Principles Of Enhanced Elimination


Enhanced Elimination: Drug Characteristics and Examples
TECHNIQUE DRUG CHARACTERISTIC EXAMPLES
Multiple-dose activated charcoal Enterohepatic circulation Phenobarbital
Carbamazepine
Theophylline
Aspirin
Dapsone
Urinary alkalinization Weak organic acid with renal excretion Aspirin
Phenobarbital
Formic acid
Hemodialysis Low molecular weight, low plasma protein binding, small volume of distribution, poor endogenous clearance
OR
Acidosis caused by toxin
Lithium
Aspirin
Alcohols
+/- Digoxin

Metformin

Charcol Hemoperfusion

Background

  • Enhances elimination of various drugs in overdose

Indications

  • Toxins that are absorbed by an absorbent, low Vd, low molecular weight
  • Less dependent on water solubility (vs. dialysis)
  • Preferred over dialysis in high protein binding drugs
  • Drugs
    • Phenobarbital, glutethimide, theophylline, paraquat
    • Carbamazepine, carbon tetrachloride, chloral hydrate, clonidine, diltiazem
    • Ethylene oxide, levothyroxine, meprobamate, parathion, pheytoin, quinidine
    • Thallium, theophylline, valproic acid, verapamil

Contraindications

  • Do not delay other treatment if not readily available

Cautions

  • Invasive: requires central access
  • Requires anticoagulation

Procedure

  • Consult nephrology

Complications

  • Bleeding, hypotension, infection, air embolism
  • Leukopenia, thrombocytopenia, hypocalcemia

Urinary Alkalinization

Background

  • Diuresis in overdose pt may increase elimination of some drugs
  • Weakly acidic drugs' elimination increased by ion trapping in urine (alkalinization)

Indications

  • Forced saline diuresis may be indicated with
    • Metals: barium, iodine/iodide, chromium, nickel, cis-platinum, thallium
    • Cyclophosphamide, hydrazine, INH, meprobamate, mushrooms (grp. 1)
  • Urinary alkalinization
    • Drugs w/ low pKa, moderate to severe toxicity, good baseline renal function
    • Salicylates, phenobarbital, chlorpropamide, flouride, INH, methotrexate, MCPA
    • Quinolones, uranium, sufisoxazole, 2,4-dichlorophenoxyacetic acid (2,4-D)
    • Barbital (serum levels >10 mg/dL), mephobarbital, primidone

Contraindications

  • Intense fluid resuscitation in toxic pt not clinically indicated for most OD's
  • Urine acidification never indicated
  • Rhabdomyolysis: no clinical evidence to support benefit for renal function (alkalinization)
    • Increased fluid load may be protective however

Cautions

  • Must watch fluid balance closely
  • Difficult to achieve alkaline urine with severe toxicity

Procedure

  • Forced diuresis: maintain urine output 3-5 mL/kg/hr
    • IVF D5W at 250 mL/hr
    • After volume replacement add 25 g mannitol/40 mg furosemide if anuric
    • Avoid NSAIDs; unfavorably alters renal hemodynamics
  • Urine alkalinization
    • Alkalinization is accomplished via a sodium bicarbonate (NaHCO3) infusion.
    • The most common method uses 150 mEq of NaHCO3 (3 amps) in 1 L D5W, infused at 1.5 - 2 x the normal IV fluid maintenance rate.
      •  Na HCO3 8.4% (1mEq/ml) @ 50 cc/hr
    • NaHCO3 1-2 mEq/kg [1-2 mmol/L] IV over 5 min then
    • IV drip: 2-3 amps NaHCO3 to 1 L D5W at 200 mL/hr IV
    • May need to add 20-40 mEq/L [20-40 mmol/L] KCl (normal renal function only)
      • Hypokalemic pts can't alkalinize urine
    • Titrate to pH 7-8

Complications

  • Increase risks of pulmonary edema, hyponatremia, incr ICP
  • Worsens SIADH
Clinical Pearls
  • Urinary alkalinization will not occur unless hypokalemia is corrected.
  • Urinary alkalinization is used for weak organic acids: Aspirin, phenobarbital, formic acid (methanol metabolite).

Hemodialysis

Background

  • Patients may benefit from hemodialysis (and other extracorporeal elimination techniques) after poisonings under specific conditions
  • USA: improved supportive care and novel antidotes has decreased use of hemodialysis (HD) after poisonings
  • HD should be initiated in consultation with a nephrologist

Indications

  • Agent specific
  • In general, the following conditions suggest that extracorporeal elimination techniques may play a role in a chemical exposure
    • Patients in whom the normal route of elimination is impaired
    • Patients with a concomitant acid-base or electrolyte abnormality
    • Poisonings in which the use of HD has a demonstrated survival benefit
  • The following pharmacokinetic properties of a chemical favor success with hemodialysis
    • Low volume of distribution or HD is initiated during the absorptive phase of the poisoning
    • Low protein-binding
    • Low molecular weight
      • Classically < 500 Daltons
      • With modern high-efficiency dialysis membranes < 10,000 Daltons
  • Drugs traditionally considered amenable to HD
    • Ethylene glycol
    • Lthium
    • Methanol
    • Metformin (with lactic acidosis)
    • Salicylates
    • Theophylline
    • Valproate
  • Drug poisonings in which extracorporeal elimination has been used successfully
    • Aminoglycosides
    • Atenolol
    • Carbamazepine
    • Carisoprodol
    • Chloral hydrate
    • Disopyramide
    • Ethanol, ethchlorvynol, isopropanol, trichloroethanol
    • Meprobamate
    • Methotrexate
    • Mushroom ingestion
    • Paraquat
    • Phenobarbital
    • Phenothiazines
    • Phenytoin
  • Chronic or acute-on-chronic poisoning of drugs that accumulate in extravascular compartments
    • May benefit from combining HD with continuous renal replacement therapy to prevent rebound serum level increases
      • Lithium is an example of such a poisoning

Contraindications/Cautions

  • Patients undergoing HD typically require anticoagulation
  • Patients undergoing HD require surgical placement of a dialysis catheter
  • Hypotensive patients may not be able to tolerate significant fluid shifts during HD
  • Invasive: requires central access
  • Requires anticoagulation

Materials

  • Materials required for HD are typically supplied by the nephrology consultant

Procedure

  • Consult nephrology
  • The HD procedure is typically arranged and administered by a nephrology consultant
  • Peritoneal dialysis should only be considered with Vancomycin or Boric Acid

Complications

  • Bleeding at the HD catheter site
  • Hypotension
  • Dialysis Dementia
    • Aluminum toxicity manifesting as encephalopathy after exposure to high-aluminum dialysate
    • Rare with modern HD technologies
  • Bacterial infection from contaminated dialysate
    • Rare with modern HD technologies