Morphine PK Subgroup Analysis
Condition: Post Operative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      This study was originally undertaken to evaluate the analgesic efficacy of an intravenously
      administered dose of ketorolac compared with intravenous morphine in the relief of acute,
      postoperative pain in children admitted to the Intensive Care Unit. Using the urine and
      plasma samples originally collected from patients in the morphine treatment group and which
      were never analyzed, this proposal seeks to study the pharmacokinetics and metabolism of
      intravenous morphine in critically-ill children along with its concentration-related efficacy
      using prior measures of pain.
    

Detailed description: 
      This was a randomized, double-blind, parallel, single-dose study. All children admitted to
      the ICU at Children's Hospital of Michigan postoperatively who required pain management were
      candidates. Enrollment required a Children's Hospital of Eastern Ontario Pain Scale (CHEOPS)
      and/or Oucher pain score meeting the protocol definition of moderate to severe pain. Each
      patient was randomly assigned to receive a single dose of either morphine 0.1 mg/kg or
      ketorolac 0.6 mg/kg IV as the first postoperative analgesic after arriving in the ICU.
      Two-milliliter venous blood samples were drawn from a site contralateral to the infusion
      site. Samples were obtained before the dose and at 15, 30, and 60 minutes, hourly from 1-6
      hours, and at 8 and 12 hours timed from the beginning of the infusion. Pain scales were
      assessed at the time of each pharmacokinetic sample. Plasma was immediately separated and
      frozen at -80°C. Urine was quantitatively collected for 12-24 hours after the study drug was
      administered. Urine was kept on ice at 3°C throughout the collection. At completion of the
      collection, the urine volume was measured and recorded, and an aliquot was frozen and
      maintained at -80°C. The plasma and urine samples from the morphine treated group in the
      original study were stored at -80°C and were not analyzed. Sets of samples of urine and
      plasma from 6 subjects over a range of ages have been analyzed to insure that the samples
      have not deteriorated during storage. This subanalysis study will provide chemical analysis
      of the plasma and urine samples for morphine, morphine 3 glucuronide (M3G) and morphine 6
      glucuronide (M6G); pharmacokinetic analysis of morphine and its metabolites with comparison
      to demographics; and comparison of the morphine concentrations to the measures of analgesia.
      The ratio of the area under the plasma concentration vs time curves (AUC)of M6G with twice
      the analgesic potency as morphine and M3G with theoretical anti-analgesic properties will be
      compared to analgesic effects measured by the age-appropriate pain scales.
    

Intervention name(s): Morphine
Intervention type(s): Drug
Intervention description(s): A single dose of morphine 0.1 mg/kg infused by syringe pump over 10 minutes; urine and blood sample frozen at -80 degrees Celsius
Intervention MeSH terms: Morphine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: pain, pain management, pediatrics, morphine pharmacokinetics