IV and PO NAC are equally effective except in cases where liver failure is already present.Treats toxicity at the cellular level (poorly understood).Detoxifies NAPQI by acting as both precursor and substitute for glutathione.Prevents toxicity by increasing sulfation.NAC Pharmacology (Goldfrank’s Toxicology) Activated charcoal can decrease the probability of the 4-hour being above the treatment line ( Buckley 1999).
Charcoal should only be administered in patients who are awake and able to take it orally OR have a protected airway and no contraindications. Indicated if patient presents < 4 hours after APAP overdose. Transfusions prn (platelets/plasma for coagulopathy pRBC if anemia from GIB). If patient arrives after 4 hours, get initial level and plot on nomogram above prior to 4 hours after ingestion are not helpful and rather may be harmful by skewing management decisions ( Seifert 2015). When time of ingestion is in doubt, use the earliest possible time of ingestion (similar to “last known well” in stroke care) as this provides the most conservative approach. If is below the 150-line, there is no need to treat or gather further data points. If is above the 150-line, treat with NAC as below. Measure APAP concentration at 4 hours from time of ingestion and plot on Rumack-Matthew Nomogram. Definition: Entire ingestion occurring within 8-hour period. In other words, ~1% of patients below the line who are untreated will develop hepatotoxicity (defined as transaminitis) With this cutoff, failure rate of the line in acute ingestions is ~1%. 
In the US, the line was further arbitrarily lowered 25% to current “150-line” from =150 at 4 hours to =37.5 at 12 hours (purple line above). With this threshold, only 60% of patients above the line would go on to develop hepatotoxicity. Threshold initially lowered to a “200-line” from =200 at 4 hours to =50 at 12 hours (dotted yellow line above) to be more conservative. This approach led to a “300-line” from =300 at 4 hours to =50 at 12 hours (not pictured above) dividing patients with hepatotoxicity and those without. Empirically derived by plotting untreated patients with acute APAP ingestion on the graph above and dividing those who developed hepatotoxicity from those who didn’t (defined as AST/ALT >1000). 
X-axis: Hours post-ingestion Y-axis APAP concentration.
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