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Clin J Pain. 2015 Oct;31(10 Suppl):S20-37. doi: 10.1097/AJP.0000000000000264.

Procedural and Physical Interventions for Vaccine Injections: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials.

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*Clinical Social and Administrative Pharmacy, Leslie Dan Faculty of Pharmacy §Faculty of Medicine, University of Toronto †Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario ††Department of Paediatrics, The Hospital for Sick Children ‡Department of Pediatrics, Mount Sinai Hospital ‡‡Department of Psychology, York University, Toronto ∥Department of Psychology, University of Guelph, Guelph, Ontario ¶Children's Health Research Institute #Department of Paediatrics, Western University, London, ON **Department of Paediatrics, IWK Health Centre, Dalhousie University and Canadian Center for Vaccinology ∥∥Department of Pediatrics and Psychology, Faculty of Science, Dalhousie University, IWK Health Centre, Halifax, NS, Canada §§Department of Psychology, University of Calgary, AB, Canada.



This systematic review evaluated the effectiveness of physical and procedural interventions for reducing pain and related outcomes during vaccination.


Databases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Data were extracted according to procedure phase (preprocedure, acute, recovery, and combinations of these) and pooled using established methods.


A total of 31 studies were included. Acute infant distress was diminished during intramuscular injection without aspiration (n=313): standardized mean difference (SMD) -0.82 (95% confidence interval [CI]: -1.18, -0.46). Injecting the most painful vaccine last during vaccinations reduced acute infant distress (n=196): SMD -0.69 (95% CI: -0.98, -0.4). Simultaneous injections reduced acute infant distress compared with sequential injections (n=172): SMD -0.56 (95% CI: -0.87, -0.25). There was no benefit of simultaneous injections in children. Less infant distress during the acute and recovery phases combined occurred with vastus lateralis (vs. deltoid) injections (n=185): SMD -0.70 (95% CI: -1.00, -0.41). Skin-to-skin contact in neonates (n=736) reduced acute distress: SMD -0.65 (95% CI: -1.05, -0.25). Holding infants reduced acute distress after removal of the data from 1 methodologically diverse study (n=107): SMD -1.25 (95% CI: -2.05, -0.46). Holding after vaccination (n=417) reduced infant distress during the acute and recovery phases combined: SMD -0.65 (95% CI: -1.08, -0.22). Self-reported fear was reduced for children positioned upright (n=107): SMD -0.39 (95% CI: -0.77, -0.01). Non-nutritive sucking (n=186) reduced acute distress in infants: SMD -1.88 (95% CI: -2.57, -1.18). Manual tactile stimulation did not reduce pain across the lifespan. An external vibrating device and cold reduced pain in children (n=145): SMD -1.23 (95% CI: -1.58, -0.87). There was no benefit of warming the vaccine in adults. Muscle tension was beneficial in selected indices of fainting in adolescents and adults.


Interventions with evidence of benefit in select populations include: no aspiration, injecting most painful vaccine last, simultaneous injections, vastus lateralis injection, positioning interventions, non-nutritive sucking, external vibrating device with cold, and muscle tension.

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