A Systematic Review Of Repeated Sucrose For Repeated Procedural Pain In Neonates And A Randomized Controlled Trial Of Combined Sucrose And Non-nutritive Sucking For Repeated Pain Relief In Preterm Infants

Part I Efficacy and safety of repeated oral sucrose for repeated procedural pain in neonates:A systematic reviewBackground:Although sucrose is most extensively examined for its analgesia effect on a single procedural pain, neonates in neonatal intensive care units can be exposed to numerous painful procedures every day requiring multiple doses of sucrose. Some experiments have been performed to examine the efficacy and safety of repeated sucrose administration for repeated procedural pain; however, a systematic review of this topic has not yet been carried out.Objective:To identify and assess the evidence demonstrating the efficacy and safety of repeated sucrose for repeated procedural pain in neonates.Method:A systematic review was conducted using the Cochrane methodology. Pubmed, Cochrane Library, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CBMdisc, CNKI, VIP, and Wanfang databases were searched through December 2015. All related abstracts were reviewed and the full texts of relevant articles were studied. Randomized controlled trials (RCTs) were included. Risk of bias was assessed for RCTs using quality critical appraisal criteria recommended by Cochrane Handbook. A standardized data form was used to extract information.Results:Eight RCTs met our inclusion criteria. Different study designs were used in the included RCTs, which did not allow us to carry out a meta-analysis. The findings from this review indicated that repeated sucrose was effective in reducing both behavioral pain response and composite pain scores during repeated procedural pain. However, as for physiological pain response, one trial found less variability in physiological pain response for term neonates in the sucrose group than the sterile water group, while two trials demonstrated repeated sucrose was inefficacious for preterm infants. Regarding the clinical outcomes, no study reported adverse effects related to the repeated sucrose administration. Regarding the neurobehavioral development, two trials reported repeated sucrose for repeated procedural pain would not lead to poor neurologic development, while one trial reported that preterm infants <31 weeks’ gestational age who received>10 doses of sucrose per 24 hours in the first week of life had poorer neurologic development compared with infants who received fewer sucrose doses. What’s more, no study reported the long-term neurobehavioral development outcome of neonates who repeatedly received sucrose across repeated procedural pain.Conclusion:Evidence regarding the efficacy and safety of repeated sucrose across repeated procedural pain for neonates is limited. More prospective, multi-centered, large randomized controlled clinical trials with a standardised study design are required before sucrose can be recommended widely as an analgesia for repeated procedural pain in neonates.Part Ⅱ Effect of combined sucrose and non-nutritive sucking for repeated procedural pain in preterm infants:A randomized controlled trialBackground:Preterm infants’repeated exposure to painful procedures may lead to negative consequences. Thus, non-pharmacological pain management is essential due to medication side effects. Sucrose is the most frequently studied non-pharmacological intervention for relief of procedural pain in neonates, and has been recommended by many national and international clinical guidelines to prevent or treat procedural pain. There have been studies demonstrating the analgesic effect of combined sucrose and non-nutritive sucking is better than sucrose alone on a single procedural pain. However, there are few studies examining the efficacy and safety of combined sucrose and non-nutritive sucking for repeated procedural pain in peterm neonates. Objective:To test the efficacy and safety of combined sucrose and non-nutritive sucking for repeated procedural pain in preterm infants.Method:Preterm infants (gestational age less than 37 weeks) (n=70) were recruited and randomly assigned to either an control group (n=35) or combined sucrose and non-nutritive sucking group (n=35). Pain assessments were carried out during all painful procedures. Each procedure included 3 phases:baseline, blood collection and recovery. Heart rate, oxygen saturation, crying, grimacing and score by preterm infant pain profile-revised (PIPP-R) in response to pain were evaluated at each phase across all painful procedures by four trained independent observers who were blinded to the purpose of the study. The incidence of side effects such as abdominal distension, vomiting, tachypnea and hyperglycemia, weight gain between birth and discharge in preterm infants, were recorded by one trained independent observer who was blinded to the purpose of the study.Results:Between-group comparison revealed that preterm infants’heart rate was significantly lower, oxygen saturation was significantly higher, the duration of crying and facial grimacing were both significantly shorter, and PIPP-R score was significantly lower in the combined sucrose and non-nutritive sucking group than the control group during repeated procedural pain. The two groups had no significant difference neither in the incidence of side effects nor in the weight gain between birth and discharge.Conclusion:The effect of combined sucrose and non-nutritive sucking analgesia remains stable in preterm infants over repeated painful procedures. Moreover, sucrose combined with non-nutritive sucking was safe for preterm infants. Given the many invasive procedures that are part of clinical care in preterm infants, sucrose combined with non-nutritive sucking may be a safe analgesic alternative in preterm infants in whom it is feasible.