Abstract Objectives Arterial puncture/cannulation is considered to be a severely painful procedure. Both non-pharmacological and pharmacological interventions are recommended by professional organizations to alleviate pain in neonates undergoing arterial puncture/cannulation, but these recommendations are not based on systematic review of the literature. The primary objective of this systematic review and meta-analysis was to synthesize the literature on pain management strategies in this setting. Methods Databases were searched for randomized trials evaluating pharmacological and non-pharmacological interventions for pain mitigation for arterial puncture/cannulation from inception to July 2024. The literature search was updated in June 2025 and no additional eligible articles were identified for inclusion. Title and abstract screening, full-text screening, and data extraction were performed in duplicate. The risk of bias was assessed using Cochrane’s risk of bias (RoB) 2.0 tool. The critically important outcome was pain measured using validated tools including unidimensional behaviour and multidimensional (comprising combinations of contextual, behavioural, and/or physiological components) tools. Secondary outcomes included procedure success and adverse events. Pooled effect estimates were standardized mean difference (SMD) and relative risk (RR) with 95% confidence intervals (CI) using random effects models. A GRADE assessment of the overall certainty of the evidence for each outcome was completed. Results Five studies including a total of 358 neonates were included. All assessed pain from arterial puncture rather than cannulation. The interventions evaluated in the included studies were: 1) white noise (50 dB) compared to control (0 dB), 2) expressed breast milk compared to 25% oral dextrose, 3) music, 25% oral dextrose or both, 4) familiar scent compared to unfamiliar scent or control, and 5) 24% oral sucrose compared to no intervention. Expressed breast milk was effective in reducing procedural pain compared to 25% oral dextrose (SMD -0.95 95% CI -1.64, -0.24; n = 36). The familiar scent was effective in reducing the duration of cry when compared to unfamiliar scent (MD -22.96 95% CI -33.20, -12.72; n = 90) and control (MD -25.22 95% CI -35.22, -15.22; n = 90) respectively. There was low certainty of evidence for all critical outcomes. No statistically significant difference was demonstrated for other comparisons. Conclusion: Expressed breast milk and familiar scent may be effective in reducing pain during arterial puncture based on single studies, however, there is low confidence in the estimates of effect. There is a need for further research on pharmacological interventions for this procedure.
Chirinian et al. (Mon,) studied this question.