Comparison of the Effects of Low-Dose Dexmedetomidine and Low-Dose Neostigmine as Adjuvants to Bupivacaine on Postoperative Pain after Cesarean Section under Spinal Anesthesia
-
Goli Aezzi Pashakollaei
,
Frashad Hassanzadeh Kiabi
,
Samira Sobhani
,
Keihan Shabankhani
,
Babak Kabiri
,
Hossein Meskar
Abstract
Background: Effective postoperative pain management after cesarean section enhances maternal recovery, facilitates early newborn care, and reduces postoperative complications. Due to the limitations and adverse effects of neuraxial opioids, non-opioid adjuvants have become an attractive alternative. This study compared the analgesic efficacy of dexmedetomidine and low-dose neostigmine as adjuvants to bupivacaine in spinal anesthesia for cesarean delivery.
Methods: In this double-blind randomized clinical trial, 110 women undergoing elective cesarean were randomly allocated to receive either dexmedetomidine plus bupivacaine (Group D) or neostigmine plus bupivacaine (Group N). Demographic and intraoperative data were recorded. Sensory and motor block characteristics, postoperative pain intensity (VAS scores at 2, 4, 8, and 12 hours), time to first analgesic request, total 24-hour analgesic consumption, sedation levels, muscle relaxation quality, Apgar scores, and side effects (nausea, vomiting, shivering, pruritus) were assessed.
Results: Baseline characteristics, sedation scores, muscle relaxation quality, and neonatal outcomes were comparable between groups. The onset of sensory and motor block was significantly faster in the neostigmine group, whereas their regression was markedly prolonged in the dexmedetomidine group (P<0.001). Pain scores were consistently lower, the first analgesic request was delayed, and total analgesic use was reduced in Group D (P<0.001). Nausea and vomiting occurred more frequently in Group N (P=0.007).
Conclusion: Dexmedetomidine as an intrathecal adjuvant to bupivacaine provides superior and longer-lasting analgesia with fewer gastrointestinal side effects than neostigmine in cesarean sections under spinal anesthesia.
[1] Hamilton BE, Martin JA, Osterman MJ, Curtin SC, Matthews TJ. Births: Final Data for 2014. Natl Vital Stat Rep. 2015; 64(12):1-64.
[2] Pourshirazi M, Heidarzadeh M, Taheri M, Esmaily H, Babaey F, Talkhi N, et al. Cesarean delivery in Iran: a population-based analysis using the Robson classification system. BMC Pregnancy Childbirth. 2022; 22(1):185.
[3] Carvalho B, Cohen SE, Lipman SS, Fuller A, Mathusamy AD, Macario A. Patient preferences for anesthesia outcomes associated with cesarean delivery. Anesth Analg. 2005; 101(4):1182-7.
[4] Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016; 17(2):131-57.
[5] American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Anesthesiology. 2007; 106(4):843-63.
[6] Dahl JB, Jeppesen IS, Jørgensen H, Wetterslev J, Møiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology. 1999; 91(6):1919-27.
[7] Bonnet MP, Mignon A, Mazoit JX, Ozier Y, Marret E. Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Eur J Pain. 2010; 14(9):894.e1-9.
[8] Sultan P, Halpern SH, Pushpanathan E, Patel S, Carvalho B. The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis. Anesth Analg. 2016; 123(1):154-64.
[9] Chan JK, Leung RC, Lai CK. Diagnosis and treatment of obstructive sleep apnea. Clin Pulm Med. 1998; 5(1):60-8.
[10] Zamani Kiasari A, Razavi R, Sobhani S, Shirvani Ghadikolaee N, Mousavi Khorshidi N, Shabankhani K, et al. Comparison of the Effect of Adding Dexmedetomidine Versus Dexamethasone to Bupivacaine in Transverse Abdominis Plane Block on Postoperative Pain Intensity in Patients Undergoing Laparoscopic Cholecystectomy. Anesth Pain Med. 2025; 15(4):e162462.
[11] Gautier PE, De Kock M, Fanard L, Van Steenberge A, Hody JL. Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology. 1998; 88(3):651-6.
[12] Savola JM, Virtanen R. Central alpha 2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol. 1991; 195(2):193-9.
[13] Liu Y, Liang F, Liu X, Shao X, Jiang N, Gan X. Dexmedetomidine Reduces Perioperative Opioid Consumption and Postoperative Pain Intensity in Neurosurgery: A Meta-analysis. J Neurosurg Anesthesiol. 2018; 30(2):146-55.
[14] Marhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a volunteer study. Br J Anaesth. 2013; 110(3):438-42.
[15] Roelants F. The use of neuraxial adjuvant drugs (neostigmine, clonidine) in obstetrics. Curr Opin Anaesthesiol. 2006; 19(3):233-7.
[16] Fairbanks CA, Wilcox GL. Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. J Pharmacol Exp Ther. 1999; 288(3):1107-16.
[17] Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand. 2006; 50(2):222-7.
[18] Mohamed AA, Fares KM, Mohamed SA. Efficacy of intrathecally administered dexmedetomidine versus dexmedetomidine with fentanyl in patients undergoing major abdominal cancer surgery. Pain Physician. 2012; 15(4):339-48.
[19] Kim JE, Kim NY, Lee HS, Kil HK. Effects of intrathecal dexmedetomidine on low-dose bupivacaine spinal anesthesia in elderly patients undergoing transurethral prostatectomy. Biol Pharm Bull. 2013; 36(6):959-65.
[20] Abdelhamid SA, El-Lakany MH. Intrathecal dexmedetomidine: Useful or not. J Anesth Clin Res. 2013; 4(9):351.
[21] Eid HE, Shafie MA, Youssef H. Dose-related prolongation of hyperbaric bupivacaine spinal anesthesia by dexmedetomidine. Ain Shams J Anesthesiol. 2011; 4(2):83-95.
[22] Sullivan AF, Kalso EA, McQuay HJ, Dickenson AF. The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat. Eur J Pharmacol. 1992; 215(1):127-33.
[23] Lauretti GR, Reis MP, Prado WA, Klamt JG. Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Anesth Analg. 1996; 82(6):1182-7.
[24] Hood DD, Mallak KA, Eisenach JC, Tong C. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Anesthesiology. 1996; 85(2):315-25.
[25] Liu SS, Hodgson PS, Moore JM, Trautman WJ, Burkhead DL. Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers. Anesthesiology. 1999; 90(3):710-7.
[26] Reghunathan U. Intrathecal neostigmine with hyperbaric bupivacaine on the effects of spinal anaesthesia and postoperative analgesia–randomised prospective double blind study. Indian J Clin Anaesth. 2021.
[27] Pandey V, Mohindra BK, Sodhi GS. Comparative evaluation of different doses of intrathecal neostigmine as an adjuvant to bupivacaine for postoperative analgesia. Anesth Essays Res. 2016; 10(3):538-45.
[28] Yoganarasimha N, Raghavendra T, Amitha S, Shridhar K, Radha M. A comparative study between intrathecal clonidine and neostigmine with intrathecal bupivacaine for lower abdominal surgeries. Indian J Anaesth. 2014; 58(1):43-7.
[29] Suryawanshi C, Jawale R, Sathvika P, Ravindran DG. Comparison of epidural dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in lower limb surgeries. J Pharm Negat Results. 2022; 13.
[30] Hegde Uthkala Bhaskar SK, Reddy GN. A Comparative Study of Intrathecal Neostigmine and Dexmedetomidine as Adjuvant to Bupivacaine Spinal Analgesia in Sub Umbilical Regional Surgeries. Acad Anesthesiol Int. 2019; 4(1):53-6.
[31] Singh AK, Kumar A, Kumar A, Prasad BK, Tiwary PK, Kumar R. A Comparison of Intrathecal Dexmedetomidine and Neostigmine as Adjuvant to Ropivacaine for Lower Limb Surgeries: A Double-blind Randomized Controlled Study. Anesth Essays Res. 2017; 11(4):987-92.
[32] Sharma A, Kumar NJ, Azharuddin M, Mohan LC, Ramachandran G. Evaluation of low-dose dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in orthopedic surgeries: A prospective randomized double-blind study. J Anaesthesiol Clin Pharmacol. 2016; 32(2):187-91.
[2] Pourshirazi M, Heidarzadeh M, Taheri M, Esmaily H, Babaey F, Talkhi N, et al. Cesarean delivery in Iran: a population-based analysis using the Robson classification system. BMC Pregnancy Childbirth. 2022; 22(1):185.
[3] Carvalho B, Cohen SE, Lipman SS, Fuller A, Mathusamy AD, Macario A. Patient preferences for anesthesia outcomes associated with cesarean delivery. Anesth Analg. 2005; 101(4):1182-7.
[4] Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016; 17(2):131-57.
[5] American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Anesthesiology. 2007; 106(4):843-63.
[6] Dahl JB, Jeppesen IS, Jørgensen H, Wetterslev J, Møiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology. 1999; 91(6):1919-27.
[7] Bonnet MP, Mignon A, Mazoit JX, Ozier Y, Marret E. Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Eur J Pain. 2010; 14(9):894.e1-9.
[8] Sultan P, Halpern SH, Pushpanathan E, Patel S, Carvalho B. The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis. Anesth Analg. 2016; 123(1):154-64.
[9] Chan JK, Leung RC, Lai CK. Diagnosis and treatment of obstructive sleep apnea. Clin Pulm Med. 1998; 5(1):60-8.
[10] Zamani Kiasari A, Razavi R, Sobhani S, Shirvani Ghadikolaee N, Mousavi Khorshidi N, Shabankhani K, et al. Comparison of the Effect of Adding Dexmedetomidine Versus Dexamethasone to Bupivacaine in Transverse Abdominis Plane Block on Postoperative Pain Intensity in Patients Undergoing Laparoscopic Cholecystectomy. Anesth Pain Med. 2025; 15(4):e162462.
[11] Gautier PE, De Kock M, Fanard L, Van Steenberge A, Hody JL. Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology. 1998; 88(3):651-6.
[12] Savola JM, Virtanen R. Central alpha 2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol. 1991; 195(2):193-9.
[13] Liu Y, Liang F, Liu X, Shao X, Jiang N, Gan X. Dexmedetomidine Reduces Perioperative Opioid Consumption and Postoperative Pain Intensity in Neurosurgery: A Meta-analysis. J Neurosurg Anesthesiol. 2018; 30(2):146-55.
[14] Marhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a volunteer study. Br J Anaesth. 2013; 110(3):438-42.
[15] Roelants F. The use of neuraxial adjuvant drugs (neostigmine, clonidine) in obstetrics. Curr Opin Anaesthesiol. 2006; 19(3):233-7.
[16] Fairbanks CA, Wilcox GL. Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. J Pharmacol Exp Ther. 1999; 288(3):1107-16.
[17] Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand. 2006; 50(2):222-7.
[18] Mohamed AA, Fares KM, Mohamed SA. Efficacy of intrathecally administered dexmedetomidine versus dexmedetomidine with fentanyl in patients undergoing major abdominal cancer surgery. Pain Physician. 2012; 15(4):339-48.
[19] Kim JE, Kim NY, Lee HS, Kil HK. Effects of intrathecal dexmedetomidine on low-dose bupivacaine spinal anesthesia in elderly patients undergoing transurethral prostatectomy. Biol Pharm Bull. 2013; 36(6):959-65.
[20] Abdelhamid SA, El-Lakany MH. Intrathecal dexmedetomidine: Useful or not. J Anesth Clin Res. 2013; 4(9):351.
[21] Eid HE, Shafie MA, Youssef H. Dose-related prolongation of hyperbaric bupivacaine spinal anesthesia by dexmedetomidine. Ain Shams J Anesthesiol. 2011; 4(2):83-95.
[22] Sullivan AF, Kalso EA, McQuay HJ, Dickenson AF. The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat. Eur J Pharmacol. 1992; 215(1):127-33.
[23] Lauretti GR, Reis MP, Prado WA, Klamt JG. Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Anesth Analg. 1996; 82(6):1182-7.
[24] Hood DD, Mallak KA, Eisenach JC, Tong C. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Anesthesiology. 1996; 85(2):315-25.
[25] Liu SS, Hodgson PS, Moore JM, Trautman WJ, Burkhead DL. Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers. Anesthesiology. 1999; 90(3):710-7.
[26] Reghunathan U. Intrathecal neostigmine with hyperbaric bupivacaine on the effects of spinal anaesthesia and postoperative analgesia–randomised prospective double blind study. Indian J Clin Anaesth. 2021.
[27] Pandey V, Mohindra BK, Sodhi GS. Comparative evaluation of different doses of intrathecal neostigmine as an adjuvant to bupivacaine for postoperative analgesia. Anesth Essays Res. 2016; 10(3):538-45.
[28] Yoganarasimha N, Raghavendra T, Amitha S, Shridhar K, Radha M. A comparative study between intrathecal clonidine and neostigmine with intrathecal bupivacaine for lower abdominal surgeries. Indian J Anaesth. 2014; 58(1):43-7.
[29] Suryawanshi C, Jawale R, Sathvika P, Ravindran DG. Comparison of epidural dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in lower limb surgeries. J Pharm Negat Results. 2022; 13.
[30] Hegde Uthkala Bhaskar SK, Reddy GN. A Comparative Study of Intrathecal Neostigmine and Dexmedetomidine as Adjuvant to Bupivacaine Spinal Analgesia in Sub Umbilical Regional Surgeries. Acad Anesthesiol Int. 2019; 4(1):53-6.
[31] Singh AK, Kumar A, Kumar A, Prasad BK, Tiwary PK, Kumar R. A Comparison of Intrathecal Dexmedetomidine and Neostigmine as Adjuvant to Ropivacaine for Lower Limb Surgeries: A Double-blind Randomized Controlled Study. Anesth Essays Res. 2017; 11(4):987-92.
[32] Sharma A, Kumar NJ, Azharuddin M, Mohan LC, Ramachandran G. Evaluation of low-dose dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in orthopedic surgeries: A prospective randomized double-blind study. J Anaesthesiol Clin Pharmacol. 2016; 32(2):187-91.
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How to Cite
1.
Aezzi Pashakollaei G, Hassanzadeh Kiabi F, Sobhani S, Shabankhani K, Kabiri B, Meskar H. Comparison of the Effects of Low-Dose Dexmedetomidine and Low-Dose Neostigmine as Adjuvants to Bupivacaine on Postoperative Pain after Cesarean Section under Spinal Anesthesia. Arch Anesth & Crit Care. 2026;.
