This chapter provides a description of the mechanism, indications, contraindications, and pitfalls for each of the following elimination procedures: cardiopulmonary bypass, exchange transfusion, hemodialysis, hemoperfusion, hemofiltration, multiple-dose activated charcoal, peritoneal dialysis, urinary alkalinization, urinary acidification
Cardiopulmonary bypass (CPB) provides hemodynamic support, allowing endogenous hepatic or renal clearance of the poison. It essentially "buys time" until patients can detoxify themselves.
CPB allows continued clearance of therapeutic drugs, as well.
CPB is generally performed in cases of severe overdose with hemodynamic instability from a toxicant that is normally cleared by the liver. The two drugs it has been most successful in eliminating are lidocaine and flecainide.
Contraindications and Adverse Effects
The attendant risks associated with central venous access and anticoagulation.
It is important to anticipate the need for this procedure and obtain consultation early because:
- CPB requires the involvement of other specialists to initiate.
- CPB is not useful if the patient has hepatic failure.
Serial phlebotomy and transfusion such that the patient's blood is gradually replaced with banked blood.
This procedure eliminates substantial amounts of most therapeutic drugs.
Exchange transfusion is generally performed in cases of:
- severe methemoglobinemia where the patient is unresponsive to methylene blue therapy.
- severe intoxication of an infant or neonate in whom other methods (e.g., hemodialysis and hemoperfusion) cannot be used.
- toxicant-induced massive hemolysis.
Contraindications and Adverse Effects
- The patient may experience transfusion reaction, hypothermia, hypotension, or hypocalcemia or may acquire a blood-borne infection (e.g., hepatitis).
- Thrombocytopenia and coagulopathy can develop if components other than red blood cells are not replaced appropriately.
Exchange transfusion eliminates only those substances whose distribution is limited primarily to the blood volume.
Toxicants diffuse through a semipermeable membrane down a concentration gradient from blood to dialysate.
This procedure eliminates those poisons with low molecular weight, limited protein binding, and small volume of distribution.
Hemodialysis is generally performed in cases of:
- severe intoxication with water-soluble substances of molecular weight less than 500 daltons, limited plasma protein binding, and low volume of distribution (less than 1 L/kg). Some of these substances include alcohols, bromides, chloral hydrate, ethylene glycol, lithium, methanol, potassium, procainamide, quinidine, salicylate, and theophylline, among others.
- severe acidosis where the patient is unresponsive to therapy.
- severe intoxication with a substance normally eliminated by the kidney in the setting of renal failure (e.g., potassium).
Although elimination of poisons such as ethanol, isopropanol, phenobarbital, acetaminophen, and many others is increased, hemodialysis is rarely needed for these substances.
Contraindications and Adverse Effects
Hypotension, fluid and electrolyte disturbance, seizure, and the attendant risks associated with central venous access and systemic heparinization.
- It is important to anticipate the need for this procedure and obtain consultation early because the initiation of hemodialysis requires the involvement of other specialists.
- Ethanol and fomepizole, used as antidotes, are also eliminated by hemodialysis. Additional doses should be administered as indicated in the Ethanol and Fomepizole chapters.
- Blood levels of toxicants may rebound after termination of dialysis. Repeated dialysis sessions may be required.
- Hemodialysis cannot be performed in severely hypotensive patients and should be initiated before intoxication becomes life threatening.
Blood perfuses across an activated charcoal cartridge, which adsorbs the poison.
This procedure also eliminates therapeutic drugs with a low volume of distribution and which are adsorbed by charcoal.
Hemoperfusion is generally performed in cases of severe intoxication of drugs with a low volume of distribution (less than 1 L/kg), low endogenous clearance, and which are adsorbed by activated charcoal. It is most commonly used for theophylline, carbamazepine, phenobarbital, and procainamide.
Contraindications and Adverse Effects
- The attendant risks associated with central venous access and systemic anticoagulation.
- Thrombocytopenia often limits the duration of hemoperfusion.
- It is important to anticipate the need for this procedure and obtain consultation early because the initiation of hemoperfusion requires the involvement of other specialists.
- In most facilities, hemodialysis can be initiated much more rapidly and is usually preferred (even if hemoperfusion attains higher clearance rates under ideal conditions).
- Hemoperfusion does not correct acidemia or electrolyte abnormalities.
- Blood levels of toxicants may rebound after termination of hemoperfusion. Repeated sessions may be required.
- Hemoperfusion cannot be performed in severely hypotensive patients, and it should be initiated before intoxication becomes life threatening.
- Blood is pumped through numerous hollow fiber filters with semipermeable membranes. The toxicants are then slowly filtered out along with water, electrolytes, urea, and creatinine.
- The patient's blood pressure can be used as the pump, and hemofiltration can be performed continuously, minimizing rebound as the toxicant redistributes from peripheral tissues.
This procedure also will eliminate many therapeutic drugs.
Hemofiltration is generally performed in cases of:
- serious intoxication with compounds having a low volume of distribution (less than 1 L/kg), low endogenous clearance, and a molecular weight of less than 10,000 or 40,000 daltons (depending on the hemofilter).
- lithium and aminoglycosides intoxication, but only occasionally.
Contraindications and Adverse Effects
- The attendant risks associated with central venous access and systemic anticoagulation. However, some hemofilters do not require anticoagulation.
- Elimination rates are much lower than with hemodialysis or hemoperfusion.
- Fluid and electrolyte disturbances can develop.
- Hemofiltration is a relatively new technique; its utility is not well established.
- It is important to anticipate the need and obtain consultation early because initiation of hemofiltration requires the involvement of other specialists.
- Hemofiltration cannot be performed in severely hypotensive patients, and it should be initiated before intoxication becomes life threatening.
MULTIPLE-DOSE ACTIVATED CHARCOAL
- Repeated administration of activated charcoal may enhance elimination of the toxicant by adsorbing either the drug or the metabolite that is secreted in bile (interrupting enterohepatic recirculation).
- Alternatively, toxicant may diffuse across the intestinal wall down the concentration gradient from mesenteric vasculature into the gastrointestinal lumen, where it can be adsorbed by activated charcoal (gastrointestinal dialysis).
- Most effective for drugs that undergo substantial enterohepatic recirculation or those that have small volumes of distribution, low protein binding, and are highly adsorbed by activated charcoal.
May increase elimination of other drugs with same characteristics.
Multiple-dose activated charcoal has been used in cases of:
- Theophylline intoxication.
- Increasing elimination of phenobarbital, phenytoin, carbamazepine, quinine, dapsone, cardiac glycosides, valproate, and meprobamate intoxications. However, it has not been shown to affect the outcome for any of these poisonings.
Contraindications and Adverse Effects
- Ileus, bowel obstruction, or perforation
- Bowel obstruction or impaction, pulmonary aspiration, and fluid and electrolyte disturbances from multiple doses of cathartic
- The risk of aspiration, obstruction, impaction, and fluid and electrolyte imbalance often outweigh the potential benefit.
- Never administer multiple doses of cathartics, especially to children, because fatal fluid and electrolyte disturbances may occur.
Aqueous dialysate is instilled into the peritoneal cavity. The toxicant then diffuses down the concentration gradient from blood to dialysate across the peritoneum.
This procedure eliminates therapeutic drugs that are water soluble and have a low volume of distribution, molecular weights of less than 500 daltons, and low protein binding.
Peritoneal dialysis is generally performed in cases of:
- severe intoxication with water-soluble toxicants that have a low volume of distribution (less than 1 L/kg), a molecular weight less than 500 daltons, and low protein binding. However, in most cases, hemodialysis is the preferred procedure.
- severe intoxication of an infant or neonate in whom other methods (e.g., hemodialysis and hemoperfusion) cannot be used.
- patients being transferred to a facility where hemodialysis or hemoperfusion is available because it may be useful as an initial procedure.
- methanol, ethylene glycol, salicylate, and theophylline intoxication when other methods are not available.
Contraindications and Adverse Effects
- There is a risk of peritonitis, bowel injury, fluid and electrolyte disturbance, hypotension, and volume overload.
- Previous abdominal surgery or adhesions may make insertion of a peritoneal catheter difficult.
- Contraindicated in pregnancy.
- It is important to anticipate the need and obtain consultation early because the initiation of peritoneal dialysis may require the involvement of other specialists.
- It is ineffective in severely hypotensive patients, and it should be initiated before intoxication becomes life threatening.
Sodium bicarbonate is administered to raise the urine pH above 7.5. Drugs in which the parent compound is a weak acid with a pKa below 7.0 and which undergo significant urinary excretion become ionized in the kidney tubular fluid and are "trapped" because ionized forms do not readily cross cell membranes.
This procedure eliminates other therapeutic drugs with similar characteristics.
Urinary alkalinization is generally performed in cases of:
- mild to moderate salicylate intoxication.
- increasing elimination of phenobarbital, chlorpropamide, and 2,4-dichlorophenoxyacetic acid. However, it has not been shown to affect the outcome of any of these poisonings.
- preventing nephrotoxicity with a high dose of methotrexate.
Contraindications and Adverse Effects
- Urinary alkalinization is contraindicated in renal failure.
- Complications include volume overload, congestive heart failure, alkalosis, hypokalemia, and hypomagnesemia.
Urinary alkalinization should be used for mild to moderate intoxication only. Hemodialysis is the preferred procedure in patients with serious intoxication.
Urine pH is manipulated below the pKa of compounds that are weak bases. The ionized molecule is "trapped" in the kidney tubule because ionized forms do not readily cross cell membranes.
There are no indications to use this procedure. The risk of systemic acidemia, worsening acute tubular necrosis from precipitation of hemoglobin, or myoglobin in tubules far outweighs any benefits.