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Thank you all for your thoughtful input.  Great discussion that brought up the many different scenarios we have to take into consideration.
So good to have your expertise specific to the conundrum of pediatric "possible" ingestions Dr. Tenebein that present to our ERs on a regular basis.
I'm glad that I asked :)
Kathey

Kathleen Goetz, MD
Medical Director, Swedish Pediatric Emergency Services
Swedish FH ED
747 Broadway
Seattle, WA  98122-4307
Ofc: 206-386-3313   FH ED: 206-386-2573   Fax: 206-386-2577   Cell: 253-370-7571
[Description: untitled]

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From: Milton Tenenbein [mailto:[log in to unmask]]
Sent: Wednesday, February 18, 2015 2:43 PM
To: Goetz, Kathleen; [log in to unmask]
Cc: Jeff Linzer; Sophie Gosselin
Subject: RE: Possible Acetaminophen ingestion - level timing


Dear All,



I have chosen the original post to base my response.

I have read all of the posts including yesterday's post by Dr. Nemeth of Dr. Gosselin's opinion.

While I do not take issue with Dr. Gosselin's points - they are not relevant to the original post.

Her opinion is relevant to the adult poly-substance overdose patient in whom there is the potential for delayed gastric emptying as a consequence of the co-ingested drugs.

I suspect that Dr. Gosselin did not see the original post.



Here is the essence of Dr. Goetz'S query:



2.5yo healthy child found with open tylenol bottle, 1 pill on floor, ingestion uncertain. Event 1.5 hours prior to ER evaluation, patient very active, no distress, no emesis or evident abdominal pain, neuro intact, VS normal.

Questions:

1 - Any value in a 2 hour acetaminophen level?

2 - If 2 hour acetaminophen level = 0 is that a reliable predictor of no ingestion and safe to discharge?

Poison Control says no, must get 4 hour level.



My answer:

1.       Yes there is value for a 2 hour blood concentration determination.

2.       If acetaminophen is not detected then send the child home.

In fact I cite this very scenario in one of my CME talks with the point being that a 2 hour serum acetaminophen concentration is very helpful if it is zero.



In this situation we are using the blood test for a different reason.

The typical indication is to assess the risk for hepatotoxicity,

For that, as we all know, the blood draw needs to be at a minimum of 4 hours after drug ingestion.



Here we are using the test to assess whether an ingestion has occurred rather than for prediction of toxicity.

So, if none is detected at 2 hours - there has been no ingestion.

Over the counter analgesics are designed by industry to have rapid dissolution times - for acetaminophen - it is less than 20 minutes.

If this were not the case- then there would not be "rapid relief of the headache" and consumers would not purchase the product.



Evidence:

One commentator cited the famous "how do we know that parachutes work without having an RCT to prove it?"

I believe that this metaphor is apt.



Several commentators (in addition to Dr. Goetz) remarked that poison control insists on a four hour determination.

This is the advice from a nurse who is reading a protocol from a database (a proxy textbook).



Several commentators remarked that the four hour determination was the "peak level."

Actually it is not the peak level.

The reason for waiting this long is that this typically represents the post distribution phase after oral dosing.



Now (ugh) some pharmacokinetic principles:



After acute oral dosing there are three phases; absorption, distribution and excretion.

Below is a classic plot of concentration vs. time after acute oral dosing of conventional (non-modified release) pharmaceuticals.

In this instance the absorptive phase is 0 to approximately 4 hours - its conclusion is marked by the peak concentration of 8 ng/mL.



Distribution is the second phase.

This phase is during the vertically oriented downward slope of this curve beginning at or about 4 hours and concluding at or about 12 hours.

The corresponding concentrations are 8 and 3 ng/mL.



The key principle is that during distribution drug is leaving the blood stream and binding to cell receptors.

During distribution there is no proportional relationship between blood concentration and tissue concentration.

Thus during this phase it  cannot be a predictor of toxicity.

Proportionality exists when distribution is complete which is the onset of the third phase - excretion.



This is depicted on the graph by the horizontally oriented downward slope.

In this instance - beginning at or about 12 hours.



The reason why we wait for 4 hours after acetaminophen ingestion is that we are waiting for distribution to be complete.

When this occurs there is a proportional relationship between blood and tissue acetaminophen concentrations making it a reliable risk assessment criterion.



Best wishes,



Milton Tenenbein






[http://omicsonline.org/ArchiveJBB/2009/October/03/images/JBB1.86Figure3.gif]









-----Original Message-----
From: Pediatric Emergency Medicine Discussion List [mailto:[log in to unmask]] On Behalf Of Goetz, Kathleen
Sent: Saturday, February 14, 2015 4:23 PM
To: [log in to unmask]<mailto:[log in to unmask]>
Subject: Possible Acetaminophen ingestion - level timing



Hi all,

2.5yo healthy child found with open tylenol bottle, 1 pill on floor, ingestion uncertain. Event 1.5 hours prior to ER evaluation, patient very active, no distress, no emesis or evident abdominal pain, neuro intact, VS normal.

Questions:

1 - Any value in a 2 hour acetaminophen level?

2 - If 2 hour acetaminophen level = 0 is that a reliable predictor of no ingestion and safe to discharge?

Poison Control says no, must get 4 hour level.

Can't find any literature to support 2 hour level (quick lit search).

Input appreciated.  Happy Valentines Day Kathey Goetz



Kathleen Goetz, MD

Medical Director, Swedish Pediatric Emergency Services Swedish FH ED

747 Broadway

Seattle, WA  98122-4307

Ofc: 206-386-3313   FH ED: 206-386-2573   Fax: 206-386-2577   Cell: 253-370-7571





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From: Pediatric Emergency Medicine Discussion List [[log in to unmask]] on behalf of Itai Shavit [[log in to unmask]]

Sent: Friday, February 13, 2015 12:54 AM

To: [log in to unmask]<mailto:[log in to unmask]>

Subject: PEM-Database Studies update - Feb 13, 2015



PEM-Database Studies update - Feb 13, 2015





http://www.pemdatabase.org/



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