• Wenjie Guo, Xinmei Liu, Xue Zhou, Tianxing Wu, and Jiao Sun.
• The First Bethune Hospital of Jilin University, Changchun, China.
• Int J Nurs Stud. 2020 Feb 1; 102: 103471.

IntroductionPremature infants undergo numerous painful procedures during hospitalization. Some trials have examined the effectiveness and safety of combined nonpharmacological interventions in which two or more non-pharmacological interventions are used simultaneously or continuously to relieve repeated procedural pain via multisensory stimulation in preterm neonates. However, a systematic review of this topic has not yet been carried out.ObjectiveTo review the evidence on the efficacy and safety of combined nonpharmacological interventions for repeated procedural pain in preterm neonates.MethodEight databases were searched using keywords to identify peer-reviewed journal articles in English or Chinese. Randomized controlled trials (RCTs) focusing on combined nonpharmacological interventions for repeated procedural pain in preterm neonates published from database inception until May 2019 were included.ResultsEight RCTs were retrieved that included ten different combined nonpharmacological interventions. Different study designs were used in the included trials, which did not allow us to carry out a meta-analysis. The findings from the included articles were categorized in terms of efficacy and safety. With respect to efficacy, 1. two trials reported that combined nonpharmacological interventions were more effective than usual care during painful procedures; 2. three trials reported that combined nonpharmacological interventions were more effective than single nonpharmacological interventions; 3. three trials reported the effects of different combinations of nonpharmacological interventions and found that their effect depends on intervention type rather than number of interventions. Only four trials reported on safety, and they found that combined nonpharmacological interventions were safe for repeated procedural pain in preterm neonates.ConclusionAccording to the literature, combined nonpharmacological interventions may be effective and safe for repeated procedural pain in premature infants. However, due to the diversity of interventions included in this systematic review, the evidence is not strong enough to produce a best practice guideline. Further research is needed with larger sample sizes and less heterogeneity to adequately explore the efficacy and safety of combined nonpharmacological interventions for repeated procedural pain in premature infants.Copyright © 2019. Published by Elsevier Ltd.

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