Following an acute overdosage, toxicity may result from codeine or acetaminophen.
Signs and Symptoms
Toxicity from codeine poisoning includes the opioid triad of pinpoint pupils, depression of respiration, and loss of consciousness. Convulsions may occur.
In acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.
Early symptoms following a potentially hepatotoxic overdose may include nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.
A single or multiple drug overdose with acetaminophen and codeine is a potentially lethal polydrug overdose and consultation with a regional poison control center is recommended.
Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered. For respiratory depression due to overdosage or unusual sensitivity to codeine, parenteral naloxone is a specific and effective antagonist.
Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 or more hours after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose-dependent and occurs early in the course of intoxication.