Toxicology – Enhanced Elimination Techniques II

Hemofiltration

Mechanism of Action

Hemofiltration passes blood through a semipermeable membrane, removing water and dissolved substances by convection.

It can remove:

• Certain toxicants
• Electrolytes
• Urea and creatinine
• Some therapeutic medications

Continuous renal replacement techniques provide slower, prolonged clearance. Because treatment continues while a toxicant redistributes from tissues into the bloodstream, they may reduce post-treatment rebound.

Potential Indications

Hemofiltration may be considered for selected severe poisonings involving substances with:

• Relatively small volume of distribution
• Low endogenous clearance
• Suitable molecular size

It has occasionally been used for substances such as:

• Lithium
• Certain aminoglycosides

However, for many dialyzable poisons, intermittent hemodialysis provides substantially faster clearance and is preferred when the patient can tolerate it.

Advantages

• Continuous and gradual removal
• Better tolerated than intermittent hemodialysis in some hemodynamically unstable patients
• Useful when continuous renal replacement therapy is already required for renal failure

Limitations / Complications

• Slower toxicant clearance than conventional hemodialysis
• Fluid and electrolyte disturbances
• Vascular-access complications
• Bleeding or anticoagulation-related complications

Key Point

Modern continuous renal replacement therapy can be useful when conventional hemodialysis is poorly tolerated, but slower clearance makes it unsuitable as a direct substitute for rapid hemodialysis in many severe poisonings.

Multiple-Dose Activated Charcoal (MDAC)

Mechanism of Action

Multiple-dose activated charcoal involves repeated administration of charcoal to increase elimination of certain already-absorbed toxicants.

It works mainly through two mechanisms:

• Interrupting enterohepatic/enteric recycling: drugs secreted back into the GI tract are bound by charcoal before they can be reabsorbed.
• “Gastrointestinal dialysis”: some drugs diffuse from the bloodstream across the intestinal wall into the GI lumen, where charcoal traps them.

This maintains a concentration gradient favoring movement of the toxicant from blood into the intestine.

Best Candidates

MDAC is most effective for drugs that:

• Bind strongly to activated charcoal
• Have relatively small volumes of distribution
• Remain in the circulation long enough for enhanced GI elimination

The classic drugs for which MDAC may meaningfully enhance elimination include:

• Carbamazepine
• Dapsone
• Phenobarbital
• Quinine
• Theophylline

Enhanced elimination has been demonstrated for several other substances, but evidence that this improves clinical outcomes is more limited.

Contraindications

MDAC should generally be avoided with:

• Unprotected airway or high aspiration risk
• Ileus
• Bowel obstruction
• GI perforation

Complications

• Vomiting
• Aspiration pneumonitis
• Constipation
• Bowel obstruction or charcoal impaction
• Fluid and electrolyte disturbances, particularly when cathartics are repeatedly administered

Important Precaution

Repeated cathartic administration should be avoided because it can cause dangerous fluid and electrolyte losses, especially in children.

Key Points

• MDAC is an enhanced elimination technique, not simply repeated GI decontamination.
• Remember the classic MDAC drugs: carbamazepine, dapsone, phenobarbital, quinine, and theophylline.
• The airway must be protected before charcoal is considered in a patient with significant CNS depression.
• Ileus or bowel obstruction substantially increases the risk of complications.
• Continuous hemofiltration provides slower clearance than intermittent hemodialysis but may be useful when hemodynamic instability limits conventional dialysis.