A Randomized Controlled Trial for Prevention of Postoperative Nausea and Vomiting after Laparoscopic Sleeve Gastrectomy: Aprepitant/Dexamethasone vs. Mirtazapine/Dexamethasone

Tarek M Ashoor, Dina Y Kassim, Ibrahim M Esmat, Tarek M Ashoor, Dina Y Kassim, Ibrahim M Esmat

Abstract

Background: Coadministration of different antiemetics proved to decrease postoperative nausea and vomiting (PONV) after laparoscopic sleeve gastrectomy (LSG). This trial compared aprepitant/dexamethasone (A/D) combination vs mirtazapine/dexamethasone (M/D) combination vs dexamethasone (D) alone for prevention of PONV in morbidly obese patients undergoing LSG.

Methods: Ninety patients scheduled for LSG were randomly allocated to receive 8 mg dexamethasone intravenous infusion (IVI) only in the D group or in addition to 80 mg aprepitant capsule in the A/D group or in addition to 30 mg mirtazapine tablet in the M/D group. Assessment of PONV was carried out at 0-2 h (early) and 2-24 h (late). The primary outcome was the complete response 0-24 h after surgery. Collective PONV, postoperative pain, side effects and patient satisfaction score were considered as secondary outcomes.

Results: The A/D and M/D groups were superior to the D group for a complete response within 0-24 h after surgery (79.3% for the A/D group, 78.6% for the M/D group, and 20.7% for the D group). The D group was inferior to the A/D and M/D groups regarding collective PONV and use of rescue antiemetic 0-24 h after surgery (P < 0.001, P < 0.001, respectively). The peak nausea scores (2-24 h) were significantly reduced in the M/D group in comparison to the D group (P=0.005). Patients in the M/D group showed high sedation scores, while those in the A/D group showed low pain scores (2-24 h) and less analgesic requirements (P < 0.001, P < 0.001, P < 0.001, respectively). The A/D and M/D groups were superior to the D group with regard to the patient satisfaction score (P < 0.001).

Conclusion: Aprepitant/dexamethasone combination and mirtazapine/dexamethasone combination were superior to dexamethasone alone in alleviating postoperative nausea and vomiting in morbidly obese patients scheduled to undergo laparoscopic sleeve gastrectomy. Trial Registration: ClinicalTrials.gov identifier: NCT04013386.

Conflict of interest statement

All the authors declare that they have no conflicts of interest.

Copyright © 2022 Tarek M. Ashoor et al.

Figures

Figure 1
Figure 1
Flow chart of the study. A/D group: aprepitant/dexamethasone group, M/D group: mirtazapine/dexamethasone group, and D group: dexamethasone group.
Figure 2
Figure 2
Kaplan–Meier curve for vomiting rate (Log rank test, Pvalue <0.001). A/D group: aprepitant/dexamethasone group, M/D group: mirtazapine/dexamethasone group, and D group: dexamethasone group.
Figure 3
Figure 3
Relative risk with 95% CI for A/D group vs. M/D group for complete response in the first 24 h after surgery; showing that the probability of complete response relative to the D group was in the M/D group close to that in the A/D group. A/D group: aprepitant/dexamethasone group, M/D group: mirtazapine/dexamethasone group, and D group: dexamethasone group.

References

    1. Fuchs H. F., Broderick R. C., Harnsberger C. R., et al. Benefits of bariatric surgery do not reach obese men. Journal of Laparoendoscopic and Advanced Surgical Techniques . 2015;25(3):196–201. doi: 10.1089/lap.2014.0639.
    1. Eisenlohr J., Zeuzem C., Dudok S., Karcz K., Hofmann-Kiefer K., Groene P. Postoperative nausea and vomiting in bariatric surgery in comparison to non-bariatric gastric surgery. Wideochirurgia I Inne Tech Maloinwazyjne . 2019;14:90–95.
    1. Gan T. J., Belani K. G., Bergese S., et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia and Analgesia . 2020;131
    1. Apfel C. C., Korttila K., Abdalla M., et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. Obstetrics and Gynecology . 2004;104:p. 626.
    1. Gupta P., Jain S. Postoperative nausea and vomiting prophylaxis: a comparative study of ondansetron, granisetron and granisetron and dexamethasone combination after modified radical mastectomy. Saudi Journal of Anaesthesia . 2014;8:S67–S71. doi: 10.4103/1658-354X.144081.
    1. Elhakim M., Nafie M., Mahmoud K., Atef A. Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy. Canadian Journal of Anesthesia . 2002;49(9):922–926. doi: 10.1007/bf03016875.
    1. Henzi I., Walder B., Tramèr M. R. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesthesia and Analgesia . 2000;90(1):186–194. doi: 10.1097/00000539-200001000-00038.
    1. Kovac A. L. Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies. The Annals of Pharmacotherapy . 2006;40(5):873–887. doi: 10.1345/aph.1g338.
    1. Okafor D., Kaye A. D., Kaye R. J., Urman R. D. The role of neurokinin-1 (substance P) antagonists in the prevention of postoperative nausea and vomiting. Journal of Anaesthesiology, Clinical Pharmacology . 2017;33:441–445. doi: 10.4103/0970-9185.222511.
    1. Sinha A. C., Singh P. M., Williams N. W., Ochroch E. A., Goudra B. G. Aprepitant’s prophylactic efficacy in decreasing postoperative nausea and vomiting in morbidly obese patients undergoing bariatric surgery. Obesity Surgery . 2014;24(2):225–231. doi: 10.1007/s11695-013-1065-1.
    1. Chang F.-L., Ho S.-T., Sheen M. J. Efficacy of mirtazapine in preventing intrathecalmorphine-induced nausea and vomiting after orthopaedic surgery∗. Anaesthesia . 2010;65(12):1206–1211. doi: 10.1111/j.1365-2044.2010.06561.x.
    1. Timmer C. J., Ad Sitsen J. M., Delbressine L. P. Clinical pharmacokinetics of mirtazapine. Clinical Pharmacokinetics . 2000;38(6):461–474. doi: 10.2165/00003088-200038060-00001.
    1. Moon H. Y., Baek C. W., Choi G. J., et al. Palonosetron and aprepitant for the prevention of postoperative nausea and vomiting in patients indicated for laparoscopic gynaecologic surgery: a double-blind randomised trial. BMC Anesthesiology . 2014;14:68–77. doi: 10.1186/1471-2253-14-68.
    1. Liu L. L., Gropper M. A. Postoperative analgesia and sedation in the adult intensive care unit. Drugs . 2003;63(8):755–767. doi: 10.2165/00003495-200363080-00003.
    1. Boogaerts J. G., Vanacker E., Seidel L., Albert A., Bardiau F. M. Assessment of postoperative nausea using a visual analogue scale. Acta Anaesthesiologica Scandinavica . 2000;44(4):470–474. doi: 10.1034/j.1399-6576.2000.440420.x.
    1. Streiner D. L., Norman G. R. Health measurement scales: a practical guide to their development and use. 2008. .
    1. Hintze J. PASS (power analysis and sample size system) quick start manual. 2011. .
    1. Jaccard J., Becker M. A., Wood G. Pairwise multiple comparison procedures: a review. Psychological Bulletin . 1984;96(3):589–596. doi: 10.1037/0033-2909.96.3.589.
    1. Suh S., Helm M., Kindel T. L., Goldblatt M. I., Gould J. C., Higgins R. M. The impact of nausea on post-operative outcomes in bariatric surgery patients. Surgical Endoscopy . 2020;34(7):3085–3091. doi: 10.1007/s00464-019-07058-5.
    1. Kawano H., Matsumoto T., Hamaguchi E., et al. Antiemetic efficacy of combined aprepitant and dexamethasone in patients at high-risk of postoperative nausea and vomiting from epidural fentanyl analgesia. Minerva Anestesiologica . 2015;81:362–368.
    1. Chen C.-C., Lin C.-S., Ko Y.-P., Hung Y.-C., Lao H.-C., Hsu Y.-W. Premedication with mirtazapine reduces preoperative anxiety and postoperative nausea and vomiting. Anesthesia and Analgesia . 2008;106(1):109–113. doi: 10.1213/01.ane.0000289636.09841.bc.
    1. De Oliveira G. S., Almeida M. D., Benzon H. T., McCarthy R. J. Perioperative single dose systemic dexamethasone for postoperative pain. Anesthesiology . 2011;115(3):575–588. doi: 10.1097/aln.0b013e31822a24c2.
    1. Yamanaga S., Posselt A. M., Freise C. E., Kobayashi T., Tavakol M., Kang S.-M. A single perioperative injection of dexamethasone decreases nausea, vomiting, and pain after laparoscopic donor nephrectomy. Journal of Transplantation . 2017;2017:8. doi: 10.1155/2017/3518103.3518103
    1. Tien M., Gan T. J., Dhakal I., et al. The effect of anti-emetic doses of dexamethasone on postoperative blood glucose levels in non-diabetic and diabetic patients: a prospective randomised controlled study. Anaesthesia . 2016;71(9):1037–1043. doi: 10.1111/anae.13544.
    1. Singh P. M., Borle A., Rewari V., et al. Aprepitant for postoperative nausea and vomiting: a systematic review and meta-analysis. Postgraduate Medical Journal . 2016;92(1084):87–98. doi: 10.1136/postgradmedj-2015-133515.
    1. Kakuta N., Tsutsumi M. Y., Horikawa Y. T., et al. Neurokinin-1 receptor antagonism, aprepitant, effectively diminishes post-operative nausea and vomiting while increasing analgesic tolerance in laparoscopic gynecological procedures. Journal of Medical Investigation . 2011;58(3,4):246–251. doi: 10.2152/jmi.58.246.
    1. Jeyabalan S., Thampi S. M., Karuppusami R., Samuel K. Comparing the efficacy of aprepitant and ondansetron for the prevention of postoperative nausea and vomiting (PONV): a double blinded, randomised control trial in patients undergoing breast and thyroid surgeries. Indian Journal of Anaesthesia . 2019;63:289–294. doi: 10.4103/ija.IJA_724_18.
    1. Gan T. J., Apfel C. C., Kovac A., et al. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesthesia and Analgesia . 2007;104(5):1082–1089. doi: 10.1213/01.ane.0000263277.35140.a3.
    1. Diemunsch P., Gan T. J., Philip B. K., et al. Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery†. British Journal of Anaesthesia . 2007;99(2):202–211. doi: 10.1093/bja/aem133.
    1. Habib A. S., Keifer J. C., Borel C. O., White W. D., Gan T. J. A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy. Anesthesia and Analgesia . 2011;112(4):813–818. doi: 10.1213/ane.0b013e3181ff47e2.
    1. Bilgen S., Kizilcik N., Haliloglu M., Yildirim G., Kaspar E. C., Koner O. Effect of the dexamethasone-ondansetron combination versus dexamethasone-aprepitant combination to prevent postoperative nausea and vomiting. Turkish Journal of Anesthesia and Reanimation . 2018;46:373–380. doi: 10.5152/tjar.2018.53179.
    1. Ahmed Omran H. A. S., Abdelhamid Mohamed Nasr D., Ezzat Ali Eid H. Effect of premedication with mirtazapine versus ondansetron on postoperative nausea and vomiting in breast surgery. Egyptian Journal of Anaesthesia . 2011;27(3):135–139. doi: 10.1016/j.egja.2011.06.003.
    1. Teixeira F. V., Novaretti T. M. S., Pilon B., Pereira P. G., Breda M. F. C. L. Mirtazapine (Remeron) as treatment for non-mechanical vomiting after gastric bypass. Obesity Surgery . 2005;15(5):707–709. doi: 10.1381/0960892053923923.
    1. Hsu Y.-W., Ko Y.-P., Lao H.-C., Hung Y.-C. Effects of mirtazapine premedication on general anesthesia and postoperative nausea and vomiting. Anesthesiology . 2006;105:p. A626.
    1. Schreiber S., Rigai T., Katz Y., Pick C. G. The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain Research Bulletin . 2002;58(6):601–605. doi: 10.1016/s0361-9230(02)00825-0.
    1. Chou W.-H., Lin F.-S., Lin C.-P., Lin W.-Y., Yie J.-C., Sun W.-Z. Mirtazapine, in orodispersible form, for patients with preoperative psychological distress: a pilot study. Acta Anaesthesiologica Taiwanica . 2016;54(1):16–23. doi: 10.1016/j.aat.2015.12.002.
    1. Sheen M. J., Ho S.-T. Mirtazapine relieves postdural puncture headache. Anesthesia and Analgesia . 2008;107(1):p. 346. doi: 10.1213/ane.0b013e3181771074.
    1. Mansour E. E. Mirtazapine premedication: effect on preoperative anxiety and propofol dose requirements at different stages of hypnosis. Egyptian Journal of Anaesthesia . 2013;29(2):143–147. doi: 10.1016/j.egja.2012.10.004.
    1. Ashoor T., Kassim D. Y., Hasseb A. M., Esmat I. M. Effects of aprepitant/dexamethasone versus mirtazapine/dexamethasone on postoperative nausea and vomiting after laparoscopic sleeve gastrectomy: a randomized controlled trial. 2020. .

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