Question 29

Last updated 21/04/2017 - 00:37
 Topic: Pharmacology and Toxicology
Pass rate
69%
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A 16 year old female is admitted to the ICU following a multiple drug overdose.

a)Outline  the  role  of  activated  charcoal  in  the  management   of  drug overdose.

b) What are the complications of activated charcoal therapy?

c) When is dialysis utilised in toxic syndromes?

d) In   the   context   of   an   overdose,   list   3  drugs   for   which   charcoal haemoperfusion may be useful.

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College Answer

a)         Outline  the  role  of  activated  charcoal  in  the  management   of  drug overdose.

•          Single dose activated charcoal is generally preferred method of decontamination but does not improve outcome when applied to unselected patients and should not be regarded as routine.

•          Indicated when likely that toxic agent is still within the GI tract (1st hour for most agents) and potential benefits outweigh risks.

b)         What are the complications of activated charcoal therapy?

•           Vomiting
•          Pulmonary aspiration
•          Direct administration to lung via misplaced NG tube (potentially fatal)
•          Impaired absorption of oral medications / antidotes
•          Corneal abrasions
•          Constipation / bowel obstruction (MDAC)

c)         When is dialysis utilised in toxic syndromes?

•          Best if drug is:
•          Water soluble
•          MW <500
•          Not highly protein bound
•          Eg Lithium, Ethylene glycol, Salicylates, Na Valproate
•          Also good for correcting fluid and electrolyte abnormalities

d)         In   the   context   of   an   overdose,   list   3  drugs   for   which   charcoal haemoperfusion may be useful.

•          Common drugs carbamazepine, theophylline, paraquat

Discussion

a)

Rationale for the use of activated charcoal

  • Activated charcoal is the product of the pyrolysis (i.e. decomposition by heat and in the absence of oxygen ) of organic matter. It is "activated" by a series of processes, among them heating it in steam or CO2 at a temperature of 600 Cº, washing with organic acids and drying with hot air. The activation process produces a highly porous substance with a massive surface area, up to 2000m2/g (LITFL quotes 3000 m2/g)
  • Once activated, charcoal can act as a broad-spectrum gastrointestinal adsorbent (Andersen, 1948)
  • Its highest affinity is for compounds with a molecular weight of 100–1000 Da (Krenzelok, 2002)
  • Many pharmacologically active substances fall within this range.
  • Most lifethreatening overdoses are by ingestion.
  • Many such overdoses may present early.
  • Gastric emptying rate may be affected (slowed) by the toxin itself.
  • Ergo, giving charcoal early may reduce the absorption of the drug.

Single-dose activated charcoal

  • Time is the most important factor determining efficacy.
  • If the poison is not in the stomach, single-dose activated  charcoal will be useless.
  • Otherwise, activated charcoal should probably be given soon after most significant ingestions:
    • The frequency of serious complications is low
    • The worst thing that would usually happen is that it simply does not work
    • After a drug is absorbed, there are few effective techniques to enhance its elimination
    • Efficacy is inversely related to the time elapsed after the ingestion. The longer you deliberate about the usefullness of charcoal, the more useless the charcoal becomes. Stop wasting time and just give it
    • This pragmatic why-not-have-a-go approach was championed by Isbister and Kumar in their 2011 recommendation paper for Current  Opinion in Critical Care.
  • However:
    • At least one RCT did not demonstrate any benefit (Eddleston, 2002)
    • In fact, the ED stay was longer, and there was more vomiting.
    • Several similar studies have confirmed a relative lack of benefit in unselected patients
    • On this basis of this, the AACT/EAPCCT recommendation in 2004 was not to give single dose charcoal unless it is clearly within 1 hour of the overdose, and unless the drug is well known to adsorb onto charcoal. In short, they were against the random use of charcoal for the undifferentiated overdose.
    • This recommendation cannot be generalised to the severely intoxicated ICU population, as the major risk from charcoal is aspiration, and if your airway is protected with a big tube, that risk is minimal.

Multiple doses of activated charcoal

The rationale for multiple-dose charcoal is slightly different. It's not a matter of "just give more of it for more effect".

  • Many drugs are excreted via the bile, and undergo extensive enterohepatic recirculation.
  • Multiple dose choarcoal ensures that the cycle of recirculation is interrupted (i.e. the excreted drug is bound by charcoal instead of beaing reabsorbed).
  • In this manner, it is a method of enhanced elimination.

The following is a list of well-accepted indications for multiple dose activated charcoal (from Pierre Gaudrealt, 2005)

  •  Amitriptyline
  • Carbamazepine
  • Cyclosporine
  • Dapsone
  • Dextropropopxyphene
  • Digitoxin
  • Digoxin
  • Disopyramide
  • Nadolol
  • Phenobarbital
  • Phenylbutazone
  • Phenytoin
  • Piroxicam
  • Propoxyphene
  • Quinine
  • Sotalol
  • Theophylline

Substances for which activated charcoal is known to be ineffective

Drugs which are absorbed too rapidly

  • Ethanol
  • Paraquat

Drugs which do not adsorb on to charcoal

  • Corrosive substances, eg. strong acids and alkalis,
  • Iron
  • Lithium.

b)

Complications of charcoal administration

  • Its gross. Patients complain. However, actual vomiting appears to be rare (Isbister et al, 2011)
  • It may absorb usueful medications as well as the toxin.
  • It may increase the risk of aspiration (but if it does, then not y much)
  • Aspirated, it may be more harmful than sterile gastric contents (but if it is, then not by much). In their answer to Question 29 from the second paper of 2010, the college lists direct administration of charcoal into the lung as a valid concern.
  • It may cause bowel obstruction; this is rare, and usually associated with multiple dose charcoal in patients who are poisoned with an agent which affects gut motility.

c)

Use of dialysis in toxicology:

  • the drug is easily dialysed:
    • small molecule
    • water soluble
    • not extensively protein bound
    • small volume of distribution
  • The drug produces dialysable matabolites, which are toxic (eg. ethylene glycol)
  • The toxicity produces an acid-base disturbance which cannot be addressed by any other means (eg. lactic acidosis in cyanide toxicity)

d)

  • Paraquat
  • Parathion
  • Theophylline
  • Carbamazepine
  • Phenytoin
  • Paracetamol
  • Digoxin
  • Diltiazem
  • Metoprolol
  • Colchicine
  • Promethazine
  • Amanita phalloides mushroom toxin (phalloidin)

References

The website of the American Academ of Clinical Toxicology has several position statements which might be useful to the fellowship candidate:

Ipecac Syrup

Single-Dose Activated Charcoal

Multi-Dose Activated Charcoal

Cathartics

Whole Bowel Irrigation

Gastric Lavage

Urine Alkalization

Gaudreault, Pierre. "Activated charcoal revisited." Clinical Pediatric Emergency Medicine 6.2 (2005): 76-80.

Andersen, A. Harrestrup. "Experimental Studies on the Pharmacology of Activated Charcoal. III. Adsorption from Gastro‐Intestinal Contents." Acta Pharmacologica et Toxicologica 4.3‐4 (1948): 275-284.

Krenzelok, Edward P. "New developments in the therapy of intoxications." Toxicology letters 127.1 (2002): 299-305.

Eddleston, Michael, et al. "Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial." The Lancet 371.9612 (2008): 579-587.

Isbister, Geoffrey K., and Venkata V. Pavan Kumar. "Indications for single-dose activated charcoal administration in acute overdose." Current opinion in critical care 17.4 (2011): 351-357.

Chyka, P. A., and D. Seger. "Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists." Journal of toxicology. Clinical toxicology 35.7 (1996): 721-741.

Harris, Carson R., and Dean Filandrinos. "Accidental administration of activated charcoal into the lung: aspiration by proxy." Annals of emergency medicine22.9 (1993): 1470-1473.

Chyka, P. A., and D. Seger. "Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists." Journal of toxicology. Clinical toxicology 35.7 (1996): 721-741.

Isbister, Geoffrey K., and Venkata V. Pavan Kumar. "Indications for single-dose activated charcoal administration in acute overdose." Current opinion in critical care 17.4 (2011): 351-357.

Harris, Carson R., and Dean Filandrinos. "Accidental administration of activated charcoal into the lung: aspiration by proxy." Annals of emergency medicine22.9 (1993): 1470-1473.

UpToDate has a nice table of drugs which are removed by haemoperfusion.

Nenov, Vesselin D., et al. "Current applications of plasmapheresis in clinical toxicology." Nephrology dialysis transplantation 18.suppl 5 (2003): v56-v58.

Holubek, William J., et al. "Use of hemodialysis and hemoperfusion in poisoned patients." Kidney international 74.10 (2008): 1327-1334.

Ghannoum, Marc, et al. "Hemoperfusion for the treatment of poisoning: technology, determinants of poison clearance, and application in clinical practice." Seminars in dialysis. Vol. 27. No. 4. 2014.

Ghannoum, Marc, et al. "Blood purification in toxicology: nephrology’s ugly duckling." Advances in chronic kidney disease 18.3 (2011): 160-166.

Takki, S., et al. "Pharmacokinetic evaluation of hemodialysis in acute drug overdose." Journal of pharmacokinetics and biopharmaceutics 6.5 (1978): 427-442.

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