Ramsook 2001.

Methods	Randomized placebo‐controlled trial in the emergency department of a children's hospital in the USA
Participants	222 patients, aged 3 to 18 years, who presented to the emergency department "requiring IV cannulation for fluids or medication administration and venipuncture for diagnostic tests" "There were no statistically significant differences for age, gender, or report of pain score for a previous intravenous cannulation and/or venipuncture between the two groups" Excluded were "pre‐verbal or developmentally delayed patients who could not complete the required self report pain scale, and patients presenting with a painful condition" 56% of intervention group and 53% of placebo group were female
Interventions	Standardized skin cleaning followed by spray from 6 inches for 5 seconds followed by immediate venipuncture. "Spraying was terminated if frosting of the skin occurred, due to cooling of skin moisture, or if the patient felt any discomfort" Intervention group (114) received ethyl chloride spray Placebo group (108) received isopropyl alcohol spray
Outcomes	Self reported pain of cannulation, difficulty of insertion, number of attempts before success, degree of impairment of the spray of vein visibility
Funding	None declared
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Blinded randomization tables"
Allocation concealment (selection bias)	Low risk	"The pharmacist provided the appropriate spray to the nurse caring for the patient"
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants enrolled included in analysis
Selective reporting (reporting bias)	Unclear risk	Protocol not available, but all expected outcomes reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The manufacturer provided identically matched cans of isopropyl alcohol as placebo"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Nurses may have been able to recognise ethyl chloride by the white precipitate during application. However they were not involved in pain assessment and could not have influenced these results. The nurse may have reported on the operator difficulty and impairment of vein visibility knowing which spray they had used"