What is the best non-codeine postadenotonsillectomy pain management for children?

LITERATURE REVIEW A 2011 evidence-based Clinical Practice Guideline on Tonsillectomy in Children from the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) reported that the main morbidity in children following tonsillectomy is pain resulting in decreased oral intake, dysphagia, dehydration, and weight loss. Acetaminophen alone was shown to be as effective as acetaminophen with codeine. However, often neither acetaminophen alone nor acetaminophen with codeine provide adequate analgesia. In February 2013, the FDA reviewed 13 cases of children, ages 21 months to 9 years, who either died (n510) or had overdose signs and symptoms (n5 3) associated with codeine that were reported to their Adverse Event Reporting system. These were collected from 1969 to 2012 from an estimated> 22 million pediatric tonsillectomies. A total of 11/13 cases had either adenotonsillectomy (n5 8) or respiratory tract infection (n53). Of the seven cases also described in the literature, three were described as ultra-rapid metabolizers, three as extensive metabolizers, and one as a likely ultra-rapid metabolizer. Most appeared to have received appropriate doses of codeine. Codeine is metabolized in the liver to its active moiety morphine by a P450 isozyme, CYP2D6. CYP2D6 is highly polymorphic. These variations create four phenotypes for codeine metabolism: ultra-rapid (produce excessive amounts of morphine: overdose), extensive (produce normal amounts of morphine: good analgesia), intermediate (produce less than normal amounts of morphine: poor analgesia), and poor metabolizers (produce minimal morphine: no analgesia). Poor metabolizers (10% of the population), obtain no analgesia from codeine. These polymorphisms lead to widely varying analgesic results and toxicity. Approximately 7% of Caucasians, and up to 30% of Asians and Africans are over-metabolizers of codeine, while 6% to 10% are slow metabolizers. Routine CYP2D6 genotype testing may not be useful because: 1) Patients with normal metabolism may, in some cases, convert codeine to morphine at levels similar to ultra-rapid metabolizers; 2) more than 80 CYP2D6 alleles have been identified (http://www.cypalleles.ki.se). Testing may not be available clinically, and the metabolism of codeine has not been evaluated for all alleles. It is important to note that children with sleep disordered breathing (a main indication for adenotonsillectomy) are known to be particularly susceptible to respiratory depression from opioids. A recent study compared the efficacy of acetaminophen with hydrocodone administered as-needed versus scheduled around the clock. Scheduled dosing was more effective than as-needed dosing, but moderate pain was From the Division of Pediatric Otolaryngology (R.F.Y.); the Department of Anesthesiology (F.P.C.); Clinical Pharmacy Specialist (W.M.); Anesthesiologist-in-Chief (P.J.D.), Children’s Hospital of Pittsburgh of UPMC; University of Pittsburgh School of Pharmacy (W.M.); the Department of Anesthesia and Pediatrics (P.J.D.); the Department of Otolaryngology (R.F.Y.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; the Department of Otology and Laryngology, Harvard Medical School (M.A.K.), U.S.A; and the Department of Otolaryngology and Communication Enhancement (M.A.K.), Boston Children’s Hospital, Boston, Massachusetts, U.S.A. Send correspondence to Robert F. Yellon, MD, FACS, Director of Clinical Services, Division of Pediatric Otolaryngology, Children’s Hospital of Pittsburgh of UPMC, Professor, Department of Otolaryngology, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224. E-mail: [email protected] or Margaret A. Kenna, MD, MPH, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; the Department of Otology and Laryngology, Harvard Medical School U.S.A; and the Department of Otolaryngology and Communication Enhancement, Boston Children’s Hospital, Boston, Massachusetts, U.S.A. E-mail: [email protected]