Controlled Clinical Trial of Supplemental Oxygen for the Prevention of Post-Cesarean Infectious Morbidity
Condition: Infection; Cesarean Section; Surgical Wound Infection; Endometritis
MeSH terms: Infections; Communicable Diseases; Wound Infection; Surgical Wound Infection; Endometritis; Surgical Wound
Study type: Interventional

Summary: 
      Previous studies have demonstrated that patients who undergo surgery while they under general
      anesthesia have fewer wound infections if they receive higher concentrations of oxygen but
      this has never been studied in women who are undergoing cesarean section. We plan to
      randomize women who are undergoing cesarean to receive either standard of care oxygen flow
      through a nasal cannula during their cesarean section only or a higher concentration of
      oxygen than they would typically receive through a face mask. Women will receive this therapy
      during their cesarean and for 2 hours afterwards. We will follow them after their surgery for
      evidence of infection either in their wound or their uterus.
    

Detailed description: 
      We designed a randomized controlled trial of supplemental oxygen for the prevention of post
      cesarean delivery infectious morbidity at Washington University in St. Louis, MO. Patients
      who underwent scheduled or intrapartum cesarean delivery with regional anesthesia were
      eligible for participation. Women were recruited for study participation from the antepartum
      service and labor and delivery. Exclusion criteria included emergency surgery in which the
      participant was unable to provide informed consent, human immunodeficiency virus infection,
      chronic corticosteroid therapy or other immunosuppressive therapy, general anesthesia, and a
      diagnosis of extra uterine infection (i.e., pyelonephritis or pneumonia) before cesarean
      delivery. Acute chorioamnionitis was not an exclusion criterion.

      After written consent was obtained, patients were randomly assigned in a 1:1 scheme to
      receive either supplemental oxygen or standard care. Randomization was achieved with opaque
      envelopes that contained the assigned study group; the envelopes were opened after the
      patients had agreed to participate in the study but before surgery. Women in the supplemental
      oxygen group received oxygen at a flow rate of 10 L/min (corresponding to a FiO2 of
      approximately 80%) by nonrebreather mask (CareFusion, Yorba Linda, CA) during and for 2 hours
      after cesarean delivery. Compliance with supplemental oxygen by face mask was assessed by the
      anesthesiologist intraoperatively and by the postpartum nurse at 30, 60, 90, and 120 minutes
      after surgery. Women who were assigned to the standard care group received oxygen at a flow
      rate of 2 L/min (corresponding to a FiO2 of 25-30%) by nasal cannula (Salter Labs, Arvin, CA)
      during the cesarean delivery only. Oxygen saturation was assessed both intraoperatively and
      postoperatively for both groups; women with oxygen saturations 95% were supplied supplemental
      oxygen, as needed, to maintain appropriate oxygenation. Women in both groups received
      standard preoperative skin preparation and prophylactic antibiotics. Subcutaneous depth was
      measured by the primary operative team with a sterile ruler; demographic, intrapartum, and
      operative information was abstracted from the medical records. The operative decision to
      place subcutaneous sutures was left to the surgical team.

      The primary outcome for this study was a composite outcome that consisted of endometritis and
      wound infection. Strict diagnostic criteria were used for infectious outcomes. A patient was
      diagnosed with endometritis if she had an oral temperature of 38°C after the first 24 hours
      following the procedure and either (1) fundal or lower abdominal tenderness greater than
      expected or (2) foul-smelling or purulent lochia.16 Endometritis was diagnosed only if other
      causes for the patient's signs and symptoms were not identified. Patients had to be treated
      with intravenous antibiotics for a diagnosis of endometritis to meet our study definition.
      The diagnosis of wound infection required wound opening >1 cm or other surgical intervention
      (such as laparotomy or debridement of tissue) plus at least 1 of the following: (1) purulent
      drainage from the wound, (2) erythema or induration of the surrounding tissues, (3) maternal
      oral temperature >38°C, or (4) radiographic evidence of infection. Secondary outcomes were
      defined before the study was initiated and included the need for wound opening >1 cm because
      of wound hematoma or seroma, hospital readmission, and need for intravenous antibiotics after
      the first 24 hours after the procedure. We also collected data on immediate neonatal outcomes
      that included Apgar scores, special care nursery or neonatal intensive care unit (NICU)
      admission, umbilical artery pH, O2, and CO2, and antibiotic administration after birth.
      Physicians were provided with educational materials regarding the diagnosis of endometritis
      and wound infection before study initiation and intermittently throughout the study period.
      All outcomes were assessed by the primary care team, and the diagnoses were abstracted from
      the chart by study personnel (research nurse or investigator). The medical record was
      reviewed at the time of the 2-4 week postoperative visit, and all women who did not return
      for a postoperative visit within 4 weeks or who had planned follow-up visits at an outside
      clinic were contacted by the research nurse by telephone to inquire about postoperative
      complications. The data collection form was used as a prompt during the telephone interviews
      to ensure standardization. The primary comparison for our study was supplemental oxygen vs
      standard care with respect to the primary outcome of infectious morbidity. Data were analyzed
      with the intent-to-treat principle, and a separate analysis was completed that analyzed only
      those patients who were treated according to protocol.

      Analysis included unpaired t tests for normally distributed continuous variables,
      Mann-Whitney U test for nonnormally distributed continuous variables, and chi-squared or
      Fisher's exact tests for categorical data. Stratified analyses with the Mantel-Haenszel test
      and logistic regression were performed to assess for confounding and interaction. Risk ratios
      with 95% confidence intervals were calculated for outcomes by treatment arms. A probability
      value of < .05 was considered significant. No interim analyses were planned or conducted. The
      study protocol included a continuous (daily) process of monitoring and reporting of maternal
      and neonatal adverse events by the research team. Adverse events were reported to the Human
      Research Protection Office and the institutional review board as they occurred.

      For the initial sample size calculation, we estimated the rate of infectious morbidity, which
      consisted of endometritis and wound infection, to be 15%. To detect a 50% reduction in
      surgical site infection with 80% power and an alpha error of 0.05, 278 women per arm were
      required. After 50% of the subjects had been enrolled, the calculated sample size of 556
      women was increased by approximately 10% to account for the observed loss to follow-up rate,
      which resulted in a final sample size of 606 women.
    

Intervention name(s): 80% inhaled oxygen via non-rebreather mask; 30% inhaled oxygen via nasal cannula
Intervention type(s): Other; Other
Intervention description(s): Patients randomized to treatment group will receive 80% inhaled oxygen via a non-rebreather face mask during their cesarean section and for 2 hours afterwards.; Patients randomized to treatment group will receive 30% inhaled oxygen via a nasal cannula (standard of care)during their cesarean section.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: C-section; Surg Wound Infect