Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2008

Open Access 01-12-2008 | Study protocol

Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

Authors: Christian S Meyhoff, Jørn Wetterslev, Lars N Jorgensen, Steen W Henneberg, Inger Simonsen, Therese Pulawska, Line R Walker, Nina Skovgaard, Kim Heltø, Peter Gocht-Jensen, Palle S Carlsson, Henrik Rask, Sharaf Karim, Charlotte G Carlsen, Frank S Jensen, Lars S Rasmussen, the PROXI Trial Group

Published in: Trials | Issue 1/2008

Login to get access

Abstract

Background

A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO 2 = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO 2 = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery.

Methods and design

The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO 2 = 0.80) or 30% oxygen (FiO 2 = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power.

Discussion

This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy.

Trial registration

ClinicalTrials.gov identifier: NCT00364741.
Appendix
Available only for authorised users
Literature
1.
Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P: Adverse impact of surgical site infections in English hospitals. J Hosp Infect. 2005, 60: 93-103. 10.1016/j.jhin.2004.10.019.CrossRefPubMed
2.
Miles AA, Miles EM, Burke J: The value and duration of defence reactions of the skin to the primary lodgement of bacteria. Br J Exp Pathol. 1957, 38: 79-96.PubMedPubMedCentral
3.
Babior BM: Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978, 298: 659-668.CrossRefPubMed
4.
Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, Chang M, Le AX, Hopf HW, Hunt TK: Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 1997, 132: 991-996.CrossRefPubMed
5.
Hopf HW, Hunt TK, West JM, Blomquist P, Goodson WH, Jensen JA, Jonsson K, Paty PB, Rabkin JM, Upton RA, von Smitten K, Whitney JD: Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg. 1997, 132: 997-1004.CrossRefPubMed
6.
Niinikoski J, Jussila P, Vihersaari T: Radical mastectomy wound as a model for studies of human wound metabolism. Am J Surg. 1973, 126: 53-58. 10.1016/S0002-9610(73)80094-7.CrossRefPubMed
7.
Wetterslev J, Thorlund K, Brok J, Gluud C: Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2008, 61: 64-75. 10.1016/j.jclinepi.2007.03.013.CrossRefPubMed
8.
Brok J, Thorlund K, Gluud C, Wetterslev J: Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008, 61: 763-769. 10.1016/j.jclinepi.2007.10.007.CrossRefPubMed
9.
Thorlund K, Devereaux PJ, Wetterslev J, Gyuatt G, Ioannidis JP, Thabane L, Gluud LL, Als-Nielsen B, Gluud C: Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses?. Int J Epidemiol. 2008
10.
11.
Young C, Horton R: Putting clinical trials into context. Lancet. 2005, 366: 107-108. 10.1016/S0140-6736(05)66846-8.CrossRefPubMed
12.
Belda FJ, Aguilera L, Garcia de la Asunción J, Alberti J, Vicente R, Ferrandiz L, Rodriguez R, Company R, Sessler DI, Aguilar G, Botello SG, Orti R: Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial. JAMA. 2005, 294: 2035-2042. 10.1001/jama.294.16.2035.CrossRefPubMed
13.
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: 161-167. 10.1056/NEJM200001203420303.CrossRefPubMed
14.
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: 21-25.PubMed
15.
Pryor KO, Fahey 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: 79-87. 10.1001/jama.291.1.79.CrossRefPubMed
16.
Akca O, Podolsky A, Eisenhuber E, Panzer O, Hetz H, Lampl K, Lackner FX, Wittmann K, Grabenwoeger F, Kurz A, Schultz AM, Negishi C, Sessler DI: Comparable postoperative pulmonary atelectasis in patients given 30% or 80% oxygen during and 2 hours after colon resection. Anesthesiology. 1999, 91: 991-998. 10.1097/00000542-199910000-00019.CrossRefPubMed
17.
Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G: Optimal oxygen concentration during induction of general anesthesia. Anesthesiology. 2003, 98: 28-33. 10.1097/00000542-200301000-00008.CrossRefPubMed
18.
Carpagnano GE, Kharitonov SA, Foschino-Barbaro MP, Resta O, Gramiccioni E, Barnes PJ: Supplementary oxygen in healthy subjects and those with COPD increases oxidative stress and airway inflammation. Thorax. 2004, 59: 1016-1019. 10.1136/thx.2003.020768.CrossRefPubMedPubMedCentral
19.
Bandali KS, Belanger MP, Wittnich C: Does hyperoxia affect glucose regulation and transport in the newborn?. J Thorac Cardiovasc Surg. 2003, 126: 1730-1735. 10.1016/S0022-5223(03)01044-4.CrossRefPubMed
20.
Harten JM, Anderson KJ, Angerson WJ, Booth MG, Kinsella J: The effect of normobaric hyperoxia on cardiac index in healthy awake volunteers. Anaesthesia. 2003, 58: 885-888. 10.1046/j.1365-2044.2003.03333.x.CrossRefPubMed
21.
Garcia-Botello SA, Garcia-Granero E, Lillo R, Lopez-Mozos F, Millan M, Lledo S: Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis. Br J Surg. 2006, 93: 698-706. 10.1002/bjs.5370.CrossRefPubMed
22.
Greif R, Laciny S, Rapf B, Hickle RS, Sessler DI: Supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Anesthesiology. 1999, 91: 1246-1252. 10.1097/00000542-199911000-00014.CrossRefPubMed
23.
Turan A, Apfel CC, Kumpch M, Danzeisen O, Eberhart LH, Forst H, Heringhaus C, Isselhorst C, Trenkler S, Trick M, Vedder I, Kerger H: Does the efficacy of supplemental oxygen for the prevention of postoperative nausea and vomiting depend on the measured outcome, observational period or site of surgery?. Anaesthesia. 2006, 61: 628-633. 10.1111/j.1365-2044.2006.04703.x.CrossRefPubMed
24.
Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG: A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990, 97: 922-929.CrossRefPubMed
25.
Gotzsche PC: Blinding during data analysis and writing of manuscripts. Control Clin Trials. 1996, 17: 285-290. 10.1016/0197-2456(95)00263-4.CrossRefPubMed
26.
Fearon KC, Ljungqvist O, von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, Nygren J, Hausel J, Soop M, Andersen J, Kehlet H: Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr. 2005, 24: 466-477. 10.1016/j.clnu.2005.02.002.CrossRefPubMed
27.
Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ: Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997, 41: 1095-1103.CrossRefPubMed
28.
Arkilic CF, Taguchi A, Sharma N, Ratnaraj J, Sessler DI, Read TE, Fleshman JW, Kurz A: Supplemental perioperative fluid administration increases tissue oxygen pressure. Surgery. 2003, 133: 49-55. 10.1067/msy.2003.80.CrossRefPubMed
29.
Kabon B, Akca O, Taguchi A, Nagele A, Jebadurai R, Arkilic CF, Sharma N, Ahluwalia A, Galandiuk S, Fleshman J, Sessler DI, Kurz A: Supplemental intravenous crystalloid administration does not reduce the risk of surgical wound infection. Anesth Analg. 2005, 101: 1546-1553. 10.1213/01.ANE.0000180217.57952.FE.CrossRefPubMedPubMedCentral
30.
Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, Rasmussen MS, Lanng C, Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen IS, Teilum D, Christensen AM, Graungaard B, Pott F: Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003, 238: 641-648. 10.1097/01.sla.0000094387.50865.23.CrossRefPubMedPubMedCentral
31.
Bratzler DW, Houck PM: Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Am J Surg. 2005, 189: 395-404. 10.1016/j.amjsurg.2005.01.015.CrossRefPubMed
32.
Haley RW, Culver DH, Morgan WM, White JW, Emori TG, Hooton TM: Identifying patients at high risk of surgical wound infection. A simple multivariate index of patient susceptibility and wound contamination. Am J Epidemiol. 1985, 121: 206-215.PubMed
33.
Culver DH, Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG, Banerjee SN, Edwards JR, Tolson JS, Henderson TS: Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med. 1991, 91 (Suppl 3B): 152-157. 10.1016/0002-9343(91)90361-Z.CrossRef
34.
Wilson AP, Treasure T, Sturridge MF, Gruneberg RN: A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet. 1986, 1: 311-313. 10.1016/S0140-6736(86)90838-X.CrossRefPubMed
35.
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR: Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999, 20: 250-278. 10.1086/501620.CrossRefPubMed
36.
37.
Ioannidis JP, Evans SJ, Gotzsche PC, O'Neill RT, Altman DG, Schulz K, Moher D: Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004, 141: 781-788.CrossRefPubMed
38.
Engels JM, Diehr P: Imputation of missing longitudinal data: a comparison of methods. J Clin Epidemiol. 2003, 56: 968-976. 10.1016/S0895-4356(03)00170-7.CrossRefPubMed
39.
Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull. 1999, 46: 263-268.PubMed
40.
ICH Harmonised Tripartite Guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 Expert Working Group. Stat Med. 1999, 18: 1905-1942.
41.
ICH Steering Committee: International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH Harmonised Tripartite Guideline for Good Clinical Practice. 1998, London: Brookwood Medical Publications Ltd, 3
42.
Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E: Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007, 107: 221-231. 10.1097/01.anes.0000270723.30772.da.CrossRefPubMed
43.
Fleischmann E, Lenhardt R, Kurz A, Herbst F, Fulesdi B, Greif R, Sessler DI, Akca O: Nitrous oxide and risk of surgical wound infection: a randomised trial. Lancet. 2005, 366: 1101-1107. 10.1016/S0140-6736(05)67422-3.CrossRefPubMed
44.
Squadrone V, Coha M, Cerutti E, Schellino MM, Biolino P, Occella P, Belloni G, Vilianis G, Fiore G, Cavallo F, Ranieri VM: Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial. JAMA. 2005, 293: 589-595. 10.1001/jama.293.5.589.CrossRefPubMed
45.
Schulz KF, Chalmers I, Hayes RJ, Altman DG: Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995, 273: 408-412. 10.1001/jama.273.5.408.CrossRefPubMed
46.
Molina-Cabrillana J, Valle-Morales L, Hernandez-Vera J, Lopez-Carrio I, Garcia-Hernandez JA, Bolanos-Rivero M: Surveillance and risk factors on hysterectomy wound infection rate in Gran Canaria, Spain. Eur J Obstet Gynecol Reprod Biol. 2008, 136: 232-238. 10.1016/j.ejogrb.2006.11.005.CrossRefPubMed
Metadata
Title
Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial
Authors
Christian S Meyhoff
Jørn Wetterslev
Lars N Jorgensen
Steen W Henneberg
Inger Simonsen
Therese Pulawska
Line R Walker
Nina Skovgaard
Kim Heltø
Peter Gocht-Jensen
Palle S Carlsson
Henrik Rask
Sharaf Karim
Charlotte G Carlsen
Frank S Jensen
Lars S Rasmussen
the PROXI Trial Group
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Trials / Issue 1/2008
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-9-58

Other articles of this Issue 1/2008

Trials 1/2008 Go to the issue

Research

Echocardiographic predictors of severe heart failure symptoms in hypertrophic cardiomyopathy patients with sinus rhythm

Book review

Furberg Bengt D, Furberg Curt D: Evaluating Clinical Research – All that Glitters is not Gold

Study protocol

Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

Research

Randomised, crossover clinical trial, in healthy volunteers, to compare the systemic availability of two topical intranasal budesonide formulations

Study protocol

Randomised controlled trial of thermostatic mixer valves in reducing bath hot tap water temperature in families with young children in social housing: A protocol

Study protocol

Rationale, design and methodology for a Prospective Randomized Study of graft patency in Off-pump and On-pump MultI-Vessel coronary artery bypasS Surgery (PROMISS) using multidetector computed tomography