Optimal Dose of Prophylactic Naloxone in Reducing Opioid-Induced Side Effects in Children/Adolescents
Condition: Pain; Nausea; Pruritus
MeSH terms: Pruritus
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an investigator initiated dose finding study designed to determine the optimal dose
      of naloxone to prevent or minimize the most common side effects induced by opioids, namely
      itching, nausea, and vomiting. Male and female inpatients of the Children's Center of the
      Johns Hopkins Hospital, who are greater than 6 and less than 18 years of age with acute,
      moderate to severe pain, and who are to be treated with intravenous Patient controlled
      analgesia (IVPCA) morphine will be eligible for inclusion in this study. Patients will be
      recruited by a study investigator prior to the initiation of IVPCA therapy. The majority of
      patients will be post operative patients, and will start therapy and the investigational drug
      in the Post Anesthesia Care Unit or the Pediatric Intensive Care Unit. The investigators plan
      on studying between 10 and 99, male and female patients over a 2 year period.
    

Detailed description: 
      In patients of all ages, opioids are the cornerstone of management of moderate to severe
      pain. Regardless of method of administration, all opioids produce unwanted side effects,
      including pruritus, nausea and vomiting, constipation, urinary retention, cognitive
      impairment, tolerance, dependence, and (rarely) respiratory depression. Based on the results
      of a previously completed randomized controlled trial, children and adolescents with moderate
      to severe pain, are now routinely treated in the Children's Center of the Johns Hopkins
      Hospital with a low dose naloxone infusion (0.25 mcg/kg/HOUR) whenever morphine intravenous
      patient controlled analgesia (IVPCA) or parent/nurse controlled analgesia (IVPNCA) is
      initiated. Although the previous study showed a marked reduction in the incidence and
      severity of pruritus and nausea, approximately a third of the patients still experience these
      side effects. The primary purpose of this study is to reduce this failure rate by determining
      if there is an optimal dose of naloxone to prevent opioid induced side effects as determined
      by a dose finding classic up down dose escalation method. The second aim is to determine the
      pharmacokinetics of morphine and naloxone and their metabolites at each of the naloxone
      infusion rates attempted. The investigators will measure morphine, naloxone, and their
      metabolites using a liquid chromatographic-electrospray ionization-tandem mass spectrometric
      method (LC/MS/MS). The final aim is to determine the pharmacogenetics of responders and
      non-responders using DNA isolated from patient blood. To accomplish this the investigators
      will need a single blood collection from patients currently being treated with IVPCA morphine
      and low dose intravenous naloxone.
    

Intervention name(s): naloxone
Intervention type(s): Drug
Intervention description(s): continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour
Intervention MeSH terms: Naloxone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: morphine; naloxone; pediatrics; adverse effects; pain