Codeine-related adverse drug reactions in children following tonsillectomy: A prospective study

Authors

  • Cynthia A. Prows MSN, CNS, FAAN,

    Corresponding author
    1. Division of Human Genetics, University of Cincinnati, Cincinnati, Ohio
    2. Division of Pharmacy, University of Cincinnati, Cincinnati, Ohio
    • Send correspondence to Cynthia A. Prows, MSN, CNS, FAAN, Children's Hospital, Division of Human Genetics and Division of Patient Services, Bldg. E, 5-259, MLC 4006, 3333 Burnet Ave. Cincinnati, OH, 45229. E-mail: cindy.prows@cchmc.org

    Search for more papers by this author
  • Xue Zhang PhD, MsPH,

    1. Division of Human Genetics, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Myra M. Huth PhD, RN, FAAN,

    1. JoAnn McGrath School of Nursing, Alverno College, Milwaukee, Wisconsin
    Search for more papers by this author
  • Kejian Zhang MD, MBA,

    1. Division of Human Genetics, University of Cincinnati, Cincinnati, Ohio
    2. Department of Otolaryngology Head and Neck Surgery, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Shannon N. Saldaña PharmD, MS, BCPP,

    1. Division of Pharmacy, University of Cincinnati, Cincinnati, Ohio
    2. Department of Pharmacy, Intermountain Primary Children's Medical Center, Salt Lake City, Utah, U.S.A.
    Search for more papers by this author
  • Nancy M. Daraiseh PhD,

    1. Division of Patient Services, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Hope R. Esslinger MPT,

    1. Department of Anesthesia and Pain Management, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Edita Freeman MBA,

    1. Division of Human Genetics, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • John H. Greinwald MD,

    1. Division of Pediatric Otolaryngology, Children's Hospital; University of Cincinnati, Cincinnati, Ohio
    2. Department of Anesthesia, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Lisa J. Martin PhD,

    1. Division of Human Genetics, University of Cincinnati, Cincinnati, Ohio
    2. Department of Otolaryngology Head and Neck Surgery, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author
  • Senthilkumar Sadhasivam MD, MPH

    1. Department of Anesthesia and Pain Management, University of Cincinnati, Cincinnati, Ohio
    2. Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
    3. Department of Anesthesia, University of Cincinnati, Cincinnati, Ohio
    Search for more papers by this author

  • This work was supported in part by USPHS Grant UL1 RR026314 from the National Center for Research Resources, National Institutes of Health (NIH), and by the Place Outcomes Research Award and Translational Research Award, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, U.S.A. Additional research funding support was provided by the Department of Anesthesia and Department of Pediatrics, Division of Human Genetics, CCHMC, Cincinnati, Ohio, U.S.A. The study sponsor, CCHMC, provided funding support for the genetic analyses and supported salary of the research team while employed at CCHMC. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis

To prospectively determine factors associated with codeine's adverse drug reactions (ADRs) at home in a large homogenous population of children undergoing outpatient tonsillectomy.

Study Design

Prospective, genotype blinded, observational study with a single group and repeated ADR measures documented by parents at home.

Methods

A total of 249 children 6 to 15 years of age scheduled for tonsillectomy were enrolled. The primary outcome was number of daily codeine-related ADRs. We examined the number and type of ADR by race and by days and further modeled factors potentially associated with ADR risk in a subcohort of white children. Sedation following a dose of codeine was a secondary outcome measure. Parents recorded their children's daily ADRs and sedation scores during postoperative days (POD) 0 to 3 at home.

Results

Diaries were returned for 134 children, who were given codeine. A total of 106 (79%) reported at least one ADR. The most common ADRs were nausea, lightheadedness/dizziness for white children and nausea, and vomiting for African American children. In a subcohort of white children 45 kg, increased ADR risk was associated with the presence of one or more full function CYP2D6 alleles (P < 0.001), POD (P < 0.001), and sex (P = 0.027). Increased pain intensity (P = 0.009) and PODs 0 and 1 (P = 0.001) contributed to a higher sedation risk. Neither obstructive apnea nor predicted CYP2D6 phenotype were associated with sedation risk.

Conclusions

Our results provide evidence that multiple factors are associated with codeine-related ADRs and support the FDA recommendation to avoid codeine's routine use following tonsillectomy in children.

Level of Evidence

4. Laryngoscope, 124:1242–1250, 2014

Ancillary