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.
