Abstract
Background: - The objective of this systematic review was to examine the effectiveness of pharmacological and physical interventions that target the injection site area on reducing distress during vaccinations in vaccine recipients across the lifespan. Method(s): - GRADE and Cochrane methodology were used. Searches were conducted in MEDLINE, EMBASE, APA PsycINFO, CINAHL, and ProQuest Dissertations to identify relevant randomized and quasi-randomized controlled trials. Included interventions and critical outcomes were determined using a voting process. Studies were reviewed and data extracted by at least two reviewers. Meta-analyses were conducted separately for infants (0-12 mo) and older vaccine recipients (>12 mo), with individual interventions included as subgroups. Point estimates were calculated using standardized mean difference (SMD) with 95% confidence intervals using a random effects model. Results were summarized according to certainty of evidence (4-levels: high to very low) and effect size (4-levels: trivial to large). Result(s): - Altogether, 71 studies were included with a certainty of evidence ranging from high to very low. The magnitude of effect exceeded the minimum threshold (SMD >= 0.2) in all but one analysis. For infants, topical anesthesia and manual tapping (Helfer technique) are preferred interventions for reducing distress (critical outcome), followed by manual or device-facilitated pressure, cold/ice, or vibration with an external device with cold. Use of a vapocoolant is next, followed by vibration with an external device without cold. Manual rubbing has insufficient evidence of benefit. For older vaccine recipients, topical anesthesia is preferred, followed by manual tapping. Vibration with an external device with or without cold, follows thereafter. Manual or device-facilitated pressure, cold/ice, or vapocoolant are less preferred, and the evidence is very uncertain for manual rubbing. Conclusion(s): - Across all ages, topical anesthetics and manual skin tapping emerge as preferred interventions. Implementation should consider the strength of the evidence base as well as vaccine recipient preferences.Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.
