Objectives To determine if the addition of an inhaled equimolar mixture of nitrous oxide (N₂O) and oxygen (EMONO) would produce superior pain relief to standard pharmacological and non-pharmacological measures during eye examination screening for retinopathy of prematurity (ROP) in premature infants.

Study design A randomised, double-blind controlled trial was conducted.

Setting Royal Victoria Hospital, a tertiary neonatal intensive care unit in Montreal, Canada.

Patients Stable spontaneously breathing premature infants with birth weights less than 1500 g or gestation of 30 weeks and less.

Intervention During the eye examination, all infants were swaddled, received oral sucrose and topical anaesthetics. Control group infants received a mixture of 50% oxygen and 50% nitrogen (n=18) administered by nasal cannula, while the intervention group received EMONO (50% oxygen and 50% N₂O).

Main outcome measures Pain was assessed by the premature infant pain profile (PIPP).

Results The mean PIPP score at speculum insertion in the control group (8.4, 95% CI 7.6 to 9.3) was comparable with the EMONO group (8.5, 95% CI 7.3 to 9.8) with a p value of 0.94. There were no significant differences in heart rate or saturation between the two groups. EMONO inhalation was tolerated without any measured side effects.

Conclusion EMONO does not produce any additional pain relief over currently used measures during ROP screening eye examinations. Systematically combining pharmacological and non-pharmacological treatment modalities appears to be the best option until newer treatments are proven effective.

Clinical trials registration number NCT00623220