After appropriate diagnostic and decontamination procedures and administration of antidotes, it is important to consider whether measures for enhancing elimination, such as hemodialysis or urinary alkalinization, can improve the clinical outcome. Table 58–2 lists intoxications for which dialysis may be beneficial.
A. Dialysis Procedures 1. Peritoneal dialysis—Although it is a relatively simple and available technique, peritoneal dialysis is inefficient in removing most drugs.
2. Hemodialysis—Hemodialysis is more efficient than peritoneal dialysis and has been well studied. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites (eg, formic acid in methanol poisoning; oxalic and glycolic acids in ethylene glycol poisoning). The efficiency of both peritoneal dialysis and hemodialysis is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin. Hemodialysis is especially useful in overdose cases in which the precipitating drug can be removed and fluid and electrolyte imbalances are present and can be corrected (eg, salicylate intoxication).
B. Forced Diuresis and Urinary pH Manipulation
Previously popular but of unproved value, forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphetamines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication.
Acetaminophen is one of the drugs commonly involved in suicide attempts and accidental poisonings, both as the sole agent and in combination with other drugs. Acute ingestion of more than 150–200 mg/kg (children) or 7 g total (adults) is considered potentially toxic. A highly toxic metabolite is produced in the liver (see Figure 4–5).
Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24–36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrombinemia. Fulminant liver failure may ensue, leading to metabolic acidosis, hypoglycemia, encephalopathy, and death. Renal failure may also occur. With acute massive ingestion and very high serum levels, metabolic acidosis can occur in the absence of liver failure. Rarely, acetaminophen ingestion can cause 5-oxoprolinuria due to glutathione depletion.
The severity of poisoning is estimated from a serum acetaminophen concentration measurement. If the level is greater than 150 mg/L approximately 4 hours after ingestion, the patient is at risk for liver injury. (Chronic alcoholics or patients taking drugs that enhance P450 production of toxic metabolites may be at risk with lower levels.) The antidote acetylcysteine acts as a glutathione substitute, binding the toxic metabolite as it is produced. It is most effective when given early and should be started within 8–10 hours if possible. Liver transplantation may be required for patients with fulminant hepatic failure.
TABLE 58–3 Examples of specific antidotes.
Acetylcysteine Acetaminophen (Acetadote, Mucomyst)
Best results if given within 8–10 hours of overdose. Follow liver function tests and acetaminophen blood levels. Acetadote is given intravenously; Mucomyst is given orally.