The Effects of Hypercapnia, Supplemental Oxygen, and Dexamethasone on Surgical Wound Infection

This study has been completed.
Sponsor:
Information provided by:
Outcomes Research Consortium
ClinicalTrials.gov Identifier:
NCT00273377
First received: January 5, 2006
Last updated: October 20, 2008
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
Surgical Wound Infection
Surgery, Colon
Other: Mild intraoperative hypercapnia (50 mmHg vs. 30 mmHg)
Other: Supplemental oxygen (80% vs. 30%)
Drug: Dexamethasone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effects of Hypercapnia, Supplemental Oxygen, and Dexamethasone on Surgical Wound Infection

Resource links provided by NLM:


Further study details as provided by Outcomes Research Consortium:

Primary Outcome Measures:
  • Surgical wound infection [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of hospitalization [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Suture removal [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Cost of care [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Return to work [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Nosocomial pneumonia [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 2000
Study Start Date: May 2002
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Mild intraoperative hypercapnia (50 mmHg vs. 30 mmHg) Other: Supplemental oxygen (80% vs. 30%) Drug: Dexamethasone
    4 mg
    Drug: Placebo
    placebo
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Colon resection expected to last >2 and <6 hours

Exclusion Criteria:

  • Bowel obstruction
  • Fever
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00273377

Locations
United States, Kentucky
Outcomes Research Institute
Louisville, Kentucky, United States, 40222
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Austria
University of Vienna
Vienna, Austria
Ireland
Mater Misericordiae Hospital
Dublin, Ireland, 7
Sponsors and Collaborators
Outcomes Research Consortium
Investigators
Study Director: Daniel I Sessler, M.D. The Cleveland Clinic
Principal Investigator: Ozan Akca, M.D. University of Louisville
  More Information

No publications provided by Outcomes Research Consortium

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Sessler, MD, Outcomes Research Consortium
ClinicalTrials.gov Identifier: NCT00273377     History of Changes
Other Study ID Numbers: 302, NIH Grant GM 061655, Gheens Foundation, Joseph Drown Foundation
Study First Received: January 5, 2006
Last Updated: October 20, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Outcomes Research Consortium:
Anesthesia
Oxygen
Carbon dioxide
Hypercapnia
Hypercarbia
Dexamethasone
Steroid
Postoperative nausea and vomiting (PONV)

Additional relevant MeSH terms:
Hypercapnia
Surgical Wound Infection
Wound Infection
Signs and Symptoms, Respiratory
Signs and Symptoms
Infection
Postoperative Complications
Pathologic Processes
Wounds and Injuries
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014