Analgesic Effect of Cocaine and Lidocaine/Xylometazoline in Healthy Volunteers Undergoing Awake Nasal Intubation: A Randomized Controlled Crossover Trial

Mo Haslund Larsen*, Oscar Rosenkrantz, Rasmus Linnebjerg Knudsen, Rasmus Hesselfeldt, Ole Hilberg, Volkert Siersma, Johan Heiberg, Lars Simon Rasmussen, Dan Isbye

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Background: Several drugs may be used to minimize pain during nasal intubation in awake patients. We hypothesized that the analgesic effect of cocaine would be at least as good (non-inferior) as that of lidocaine with xylometazoline rated as maximum pain felt during awake nasal intubation of healthy volunteers. Methods: We conducted an outcome assessor blinded, randomized, triple crossover, non-inferiority study following approval from the local research ethics committee and the national medicine agency. Healthy volunteers came for three visits and received 2 mL 4% cocaine, 0.5 mL 4% lidocaine + 1.5 mL 0.1% xylometazoline, and 2 mL 0.9% saline in random order prior to nasal insertion of an endotracheal tube. Maximum pain felt during insertion was evaluated on a visual analogue scale of 0–100 mm. The non-inferiority margin was set to 11 mm on the visual analogue scale. Results: A total of 16 volunteers were enrolled, and 14 completed all three visits. Maximum pain felt during tube insertion was a median of 69 mm (interquartile range [IQR]: 56–73 mm) after cocaine, 60 mm (IQR: 50–76 mm) after lidocaine/xylometazoline, and 70 mm (IQR: 63–81 mm) after saline. The mean difference in maximum pain scores between cocaine and lidocaine/xylometazoline was 3.3 mm (95% confidence interval: −4.6 to 11.1; p = 0.40). Conclusion: We found no statistically significant difference in pain scores between cocaine and lidocaine/xylometazoline when administered prior to awake nasal intubation but cannot conclude that cocaine was non-inferior to lidocaine/xylometazoline. Editorial Comment: Nasal intubation may be uncomfortable and can be complicated by epistaxis. Cocaine has both vasoconstrictive and analgesic properties and was compared with placebo and lidocaine/xylometazoline for awake intubation in healthy volunteers. The trial did not identify any clinically important differences between groups in terms of pain or serious adverse events. Differences were numerically small, and non-inferiority between the active treatments was not demonstrated. Trial Registration: Clinicaltrials.gov identifier: NCT06443255.

Original languageEnglish
Article numbere70056
JournalActa Anaesthesiologica Scandinavica
Volume69
Issue6
ISSN0001-5172
DOIs
Publication statusPublished - Jul 2025

Keywords

  • cocaine
  • nasal
  • nasotracheal intubation
  • pain

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