A) SUMMARY
1) Appropriate use of techniques to enhance elimination of toxins depends on specific knowledge of chemical properties (pKa, molecular size), active forms, kinetics (volume of distribution, metabolism and route of elimination), and protein binding. All of these techniques have inherent risks and should not be utilized unless specifically indicated.
B) DIURESIS
1) FORCED DIURESIS: May be useful in serious poisonings if the drug is excreted in the urine in active form. The technique should not be used unless it is specifically indicated, as it may increase the problem of pulmonary or cerebral edema, common complications in the poisoned patient.
a) Hypertonic or pharmacologic diuretics should be given along with adequate fluids. Usual urine flow is 0.5 to 2 milliliters/kilogram/hour and with forced diuresis should be 3 to 6 milliliters/kilogram/hour.
b) Forced diuresis may enhance the excretion of lithium, bromides, and other drugs excreted primarily by the kidneys.
2) URINARY ALKALINIZATION/EFFICACY
a) ALKALINE DIURESIS: is effective in enhancing the elimination of drugs in which (1) significant amounts of the drug are excreted in the urine, and (2) the drug's Pka is such that urinary alkalinization will trap ionized drug in the tubular lumen and prevent reabsorption.
1) ALKALINE FORCED DIURESIS: May enhance the excretion of acidic agents: barbiturates, isoniazid, and salicylates.
3) SODIUM BICARBONATE/INITIAL DOSE
a) Administer 1 to 2 milliequivalents/kilogram of sodium bicarbonate as an intravenous bolus. Add 132 milliequivalents (3 ampules) sodium bicarbonate and 20 to 40 milliequivalents potassium chloride (as needed) to one liter of dextrose 5 percent in water and infuse at approximately 1.5 times the maintenance fluid rate. In patients with underlying dehydration additional administration of 0.9% saline may be needed to maintain adequate urine output (1 to 2 milliliters/kilogram/hour). Manipulate bicarbonate infusion to maintain a urine pH of at least 7.5.
4) SODIUM BICARBONATE/REPEAT DOSES
a) Additional sodium bicarbonate (1 to 2 milliequivalents per kilogram) and potassium chloride (20 to 40 milliequivalents per liter) may be needed to achieve an alkaline urine.
5) CAUTION
a) Obtain hourly intake/output and urine pH. Assure adequate hydration and renal function prior to alkalinization. Do not administer potassium to an oliguric or anuric patient. Monitor fluid and electrolyte balance carefully. Monitor blood pH, especially in intubated patients, to avoid severe alkalemia.
6) Osmotic load is also important and either type of diuretic should be given at intervals. Proximal reabsorption may occur if adequate osmotic load is not maintained in the tubule.
7) CAUTION: Assure adequate hydration and renal function prior to alkalinization. Never give potassium to an oliguric patient. Follow serum calcium, phosphorus and magnesium during alkalinization.
8) ACID FORCED DIURESIS: NO longer recommended for ANY agent including amphetamines, strychnine, and phencyclidine.
C) DIALYSIS
1) May be considered in those patients not responding to standard therapeutic measures to treat a dialyzable toxicant. It also may be considered a part of supportive care whether the toxicant is or is not dialyzable to treat the following: Stage 3 or 4 coma or hyperactivity caused by a dialyzable agent which cannot be treated by conservative means, marked hyperosmolality which is not due to easily corrected fluid problems, severe acid base disturbance not responding to therapy, or severe electrolyte disturbance not responding to therapy. Most effective in intoxication from chemicals with a volume of distribution of less than 1 liter/kilogram, which have low endogenous clearance, are not highly protein bound, are water soluble and have a molecular mass less than 500 (Pond, 1991).
2) DEFINITE INDICATIONS: Dialysis should be initiated, regardless of clinical condition, in the following situations - following heavy metal chelation in patients with renal failure, following significant ethylene glycol or methanol ingestion.
3) PROBABLE INDICATIONS: Dialysis is indicated in patients with severe intoxications with the following agents. The need for dialysis is based more on the patient's clinical condition than on specific drug levels. See specific drug managements for more detailed information.
1) lithium
2) phenobarbital
3) salicylate
4) theophylline
4) POSSIBLE INDICATIONS: Dialysis MAY be initiated following exposure to the following agents, if clinical condition deems the procedure necessary (patient deteriorating despite intense supportive care):
1) alcohols
2) amphetamines
3) anilines
4) antibiotics
5) boric acid
6) barbiturates
7) bromides
8) calcium
9) chlorates
10) chloral hydrate
11) ethanol
12) iodides
13) isopropanol
14) isoniazid
15) meprobamate
16) paraldehyde
17) fluorides
18) potassium
19) quinidine
20) quinine
21) strychnine
22) thiocyanates
5) RARE INDICATIONS: There is NO indication for dialysis, other than as a supportive measure in the presence of renal failure, following exposure to
1) acetaminophen
2) antidepressants
3) antihistamines
4) belladonna compounds
5) benzodiazepines
6) digitalis and related agents
7) glutethimide
8) hallucinogens
9) heroin and other opioids
10) methaqualone
11) phenothiazines
12) synthetic anticholinergics
D) EXTRACORPOREAL ELIMINATION
1) PERITONEAL DIALYSIS/EXCHANGE TRANSFUSION - May be more useful in small children than hemodialysis. The main point of these procedures may not be for removal of poison but restoration of fluid or acid-base balance. The infant who has been poisoned and whose serum sodium is rising because of excessive bicarbonate may be helped considerably by an exchange even if little poison is removed.
E) HEMOPERFUSION
1) Hemoperfusion may be more effective than dialysis in removing substances with larger molecular weights, poor water solubility or significant protein binding. Toxicants most effectively cleared by hemoperfusion have a volume of distribution less than 1 Liter/kilogram, are adsorbed by activated charcoal and have a low endogenous clearance (Pond, 1991). Complications include thrombocytopenia, air embolism, reduced glucose, calcium and urate levels, and hemorrhage secondary to the loss of clotting factor and the need for heparinization. Hemoperfusion may be more difficult to initiate and less effective from a practical standpoint than hemodialysis because it is less frequently performed in most institutions.
2) It may be more effective than hemodialysis in clearing the following drugs:
1) chloramphenicol
2) diphenylhydantoin
3) ethchlorvynol
4) glutethimide
5) phenobarbital
6) pentobarbital
7) theophylline
F) HEMOFILTRATION
1) Hemofiltration has the advantage of being able to remove compounds of larger molecular mass, up to 40,000, including metal chelate complexes. It is most effective for substances with a volume of distribution less than 1 Liter/kilogram and low endogenous clearance (Pond, 1991).