A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial.

Purpose: Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65 μg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization.

Methods: In this randomized controlled trial, children meeting the inclusion criteria (aged 8-18 yr, American Society of Anesthesiologists physical status I-III, normal developmental profile and prescribed COI/PCA morphine for postoperative analgesia) were randomized to receive an infusion containing a naloxone, opioid, and saline admixture (NOSA) of 12 μg naloxone per 1 mg morphine per 1 mL normal saline or morphine only (control). The severity of opioid-induced pruritus was assessed by self-report using a modified colour analogue scale (mCAS; score 0-10). The groups were also compared for opioid utilization, pain scores, and administration of antipruritic medications, which were recorded for up to 48 hr or until the COI/PCA was discontinued.

Results: Ninety-two participants were enrolled in the study. The median [interquartile range] dose of naloxone administered to the NOSA participants was 0.37 [0.30-0.48] μg·kg(-1)·hr(-1). The incidence of OIP, determined by self-report and treatment, was not different between groups: 22% in the NOSA group vs 36% in the control group (mean difference, -15%; 95% confidence interval [CI], -33 to 4; P = 0.164). The severity of opioid-induced pruritus was similar in the two groups, with a median difference in the participants' mean mCAS score of -0.29 (95% CI, -0.75 to 0.26; P = 0.509). Opioid utilization did not differ between groups, with a median difference of -1.35 μg·kg(-1)·hr(-1) (95% CI, -5.85 to 7.55; P = 0.518), and pain scores did not differ, with a median difference of 0.0 (95% CI, -1.0 to 1.5; P = 0.659).

Conclusion: This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).