title: Efficacy and safety of repeated oral sucrose for repeated procedural pain in neonates: A systematic review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 standardised 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 neonates. 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 24h 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Gao
authors.affiliation: Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Gao
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: bpn456@163.com.
authors.forename: Guihua
authors.initials: G
authors.lastname: Xu
authors.affiliation: Nanjing Children's Hospital, China. Electronic address: etyyhlb06@sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Shizheng
authors.initials: S
authors.lastname: Du
authors.affiliation: Nanjing Children's Hospital, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Danwen
authors.initials: D
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D006801:Humans; D007231:Infant, Newborn; D059408:Pain Management / Q000379:methods*; D061214:Patient Safety; D013395:Sucrose / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D013395:Sucrose
keywords: Infant; Neonates; Pain; Sucrose; Systematic review