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Background: Although it is a commonly held belief that the ingestion of drugs with an anticholinergic action would prolong the duration of time after drug ingestion for effective gastrointestinal decontamination, data are lacking to support this belief. The purpose of this study is to determine whether activated charcoal is more effective in the presence of concurrent anticholinergic activity., Methods: A three-limbed randomized crossover study in 10 healthy volunteers was completed to determine the ability of a 50 g dose of activated charcoal to reduce the bioavailability of a simulated overdose of acetaminophen (12 x 325 mg tablets) in the presence and absence of a concurrently present anticholinergic drug, atropine (0.01 mg/kg I. M. administered 15 min prior to the acetaminophen ingestion)., Results: After the acetaminophen ingestion, median Cmax occurred at 1 h for all three exposures but was lower in the atropine-treated study arm (31+/-19 mg/L) than in the control or charcoal alone intervention arms (49+/-13 and 51+/-16 mg/L, respectively) (P<0.05). Compared to the control area under the serum concentration vs. time curve, a single dose of activated charcoal 1 h after drug ingestion reduced acetaminophen bioavailability by 20% (95% CI 4-36%) and by 47% (95% CI 35-59%) in the presence of atropine (P<0.05 atropine plus charcoal vs. charcoal alone)., Conclusions: Our data support the belief that activated charcoal is more effective in the presence of anticholinergic activity. Additional study is required to determine whether in patients with anticholinergic drug overdose, activated charcoal is effective at times beyond the recommendation for overdoses of drugs without this pharmacodynamic effect.

Study Objective: To determine if the presence of N-acetylcysteine reduces the ability of activated charcoal to adsorb acetaminophen both in the absence and presence of a coingestant., Design: In vitro laboratory study., Setting: University hospital research laboratory., Measurements and Main Results: The adsorption of acetaminophen and salicylic acid by activated charcoal in the presence and absence of N-acetylcysteine was measured in vitro. Acetaminophen and salicylic acid analyses were conducted with high-performance liquid chromatography. Adsorption data were compared using the appropriate parametric statistical test. The addition of N-acetylcysteine significantly decreased the binding of acetaminophen by activated charcoal (p<0.005). When salicylic acid was added to simulate a coingestant, N-acetylcysteine significantly decreased salicylate adsorption by charcoal (p<0.001)., Conclusions: The presence of N-acetylcysteine reduces the ability of activated charcoal to adsorb acetaminophen and coingestants. In vivo data will be required to determine the clinical relevance of these interactions.

Objective: The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion., Methods: This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis., Results: Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies., Conclusion: Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.

Background: This study assesses whether oral multiple-dose charcoal therapy (MDC) or whole-bowel irrigation (WBI) enhances the excretion of previously absorbed salicylate., Methods: A controlled, randomized, three-limbed crossover protocol was used in nine humans who ingested aspirin. Salicylate levels were measured in serial serum specimens and 32-hour urine collections and kinetic parameters were calculated., Results: There were no differences among the control (CTL), MDC, or WBI groups for area under the serum concentration vs time curve (CTL, 2320 +/- 501 mg/L.h MDC, 2040 +/- 454 mg/L.h; WBI, 2093 +/- 418 mg/L.h) or for urinary salicylates (CTL, 54.9% +/- 9.4%; MDC, 50.9% +/- 8.0%, WBI, 52.4% +/- 13.7% of ingested dose)., Conclusions: Our data do not support the use of either MDC or WBI to enhance the excretion of previously absorbed salicylate in poisoned patients. In patients with drug overdoses, a clear rectal effluent remains as the endpoint for WBI.

We describe a 38 year-old female who ingested 900 mg of diltiazem. She experienced hypotension, bradycardia and heart block but responded well to supportive care that included normal saline infusion and vasopressors. Calcium administration was not beneficial. Serial plasma concentrations of diltiazem, N-demethyldiltiazem and desacetyldiltiazem were quantified. By comparing the elimination half-life for diltiazem with historical controls, it is concluded that multiple dose charcoal therapy was not beneficial for our patient.

Study Objectives: The purpose of this study was to address the issues of safety and efficacy of combining whole-bowel irrigation and activated charcoal administration for the treatment of toxic ingestions., Study Design: Two in-vitro studies were performed. In the first, serial ratios of polyethylene glycol (PEG) and activated charcoal (AC) powders were added to water and the solutions were analyzed for PEG concentration and osmolality. In the second, serial ratios of a pharmaceutical bowel irrigation solution and an AC preparation were combined with a constant amount of salicylic acid. Solution osmolalities, PEG, and salicylic acid concentrations were then quantified., Results: Adsorption of PEG powder by AC was demonstrated; however, changes in solution osmolality were negligible. Thus, concurrent administration of these therapies appears safe. However, combining bowel irrigation solution with AC resulted in decreased salicylic acid adsorption. This was especially so with smaller amounts of AC that would pertain more to the smaller doses of AC used for multiple-dose charcoal therapy., Conclusion: If these in-vitro data are applicable to overdose patients, the administration of a routine initial charcoal dose to those who will be treated with whole-bowel irrigation would be appropriate. However, it is unlikely that the addition of multiple-dose charcoal therapy to whole-bowel irrigation would provide additional benefit for the patient.

Multiple-dose charcoal therapy has been shown to increase the excretion of some drugs. This study assesses the effects of this intervention on salicylate excretion in the postabsorptive phase. Ten human volunteers participated in this randomized, controlled, crossover, two-limbed protocol. On two occasions each volunteer ingested 2880 mg of aspirin. During the experimental limb, 25 g of activated charcoal was ingested at 4, 6, 8, and 10 hours after drug ingestion. Pharmacokinetic data were derived from serial serum salicylate concentrations, and urinary salicylate excretion was quantified. Treatment effects were 9% and 18%, respectively. Although both are significant, they are clinically modest, making multiple-dose charcoal therapy of questionable value for acute salicylate poisoning. Controlled data demonstrating the clinical efficacy of this therapy are required to validate it as an intervention for this condition.

Overdose with modified-release pharmaceuticals is an increasing phenomenon. This study examines whole-bowel irrigation as a potential decontamination strategy after overdose with enteric-coated acetylsalicylic acid and compares it with administration of activated charcoal in sorbitol, which is currently the recommended intervention. A three-phase randomized crossover protocol was used in 10 adult volunteers. Each volunteer ingested nine 325 mg doses of enteric-coated acetylsalicylic acid on three occasions, with at least 1 week between each administration period. Serum samples were analyzed for salicylic acid concentration by HPLC. Both interventions decreased peak salicylic acid concentration, time-to-zero salicylic acid concentration, and AUC when compared with control (p less than 0.01). Whole-bowel irrigation was superior to activated charcoal in sorbitol by all three criteria (p less than 0.05). Adverse effects were qualitatively and quantitatively greater during activated charcoal in sorbitol, and the volunteers preferred whole-bowel irrigation over charcoal in sorbitol. Our data suggest that whole-bowel irrigation should be considered for overdose of other modified-release pharmaceuticals.

The efficacy of ipecac-induced emesis, large-bore orogastric lavage, and activated charcoal as gastrointestinal decontamination procedures after acute drug overdose is unknown. Using an ampicillin overdose model, these three procedures were compared with one another and to a control ingestion in ten human volunteers. Serial serum ampicillin levels were used to compute the areas under the concentration vs time curves (AUC) for each study. The reductions of ampicillin absorption compared to control were as follows: orogastric lavage 32% (NS), ipecac-induced emesis 38% (P less than .01), and activated charcoal 57% (P less than .01). This model examines each intervention in a mutually exclusive fashion. It supports activated charcoal administration as the primary gastrointestinal decontamination procedure after acute drug overdose.