October 14, 2012

Deaths Associated with Codeine Usage in Young Kids

For decades, surgeons have provided young children with prescriptions for pain control after tonsillectomy and/or adenoidectomy surgery, most commonly tylenol with codeine (otherwise known as tylenol #3), but also related narcotics including morphine, lortab, hydrocodone, etc. Millions upon millions of such prescriptions have been filled and taken without any problems, but there is now a growing concern that such narcotics may be causing more harm than good in a small percentage of kids and perhaps an even greater percentage where it absolutely does nothing. Furthermore, it has now become the subject of an FDA investigation.

Why the sudden concern?

There has been a small but increasing number of children who have suffered anoxic brain damage and even fatalities due to respiratory suppression associated with codeine use. This association was not figured out until recently as such unfortunate incidences were initially felt to be due to medication overdosage, poor care, and/or surgical error.

But now, it is felt that such adverse events were probably due to the administration of codeine itself.

What's going on?

All of the children who died following codeine administration had extra copies of the liver enzyme CYP2D6 which metabolizes codeine to its more potent form morphine [study]. Referred to as ultra-rapid metabolizers, these children metabolize codeine so rapidly to morphine that it leads to respiratory depression or arrest. Substituting codeine for hydrocodone, oxycodone, or other opioids is also unsafe as such narcotics are also metabolized by CYP2D6 and cause even more problems because the CYP2D6 metabolites of hydrocodone and oxycodone are even more potent than morphine. (Of course, on the flip side, there are patients who have minimal CYP2D6 functionality which leads to minimal if any pain relief with codeine.)

Although rare, there has been an increasing number of case reports describing children who have died after receiving codeine for post-operative pain, particularly after tonsillectomy. The most recent report published in 2012 documented the cases of three children who died after receiving standard treatment with tylenol with codeine after tonsillectomy between 2010 and 2011. However, these are only the known documented cases.

Given how rare, changing prescribing patterns may not be warranted... BUT...

What about the possibility that there may be numerous other cases which are not documented or close-calls? As we all know, for every documented case, there's probably numerous other undocumented cases.

To investigate this possibility, a close proxy would be to look at malpractice lawsuits after tonsillectomy. This report did just that looking closely at lawsuits stemming from tonsillectomy complications between 1984 and 2010 and found that the incidence of codeine-related deaths was much higher than the researchers expected. They found that 18 percent of death claims and 5 percent of injury claims resulted from the use of opioids, largely codeine. Indeed, after bleeding, opioid usage was the second most common cause of death in patients after tonsillectomy.

Additionally, death and anoxic brain injury claims associated with narcotic usage were associated with the greatest indemnity with a median payment of more than $900,000 per case.

Though likely impossible to do retrospectively, it would have been interesting to see whether all these children in these lawsuits had multiple CYP2D6 copies or not.

Alternatives to Narcotics

First, there is the question whether tylenol with codeine even helps with pain. Apparently not according to one study. In fact, children who took tylenol alone resumed a normal diet more quickly than kids who received codeine.

In fact, tylenol with codeine is associated with adverse side effects (nausea, dizziness, vomiting, etc) in up to 79% of children who take it [link].

Ibuprofen may also be given for pain control. Though ibuprofen theoretically can increase risk of bleeding due to its anti-platelet activity, numerous studies have not found this to be true.

Given codeine helps minimally with pain and tylenol alone seems to provide adequate pain control, why even given narcotics, especially given the small but significant risk of death associated with this drug?

Pain Control Protocol

Based on all these findings, we feel that narcotics for pain control after tonsillectomy for kids under 7 years of age is not recommended.

Rather, the following protocol is what we will now be implementing:

Tylenol and Ibuprofen over-the-counter as needed to help with pain control. The dosing is weight-based and exact dosing for a given child can be found on the bottle. These medications can be given alternating between Tylenol and ibuprofen every 3-4 hours (Tylenol first, followed by ibuprofen 3-4 hours later, followed by Tylenol 3-4 hours after that, etc). A prescription for a single dose of steroids is also provided which is meant as a one-time dose that can be given anytime 3 days after surgery if the child suddenly seems to have significantly more pain that is not controlled with Tylenol and ibuprofen. Pain in this scenario is often due to inflamed tissues that can be quickly minimized with steroids.

Watch a video showing how a tonsillectomy is performed here!

FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death. FDA 8/15/12

Post-Operative Pain in Children Undergoing Tonsillectomy. ENT Today. Sept 2012.

FDA Investigates Codeine Safety After Children’s Deaths. ABC News. 8/15/12

Ibuprofen with Acetaminophen for Postoperative Pain Control following Tonsillectomy Does Not Increase Emergency Department Utilization. Otolaryngol Head Neck Surg. 2014 Sep 9. pii: 0194599814549732. [Epub ahead of print]

More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012 May;129(5):e1343-7. Epub 2012 Apr 9.

Preventing opioid-related deaths in children undergoing surgery. Pain Med. 2012 Jul;13(7):982-3; author reply 984. doi: 10.1111/j.1526-4637.2012.01419.x. Epub 2012 Jun 13.

Complications and legal outcomes of tonsillectomy malpractice claims. Laryngoscope. 2012 Jan;122(1):71-4. doi: 10.1002/lary.22438. Epub 2011 Nov 10.

Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000 Nov;110(11):1824-7.

Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003591.

Morphine or Ibuprofen for Post-Tonsillectomy Analgesia: A Randomized Trial. Published online January 26, 2015 (doi: 10.1542/peds.2014-1906)

Outcomes of an Alternating Ibuprofen and Acetaminophen Regimen for Pain Relief After Tonsillectomy in Children. Ann Otol Rhinol Laryngol. 2015 Apr 22. pii: 0003489415583685. [Epub ahead of print]
Fauquier blog
Fauquier ENT

Dr. Christopher Chang is a private practice otolaryngology, head & neck surgeon specializing in the treatment of problems related to the ear, nose, and throat. Located in Warrenton, VA about 45 minutes west of Washington DC, he also provides inhalant allergy testing/treatment, hearing tests, and dispenses hearing aids.

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