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Clin J Pain. 2015 Oct;31(10 Suppl):S38-63. doi: 10.1097/AJP.0000000000000281.

Pharmacological and Combined Interventions to Reduce Vaccine Injection Pain in Children and Adults: Systematic Review and Meta-Analysis.

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*Mount Sinai Hospital †Faculty of Medicine ‡Leslie Dan Faculty of Pharmacy, University of Toronto §The Hospital for Sick Children ‡‡Department of Psychology, York University, Toronto ∥Department of Psychology, University of Guelph, Guelph ¶Children's Health Research Institute, London #Department of Paediatrics, Western University, London, ON **Departments of Pediatrics and Microbiology and Immunology, IWK Health Centre, Dalhousie University §§Department of Pediatrics and Psychology, Faculty of Science, IWK Health Centre, Dalhousie University, Halifax, NS, Canada ††Department of Psychology, University of Calgary, AB, Canada.



This systematic review assessed the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in individuals across the lifespan.


Electronic databases were searched for relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear as well as observer-rated distress were critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk with 95% confidence intervals (CI).


Fifty-five studies that examined breastfeeding (which combines sweet-tasting solution, holding, and sucking), topical anesthetics, sweet-tasting solutions (sucrose, glucose), vapocoolants, oral analgesics, and combination of 2 versus 1 intervention were included. The following results report findings of analyses of critical outcomes with the largest number of participants. Compared with control, acute distress was lower for infants breastfed: (1) during vaccination (n=792): SMD -1.78 (CI, -2.35, -1.22) and (2) before vaccination (n=100): SMD -1.43 (CI, -2.14, -0.72). Compared with control/placebo, topical anesthetics showed benefit on acute distress in children (n=1424): SMD -0.91 (CI, -1.36, -0.47) and self-reported pain in adults (n=60): SMD -0.85 (CI, -1.38, -0.32). Acute and recovery distress was lower for children who received sucrose (n=2071): SMD -0.76 (CI, -1.19, -0.34) or glucose (n=818): SMD -0.69 (CI, -1.03, -0.35) compared with placebo/no treatment. Vapocoolants reduced acute pain in adults [(n=185), SMD -0.78 (CI, -1.08, -0.48)] but not children. Evidence from other needle procedures showed no benefit of acetaminophen or ibuprofen. The administration of topical anesthetics before and breastfeeding during vaccine injections showed mixed results when compared with topical anesthetics alone. There were no additive benefits of combining glucose and non-nutritive sucking (pacifier) compared with glucose or non-nutritive sucking (pacifier) alone or breastfeeding and sucrose compared with breastfeeding or sucrose alone.


Breastfeeding, topical anesthetics, sweet-tasting solutions, and combination of topical anesthetics and breastfeeding demonstrated evidence of benefit for reducing vaccine injection pain in infants and children. In adults, limited data demonstrate some benefit of topical anesthetics and vapocoolants.

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