Dexamethasone and Mild intraoperative hypercapnia (50 mmHg vs. 30 mmHg) and Supplemental oxygen (80% vs. 30%) in Surgical Wound Infection and Surgery, Colon - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

2000

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Austria
- - Vienna, Austria
    - University of Vienna
Ireland
- - Dublin, Ireland, 7
    - Mater Misericordiae Hospital
United States
- Kentucky
  - Louisville, Kentucky, United States, 40222
    - Outcomes Research Institute
- Ohio
  - Cleveland, Ohio, United States, 44195
    - Cleveland Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Colon resection expected to last >2 and <6 hours

Exclusion Criteria:

Bowel obstruction
Fever

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Interventional Model: Factorial Assignment
Masking: Triple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Surgical wound infection Time Frame: 30 days	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of hospitalization Time Frame: 30 days	30 days
Suture removal Time Frame: 30 days	30 days
Cost of care Time Frame: 30 days	30 days
Return to work Time Frame: 30 days	30 days
Nosocomial pneumonia Time Frame: 30 days	30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Cleveland Clinic

Investigators

Study Director: Daniel I Sessler, M.D., The Cleveland Clinic
Principal Investigator: Ozan Akca, M.D., University of Louisville

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

January 5, 2006

First Submitted That Met QC Criteria