Why the study?
Do perioperative optimization strategies including maintenance of normothermia and supplemental oxygen reduce surgical site infections in surgical patients?
Do perioperative optimization strategies including maintenance of normothermia and supplemental oxygen reduce surgical site infections in surgical patients?
Anesthesiologists play a critical role in preventing surgical site infections through perioperative management strategies such as maintaining normothermia and optimizing tissue oxygenation.
Hypothesis-generating for normothermia and high FiO2 in SSI prevention; prospective RCTs needed before practice change.
SURGICAL site infections (SSIs) continue to be a substantial source of morbidity and mortality in the surgical patient population. They are the second most common cause of nosocomial infection after urinary tract infections and account for approximately 17% of all hospital-acquired infections.1These infections lead to longer hospital and intensive care unit stays, lead to substantially increased mortality, and contribute significantly to healthcare costs.2In a 1999 series of cardiac surgery patients, each deep sternal wound infection added an average of $26,400 in hospital charges and increased the average duration of stay by 16 days.3The incidence of SSI varies for each operative procedure, each surgeon, and each hospital. In addition, each patient presents with his or her own unique risk profile for the development of a SSI. Although sterile surgical technique is extremely important to the prevention of SSIs, there is increasing evidence that anesthesiologists play a prominent yet under appreciated role in the prevention of SSIs. While infections typically present several days postoperatively, the first few hours after bacterial contamination are the critical window for the establishment of infection.4,5Therefore, decreasing SSIs hinges on the optimization of perioperative conditions, many of which are controlled by anesthesiologists.In this review, we will discuss the literature surrounding six perioperative factors over which anesthesiologists have at least partial control and how these factors may influence the risk of postoperative surgical site infection. Although we acknowledge that many anesthesiologists care for patients in the intensive care unit, we limit our discussion here to the immediate perioperative period.Mild perioperative hypothermia (core body temperature 34°–36°C) is commonly observed in surgical patients. The complications of mild perioperative hypothermia have been studied extensively and include increased duration of hospitalization,5increased intraoperative blood loss and transfusion requirements, increased adverse cardiac events, and an increase in patient thermal discomfort in the recovery room.6The effects of mild hypothermia on SSI have also been studied.A series of 200 patients undergoing colorectal surgery were randomized to a hypothermic group (34.4°± 0.4°C) or a normothermic group (37°± 0.3°C) and followed for 2 weeks postoperatively.5The authors had planned to enroll 400 patients; however, the trial was stopped early because of a statistically significant difference in infection between the two groups. The incidence of SSI was 5.8% in the normothermic group and 18.8% in the hypothermic group. The patients who developed SSIs required hospital stays nearly 1 week longer than those who did not develop a SSI, indicating that these were clinically significant complications. The normothermic patients were also found to have significantly more collagen near the wound, had their staples removed a day sooner, and tolerated food earlier.5In addition, the authors determined that intraoperative vasoconstriction was present in 74% of the hypothermic patients but only 6% of the normothermic patients. This difference remained statistically significant throughout the 6-h recovery period.5This randomized, double-blind trial suggests hypothermia is a major risk factor for postoperative SSI and that maintenance of perioperative normothermia may reduce the incidence of SSIs. One criticism of this study has focused on the increased allogeneic blood requirement in the hypothermic group (0.8 ± 1.2 vs. 0.4 ± 1.0 units P = 0.01). Indeed, erythrocyte transfusions have been implicated as a risk factor for SSI and will be discussed in detail below. In their discussion, these authors state that “on multivariate regression analysis a requirement for transfusion did not independently contribute to the incidence of wound infection.”5Further, although the hypothermic patients received more allogenic blood per patient, the number of patients requiring transfusion was not significantly different (P = 0.054).In 2001, Flores-Maldonado et al. 7reported on a series of 290 consecutive cholecystectomy patients with a 30-day follow-up. This series excluded patients that received blood transfusions preoperatively, intraoperatively, or postoperatively. The average temperature in their hypothermic group was 35.4°± 0.4°C versus 36.2°± 0.2°C in the normothermic group based on tympanic membrane immediately postoperatively. The incidence of SSI was 11.5% in the hypothermic group and 2% in the normothermic group.7This study implicates mild hypothermia as a risk factor for SSI but excludes the possible contribution of perioperative blood transfusion.Although a few studies have not shown an increased risk of infection in hypothermic patients,8most studies, including those reviewed here, implicate mild intraoperative hypothermia as a risk factor for postoperative SSI. Indeed, Kurz et al. 5performed the only double-blind randomized trial evaluating hypothermia and found a strong correlation between hypothermia and infection. Although the authors acknowledge that this study may not necessarily reflect current practice (in the study, the antibiotics were administered during anesthesia induction and may not have preceded skin incision as is currently recommended, and antibiotics were continued for 4 postoperative days) and that the study only observed patients undergoing colorectal surgery, it is likely that the findings are applicable to other surgical patient populations today. With all that is now known regarding the complications of hypothermia,6it should be every clinician's goal to maintain normothermia unless contraindicated.The major relation between hypothermia and increased SSI is thought to be a decrease in subcutaneous tissue perfusion mediated by vasoconstriction.9Hopf et al. 10demonstrated that subcutaneous oxygen tension at a surrogate wound inversely correlated with the risk of SSI. In patients with a subcutaneous oxygen tension greater than 90 mmHg, there were no infections, whereas patients with a subcutaneous oxygen tension of 40–50 mmHg had an infection rate of 43%.10This illustrates the critical importance of providing adequate oxygen stores to maintain oxidative killing by neutrophils. Not only does hypothermia decrease perfusion and thus oxygen supply to the wound, it also reduces the production of superoxide radicals for any given oxygen tension. Indeed, bacterial killing by neutrophils is reduced in the face of hypothermia.6In addition, animal models have demonstrated that hypothermia induces an antiinflammatory T-cell cytokine profile with increased levels in interleukin 10 and decreased levels of interleukin 2. This profile is similar to that of other “proinfectious” states such as severe burn and hemorrhage. It should also be noted that mild hypothermia increases nitrogen losses and decreases collagen production, which may serve to slow would healing and contribute to the risk of infection.5,11These points are summarized in figure 1.Heat loss during the first hour of anesthesia is typically a result of the redistribution of core to peripheral temperature gradients caused by an anesthetic-induced decrease in vasoconstriction. Actively prewarming patients for 2 h before the induction of either general or regional anesthesia can attenuate this effect.6The two most important causes of continued heat loss in the operating room are radiation and convection. The most effective means of preventing these causes of ongoing losses are forced air warming and administration of warmed fluids.6Many detailed reviews exist on the causes, treatment, and prevention of perioperative hypothermia.6,9,12In most clinical situations, oxygen delivery is vastly more dependent on the amount of oxygen bound to hemoglobin than the amount of oxygen dissolved in the blood. However, the subcutaneous tissue consumes little oxygen compared with the rest of the body, approximately 0.7 ml/100 ml of blood.13This amount of oxygen can be supplied by the plasma alone in a normal perfusion state.13In fact, the mean extracellular partial pressure of oxygen in the subcutaneous tissue is around 60 mmHg, a level above the range in which oxygen readily dissociates from hemoglobin. In addition, trauma-induced injury of the microvasculature at the site of the wound increases the diffusion distance required for oxygen, further decreasing the impact of hemoglobin transported oxygen on wound oxygen tension. Adequate wound oxygen tension is important not only for oxygen radical production by neutrophils (fig. 1) but also in the development of collagen and epithelium, instrumental factors in wound healing.13These facts have led some researchers to hypothesize that providing supplemental oxygen during the perioperative period would lead to higher oxygen tensions in the wound and a decrease in the incidence of SSIs. To date, two randomized, double-blind trials involving 800 patients for elective colorectal surgery have evaluated the effects 80% inspired oxygen versus 30% inspired oxygen intraoperatively and for 2 h (500 patients) or 6 h (300 patients) postoperatively. Both of these studies found statistically significant reductions in the rates of SSIs in the 0.8 fraction of inspired oxygen (Fio2) group versus the 0.3 Fio2group.14,15Pooling the data from these two studies yields an absolute risk reduction in SSI of 7% and a relative risk reduction of 45% (P = 0.02).16Although halving the rate of SSI after colorectal surgery with a simple maneuver such as increasing the inspired oxygen percentage to 80% would have broad implications, the findings of these authors have not been supported by other studies. Pryor et al. 17reported a study of 160 patients undergoing major abdominal surgery including hemicolectomy, sigmoidectomy, low anterior resection, gastrectomy, pancreaticoduodenectomy, exploratory laparotomy, and large gynecologic staging or debulking procedures. They randomized patients to either 35% inspired oxygen or 80% inspired oxygen. The assigned oxygen level was also maintained for 2 h postoperatively. This study was terminated at interim analysis secondary to a statistically significant increase in the rate of SSI in the 80% oxygen group.17It is difficult to reconcile the results of these three randomized, double-blind studies with opposing results. An editorial provides a potential explanation of these conflicting results.16The study by Pryor et al. is limited by its smaller size. In addition, perioperative conditions were not standardized between groups, as they were in the two positive studies. The patient groups in the study of Pryor et al. were also not as closely matched, the blinding was less rigorous, and the determination of SSI was retrospective as opposed to the prospective evaluation that was performed in the two positive studies.16It would seem from two well-done, randomized trials that high-inspired oxygen levels in the perioperative period confers some benefit in reducing the incidence of SSIs. Although there is one study with nearly an opposite outcome, this study is likely outweighed by the larger patient populations in two positive trials. While providing 80% inspired oxygen in the operating room is simple and likely without significant risk, the continuation of high Fio2for 2–6 h postoperatively is not without potential procedural complications and delays in moving patients out of the recovery room. Therefore, the question still remains as to whether high inspired oxygen levels intraoperatively, without continuation into the recovery room, would confer the same benefit.Although the subcutaneous tissue requires little total oxygen, wound healing and the prevention of infection are critically dependent on adequate perfusion to deliver oxygen.10Also important to oxygen delivery is the maintenance of an adequate perfusion state by the preservation of euvolemia.18Appropriate fluid management in surgical patients has been studied and debated for decades, and the discussion surrounding SSIs and fluid management is no less unsettled.Perioperative physicians typically administer intravenous fluids to replace fasting deficits, third space losses, and blood loss with a goal of maintaining adequate cardiac output, blood pressure, and urine output. However, mild to moderate total body hypovolemia is well tolerated by relatively healthy adults as interstitial fluid moves into the intravascular space to help preserve cardiac output. This may result in adequate renal function with preserved urine output and hemodynamic stability while leaving the subcutaneous tissue relatively hypovolemic. By measuring subcutaneous tissue oxygen tensions in postoperative patients, it has been shown that increasing intravascular volume can improve oxygen tensions in previously underperfused patients (fig. 1).18The hypothesis that aggressive fluid administration would better maintain subcutaneous perfusion and wound oxygen tension was tested in a randomized, double-blind trial. Fifty-six patients undergoing elective colon surgery were randomized to receive traditional fluid management (8–10 ml · kg−1· h−1intraoperatively and 1 h postoperatively) or aggressive fluid management (10 ml/kg bolus followed by 16–18 ml · kg−1· h−1intraoperatively and 1 h postoperatively). Additional fluid was given to both groups in a 3:1 ratio to replace blood loss and for urine output less than 1 ml · kg−1· h−1or blood pressure less than 70% of baseline. Although patients in the aggressively hydrated group had statistically significant higher intraoperative and postoperative tissue oxygen tension, no outcome data regarding the incidence of SSIs was presented.19This trial was subsequently expanded in a randomized, prospective manner to measure clinical outcomes. The authors could not show a statistically significant difference in the incidence of SSI or wound-healing scores with aggressive versus traditional fluid management.20The use of colloids has also been evaluated with regard to improving tissue oxygen tension. Lang et al. 21have shown that using hydroxyethyl starch intraoperatively and postoperatively decreases the amount of crystalloid required to maintain stable hemodynamics and urine output while increasing the tissue oxygen tension. In this study, the colloid group had an increase in tissue oxygen tension of 54%, whereas a group of similar patients who received crystalloid had a 29% decrease in tissue oxygen tension.21Although there is evidence that aggressive fluid management and the use of hydroxyethyl starch improve tissue oxygenation, the only trial that reported on the incidence of SSI with aggressive hydration did not show any statistically significant improvement in the incidence of SSI. In addition, concern over decreased pulmonary function and bowel edema leading to an increase in the time to return of GI function have tempered enthusiasm for aggressive fluid management in general surgical patients. A recent randomized trial has shown that restricting intravenous fluids to patients undergoing major abdominal procedures resulted in fewer complications, improved times to return of gastrointestinal function, decreased wound-healing complications, and shortened the duration of hospital stay by 1 day.22At this time, it seems that aggressive fluid resuscitation does not decrease the incidence of SSI, and maintenance of euvolemia is recommended based on clinical parameters.It has been well established that patients with diabetes are at increased risk for infections, including SSIs. Even in nondiabetics, hyperglycemia is associated with an increased risk of morbidity and mortality.23In one recent trial, the use of to maintain at less than in critically patients decreased the mortality rate from to of diabetes In fact, of the study had no of The of the reduction in mortality by reducing the incidence of with it is whether this data from the intensive care unit can be to the perioperative it has an in the effects of control on the risk of SSI. The of study in this has in cardiac surgery there is evidence that control may reduce the rates of SSI in a of surgical recent studies have now shown a correlation between hyperglycemia and the risk of SSI (fig. most of these complications in cardiac surgery patients are deep sternal wound infections, leading to which increases operative mortality to series from the same studied the effects of a to maintain blood levels between and 200 in patients undergoing cardiac in the groups were with who had received every 4 h with a goal of maintaining levels less than 200 authors noted a reduction in the incidence of deep sternal wound infections in patients using is important to that were continued into the postoperative period during this This the relative importance of perioperative conditions, not intraoperative studies have to the effects of hyperglycemia on A in healthy has been shown to a reduction in and all also results in the effective of by In addition, the of the of to bacterial discussed neutrophils play an important role in preventing from have been shown in the neutrophils of patients. include decreased and in studies, it has been shown that these can be at least by a study in function in cardiac surgery patients was aggressively controlled with an and compared with patients was controlled with at a level for that authors found that function was better preserved at 1 h after from in the aggressively controlled patients versus the randomized trials the effects of control in the perioperative are a body of evidence is to control at the time of The that hyperglycemia is associated with increased morbidity and mortality, of the importance of maintaining a low for measuring levels in any patient thought to be at risk of increased perioperative Although currently data not the authors to a for the of there is evidence to that only blood greater than 200 has been is Indeed, aggressive of hyperglycemia with and of levels is an established blood transfusions are known to have important than studies have now been regarding the transfusion of blood and the risk of postoperative infection. and retrospective limit the is the that early studies which is In addition, currently erythrocyte units less than plasma and less than versus units in the the that transfusion has been shown to increase many recent prospective studies have perioperative transfusion to infection in surgical populations including cardiac colorectal these studies that the transfusion of blood increases the risk of some studies have not noted an increased have that the of transfusion is the risk of infection with transfusion can be decreased using blood allogenic blood. In fact, in most studies, the infection rates with blood those of patients who did not have This further evidence to the relation between allogeneic erythrocyte transfusions and the risk of of the discussion in the literature surrounding the effects of transfusion implicates this has thought to be Indeed, some have for reductions and this is debated in the analysis in throughout that after of a cardiac surgery, and patients had decreased mortality rates and a decreased incidence of but nosocomial infections did not date, the results of randomized controlled trials have been of these trials using all randomized patients no significant difference in infection in some of the patients were on an and thus their data were of whether they received a the data were patients who did not have a significant reduction in the risk of wound infection were these authors their results should be with because analysis is to be the most study also did not an between postoperative infections and the use of blood in cardiac surgery patients; however, an increased incidence of postoperative infections was observed with blood transfusions in has an amount of discussion, and is no that transfusion has an but the clinical impact and the most effective of prevention are still this there are not adequate clinical data to the use of wound infection in the analysis of the and most effective role the can play in the prevention of SSIs is the administration of The goal of perioperative administration is to blood and tissue levels that the of the likely to be a by the for and and the for an of the will be summarized however, all perioperative physicians should with this Indeed, there are significant data indicating that with is are also data to that is improved anesthesia for administration of first clinical trial in that antibiotics to patients undergoing bowel surgery could decrease the incidence of wound infection and This trial also that the most effective time period for administration was 1 h before who received the first postoperatively received no benefit in of preventing studies have that effective administration is dependent on adequate blood and tissue levels before state that of the first of should 60 of This period can be to for such as high rates have been associated with complications. a is to be it is critical that administration of the be before should be noted that these are based on the retrospective data should also be noted that to a of benefit and the potential for the of that should perioperative at the most commonly should not be administered with the goal of all possible because this may lead to the of most not the most common will be skin the and A these in a involving the bowel and for which and are the use of for surgical is not supported by any there is some discussion that may be the of a of or SSI to has been have that should be the of at with a high of however, there is no evidence that this practice decreases the incidence of common physicians face is the most effective for patients with of all patients studied in one series reported that they had a other range from to studies, have shown that the number of patients is these patients be at their they present for surgery, given the significant morbidity associated with perioperative question how to a trials of in patients. patients had a rate of of approximately the of care the of in these patients. However, the early a similar to the and were with that was in the This may have led to these high rates of studies have now shown the relative clinical of to a result of the above evidence as well as other studies, are now for these patients. Although skin for has been shown not to be effective in to in any patient who has had a to before administration of a is one potential a study that skin of patients with a of was more than the use of in these patients with to can be with a the potential for to a is and are for it should be noted that patients with a are more likely to an to other in surgical technique and the care of postoperative patients, SSIs an important cause of patient morbidity and are at least six perioperative factors that may play a role in the prevention of this some of these there are strong data their A of studies exist indicating that hypothermia is to many surgical patients on several including an increased risk of SSIs. The and of antibiotics are important not only in preventing SSIs, but also in decreasing adverse such as the of Although clinical evidence that 200 has yet to be shown in studies, there is strong evidence from the critical care literature by data from the perioperative period that may be an of the perioperative by the can have an important on the incidence of authors of of for his regarding the
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Mauermann et al. (2006) studied this question.
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