FIO2 indicates fraction of inspired oxygen.
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Belda FJ, Aguilera L, García de la Asunción J, et al. Supplemental Perioperative Oxygen and the Risk of Surgical Wound InfectionA Randomized Controlled Trial. JAMA. 2005;294(16):2035–2042. doi:10.1001/jama.294.16.2035
Context Supplemental perioperative oxygen has been variously reported to halve
or double the risk of surgical wound infection.
Objective To test the hypothesis that supplemental oxygen reduces infection risk
in patients following colorectal surgery.
Design, Setting, and Patients A double-blind, randomized controlled trial of 300 patients aged 18
to 80 years who underwent elective colorectal surgery in 14 Spanish hospitals
from March 1, 2003, to October 31, 2004. Wound infections were diagnosed by
blinded investigators using Centers for Disease Control and Prevention criteria.
Baseline patient characteristics, anesthetic treatment, and potential confounding
factors were recorded.
Interventions Patients were randomly assigned to either 30% or 80% fraction of inspired
oxygen (FIO2) intraoperatively and for 6 hours after
surgery. Anesthetic treatment and antibiotic administration were standardized.
Main Outcome Measures Any surgical site infection (SSI); secondary outcomes included return
of bowel function and ability to tolerate solid food, ambulation, suture removal,
and duration of hospitalization.
Results A total of 143 patients received 30% perioperative oxygen and 148 received
80% perioperative oxygen. Surgical site infection occurred in 35 patients
(24.4%) administered 30% FIO2 and in 22 patients
(14.9%) administered 80% FIO2 (P=.04). The risk of SSI was 39% lower in the 80% FIO2 group (relative risk [RR], 0.61; 95% confidence interval [CI], 0.38-0.98)
vs the 30% FIO2 group. After adjustment for important
covariates, the RR of infection in patients administered supplemental oxygen
was 0.46 (95% CI, 0.22-0.95; P = .04).
None of the secondary outcomes varied significantly between the 2 treatment
Conclusions Patients receiving supplemental inspired oxygen had a significant reduction
in the risk of wound infection. Supplemental oxygen appears to be an effective
intervention to reduce SSI in patients undergoing colon or rectal surgery.
Trial Registration ClinicalTrials.gov Identifier: NCT00235456
Surgical wound infections prolong hospitalization by an average of 1
week and substantially increase the cost of care.1,2 These
infections are possibly the most common serious complication of surgery and
anesthesia.3 The primary defense against surgical
pathogens is oxidative killing by neutrophils. Oxidative killing is a function
of tissue oxygen partial pressure throughout the range of observed values.4 As might be expected, infection risk depends on tissue
oxygen partial pressure5 and, therefore, interventions
that increase tissue oxygen may reduce infection risk.
Greif et al6 have shown that providing
80% oxygen throughout surgery and for 2 postoperative hours decreased infection
risk by half compared with patients who were administered 30% oxygen (5% vs
11%). However, a recent study by Pryor et al7 concluded
that the risk of infection in a general surgical population doubled in patients
who were administered supplemental oxygen during surgery (25% vs 11%). In
light of this disparity, we tested the hypothesis that supplemental perioperative
oxygen reduces the risk of wound infection.
We enrolled 300 patients aged 18 to 80 years between March 1, 2003,
and October 31, 2004, who underwent elective colorectal resection in 14 hospitals
in Spain. Patients having abdominal-peritoneal reconstructions were included
but not those scheduled for minor colon surgery (eg, polypectomy, isolated
colostomy) or laparoscopic surgery. The ethics committee at each hospital
approved the protocol and written informed consent was obtained from each
Exclusion criteria included expected surgery time of less than 1 hour,
fever or existing signs of infection, diabetes mellitus (type 1 or 2), human
immunodeficiency virus infection, weight loss exceeding 20% in the previous
3 months, serum albumin concentration of less than 30 g/L, and a leukocyte
count of less than 2500 cells/mL.
Mechanical bowel preparation was performed with an electrolyte solution
that did not contain antibiotics or antiseptics. Antibiotic prophylaxis with
metronidazole plus cefoxitin or a third-generation cephalosporin was administered
60 to 90 minutes before the surgical incision and continued postoperatively
for up to 48 hours. Aminoglycosides were used as an alternative to β-lactam
antibiotics in patients who reported a history of cephalosporin allergy. Anesthesia
induction and treatment were standardized across all patients.
Randomization to intervention was stratified by study center. Computer-generated
codes were maintained in sequentially numbered opaque envelopes. The randomization
envelopes were opened in the operating department after induction of anesthesia
by the anesthesiologist. Patients were assigned to an oxygen/air mixture with
a fraction of inspired oxygen (FIO2) of 30% or 80%.
The displays of the anesthesia machine and gas monitors were covered with
cardboard shields in both the operating department and postanesthesia care
unit to keep the surgical team blinded to group assignment. Patients were
not informed of their group assignments.
When the operation was finished, the inhaled anesthetic was stopped
and FIO2 was increased to 100% during extubation.
During the first 6 postoperative hours, all patients were administered nonrebreathing
facemasks with a reservoir (Intersurgical, Wokingham, Berkshire); oxygen was
provided at the randomly designated concentration at a total flow of 16 L/min.
Subsequently, patients breathed ambient air, although supplemental oxygen
was provided as necessary to maintain oxygen saturation as measured by pulse
oximetry (SpO2) of at least 92%.
The attending anesthesiologist in the operating department and during
the initial 6 postoperative hours was independent of the team doing the wound
evaluation. At the end of 6 hours, the anesthesia and postoperative records
were sealed in an envelope to maintain blinding of the surgical team and the
investigators who evaluated wound status. This allowed the surgical team and
the wound evaluators to remain blinded during data collection.
Perioperative normothermia was maintained with circulating-water mattresses
and forced-air heaters. Fluids were administered intraoperatively at a rate
of 15 mL/kg per hour; blood loss was restored with crystalloids or colloids
and, when necessary, with leukocyte-filtered allogeneic red blood cell concentrate.
Fluid was administered at 3 mL/kg per hour during the first 6 postoperative
hours and then reduced to 2 mL/kg per hour after patients were transferred
to the ward. Surgical wounds were covered with conventional gauze bandages.
An antiseptic solution was applied on the surface of the surgical wound, but
neither intraperitoneal antibiotics nor antiseptics were instilled.
If patients reported a postoperative pain score of more than 3 cm on
a 10-cm visual analog scale (0 cm indicates no pain and 10 cm indicates worst
pain imaginable), they were administered intramuscular or intravenous morphine
and nonsteroidal anti-inflammatory drugs. The attending surgeon, who was unaware
of the patient’s oxygen treatment, controlled the use of analgesic agents.
The attending surgeon also determined initiation of feeding, ambulation, and
the duration of hospitalization.
Medical history was recorded and a systematic physical examination was
performed preoperatively. Patients were considered to have respiratory disease
when they had a history of chronic obstructive pulmonary disease, asthma requiring
routine medication, or other clinically important respiratory impairment.
Laboratory testing included a complete blood cell count; biochemical analysis,
including blood glucose; and coagulation tests. Infection risk was evaluated
using the Study on the Efficacy of Nosocomial Infection Control (SENIC) scale.3 The National Nosocomial Infections Surveillance System
(NNISS) scale8 was also used, which includes
an evaluation of physical condition according to the American Society of Anesthesiologists
physical status score.9 The SENIC and NNISS
scores have been extensively validated, and larger values with these scores
indicate a greater risk of infection.
Electrocardiogram, heart rate, noninvasive blood pressure, FIO2, SpO2, and end-tidal concentrations
of carbon dioxide and sevoflurane were continuously monitored during the surgery.
Electrocardiogram, heart rate, noninvasive blood pressure, SpO2, and FIO2 were monitored while the patient
remained in the recovery room. An arterial blood sample was obtained 1 hour
after induction of anesthesia to evaluate partial pressure of oxygen (PaO2); another sample was obtained 2 hours after extubation.
Core temperature was recorded from the tympanic membrane.
Surgical wounds were assessed daily for infection by surgeons who were
unaware of patients’ treatment groups. Wounds were considered infected
when they met Centers for Disease Control and Prevention definitions.10 Purulent exudates were cultured and, when positive
for pathogenic bacteria, appropriate antibiotic treatment was initiated. Only
those infections diagnosed during the first 14 postoperative days were included.
Wound healing characteristics were also evaluated using the ASEPSIS
score (Additional treatment, Serous discharge, Erythema, Purulent exudate,
Separation of deep tissues, Isolation of bacteria, and duration of inpatient
Stay).11 This is an established and validated
system that is derived from the weighted sum of points assigned for the following
factors: duration of antibiotic administration; drainage of pus with the patient
under local anesthesia; debridement of the wound with the patient under general
anesthesia; serous discharge; erythema; purulent exudate; separation of deep
tissues; isolation of bacteria from discharge; and hospitalization exceeding
14 days. A daily score of 20 or more was considered evidence of infection.12
Discharged patients were observed in the outpatient surgical clinic
to assess wound status on day 15. Records were kept of physical examinations,
heart rate, noninvasive blood pressure, temperature, and laboratory test results
(similar to those obtained preoperatively) after 24 hours and on the day of
hospital discharge; these values were also recorded on postoperative days
4, 7, 10, and 14 in patients who remained hospitalized. The times of return
of bowel function, restarting feeding, ambulation, and removal of staples
were also recorded. A record was also kept of whether patients had any of
the following risk factors: urinary catheter, central venous catheter, mechanical
ventilation, treatment with immunosuppressant medications, or parenteral nutrition.
A preliminary study indicated that the baseline infection rate in patients
undergoing major colon or rectal surgery was 25% in 3 of the participating
centers. Although this incidence appears large, it is consistent with literature
indicating that the infection rate in high-risk patients, such as in our study,
ranges up to 36%13 and that rates of infection
are usually underestimated by clinicians.14 Sample
size analysis indicated that 300 patients would be required to provide 80%
power for detecting a 50% reduction in wound infection rate at α=.05.
We therefore planned to enroll 300 patients. Our primary outcome was any surgical
site infection (SSI); secondary outcomes included return of bowel function
and ability to tolerate solid food, ambulation, suture removal, and duration
An independent data and safety monitoring board blinded to group assignment
evaluated the case-report forms from each patient. Data from forms that were
substantially incomplete, either because the patient dropped out of the study
or because of data collection problems, were excluded from further analysis
but included in a sensitivity analysis. Data from patients who were unexpectedly
switched to laparoscopic procedures after enrollment were excluded from the
Intraoperative values were averaged over time in each patient; these
means were then averaged across the entire treatment group. The distribution
of the principal continuous variables in each group was compared using 2-tailed t tests for parametric data. χ2 Tests were
used for discrete variables. Mann-Whitney U (Wilcoxon)
tests were used for nonparametric data. Data were reported as mean (SD), unless
otherwise indicated; P<.05 was considered statistically
significant. Statistical analyses were performed by using SPSS version 11.0
(SPSS Inc, Chicago, Ill).
The risk of SSI associated with each study group and other potential
risk factors was determined by calculating the cumulative incidence. To evaluate
the relationship between the FIO2 group and other
potentially predictive factors and wound infection, the respective relative
risks (RRs) were calculated. Finally, a logistic regression analysis was performed
to determine the effect of 80% FIO2 adjusted for
the remaining potential risk factors for wound infection and the effect of
participating hospitals. Those variables with P<.25
in the univariate (simple) analysis were included in the multivariate logistic
regression analysis. These variables included sex, weight, age, coexisting
respiratory disease, allergy, lymphocyte count, hemoglobin, glucose, and other
potential wound infection predictive factors, such as SENIC and tobacco smoking.
Manipulation of variables in the model was performed using the Enter
method, which forces the introduction of all the variables of interest under
the specified criteria. The goodness-of-fit of the model was evaluated with
the Hosmer-Lemeshow method.
We collected data from 300 patients who were enrolled and randomized;
however, 9 patients were excluded from the main analysis because 2 had low
preoperative albumin values, 2 had laparoscopic surgery (surgeon changed to
laparoscopic surgery after induction of anesthesia), and 5 had incomplete
case-report forms (Figure). Among the
remaining 291 patients, 143 received 30% perioperative oxygen and 148 received
80% perioperative oxygen. Type and duration of antibiotics administered during
the first 48 hours were similar in the 2 groups. The mean (SD) duration of
surgery was 159 (61) minutes in patients assigned to 30% oxygen and 161 (62)
minutes in those assigned to 80% oxygen (P = .80).
Morphometric, demographic, and other preoperative characteristics were
similar in the 2 treatment groups except that patients assigned to 80% oxygen
were slightly shorter in height and more often women (Table 1). Other than the percentage of inspired FIO2 and resulting PaO2, there were no significant
differences between the groups for any of the more than 30 other potential
confounding factors during the operation or in the postoperative care unit.
Other than postoperative hemoglobin, all physiological variables, laboratory
test results data (including blood glucose concentrations), ASEPSIS index,
and extrinsic infection risk factors were also similar during the postoperative
period through hospital discharge.
Fifty-seven patients (39.3%) were diagnosed with SSI (of these, 50 patients
had cultures positive for pathogenic bacteria): 35 patients (24.4%) had an
SSI in the 30% FIO2 group and 22 (14.9%) in the
80% FIO2 group (P = .04)
(Table 2). The risk of SSI was 39% lower
in the 80% FIO2 group (RR, 0.61; 95% confidence
interval [CI], 0.38-0.98) vs the 30% FIO2 group
(Table 3). Among the 9 patients who
were excluded from the data analysis, none appeared to have wound infections;
however, follow-up was incomplete in this group and 1 patient died of sepsis.
Because a true intention-to-treat analysis could not be completed secondary
to incomplete follow-up data, we conducted a sensitivity analysis based on
treatment group assignment that included all patients except those 4 who should
have been excluded based on a priori exclusion criteria (2 had laparoscopic
surgery and 2 had low preoperative albumin values). Repeating the analysis,
assuming that none of the other 5 excluded patients developed an SSI, resulted
in an RR reduction of 0.62 (95% CI, 0.38-1.00; P = .05)
associated with 80% FIO2. Repeating the analysis,
assuming that these 5 excluded patients all developed infection, resulted
in an RR reduction of 0.58 (95% CI, 0.37-0.92; P = .02).
Other outcomes did not vary significantly between treatment groups (Table 2), although fewer patients in the 80%
group had ASEPSIS scores exceeding 20 on any postoperative day (25 [16.9%]
vs 37 [25.9%], P = .06). Nine patients
had to be admitted in the intensive care unit immediately after the operation
because of postsurgical complications. Two patients died during the study
period (including the 1 patient mentioned above), both from multiorgan failure
of septic origin. Both of these patients were assigned to the 30% oxygen group.
Patients with infection had mean (SD) ASEPSIS scores on the first 6 postoperative
days of 8.8 (0.81), whereas those without infections had mean (SD) scores
of 6.0 (0.41) (P = .003). Patients with
infection took longer to ambulate (mean [SD], 4.9 [3.2] vs 3.9 [2.1] days; P = .008), had their staples removed later (11.6
[3.6] vs 10.1 [3.2] days; P = .007), and
had longer hospital stays (15.1 [8.2] vs 10.7 [4.8] days; P = .001).
In unadjusted analyses, men and those with coexisting respiratory disease
were at increased risk of SSI (RR, 1.95; 95% CI, 1.06-3.61; and RR, 2.15;
95% CI, 1.03-4.48; respectively) (Table 3).
After multivariate adjustment, only the percentage of inspired oxygen and
coexisting respiratory disease were significantly associated with the risk
of infection. After adjustment for all covariates, the risk of SSI was reduced
54% in patients assigned to 80% oxygen (RR, 0.46; 95% CI, 0.22-0.95; P = .04). Patients with coexisting respiratory disease had
a 3.23-fold (95% CI, 1.18-8.86) greater probability of SSI. Including the
effect of participating hospitals in the multivariate analysis did not change
the RR of SSI for FIO2.
In this randomized trial of 80% vs 30% inspired supplemental oxygen
in the operative and perioperative period, we found that 80% supplemental
oxygen reduced the risk of SSI by 39%. When controlling for multiple contributing
factors, the reduction in SSI risk associated with 80% FIO2 was nearly 54%. Patients with infections had significantly longer
hospital stays and delays to ambulation. This observed risk reduction was
similar to the 2-fold reduction reported by Greif et al6 in
500 patients and also consistent with the study by Hopf et al,5 showing
that infection risk is inversely related to tissue oxygenation. In contrast,
a recent study by Pryor et al7 with only 160
patients reported that supplemental oxygen increases the risk of infection.
It is thus worth considering why the results of Pryor et al differ so markedly
from other available data.
Pryor et al7 did not specify the baseline
infection rate they used, making it impossible to confirm their estimate that
300 patients would be required to detect a 40% reduction in the infection
rate. But to have an 80% power to detect the 40% risk reduction that they
specified from 25% (our baseline) or from 11% (baseline by Greif et al6) would require 540 or 651 patients, respectively;
and to detect a 40% increase would require 698 or 930 patients, respectively.
The study thus appears to have been underpowered and then stopped after only
160 patients were randomized. The authors specify that 160 patients was an
a priori stopping point, although 53.3% of the anticipated sample size is
a curious a priori stopping point.
A second limitation is that the treatment groups in the study by Pryor
et al7 were not homogeneous. For example, in
their study, patients assigned to 80% oxygen weighed more and were more than
twice as likely to have a body mass index (calculated as weight in kilograms
divided by the square of height in meters) exceeding 30. Patients assigned
to 80% oxygen also had longer operations, lost significantly more blood, and
required significantly more fluid replacement. Furthermore, Pryor et al7 failed to control many variables believed to influence
infection risk, including anesthetic, fluid, antibiotic, and pain treatment.
In contrast, characteristics of the patients we randomized to each treatment
group were comparable, aside from minor differences in height and sex, neither
of which is known to influence infection risk.
A third limitation of the study by Pryor et al7 is
that wound infections were determined by retrospective chart review; a review
that was apparently conducted by unblinded investigators. This insensitive
method contrasts markedly with the daily blinded wound evaluations used in
our study and in the study by Greif et al.6 It
is possible that these method problems contributed to a result that is inconsistent
with considerable in vitro, in vivo, and clinical data.
All surgical wounds become contaminated to some degree. The primary
determinant of whether contamination is established as a clinical infection
is host defense. Host defense is most critical during a decisive period lasting
a few hours after contamination. For example, antibiotics ameliorate infections
and hypoperfusion aggravates infections only during the first few hours after
contamination.15 The decisive period for oxygen
remains unknown but may be far longer than for antibiotics. Our patients were
maintained at the designated oxygen concentration during surgery and for 6
postoperative hours. In contrast, Greif et al6 provided
supplemental oxygen for only 2 postoperative hours. The results, however,
were nearly identical, which suggests that 2 hours may be sufficient. Only
a direct comparison within a single study will identify the optimal postoperative
duration of supplemental oxygen therapy. As an exploratory analysis, we considered
the relationship of tobacco smoking and SSI. Tissue oxygenation decreases
significantly for 1 hour after cigarette smoking16 and
it has been suggested that smokers have a higher infection risk.2,17,18 Consistent
with recent studies,6,19 however,
we found no significant increase in the risk of infection among smokers. One
explanation for this finding is that the effect of smoking on tissue oxygenation
is time-limited. Because patients are no longer allowed to smoke in the hospital,
sustained smoking-related reductions in tissue oxygenation may be occurring
There are several limitations to our study. The baseline infection rate
in our patients was roughly twice that in the study of Greif et al.6 However, infections are multifactorial and depend
on numerous factors, including the type of procedure,8 duration
of anesthetic,3 control of anesthetic factors,
and body temperature.2 The baseline rate identified
in our study was well within values reported in recent series20,21 and
the groups were homogeneous and treated comparably except for the randomized
inspired oxygen concentration. Furthermore, the diagnostic method used to
describe infection may have affected our results. In the study by Greif et
al,6 infection was considered only when cultures
of the wound were positive. However, according to Centers for Disease Control
and Prevention criteria, infection can be present without laboratory confirmation
and, in our study, the blinded wound evaluator considered any of the following
as confirmation of infection: purulent drainage, with or without laboratory
confirmation; organisms isolated from an aseptically obtained culture of fluid
or tissue; at least 1 of the following signs or symptoms of infection (pain
or tenderness, localized swelling, redness, or heat, and the incision was
deliberately opened by surgeon, unless incision was culture-negative); or
independent diagnosis of incisional SSI by the surgeon or attending physician.
Another potential limitation is that we only considered infections that occurred
in the first 15 days after operation and may have missed subsequent infectious
events. Previous studies2,5,6 indicate
that wound infections are usually detected within this time frame; however,
70% of the wound infections in the study by Grief et al6 were
detected in the first 10 days after surgery.22
In conclusion, supplemental 80% FIO2 during
and for 6 hours after major colorectal surgery reduced postoperative wound
infection risk by roughly a factor of 2. This result is consistent with most
available in vitro data and 1 other appropriately designed RCT.6 Supplemental
oxygen appears to confer few risks to the patient, has little associated cost,
and should be considered part of ongoing quality improvement activities related
to surgical care.
Corresponding Author: F. Javier Belda, MD,
PhD, Department of Anesthesiology and Critical Care, Hospital Clínico
Universitario de Valencia, Avenida Blasco Ibáñez, 17, 46010
Valencia, Spain (firstname.lastname@example.org).
Author Contributions: Dr Belda had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Belda, Garcia de
la Asuncion, Sessler.
Acquisition of data: Belda, Aguilera, Garcia
de la Asuncion, Alberti, Vicente, Ferrandiz, Rodriguez, Company, Aguilar,
Analysis and interpretation of data: Belda,
Aguilera, Vicente, Rodriguez, Company, Sessler, Orti.
Drafting of the manuscript: Belda, Aguilera,
Garcia de la Asuncion, Vicente, Ferrandiz, Rodriguez, Sessler, Aguilar, Botello,
Critical revision of the manuscript for important
intellectual content: Belda, Alberti, Sessler.
Statistical analysis: Belda, Alberti, Vicente,
Company, Sessler, Orti.
Obtained funding: Belda, Aguilera, Garcia de
la Asuncion, Ferrandiz, Company.
Administrative, technical, or material support:
Belda, Garcia de la Asuncion, Alberti, Ferrandiz, Rodriguez, Aguilar.
Study supervision: Belda, Garcia de la Asuncion,
Financial Disclosures: None reported.
The Spanish Reduccion de la Tasa de Infeccion Quirurgica
Group:Hospital Clínico, Valencia:
F. Javier Belda, MD, PhD, José García de la Asunción,
MD, PhD, José V. Juste, MD, Antonio Guillén, MD, Gerardo Aguilar,
MD, PhD, Marina Soro, MD, PhD, Rafael Ortí, PhD, Eduardo García-Granero,
MD, PhD; Hospital de la Princesa, Madrid: Javier
Alberti, MD, Guadalupe Blanc, MD, Rosario Roser, MD; Hospital
Severo Ochoa, Leganés: Patricia Lloreda, MD, Enrique Alonso,
MD, María S. Asuero, MD, PhD; Hospital Virgen de
la Salud, Toledo: Raquel Casas, MD, Manuela Carrero, MD, Alberto Cortés,
MD; Hospital La Fe, Valencia: Rosario Vicente, MD,
Vicente Ramos, MD, Miguel Sánchez, MD, Cristina Sánchez, MD,
María D. Sánchez, MD; Hospital Dr. Peset,
Valencia: Manuel Barberá, MD, PhD, Lucía Ferrándiz,
MD, Rocío Armero, MD; Hospital Virgen de la Macarena,
Sevilla: Rafael Rodríguez, MD, José L. Casielles, MD,
Diego Toro, MD, Antonio Gutiérrez, MD, Juan C. Herreras, MD; Hospital Clínico, Zaragoza: José M. Mateo,
MD, Pilar Lirola, MD, Javier González, MD, Rosa Aparicio, MD; Hospital Clínico, Málaga: Aurelio Gómez,
MD, Antonio García, MD, Ana Navajas, MD, Manuel Rubio, MD, José
Sarmiento, MD; Hospital Galdakao, Bizkaia: Luciano
Aguilera, MD, PhD, Carmelo Intxaurraga, MD, Sarkundde Telletxea, MD, José
R. Onandía, MD, Aitor Landaluce, MD; Hospital General,
Alicante: Roque Company, PhD, Joaquín Mateu, MD, Javier Rubio,
MD; Hospital Carlos Haya, Málaga: Sigfredo
Rodríguez, MD, Ana Medina, MD, Esperanza Cruz, MD; Hospital Juan Canalejo, A Coruña: César Bonome, MD, PhD,
Felisa Álvarez-Refojo, MD; Hospital Río Hortega,
Valladolid: Eugenio Ruíz, MD, Ana Alonso, MD, César Aldecoa,
MD, Jesús Rico, MD, José I. Gómez-Herreras, MD, PhD.
Funding/Support: This study was largely performed
with institutional support from the participating centers. There was complementary
funding from Air-Liquide Medicinal, Spain, and Air-Liquide Santé, France;
Dr Sessler’s effort was supported by grant GM 061655 from the National
Institutes of Health, Bethesda, Md; the Gheens Foundation, Louisville, Ky;
and the Joseph Drown Foundation, Los Angeles, Calif.
Role of the Sponsors: Air-Liquide Medicinal
and Air-Liquide Santé participated in the study design and the logistics
of the trial, but agreed a priori that the investigators, regardless of the
results, would publish the findings. The sponsors had no role in data interpretation
or manuscript preparation, and the steering committee statistician independently
validated the outcome. All decisions related to publication, including data
interpretation, were entirely controlled by the data and safety monitoring
board, Dr Belda, and co-author members of the Spanish Reduccion de la Tasa
de Infeccion Quirurgica Group. None of the authors has a personal financial
interest in this research.
Acknowledgment: We thank Gorka Solaun, BS,
medical student, University of Valencia, Spain, for his assistance in coordinating
patient recruitment, and Nancy Alsip, PhD, medical editor, University of Louisville,
Kentucky, for her paid editorial contributions. Mr Solaun was paid by the
University of Valencia for his contribution to our study.