Prevention of Anastomotic Leakage after Total Gastrectomy with Perioperative Supplemental Oxygen Administration: A Prospective Randomized, Double-blind, Controlled, Single-center Trial

Abstract

Background

The role of supplemental oxygen therapy in the healing of esophagojejunal anastomosis is still very much in an experimental stage. The aim of the present prospective, randomized study was to assess the effect of administration of perioperative supplemental oxygen therapy on esophagojejunal anastomosis, where the risk of leakage is high.

Methods

We enrolled 171 patients between January 2009 and April 2012 who underwent elective open esophagojejunal anastomosis for gastric cancer. Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30 % (n = 85) or 80 % (n = 86). Administration commenced after induction of anesthesia and was maintained for 6 h after surgery.

Results

The overall anastomotic leak rate was 14.6 % (25 of 171): 17 patients (20 %) had an anastomotic dehiscence in the 30 % FiO2 group and 8 (9.3 %) in the 80 % FiO2 group (P < 0.05). The risk of anastomotic leak was 49 % lower in the 80 % FiO2 group (relative risk 0.61; 95 % confidence interval 0.40–0.95) versus 30 % FiO2.

Conclusions

Supplemental 80 % FiO2 provided during and for 6 h after major gastric cancer surgery to reduce postoperative anastomotic dehiscence should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost.

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References

  1. 1.

    Bonenkamp JJ, Songun I, Hermans J, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995;345:745–8.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Roder JD, Böttcher K, Siewert JR, Busch R, Hermanek P, Meyer HJ. Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992. Cancer. 1993;72:2089–97.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Budisin N, Budisin E, Golubovic A. Early complications following total gastrectomy for gastric cancer. J Surg Oncol. 2001;77:35–41.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Seufert RM, Schmidt-Matthiesen A, Beyer A. Total gastrectomy and oesophagojejunostomy—a prospective randomized trial of hand-sutured versus mechanically stapled anastomoses. Br J Surg. 1990;77:50–2.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Nomura S, Sasako M, Katai H, Sano T, Maruyama K. Decreasing complication rates with stapled esophagojejunostomy following a learning curve. Gastric Cancer. 2000;3:97–101.

    PubMed  Article  Google Scholar 

  6. 6.

    Halsted WS. Circular suture of the intestine: an experimental study. Am J Med Sci. 1887;94:436–61.

    Article  Google Scholar 

  7. 7.

    Adams W, Ctercteko G, Bilous M. Effect of an omental wrap on the healing and vascularity of compromised intestinal anastomoses. Dis Colon Rectum. 1992;35:731–8.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Abele D. Toxyc oxygen: the radical life-giver. Nature. 2002;420:27.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Clarkson AN, Sutherland BA, Appleton I. The biology and pathology of hypoxia–ischemia: an update. Arch Immunol Ther Exp. 2005;53:213–25.

    CAS  Google Scholar 

  10. 10.

    Mariani E, Polidori MC, Cherubini A, Mecocci P. Oxidative stress in brain aging, neurodegenerative and vascular disease: an overview. J Chromatogr B Anal Technol Biomed Life Sci. 2005;827:65–75.

    Article  CAS  Google Scholar 

  11. 11.

    Shannon AM, Bouchier-Hayes DJ, Condrom CM, Toomey D. Tumor hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev. 2003;29:297–307.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Sheridan WG, Lowndes RH, Young HL. Tissue oxygen tension as a predictor of colonic anastomotic healing. Dis Colon Rectum. 1987;30:867–71.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Hamzaoğlu I, Karahasanoğlu T, Aydin S, et al. The effects of hyperbaric oxygen on normal and ischemic colon anastomoses. Am J Surg. 1998;176:458–61.

    PubMed  Article  Google Scholar 

  14. 14.

    Semenza GL. HIF-1, O2 and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell. 2001;107:1–3.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    West JB. Respiratory physiology—the essentials. Bethesda, MD: Williams & Willkins; 1999.

    Google Scholar 

  16. 16.

    Hockel M, Vaupel P. Tumour hypoxia: definitions and current clinical, biologic and molecular aspects. J Natl Cancer Inst. 2001;93:266–76.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Hunt TK, Pai MP. The effect of vaying oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet. 1972;135:561–7.

    PubMed  CAS  Google Scholar 

  18. 18.

    Belda FJ, Aguilera L, García de la Asunción J, et al.; Spanish Reduccion de la Tasa de Infeccion Quirurgica Group. Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial. JAMA. 2005;294:2035–42.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    American Society of Anesthesiologists. New classification of physiology status. Anesthesiologists. 1963;24:111.

    Google Scholar 

  20. 20.

    Franchi M, Ghezzi F, Zanaboni F, Scarabelli C, Beretta P, Donadello N. Nonclosure of peritoneum at radical abdominal hysterectomy and pelvic node dissection: a randomized study. Obstet Gynecol. 1997;90:622.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr. 2003;22:321–36.

    PubMed  Article  Google Scholar 

  22. 22.

    Hermanek P, Sobin LH, eds. UICC TNM classification of malignant tumors. 4th ed. 2nd revised edition. Berlin: Springer; 1982.

  23. 23.

    Greif R, Akca O, Horn EP, Kurz A, Sessler DI. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. Outcomes Research Group. N Engl J Med. 2000;342:161–7.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Brasel K, McRitchie D, Dellinger P; EBRS Group. Canadian Association of General Surgeons and American College of Surgeons Evidence Based Reviews in Surgery 21. The risk of surgical site infection is reduced with perioperative oxygen. Can J Surg. 2007;50:214–6.

    PubMed  Google Scholar 

  25. 25.

    Caldwell PRB, Lee WL Jr, Schildkraut HS, Archibald ER. Changes in lung volume, diffusing capacity, and blood gases in men breathing oxygen. J Appl Physiol. 1966;21:1477–83.

    PubMed  CAS  Google Scholar 

  26. 26.

    Turan A, Apfel CC, Kumpch M, et al. Does the efficacy of supplemental oxygen for the prevenction of postoperative nausea and vomiting depend on the measured outcome, observational period or site of surgery? Anaesthesia. 2006;61:628–33.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Mayzler O, Weksler N, Domchik S, Klein M, Mizrahi S, Gurman GM. Does supplemental perioperative oxygen administration reduce the incidence of wound infection in elective colorectal surgery? Minerva Anestesiol. 2005;71:21–5.

    PubMed  CAS  Google Scholar 

  28. 28.

    Pryor KO, Fahey TJ III, Lien CA, Goldstein PA. Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial. JAMA. 2004;291:79–87.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Gardella C, Goltra LB, Laschansky E, et al. High concentration supplemental perioperative oxygen to reduce the incidence of postcesarean surgical site infection: a randomized controlled trial. Obstet Gynecol. 2008;112:545–52.

    PubMed  Article  Google Scholar 

  30. 30.

    Qadan M, Akça O, Mahid SS, Hornung CA, Polk HC Jr. Perioperative supplemental oxygen therapy and surgical site infection: a meta-analysis of randomized controlled trials. Arch Surg. 2009;144:359–67.

    PubMed  Article  Google Scholar 

  31. 31.

    Meyhoff CS, Wetterslev J, Jorgensen LN, et al.; PROXI Trial. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery. JAMA. 2009;302:1543–50.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    García-Botello SA, García-Granero E, Lillo R, López-Mozos F, Millán M, Lledó S. Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis. Br J Surg. 2006;93:698–706.

    PubMed  Article  Google Scholar 

  33. 33.

    Tornero-Campello G. Letter: Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis (Br J Surg. 2006;93:698–706). Br J Surg. 2006;93:1148.

  34. 34.

    García-Botello SA. Author's reply: Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis (Br J Surg. 2006;93:698–706). Br J Surg. 2006;93:1148–1149.

    Google Scholar 

  35. 35.

    Schietroma M, Carlei F, Cecilia EM, Piccione F, Bianchi Z, Amicucci G. Colorectal infraperitoneal anastomosis: the effects of perioperative supplemental oxygen administration on the anastomotic dehiscence. J Gastrointest Surg. 2012;16:427–34.

    PubMed  Article  Google Scholar 

  36. 36.

    Sala C, García-Granero E, Martí R. Anastomotic pHi monitoring after colorectal surgery. Design and preliminary results. Br J Surg. 1994;81:35.

    Google Scholar 

  37. 37.

    García-Granero E, García J, Sala C. Is intramucosal pH associated with wound anastomotic complications after colorectal surgery? Dis Colon Rectum. 1998;41:56.

    Article  Google Scholar 

  38. 38.

    Comroe JH Jr, Dripps RD, Dumke PR. Oxygen toxicity. The effect of inhalation of high concentrations of oxygen for twenty-four hours on normal men at sea level and at simulated altitude of 18000 feet. JAMA. 1945;128:710–7.

    Article  CAS  Google Scholar 

  39. 39.

    Dubois AB, Turaids T, Mammen RE, Nobrega FT. Pulmonary atelectasis in subjects breathing oxygen at sea level or at simulated altitude. J Appl Physiol. 1966;21:828–36.

    PubMed  CAS  Google Scholar 

  40. 40.

    Montgomery AB, Luce JM, Murray JF. Retrosternal pain is an early indicator of oxygen toxicity. Am Rev Respir Dis. 1989;139:1548–50.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Kabon B, Kurz A. Optimal perioperative oxygen administration. Curr Opin Anaesthesiol. 2006;19:11–8.

    PubMed  Article  Google Scholar 

  42. 42.

    Knighton DR, Halliday B, Hunt TK. Oxygen as an antibiotic: the effect of inspired oxygen on infection. Arch Surg. 1984;119:199–204.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Allen DB, Maguire JJ, Mahdavian M, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 1997;132:991–6.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Emanuela Marina Cecilia MD.

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Schietroma, M., Cecilia, E.M., Carlei, F. et al. Prevention of Anastomotic Leakage after Total Gastrectomy with Perioperative Supplemental Oxygen Administration: A Prospective Randomized, Double-blind, Controlled, Single-center Trial. Ann Surg Oncol 20, 1584–1590 (2013). https://doi.org/10.1245/s10434-012-2714-7

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Keywords

  • Anastomotic Leakage
  • Supplemental Oxygen
  • Anastomotic Dehiscence
  • Ketorolac Tromethamine
  • Esophagojejunal Anastomosis