++
Activated charcoal continues to be recognized as an effective method for reducing the systemic absorption of many xenobiotics.2,7,16,20,77,86,110,119,160,166 For certain xenobiotics, it also enhances elimination through interruption of either the enterohepatic or enteroenteric cycle.49 Its superb adsorptive properties theoretically make it the single most useful management strategy for diverse patients with acute oral overdoses.12, 13, and 14,26,42,49,50,79,102,173,174 However, as is true for the other methods of GI decontamination, there is a lack of sound evidence of its benefits as defined by clinically meaningful endpoints. This opinion is reflected both in the consensus statements and reviews and in the overall trend toward not performing decontamination as shown in poison center data7,31,44,110,147 (Chap. 136). The consensus opinion concluded that a single dose of activated charcoal should not be administered routinely in the management of poisoned patients and, based on volunteer studies, the effectiveness of activated charcoal decreased with time, providing the greatest benefit in severely poisoned patients if dosed within one hour of ingestion. There was no evidence that the administration of a single dose of activated charcoal improved clinical outcome. These opinions are unfortunately biased by the fact that most “routinely” poisoned patients have low-risk exposures and do well with minimal intervention. Additionally, it is generally accepted that unless either airway protective reflexes are intact (and expected to remain so) or the patient’s airway has been protected, the administration of activated charcoal is contraindicated.44 Despite little scientific basis or support from clinical trials, less severely poisoned patients might benefit from activated charcoal in terms of reduced need for life support, monitoring, and antidotes.110
++
Theoretically, the early administration of activated charcoal to patients presenting with a significant oral overdose of a potentially toxic xenobiotic would lower systemic exposure to that xenobiotic and thus be of benefit to the patient. Surprisingly, this intuitive result has been difficult to demonstrate using clinically relevant endpoints in large unselected populations of poisoned patients, again most likely as a result of inclusion of large numbers of minimally exposed low-risk individuals.
++
A randomized, controlled clinical trial of all orally overdosed patients (n = 327) presenting to the ED of a large hospital in an urban setting during 16 consecutive months found no difference in clinical endpoints such as length of stay or other outcomes between patients treated with a single dose of activated charcoal compared with no decontamination. The study excluded seven severely poisoned patients who all arrived within one hour of ingestion; the majority of the patients in the trial (nearly 60%) arrived within 2 hours postingestion. The most common xenobiotics ingested were APAP, benzodiazepines, and newer antidepressants all of which have low case-fatality rates.54
++
A larger trial (n = 4629) studying self-poisoned patients from a rural and resource-poor location found no difference in mortality rates between those who received no activated charcoal, single-dose activated charcoal, or multiple-dose activated charcoal (MDAC). The patients primarily ingested pesticides and yellow oleander (Thevetia peruviana) seeds, both xenobiotics having very different kinetic properties compared to pharmaceuticals. It is important to note that the first 1904 patients in the control group actually received orogastric lavage, as was the case for all patients presenting within 2 hours of ingestion of substantial amounts of pesticides or potentially toxic xenobiotics because of pressure from the national doctors’ union. Although the authors claim that logistic regression analysis found no influence of lavage on their results, the data are not presented.65 Furthermore, in an article on compliance related to activated charcoal, nested within this randomized, controlled trial, it is stated that a large number of patients included in the trial had undergone gastric emptying in some form before being transferred from peripheral hospitals.150 The results of this trial are probably valid for the authors’ particular setting and patient profiles but cannot be generalized to developed nations. In contrast with the lack of effect on clinical endpoints such as death, a pharmacokinetic analysis from another subset of patients (n = 104) from this large trial found a significant increase in plasma clearance of the Thevetia peruviana cardenolides in patients administered both single-dose activated charcoal and MDAC. There was no difference between groups in mortality, but given the absolute numbers of two to three deaths per group, this could be related to a lack of power in the study design.182
++
The entire effect of activated charcoal takes place in the GI tract. Oral activated charcoal is not absorbed through the GI wall but passes straight through the gut unchanged. Administration of xenobiotics may happen by a variety of routes, and these xenobiotics enter or are transported into the GI tract by different mechanisms determined by the specific physical-chemical properties of the individual xenobiotic. To be adsorbed to activated charcoal, the xenobiotic must be dissolved in the GI liquid phase and be in physical contact to the activated charcoal. The surface (internal and external) of activated charcoal is manufactured to possess a chemical nature that attracts certain molecules (xenobiotics). The possible sites of adsorption are indicated in Fig. 8–1. Activated charcoal forms an equilibrium between free xenobiotic and xenobiotic that is adsorbed to it through relatively weak intermolecular forces.
++
Free xenobiotic + Activated charcoal ⇔ Xenobiotic/Activated charcoal complex
++
Desorption of the adsorbed xenobiotic may occur, but if sufficient activated charcoal is present (see dosing below), the equilibrium will be shifted toward the xenobiotic–activated charcoal complex. The effect is a low free xenobiotic concentration in the liquid phase and reduced xenobiotic absorption.49
++
++
The general statement in the literature is that administration of a single dose of activated charcoal should be considered if a patient has ingested a potentially toxic amount of a xenobiotic that is known to be adsorbed to activated charcoal in the previous hour. This position was chosen based primarily on case reports and volunteer studies using nontoxic doses of xenobiotics because it was believed that there were insufficient data to support or exclude the use of single-dose activated charcoal therapy more than one hour beyond ingestion.43,44 However, the efficacy of activated charcoal administered more than one hour after xenobiotic ingestion has been evaluated in several studies. These investigations confirm enhanced effect of activated charcoal if dosed as early as possible but also demonstrate a significant effect if dosing is delayed up to 4 hours after the xenobiotic ingestion.75,106,109,110,116,152,202 In fact, a few studies suggest efficacy up to 6 hours after ingestion.116,236 Furthermore, prolonged gastric emptying time caused by massive xenobiotic ingestion or specific properties of an ingested xenobiotic or bezoar formation possibly increase the time frame when activated charcoal might effectively adsorb the xenobiotic.1,121 The studies below emphasize this concept.
++
In volunteers, the effect of activated charcoal administered 2 and 4 hours after ingestion of acetaminophen demonstrated no significant difference in plasma acetaminophen concentration compared with control participants. In contrast, when administered one hour after a simulated acetaminophen ingestion, activated charcoal reduced serum acetaminophen concentrations significantly.239 Likewise, when the effectiveness of activated charcoal administered 1, 2, and 3 hours after xenobiotic ingestion was determined, only the one-hour group had a pharmacokinetic profile that differed from the control group.82 Although these data do not support the administration of activated charcoal as a GI strategy more than one hour after an overdose, the applicability of these results to actual overdosed patients has not been adequately evaluated. The method in this volunteer study was an 8-hour fast followed by a small meal 1 hour before the administration of 3 to 4 g of acetaminophen.82,239 Considering the rapid absorption of acetaminophen, the small 3- to 4-g doses used, and the absence of food in the stomach, it is highly probable that little or no acetaminophen would be left in the GI tract to be adsorbed by activated charcoal, limiting the potential time to benefit from activated charcoal to approximately one hour.
++
In contrast, activated charcoal given 3 hours after an overdose was investigated in vivo, again using acetaminophen and a larger-than-standard dose (ie, 75 g) of activated charcoal. The results demonstrated some benefit in administering activated charcoal 3 hours after an overdose because there were significantly lower serum acetaminophen concentrations in the activated charcoal group than in the control group, 23% lower at 4 hours and 62% lower at 7 hours after ingestion.191 In a similar study, activated charcoal was effective in reducing the systemic absorption of acetaminophen when administered both 1 and 2 hours after ingestion, although the effect of the 2-hour intervention was substantially less than at one hour, reemphasizing the importance of early intervention.42
++
The efficacy of activated charcoal was studied in 53 patients following 63 episodes of citalopram overdose.75 When activated charcoal was administered between 0.5 and 4 hours to 17 patients who had ingested potentially toxic doses of citalopram, there was a 72% increase in clearance and a 22% decrease in bioavailability. In most patients, the activated charcoal was dosed more than one hour after ingestion. Only one patient received activated charcoal within one hour, nine patients received activated charcoal within 1 to 2 hours, and seven patients received activated charcoal within 2 to 4 hours.
++
Despite a delay to activated charcoal of 0.5 to 6.0 hours after a quetiapine overdose, a significant benefit for a single dose of activated charcoal was demonstrated. Activated charcoal decreased the fraction absorbed of quetiapine by 35%. No apparent effect on clearance was demonstrated.107 In a later study by the same investigators, only early use (<2 hours) of activated charcoal was able to reduce the probability of intubation in quetiapine overdose patients. Activated charcoal administered between 2 and 4 hours did not reduce the probability of intubation. The study included 286 patients overdosed with quetiapine alone or in combination with other drugs. However, only a total of 42 patients (15%) received activated charcoal based on unknown criteria, four patients (1%) received activated charcoal within1 hour but were excluded from analysis, 19 patients (7%) received activated charcoal within 2 hours, and 36 patients (13%) received activated charcoal within 4 hours from quetiapine ingestion.109
++
A meta-analysis was performed to evaluate the effect of activated charcoal on xenobiotic absorption during the first 6 hours after ingestion. Data were obtained from 64 controlled studies in which activated charcoal was compared with placebo up to 6 hours after drug ingestion in volunteers. Additional considerations were given to assess the influence of physical and pharmacologic properties and the activated charcoal-to-drug ratio. The authors concluded that activated charcoal was most effective when administered immediately after xenobiotic ingestion. However, even with a delay of 4 hours after ingestion, 25% of the participants achieved at least a 32% reduction in absorption, especially when activated charcoal was given with large activated charcoal-to-drug ratios.116
++
Similarly, when aminotransferase elevations (>1000 IU/L) were measured in patients with acetaminophen overdose who presented more than 4 hours after ingestion, patients who received activated charcoal along with N-acetylcysteine (NAC) had less elevation than those who received NAC alone. Although this study was limited by its observational methodology, the findings are both consistent with studies described earlier and are biologically plausable.202
++
Efforts to reduce time to activated charcoal administration have been evaluated using pre-arrival communication between a poison center and both emergency medical services and an ED.221,222 Both approaches reduced the time from overdose to activated charcoal dosing to less than one hour.
++
Thus, it should be clear that the use of a one-hour time frame should serve as a guideline rather than an absolute concept. It is only logical that if an intervention is effective at 59 minutes, it will also be beneficial at 61 minutes.Although it is logical that efficacy decreases as time from ingestion increases, in certain cases, some benefit may be derived many hours after ingestion. Because after massive life-threatening ingestions, the absorption of xenobiotics may be prolonged, there is no exact time limit for activated charcoal use.157 As discussed earlier, good data from patients with actual ingestions demonstrate that a significant amount of xenobiotic can be found in the stomach beyond this arbitrary one-hour time frame. Activated charcoal should therefore be considered to prevent absorption in poisoned patients even when they present late to medical care. Additional benefits on enhanced elimination are discussed below.
++
Adherence to the recommendation that activated charcoal should be administered within one hour of ingestion limits the potential to treat most poisoned patients. A study over a 6-month period identifying 63 patients who had taken potentially serious overdoses demonstrated a median time of arrival to health care of 136 minutes after the overdose. Only 15 patients presented within 1 hour, and only four of 10 patients who qualified actually received activated charcoal within 1 hour. The results demonstrate not only the difficulty in clinically assessing patients before1 hour but also the difficulty in adhering to the principle of treating patients with activated charcoal when they arrive within 1 hour unless activated charcoal could be safely administered to appropriate patients in the prehospitalization setting.118
++
Prehospital use of activated charcoal has not gained wide acceptance because of the concern that it would not be administered properly by the untrained lay public and that many children would refuse to drink the charcoal slurry. In fact, an 18 month consecutive case series demonstrated that activated charcoal can be administered successfully in the home by the lay public. Home use of activated charcoal significantly reduced the time to activated charcoal administration after xenobiotic ingestion from a mean of 73 ± 18.1 minutes for ED treatment to a mean of 38 ± 18.3 minutes for home treatment.201 However, many authorities still recommend that activated charcoal should not be standard home treatment, but administration should only be carried out by health professionals.10,45,141,144,156,195,196
++
A prospective follow-up study from Finland evaluated the adherence to a new protocol of administering activated charcoal in the prehospital setting. The protocol was implemented by either the first-response unit or paramedics. Activated charcoal was indicated in 722 of 2047 patients. Of these patients, 555 actually received activated charcoal at a mean of88 minutes after ingestion. There were no adverse effects noted, although 72 patients refused to drink the activated charcoal. This study shows that it is feasible to administer activated charcoal in the prehospital setting, but its clinical implications are unknown.5
++
In reality, many factors, such as the presence of food in the stomach, sustained-release formulations, and co-ingestions that delay gastric emptying, can slow the rate of absorption of a xenobiotic. These factors increase the time frame for possible adsorption to activated charcoal. This increased effect of activated charcoal was demonstrated in a randomized, crossover study in which volunteers were administered acetaminophen in either the presence or absence of the anticholinergic drug atropine and subsequently given a single dose of activated charcoal 1 hour later. Activated charcoal was more effective in reducing acetaminophen bioavailability in the presence of atropine.83
++
The optimal dose of oral activated charcoal has never been fully established. Since the beginning of its clinical use as a GI decontaminant, various factors have been recommended for determining the optimal dose of activated charcoal. Two factors commonly discussed are the patient’s weight and the quantity of the xenobiotic ingested. The problem in using the quantity of the xenobiotic as a basis for activated charcoal dosing is that the amount is usually unknown, and there is an implication that nothing else in the GI tract will occupy binding sites on activated charcoal. Additionally, the xenobiotic is often unknown, and xenobiotics vary enormously in their toxicities, rate of absorption, and the clinical effects they produce (eg, respiratory depression, convulsions, and effect on gastric emptying rate). Some xenobiotics are well adsorbed to activated charcoal, but others are not.49 Because of variables such as the physical properties of the formulation ingested (liquid, solid, or sustained-release tablet), the volume and pH of gastric and intestinal fluids, and the presence of other xenobiotics adsorbed by activated charcoal,14,18,92,95,133,162,164 the optimal dose cannot be known with certainty in any given patient.
++
Information concerning the maximum adsorptive capacity of activated charcoal for the particular xenobiotic ingested permits a theoretical calculation of an adequate dose,8,12,17,19,40,50,158,159,162,163,183,184,186,199,214,219 assuming that the amount of xenobiotic ingested is known. However, clinicians must remain cognizant of the risk of approaching or exceeding the adsorptive capacity of the standard dose of approximately 1 g/kg of body weight of activated charcoal. This possibility has been investigated in some studies.8,19,36,95,104,155,186,231
++
Thus, the idea that a fixed activated charcoal-to-xenobiotic ratio is appropriate for all xenobiotics is clearly imperfect. It is possible, however, to develop a logical approach to dosing based on available data. The effect of the activated charcoal:xenobiotic ratio is such that theoretically increasing the ratio enhances the completeness of adsorption corresponding to a higher percentage of adsorption and total amount of adsorbed xenobiotic (Fig. 8–2).157 This was confirmed by Jürgens et al., demonstrating an increasing effect of activated charcoal with increasing activated charcoal–xenobiotic dose, up to a 40:1 ratio.116 The optimal activated charcoal dose is theoretically the minimum dose that completely adsorbs the ingested xenobiotic and, if relevant, that maximizes enhanced elimination. The results of in vitro studies show that the ideal activated charcoal:xenobiotic ratio varies widely, but a common recommendation is to deliver an activated charcoal:xenobiotic ratio of 10:1, or 50 to 100 g of activated charcoal to adult patients, whichever is greater. From a theoretical perspective, this amount will adsorb 5 to 10 g of a xenobiotic, which should be adequate for most poisonings.12,13,44,49,163 In human volunteers, the acetaminophen clearance was increased with increasing doses of activated charcoal.87 Fixed doses of 50, 25, or 5 g activated charcoal were administered 1 hour after 50 mg/kgof acetaminophen was given. The apparent half-life of acetaminophen was significantly reduced from 2.5 hours for the 5 g activated charcoal dose to 1.9 hours and 1.6 hours for the 25 and 50 g doses, respectively.87 The effect of larger doses of activated charcoal, adsorbing larger amounts of xenobiotics was supported by the meta-analysis mentioned earlier.116 Based on available data from in vivo and in vitro studies, the actual recommended dosing regimen for activated charcoal is 50 to 100 g in adults (1 g/kg of body weight) and 0.5 to 1.0 g/kg of body weight in children.44,49 These recommendations are generally based more on activated charcoal tolerance than on efficacy. When calculation of a 10:1 ratio exceeds these recommendations, either gastric emptying or MDAC therapy should be considered.
++
++
For example, consider a patient who intentionally overdosed by ingesting 30 (0.25-mg) digoxin tablets (total dose, 7.5 mg). Achieving a 10:1 ratio is quite easy, and a standard dose of 1 g/kg might exceed a 10,000:1 ratio. In comparison, consider a patient who intentionally ingests 30 (325-mg) aspirin tablets (total dose, 9.75 g). In this case, obtaining a 10:1 activated charcoal:xenobiotic ratio is quite difficult and is even less likely if a patient ingests 60 or 100 of the aspirin tablets. Poisoning with a combination of xenobiotics may also approach or exceed the maximum adsorptive capacity for the standard dose of activated charcoal, and increasing the dose to reach a higher activated charcoal:xenobiotic ratio might be necessary to consider in multiple-xenobiotic poisonings.95
+++
Methods to Increase the Palatability of Activated Charcoal.
++
Activated charcoal has a pronounced gritty texture, and it immediately sticks in the throat because it adheres to the mucosal surfaces and begins to cake.49 In addition, the black appearance and insipid taste of activated charcoal make it less attractive.
++
There have been numerous attempts at making activated charcoal more appealing by providing flavors, including jam,58 chocolate syrup,142,154 cherry extract or syrup,88,168,238 cookie,122 juice,168 sorbitol,51,55,143 saccharin,52 strawberry flavor,167 orange or peppermint oil,49 melted milk chocolate,66,67 chocolate milk,39,88,168 soda,39,88,168,179 yogurt,94 and ice cream.40,93,210 The general recommendation, however, remains that activated charcoal should be mixed with water.10,115 Because activated charcoal adsorbs the flavoring agents, the palatable taste from added flavors often disappears within minutes after mixing.49,51,52,58 However, in cases in which the activated charcoal does not completely adsorb the flavoring agents, they provided a pleasant taste without significantly reducing the adsorptive properties of the activated charcoal.49,51,52,93,94
+++
Effect on Oral Therapeutics.
++
The nonspecific nature and high adsorptive capacity of activated charcoal raises concerns about the simultaneous use of orally administered therapeutics. It would be expected that therapeutics administered shortly before or simultaneously with activated charcoal would be extensively adsorbed, greatly reducing therapeutic efficacy. Restored utility of a therapeutic would be as complex and would depend on all of the factors that influence the efficacy of activated charcoal. Although there is some concern over activated charcoal limiting the efficacy of common oral antidotes such as NAC and succimer, additional concerns arise regarding the administration of oral maintenance medications. For example, activated charcoal might alter the kinetics of the new oral anticoagulants (dabigatran, apixaban, and rivaroxaban).197 The issue is described to a limited extent and not in the context of poisoning.178,203
+++
Contraindications and Complications.
++
Few clinically significant adverse effects are associated with the use of activated charcoal for poisoned patients.49,178 Adverse GI effects are most commonly described, but the frequency varies,178 and it might be difficult to differentiate from adverse effects resulting from the ingested xenobiotic.190 In a study of 24 volunteers, mild adverse effects such as abdominal fullness or constipation (46%) and nausea (17%) were most common.190 In a randomized clinical trial, vomiting was not more frequent in patients treated with activated charcoal compared with the control group, which received no activated charcoal.54 Similarly, although vomiting was observed in 22% of patients in a randomized controlled trial of 1103 patients with intentional poisoning, a nonsignificant difference in incidence was reported between patients who had or had not received GI emptying procedures.150 A prospective cohort study estimating the incidence of vomiting subsequent to the therapeutic administration of activated charcoal to poisoned children younger than 18 years of age showed that one of five of these children vomited. Children with previous vomiting or nasogastric tube administration were at highest risk.169 This incidence of vomiting appears to be greater when activated charcoal is administered with sorbitol225 and after rapid ingestion of larger doses.157
++
Pulmonary aspiration of gastric contents containing activated charcoal and inadvertent direct instillation of activated charcoal into the lungs from a misplaced nasogastric tube are rare but severe incidents54,74,198 that might lead to airway obstruction, bronchospasm, hypoxemia, aspiration, permanent lung injury, and even death.161,166 Administration of activated charcoal to already intubated patients is associated with a low incidence of aspiration pneumonia.151 In fact, pulmonary complications associated with activated charcoal aspiration might be primarily related to the aspiration of acidic gastric contents and not directly related to aspiration of activated charcoal.185 A retrospective study found that only 1.6% of unselected overdose patients aspirated and that administration of activated charcoal was not found to be an associated risk factor.106 Pulmonary aspiration in overdose patients who have received activated charcoal is more easily documented because activated charcoal is a very identifiable marker.
++
Although relatively few reports of clinically significant emesis and pulmonary aspiration resulting from the administration of activated charcoal exist, the severity of these complications is clear. Consequently, it is important to evaluate, particularly in patients determined to be at limited risk from their exposures, whether single-dose activated charcoal therapy is likely to be beneficial based on the indications and contraindications listed in Table 8–4. This is especially true in small children, in whom the risks of nasogastric tube use might outweigh the benefits of activated charcoal.
++