Combined Spinal–General Anaesthesia with Low-Dose Intrathecal Morphine and Atropine for Abdominal Laparoscopy: A Randomised Controlled Trial of Postoperative Nausea, Vomiting and Pain
DOI:
https://doi.org/10.46799/adv.v4i11.722Keywords:
Atropine, Intrathecal, Laparoscopy, Morphine, Postoperative Nausea and Vomiting, Spinal Anesthesia, Combined anesthesiaAbstract
Postoperative nausea and vomiting (PONV) and pain remain significant concerns following abdominal laparoscopic surgery. This study compared combined spinal–general anesthesia (CSGA) incorporating low-dose intrathecal morphine and atropine with general anesthesia (GA) alone. A single-center, open-label, randomized controlled trial was conducted in Jakarta, Indonesia, from February to March 2026. Adults undergoing elective abdominal laparoscopic surgery received either CSGA with intrathecal bupivacaine (10 mg), morphine (100 ?g), and atropine (100 ?g) or GA alone. Both groups received prophylactic ondansetron and multimodal analgesia. Sixty patients were included in the per-protocol analysis, comprising 33 in the CSGA group and 27 in the GA group. The primary outcome was the incidence of PONV within 24 hours postoperatively, while secondary outcomes included pain scores, rescue medication requirements, fentanyl consumption, and hemodynamic parameters. PONV occurred in 6.1% of CSGA patients compared with 74.1% of GA patients (P < 0.001), corresponding to an absolute risk reduction of 68.0 percentage points. The CSGA group demonstrated lower pain scores at 6–24 hours, reduced postinduction fentanyl consumption, and decreased requirements for rescue ondansetron. No patients in the CSGA group required rescue morphine, compared with 59.3% in the GA group. Three CSGA patients required vasopressor support. These benefits may have been partially associated with reduced opioid exposure, although a mediating effect was not established. CSGA was associated with improved postoperative symptom control under the study conditions; however, the independent contribution of intrathecal atropine remains uncertain. Larger, blinded, multicenter randomized controlled trials are warranted to confirm efficacy and evaluate safety, particularly potential neurological complications associated with intrathecal atropine administration.
References
Abdalla, E., Kamel, E. Z., & Farrag, W. S. (2019). Intravenous dexamethasone combined with intrathecal atropine to prevent morphine-related nausea and vomiting after cesarean delivery: a randomized double-blinded study. Egyptian Journal of Anaesthesia, 35(1), 65–70. https://doi.org/10.1080/11101849.2019.1636497
Alcalay, M., Izraeli, S., Wallach-Kapon, R., Tochner, Z., Benjamini, Y., & Akselrod, S. (1992). Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations. Clinical Pharmacology & Therapeutics, 52(5), 518–527. https://doi.org/10.1038/clpt.1992.180
Ali-Melkkilä, T., Kaila, T., Antila, K., Halkola, L., & Iisalo, E. (1991). Effects of glycopyrrolate and atropine on heart rate variability. Acta Anaesthesiologica Scandinavica, 35(5), 436–441. https://doi.org/10.1111/j.1399-6576.1991.tb03324.x
Apfel, C. C., Heidrich, F. M., Jukar-Rao, S., Jalota, L., Hornuss, C., & Whelan, R. P. (2012). Evidence-based analysis of risk factors for postoperative nausea and vomiting. British Journal of Anaesthesia, 109(5), 742–753. https://doi.org/10.1093/bja/aes276
Baciarello, M., Cornini, A., Zasa, M., Pedrona, P., Scrofani, G., & Venuti, F. S. (2011). Intrathecal atropine to prevent postoperative nausea and vomiting after Cesarean section: a randomized, controlled trial. Minerva Anestesiologica, 77(8), 781–788.
Bianchi, E., Seidl, A., Krombholz, E., Frey, M. C., Obrecht, I., & Hasler-Gehrer, S. (2026). Spinal anesthesia in laparoscopic colorectal surgery: analgesia and recovery outcomes, a cohort study and systematic review of randomized controlled studies. Langenbeck’s Archives of Surgery. https://doi.org/10.1007/s00423-026-04152-w
Cheng, L., Liu, J., Qin, S., Geng, X., Jing, L., & Fang, S. (2025). Safety and effectiveness of multimodal opioid-free anaesthesia for pain and recovery after laparoscopic surgery: a systematic review and meta-analysis. BMJ Open, 15(3), e085988. https://doi.org/10.1136/bmjopen-2024-085988
Farahat, T. E. M., & Abdelhafez, M. S. (2019). Intrathecal atropine versus intravenous metoclopramide for prevention of nausea and vomiting during cesarean section under spinal anesthesia. Research and Opinion in Anesthesia and Intensive Care, 6(4), 393–398.
Gan, T. J., Belani, K. G., Bergese, S., Chung, F., Diemunsch, P., & Habib, A. S. (2020). Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia & Analgesia, 131(2), 411–448. https://doi.org/10.1213/ANE.0000000000004833
Ho, K. M., Ismail, H., Lee, K. C., & Branch, R. (2005). Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis. Anaesthesia and Intensive Care, 33(1), 41–53. https://doi.org/10.1177/0310057X0503300107
Kumar, L., Anantharaman, R., Thomas, D. E., Nair, A. S., Kartha, A. P., & Kumar, K. (2024). Evaluation of the analgesic efficacy of a low dose of intrathecal morphine in laparoscopic abdominal surgery: a randomised control trial. Journal of Minimal Access Surgery, 22(3), 261–267. https://doi.org/10.4103/jmas.jmas_141_24
Luo, D., Huang, Z., Tang, S., Cheng, J., Deng, Y., & Zhang, X. (2024). Risk analysis of postoperative nausea and vomiting in patients after gynecologic laparoscopic surgery. BMC Anesthesiology, 24(1), 345. https://doi.org/10.1186/s12871-024-02727-y
Meylan, N., Elia, N., Lysakowski, C., & Tramèr, M. R. (2009). Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials. British Journal of Anaesthesia, 102(2), 156–167. https://doi.org/10.1093/bja/aen368
Nelson, G., Altman, A. D., Metcalfe, A., Fotopoulou, C., Taylor, J., & Glaser, G. (2026). Enhanced recovery after surgery (ERAS) society guidelines for gynecologic oncology: 2026 update. Gynecologic Oncology, 210, 153–173. https://doi.org/10.1016/j.ygyno.2026.05.022
Pan, H. L., Chen, S. R., & Eisenach, J. C. (1999). Intrathecal clonidine alleviates allodynia in neuropathic rats: interaction with spinal muscarinic and nicotinic receptors. Anesthesiology, 90(2), 509–514. https://doi.org/10.1097/00000542-199902000-00027
Pedigo Jr., N. W., & Brizzee, K. R. (1985). Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis. Brain Research Bulletin, 14(2), 169–177. https://doi.org/10.1016/0361-9230(85)90076-0
Pramadika, T., Mochamat, Nurcahyo, W. I., Wicaksono, S. A., Saputra, T., & Manapa, C. H. (2025). Intrathecal atropine as an adjuvant in spinal anesthesia: a systematic review of efficacy and safety. Anaesthesia, Pain & Intensive Care, 29(7), 796–807. https://doi.org/10.35975/apic.v29i7.2947
Renard, Y., El-Boghdadly, K., Rossel, J. B., Nguyen, A., Jaques, C., & Albrecht, E. (2024). Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression. British Journal of Anaesthesia, 133(4), 823–838. https://doi.org/10.1016/j.bja.2024.05.045
Russo, A., Perelli, F., Aceto, P., Arcieri, M., Bernardini, F., & Pregnolato, S. (2026). Intrathecal morphine dose optimization in robotic-assisted laparoscopic hysterectomy: a dual-center cohort study. Journal of Robotic Surgery, 20(1). https://doi.org/10.1007/s11701-026-03445-y
Schulz, K. F., Altman, D. G., Moher, D., & Group, C. (2010). CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ, 340, c332. https://doi.org/10.1136/bmj.c332
Soliman, F. I., Mousa, E. A., Ahmed, S. M., & Hassan, A. H. (2023). Intrathecal atropine versus preoperative intravenous ondansetron for prevention of postoperative nausea and vomiting due to intrathecal morphine in perineal surgery. Research and Opinion in Anesthesia and Intensive Care, 10(3). https://doi.org/10.4103/roaic.roaic_24_23
Song, M., Hu, H., Jiang, L., & Wei, J. (2026). Comparative efficacy of regional analgesic interventions in open versus laparoscopic hepatic surgery: a network meta-analysis. Journal of Pain Research, 19, 577411. https://doi.org/10.2147/JPR.S577411
Turai, A., & Rachana, P. P. (2019). A clinical study to evaluate the effect of intrathecal atropine on postoperative nausea and vomiting in patients receiving intrathecal morphine and hyperbaric bupivacaine for spinal anaesthesia: prospective randomized trial. Karnataka Anaesthesia Journal, 17(Suppl), 1–2.
Xu, P., Hu, Z., & Chen, J. (2025). The effect of opioid-free anaesthesia on pain and prognosis in gynaecological laparoscopic surgery: a systematic review and meta-analysis. Journal of Obstetrics and Gynaecology, 45(1), 2583014. https://doi.org/10.1080/01443615.2025.2583014
Zheng, L., Lu, Y., Lu, X., You, L., Yu, C., & Lai, J. (2026). Intrathecal morphine for enhanced recovery after laparoscopic colorectal surgery: a randomized clinical trial. JAMA Surgery, 161(2), 124–131. https://doi.org/10.1001/jamasurg.2025.5699







