OVERDOSAGE
Following an acute overdosage, toxicity may resultfrom hydrocodone or acetaminophen.
Signs and Symptoms
Hydrocodone
Serious overdose with hydrocodone is characterizedby respiratory depression (a decrease in respiratory rate and/or tidal volume,Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stuporor coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardiaand hypotension. In severe overdosage, apnea, circulatory collapse, cardiacarrest and death may occur.
Acetaminophen
In acetaminophen overdosage: dose-dependent,potentially fatal hepatic necrosis is the most serious adverse effect. Renaltubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur.
Early symptoms following a potentially hepatotoxic overdosemay include: nausea, vomiting, diaphoresis and general malaise. Clinicaland laboratory evidence of hepatic toxicity may not be apparent until 48 to72 hours post-ingestion.
In adults, hepatictoxicity has rarely been reported with acute overdoses of less than 10 grams,or fatalities with less than 15 grams.
Treatment
A single or multiple overdose with hydrocodone andacetaminophen is a potentially lethal polydrug overdose, and consultationwith a regional poison control center is recommended.
Immediatetreatment includes support of cardiorespiratory function and measures to reducedrug absorption. Vomiting should be induced mechanically, or with syrup ofipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The firstdose should be accompanied by an appropriate cathartic. If repeated dosesare used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. Vasopressorsand other supportive measures should be employed as indicated. A cuffed endo-trachealtube should be inserted before gastric lavage of the unconscious patient and,when necessary, to provide assisted respiration.
Meticulousattention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysismay be considered. If hypoprothrombinemia occurs due to acetaminophen overdose,vitamin K should be administered intravenously.
Naloxone,a narcotic antagonist, can reverse respiratory depression and coma associatedwith opioid overdose. Naloxone hydrochloride 0.4 mg to 2 mg is given parenterally. Since the duration of action of hydrocodone may exceed that of the naloxone,the patient should be kept under continuous surveillance and repeated dosesof the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinicallysignificant respiratory or cardiovascular depression.
Ifthe dose of acetaminophen may have exceeded 140 mg/kg, acetylcysteine shouldbe administered as early as possible. Serum acetaminophen levels should beobtained, since levels four or more hours following ingestion help predictacetaminophen toxicity. Do not await acetaminophen assay results before initiatingtreatment. Hepatic enzymes should be obtained initially, and repeated at24-hour intervals.
Methemoglobinemia over 30%should be treated with methylene blue by slow intravenous administration.
The toxic dose for adults for acetaminophen is 10 g.
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