RRSIDEAD • Enhanced Elimination

Enhanced Elimination Overview

As with any basic and advanced life support it is important to have a systematic approach to managing toxicological emergency presentations. Pioneers in the field developed RRSIDEAD as a mnemonic to remember the key steps in Tox patient assessment and management.

E is for Enhanced Elimination


RRSIDEAD Tox Tutes: Enhanced Elimination

Listen to the Tox Tutes below and find out who gets multi-dose activated charcoal and gets plumbed up for dialysis. We also talk you through alkalisation of the urine, how and why this works and what drugs to use it for.

Tox Tute AUDIO
Tox Tute VIDEO

Toxicology Notes:

Multiple-dose activated charcoal eliminates drug in two ways:

  1. Interruption of the enterohepatic circulation, therefore it is only useful in drugs that are excreted in the bile to be reabsorbed in the distal ileum. If charcoal is present in the small intestines this may prevent reabsorption. (Need drugs with a low volume of distribution)
  2. Gastrointestinal dialysis – drugs that pass freely across the gut mucosa will travel down the concentration gradient from the relatively high intravascular compartment to the gut lumen if charcoal is used to set up this gradient. (Need drugs that are relatively small molecules, lipid soluble, low volume of distribution and low protein binding)

Questions

Q1. Which five drugs in a significant overdose should multiple-dose activated charcoal be used?

Reveal the Answer
  • Carbamazepine
  • Dapsone
  • Phenobarbitone
  • Quinine
  • Theophylline

Q2. What are the contraindications of multiple-dose activated charcoal?

Reveal the Answer
  • Decreased level of consciousness or anticipated decreased level of consciousness without prior airway protection
  • Ileus or bowel obstruction

Q3. How do you perform multiple-dose activated charcoal?

Reveal the Answer
  • Give the initial dose of charcoal (50g in adults, 1g/kg in children) PO
  • Repeat doses every 2 hours at 25g in adults and 0.5g/kg in children
  • Prior to dosing check for bowel sounds and if an nasogastric tube is in place check there are not large amounts of charcoal on aspiration.
  • If large aspirate or no bowel sounds then stop therapy.
  • Re-evaluate multiple-dose activated charcoal at 6 hours, rarely is it continued beyond this point.

Urinary alkalisation:

As you will recall from your chemistry days, acids donate hydrogen ions to for a conjugate base and a hydrogen ion usually shown by the following equation:

HA ⇔ A + H+

Strong acids completely dissociate to the right side of the equation but weak acids dissociate varying amounts, so there is an equilibrium between ionised and non-ionised(or left and right of the equation). We can take advantage of this situation in the renal tubules as the non-ionised form of an acid is more lipid soluble and conversely the ionised for is less lipid soluble. If we alkalinise the urine this drives the equilibrium to the ionised side of the equation, thus with more of the weak acid is in its ionised it can be trapped inside the renal tubules and will not be reabsorbed. This equates to more of the weak acid excreted in the urine. See the ion trapping video for a more detailed explanation and a worked example.

** Ion Trapping Explanation video

Q4. What properties must the drug have for urinary alkalinisation to be worthwhile?

Reveal the Answer
  • Weak acid (pKa >3.0)
  • Renal excretion as a major component of total excretion (as with salicylates this only occurs in overdose when systems are saturated)
  • Clinical significant toxicity

Q5. What 4 potential drugs could you alkalinise the urine for to increase excretion?

Reveal the Answer
  • Salicylates (this is the most common)
  • Phenobarbitone (sometimes done if the risk of withdrawal is low)
  • Chlorpropamide
  • Chlorphenoxy herbicides

Q6. How do you alkalinise the urine?

Reveal the Answer
  • Give 1-2 mmol/kg of sodium bicarbonate IV bolus
  • Commence an infusion of 150 mmol sodium bicarbonate in 850 ml 5% dextrose at 250ml/hr
  • 20 mmol of potassium chloride may need to be added to maintain normokalaemia. (Hypokalaemia will result in more hydrogen ions in the renal tubule as potassium and hydrogen are often interchangeable at the pump level. Less potassium available for excretion into the renal tubule results in hydrogen ion excretion and therefore the urine becomes acidotic).
  • Monitor serum bicarbonate and potassium every 4 hours
  • Regularly dipstick the urine and aim for a urinary pH >7.5
  • Continue until there is evidence toxicity is resolving

Q7. What are the contraindications and complications of urinary alkalinisation?

Reveal the Answer
  • Fluid overload
  • Hypokalaemia
  • Hypocalcaemia (usually well tolerated)

Q8. What properties does the drug have to have in order for haemodialysis to be useful in a life-threatening overdose?

Reveal the Answer
  • Small molecule
  • Small volume of distribution
  • Rapid redistribution from tissues and plasma
  • Slow endogenous elimination

Q9. Which poisons fulfill that criteria?

Reveal the Answer
  • Toxic alcohol poisoning (methanol, ethylene glycol)
  • Theophylline poisoning
  • Severe salicylate intoxication (chronic with altered mental status, late presentation acute overdose with established severe toxicity)
  • Severe chronic lithium intoxication
  • Phenobarbitone coma
  • Metformin lactic acidosis
  • Massive valproate overdose
  • Massive carbamazepine overdose
  • Potassium salt overdose with life-threatening hyperkalaemia

References

  • Position Statement and Practise Guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. Clinical Toxicology 1999; 37(6):731-751
  • Torrington CL, Johnson DW, Brant R. The frequency of complications associated with the use of multi-dose activated charcoal. Annals of Emergency Medicine 2003; 41(3):370-377
  • Ouellet GI, Bouchard J, Ghannoum M, Decker BS. Available extracorporeal treatments for poisoning: overview and limitations. Seminars in Dialysis 2014; dos: 10.1111/sdi.12238.
  • Pond SM, Olson KR, Osterloh JD et al. Randomised study of the treatment of phenobarbital overdose with repeated doses of activated charcoal. Journal of the American Medical Association 1984; 251:3104-3108
  • Proud foot AT, Krenzelok EP, Vale JA. Position paper on urine arlkalinization. Journal of Toxicology Clinical Toxicology 2004; 42:1-26
  • FAST HUGS in BED Please

LITFL Further Reading

Further Reading

toxicology library antidote 700 1

Toxicology Library

BASICS

Emergency Physician and Clinical Toxicologist who thinks that life exists outside Emergency Departments and that there is a wide and wonderful world outside the web.

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.