Effects of Remimazolam Dose and Bolus Injection Rate on Hiccups During Painless Colonoscopy: A Double-Blind Randomized Clinical Trial

Background: Remimazolam is increasingly used for procedural sedation because of its rapid onset, rapid recovery and favourable haemodynamic profile. However, hiccups remain a clinically relevant adverse event that may interfere with endoscopic manipulation. The independent and combined effects of remimazolam dose and injection rate on hiccup occurrence have not been well characterized. Methods: In this prospective, randomized, double-blind, 2× 2 factorial trial, adult patients undergoing painless colonoscopy were randomized to receive remimazolam at 0.3 or 0.4 mg kg − 1 , administered over 10s or 20s. The primary endpoint was hiccup incidence. Secondary endpoints included body movement, supplemental bolus requirements, time to loss of eyelash reflex, recovery time, haemodynamic changes, Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores and postoperative Numeric Rating Scale (NRS) scores. Multivariable logistic regression evaluated the independent effects of dose and injection rate on hiccup incidence and tested for interaction. Results: Both the higher remimazolam dose (0.4 mg kg − 1 ) and the slower bolus injection rate (20s) were independently associated with a lower incidence of hiccups. After adjustment for age, sex, body mass index, smoking status, hypertension and diabetes, the 0.4 mg kg − 1 regimen showed lower odds of hiccups than the 0.3 mg kg − 1 regimen, and 20s administration showed lower odds than 10s. No significant dose × rate interaction was detected. The higher-dose regimen was additionally associated with fewer body movements and supplemental boluses, without increased haemodynamic compromise. Conclusion: Both a higher remimazolam dose and a slower bolus injection rate were independently associated with a lower incidence of hiccups during painless colonoscopy. Remimazolam 0.4 mg kg − 1 administered over 20s may offer the most favourable balance between hiccup prevention, procedural conditions and haemodynamic stability. Keywords: remimazolam, hiccups, colonoscopy, injection rate, factorial trial