this same period from 2 in 2000 to 14 in 2004. Conclusion: Media coverage of stories involving Poisonings may result in copycat events, applicable to both self-Poisonings and concern for malicious Poisonings. Poison centers should be aware of this phenomenon, pay attention to local media and plan accordingly if a Poisoning event receives significant media coverage. The media should be more sensitive to the content of their coverage and avoid providing “how to” Poisoning information. [West J Emerg Med. 2011;12(3):296-299.]
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Intentional Ethylene Glycol Poisoning Increase after Media Coverage of Antifreeze Murders
The western journal of emergency medicine, 2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of malicious EG Poisonings also increased during this same period from 2 in 2000 to 14 in 2004. Conclusion: Media coverage of stories involving Poisonings may result in copycat events, applicable to both self-Poisonings and concern for malicious Poisonings. Poison centers should be aware of this phenomenon, pay attention to local media and plan accordingly if a Poisoning event receives significant media coverage. The media should be more sensitive to the content of their coverage and avoid providing “how to” Poisoning information. [West J Emerg Med. 2011;12(3):296-299.]
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Intentional Ethylene Glycol Poisoning Increase after Media Coverage of Antifreeze Murders
2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of maliciou
Dag Jacobsen - One of the best experts on this subject based on the ideXlab platform.
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Glycolate causes the acidosis in Ethylene Glycol Poisoning and is effectively removed by hemodialysis
Acta Medica Scandinavica, 2009Co-Authors: Dag Jacobsen, Jens Ostborg, Steinar Øvrebø, Ole M. SejerstedAbstract:Six male patients with severe Ethylene Glycol Poisoning were studied with respect to the origin of the metabolic acidosis. The plasma concentrations of Ethylene Glycol were 4–41 mmol/l and treatment included alkali, ethanol and hemodialysis. Plasma analysis by isotachophoresis and whole blood lactate determinations showed that Glycolate (17.0–29.3 mmol/l), lactate (1.4–6.2 mmol/l) and β-hydroxybutyrate (≤1.8 mmol/l) were present in elevated concentrations contributing to the acidosis. Oxalate (≤0.33 mmol/l), glyoxylate (<0.2 mmol/l) and formate (<0.4 mmol/l) concentrations were negligible and did not contribute to any significant degree to the acidosis. The elevated plasma Glycolate concentration was highly correlated to the anion gap (r=0.923) and the Glycolate made up for 96.1% (n=6, range 84.7–108.8) of the increased anion gap. We conclude that Glycolate accumulation is the main reason for the metabolic acidosis in Ethylene Glycol Poisoning. The mean dialysator (1.6 m2) clearances of Glycolate at a blood flow of 200 ml/min in two patients were 137 ml/min (n=9, SD±8, range 125–149) and 144 ml/min (n=11, SD±8, range 133–158). By applying first order kinetics during hemodialysis a volume of distribution of Glycolate of 0.55 l/kg was found, assuming that the dialysator clearance equals the total body clearance of Glycolate. Thus Glycolate, the probable main metabolite of Ethylene Glycol, is efficiently removed by hemodialysis.
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anion and osmolal gaps in the diagnosis of methanol and Ethylene Glycol Poisoning
Acta Medica Scandinavica, 2009Co-Authors: Dag Jacobsen, Jan E Bredesen, Ivar Eide, Jens OstborgAbstract:The diagnostic value of determination of the anion and osmolal gaps was studied in 6 patients poisoned with methanol and in 5 poisoned with Ethylene Glycol. Increased osmolal gap was present on admission in all patients, whereas increased anion gap was present in all except one. In the methanol-poisoned patients the mean blood values were: pH 7.27, anion gap 24 mmol/l, osmolal gap 81 mosmol/kg H2O, methanol 67 mmol/l, ethanol 11 mmol/l and in the Ethylene Glycol-poisoned patients: pH 6.93, anion gap 38 mmol/l, osmolal gap 35 mosmol/kg H2O and Ethylene Glycol 24 mmol/l. In the absence of alcoholic acidosis or diabetic coma the finding of a simultaneous increase in both the anion and osmolal gaps indicates methanol or Ethylene Glycol Poisoning. Thus determinations of the anion and osmolal gaps are mandatory whenever facing metabolic acidosis of unknown etiology.
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severe Ethylene Glycol Poisoning treated wtih fomepizole 4 methylpyrazole
Tidsskrift for Den Norske Laegeforening, 2002Co-Authors: Odd Aakervik, J H Svendsen, Dag JacobsenAbstract:BACKGROUND Poisoning with Ethylene Glycol causes severe metabolic acidosis and renal failure, and is potentially lethal if not treated rapidly. Until recently the standard therapy for this Poisoning has been bicarbonate to counteract the metabolic acidosis, inhibition of alcohol dehydrogenase (ADH) with ethanol to prevent the production of toxic metabolites and haemodialysis to remove Ethylene Glycol and its toxic metabolites. The new potent inhibitor of ADH, 4-methylpyrazole (fomepizole), has recently been approved for the treatment of methanol and Ethylene Glycol Poisonings. MATERIAL AND METHODS Three patients severely poisoned by Ethylene Glycol and treated with fomepizole are presented. RESULTS Of our three patients treated with fomepizole two were managed without haemodialysis. One patient had an exceptionally high serum Ethylene Glycol concentration (90 mmol/l; 585 mg/dl) and was successfully treated with fomepizole without the need for haemodialysis despite pronounced metabolic acidosis. INTERPRETATION Ethylene Glycol Poisonings may be treated effectively with fomepizole without haemodialysis.
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antidotes for methanol and Ethylene Glycol Poisoning
Clinical Toxicology, 1997Co-Authors: Dag Jacobsen, Kenneth E. McmartinAbstract:(1997). Antidotes for Methanol and Ethylene Glycol Poisoning. Journal of Toxicology: Clinical Toxicology: Vol. 35, No. 2, pp. 127-143.
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4 methylpyrazole 4 mp is effectively removed by haemodialysis in the pig model
Human & Experimental Toxicology, 1996Co-Authors: Dag Jacobsen, J Ostensen, L Bredesen, E Ullstein, Kenneth E. McmartinAbstract:The safety and pharmacokinetics of the alcohol dehydro genase inhibitor 4-MP have recently been evaluated and its clinical use in Ethylene Glycol Poisoning in France is promising. The dialysability of 4-MP is not known. This is important as hemodialysis is one of the cornerstones in the treatment of (late) Ethylene Glycol and methanol poison ings. We therefore studied the dialysability of 4-MP in the pig model. Anesthesized pigs (maintained on respirator) given 4-MP, 10 mg/kg, served as controls (n=3) to the pigs (n=3) given 15 mg/kg and hemodialyzed for 4 h. 4-MP plasma elimination curves for both groups were compared for 12 h and dialysance data calculated. 4-MP (MW 82) was removed by the same rate as urea (MW 60) by the 0.3 m2 dialysator, thus indicating no significant protein binding of 4-MP. The mean dialysance of 4-MP (and urea) in the three pigs were 61 (63), 51 (53) and 56 (48) ml/min, at a blood flow of 75 ml/min. The amount of 4-MP removed by hemodialysis in 4 h was 57-76 mg compared to a urinar...
Brent W Morgan - One of the best experts on this subject based on the ideXlab platform.
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intentional Ethylene Glycol Poisoning increase after media coverage of antifreeze murders
Western Journal of Emergency Medicine, 2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of malicious EG Poisonings also increased during this same period from 2 in 2000 to 14 in 2004. Conclusion: Media coverage of stories involving Poisonings may result in copycat events, applicable to both self-Poisonings and concern for malicious Poisonings. Poison centers should be aware of this phenomenon, pay attention to local media and plan accordingly if a Poisoning event receives significant media coverage. The media should be more sensitive to the content of their coverage and avoid providing “how to” Poisoning information. [West J Emerg Med. 2011;12(3):296-299.]
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Intentional Ethylene Glycol Poisoning Increase after Media Coverage of Antifreeze Murders
The western journal of emergency medicine, 2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of malicious EG Poisonings also increased during this same period from 2 in 2000 to 14 in 2004. Conclusion: Media coverage of stories involving Poisonings may result in copycat events, applicable to both self-Poisonings and concern for malicious Poisonings. Poison centers should be aware of this phenomenon, pay attention to local media and plan accordingly if a Poisoning event receives significant media coverage. The media should be more sensitive to the content of their coverage and avoid providing “how to” Poisoning information. [West J Emerg Med. 2011;12(3):296-299.]
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Intentional Ethylene Glycol Poisoning Increase after Media Coverage of Antifreeze Murders
2011Co-Authors: Brent W Morgan, Robert J Geller, Ziad N KazziAbstract:Background: The media can have a profound impact on human behavior. A sensational murder by Ethylene Glycol (EG) Poisoning occurred in our state. The regional media provided extensive coverage of the murder. We undertook this investigation to evaluate our incidence of EG Poisoning during the timeframe of before the first report linking a death to Ethylene Glycol to shortly after the first murder trial. Methods: Descriptive statistics and linear regression were used to describe and analyze the number of EG cases over time. A search of the leading regional newspaper’s archives established the media coverage timeline. Result: Between 2000 and 2004, our poison center (PC) handled a steady volume of unintentional exposures to EG [range: 105–123 per year, standard deviation (SD)=7.22]. EG exposures thought to be suicidal in intent increased from 12 cases in 2000 to 121 cases in 2004. In the 19 months prior to the first media report of this story, our PC handled a mean of 1 EG case with suicidal intent per month [range: 0–2, SD=.69]. In the month after the first media report, our PC handled 5 EG cases with suicidal intent. When media coverage was most intense (2004), our PC received a mean of 10 EG suicidal-intent calls per month [range: 5–17, SD=3.55]. Although uncommon, reports of maliciou
Paul Mahieu - One of the best experts on this subject based on the ideXlab platform.
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two cases of acute methanol Poisoning partially treated by oral 4 methylpyrazole
Intensive Care Medicine, 1999Co-Authors: Philippe Hantson, Vincent Haufroid, Pierre Wallemacq, M Brau, Roger Vanbinst, Paul MahieuAbstract:Objective: Since the use of 4-methylpyrazole (4-MP) in the treatment of humans with methanol Poisoning is poorly documented, we report two cases of acute methanol intoxication partially treated by this potent alcohol dehydrogenase (ADH) inhibitor. Setting: Intensive Care Unit in a university hospital. Patients: A 56-year-old man and an 18-year-old woman were observed, respectively, 41 and 16 h after the voluntary ingestion of an unknown amount of methanol. Intervention: In both cases, ethanol was used as the first antidote. In the first patient, hemodialysis was also performed on admission because a high methanol level (0.72 g/l) and visual impairment were noted. In the second patient, ethanol therapy was withdrawn after 12 h when clinical and biological signs of acute pancreatitis became evident. Both patients received multiple oral doses of 4-MP. No recurrence of metabolic acidosis occurred and the 4-MP therapy was well tolerated. Conclusion: While the use of 4-MP is better documented in cases of Ethylene Glycol Poisoning, it could also become an accepted option for the management of methanol Poisoning since 4-MP offers advantages over ethanol therapy.
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Ethylene Glycol Poisoning treated by intravenous 4 methylpyrazole
Intensive Care Medicine, 1998Co-Authors: A Hassoun, Paul MahieuAbstract:A 19-year-old woman was admitted 45 min after Ethylene Glycol (EG) ingestion. The initial serum EG concentration was 1.34 g/l (21.6 mmol/l), the anion gap 14.5, and the osmolal gap 24. Renal function was preserved (serum creatinine 75.1 micromol/l). As the patient was seen soon after Poisoning, before the development of metabolic acidosis, therapy with 4-methylpyrazole (4-MP) was proposed as an antidote. 4-MP was administered via the intravenous route (7 mg/kg as loading dose, followed by 3.6, 1.2, 0.6, and 0.6 mg/kg at intervals of 12 h). 4-MP alone was effective in preventing EG biotransformation to toxic metabolites (absence of metabolic acidosis and renal injury). Ethanol therapy, hemodialysis, and sodium bicarbonate administration were not required. The half-life of EG during 4-MP therapy was 11 h, with a mean EG renal clearance of 26.9 ml/min, and a total of 65.3 g EG was eliminated unchanged in the urine. 4-MP therapy was also well tolerated.