A Clinical Investigation Of An Appropriate Dosage Regimen Of Midazolam And Fentanyl For Sedation During Regional Anesthesia

Objective: To investigate the efficacy and respiratory complications of midazolam combined with different dose fentanyl for sedation during regional anesthesia, and to determine the appropriate dosage regimen.Methods: Three hundred patients undergoing surgery with regional anesthesia were enrolled in this multicenter, double-blind, randomized study. Patients were randomly assigned to five groups of 60 patients each according to the dosage of midazolam and fentanyl in a bolus. (groupM+F₁₀₀: midazolam 1mg/ fentanyl 10μg; groupM+F₂₀₀: midazolam 1mg/ fentanyl 20μg; groupM+F₃₀₀: midazolam 1mg/ fentanyl 30μg; groupM+F₄₀₀: midazolam 1mg/ fentanyl 40μg; groupM+F₅₀₀: midazolam 1mg/ fentanyl 50μg).Patients received 2 ml mixture (a bolus) of midazolam and fentanyl every 5min until a Modified Wilson Sedation Scale of 2 was achieved. BP,HR,RR,SpO₂,and PetCO₂ were measured every 5min for 45min. Intraoperative amnesia effects was assessed using picture recall test. The time required to achieve Modified Wilson sedation scale of 2, total dose of midazolam and fentanyl, and perioperative complications were recorded. The investigator's overall satisfaction with the sedation protocol was assessed using the visual analog scale (VAS). Data was analyzed using SPSS program.Results: The groups were comparable in terms of sex, age, height and weight. The time to achieve Modified Wilson sedation scale score of 2 in groupM+F₁₀₀, groupM+F₂₀₀, groupM+F₃₀₀, groupM+F₄₀₀, and groupM+F₅₀₀ were 19.1±7.0min, 17.8±7.9min, 16.2±7.0min, 14.2±6.0min, and 13.0±6.1 min, respectively. The overall amnesia effects among 5 groups was 70.0%, there were no significant differences in the amnesia effects between 5 groups. The investigator's overall satisfaction with the sedation protocol in groupM+F₃₀₀ was 9.2±0.7 which was significantly higher than that in groupM+F₁₀₀, groupM+F₄₀₀,and groupM+F₅₀₀, there were no significant differences in the investigator's overall satisfaction with the sedation protocol between groupM+F₂₀₀ and groupM+F₃₀₀(8.9±0.7). Each group had a stable hemodynamics, there were no significant differences in the hemodynamic variables between 5 groups. With increasing the doses of fentanyl, respiratory complications progressively increased. Patients in groupM+F₁₀₀ received smaller doses fentanyl (38.8±13.4μg), resulted in fewer respiratory complications: 3.3% patients experienced bradypnea (＜8 breaths/min), 21.7% patients experienced moderate oxygen desaturation (SpO₂＜95%), and 3.3% patients experienced upper respiratory obstruction. Respiratory complications occurred more often in group M+F₄₀₀ and group M+F500 due to their relatively more fentanyl doses (117.3±41.7μg and 140.0±57.3μg, respectively),23.3% patients in group M+F₄₀₀ and 35.0% patients in group M+F₅₀₀ experienced severe oxygen desaturation (SpO₂＜90%), 38.3% patients in group M+F₄₀₀ and 50.0% patients in group M+F₅₀₀ experienced moderate oxygen desaturation (SpO₂＜95%), 20.0% patients in group M+F₄₀₀ and 30.0% patients in group M+F₅₀₀ experienced bradypnea (＜8 breaths/min), 10.0% patients in group M+F₄₀₀ and 28.3% patients in group M+F₅₀₀ experienced upper respiratory obstruction. A moderate dose of fentanyl (66.3±31.9μg and 99.6±39.1μg) was administered to the patients in group M+F₂₀₀ and groupM+F₃₀₀ respectively.25.0% patients in group M+F₂₀₀ and 33.3% patients in group M+F₃₀₀ experienced moderate oxygen desaturation ((SpO₂＜95%),11.7% patients and 8.3% patients in both groups experienced severe oxygen desaturation ((SpO₂＜90%) and upper airway obstruction, respectively; 6.7% patients in group M+F₂₀₀ and 11.7% patients in group M+F₃₀₀ experienced bradypnea (＜8 breaths/min).Conclusion: Intravenous sedation with intermittent midazolam 1mg combined with fentany 20μg or 30ug was a safe and effective dosage regimen for regional anesthesia, provided adequate sedation and amnesia with a stable hemodynamics, and resulted in fewer respiratory complications.