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Do We Need a 4-Hour Level for APAP

January 12, 2017

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Short Attention Span Summary

Could this be a dogma bust?  Nope.
Do you really need a 4-hour acetaminophen (APAP) level?  Couldn’t we get a 2-hour level?  Turns out, you actually need to do a 4-hour level.  There were a few cases with 2-4 hour levels <100 μg/mL that subsequently had toxic 4 hour levels >150 μg/mL.  Sensitivity for the 100 μg/mL cut point at 2-4 hours was 96% but was signifcantly degraded by coingestion of opiates and antimuscarinic agents.  However, if levels were “very low” or undetectable at 2-4 hours, none had subsequent toxic 4-hour levels.

Spoon Feed
You really do need a 4-hour APAP level.  But if the <4 hour level is undetectable or “very low” you are in the clear.


Clin Toxicol (Phila). 2016 Oct 28:1-7. [Epub ahead of print]

Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not require treatment with acetylcysteine?

Yarema MC1,2,3, Green JP4, Sivilotti ML5,6, Johnson DW1,7, Nettel-Aguirre A7,8,9, Victorino C10, Spyker DA11, Rumack BH12.

Author information:

1a Poison and Drug Information Service , Alberta Health Services , Alberta , Canada.

2b Department of Emergency Medicine , University of Calgary , Alberta , Canada.

3c Section of Clinical Pharmacology and Toxicology , Alberta Health Services , Alberta , Canada.

4d Department of Pediatrics , McMaster University , Ontario , Canada.

5e Department of Emergency Medicine , Queen’s University , Ontario , Canada.

6f Department of Biomedical & Molecular Sciences , Queen’s University , Ontario , Canada.

7g Department of Pediatrics , University of Calgary , Alberta , Canada.

8h Alberta Children’s Hospital Research Institute for Child & Maternal Health , Alberta , Canada.

9i Department of Community Health Sciences , University of Calgary , Alberta , Canada.

10j Prairie Regional Research Data Centre, Statistics Canada , Alberta , Canada.

11k Department of Emergency Medicine , Oregon Health Sciences University , Portland , OR , USA.

12l Department of Pediatrics , University of Colorado School of Medicine , Denver , CO , USA.



The interpretation of acetaminophen concentrations obtained prior to 4 hours after an acute, single overdose remains unclear. Patient care decisions in the Emergency Department could be accelerated if such concentrations could reliably exclude the need for treatment.


To determine the agreement between a serum acetaminophen concentration obtained less than 4 hours after an acute ingestion and the subsequent 4 + hour concentration, and the predictive accuracy of early concentrations for identifying patients with potentially toxic exposures.


A secondary analysis of patients admitted for acetaminophen poisoning at one of the 34 hospitals in eight Canadian cities from 1980 to 2005. We examined serum acetaminophen concentrations obtained less than 4 hours post-ingestion, and again 4 or more hours post-ingestion. For the diagnostic accuracy analysis, we specified a cutpoint of 100 μg/mL (662 μmol/L) obtained between 2 and 4 hours and a subsequent 4 to 20 hour acetaminophen concentration above the nomogram treatment line of 150 μg/mL (993 μmol/L).


Of 2454 patients identified, 879 (36%) had a subsequent acetaminophen concentration above the nomogram treatment line. The 2-4 hour concentration demonstrated a sensitivity of 0.96 [95% CI; 0.94, 0.97] and a negative likelihood ratio of 0.070 [0.048, 0.10]. Coingested opioids reduced this sensitivity to 0.91 [0.83, 0.95], and antimuscarinics to 0.86 [0.72, 0.94]. Only very low to undetectable acetaminophen concentrations prior to 4 hours reliably excluded a subsequent concentration over the treatment line.


Applying an acetaminophen concentration cutpoint of 100 μg/mL (662 μmol/L) at 2-4 hours after an acute ingestion as a threshold for repeat testing and/or treatment would occasionally miss potentially toxic exposures. Absorption of acetaminophen is only slightly delayed by coingested opioids or antimuscarinics. Our analysis validates the practice of not retesting when the first post-ingestion acetaminophen concentration is below the lower limit of quantification.

PMID: 27788602 [PubMed – as supplied by publisher]

What are your thoughts?