The Protective Effects of Butorphanol on Pulmonary Function of Patients with Obesity Undergoing Laparoscopic Bariatric Surgery: a Double-Blind Randomized Controlled Trial



Obesity is a risk factor for postoperative pulmonary complications (PPCs). Recent studies have reported the pulmonary protective role of the kappa opioid receptor (KOR). Butorphanol is a narcotic with strong KOR agonist action, and the role in pulmonary protection is uncertain. Here, we hypothesized that butorphanol exerts protective effects on pulmonary function in patients with obesity undergoing laparoscopic bariatric surgery.


Patients with a body mass index ≥ 30 kg/m2 scheduled for laparoscopic bariatric surgery were randomized to receive butorphanol or normal saline. Butorphanol was administered as an initial loading dose of 10 μg/kg at 5 min before induction followed by 5 μg/(kg h) during surgery. The primary outcome was arterial-alveolar oxygen tension ratio (a/A ratio). Secondary outcomes included other pulmonary variables, biomarkers reflecting pulmonary injury, and incidence of PPCs within 7 days after surgery.


Patients in the butorphanol group had a significantly higher a/A ratio at 1 h after the operation began (68 ± 7 vs. 55 ± 8, P < 0.001), end of the operation (73 ± 8 vs. 59 ± 7, P < 0.001), and 1 h after extubation (83 ± 9 vs. 70 ± 5, P < 0.001) compared with those in the control group. In addition, in the butorphanol group, dead space to tidal volume ratios were significantly lower than those in the control group at the same time points (all P < 0.001). In the control group, the levels of biomarkers reflecting pulmonary injury were significantly higher than those in the butorphanol group at 3 h, 6 h, 12 h, and 24 h postoperatively (P < 0.001). The incidence of PPCs was similar in both groups.


Butorphanol administration protected pulmonary function by improving oxygenation and reducing dead space ventilation in patients with obesity undergoing laparoscopic bariatric surgery. Butorphanol may therefore provide clinical benefits in patients with obesity.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

Change history

  • 29 June 2020

    In the original article some of the references were ordered incorrectly.


  1. 1.

    Abarca-Gómez L, Abdeen ZA, Hamid ZA, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390:2627–42.

    Google Scholar 

  2. 2.

    Ball L, Hemmes SNT, Serpa Neto A, et al. Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients. Br J Anaesth. 2018;121(4):899–908.

    CAS  PubMed  Google Scholar 

  3. 3.

    Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - an observational study in 29 countries. Eur J Anaesthesiol. 2017;34(8):492–507.

  4. 4.

    Fernandez-Bustamante A, Frendl G, Sprung J, et al. Postoperative pulmonary complications, early mortality, and hospital stay following noncardiothoracic surgery: a multicenter study by the Perioperative Research Network Investigators. JAMA Surg. 2017;152(2):157–66.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Shashaty MG. Physiological and management implications of obesity in critical illness. Ann Am Thorac Soc. 2014;11(8):1286–97.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tang J, Yan H. Inflammation and oxidative stress in obesity-related glomerulopathy. Int J Nephrol. 2012;2012:608397.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Reho JJ, Rahmouni K. Oxidative and inflammatory signals in obesity-associated vascular abnormalities. Clin Sci (Lond). 2017;131(14):1689–700.

    CAS  Google Scholar 

  8. 8.

    Aroor AR, Jia G, Sowers JR. Cellular mechanisms underlying obesity-induced arterial stiffness. Am J Phys Regul Integr Comp Phys. 2018;314(3):R387–8.

    Google Scholar 

  9. 9.

    Schinzari F, Tesauro M, Cardillo C. Endothelial and perivascular adipose tissue abnormalities in obesity-related vascular dysfunction: novel targets for treatment. J Cardiovasc Pharmacol. 2017;69(6):360–8.

    CAS  PubMed  Google Scholar 

  10. 10.

    Gutt CN, Müller-Stich BP. Success and complication parameters for laparoscopic surgery: a benchmark for natural orifice transluminal endoscopic surgery. Endoscopy. 2009;41(01):36–41.

    CAS  PubMed  Google Scholar 

  11. 11.

    Nishiyama T, Kohno Y. Anesthesia for bariatric surgery. Obes Surg. 2012;22(2):213–9.

    PubMed  Google Scholar 

  12. 12.

    Rivas E, Arismendi E, Agustí A, et al. Ventilation/perfusion distribution abnormalities in morbidly obese subjects before and after bariatric surgery. Chest. 2015;147(4):1127–34.

    PubMed  Google Scholar 

  13. 13.

    Tai KK, Jin WQ, Chan TK. Characterization of [3H]U69593 binding sites in the rat heart by receptor binding assays. J Mol Cell Cardiol. 1991;23(11):1297–302.

    CAS  PubMed  Google Scholar 

  14. 14.

    Wittert G, Hope P. Tissue distribution of opioid receptor gene expression in the rat. Biochem Biophys Res Commun. 1996;218(3):877–81.

    CAS  PubMed  Google Scholar 

  15. 15.

    Li J, Shi QX, Fan R, et al. Vasculoprotective effect of U50,488H in rats exposed to chronic hypoxia: role of Akt-stimulated NO production. J Appl Physiol. 2013;114(2):238–44.

    CAS  PubMed  Google Scholar 

  16. 16.

    Li J. Role of κ-opioid receptor activation in anti-hypoxic pulmonary hypertension and its underlying mechanisms [dissertation]. China: FourthMilitary Medical University; 2017.

  17. 17.

    Wu Q, Wang HY, Li J, et al. κ-opioid receptor stimulation improves endothelial function in hypoxic pulmonary hypertension. PLoS One. 2013;8:e60850.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Cui Y, Feng N, Gu X, et al. κ-Opioid receptor stimulation reduces palmitate-induced apoptosis via Akt/eNOS signaling pathway. Lipids Health Dis. 2019;18(1):52.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Jose DE, Ganapathi P, Anish Sharma NG, et al. Postoperative pain relief with epidural buprenorphine versus epidural butorphanol in laparoscopic hysterectomies: a comparative study. Anesth Essays Res. 2016;10(1):82–7.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Wu Y, Wan J, Zhen WZ, et al. The effect of butorphanol postconditioning on myocardial ischaemia reperfusion injury in rats. Interact Cardiovasc Thorac Surg. 2014;18(3):308–12.

    PubMed  Google Scholar 

  21. 21.

    Huang LH, Li J, Gu JP, et al. Butorphanol attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria-mediated apoptosis in mice. Eur Rev Med Pharmacol Sci. 2018;22:1819–24.

    PubMed  Google Scholar 

  22. 22.

    Yang L, Sun DF, Wu Y, et al. Intranasal administration of butorphanol benefits old patients undergoing H-uvulopalatopharyngoplasty: a randomized trial. BMC Anesthesiol. 2015;15(1):20.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    La Colla L, Albertin A, La Colla G, et al. Predictive performance of the ‘Minto’ remifentanil pharmacokinetic parameter set in morbidly obese patients ensuing from a new method for calculating lean body mass. Clin Pharm. 2010;49(2):131–9.

    Google Scholar 

  24. 24.

    The ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301–8.

    Google Scholar 

  25. 25.

    Canet J, Gallart L, Gomar C, et al. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 2010;113(6):1338–50.

    PubMed  Google Scholar 

  26. 26.

    Mazo V, Sabaté S, Canet J, et al. Prospective external validation of a predictive score for postoperative pulmonary complications. Anesthesiology. 2014;121(12):219–31.

    PubMed  Google Scholar 

  27. 27.

    Scholes RL, Browning L, Sztendur EM, et al. Duration of anaesthesia, type of surgery, respiratory co-morbidity, predicted VO2max and smoking predict postoperative pulmonary complications after upper abdominal surgery: an observational study. Aust J Physiother. 2009;55(3):191–8.

    PubMed  Google Scholar 

  28. 28.

    Haines KJ, Skinner EH, Berney S, et al. Association of postoperative pulmonary complications with delayed mobilisation following major abdominal surgery: an observational cohort study. Physiotherapy. 2013;99(2):119–25.

    CAS  PubMed  Google Scholar 

  29. 29.

    Browning L, Denehy L, Scholes RL. The quantity of early upright mobilisation performed following upper abdominal surgery is low: an observational study. Aust J Physiother. 2007;53(1):47–52.

    PubMed  Google Scholar 

  30. 30.

    Parry S, Denehy L, Berney S, et al. Clinical application of the Melbourne risk prediction tool in a high-risk upper abdominal surgical population: an observational cohort study. Physiotherapy. 2014;100:47–53.

    CAS  PubMed  Google Scholar 

  31. 31.

    Samnani SS, Umer MF, Mehdi SH, et al. Impact of preoperative counselling on early postoperative mobilization and its role in smooth recovery. Int Sch Res Notices. 2014;2014:250536.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Boden I, Browning L, Skinner EH, et al. The LIPPSMAck POP (Lung Infection Prevention Post Surgery-Major Abdominal-with PreOperative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial. Trials. 2015;16(1):1–15.

    Google Scholar 

  33. 33.

    Boden I, Skinner EH, Browning L, et al. Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial. BMJ. 2018;360:461–7.

    Google Scholar 

  34. 34.

    Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer’s Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990;10(4):244e51.

    Google Scholar 

  35. 35.

    Flier S. How to inform a morbidly obese patient on the specific risk to develop postoperative pulmonary complications using evidence-based methodology. Eur J Anaesthesiol. 2006;23(2):154–9.

    CAS  PubMed  Google Scholar 

  36. 36.

    Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology. Effect of intraoperative high positive end-expiratory pressure (PEEP) with recruitment maneuvers vs low PEEP on postoperative pulmonary complications in obese patients: a randomized clinical trial. JAMA. 2019;321(23):2292–305.

    Google Scholar 

  37. 37.

    Matthay MA, Bhattacharya S, Gaver D, et al. Ventilator-induced lung injury: in vivo and in vitro mechanisms. Am J Phys Lung Cell Mol Phys. 2002;283(4):L678–82.

    CAS  Google Scholar 

  38. 38.

    Zhang S, Zhou Y, Zhao L, et al. κ-Opioid receptor activation protects against myocardial ischemia-reperfusion injury via AMPK/Akt/eNOS signaling activation. Eur J Pharmacol. 2018;833:100–8.

    CAS  PubMed  Google Scholar 

  39. 39.

    Zhou Y, Wang Y, Wang X, et al. The protective effects of κ-opioid receptor stimulation in hypoxic pulmonary hypertension involve inhibition of autophagy through the AMPK-MTOR pathway. Cell Physiol Biochem. 2017;44(5):1965–79.

    CAS  PubMed  Google Scholar 

  40. 40.

    Franklin C, Fortepiani L, Nguyen T, et al. Renal responses produced by microinjection of the kappa opioid receptor agonist, U50-488H, into sites within the rat lamina terminalis. Pharmacol Res Perspect. 2015;3(2):e00117.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Peng P, Huang LY, Li J, et al. Distribution of kappa-opioid receptor in the pulmonary artery and its changes during hypoxia. Anat Rec (Hoboken). 2009;292(7):1062–7.

    Google Scholar 

  42. 42.

    Shekar K, Fraser JF. Ventilator-induced lung injury. N Engl J Med. 2014;370(4):979.

    CAS  PubMed  Google Scholar 

  43. 43.

    Gao TT, Jiang L. Obesity exacerbates pulmonary vascular endothelial injury caused by mechanical ventilation. Int J Anesth Resu. 2018;(3):250–3. Chinese

  44. 44.

    Shah RJ, Wickersham N, Lederer DJ, et al. Preoperative plasma club (Clara) cell secretory protein levels are associated with primary graft dysfunction after lung transplantation. Am J Transplant. 2014;14(2):446–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Ide S, Minami M, Ishihara K, et al. Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in mu-opioid receptor knockout mice. Neuropharmacology. 2008;54(8):1182–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Black D. The kappa opioid receptor is associated with the perception of visceral pain. Gut. 1998;43(3):312–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Boom M, Niesters M, Sarton E, et al. Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994–6004.

    CAS  PubMed  Google Scholar 

  48. 48.

    Pasternak GW. Mu opioid pharmacology: 40 years to the promised land. Adv Pharmacol. 2018;82:261–91.

    PubMed  Google Scholar 

  49. 49.

    Commiskey S, Fan LW, Ho IK. Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005;98(2):109–16.

    CAS  PubMed  Google Scholar 

  50. 50.

    Hardman JG, Aitkenhead AR. Estimating alveolar dead space from the arterial to end-tidal CO2 gradient: a modeling analysis. Anesth Analg. 2003;97(6):1846–51.

    PubMed  Google Scholar 

Download references


The authors thank Long Wang at University of Xuzhou Medical University for his stimulating discussion and help on enzyme-linked immunosorbent assay techniques.


This work was supported by the National Natural Science Foundation of China (NSFC-81371242, NSFC-81671084); Qing Lan Project of Jiangsu province, Nature Science Foundation of Jiangsu province (BK20161175); “Six One” Project of Jiangsu province (LGY2016039); and The Science Funds for Health and Family Planning Commission of Sichuan Province (18PJ157).

Author information



Corresponding author

Correspondence to Su Liu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the local institutional review board (XYFY2019-KL082-01).

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Zeng, S., Li, X. et al. The Protective Effects of Butorphanol on Pulmonary Function of Patients with Obesity Undergoing Laparoscopic Bariatric Surgery: a Double-Blind Randomized Controlled Trial. OBES SURG (2020).

Download citation


  • Obesity
  • Butorphanol
  • Kappa opioid receptor
  • Pulmonary protection
  • Laparoscopic bariatric surgery