Pharmacogenomics Analysis of Morphine Pharmacokinetics in Pediatric Tonsillectomy and Adenoidectomy
Condition: Tonsillectomy; Adenoidectomy; Pharmacokinetics
Study type: Observational

Summary: 
      Intravenous (IV) morphine requirement for immediate postoperative pain control depends upon
      the complex interplay of patient history, wound severity, environment, and genetics. Even for
      relatively uniform stimulus intensity, such as that associated with tonsillectomy and
      adenoidectomy (T&A), there can be marked individual variability in response to morphine. Some
      patients are refractory to standard doses and need increased amounts. Others are sensitive,
      require less drug to attain acceptable pain levels, and/or experience unwanted side effects
      that limit dosing. A significant number must be switched to different analgesics altogether.
      Despite the long clinical history of morphine as a postoperative analgesic, researchers have
      only begun to examine the origins of response variability.

      The investigators will look at 2000 retrospective Tonsillectomy and Adenoidectomy (T&A) cases
      and using this data and incorporating additional patient, surgical, and environmental factors
      that may contribute to response variability, the investigators then propose a prospective
      genome-wide association (GWA) study of 1500 children ages 4 to 18 years treated with IV
      morphine sulfate for day surgery T&A.
    

Detailed description: 
      Morphine Tonsilectomy and Adenoidectomy (T&A) Pharmacokinetics (PK) study will be done as a
      part of the larger institutional Center for Applied Genomics (CAG) project entitled "A Study
      of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the
      Children's Hospital of Philadelphia (CHOP) IRB, 2006-7-4886. By combining Genome Wide
      Association (GWA) and PK data, we wish to conduct a Pharmacogenomic (PG) study of IV morphine
      administered as standard of care during and after pediatric day surgery T&A. Because we
      expect several genes to play a role in the morphine response, we must use a large, relatively
      uniform pediatric surgical population such that for T&A. Through observation and minimal-risk
      blood sampling of this cohort of children, we hope to identify genetic variants that predict
      analgesic response to (and serum levels of) morphine sulfate. Pediatric patients ages 4-18 y,
      presenting with significant tonsillar/adenoidal tissue hypertrophy, sleep disordered
      breathing and/or recurrent infection, and requiring T&A are eligible. Morphine is the most
      common IV analgesic used for T&A at the Children's Hospital of Philadelphia (CHOP). As is
      necessary for accurately defining analgesic response phenotype, morphine will be administered
      in a structured manner consistent with standard of care at this institution. As defined
      below, children resistant to morphine (MR) and those sensitive to it (MS) will be identified
      as specific phenotypes to be compared with normal responders (NR) in a GWA study.

      This study begins with a retrospective electronic database query of 2000 day surgery T&A
      cases between 11/1/2005 and 10/31/2008 in which morphine was used as the sole IV analgesic.
      Data from this portion of the study will help us refine phenotype parameters, should robust
      subpopulations of response types emerge, and provide background information required for
      eventual project funding by the National Institutes of Health (NIH). The prospective portion
      of the study will follow an additional 1650 children newly enrolled in the CAG study and now
      presenting for T&A.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Children having Tonsillectomy and Adenoidectomy procedures done at The Children's Hospital
        of Philadelphia, at the Main Hospital and also at the satellite surgical centers, who have
        also consented to participate in "A Study of the Genetic Causes of Complex Pediatric
        Disorders" (GCPD study), as approved by the CHOP IRB, 2006-7-4886.
      
Biospecimen description: 
      PK plasma samples will be obtained
    
Keywords: Morphine; Phenotype; Genotype; Tonsillectomy; Adenoidectomy; Opioid Receptors; Genome-Wide Association; Pharmacokinetics