Multiple Doses Of Activated Charcoal Research Articles

Clinical characteristics, treatment and outcomes of acute propanil poisoning in a 7-year retrospective cohort study

The present study was a 7-year retrospective cohort study (2012–2018) of patients treated for acute propanil poisoning by ingestion, using data from Ramathibodi Poison Center, Thailand. The aim of this study was to describe the clinical characteristics, treatment, outcomes and factors associated with moderate to severe outcomes and death following acute exposure to propanil. The effect of administering multiple-dose activated charcoal (MDAC) on clinical outcomes was also evaluated. A total of 275 cases were included. The results show that two thirds of patients were male and mean age was 40 years. Patients ingested either propanil or a mixture of propanil and other herbicides. The majority (98%) of exposures was intentional. Most patients (65.5%) presented with gastrointestinal symptoms. Methemoglobinemia and hemolysis were observed in 108 patients (39.3%) and 25 patients (9.1%), respectively. Median time to onset of methemoglobinemia and hemolysis after propanil ingestion was 5.5 and 48 h, respectively. One hundred and forty-one patients (51.3%) were treated with MDAC, and some patients received methylene blue (21.5%), intubation (18.5%), or blood transfusions (8%). All patients were admitted to hospitals. The median length of hospital stay of patients who survived was 3 days. Multivariate analysis indicated that neurological symptoms at presentation, methemoglobinemia and acute kidney injury during admission, were associated with moderate to severe outcomes. Factors associated with mortality were older age, larger amount of ingestion, neurological symptoms at presentation and hypotension during admission. The overall mortality rate was 6.2%. The mortality rate was 3.6% in patients that received MDAC and 9% in patients that did not, although the difference was not statistically significant. Subgroup analysis of patients who developed methemoglobinemia or both methemoglobinemia and hemolysis found a statistically significant lower mortality rate in patients that received MDAC. In conclusion, methemoglobinemia and hemolysis contribute to poor outcomes in acute propanil poisoning. Age, amount of ingestion, neurological symptoms at presentation and hypotension during admission could prognosticate deaths, and patients with these factors should be closely observed and aggressively managed.

The effect of activated charcoal on drug exposure following intravenous administration: A meta-analysis.

Activated charcoal both reduces primary drug absorption and enhances drug elimination. However, the two mechanisms of action overlap and are indistinguishable from each other. In order to estimate the extend of enhanced elimination, we summarized the effect of activated charcoal on intravenously administered drugs, where reduced drug exposure can be attributed to enhanced elimination. We performed a meta-analysis of randomized controlled studies evaluating the effect of orally administered activated charcoal on the systemic exposure of intravenously administered drugs. We searched the bibliographic databases PubMed, Embase and Cochrane. Meta-regression analyses of selected physiochemical drug properties on the effect sizes of activated charcoal were performed. All but one of 21 included studies used multiple-dose activated charcoal (MDAC). MDAC reduced the median half-life of the intravenously administered study drugs by 45.7% (interquartile range: 15.3%-51.3%) and area under the concentration time curve by 47.0% (interquartile range: 36.4%-50.2%). MDAC significantly improved drug elimination across nine different intravenously administered drugs, but we were unable to identify factors allowing extrapolation to other drugs. The results offer a possible and plausible rationale for the previously observed effects of single-dose activated charcoal beyond the timeframe where ingested drug is present in the gastro-intestinal tract.

Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic polymorphism

Introduction. Phenytoin is metabolised in the liver by cytochrome (CYP)2C9 and 2C19 enzymes. Due to saturation of enzyme capacity, the elimination half-life is prolonged at supratherapeutic levels. Genetic polymorphisms of CYP2C9 and 2C19 are reasonably common and further prolong the elimination of phenytoin. There are conflicting reports regarding whether multiple-dose activated charcoal (MDAC) significantly increases the clearance of phenytoin in poisoning. Case report. We present 3 patients with phenytoin toxicity and very slow elimination secondary to reduced CYP enzyme function from genetic polymorphisms. MDAC was used in two patients and led to rapid and large reductions in the measured elimination half-lives. This is contrasted with very prolonged elimination in a third patient who did not receive MDAC. Conclusion. MDAC may play a role in the management of chronic phenytoin toxicity, especially in those with very slow endogenous elimination secondary to genetic polymorphisms.

Randomized controlled study on the use of multiple-dose activated charcoal in patients with supratherapeutic phenytoin levels

Introduction. We conducted a prospective randomized controlled study on the influence of multiple doses of activated charcoal (MDAC) in patients with supratherapeutic serum phenytoin levels; Methods. Patients with serum phenytoin levels greater than 30 mg/L upon presentation to the ED were recruited from two urban teaching hospitals. Patients enrolled were older than 18, nonpregnant, able to tolerate activated charcoal by mouth and able to give written consent. They were randomized to receive 50 g activated charcoal by mouth every 4 hours or no activated charcoal. They continued in the study until the patient was discharged or the serum level was <25 mg/L. Serum levels were drawn every 6 hours initially, then every 24 hours after the 1st day. The presence of gait abnormalities and nystagmus was recorded and mini-mental status exam (MMSE) scores were collected from each patient enrolled. Time to reach subtoxic levels was recorded; Results. Seventeen patients were enrolled in the study. Seven patients received MDAC, eight patients served as controls and two patients who were initially enrolled as controls inadvertently received one dose of activated charcoal and were excluded from the analysis. Both groups were comparable in age and all were male. The median time to reach a subtoxic level was 41.1 hours (range, 11.6–196) and 19.3 hours (range, 13–33) in the control and charcoal groups, respectively (p = 0.049). The median and range peak serum levels were 40.0 hours (range, 32.0–47.6) and 35.6 hours (range, 32.5–40.0) in the control and charcoal groups, respectively (p = 0.082). The median and range MMSE scores were 20 points (range, 12–30) and 19.5 points (range, 16–29) in the control and charcoal groups, respectively; Conclusion. Further study is needed to determine if MDAC decreases the time to reach a subtoxic level of phenytoin in patients with supratherapeutic phenytoin levels.

Case Report of Aspirin Overdose: Bezoar Formation and Controversies of Multiple‐Dose Activated Charcoal in Salicylate Poisoning

Bezoar formation is cited to be the cause of delayed absorption of aspirin in overdose of enteric‐coated aspirin preparation. However, such phenomenon from oral overdose of regular aspirin preparation has not been clearly demonstrated in human. The use of multiple‐dose activated charcoal (MDAC) in salicylate poisoning remains controversial. We report a case of regular‐preparation salicylate poisoning with rebound of the serum salicylate level after discontinuation of MDAC administration. Bezoar formation as the underlying cause of the rebound and the effect of MDAC on serum salicylate level are discussed.

Limited Efficacy of Gastrointestinal Decontamination in Severe Slow-Release Carbamazepine Overdose

To report the limited efficacy of both multiple doses of activated charcoal (MDAC) and whole bowel irrigation (WBI) in a patient with severe overdose of slow-release carbamazepine. A 25-year-old man was admitted in a comatose state with seizures after a suicide attempt with slow-release carbamazepine. Serum carbamazepine concentration on admission (16 h postingestion) was 52.08 microg/mL. The patient was mechanically ventilated and treated with MDAC and a 4 hour charcoal hemoperfusion. Carbamazepine concentration at the end of hemoperfusion was 27.16 microg/mL. Despite continuous treatment with MDAC, a rebound in carbamazepine concentration to 36 microg/mL was observed 32 hours after hemoperfusion (58 h postingestion). WBI was performed over a 10 hour period. The carbamazepine concentration continued to increase to 38.55 microg/mL and seizures recurred. After WBI was performed, MDAC was reinstituted; 33 hours later (102 h postingestion), the carbamazepine concentration began to decline. The hospitalization course was complicated by pneumonia, which necessitated continuation of mechanical ventilation and administration of antibiotics. The patient recovered completely and was discharged without sequelae 15 days after admission. Serum carbamazepine concentration and toxicity were effectively reduced by hemoperfusion. The role of MDAC coadministered during hemoperfusion cannot be ruled out. However, a rebound in carbamazepine concentration with recurrent seizures was observed despite MDAC and WBI. The most likely explanation for this rebound (65 h postingestion, 39 h posthemoperfusion) is prolonged absorption, possibly from a pharmacobezoar. Redistribution cannot be excluded, but this is not supported by the concentration-time course and previous reports. Both MDAC and WBI may be ineffective in reducing absorption and enhancing elimination in overdose of slow-release carbamazepine. Repeated hemoperfusion or other elimination enhancement techniques should be considered when the clinical and toxicokinetic course suggests the presence of a refractory pharmacobezoar.

Antidotes for acute cardenolide (cardiac glycoside) poisoning

Cardenolides are naturally occurring plant toxins which act primarily on the heart. While poisoning with the digitalis cardenolides (digoxin and digitoxin) are reported worldwide, cardiotoxicity from other cardenolides such as the yellow oleander are also a major problem, with tens of thousands of cases of poisoning each year in South Asia. Because cardenolides from these plants are structurally similar, acute poisonings are managed using similar treatments. The benefit of these treatments is of interest, particularly in the context of cost since most poisonings occur in developing countries where resources are very limited. To determine the efficacy of antidotes for the treatment of acute cardenolide poisoning, in particular atropine, isoprenaline (isoproterenol), multiple-dose activated charcoal (MDAC), fructose-1,6-diphosphate, sodium bicarbonate, magnesium, phenytoin and anti-digoxin Fab antitoxin. We searched MEDLINE, EMBASE, the Controlled Trials Register of the Cochrane Collaboration, Current Awareness in Clinical Toxicology, Info Trac, www.google.com.au, and Science Citation Index of studies identified by the previous searches. We manually searched the bibliographies of identified articles and personally contacted experts in the field. Randomised controlled trials where antidotes were administered to patients with acute symptomatic cardenolide poisoning were identified. We independently extracted data on study design, including the method of randomisation, participant characteristics, type of intervention and outcomes from each study. We independently assessed methodological quality of the included studies. A pooled analysis was not appropriate. Two randomised controlled trials were identified, both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified. There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.

Anticonvulsants

Clinical features—carbamazepine is structurally related to the tricyclic antidepressants and has similar anticholinergic features in overdose (dry mouth, coma and convulsions). In addition, drowsiness, nystagmus, ataxia and incoordination are often seen, the pupils are often dilated and divergent strabismus may be present. Complete external ophthalmoplegia has been reported. Hallucinations may occur, particularly in the recovery phase. Management—a single dose of charcoal within 1 hour of ingestion substantially reduces absorption. Multiple-dose activated charcoal (MDAC) has been shown to significantly increase elimination of carbamazepine (Boldy et al., 1987, Montoya-Cabrera, 1996). Activated charcoal should therefore be given in severe cases of carbamazepine poisoning in an initial dose of 50-100 g for adults, with repeated doses of 12.5 g/hour (or the equivalent).

Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose.

This work was performed to study the pharmacokinetics of phenobarbital during renal clearance enhancement, intestinal clearance enhancement, and a combination of both to determine which method is clinically more effective in the management of drug poisoning. Thirty young patients with phenobarbital overdose were enrolled in the study. They were classified according to the method of treatment to enhance the elimination of phenobarbital into three equal groups: those treated with multiple-dose activated charcoal (MDAC) alone; those treated with urinary alkalinization alone; and those treated with a combination of the two methods. All patients received the required supportive care at the same time as the elimination procedures. Plasma phenobarbital levels were determined on admission and at 6, 12, 18, 24, 30, 36, 42, and 48 hours after admission by the enzyme multiplied immunoassay technique. The results showed that the decrease in plasma phenobarbital levels with MDAC was significantly greater than with either urinary alkalinization or the combined use of both. The results also revealed statistically significant greater total body clearance for phenobarbital and consequently a shorter half-life with MDAC treatment versus either urinary alkalinization alone or the combined use of both. Thus, the authors conclude that the management of drug overdose in the case of weak acidic drugs that have small volumes of distribution should include the sole use of MDAC and supportive care, without urinary alkalinization.

Activated charcoal as the sole intervention for treatment after childhood poisoning.

Childhood poisonings account for approximately two thirds of all human toxic exposures reported annually to the American Association of Poison Control Centers. Activated charcoal (AC) is the mainstay of decontamination in the emergency department setting. This review focuses on six concepts: 1) description of AC and its method of action, 2) evolution of AC in the gastrointestinal decontamination process, 3) prehospital use of AC, 4) superactivated charcoal, 5) multiple-dose AC, and 6) complications of AC administration. The most recent evolving trends in decontamination of the pediatric patient include trends toward earlier decontamination, either in the home or by paramedics in the field. The newer, "super" activated charcoals, with their greater surface area, may improve compliance of oral administration of AC. Finally, guidelines have been set to limit use of multiple-dose activated charcoal regimens to certain pharmaceuticals only, as well as discouraging cathartic use with charcoal dosing.

Effect of Multiple-Dose Activated Charcoal on the Clearance of High-Dose Intravenous Aspirin in a Porcine Model

Study objective: To study the effect of multiple-dose activated charcoal (MDAC) on salicylate clearance in pigs given high-dose IV aspirin. Design: In a crossover design, six fasted pigs received 300 mg/kg IV aspirin followed by no treatment or MDAC (1 g/kg hourly for 6 doses by gastrostomy). Serum salicylate samples were obtained every 30 minutes for 6 hours. Results: The mean peak salicylate concentrations were 47.4±6.2 mg/dL and 48.4±3.9 mg/dL ( P =.74), and the areas under the time-serum salicylate concentration curve over 6 hours were 171,000±24,000 mg×minute/L and 188,000±18,000 mg×minute/L for the control and treatment arms, respectively ( P =.22). This study had a 90% power to detect a 30% difference between arms. Conclusion: MDAC does not enhance the clearance of salicylate after administration of high-dose IV aspirin. [Johnson D, Eppler J, Giesbrecht E, Verjee Z, Rais A, Wiggins T, Fraga C, Ito S: Effect of multiple-dose activated charcoal on the clearance of high-dose intravenous aspirin in a porcine model. Ann Emerg Med November 1995;26:569-574.]

Correlation of Drug Pharmacokinetics and Effectiveness of Multiple-Dose Activated Charcoal Therapy

Study objective: To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC.Design: Prospective, randomized, controlled, crossover design. Setting: A university animal research facility. Participants: Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube. Interventions: Acetaminophen (30 mg/kg), digoxin (30 μg/kg), theophylline (8.9 mg/kg), and valproic acid (18 mg/kg) were simultaneously administered intravenously over 12 minutes. In the experimental arm, 25 g activated charcoal was administered at 0, 2, 4, 6, 12, 18, 24, and 30 hours through the gastric tube. In the control arm, an equal volume of water was given at the same times. Blood specimens were obtained over 36 hours to measure serum drug concentrations. Results: Each drug exhibited enhanced elimination (P<.01) in the MDAC group except valproic acid. Lower intrinsic clearance was correlated (P<.05) with increased systemic elimination during the charcoal arm. Volume of distribution, half-life, and protein binding were not significantly correlated with charcoal-enhanced systemic drug elimination. Conclusion: The response of a drug to MDAC may be affected by its intrinsic clearance. The restrictive nature of the protein binding of valproic acid may be responsible for its lack of response. Results with the porcine model are consistent with the effects observed in human beings. [Chyka PA, Holley JE, Mandrell TD, Sugathan P: Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. Ann Emerg Med March 1995;25:356-362.]

Pharmacokinetic Simulation of the Effect of Multiple-Dose Activated Charcoal in Phenytoin Poisoning—Report of Two Pediatric Cases

Activated charcoal is commonly used to inhibit the absorption of phenytoin after acute overdose. There are also reports of multiple-dose activated charcoal (MDAC) increasing the clearance of phenytoin in adults. We describe our experience modeling phenytoin pharmacokinetics during therapy with MDAC in the treatment of two cases of acute phenytoin poisoning in children. After extensive attempts at modeling the serum phenytoin concentrations, simulations were performed to identify the possible consequences of MDAC administration. Phenytoin elimination was more rapid than was expected, based on previously reported phenytoin pharmacokinetic parameters. Moreover, the time to peak phenytoin concentration and time course of phenytoin intoxication appeared to be shorter than available reports of phenytoin intoxication treated with a single dose of activated charcoal. MDAC may prevent continued phenytoin absorption and increase phenytoin elimination rate via gastrointestinal dialysis. The effect of MDAC on the clearance of phenytoin can be described by a first-order elimination rate constant of approximately 0.02-0.04/h.

Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant

A 28-day-old infant developed lethargy, hypotonia, and hypothermia following a phenobarbital overdose secondary to a pharmacist's error. He was treated with multiple dose activated charcoal (MDAC) and alkalinization of the urine, which resulted in prompt recovery with rapid elimination of the drug ( t 1 2 − 11.2 hours , expected 45 to 118 hours). The use of MDAC in this newborn was safe and effective. We suggest that age should not pose a barrier to the use of MDAC, when indicated.

The new black magic: activated charcoal and new therapeutic uses.

Activated charcoal has been used for centuries as antidotal therapy for poisonings. New variations of charcoal therapy have developed over the last two decades. These modifications include multiple-dose activated charcoal (MDAC) therapy, charcoal hemoperfusion, and a new "superactive" charcoal (SAC). Recent literature suggests using initial charcoal therapy instead of ipecac as a first-line antidotal agent for many acute poisonings. The palatability of charcoal slurries has been enhanced by the addition of carboxymethylcellulose, sucrose, saccharin, chocolate syrup, or sorbitol. The new SAC has shown to adsorb 1.7 to 4 times the amount of substance tested compared with other activated charcoal preparations. Multiple-dose activated charcoal therapy has been shown effective in treating phenobarbital, digoxin, digitoxin, theophylline, and dapsone intoxications, among others. The problems associated with charcoal hemoperfusion therapy have been partially alleviated, and it is now alternative therapy for the seriously intoxicated patient.

Publications received

Clinical features—carbamazepine is structurally related to the tricyclic antidepressants and has similar anticholinergic features in overdose (dry mouth, coma and convulsions). In addition, drowsiness, nystagmus, ataxia and incoordination are often seen, the pupils are often dilated and divergent strabismus may be present. Complete external ophthalmoplegia has been reported. Hallucinations may occur, particularly in the recovery phase.Management—a single dose of charcoal within 1 hour of ingestion substantially reduces absorption. Multiple-dose activated charcoal (MDAC) has been shown to significantly increase elimination of carbamazepine (Boldy et al., 1987, Montoya-Cabrera, 1996). Activated charcoal should therefore be given in severe cases of carbamazepine poisoning in an initial dose of 50-100 g for adults, with repeated doses of 12.5 g/hour (or the equivalent).