Comparative Evaluation of Dexmedetomidine-Midazolam and Fentanyl-Midazolam for Sedation and Analgesia in Lower Extremity Orthopedic Surgery under Spinal Anesthesia: A Randomized Double-Blind Clinical Trial
,
Abstract
Background: Spinal anesthesia is a very commonly used procedure in modern-day anesthesia practice. Today most of the lower limb surgeries are performed under spinal anesthesia. Midazolam, dexmedetomidine, and fentanyl are common intravenous adjuvants used during anesthesia to allay anxiety and sedation. The aim of this study was to compare the effects of intravenous dexmedetomidine-midazolam versus fentanyl-midazolam in terms of analgesic characteristics, sedation, and adverse effects.
Methods: This is a randomized prospective study that included 35 patients in each group, posted for lower limb orthopedic surgery. Intravenous dexmedetomidine, fentanyl, and midazolam were administered after subarachnoid block. Data for sedation, analgesia, hemodynamic parameters, and adverse effects were recorded.
Results: RR for FM group showed significant intra-group variability in RR across perioperative stages (p<0.05), whereas the DM group maintained greater respiratory stability (p=0.243). HR for DM group exhibited significantly lower intraoperative and postoperative HR compared to FM group (p<0.001), with notable within-group changes, unlike the FM group. MAP for both groups remained stable over time (DM: p= 0.283, FM: p= 0.260), although the FM group had slightly higher values in the postoperative recovery phase. Sedation (RSS): DM produced deeper and more sustained sedation intraoperatively and postoperatively (p<0.001), while FM showed quicker sedation decline. Patient satisfaction was significantly higher in the DM group (VAS: 3.0 vs. 4.0, p= 0.001), although surgeon satisfaction did not differ notably. Adverse events were rare and comparable, though hypotension was more frequent in the DM group (22.9% vs. 8.6%).
Conclusion: Dexmedetomidine plus midazolam provided superior sedation quality and patient satisfaction, with more stable cardiopulmonary parameters during orthopedic surgery under spinal anesthesia. Despite a slightly higher rate of hypotension, DM appears to offer a more favorable sedative profile compared to fentanyl plus midazolam.
[1] Arefayne NR, Tegegne SS, Gebregzi AH, Mustofa SY. Incidence and associated factors of post-operative pain after emergency Orthopedic surgery: A multi-centered prospective observational cohort study. Int J Surg Open. 2020; 27:103-13.
[2] García LTC, Ponce FEEO, Esparza ACM. Postoperative Pain in Orthopedics. Topics Postoper Pain. IntechOpen. 2023.
[3] Ranjbar Moghaddam M, Merajikhah A, Mahdood B, Mousavi E, Bastami M. Analyzing outcomes of platelet-rich plasma usage on surgical wounds: A systematic review. Curr Probl Surg. 2025; 64:101704.
[4] Vasigh A, Tarjoman A, Borji M. The effect of spiritual-religious interventions on patients' pain status: Systematic review. Anaesth Pain Intensive Care. 2018; 22(4).
[5] Sarafi M, Azimi B, Vasigh A, Ebrahimisaraj G. Assessment of Chronic Postoperative Inguinal Hernia Pain (CPIP) in Children. Arch Anesth Crit Care. 2025.
[6] Sampognaro G, Harrell R. Multimodal Postoperative Pain Control After Orthopaedic Surgery. StatPearls [Internet]. StatPearls Publishing. 2025.
[7] Pogatzki-Zahn EM, Segelcke D, Schug SA. Postoperative pain-from mechanisms to treatment. Pain Rep. 2017; 2(2):e588.
[8] Dafny NPPS. Chapter 6) Neuroscience Online: An Electronic Textbook for the Neurosciences. Dept Neurobiol Anat UT Med Sch Houston.
[9] Ghasembandi M, Jazini Dorcheh S, Farahmand H, Zabihi Rad J, Mousavi E. The Frequency and the Causes of Damages to Surgical Gloves in Orthopedic Surgeries. J Isfahan Med Sch. 2019; 37(527):522-8.
[10] Hatefi M, Parvizi R, Borji M, Tarjoman A. Effect of Self-Management Program on Pain and Disability Index in Elderly Men with Osteoarthritis. Anesth Pain Med. 2019; 9(4):e92672.
[11] Chunduri A, Aggarwal AK. Multimodal Pain Management in Orthopedic Surgery. J Clin Med. 2022; 11(21):6386.
[12] Mousavi E, Kavi E, Larti N, Gharahzadeh A. The relationship between attitude toward the effectiveness of teamwork and observing safety standards in Isfahan educational hospitals. Rev Lat Am Hipertens. 2018; 13(3):271-6.
[13] Tan M, Law LS, Gan TJ. Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways. Can J Anaesth. 2015; 62(2):203-18.
[14] Sarafi M, Azimi B, Vasigh A, Ebrahimisaraj G. Prevalence and Factors Affecting Postsurgical Pain in Pediatric and Adolescent Patients. Arch Anesth Crit Care. 2025.
[15] Azimi B, Sarafi M, Karimian M, Ebrahimisaraj G. Comparison of Patterns and Outcomes of Patients with Penetrating and Blunt Abdominal Trauma: A Retrospective Study. Govaresh. 2025; 1(1):25-9.
[16] Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001; 14(1):13-21.
[17] Yoon DK, Ban JS, Lee SG, Lee JH, Kim E, An J. Dexmedetomidine combined with midazolam vs. dexmedetomidine alone for sedation during spinal anesthesia. Korean J Anesthesiol. 2016; 69(5):446-52.
[18] Choi YM, Choi EJ, Ri HS, Park JY, You JA, Byeon GJ. The effect of dexmedetomidine and midazolam on combined spinal-epidural anesthesia in patients undergoing total knee arthroplasty. Anesth Pain Med (Seoul). 2020; 15(1):111-9.
[19] Bishnoi V, Kumar B, Bhagat H, Salunke P, Bishnoi S. Comparison of Dexmedetomidine Versus Midazolam-Fentanyl Combination for Monitored Anesthesia Care During Burr-Hole Surgery for Chronic Subdural Hematoma. J Neurosurg Anesthesiol. 2016; 28(2):141-6.
[20] Jones J Jr, Southerland W, Catalani B. The Importance of Optimizing Acute Pain in the Orthopedic Trauma Patient. Orthop Clin North Am. 2017; 48(4):445-65.
[21] Drevet S, Boussat B, Grevy A, Brevet A, Olive F, Richard M, et al. Perioperative pain management intervention in older patients with hip fracture in an orthogeriatric unit. A controlled before/after study assessing an audit and feedback intervention (PAIN-AGE). BMC Geriatr. 2024; 24(1):735.
[22] Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017; 10:2287-98.
[23] Stretanski MF, Kopitnik NL, Matha A, Conermann T. Chronic Pain. StatPearls [Internet]. StatPearls Publishing. 2025.
[24] Ke HH, Liou JY, Teng WN, Hsu PK, Tsou MY, Chang WK, et al. Opioid-sparing anesthesia with dexmedetomidine provides stable hemodynamic and short hospital stay in non-intubated video-assisted thoracoscopic surgery: a propensity score matching cohort study. BMC Anesthesiol. 2023; 23(1):110.
[25] Nolan PJ, Delgadillo JA, Youssef JM, Freeman K, Jones JL, Chehrehsa A. Dexmedetomidine Provides Fewer Respiratory Events Compared With Propofol and Fentanyl During Third Molar Surgery: A Randomized Clinical Trial. J Oral Maxillofac Surg. 2020; 78(10):1704-16.
[26] Vaswani JP, Debata D, Vyas V, Pattil S. Comparative Study of the Effect of Dexmedetomidine Vs. Fentanyl on Haemodynamic Response in Patients Undergoing Elective Laparoscopic Surgery. J Clin Diagn Res. 2017; 11(9):UC04-UC08.
[27] Yousuf A, Ahad B, Mir AH, Mir AW, Wani JG, Hussain SQ. Evaluation of Effectiveness of Dexmedetomidine and Fentanyl-midazolam Combination on Sedation and Safety during Awake Fiberoptic Intubation: A Randomized Comparative Study. Anesth Essays Res. 2017; 11(4):998-1003.
[28] Roney G, Jooste EH, Callahan PM, Litchenstein SE, Davis PJ, Adams PS. Sedation and Analgesia. Crit Care Child Heart Dis. Springer. 2020:101-11.
[29] Peng K, Liu HY, Liu SL, Ji FH. Dexmedetomidine-fentanyl Compared With Midazolam-fentanyl for Conscious Sedation in Patients Undergoing Lumbar Disc Surgery. Clin Ther. 2016; 38(1):192-201.e2.
[30] Talke P, Anderson BJ. Pharmacokinetics and pharmacodynamics of dexmedetomidine-induced vasoconstriction in healthy volunteers. Br J Clin Pharmacol. 2018; 84(6):1364-72.
[31] Li CW, Li YD, Tian HT, Kong XG, Chen K. Dexmedetomidine-midazolam versus Sufentanil-midazolam for Awake Fiberoptic Nasotracheal Intubation: A Randomized Double-blind Study. Chin Med J (Engl). 2015; 128(23):3143-8.
[32] Shoraibi M, Masoudifar M, Shetabi H. Comparison of the Cardiovascular Response to Sedation with Dexmedetomidine, Midazolam, and Etomidate in Phacoemulsification under Local Topical Anesthesia; A Double-Blind Randomized Controlled Clinical Trial. Adv Biomed Res. 2024; 13:81.
[33] Yadav U, Yadav JBS, Srivastava D, Srivastava S. A Randomized Controlled Study Comparing Dexmedetomidine-Midazolam with Fentanyl-Midazolam for Sedation during awake Fiberoptic Intubation in Anticipated Difficult Airway. Anesth Essays Res. 2020; 14(2):271-6.
[34] Magazine R, Elenjickal VM, Padukone AM, Bhat A, Chogtu B. Comparison Between Dexmedetomidine and Midazolam-Fentanyl Combination in Flexible Bronchoscopy: A Prospective, Randomized, Double-blinded Study. J Bronchology Interv Pulmonol. 2024; 31(4):e0985.
[35] Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, et al. Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile. Br J Anaesth. 2017; 119(2):211-20.
[36] Joo J, Koh H, Lee K, Lee J. Effects of Systemic Administration of Dexmedetomidine on Intraocular Pressure and Ocular Perfusion Pressure during Laparoscopic Surgery in a Steep Trendelenburg Position: Prospective, Randomized, Double-Blinded Study. J Korean Med Sci. 2016; 31(6):989-96.
[37] Oriby ME, Elrashidy A, Khafagy AG, Philip Rezkalla P. Dexmedetomidine vs. Fentanyl-Midazolam Combination to Mitigate the Stress Response in Microlaryngoscopy: A Randomized Double-blind Clinical Trial. Anesth Pain Med. 2023; 13(3):e135276.
[38] Nie J, Li C, Yang G, Chang H, Ding G. An evaluation of dexmedetomidine in combination with midazolam in pediatric sedation: a systematic review and meta-analysis. BMC Anesthesiol. 2024; 24(1):210.
[39] Kostroglou A, Kapetanakis EI, Matsota P, Tomos P, Kostopanagiotou K, Tomos I, et al. Monitored Anesthesia Care with Dexmedetomidine Supplemented by Midazolam/Fentanyl versus Midazolam/Fentanyl Alone in Patients Undergoing Pleuroscopy: Effect on Oxygenation and Respiratory Function. J Clin Med. 2021; 10(16):3510.
[40] Zhang Y, Li C, Shi J, Gong Y, Zeng T, Lin M, et al. Comparison of dexmedetomidine with midazolam for dental surgery: A systematic review and meta-analysis. Medicine (Baltimore). 2020; 99(43):e22288.
[41] Hassani V, Farhadi M, Mohseni M, Safaeian R, Nikoobakht N, Kashani SS, et al. Comparing the efficacy of dexmedetomidine versus fentanyl and midazolam during awake fiberoptic intubation. Arch Anesthesiol Crit Care. 2018; 4(4):538-41.
[2] García LTC, Ponce FEEO, Esparza ACM. Postoperative Pain in Orthopedics. Topics Postoper Pain. IntechOpen. 2023.
[3] Ranjbar Moghaddam M, Merajikhah A, Mahdood B, Mousavi E, Bastami M. Analyzing outcomes of platelet-rich plasma usage on surgical wounds: A systematic review. Curr Probl Surg. 2025; 64:101704.
[4] Vasigh A, Tarjoman A, Borji M. The effect of spiritual-religious interventions on patients' pain status: Systematic review. Anaesth Pain Intensive Care. 2018; 22(4).
[5] Sarafi M, Azimi B, Vasigh A, Ebrahimisaraj G. Assessment of Chronic Postoperative Inguinal Hernia Pain (CPIP) in Children. Arch Anesth Crit Care. 2025.
[6] Sampognaro G, Harrell R. Multimodal Postoperative Pain Control After Orthopaedic Surgery. StatPearls [Internet]. StatPearls Publishing. 2025.
[7] Pogatzki-Zahn EM, Segelcke D, Schug SA. Postoperative pain-from mechanisms to treatment. Pain Rep. 2017; 2(2):e588.
[8] Dafny NPPS. Chapter 6) Neuroscience Online: An Electronic Textbook for the Neurosciences. Dept Neurobiol Anat UT Med Sch Houston.
[9] Ghasembandi M, Jazini Dorcheh S, Farahmand H, Zabihi Rad J, Mousavi E. The Frequency and the Causes of Damages to Surgical Gloves in Orthopedic Surgeries. J Isfahan Med Sch. 2019; 37(527):522-8.
[10] Hatefi M, Parvizi R, Borji M, Tarjoman A. Effect of Self-Management Program on Pain and Disability Index in Elderly Men with Osteoarthritis. Anesth Pain Med. 2019; 9(4):e92672.
[11] Chunduri A, Aggarwal AK. Multimodal Pain Management in Orthopedic Surgery. J Clin Med. 2022; 11(21):6386.
[12] Mousavi E, Kavi E, Larti N, Gharahzadeh A. The relationship between attitude toward the effectiveness of teamwork and observing safety standards in Isfahan educational hospitals. Rev Lat Am Hipertens. 2018; 13(3):271-6.
[13] Tan M, Law LS, Gan TJ. Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways. Can J Anaesth. 2015; 62(2):203-18.
[14] Sarafi M, Azimi B, Vasigh A, Ebrahimisaraj G. Prevalence and Factors Affecting Postsurgical Pain in Pediatric and Adolescent Patients. Arch Anesth Crit Care. 2025.
[15] Azimi B, Sarafi M, Karimian M, Ebrahimisaraj G. Comparison of Patterns and Outcomes of Patients with Penetrating and Blunt Abdominal Trauma: A Retrospective Study. Govaresh. 2025; 1(1):25-9.
[16] Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001; 14(1):13-21.
[17] Yoon DK, Ban JS, Lee SG, Lee JH, Kim E, An J. Dexmedetomidine combined with midazolam vs. dexmedetomidine alone for sedation during spinal anesthesia. Korean J Anesthesiol. 2016; 69(5):446-52.
[18] Choi YM, Choi EJ, Ri HS, Park JY, You JA, Byeon GJ. The effect of dexmedetomidine and midazolam on combined spinal-epidural anesthesia in patients undergoing total knee arthroplasty. Anesth Pain Med (Seoul). 2020; 15(1):111-9.
[19] Bishnoi V, Kumar B, Bhagat H, Salunke P, Bishnoi S. Comparison of Dexmedetomidine Versus Midazolam-Fentanyl Combination for Monitored Anesthesia Care During Burr-Hole Surgery for Chronic Subdural Hematoma. J Neurosurg Anesthesiol. 2016; 28(2):141-6.
[20] Jones J Jr, Southerland W, Catalani B. The Importance of Optimizing Acute Pain in the Orthopedic Trauma Patient. Orthop Clin North Am. 2017; 48(4):445-65.
[21] Drevet S, Boussat B, Grevy A, Brevet A, Olive F, Richard M, et al. Perioperative pain management intervention in older patients with hip fracture in an orthogeriatric unit. A controlled before/after study assessing an audit and feedback intervention (PAIN-AGE). BMC Geriatr. 2024; 24(1):735.
[22] Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017; 10:2287-98.
[23] Stretanski MF, Kopitnik NL, Matha A, Conermann T. Chronic Pain. StatPearls [Internet]. StatPearls Publishing. 2025.
[24] Ke HH, Liou JY, Teng WN, Hsu PK, Tsou MY, Chang WK, et al. Opioid-sparing anesthesia with dexmedetomidine provides stable hemodynamic and short hospital stay in non-intubated video-assisted thoracoscopic surgery: a propensity score matching cohort study. BMC Anesthesiol. 2023; 23(1):110.
[25] Nolan PJ, Delgadillo JA, Youssef JM, Freeman K, Jones JL, Chehrehsa A. Dexmedetomidine Provides Fewer Respiratory Events Compared With Propofol and Fentanyl During Third Molar Surgery: A Randomized Clinical Trial. J Oral Maxillofac Surg. 2020; 78(10):1704-16.
[26] Vaswani JP, Debata D, Vyas V, Pattil S. Comparative Study of the Effect of Dexmedetomidine Vs. Fentanyl on Haemodynamic Response in Patients Undergoing Elective Laparoscopic Surgery. J Clin Diagn Res. 2017; 11(9):UC04-UC08.
[27] Yousuf A, Ahad B, Mir AH, Mir AW, Wani JG, Hussain SQ. Evaluation of Effectiveness of Dexmedetomidine and Fentanyl-midazolam Combination on Sedation and Safety during Awake Fiberoptic Intubation: A Randomized Comparative Study. Anesth Essays Res. 2017; 11(4):998-1003.
[28] Roney G, Jooste EH, Callahan PM, Litchenstein SE, Davis PJ, Adams PS. Sedation and Analgesia. Crit Care Child Heart Dis. Springer. 2020:101-11.
[29] Peng K, Liu HY, Liu SL, Ji FH. Dexmedetomidine-fentanyl Compared With Midazolam-fentanyl for Conscious Sedation in Patients Undergoing Lumbar Disc Surgery. Clin Ther. 2016; 38(1):192-201.e2.
[30] Talke P, Anderson BJ. Pharmacokinetics and pharmacodynamics of dexmedetomidine-induced vasoconstriction in healthy volunteers. Br J Clin Pharmacol. 2018; 84(6):1364-72.
[31] Li CW, Li YD, Tian HT, Kong XG, Chen K. Dexmedetomidine-midazolam versus Sufentanil-midazolam for Awake Fiberoptic Nasotracheal Intubation: A Randomized Double-blind Study. Chin Med J (Engl). 2015; 128(23):3143-8.
[32] Shoraibi M, Masoudifar M, Shetabi H. Comparison of the Cardiovascular Response to Sedation with Dexmedetomidine, Midazolam, and Etomidate in Phacoemulsification under Local Topical Anesthesia; A Double-Blind Randomized Controlled Clinical Trial. Adv Biomed Res. 2024; 13:81.
[33] Yadav U, Yadav JBS, Srivastava D, Srivastava S. A Randomized Controlled Study Comparing Dexmedetomidine-Midazolam with Fentanyl-Midazolam for Sedation during awake Fiberoptic Intubation in Anticipated Difficult Airway. Anesth Essays Res. 2020; 14(2):271-6.
[34] Magazine R, Elenjickal VM, Padukone AM, Bhat A, Chogtu B. Comparison Between Dexmedetomidine and Midazolam-Fentanyl Combination in Flexible Bronchoscopy: A Prospective, Randomized, Double-blinded Study. J Bronchology Interv Pulmonol. 2024; 31(4):e0985.
[35] Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, et al. Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile. Br J Anaesth. 2017; 119(2):211-20.
[36] Joo J, Koh H, Lee K, Lee J. Effects of Systemic Administration of Dexmedetomidine on Intraocular Pressure and Ocular Perfusion Pressure during Laparoscopic Surgery in a Steep Trendelenburg Position: Prospective, Randomized, Double-Blinded Study. J Korean Med Sci. 2016; 31(6):989-96.
[37] Oriby ME, Elrashidy A, Khafagy AG, Philip Rezkalla P. Dexmedetomidine vs. Fentanyl-Midazolam Combination to Mitigate the Stress Response in Microlaryngoscopy: A Randomized Double-blind Clinical Trial. Anesth Pain Med. 2023; 13(3):e135276.
[38] Nie J, Li C, Yang G, Chang H, Ding G. An evaluation of dexmedetomidine in combination with midazolam in pediatric sedation: a systematic review and meta-analysis. BMC Anesthesiol. 2024; 24(1):210.
[39] Kostroglou A, Kapetanakis EI, Matsota P, Tomos P, Kostopanagiotou K, Tomos I, et al. Monitored Anesthesia Care with Dexmedetomidine Supplemented by Midazolam/Fentanyl versus Midazolam/Fentanyl Alone in Patients Undergoing Pleuroscopy: Effect on Oxygenation and Respiratory Function. J Clin Med. 2021; 10(16):3510.
[40] Zhang Y, Li C, Shi J, Gong Y, Zeng T, Lin M, et al. Comparison of dexmedetomidine with midazolam for dental surgery: A systematic review and meta-analysis. Medicine (Baltimore). 2020; 99(43):e22288.
[41] Hassani V, Farhadi M, Mohseni M, Safaeian R, Nikoobakht N, Kashani SS, et al. Comparing the efficacy of dexmedetomidine versus fentanyl and midazolam during awake fiberoptic intubation. Arch Anesthesiol Crit Care. 2018; 4(4):538-41.
| Files | ||
| Issue | Article in Press |
|
| Section | Research Article(s) | |
| Keywords | ||
| Dexmedetomidine Regional Spinal Sedation Orthopedic surgery | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rahimi M, Sorani M, Shamsi A, Mohamad M, Hussain NA. Comparative Evaluation of Dexmedetomidine-Midazolam and Fentanyl-Midazolam for Sedation and Analgesia in Lower Extremity Orthopedic Surgery under Spinal Anesthesia: A Randomized Double-Blind Clinical Trial. Arch Anesth & Crit Care. 2025;.
