Supplemental oxygen and surgical site infection: getting to the truth
2017; Elsevier BV; Volume: 119; Issue: 1 Linguagem: Inglês
10.1093/bja/aex096
ISSN1471-6771
Autores Tópico(s)Anesthesia and Pain Management
ResumoSurgical site infection (SSI) remains one of the most serious and expensive postoperative complications.1Schweizer ML Cullen JJ Perencevich EN Vaughan Sarrazin MS. Costs associated with surgical site infections in Veterans Affairs Hospitals.JAMA Surg. 2014; 149: 575-581Crossref PubMed Scopus (120) Google Scholar Infected patients are twice as likely to need admission to critical care and twice as likely to die.2Koch AM Nilsen RM Eriksen HM Cox RJ Harthug S. Mortality related to hospital-associated infections in a tertiary hospital; repeated cross-sectional studies between 2004–2011.Antimicrob Resist Infect Control. 2015; 4: 57Crossref PubMed Scopus (36) Google Scholar The primary defence against SSI is oxidative killing by neutrophils, and molecular oxygen is the substrate.3Sheffield CW Sessler DI Hopf HW et al.Centrally and locally mediated thermoregulatory responses alter subcutaneous oxygen tension.Wound Repair Regen. 1996; 4: 339-345Crossref PubMed Scopus (104) Google Scholar Resistance to infection is thus a strong function of tissue oxygen partial pressure over the clinical range. One might thus expect that supplemental perioperative oxygen (∼80%) would reduce infection risk when compared with more traditional inspired oxygen concentrations (∼30%) during anaesthesia and surgery. Despite some early evidence supporting the role of supplemental oxygen in reducing the risk of SSI,4Greif R Akca O Horn E Kurz A Sessler D. Supplemental perioperative oxygen to reduce the incidence of surgical wound infection.N Engl J Med. 2000; 342: 161-167Crossref PubMed Scopus (859) Google Scholar there have since been conflicting results from numerous randomized clinical trials. The most compelling data come from the PROXI trial,5Meyhoff CS Wetterslev J Jorgensen LN et al.Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.JAMA. 2009; 302: 1543-1550Crossref PubMed Scopus (309) Google Scholar a large, multicentre, randomized trial enrolling 1400 patients undergoing abdominal surgery. This trial found no evidence of any beneficial effect of supplemental oxygen; SSI occurred in 131 of 685 patients (19%) receiving 80% oxygen and in 141 of 701 (20%) receiving 30% oxygen [odds ratio 0.94 (95% confidence interval 0.72–1.22), P=0.64]. Indeed, a long-term follow-up study (median 2.3 years after surgery) found poorer survival in the supplemental oxygen group.6Meyhoff CS Jorgensen LN Wetterslev J Christensen KB Rasmussen LS. Increased long-term mortality after a high perioperative inspiratory oxygen fraction during abdominal surgery: follow-up of a randomized clinical trial.Anesth Analg. 2012; 115: 849-854Crossref PubMed Scopus (126) Google Scholar Despite these conflicting reports, the World Health Organization (WHO) Guidelines Development Group has recently published a recommendation stating that adult patients undergoing relaxant general anaesthesia and tracheal intubation for surgical procedures should receive an 80% fraction of inspired oxygen intraoperatively, and if feasible, for 2–6 h afterwards, to reduce the risk of SSI (strong recommendation, moderate quality of evidence).7Allegranzi B Zayed B Bischoff P et al.New WHO recommendations on intraoperative and postoperative measures for surgical site infection prevention: an evidence-based global perspective.Lancet Infect Dis. 2016; 16: e288-e303Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar Our view is that this recommendation is not supported by current evidence. Medical research is mostly done in accordance with the scientific method in which a study hypothesis is tested. The study results are then interpreted and the null hypothesis can be accepted or rejected. It is the accruing weight of supportive evidence that gets us closer to the truth. A commonly used hierarchy of evidence reminds us that small trials are often unreliable and thus should not be automatically equated with high-quality evidence.8Djulbegovic B Guyatt GH. Progress in evidence-based medicine: a quarter century on.Lancet. 2017; (Feb 16. pii: S0140-6736(16)31592-6.)doi:10.1016/S0140-6736(16)31592-6Abstract Full Text Full Text PDF Scopus (433) Google Scholar A systematic review of the literature and a pooled summation of all relevant trials (meta-analysis) is more likely to provide an unbiased estimate of a true treatment effect. On the question of whether or not supplemental oxygen reduces SSI, initial studies showed substantial benefit of supplemental oxygen, but other more recent studies have not. Specifically, two well-conducted randomized trials (n=500 and n=300),4Greif R Akca O Horn E Kurz A Sessler D. Supplemental perioperative oxygen to reduce the incidence of surgical wound infection.N Engl J Med. 2000; 342: 161-167Crossref PubMed Scopus (859) Google Scholar9Belda FJ Aguilera L Garcia de la Asuncion J et al.Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial.JAMA. 2005; 294: 2035-2042Crossref PubMed Scopus (421) Google Scholar a smaller trial,10Turtiainen J Saimanen EI Partio TJ et al.Supplemental postoperative oxygen in the prevention of surgical wound infection after lower limb vascular surgery: a randomized controlled trial.World J Surg. 2011; 35: 1387-1395Crossref PubMed Scopus (29) Google Scholar and a registry analysis11Maragakis LL Cosgrove SE Martinez EA Tucker MG Cohen DB Perl TM. Intraoperative fraction of inspired oxygen is a modifiable risk factor for surgical site infection after spinal surgery.Anesthesiology. 2009; 110: 556-562Crossref PubMed Scopus (98) Google Scholar suggest that supplemental oxygen (80% vs 30%) halved infection risk. On the other hand, the 1400-patient PROXI trial5Meyhoff CS Wetterslev J Jorgensen LN et al.Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.JAMA. 2009; 302: 1543-1550Crossref PubMed Scopus (309) Google Scholar and another recently published 568-patient trial12Kurz A Fleischmann E Sessler DI Buggy DJ Apfel C Akca O. Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial.Br J Anaesth. 2015; 115: 434-443Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar found no benefit of supplemental oxygen, and one trial reported higher rates of SSI with supplemental oxygen.13Pryor KO Fahey 3rd, TJ 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: 79-87Crossref PubMed Scopus (291) Google Scholar Available literature thus provides no clear guidance on whether supplemental oxygen reduces infection and wound-related complications. We have several major concerns about the evidence used to generate the recommendation from the WHO Guidelines Development Group regarding the use of supplemental oxygen during and after surgery. This recommendation is too general and is based on some studies that should not have been included in the meta-analysis supporting it, as well as other relevant studies that were missed. First, the authors included data from the ENIGMA trial, for which one of us (P.M.) was the lead author.14Myles PS Leslie K Chan MT et al.Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial.Anesthesiology. 2007; 107: 221-231Crossref PubMed Scopus (301) Google Scholar The ENIGMA trial did not randomly assign surgical patients to high or low inspired oxygen; rather, it compared nitrous oxide–containing and nitrous oxide–free anaesthesia. Not all patients received low or high oxygen as a consequence, so these secondary data cannot be considered derived from a randomized comparison. Second, three of the included studies enrolled women undergoing caesarean section for which they received a spinal anaesthetic. Given that the WHO Guidelines Development Group specifically states that their recommendation should apply to 'patients undergoing general anaesthesia with endotracheal intubation', inclusion of these studies is unreasonable. Third, two key studies were missed in their analysis.12Kurz A Fleischmann E Sessler DI Buggy DJ Apfel C Akca O. Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial.Br J Anaesth. 2015; 115: 434-443Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar15Wadhwa A Kabon B Fleischmann E Kurz A Sessler DI. Supplemental postoperative oxygen does not reduce surgical site infection and major healing-related complications from bariatric surgery in morbidly obese patients: a randomized, blinded trial.Anesth Analg. 2014; 119: 357-365Crossref PubMed Scopus (19) Google Scholar Fourth, inclusion of two studies, but not three others, raises a further concern in that this unique series of small, single-centre trials all reported a 'positive' effect of supplemental oxygen. One of the papers has since been retracted,16Schietroma M Carlei F Cecilia EM et al.Retraction note: colorectal infraperitoneal anastomosis: the effects of perioperative supplemental oxygen administration on the anastomotic dehiscence.J Gastrointest Surg. 2014; 18: 219Crossref PubMed Scopus (5) Google Scholar and the others must remain in doubt. It is preferable, therefore, to not include these studies in an updated meta-analysis. The recommendation also suggests the use of 80% oxygen in all adult patients undergoing general anaesthesia with tracheal intubation for surgical procedures, and to do so in the intraoperative as well as early postoperative period. Most studies that evaluated supplemental oxygen were performed in patients undergoing colorectal or abdominal surgery. Thus to extend these results to all surgical patient populations is a far stretch. Furthermore, there is little evidence that postoperative oxygen administration decreases the incidence of postoperative wound infections. In fact, one of the few studies investigating postoperative oxygen administration in 400 obese patients did not show an effect of postoperative oxygen administration on the incidence of SSI.15Wadhwa A Kabon B Fleischmann E Kurz A Sessler DI. Supplemental postoperative oxygen does not reduce surgical site infection and major healing-related complications from bariatric surgery in morbidly obese patients: a randomized, blinded trial.Anesth Analg. 2014; 119: 357-365Crossref PubMed Scopus (19) Google Scholar If including the caesarean section studies (and thus extending the target population of the recommendations to include any surgery with a skin incision), there are 14 relevant trials (5928 patients)4Greif R Akca O Horn E Kurz A Sessler D. Supplemental perioperative oxygen to reduce the incidence of surgical wound infection.N Engl J Med. 2000; 342: 161-167Crossref PubMed Scopus (859) Google Scholar5Meyhoff CS Wetterslev J Jorgensen LN et al.Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.JAMA. 2009; 302: 1543-1550Crossref PubMed Scopus (309) Google Scholar9Belda FJ Aguilera L Garcia de la Asuncion J et al.Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial.JAMA. 2005; 294: 2035-2042Crossref PubMed Scopus (421) Google Scholar12Kurz A Fleischmann E Sessler DI Buggy DJ Apfel C Akca O. Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial.Br J Anaesth. 2015; 115: 434-443Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar13Pryor KO Fahey 3rd, TJ 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: 79-87Crossref PubMed Scopus (291) Google Scholar15Wadhwa A Kabon B Fleischmann E Kurz A Sessler DI. Supplemental postoperative oxygen does not reduce surgical site infection and major healing-related complications from bariatric surgery in morbidly obese patients: a randomized, blinded trial.Anesth Analg. 2014; 119: 357-365Crossref PubMed Scopus (19) Google Scholar17Bickel A Gurevits M Vamos R Ivry S Eitan A. Perioperative hyperoxygenation and wound site infection following surgery for acute appendicitis: a randomized, prospective, controlled trial.Arch Surg. 2011; 146: 464-470Crossref PubMed Scopus (91) Google Scholar, 18Duggal N Poddatoori V Noroozkhani S Siddik-Ahmad RI Caughey AB. Perioperative oxygen supplementation and surgical site infection after cesarean delivery: a randomized trial.Obstet Gynecol. 2013; 122: 79-84Crossref PubMed Scopus (37) Google Scholar, 19Gardella 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: 545-552Crossref PubMed Scopus (75) Google Scholar, 20Mayzler 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: 21-25PubMed Google Scholar, 21Scifres CM Leighton BL Fogertey PJ Macones GA Stamilio DM. Supplemental oxygen for the prevention of postcesarean infectious morbidity: a randomized controlled trial.Am J Obstet Gynecol. 2011; 205: 267.e1-267.e9Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 22Stall A Paryavi E Gupta R Zadnik M Hui E O'Toole RV. Perioperative supplemental oxygen to reduce surgical site infection after open fixation of high-risk fractures: a randomized controlled pilot trial.J Trauma Acute Care Surg. 2013; 75: 657-663Crossref PubMed Scopus (47) Google Scholar, 23Thibon P Borgey F Boutreux S Hanouz JL Le Coutour X Parienti JJ. Effect of perioperative oxygen supplementation on 30-day surgical site infection rate in abdominal, gynecologic, and breast surgery: the ISO2 randomized controlled trial.Anesthesiology. 2012; 117: 504-511Crossref PubMed Scopus (49) Google Scholar, 24Williams NL Glover MM Crisp C Acton AL McKenna DS. Randomized controlled trial of the effect of 30% versus 80% fraction of inspired oxygen on cesarean delivery surgical site infection.Am J Perinatol. 2013; 30: 781-786Crossref PubMed Scopus (24) Google Scholar with a pooled odds ratio using random effects (RevMan 5.3.5) of 0.93 (95% CI 0.73–1.18; I2=47%; P=0.54) (see Fig. 1) for surgical site infection. Therefore, current evidence does not support the use of supplemental oxygen to prevent surgical site infection. We thus urge the WHO Guidelines Development Group to rethink their recommendation. None declared.
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