It is said to be one of the most dramatic demonstrations in the history of toxicology. But it may not have happened, at least not in the way it's been reported.
As the 1813 story goes, French chemist Michel Bertrand publicly swallowed 5 gm of arsenic trioxide—clearly a supra-lethal dose—mixed with activated charcoal (AC). Miraculously, he survived, and so was born the idea of using AC for oral poisoning.
This account always seemed a little fishy to me. The potentially fatal dose of arsenic is about 2.5 mg/kg. Say that Bertrand, about whom little is known, weighed 170 pounds, which would make a lethal dose 192 mg; 5 gm of arsenic trioxide would represent 26 times the lethal dose! The good chemist must have been a brave man indeed if he carried out such an experiment.
But there are other considerations. Kent Olson, MD, in a superb review of activated charcoal, suggested that the optimal weight:weight ratio of AC to poison is 40:1, rather than the commonly cited figure of 10:1 (J Med Toxicol 2010;6:190.) Because he was ingesting such a massive overdose, Bertrand would certainly have wanted to take advantage of the optimal dose of AC, which would be 200 gm. That's quite a lot. Dr. Olson reported that AC is not particularly effective at absorbing arsenic trioxide.
Lawrence K. Altman, MD, writes about Bertrand's experiment in his book, Who Goes First: The Story of Self-Experimentation in Medicine, noting that “[o]ther researchers had difficulty confirming his findings.” Dr. Altman does not supply details about these failed attempts to replicate Bertrand's results, but one imagines that they could have been an early and tragic example of “publish or perish.”
I think my initial hunch was correct, and the Bertrand demonstration of AC's effectiveness never took place as it has been described in just about every medical toxicology textbook. If it had, poor Bertrand wouldn't have stood a chance. Why does this myth persist? As newspaper reporter Maxwell Scott says at the end of John Ford's great film, “The Man Who Shot Liberty Valence:” “When the legend becomes fact, print the legend.”
Waxing and Waning
Interest in AC for toxic ingestions has waxed and waned in the two centuries since Bertrand's questionable demonstration. AC wasn't considered standard treatment in poisonings until the 1960s when it started to be used routinely in almost every patient, even if the “overdose” was clearly not significant (for example, several ibuprofen pills.) Enthusiasm for this intervention has drastically decreased in recent years. Given that AC has never been proven to improve patient-oriented outcomes, some toxicologists recommend not using it at all unless it can be given within an hour after ingestion.
David Juurlink, MD, examined this topic in 2015, devising a list of factors that would increase the appropriateness of administering a dose of AC. (Table 1; Br J Clin Pharmacol 2016;81:482.) Three of these bear comment:
Serious toxicity anticipated: The days of routinely giving charcoal to every “overdose” patient are over. Medical toxicologists almost universally agree that these situations have to be evaluated on a case-by-case basis. As Dr. Juurlink noted: Single-dose AC “should be given only to patients in whom its use can reasonably be expected to reduce morbidity (or perhaps even mortality) in a manner that exceeds its risks.”
Recent ingestion: The current position paper endorsed by the major toxicology groups in North America and Europe said giving AC “may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be absorbed to charcoal) up to one hour previously.” (Clin Toxicol 2005;43:61.) I agree with Dr. Juurlink that this strict time limitation is not backed by good data and does not make logical sense. Even if the ingested poison has passed through the pylorus after one hour, AC might still bind what remains in the small intestine.
In large overdoses or co-ingestion of drugs such as anticholinergics or opioids that inhibit gastric emptying, toxic material may remain in the stomach even hours after ingestion, and bezoars may persist for days. Several recent studies suggested that single-dose AC can improve surrogate markers of toxicity even if given hours after ingestion. Giving a single dose of AC is relatively safe in the absence of contraindications, and the strict one-hour time limit should be abandoned.
Alert, cooperative patient: Single-dose AC has never been proven to improve patient outcomes, and the clinician should never feel it is mandatory. It is never appropriate to struggle with an uncooperative patient to get him to take a dose or to instill AC through an NG tube (unless the patient is already intubated.) It would also be reasonable to avoid giving AC if there is concern the patient's airway is not intact or that it might become unstable.
My bottom line: If there is a theoretical benefit to administering AC, but I'm concerned that it may be risky, I don't give it. If I think giving charcoal is safe but am not sure if it will provide benefit, I give it.
Factors that Cumulatively Increase the Appropriateness of Single-Dose AC
- Serious toxicity anticipated
- Recent ingestion
- Alert, cooperative patient
- Intact airway
- Lack of a specific antidote
- Favorable stoichiometry (mass of charcoal:mass of drug > 40:1)
- Ingestion of a modified release product
- Substance known to adsorb to activated charcoal
- Absence of ileus or intestinal obstruction
Source: Br J Clin Pharmacol 2016;81(3):482.
Contraindications to Administering Activated Charcoal
- Unprotected airway
- Depressed mental state (unless already intubated)
- Increased potential for harm from aspiration (e.g., hydrocarbons)
- Need to visualize upper GI tract (e.g., corrosive ingestion)
- Risk of gastrointestinal hemorrhage or perforation (e.g., recent surgery)
- Uncooperative patient
Adapted from Clin Toxicol 2005;43(2):61.Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.