The Effects of Hypercapnia, Supplemental Oxygen, and Dexamethasone on Surgical Wound Infection
Condition: Surgical Wound Infection; Surgery, Colon
MeSH terms: Infections; Communicable Diseases; Wound Infection; Surgical Wound Infection; Hypercapnia; Wounds and Injuries; Surgical Wound
Study type: Interventional
Phase: Phase 3

Summary: 
      The investigators will test the hypotheses that mild hypercapnia and supplemental oxygen
      reduce wound infection risk in patients undergoing colon resection. The investigators will
      simultaneously test the hypothesis that low-dose dexamethasone (a common treatment for
      postoperative nausea and vomiting) does not increase infection risk.
    

Detailed description: 
      Wound infections are common and serious complications of anesthesia and surgery. Even in
      patients who are kept normothermic and given supplemental oxygen, the incidence of wound
      infection after colon resection exceeds 5%. About 80% of these resections are done for colon
      cancer, the third leading cause of cancer death. The average surgical wound infection
      prolongs hospitalization by a week and substantially increases cost. Major factors
      influencing the incidence of surgical wound infection include the site and complexity of
      surgery, underlying illness (including treatment with immunosuppressive drugs), timely
      administration of prophylactic antibiotics, intraoperative patient temperature, hypovolemia,
      and tissue oxygen tension.

      The primary defense against surgical pathogens is oxidative killing by neutrophils. Oxygen is
      a substrate for this process, and the reaction critically depends on tissue oxygen tension
      throughout the observed physiological range. It is therefore unsurprising that subcutaneous
      tissue oxygen tension (PsqO2) is inversely correlated with the risk of surgical wound
      infection. Primary determinants of tissue oxygen availability include arterial oxygen
      tension, hemoglobin concentration, and local perfusion.

      An additional determinant of peripheral oxygen delivery is cardiac output. Mild hypercapnia
      increases cardiac output: for example, augmenting arterial carbon dioxide tension (PaCO2)
      just 10-12 mmHg increases the cardiac index 15%. Our preliminary studies confirm that mild
      hypercapnia increases cardiac output and additionally indicate the hypercapnia markedly
      improves tissue oxygenation. For example, tissue oxygen tension increased 16 mmHg, from 58 to
      74 mmHg over a 20 mmHg range of PaCO2 in anesthetized volunteers. We have also shown that
      increasing PaCO2 by just 15 mmHg increased tissue oxygen tension 16 mmHg in surgical
      patients. Similar results were observed in morbidly obese patients. Previous work indicates
      that similar increases in PsqO2 reduces the risk of surgical wound infection by about 30%. We
      thus propose to test the hypothesis that mild hypercapnia significantly reduces the incidence
      of surgical wound infection in normothermic patients undergoing colon resection. Secondary
      outcomes will include the duration of hospitalization, cost of care, the incidence of
      nosocomial pneumonia, the incidence of postoperative nausea and vomiting (PONV) and return to
      function.

      High intra- and postoperative oxygen concentration (80%, as opposed to 30% oxygen) has been
      shown to reduce the rate of wound infection by more than 50%. Therefore, the protocol
      implemented high intraoperative oxygen concentrations for all patients this trial. However,
      within the first 500 enrolled patients a recent trial reported a better outcome for patients
      with low perioperative oxygen concentrations. Although that trial was less well controlled
      and underpowered, the conflicting evidence indicates that additional study is needed. We will
      therefore simultaneously test the hypothesis that supplemental oxygen reduces infection risk.

      Patients undergoing colon surgery are generally at high risk for postoperative nausea and
      vomiting (PONV). According to results from meta-analyses, a single intraoperative dose of
      dexamethasone is effective and safe for the prophylaxis for PONV. Dexamethasone has thus been
      recommended as a first-line prophylaxis for PONV. However, none of the previous PONV trials
      have focused on wound infections nor had a sufficiently long observational period to rule out
      potential concerns of an increased incidence of wound infection. We will therefore also test
      the hypothesis that dexamethasone does not increase the risk of surgical wound infection. The
      second and third hypotheses will be added to the protocol, using a factorial design, after
      the first 500 patients are enrolled.
    

Intervention name(s): Mild intraoperative hypercapnia (50 mmHg vs. 30 mmHg); Supplemental oxygen (80% vs. 30%); Dexamethasone; Placebo
Intervention type(s): Other; Other; Drug; Drug
Intervention description(s): 4 mg; placebo
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Anesthesia; Oxygen; Carbon dioxide; Hypercapnia; Hypercarbia; Dexamethasone; Steroid; Postoperative nausea and vomiting (PONV)