Nitrous oxide remains the most commonly used anesthetic and has been given to several billion patients. In vitro, even brief exposure to nitrous oxide inactivates methionine synthetase, which reduces induction of enzymes required for immune function. Nitrous oxide also reduces chemotactic migration by monocytes. However, nitrous oxide improves neutrophil chemotaxis and facilitates oxygen radical formation, and may therefore augment the efficacy of oxidative killing by neutrophils - the primary defense against pathogenic bacteria. Preliminary results in 200 patients suggest that the beneficial effects of nitrous oxide on wound healing outweigh its toxicities. We will thus test the hypothesis that the incidence of postoperative wound infection will be less in patients given 60% nitrous oxide than in those given 60% nitrogen during elective colon surgery. We propose to study up to 1000 patients undergoing elective colon resection. Perioperative antibiotic, anesthetic, fluid, and oxygen management will be set by protocol. Patients will be anesthetized with isoflurane in 40% inspired oxygen, with the remaining ventilatory mixture randomly assigned as nitrous oxide or nitrogen. Surgical wounds will be evaluated daily by a physician blinded to group assignment. Wounds will be considered infected when they meet CDC criteria or pus is detected and they are culture-positive for pathogenic bacteria. As a secondary outcome, incidence of nosocomial pneumonia in the two groups will be determined. Results will be analyzed by Fisher Exact and unpaired, two-tailed t-tests; P < 0.05 will be considered statistically significant. We anticipate showing that substituting nitrous oxide for nitrogen reduces the incidence of surgical wound infection. Confirming our hypothesis would thus allow clinicians to make a minor modification in anesthetic practice that might reduce the incidence of a complication responsible for considerable perioperative morbidity and cost.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061655-02
Application #
6696927
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Ikeda, Richard A
Project Start
2003-02-01
Project End
2007-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
2
Fiscal Year
2004
Total Cost
$109,938
Indirect Cost
Name
University of Louisville
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Ilfeld, Brian M; Le, Linda T; Ramjohn, Joanne et al. (2009) The effects of local anesthetic concentration and dose on continuous infraclavicular nerve blocks: a multicenter, randomized, observer-masked, controlled study. Anesth Analg 108:345-50
Jokela, R M; Cakmakkaya, O S; Danzeisen, O et al. (2009) Ondansetron has similar clinical efficacy against both nausea and vomiting. Anaesthesia 64:147-51
Komatsu, Ryu; Kamata, Kotoe; Hamada, Keiko et al. (2009) Airway scope and StyletScope for tracheal intubation in a simulated difficult airway. Anesth Analg 108:273-9
Shibuya, Kazuhiro; Ishiyama, Tadahiko; Ichikawa, Manabu et al. (2009) The direct effects of propofol on pial microvessels in rabbits. J Neurosurg Anesthesiol 21:40-6
Lenhardt, Rainer; Orhan-Sungur, Mukadder; Komatsu, Ryu et al. (2009) Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers. Anesthesiology 111:110-5
Fleischmann, Edith; Marschalek, Corinna; Schlemitz, Katja et al. (2009) Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial. BMC Anesthesiol 9:1
Ilfeld, Brian M; Le, Linda T; Meyer, R Scott et al. (2008) Ambulatory continuous femoral nerve blocks decrease time to discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked, placebo-controlled study. Anesthesiology 108:703-13
Ilfeld, Brian M; Ball, Scott T; Gearen, Peter F et al. (2008) Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology 109:491-501
Doufas, Anthony G; Morioka, Nobutada; Maghoub, Adel N et al. (2008) Lower-body warming mimics the normal epidural-induced reduction in the shivering threshold. Anesth Analg 106:252-6, table of contents
Ilfeld, Brian M; Loland, Vanessa J; Gerancher, J C et al. (2008) The effects of varying local anesthetic concentration and volume on continuous popliteal sciatic nerve blocks: a dual-center, randomized, controlled study. Anesth Analg 107:701-7

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