Crecelius 1999.

Methods	Randomized placebo controlled trial at a US school of dentistry
Participants	88 patients between age 18 and 80 years, scheduled to have dental surgery Patients with scarred veins were excluded "The subject population ranged in age from 18 to 72 years," mean 28 years, 60% female, 78% white
Interventions	"All subjects were given titers with incremental increases in the concentration of nitrous oxide until the patient reported feeling relaxed, light‐headed, and tingling, with a feeling or floating or heaviness. The placebo or ethyl chloride spray was then applied" "One group received room temperature distilled water spray before cannulation. The other group received a 10 second spray of ethyl chloride prior to venous cannulation"
Outcomes	Pain and anxiety before/after nitrous oxide, pain and anxiety following application of spray, pain and anxiety following venous cannulation. Adverse events
Funding	"Supported in part by NIDR grant"
Notes	All participants also received nitrous oxide, as described above
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomly assigned" "Randomly divided" Study author contacted: "A random number table was used for the randomization rather than a random number generator"
Allocation concealment (selection bias)	Low risk	Not described. Study author contacted: "The research nurse kept the allocation concealed in envelops"
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	"Since most subjects would not have had previous experience with ethyl chloride, they were likely unable to determine the spray treatment they received. The venipuncturist was not present during the spray application"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Most subjects (51%) and venipuncturists (46%) reported they were unable to tell if ethyl chloride or placebo was applied" "Of the 43 subjects reporting which treatment they received, 6 reported receiving placebo incorrectly and 3 reported receiving ethyl chloride incorrectly" "The venipuncturists reported knowing which treatment 48 subjects received. They reported incorrectly that 5 patients received ethyl chloride when placebo was administered and incorrectly that 1 patient received water when ethyl chloride was administered"