Untreated Procedural Pain Increases Urine Markers of Adenosine Triphosphate (ATP) Utilization in Preterm Neonates

Thursday, 27 July 2017: 3:30 PM

Danilyn Mag-akat Angeles, PhD, RN
Division of Physiology, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, USA
Danilo Boskovic, PhD
Division of Biochemistry, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, USA


We previously published that a single dose of oral sucrose significantly increased plasma markers of adenosine triphosphate (ATP) utilization (hypoxanthine) and oxidative stress (xanthine, allantoin) in neonates undergoing a clinically required heel lance [1,2]. However, the effect of repeated doses of sucrose and other sweet solutions such as glucose on above markers is unknown.


Using a prospective randomized double blind clinical trial, we measured urinary markers of ATP utilization and oxidative stress in preterm neonates over days of life 3-7. Subjects were preterm neonates who are 28-34 weeks in gestation. Exclusion criteria include: significant cardiovascular and respiratory disease, IVH, NEC, on opioids or sedatives. After obtaining parental consent, subjects were randomly assigned to receive standard of care (control, n=12) or either 24% oral sucrose (n=14) or 30% oral glucose (n=13) two minutes before any tissue-damaging procedure (TDP). Demographic data for categorical variables were analyzed using Chi-square test. Repeated measures ANOVA for one between subject factor (group) and one within subject factor (time) were assessed to evaluate the effect of the procedures (control, 24% oral sucrose, 30% oral glucose) over time. Interaction terms in the General Linear Model were used for this purpose.


We found that neonates who received 24% oral sucrose tend to have higher urinary concentration of xanthine compared to those who received 30% oral glucose, specifically at day of life 4. However, the highest urinary concentrations of xanthine (P=0.019) and uric acid (P=0.028) were found in control subjects who received the least amount of oral sucrose analgesia.

Conclusion: These data support our previous findings that untreated pain results in increased ATP utilization and oxidative stress [2]. In addition, this finding suggests that 30% oral glucose may be an acceptable and metabolically less demanding alternative to oral sucrose as a non-pharmacological intervention to procedural pain. Further studies are required to examine more effective ways to decrease procedural pain in preterm neonates.