Patrick McKinney

Therapy of Brown Spider Envenomation: A Controlled Trial of Hyperbaric Oxygen, Dapsone, and Cyproheptadine

STUDY OBJECTIVE To determine whether hyperbaric oxygen (HBO), dapsone, or cyproheptadine decreases the severity of skin lesions resulting from experimental Loxosceles envenomation. DESIGN Randomized, blinded, controlled study. SETTING Animal care facility. INTERVENTIONS We used New Zealand white rabbits. All groups received 20 micrograms of pooled L deserta venom intradermally. Our control group received 4 ml of a 5% ethanol solution by oral gavage every 12 hours for 4 days. The HBO group received hyperbaric oxygen at 2.5 ATA for 65 minutes every 12 hours for 2 days, plus 5% ethanol solution for 4 days. The dapsone group received dapsone 1.1 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. The cyproheptadine group received cyproheptadine .125 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. RESULTS Total lesion size and ulcer size were followed for 10 days. The lesions were then excised, examined microscopically, and ranked by the severity of the histopathology. The groups did not differ significantly with respect to lesion size, ulcer size, or histopathologic ranking. CONCLUSION Given the negative result in this study with adequate power to detect meaningful treatment benefits, we cannot recommend hyperbaric oxygen, dapsone, or cyproheptadine in the treatment of Loxosceles envenomation.

Vitreous humor cocaine and metabolite concentrations: do postmortem specimens reflect blood levels at the time of death?

The interpretation of postmortem cocaine concentrations is made in an attempt to estimate drug concentrations present at the time of death and thus infer not only drug presence but drug toxicity. Previous data suggest that changes in postmortem blood cocaine concentrations over time are not predictable and interpretation of cocaine levels should be done with caution. However, these data come from autopsy case series where vital information, such as blood cocaine concentration at the time of death, dose and time since last use, and postmortem interval is often not known. The purpose of this study was to characterize postmortem changes in cocaine and metabolite concentrations relative to premortem concentrations over time at two anatomic sites: peripheral blood and vitreous humor, in a controlled, large animal model. Juvenile swine were given cocaine HCl 10 mg/kg as an IV bolus which resulted in seizures and wide complex tachycardia. Five minutes after cocaine administration, animals were euthanized. At time of death and eight hours postmortem, femoral venous blood and vitreous humor (VH) samples were obtained for quantitation of cocaine, benzoyl ecgonine (BE), and ecgonine methyl ester (EME) by GC/MS. There were no significant increases over time in mean femoral vein concentrations of cocaine or BE. However, a large interanimal variability in direction and magnitude of concentration changes was seen. Mean EME concentrations at the femoral site increased significantly over 8 hours (P < 0.03). Mean VH cocaine concentrations at time of death were significantly lower than corresponding blood concentrations (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Charcoal stercolith with intestinal perforation in a patient treated for amitriptyline ingestion

A case of a patient who developed an intestinal perforation secondary to a charcoal stercolith is reviewed. The case involves a young female on methadone maintenance who received multiple-dose charcoal therapy for an amitriptyline ingestion. Peritoneal signs developed several days after admission, and an exploratory laparotomy was done. A perforation measuring 4 cm in diameter was found in the posterior wall of the sigmoid colon. A 120-gm obstructing charcoal mass was found at the site of the perforation. Previous reports of intestinal obstruction secondary to charcoal inspissation are noted, and case similarities are discussed. All reported cases of charcoal obstruction involve the administration of multiple-dose-activated charcoal in the treatment of ingestions of medications known to have antiperistaltic activity. With a rare potential of mechanical obstruction, the decision to use repetitive-dose charcoal therapy should be made judiciously when the ingested toxin or coincident therapeutic medications have antiperistaltic activity.

Acute Zinc Chloride Ingestion in a Child: Local and Systemic Effects

A 16-month-old boy ingested liquid zinc chloride/ammonium chloride soldering flux. He developed severe local burns, metabolic acidosis, hepatic damage, hyperamylasemia, lethargy, and hypertension. Peak measured plasma zinc was 1,199 micrograms/dL. Because of persistent signs of systemic toxicity, he was chelated with dimercaprol (BAL) and EDTA. Although clinical improvement was noted coincident with the initiation of chelation, there was no apparent increase in urinary zinc excretion. Scarring in the gastric antrum necessitated an antrectomy. The child recovered without other apparent complications.

Methamphetamine toxicity prevented by activated charcoal in a mouse model.

STUDY OBJECTIVE To determine the effectiveness of activated charcoal in preventing toxicity from oral methamphetamine HCI. DESIGN Randomized, prospective, nonblinded, controlled animal study. SETTING Animal care facility. PARTICIPANTS CD-1 male mice. INTERVENTIONS Mice were given 100 mg/kg methamphetamine HCI (lethal dose 60) in water by oral gavage. Within 1 minute of methamphetamine administration, mice received either 1 g/kg activated charcoal or an equivalent volume of water as control. MEASUREMENTS AND MAIN RESULTS Mice were observed for time to onset of symptoms (piloerection, agitation, and tremor) and mortality at 1, 24, and 48 hours. Activated charcoal delayed onset of symptoms (5.53 +/- 1.25 minutes versus 4.27 +/- 1.22 minutes, P < .002) and decreased mortality compared to controls at 1 hour (1 of 20 versus 10 of 20, P < .003) and 24 hours (five of 20 versus 12 of 20, P < .05). There was no difference between groups in mortality at 48 hours. CONCLUSION A single dose of activated charcoal given after oral methamphetamine delayed onset of toxicity and decreased early mortality in mice. There was no effect on overall mortality.

Prevention of toxicity from oral cocaine by activated charcoal in mice

STUDY OBJECTIVE To study the effectiveness of activated charcoal in preventing toxicity after an enterally administered cocaine hydrochloride overdose in mice. DESIGN A prospective, randomized, controlled animal laboratory investigation. INTERVENTIONS Fasted mice were given aqueous cocaine hydrochloride (0.8% final concentration) 100 mg/kg body weight orally by gavage tube. One minute later, animals received one of three treatments by gavage: 1 g activated charcoal/kg body weight, 2 g activated charcoal/kg body weight, or an equivolume of water (control). All treatments consisted of 20 mL/kg body weight of an activated charcoal slurry with water. MEASUREMENTS After 24-hour observation, proportions of seizures and deaths between each group were compared using Pearson chi 2 test followed by Fishers exact test (P < .017 for significance after Bonferronis correction). MAIN RESULTS There were 20 seizures and 16 deaths in the control group (20 mice). There were four seizures (P = .0004) and one death (P = .0004) in the 1-g activated charcoal/kg group (ten mice) and five seizures (P = .0018) and three deaths (P = .015) in the 2-g activated charcoal/kg group (ten mice). CONCLUSION In this mouse model, activated charcoal decreased the incidence of seizures and death after an enteral cocaine hydrochloride overdose.

Activated Charcoal and Acetylcysteine Absorption: Issues in Interpreting Pharmacokinetic Data

Studies determining the effects of activated charcoal on drug absorption frequently use area under the plasma drug concentration versus time curve or drug and metabolite recovery in the urine as endpoints. The considerations in using these endpoints is presented using studies that have evaluated the effects of activated charcoal on acetylcysteine absorption. Acetylcysteines pharmacokinetics, quantitation of plasma concentrations, and the lack of an identifiable pharmacokinetic-pharmacodynamic relationship all contribute to the difficulties in determining whether activated charcoal inhibits the oral absorption of acetylcysteine, or alters acetylcysteines efficacy in treating acetaminophen overdoses. The results of these studies should be interpreted cautiously, with consideration of internal and external study validity.

Elevation of Breath Ethanol Measurements by Metered-Dose Inhalers

STUDY OBJECTIVE Metered-dose inhalers (MDIs) may contain as much as 38% ethanol. We evaluated the effects of ethanol-containing MDIs on breath alcohol testing. DESIGN Prospective, single-blind, crossover, controlled study. PARTICIPANTS Three healthy male volunteers 29 to 36 years old. INTERVENTION We studied three brands: Tornalate, (38% ethanol), Bronkometer, (30% ethanol), and Alupent, (0% ethanol). The effects of each MDI on breath and blood ethanol measurements were evaluated separately. Two puffs of each brand of MDI were administered. Breath ethanol measurements were obtained at baseline and .25, .5, 1, 2, 3, 5, and 10 minutes after MDI use. Blood ethanol measurements were obtained at baseline and 1 and 10 minutes after MDI use. RESULTS Overall, Tornalate had the highest breath ethanol readings, with a mean ethanol level of 189 mg/dL recorded just after MDI use. Breath ethanol levels subsequently decreased rapidly over time. Mean breath ethanol concentrations were lower after the use of Bronkometer and undetectable after the use of Alupent. Blood ethanol levels were undetectable at all times tested. CONCLUSION MDIs may cause elevations of breath alcohol above the legal criteria for intoxication. These effects are transient and may be prevented by a 10-minute interval between the use of an MDI and breath alcohol testing.

Human envenomation from a wandering garter snake

Garter snake bites are generally innocuous to human beings. We report a case of human envenomation from the Wandering Garter snake (Thamnophis elegans vagrans). The patient, who was bitten on his right third fingertip, rapidly developed local edema, ecchymosis, and hemorrhagic vesicles. Systemic signs and symptoms did not develop. The clinical picture was similar to that in three previous patients with Thamnophis envenomation in that clinical signs followed a prolonged bite. Thamnophis species have Duvernoys glands, which may be analogous to venom glands in Crotalidae (pit viper) species. The progressive local effects produced by secretions of these glands may be confused with early Crotalidae envenomation.

The preadministration of activated charcoal and aspirin absorption

There is little information describing the effects of activated charcoal preadministration on drug absorption. This study was undertaken to determine the effect of activated charcoal preadministration at two different times on aspirin absorption. Fifteen volunteer subjects completed three study phases: 1) 975 mg aspirin alone, 2) 975 mg aspirin 30 min after 10 g activated charcoal, and 3) 975 mg aspirin 60 min after 10 g activated charcoal. Urine was collected for 48 h after the initiation of each study phase, and total aspirin recovery determined by HPLC. The aspirin recovery was 88.8% +/- 4.5% for the control phase, and 84.8% +/- 9.4% (Phase 1) and 85.8% +/- 12.6% (Phase 2) for the activated charcoal treatments (p > 0.05). These results suggest that activated charcoal administered 30 and 60 min prior to drug ingestion has little effect on drug absorption. Further studies of the effect of charcoal preadministration on the absorption of other drugs may provide useful information regarding factors important in determining activated charcoal efficacy.