Naloxone for the Treatment of Opioid-Induced Pruritus

Hypothesis: Naloxone co-administered simultaneously with standard Patient Controlled Analgesia (PCA) basal and bolus morphine will significantly reduce the incidence of Opioid Induced Pruritus (OIP) without affecting analgesia or opioid consumption in children.

Specific Objectives:

1. To determine if naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml) will be effective in the prevention of opioid induced pruritus (OIP). 2. To determine if treatment with naloxone will result in attenuation of analgesia or an increase in opioid utilisation. 3. To determine if treatment with naloxone will reduce other opioid induced side effects such as nausea and vomiting.

Methods: This study is divided into two phases. Phase 1 - Although, there are studies confirming the compatibility of morphine (4 mg/mL) with naloxone (16 µg/mL) in separate infusion pumps run into the same intravenous site, there are no studies confirming the chemical and physical compatibility of morphine and naloxone in the same syringe with the standard concentrations used at BCCH. Therefore, a compatibility and stability study of naloxone and morphine solution in the same syringe will be performed.

Phase 2 - Phase 2 is a blinded clinical trial where 70 subjects will be randomized to receive either morphine mixed with naloxone or morphine mixed with placebo.With institutional review board approval, and written parental/guardian informed consent (and assent if appropriate), we will recruit children, ages 5-16 years, receiving intravenous opioids via PCA for post-operative pain control. Subjects will be evaluated every 4 hr for pain scores, frequency of vomiting, nausea, pruritus, sedation, and respiratory depression. At 24 and 48 hr, the total morphine consumption will be calculated.

Data analysis: Differences in the incidence and intensity of pruritus between the two groups will be compared. We will review side effects using the following control variables: (1) demographic data; and (2) summation of opioid use in each 4 hr period for total opioid consumption. ANOVA and crosstabs will be used where appropriate to analyze data.