Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy

Abstract
Midazolam is commonly used for sedation during gastrointestinal procedures. However, some patients experience paradoxical reactions characterized by excessive movement or excitement. To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper endoscopy. We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital, Healthcare System Gangnam Center, from July 2013 to December 2018. Among them, 361 patients with a history of paradoxical reaction during sedative upper endoscopy were enrolled. The characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic regression. Paradoxical reactions occurred in 0.86% (1054/122152) of endoscopies, and in 1.51% (888/58553) of patients. Among the 361 subjects with previous paradoxical reactions in sedative endoscopies, 111 (30.7%) experienced further paradoxical reactions. Univariable analysis revealed that the total midazolam dose used was higher in the recurrent group (6.74 ± 2.58 mg) than in the non-recurrent group (5.49 ± 2.04 mg; P < 0.0001). Patients were administered a lower dose of midazolam than previous doses: 1 mg less in the recurrent group and 2 mg less in the non-recurrent group. Multivariable analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction (odds ratio: 1.213, 95%CI: 1.099-1.338, P = 0.0001). The rate of recurrence of paradoxical reactions is significantly associated with midazolam dosage. The dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.