RANDOMIZED TRIAL OF ORAL MORPHINE FOR PAINFUL EPISODES OF SICKLE-CELLDISEASE IN CHILDREN

Background Oral controlled-release morphine can provide effective anal gesia through a non-invasive route and may facilitate outpatient manag ement of severe episodes of sickle-cell pain. We compared the clinical efficacy and safety of oral morphine with continuous intravenous morp hine in children with severe episodes of sickle-cell pain, by a double -blind, randomised, parallel-group design. Methods 56 children aged 5- 17 years received loading doses of intravenous morphine of up to 0.15 mg/kg, followed by randomly assigned oral morphine 1.9 mg/kg every 12 h plus intravenous placebo (saline), or intravenous morphine 0.04 mg k g(-1) h(-1), plus placebo tablet. Breakthrough pain was treated with o ral, immediate-release morphine 0.4 mg/kg every 2-3 h as required. Pai n was assessed daily at 0900 h, 1300 h, 1700 h, and 2100 h with a pict ure face scale, a pictorial scale (Oucher), a behavioural-observationa l scale (CHEOPS), and by an investigator. Findings 50 children complet ed the study (28 boys, 22 girls; mean age 11.2 years [SD 3.5]; mean or al morphine dose 2.99 mg/kg daily [0.75]; mean intravenous morphine do se, 0.81 mg/kg daily [0.30]). Mean overall pain scores were similar fo r oral and intravenous morphine (CHEOPS, 6.3 [1.5] vs 6.4 [1.4], p=0.8 ; Oucher, 31.5 [25.4] vs 39.2 [21.7], p=0.3; Faces, 2.2 [1.4] vs 2.4 [ 1.3], p=0.6; clinical rating, 1.7 [0.7] vs 1.9 [0.5], p=0.3). Opioid a nalgesia was required for a mean of 4.2 days (1.7) and 5.4 days (2.6), respectively (p=0.0591). Pain scores from all scales correlated signi ficantly (r=0.5865-0.8980, p=0.0001). Frequency of rescue analgesia di d not differ significantly between the oral and intravenous morphine g roups (0.7 [0.8] vs 0.9 [0.7] doses daily, p=0.2). Frequency and sever ity of adverse events did not differ significantly. Interpretation Ora l, controlled-release morphine isa reliable, non-invasive alternative to continuous intravenous morphine for the management of painful episo des of sickle-cell disease in children.