William J Meggs

Publications of William J Meggs

• A localizing circumferential compression device increases survival after coral snake envenomation to the torso of an animal model.

  Authors: Jason B Hack, Jocelyn M Deguzman, Kori L Brewer, William J Meggs, Dorcas O'Rourke

  The Journal of emergency medicine. 07/2011; 41(1):102-7.

  Pressure immobilization bandages have been shown to delay onset of systemic toxicity after Eastern coral snake (Micrurus fulvius) envenomation to the distal extremity. To assess the efficacy of aPressure immobilization bandages have been shown to delay onset of systemic toxicity after Eastern coral snake (Micrurus fulvius) envenomation to the distal extremity. To assess the efficacy of a novel compression device in delaying onset of systemic toxicity after truncal envenomations with Eastern coral snake (Micrurus fulvius) venom in a porcine model. With University approval, nine juvenile pigs (11 kg to 22 kg) were sedated, anesthetized, and intubated but not paralyzed to ensure continuous spontaneous respirations in a university animal laboratory. Each animal was injected subcutaneously with 10 mg of M. fulvius venom in a pre-selected area of the trunk. After 1 min, six animals had the application of a novel, localizing circumferential compression (LoCC) device applied to the bite site (treatment group) and three animals had no treatment (control group). The device was composed of a rigid polymer clay form molded into a hollow fusiform shape with an internal dimension of 8 × 5 × 3 cm and an elastic belt wrapped around the animal securing the device in place. Vital signs were recorded at 30-min intervals. End points included a respiratory rate below 3 breaths/min, oxygen saturation < 80%, or survival to 8 h. Survival to 8 h was analyzed using Fisher's exact test, with p < 0.05 indicating significance. Survival analysis was performed using the Mantel-Cox test to assess time to death with outcomes represented in a Kaplan-Meier Cumulative survival plot. Five of the six pigs in the treatment group survived 8 h (293-480 min). None of the control pigs survived to 8 h (Fisher's exact p = 0.04), with mean time of respiratory failure 322 min (272-382 min). Survival analysis showed a significant delay in time to event in the treatment group compared to the control group (p = 0.04). The LoCC device used in this study delayed the onset of systemic toxicity and significantly increased survival time after artificial truncal envenomation by Eastern coral snake venom.

• Toxicant exposures and the obesity epidemic.

  Authors: William J Meggs, Kori L Brewer

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 04/2010; 6(2):275.

• Efficacy of North American crotalid antivenom against the African viper Bitis gabonica (Gaboon viper).

  Authors: William J Meggs, Christopher N Wiley, Kori L Brewer, Jason B Hack

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 03/2010; 6(1):12-4.

  Envenomations by exotic snakes occur from zoological collections and private individual collectors. Antivenoms to these snakes may not be readily available. The objective of this study is toEnvenomations by exotic snakes occur from zoological collections and private individual collectors. Antivenoms to these snakes may not be readily available. The objective of this study is to determine the efficacy of North American crotalid antivenin in treating mice envenomated with venom of the African viper Bitis gabonica (Gaboon viper). The subjects of the study were Swiss Webster mice weighing approximately 30 g. The study was conducted in the University research laboratory. B. gabonica venom was obtained from Venom Supplies Pty Ltd (Tanunda, South Australia) and reconstituted in sterile water. North American Crotalid Fab2 antivenin (Anavyp, Instituto Bioclon, Mexico) was donated by the manufacturer. The experimental groups were: Group I received two times an intraperitoneal LD(50) dose of venom, 2.58 mg/kg. Group II received the same dose after incubation for 1 h with 10 mg of antivenin. Time to onset of toxicity defined as respiratory rate <10/min or absence of response to prodding. t test and Chi square with p < 0.05 considered significant. Time to onset of toxicity was 7.040 +/- 4.334 h in group I, and 20.665 +/- 2.074 in group II (p = 0.0064, 95% confidence interval of difference of means -22.694 to -4.556). Antivenin was efficacious to statistical significance at 4, 8, 12, and 16 h (p values of 0.062, 0.0067, 0.0067, and 0.0253, respectively). Improvement at 20 and 24 h (p values of 0.0673 and 0.0673, respectively) did not achieve statistical significance. North American Crotalid antivenin (Anavyp, Instituto Bioclon, Mexico) demonstrated efficacy in increasing time to onset of distress in mice poisoned with B. gabonica (Gaboon viper) venom. Based on this result, treatment of humans envenomated with B. gabonica with North American Croatlid antivenin could be considered for severe envenomations if specific B. gabonica antivenin is unavailable.

• A localizing circumferential compression device delayed death after artificial eastern diamondback rattlesnake envenomation to the torso of an animal model in a pilot study.

  Authors: Jason B Hack, Babatunde Orogbemi, Jocelyn M Deguzman, Kori L Brewer, William J Meggs, Dorcas O'Rourke

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 03/2010; 6(2):207-11.

  Nearly all prior studies to delay onset of systemic toxicity and death after snake bite use a model of distal extremity envenomation. In the first of a series of planned studies using snake venomsNearly all prior studies to delay onset of systemic toxicity and death after snake bite use a model of distal extremity envenomation. In the first of a series of planned studies using snake venoms with different toxicity profiles, the application of a novel device in a new model of torso envenomation in the setting of Eastern Coral Snake (Micrurus fulvius) venom (a potent neurotoxin) envenomation showed promise by delaying systemic intoxication. In this pilot study, we investigated this novel localizing circumferential compression (LoCC) device's ability to delay onset of life threatening systemic toxicity after Eastern Diamondback Rattlesnake (Crotalus adamanteus) envenomation, a potent hemotoxic and myotoxic venom. With university approval, four juvenile female pigs (22-25 kg) were anesthetized, sedated, and intubated but not paralyzed to allow for spontaneous respirations. Each animal was injected subcutaneously with 50 mg of C. adamanteus venom in identical preselected areas of the trunk. After 1 min, two treatment animals had the LoCC device applied; two control animals had no intervention. Vital signs were recorded every 10 min for the first 2 h and every 30 min thereafter. Endpoints included cardiovascular collapse (fatal arrhythmia, loss of mean arterial pressure, or pulse) or respiratory arrest (<3 breaths/min, saturation < 80%) or survival to 7 h. The pigs in the treatment group reached an endpoint at an average time of 355 (+/-65) min compared with control 32 (+/-3.5) min (p < 0.04). In this pilot study, the LoCC device significantly delayed onset of systemic symptoms and death after torso envenomation with Eastern Diamondback Rattlesnake venom in this model.

• Epidemics of mold poisoning past and present.

  Authors: William J Meggs

  Toxicology and industrial health. 10/2009;

  Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. ThroughoutMolds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

• Weight gain associated with chronic exposure to chlorpyrifos in rats.

  Authors: William J Meggs, Kori L Brewer

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 10/2007; 3(3):89-93.

  OBJECTIVE: This work exposed rats to low levels of the organophosphate insecticide chlorpyrifos and monitored for toxic effects, including weight gain. METHODS: Rats received either a subcutaneousOBJECTIVE: This work exposed rats to low levels of the organophosphate insecticide chlorpyrifos and monitored for toxic effects, including weight gain. METHODS: Rats received either a subcutaneous injection of chlorpyrifos, 5 mg/kg/day, or an equal volume of vehicle daily for 4 months. Subjects were observed for 30 minutes after injection for signs of acute toxicity. Body weights were recorded at baseline, 2 months, 3 months, and 4 months. At the end of the experiment, the weights of hearts, medial lobe of the livers, peri-nephric fat pads, and gastrocnemius muscles were recorded. Effects of chlorpyrifos on adipocyte differentiation in culture were studied. Results were compared using RMANOVA. RESULTS: No signs of acute cholinergic toxicity were observed after injections in any subject. Rats in the 5 mg/kg group were significantly heavier than those in the control group by 2 months (335.7 +/- 16.7 g vs. 318.6 +/- 15.8 g; p = 0.034). This difference increased at 3 months (350.1 +/- 16.4 g vs. 322.3 +/- 21.3 g p = 0.006) and 4 months (374.4 +/- 22.2 g vs. 340.2 +/- 25.2 g p = 0.006). At 4 months, the weights of the perinephric fat pads were significantly increased in the chlorpyrifos group relative to controls (2.867 + 0.516 vs. 1.130 + 0.171, p = 0.0039). The two groups showed no weight differences between hearts, livers, and gastrocnemius muscles. Chlorpyrifos did not affect adipocyte differentiation in tissue culture. CONCLUSIONS: Chronic exposure to chlorpyrifos at 5 mg/kg/day caused an increase in rat body weight when compared to controls. This increase was in adipose tissue. Chlorpyrifos did not induce differentiation of adipocytes in culture.

• Limited efficacy of calcium and magnesium in a porcine model of hydrofluoric acid ingestion.

  Authors: Jason A Coffey, Kori L Brewer, Robert Carroll, John Bradfield, William J Meggs

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 07/2007; 3(2):45-51.

  OBJECTIVE: This investigation evaluated the effectiveness of calcium and magnesium in treating oral hydrofluoric acid (HF) poisoning. METHODS: The controlled laboratory investigation usedOBJECTIVE: This investigation evaluated the effectiveness of calcium and magnesium in treating oral hydrofluoric acid (HF) poisoning. METHODS: The controlled laboratory investigation used anesthetized pigs. Subjects received HF via NG tube, titrated to abolish electrocardiographic abnormalities. The untreated group received saline infusion. The treatment group received serial injections of calcium chloride (CaCl2) and magnesium chloride (MgCl2). A third group received oral infusions of Calcium fluoride (CaF2). We measured heart rate, QRS interval, pH, bicarbonate, calcium, magnesium, and potassium. The Wilcoxon Rank Sum test was used to compare intra- and inter-subject differences. RESULTS: Fatality occurred in all pigs receiving HF. Compared to the untreated group, trends for the treatment group were toward a larger amount of HF to produce fatality (83.1 +/- 17.5 grams vs. 37.7 +/- 16.1 grams, p = 0.08), to cause QRS prolongation (72.5 +/- 25.8vs. 33.8 +/- 14.9 grams, p = 0.08), and to lower potassium at mortality (4.9 +/- 0.7 vs. 8.7 +/- 2.7 mEq/L, p = 0.08). No major changes in calcium (-1.0 +/- 0.7 mEq/L) or magnesium (0.4 +/- 0.6 mEq/L) occurred in the untreated group. Tachycardia developed in all pigs and ventricular arrhythmias occurred in 2 of 3 pigs of both groups [CaF2 administration caused no QRS prolongation or ventricular arrhythmias and had no effect on laboratory parameters]. CONCLUSION: CaCl2 and MgCl2 replacement delayed but did not prevent fatality and QRS prolongation. Although this result suggests Ca++ and Mg++ may be beneficial in the treatment of systemic HF toxicity, factors other than hypocalcemia and hypomagnesemia play a role in toxicity.

• Images in emergency medicine. Activated charcoal aspiration.

  Authors: Jason B Hack, M G F Gilliland, William J Meggs

  Annals of emergency medicine. 12/2006; 48(5):522, 531.

• Heparin reverses anaphylactoid shock in a porcine model.

  Authors: Charles R Heflin, Kori L Brewer, Jason B Hack, William J Meggs

  Annals of emergency medicine. 08/2006; 48(2):190-3.

  STUDY OBJECTIVE: Heparin binds histamine and has been advocated as a therapy for anaphylactic and anaphylactoid shock. The efficacy of heparin in treating anaphylactoid shock is compared with therapySTUDY OBJECTIVE: Heparin binds histamine and has been advocated as a therapy for anaphylactic and anaphylactoid shock. The efficacy of heparin in treating anaphylactoid shock is compared with therapy with diphenhydramine and epinephrine, as well as sham treatment with saline. METHODS: This controlled study of 9 anesthetized, intubated pigs induced shock with intravenous calcium ionophore A23187 (5 mg/kg), which is known to degranulate mast cells in vitro. Serum histamine levels were measured using an enzyme-linked immunosorbent assay. Shock, defined as a greater than 20% decrease in mean arterial blood pressure, was treated with intravenous saline, epinephrine with diphenhydramine, or heparin. Data were analyzed using Wilcoxon rank sum and analysis of variance, as appropriate. RESULTS: All pigs developed anaphylactoid shock after injection with A23187, as evidenced by hypotension, flushing, and an increase in plasma histamine. Mean arterial blood pressure fell from a mean of 73 (SD 10) mm Hg to 28 (SD 16) mm Hg after injection (P<.001; 95% confidence interval [CI] of the difference in pressures 34 to 57 mm Hg). Mean serum histamine levels increased from 712 micromol/dL (SD 731) to 1,154 micromol/dL (SD 799) after injection (Z value -2.201; P=.0277; 95% CI of the difference -610 to -99). Both epinephrine with diphenhydramine and heparin but not saline reversed shock. CONCLUSION: A23187 induced anaphylactoid shock in all subjects. Therapy with intravenous epinephrine combined with diphenhydramine reversed shock. Heparin also rapidly reversed shock.

• Sustained oxygenation without ventilation in paralyzed pigs with high-flow tracheal oxygen.

  Authors: William J Meggs, Robert G Carroll, Kori L Brewer, Jason B Hack, Timothy J Reeder

  The American journal of emergency medicine. 12/2005; 23(7):864-7.

  OBJECTIVES: It is generally assumed that ventilation is necessary for oxygenation. This study tested if paralyzed animals without respirations can maintain arterial oxygenation when administeredOBJECTIVES: It is generally assumed that ventilation is necessary for oxygenation. This study tested if paralyzed animals without respirations can maintain arterial oxygenation when administered high-flow oxygen delivered by a catheter in the trachea. METHODS: DESIGN: Prospective observational study. SETTING: University research laboratory. PARTICIPANTS: 3 anesthetized/paralyzed swine weighing 29.5 +/- 4.2 kg. INTERVENTIONS/OBSERVATIONS: Pigs were intubated, anesthetized with intravenous tiletamine and a pentobarbital drip. A femoral arterial line was placed to record arterial blood gases and vital signs every 5 minutes. Respiratory paralysis was obtained with vecuronium 150 microg/kg and repeated at any sign of movement. A catheter was placed in the trachea to deliver oxygen at 15 L/min. Outflow gas from the endotracheal tube was analyzed for O2 and CO2. O2 was discontinued at 75 minutes. The institutional animal care and use committee approved the protocol. RESULTS: All pigs survived to 75 minutes. PaO2 was more than 100 mm Hg throughout the study period. Mean PaCO2 was 37.4 +/- 2.8 mm Hg at baseline, 146 +/- 59 at 30 minutes, then rose above 200 mm Hg in all pigs by 45 minutes. Mean arterial pH fell from 7.47 +/- 0.04 at onset to 6.75 +/- 0.06 at 75 minutes. When oxygen was terminated at 75 minutes, PaO2 fell to 16.5 +/- 7.6 mm Hg within 5 minutes, and all pigs were sacrificed within 10 minutes. For outflow gas, O2 was more than 98% and expired CO2 less than 1% throughout the study period. CONCLUSIONS: Paralyzed, unventilated pigs receiving high-flow oxygen via a tracheal catheter remained alive after 75 minutes, although a profound respiratory acidosis developed.

• Pressure-immobilization bandages delay toxicity in a porcine model of eastern coral snake (Micrurus fulvius fulvius) envenomation.

  Authors: Benjamin T German, Jason B Hack, Kori Brewer, William J Meggs

  Annals of emergency medicine. 07/2005; 45(6):603-8.

  STUDY OBJECTIVES: Pressure-immobilization bandages are used in countries where neurotoxic snake envenomations are common. They impede lymphatic egress from the bite site and delay systemic venomSTUDY OBJECTIVES: Pressure-immobilization bandages are used in countries where neurotoxic snake envenomations are common. They impede lymphatic egress from the bite site and delay systemic venom toxicity. The effectiveness of these devices has not been evaluated in coral snake envenomations. We investigated the efficacy of pressure-immobilization bandages in delaying the onset of systemic toxicity in a porcine model of coral snake envenomation. METHODS: A randomized controlled trial of pressure-immobilization bandages was conducted in a university animal care center. Subjects were 12 anesthetized, spontaneously breathing pigs, ranging from 9.1 to 11.4 kg. After injection with 10 mg of Micrurus fulvius fulvius venom in the subcutaneous tissue of the distal foreleg, subjects were randomized to receive no treatment or application of a pressure-immobilization bandage at 1 minute after injection. Treated animals had elastic bandages applied to the extremity and splinting for immobilization. Vital signs and quality of respirations were recorded. Outcome was the onset of respiratory failure or survival to 8 hours. Necropsies and histologic analysis of the envenomation site was performed. RESULTS: One animal from each group was removed because of the discovery of pre-existing respiratory pathology. Four of 5 pigs in the treatment group survived to 8 hours, but none in the control group survived. Mean time to onset of respiratory compromise was 170.4 +/- 33.3 minutes in the control group. None of the pigs had histologic changes at the envenomation site consistent with ischemia or pressure-related injury. CONCLUSION: Pressure-immobilization bandages delayed the onset of systemic toxicity in our porcine model of M fulvius envenomation.

• The effect of calcium chloride in treating hyperkalemia due to acute digoxin toxicity in a porcine model.

  Authors: Jason B Hack, Jonathan H Woody, Daniel E Lewis, Kori Brewer, William J Meggs

  Journal of toxicology. Clinical toxicology. 02/2004; 42(4):337-42.

  BACKGROUND: The administration of intravenous (IV) calcium to treat hyperkalemia resulting from digoxin poisoning is considered potentially dangerous, based on a body of older literature which, inBACKGROUND: The administration of intravenous (IV) calcium to treat hyperkalemia resulting from digoxin poisoning is considered potentially dangerous, based on a body of older literature which, in sum, reported increased cardiac glycoside toxicity with calcium administration (increased arrhythmias, higher rate of death). OBJECTIVE: This pilot study sought to determine if the administration of calcium chloride when compared to normal saline would affect time to death when given to hyperkalemic, digoxin toxic swine. METHODS: Digoxin IV at 0.25 mg/kg was determined to be appropriately toxic for this study. When arrhythmias consistent with hyperkalemia developed, animals were given either IV calcium chloride (CaCl) bolus (10 mg/kg, Group 1, n=6) or normal saline volume equivalent (Group 2, n=6). Three intervals were observed: Interval 1: time interval from digoxin administration (T0) to when ECG changes consistent with hyperkalemia developed (at which point calcium chloride or normal saline was administered); Interval 2: time interval from the development of ECG changes consistent with hyperkalemia to asystole; Interval 3: time interval from digoxin administration to asystole. Both groups were monitored for changes in heart rhythms, serum potassium levels, and time to asystole. RESULTS: The intravenous digoxin dose of 0.25 mg/kg induced hyperkalemia, arrhythmias, and death approximately 1 h after administration in all animals studied. Group 1: Interval 1 averaged 18.75 (S.D. +/-7.96) min, Interval 2 averaged 16.75 (S.D. +/-17.17) min, and Interval 3 averaged 35.5 (S.D. +/-14.49) min range; Group 2: average Interval 1 24.8 (S.D. +/-4.71) min, Interval 2 averaged 19.5 (S.D.+/-15.92), Interval 3 averaged 44.3 (S.D. +/-13.80) minutes. There was no statistically significant difference between the groups at any time interval, Interval 1 (p=0.43), Interval 2 (p=0.65), Interval 3 (p=0.40). There was no difference in serum potassium throughout the study period. CONCLUSION: The administration of intravenous CaCl in the setting of hyperkalemia from acute digoxin toxicity did not affect mortality or time to death at the dose administered.

• Oral treatment of organophosphate poisoning in mice.

  Authors: Bradford J Bowls, Jack M Freeman, James A Luna, William J Meggs

  Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 04/2003; 10(3):286-8.

  OBJECTIVE: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition toOBJECTIVE: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. METHODS: The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi-square analysis was used to compare results in the different groups. RESULTS: Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. CONCLUSIONS: Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.

• Permanent paralysis at sites of dermal exposure to chlorpyrifos.

  Authors: William J Meggs

  Journal of toxicology. Clinical toxicology. 02/2003; 41(6):883-6.

  OBJECTIVE: Poisoning with organophosphate pesticides can cause sensory and motor neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has not been reported. CASE REPORT: AOBJECTIVE: Poisoning with organophosphate pesticides can cause sensory and motor neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has not been reported. CASE REPORT: A 61-year-old carpenter sprayed a nest of termites with an insecticide containing chlorpyrifos without protective equipment and with direct contact of pesticide solution to hands, lower arms, feet, and lower legs, as well as inhalation of vapors from spraying. After 30 min he became ill with nausea, abdominal cramping, arm and leg weakness, bilateral shoulder pain, chest pain, and numbness in the left hand and arm. At a hospital, he was treated with atropine 1 mg IV and pralidoxime Cl 2 g IV There was 0/5 strength in the hands and wrists and 3/5 elsewhere, a left peritoneal palsy, and urinary retention. He was transferred to a tertiary care hospital where paralysis persisted. Electromyogram studies documented widespread peripheral neuropathy. With continued progression of neuropathy, pralidoxime was repeated on the third day. By day 12, motor strength improved except for the hands and left lower leg. Right interosseous muscle strength was 1/5 and left was 0/5. Right-hand grip was 2/5, and left-hand grip was 0/5. He was transferred to a rehabilitation center. He never regained use of his hands and was disabled from employment as a carpenter. There was a disturbed gait, with inability to clear his left foot with walking. Urinary retention persisted and required self-catherization. CONCLUSION: Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy and permanent paralysis of exposed areas. The importance of protective equipment is emphasized.

• Clearance of metformin by hemofiltration in overdose.

  Authors: Fermin Barrueto, William J Meggs, M J Barchman

  Journal of toxicology. Clinical toxicology. 02/2002; 40(2):177-80.

  BACKGROUND: Metformin is prescribed with an increasing frequency for patients with Type II diabetes mellitus; the increasing availability increases the risk of intentional overdoses. Metformin mayBACKGROUND: Metformin is prescribed with an increasing frequency for patients with Type II diabetes mellitus; the increasing availability increases the risk of intentional overdoses. Metformin may cause severe lactic acidosis in overdose, especially when accompanied by co-ingestants or other medical conditions that alter lactate handling or metformin elimination. Though the clearance of therapeutic metformin by hemodialysis is known, the clearance in the setting of a large overdose has not been reported. CASE REPORT: A 58-year-old man with a history of Type II diabetes, hypertension, bipolar disease, and decreased renal function presented after ingestion of approximately 40 500-mg metformin tablets and 20 240-mg diltiazem sustained-release tablets. Clinical manifestations of poisoning included somnolence, hypotension, bradycardia, severe lactic acidosis, and ultimately death. Gastric decontamination was attempted with gastric lavage, multiple dose activated charcoal, and whole bowel irrigation. Hemodynamic support was provided with pressors, glucagon, insulin, and intra-aortic balloon pump. Due to hypotension, continuous renal replacement therapy, rather than hemodialysis, was initiated. Continuous veno-venous hemodialysis was performed with a blood flow of 180 mL/min and dialysate flow of 2.5 L/h. A Multiflow 60 kidney (Cobe) on a Prisma (Cobe) continuous renal replacement therapy machine was used. The initial metformin level was 110 microg/mL (therapeutic range 1-2 microg/mL). By continuous veno-venous hemodialysis, an absolute clearance of 50.4 mL/min was obtained. CONCLUSION: Metformin was cleared by the continuous veno-venous hemodialysis modality of continuous renal replacement therapy in this metformin overdose. Although a fatal outcome occurred in this patient, its utility in other patients with metformin overdose should be investigated.