In these cases, the provider must use risk factors, lab values, and clinical suspicion to determine whether or not there was significant ingestion.
Acetaminophen levels do not correlate well with the degree of overdose. įor chronic acetaminophen ingestions, the Rumack-Matthew Nomogram cannot be applied. It can also only be applied to single acute ingestion. Serum levels must be drawn between 4 to 24 hours from the time of ingestion to use the nomogram properly. A level greater than 150 mcg/mL at 4 hours from ingestion is considered toxic. If serum levels fall into the toxic range based on the Rumack-Matthew Nomogram, then treatment should be initiated. Co-ingestions can be important, and a urine drug screen, EKG, and metabolic panel may be useful. Normally LFTs remain elevated in the second stage at 18 to 72 hours. If the ingestion is severe, LFTs can rise within 8 to 12 hours of ingestion. Other laboratory studies needed include liver function tests (LFTs) and coagulation profile (PT/INR). The diagnosis of acetaminophen toxicity is based on serum levels of the drug, even if there are no symptoms. There are also decreased stores of glutathione in alcoholics and patients with AIDS. Glucuronidation is dependent on carbohydrate stores, and more acetaminophen is converted to NAPQI in the malnourished patient. There is also increased activity of this enzyme in alcoholics and smokers, although acute intoxication with alcohol or cirrhosis can decrease the activity of cytochrome P450. Many anti-epileptic and anti-tuberculosis medications are known to increase the activity of cytochrome P450. An overdose depletes the stores of glutathione, and once they reach less than 30% of normal, NAPQI levels increase and subsequently bind to hepatic macromolecules causing hepatic necrosis. NAPQI is a toxic substance that is safely reduced by glutathione to nontoxic mercaptate and cysteine compounds, which are then renally excreted. In an overdose, these pathways are saturated, and more acetaminophen is subsequently metabolized to NAPQI by cytochrome P450. Metabolism primarily occurs through glucuronidation and sulfuration, both of which occur in the liver.
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