Effectiveness of oral glucose as analgesic for neonates undergoing retinopathy of prematurity screening – A randomized pilot study for a parallel randomized control trial

Abstract

Background: Eye examination is a painful procedure. Neonates exposed to painful stimuli have short- and long-term behavioral and sensory problems. To determine an analgesic for alleviating pain during this mandatory painful, medical procedure is of utmost importance, to have optimal outcomes in these vulnerable preterm babies. We analyzed the effectiveness of 25% dextrose solution as analgesic for retinopathy of prematurity (ROP) screening. Objective: The objective was to study the feasibility of conducting a Phase III randomized controlled trial, for oral analgesic during ROP screening in neonates and to utilize this pilot data for calculating sample size for Phase III trial. Place of the Study: The study was conducted in a tertiary care neonatal unit, Southern India. Type of Study: This was a randomized parallel group masked Phase I/2 external pilot study. Methods: Feasibility was defined a priori; the study population was inpatient babies undergoing ROP screening procedure for the first time as per unit protocol. All subsequent babies, after a written consent from parents/legal guardian, were randomized to oral glucose (25% dextrose solution) or placebo group (distilled water). Premature infant pain profile (PIPP) scores were assessed at basal and post procedure. Babies were observed for 24 h for predefined adverse events. Statistical analysis was done using Stata 11.2. Continuous data were expressed as median based on the skewness, and Mann–Whitney U-test was used for hypothesis testing. Results: Twenty-six inpatient neonates were randomized. The median pain scores (PIPP) at 1 min post procedure for the placebo group were 7 IQ (6, 8), and median pain scores of the oral glucose group were 4 IQ (3–5). Eighty-six percent of the eligible babies were randomized for the study. Eighty-five percent of the randomized babies where available for total observation period of 24 h. Inter-rater variability was assessed by interclass correlation (ICC) coefficient. No adverse events (predefined) were recorded in both groups. Conclusion: This randomized pilot trial is feasible to deliver. Oral glucose (25% dextrose) solution has a significant pain alleviation compared to placebo, in our pilot population. Pain scores assessed were validated by independent reviewer with high ICC of 0.89.