The U.S. Food and Drug Administration (FDA) has recently issued an alert warning of the risk of fatality when codeine is used post-tonsillectomy.(1) A recent survey study by the AAO-HNSF Patient Safety and Quality Improvement Committee has also highlighted numerous cases of post-tonsillectomy death, many in the context of codeine or other narcotic use.(2) Numerous cases have also been reported in the past.(3-5) The majority of these fatalities have been seen in young and obese children with obstructive sleep apnea. The mechanism for many of these fatalities is thought to be related to genetic variation of the liver microenzyme CYP2D6.3 Functional duplication of the gene encoding CYP2D6 results in significantly increased production of morphine (ultrarapid metabolism), which can result in life threatening respiratory suppression. Opiates metabolized through the CYP2D6 pathway include codeine, tramadol, hydrocodone and oxycodone3 but each differs in their molecular structure and metabolism. Future study is needed to understand the mechanisms of metabolism of these opiates and the clinical impact on CYP2D6 "ultra-rapid metabolizers".

Morbidity and mortality in ultrarapid metabolizers undergoing tonsillectomy can be reduced by testing for the genetic variation before prescribing opiates, or avoiding opiates in all children after tonsillectomy. There is evidence that the addition of opiates to the postoperative pain regimen of children undergoing tonsillectomy does not improve pain control and may increase adverse side effects such as nausea and vomiting.(6-9)

Several non-opiate options exist for pain control after tonsillectomy.(1,3,10) A single, intraoperative dose of intravenous dexamethasone has been shown to reduce postoperative pain.(10) Appropriate dosage ranges from 0.15 mg/kg to 1 mg/kg with a maximum dosage range of 8 mg-25 mg.(10) Postoperative options include acetaminophen and ibuprofen (used individually or combined) with the appropriate dosages as follows:

 Acetaminophen: 15 mg/kg every 4-6 hours as needed; Max dose 75 mg/kg/day, do not exceed 1 g/4hour and 4 g/day

 Ibuprofen: 10 mg/kg every 6-8 hours as needed; Max dose 40 mg/kg/day

The FDA recommends that if codeine-containing medications are used, the lowest effective dose should be used for the shortest amount of time on an "as needed" basis.(1) Reduced dosages of opiate/acetaminophen combinations can be supplemented with additional acetaminophen to the 15mg/kg level. Ketorolac is not recommended as it may increase the risk of postoperative bleeding. Antibiotics are not recommended for postoperative pain control after tonsillectomy.(10)

Nonpharmacologic strategies may help with postoperative pain control as well. Preoperative counseling with the patient and the parent can reduce perioperative anxiety about the avoidance of opiates after tonsillectomy. Adequate hydration can also be stressed as an effective pain reducing measure. Parents should understand that their child's safety is a top priority in the perioperative period.

DISCLAIMER: The information in this announcement is provided for informational and educational purposes. It is not intended to create a standard of care or substitute for the judgment of individual physicians. It is the surgeon's responsibility to confirm all dosages of pain medications before prescribing. The reference to specific medications is not intended to be an endorsement or recommendation of a particular product or company.

Sincerely,
Patient Safety and Quality Improvement Committee
American Academy of Otolaryngology-Head and Neck Surgery Foundation
"Empowering otolaryngologist-head and neck surgeons to deliver the best patient care."


REFERENCES:
1. 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. http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm
2. Goldman J, Baugh RF, Davies L, Skinner M, Eisenberg L, Roberson D, et al. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope (In Press).
3. Sadhasivam S, Myer, CM. Preventing opioid-related deaths in children undergoing surgery. Pain Med 2012;13(7):982-3.
4. Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012;129:e1343-7.
5. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med 2009;361:827-8.
6. St Charles CS, Matt BH, Hamilton MM, Katz BP. A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient. Otolaryngol Head Neck Surg. 1997;117(1):76-82.
7. Moir MS, Bair E, Shinnick P, Messner A. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000;110(11):1824-7.
8. Sutters KA, Miaskowski C, Holdridge-Zuener D, Waite S, Paul SM, Savedra MC, et al. A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy. Pain. 2004;110(1-2):49-55.
9. Sutters KA, Miaskowski C, Holdridge-Zuener D, Waite S, Paul SM, Savedra MC, et al. A randomized clinical trial of the efficacy of scheduled dosing of acetaminophen and hydrocodone for the management of postoperative pain in children after tonsillectomy. Clin J Pain. 2010;26(2):95-103.
10. Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, Amin R, Burns JJ, et al. Clinical Practice Guideline: Tonsillectomy in children. Otolaryngol Head Neck Surg. 2011, 44:S1.