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Paper Chase #5 | Updated Guidelines on Tonsillectomy

Geoffrey R. Simon, MD and Roy Benaroch, MD
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 Though tonsillectomies are common, the specific indications are fairly narrow.

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Mark C. -

Why is codeine contraindicated with tonsillectomy again? Does it increase mortality? Bleeding? FWIW, I don't use that medicine.

Mizuho M., DO -

Great Question Mark. In 2017, the FDA updated their previous 2013 warnings (not to use in < 12 yo) to a BLACK BOX WARNING and increased the age minimum to 18 years of age! This is after a number of deaths due to after children used codeine prescribed after elective T&A. The doses were appropriate, but what we now know is that a % of the population are "Ultra-metabolizers" of codeine. For some background, Codeine is a prodrug, which requires metabolic breakdown for analgesia to take effect.
Its metabolized through three major pathways:
1) Majority (70%) is metabolized by the enzyme UPD-glucuronosyltransferase-2B7 (UGT2B7) into codeine-6-glucuronide an active metabolite
2) 5-10% via the CYP3A4 enzymes into inactive norcodeine
3) Lastly 10% is metabolized via the cytochrome P450 CYP2D6 pathway into another active metabolite morphine.
Its this last pathway through the cytochrome p450 pathway that has genetic variability. Depending on the # of alleles you have on the CYP2D6 gene, some individuals known as “ultra-rapid metabolizers”, can break down codeine to toxic levels of morphine. And without doing genetic testing, there is no way to predict who will be an ultra-metabolizer and who will not.
Hence FDA and AAP both state NO CODEINE for children PERIOD. Shockingly providers are still writing this stuff...for fractures, URI's (cough syrups), T&A etc. Ironically multiple head-head studies have been done showing the efficacy of pain control of NSAIDS = opiates esp when scheduled and appropriately dosed. This needs to stop. We will do a future segment elaborating more on this. In the meantime I hope this helps! Thanks for listening! ~Miz

Mark C. -

Miz,

What a great response! So much great information in it! Also, I feel like I got a social media reply from a celebrity! Thank you for taking the time to write such a thorough response. LOVE you guys!!

Mizuho M., DO -

HAHA...glad you found it helpful. Here are some great references if you want to dig a bit deeper too! Thanks for listening and sending comments! We love it! :) ~Miz

1) https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-restricts-use-prescription-codeine-pain-and-cough-medicines-and
2) https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm
3) Drendel AL, Gorelick MH et al. A randomized clinical trial of ibuprofen versus acetaminophen with codeine for acute pediatric arm fracture pain.Ann Emerg Med. 2009 Oct;54(4):553-60 [PMID 19692147]
4) Kao-Ping Chua, Mark G. Shrime et al.Effect of FDA Investigation on Opioid Prescribing to Children After Tonsillectomy/Adenoidectomy. Pediatrics December 2017, VOLUME 140, ISSUE 6. [PMID 29146621]

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You Say Tera-tomah-ta, I Say Tera-Tomay-to Full episode audio for MD edition 186:08 min - 87 MB - M4AHippo Peds RAP July 2019 Written Summary 296 KB - PDF

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