Preventing Deep Wound Infection after Coronary Artery Bypass Grafting

Abstract

The consequences of deep wound infections before, during, and after coronary artery bypass grafting have prompted research to clarify risk factors and explore preventive measures to keep infection rates at an irreducible minimum. An analysis of 42 studies in which investigators used multivariate logistic regression analysis revealed that diabetes mellitus and obesity are by far the chief preoperative risk factors. A 4-point preoperative scoring system based on a patient's body mass index and the presence or absence of diabetes is one practical way to determine the risk of mediastinitis, and other risk-estimate methods are being refined. Intraoperative risk factors include prolonged perfusion time, the use of one or more internal mammary arteries as grafts, blood transfusion, and mechanical circulatory assistance. The chief postoperative risk factor is reoperation, usually for bleeding. Unresolved issues include the optimal approach to Staphylococcus aureus nasal colonization and the choice of a prophylactic antibiotic regimen. We recommend that cardiac surgery programs supplement their audit processes and ongoing vigilance for infections with periodic, multidisciplinary reviews of best-practice standards for preoperative, intraoperative, and postoperative patient care.

Deep infections complicate between 0.25% and 4% of major cardiac surgical procedures, cause death or substantial morbidity, concern healthcare administrators as indices of hospital quality, and challenge surgeons, other healthcare workers, and hospitals to keep infection rates at an irreducible minimum.^1–4 The principles discussed in this review apply broadly to cardiac surgery, with a focus on coronary artery bypass grafting (CABG). (Of note, superficial infections complicating CABG,⁵ and also infections complicating heart transplantation, device implantation, and pediatric cardiac surgery, have somewhat different risk factors than do CABG-related deep infections.)

Pathogenesis, Risk Factors, and Preoperative Evaluation

Deep infection is defined here as infection below the level of the subcutaneous tissue with involvement of the muscle, fascia, bone (particularly the sternum), and body spaces (particularly the mediastinum). These infections typically result from contamination during surgery. The inevitability of wound contamination was shown in a study in which human albumin microspheres labeled with technetium-99m pertechnetate were applied preoperatively to patients' skin (outside the area of incision, and often to remote sites covered with a plastic drape) and to the surgeon's forehead, temples, and mask before clean orthopedic surgery. Considerable wound contamination from both the patient and the surgeon was invariable,⁶ confirming the adage that every surgical procedure is an experiment in applied microbiology. Less often, deep infection results from the postoperative tracking of organisms along the surgical wound or from hematogenous seeding (blood-borne infection from another site, such as a vascular-access catheter) to the surgically wounded tissue, which becomes a “place of least resistance” or locus minoris resistentiae.

One formula approximates the risk of infection by means of the following quotient: (number of organisms in the inoculum × virulence of the organisms) divided by host resistance to infection. Low-virulence skin-flora organisms such as coagulase-negative staphylococci require high inocula to cause infection, except in the case of implanted devices such as prosthetic heart valves. More virulent organisms such as Staphylococcus aureus and Pseudomonas aeruginosa require fewer organisms to cause infection. The likelihood that infection will complicate an operation depends on the outcome of a 6-hour “grace period” during which contaminative organisms battle the body's defense mechanisms, independent of preventive antibiotics. In patients undergoing CABG, the impairment of host defenses is the rule, and it includes conditions that are not usually mentioned in discussions about an immune-compromised host. Prominent among these conditions is obesity, which predisposes the patient to wounds that are highly contaminated, poorly perfused, and lacking in adequate antibiotic concentrations.⁷

A MEDLINE search yielded 42 studies in which multivariate regression analysis was used to identify risk factors for CABG-related deep infections (Table I).^8–59 Fifteen of these studies were performed in the United States, and 27 were conducted in 16 other nations. Diabetes mellitus and obesity— this last of which is often defined in terms of body mass index (BMI)—were the preoperative risk factors identified most often. Intraoperative risk factors included prolonged perfusion time, multiple grafts or the use of one or more internal mammary arteries, and mechanical circulatory assistance. The chief postoperative risk factor was reoperation, usually for bleeding.

TABLE I. Independent Risk Factors for Deep Infectious Complications of Coronary Artery Bypass Grafting (CABG)*

Preoperative risk evaluation improves the informed-consent process and occasionally identifies modifiable factors, such as smoking. Various frameworks for evaluating an individual patient's risks have been developed. The National Nosocomial Infections Surveillance (NNIS) risk index for surgical infection, developed by the Centers for Disease Control and Prevention (CDC),⁶⁰ is less well suited for CABG than for certain other types of surgery, in part because CABG is always “clean” surgery and the American Society of Anesthesiologists scores are by definition greater than 2.⁶¹ Australian investigators found that the NNIS risk index performed less well in CABG than in 6 other types of surgery.^62,63 The most elaborate and specific system for estimating CABG-related major infection was developed by Fowler and colleagues.¹⁹ They analyzed 331,429 CABG operations that were performed from 2002 through 2003 and were recorded in the Society of Thoracic Surgeons (STS) National Cardiac Database. A risk score based on 12 variables enabled the investigators to estimate the probability of infection, which ranged from 0.9% (risk score, 0) to 16% (risk score, ≥26). Patients with a major infection had a higher mortality rate than did patients without such infection (17.3% vs 3%) and were more likely to have a postoperative hospital stay exceeding 14 days (47% vs 5.9%).¹⁹ Investigators subsequently found that combining the use of the system developed by Fowler and colleagues (based on the STS database) and the EuroSCORE system (originally designed to predict mortality rates⁶⁴) facilitated risk stratification.^64,65 A simpler system, the Australian Clinical Risk Index, uses a 4-point score based on just 2 variables: the presence or absence of diabetes mellitus, and the patient's BMI.⁶² On the basis of 1 point for the presence of diabetes mellitus, 1 point for a BMI from 30 through 34.9, and 2 points for a BMI ≥35, a patient's risk score can vary from 0 to 3. Investigators in the United States validated this prediction method and determined that each additional point was associated with a 2-fold increase in the risk of surgical-site infection; however, the definition of infection was not limited to deep infection.⁶⁶ In view of the limitations of the NNIS risk index for CABG, the CDC proposed a new risk model in 2012. This model is being considered for endorsement as a measure for public reporting, an act that is required in 28 U.S. states and the District of Columbia.³⁹

Minimizing Preoperative Risk Factors

Most preoperative risk factors for CABG-related deep infections, or at least those identified by multivariate regression analysis (Table I), lend themselves poorly to preoperative intervention. The control of diabetes, as evaluated in accordance with hemoglobin A₁C levels, ideally should be optimized, although preoperative glucose levels probably matter less than do intraoperative and postoperative levels. The appropriate management of antiplatelet drugs such as aspirin and clopidogrel, and also of anticoagulative drugs such as warfarin, is important, complicated, and controversial.^67–71 Here, we will review 3 interventions pertaining to preoperative care: identification of nasal staphylococcal carriage and the use of decolonization therapy with mupirocin nasal ointment; preoperative bathing; and prophylactic antimicrobial therapy. We will not discuss familiar standard-of-care measures such as preoperative scrubbing or the use of clippers instead of razors for hair removal (although policies for these measures need to be rigorously implemented⁷²), or potentially useful but unproved therapy with preoperative statins^73,74 or nutritional supplements that are beneficial to the immune system.^75,76 It could be preferable to schedule patients who run a high risk of infection and other complications as first-in-the-morning cases, because the time of operation (morning vs afternoon) may make a difference.⁷⁷

Preoperative Screening for Staphylococcus aureus Nasal Carriage and the Use of Mupirocin Nasal Ointment

Many regulatory and public-reporting issues center on healthcare-associated infections from S. aureus, especially infections caused by methicillin-resistant strains (MRSA). A large body of literature, including some comprehensive reviews,^78,79 focuses on preoperative screening for S. aureus nasal carriage and the use of mupirocin nasal ointment to reduce or eliminate that bacterium. However, determining a best-practices standard is not straightforward. Reservations about universal screening for staphylococcal nasal carriage and using mupirocin in all patients include questions about efficacy, cumbersome follow-up of culture results, the potential for widespread high-level mupirocin resistance, and cost. A cardiac surgery program can adopt any of several approaches (Table II).

TABLE II. Approaches to Preoperative Nasal Cultures for Staphylococcus aureus and Decolonization Therapy with Mupirocin in CABG

Three reasons underlie the present rationale for preoperative screening and treatment with mupirocin nasal ointment. First, from 40% to more than 80% of CABG-complicating infections are due to S. aureus, increasingly including MRSA strains.^80,81 Deep surgical infections caused by MRSA possibly carry higher risks of morbidity and death than do infections caused by methicillin-susceptible S. aureus (MSSA); however, patients who contract MRSA infections tend to be older and have more comorbidities.^82,83 Second, most surgical infections arise from the patient's own flora, and data suggest that nasal colonization with S. aureus often precedes deep infection. In a multicenter study,⁸⁴ 1,640 S. aureus isolates were collected off nasal swabs from 1,278 patients over 5 years. Fourteen of the 1,278 patients subsequently developed S. aureus bacteremia, and in 12 of those 14 patients the blood isolates were clonally identical to the previous nasal isolates. Third, some studies suggest that identifying S. aureus carriage and treating the carriers with 2% mupirocin ointment lowers infection rates.⁸⁵

In 2007, the STS issued practice guidelines that included this Class IA recommendation: “Routine mupirocin administration is recommended for all patients undergoing cardiac surgical procedures in the absence of a documented negative testing for staphylococcal colonization.”⁸⁶ However, the results of individual studies^81,87 and meta-analyses of the published literature^88,89 have been conflicting. In 2008, one meta-analysis determined that mupirocin is useful⁸⁸; however, another revealed that no blanket recommendation could be made for mupirocin use in cardiac surgery patients.⁸⁹ The authors of the second analysis⁸⁹ noted that the only prospective, randomized, double-blinded trial of mupirocin in cardiac-surgery patients showed no benefit. In contrast with MSSA-related mediastinitis, none of 8 patients with post-sternotomy mediastinitis caused by MRSA had identical isolates (as tested by means of pulsed-field gel electrophoresis) in preoperative and surgical-site cultures.⁹⁰ The same clone of MRSA was found in all 8 instances, suggesting that hospital infection-control measures might be more important in MRSA infections than in MSSA infections.⁹⁰ Neither MRSA nasal carriage on admission nor topical decolonization treatment predicted MRSA surgical-site infections.⁹¹ In an evaluation of MRSA cultured from nasal and inguinal swabs, preoperative MRSA carriers undergoing elective heart surgery did not have a higher incidence of MRSA wound infections than did non-carriers.⁹² This study was one of the few to have examined extra-nasal carriage sites, which are especially important in the transmission of community-acquired MRSA strains.

The recommendation that all patients be screened preoperatively for S. aureus nasal carriage (the “screen all” approach) or, alternatively, treated empirically with mupirocin nasal ointment (the “treat all” approach), is strongly endorsed during outbreaks of MRSA or MSSA.⁹³ Screen-all or treat-all approaches also make sense in hospitals that have a high incidence of deep S. aureus infections after CABG. A hospital in which MRSA caused 56% of postoperative infections adopted the following practice: giving intranasal mupirocin to all patients (regardless of colonization status) for 5 days before surgery, giving combined mupirocin and vancomycin prophylaxis to all MRSA-colonized patients, and applying mupirocin to chest-tube sites at the time of tube removal. These steps yielded a near-complete and sustained reduction of MRSA wound infections after cardiac surgery.⁸⁵

The resistance of S. aureus to mupirocin, a natural antibiotic produced by Pseudomonas fluorescens, was recognized shortly after mupirocin was introduced into clinical practice during the 1980s.⁹⁴ High-level resistance to mupirocin (minimum inhibitory concentration [MIC], ≥512 µg/mL) is currently less than 5% among MRSA isolates in the United States.⁹⁵ However, new mechanisms of resistance continue to appear.^96,97 Few clinical laboratories currently screen S. aureus isolates for resistance to mupirocin. Although an empiric treat-all approach has been endorsed for use in cardiac and other types of surgery,⁹⁸ and although it is unclear whether short-term mupirocin for nasal colonization promotes high-level resistance, it seems reasonable to ask whether a treat-all approach is consistent with long-term social responsibility (that is, the desirability of holding down the emergence of mupirocin-resistant S. aureus strains). For this reason alone, screen-all is better for hospitals with an appreciable incidence of S. aureus-related deep infections after CABG. Screening, if performed at all, should probably be universal. A patient's medical history is a poor predictor of MRSA colonization.⁹⁹ Selective screening—that is, screening only those patients who are considered to be at high risk of infection—raises the issue of how to decide who is screened and who is not.

The major drawbacks of a screen-all approach are logistics and cost. The recommended duration of mupirocin therapy for suppressing S. aureus nasal carriage is 5 days, so therapy should ideally begin several days before surgery. However, patients who have been scheduled for elective CABG are commonly admitted to the hospital the previous afternoon or evening, because a longer preoperative stay seems to be a risk factor for infection.^20,25,40 Culture-based screening therefore necessitates outpatient procurement of the culture, someone to follow up on the culture result, and someone to prescribe timely therapy if the culture is positive. Rapid screening by means of the polymerase chain reaction (PCR), which largely overcomes these logistical problems, has been studied in cardiac-surgery patients for more than a decade.⁸⁰ As a basis for mupirocin therapy, PCR-based screening has been shown to reduce the overall usage of mupirocin while also lowering the rate of MRSA infections that complicate cardiac surgery.^101,102 Rapid PCR-based screening followed by the treatment of S. aureus nasal carriers with mupirocin ointment and chlorhexidine soap reduced the risk of postoperative infections by nearly 60% in various types of surgery.¹⁰² In an economic analysis, routine preoperative screening for MRSA was financially feasible over a wide range of MRSA-colonization prevalence levels: the incremental cost-effectiveness ratio was well under U.S. $15,000 per quality-adjusted life-year gained from hospital and third-party-payer perspectives.¹⁰³ Therefore, it behooves cardiac surgery programs that do not currently use this methodology to review its potential applicability.

Another decolonization approach is to combine a nasal ointment and an oral rinse, both containing 0.12% chlorhexidine gluconate.¹⁰⁴ The oral rinse, Peridex™ (3M ESPE; St. Paul, Minn), is approved for use in the United States.

Preoperative Bathing

When patients shower or bathe preoperatively with antiseptic agents, it reduces bacterial colonization. This approach is widely used before cardiac and other surgery. Chlorhexidine reduces skin bacterial-colony counts to a greater extent than does povidone-iodine or other agents that have been studied. However, in a comprehensive, systematic literature review published in 2012,¹⁰⁵ the authors concluded only that preoperative antiseptic showers may be effective in preventing postoperative infections. Three randomized, controlled trials yielded no difference in postoperative infection rates between 3 groups of patients who showered preoperatively (with chlorhexidine or povidone-iodine, with soap and water, or with a placebo) and a group that was given no showering instructions. The authors reported no clear advantage of one agent over another and noted the difficulty in drawing conclusions about an active ingredient, because disinfectants are often mixed with alcohol or water.¹⁰⁵

One explanation for the inability to show benefit from preoperative antiseptic showering comes from a study of quantitative cultures obtained during cardiac surgery from subcutaneous sternal tissue and skin surrounding the wound. Bacteria—predominantly coagulase-negative staphylococci and Propionibacterium acnes—were isolated from the subcutaneous sternal tissue in 89% of cases and from the skin surrounding the wound in 98%. In nearly half of these instances, the density exceeded 10,000 colony-forming units per culture pad. It was concluded that preoperative skin preparation with ethanol and chlorhexidine cannot prevent skin-flora organisms from contaminating wounds and the surrounding tissue for the duration of the operation.¹⁰⁶ Reasons include the large numbers of organisms in skin appendages such as sweat glands, and the constant turnover of surface epithelial cells.

Prophylactic Antibiotic Therapy

The benefits of appropriately administered prophylactic antibiotic therapy in patients undergoing cardiac surgery are so beyond dispute that placebo-controlled trials would no longer be permissible. Of note, however, is one small early trial in which antibiotics did not lower the incidence of infection but instead appeared to influence which organisms were causative.¹⁰⁷ Current guidelines are that a cephalosporin—usually cefazolin or cefuroxime—should be given within 60 minutes of the skin incision and be continued for no longer than 48 hours.^2,86 Vancomycin is reserved mainly for patients with a history of type I allergic reaction (anaphylaxis, urticaria, angioedema, or bronchospasm) to β-lactam agents or when MRSA is of special concern, as discussed below.

Proper timing of the preoperative antibiotic dose is now widely used as a quality-of-care indicator.^108–110 Investigators continue to study how to maintain adequate antibiotic levels in serum and tissue throughout surgery and the immediate postoperative period. Consider, for example, the following studies of cefazolin. In 2001, it was reported that intraoperative re-dosing of cefazolin reduced infection after cardiac surgery by 16%, including procedures lasting less than 4 hours; as a result, an automated reminder system was introduced.^111,112 In 2006, the need was confirmed for an intraoperative dose of cefazolin after 120 minutes of cardiopulmonary bypass time.¹¹³ In 2008, it was reported that a 24-hour, multiple-dose regimen of cefazolin more than halved the infection rate (from 8.3% to 3.6%) compared with single-dose cefazolin.¹¹⁴ In 2010, investigators reported that a cefazolin bolus followed by continuous infusion improved pharmacokinetic and pharmacodynamic values, including concentrations in the heart muscle.¹¹⁵ However, even a 2-g dose of cefazolin failed to provide adequate tissue levels in morbidly obese patients,¹¹⁶ which suggested the need for additional studies in this important subgroup. In another study, continuing cefazolin beyond 24 hours did not reduce the incidence of deep sternal wound infections,¹¹⁷ supporting the general consensus that 24-hour prophylaxis suffices in most major surgical procedures.¹¹⁸ However, a systematic review and meta-analysis of the literature led to the conclusion that perioperative antibiotic prophylaxis beyond 24 hours might be more effective than shorter regimens for preventing sternal wound infections, with the caveat that heterogeneous regimens in various studies and possible investigator bias might preclude definite conclusions.¹¹⁹

The frequent identification of MRSA as a cause of deep sternal wound infection calls into question whether older cephalosporins should still be the prophylactic drugs of choice. Specifically, should vancomycin become the preferred agent?¹²⁰ Vancomycin is often used during outbreaks of MRSA infection, in concert with other measures such as the screen-all or treat-all approaches to MRSA nasal colonization.^85,93 However, vancomycin falls short of “blockbuster” drug status. Unlike the β-lactam antibiotics (the penicillins and cephalosporins), vancomycin is only slowly bactericidal; indeed, some authorities classify vancomycin as bacteriostatic. Vancomycin is considerably less active than nafcillin and oxacillin against mutually susceptible strains of S. aureus. In a tertiary-care center with a high prevalence of MRSA infection, patients undergoing cardiac surgery were randomized to receive vancomycin or cefazolin; the overall infection rates were similar, but infections caused by MSSA occurred more often in the patients who received vancomycin.¹²¹ The activity of vancomycin is essentially limited to gram-positive bacteria. Although MRSA strains with high-level resistance to vancomycin (MIC, ≥16 µg/mL) remain rare, strains with reduced susceptibility are increasingly prevalent. This phenomenon, “MIC creep,” is of wide concern, because strains with an MIC of 2 µg/mL or more respond less well to vancomycin therapy. Because the rapid infusion of vancomycin can trigger a histamine-release phenomenon characterized by extensive flushing in the upper chest (“red man's syndrome”),¹²² many guidelines indicate that infusion should begin about 120 minutes before the skin incision. However, as with other antibiotics, the incidence of infection is lower when the drug is given within 60 minutes of incision.¹²³ In the meantime, careful attention should be given to vancomycin dosage. The preoperative dose should be 15 mg/kg (rather than the commonly used 1-g dose for all adult patients)¹²⁴; a postoperative dose (10 mg/kg) is also recommended¹²⁵; and findings in the literature should be heeded with respect to vancomycin dosing in morbidly obese patients, because the optimal dose has not been determined.¹²⁶

The current consensus is that vancomycin should not be the routine or default drug of choice for non–penicillin-allergic patients who undergo cardiac and other surgery.^86,120 Vancomycin can be an important component of an “MRSA-prevention bundle” in selected circumstances.^85,93,127 Studies performed a decade or more ago indicated that β-lactam antibiotics (in particular, the cephalosporins) surpassed vancomycin in overall performance; however, vancomycin was superior in preventing infections due to methicillin-resistant gram-positive bacteria (in particular, MRSA and MRSE—methicillin-resistant coagulase-negative staphylococci such as S. epidermidis).¹²⁸ The MIC creep of S. aureus in relation to vancomycin is disquieting to those who formulate guidelines for prophylaxis.^129,130 Should randomized controlled trials be conducted to compare the now-traditional cephalosporins (such as cefazolin and cefuroxime) against combination therapy with vancomycin and a drug active against gram-negative pathogens—for example, single-dose ceftriaxone, which has favorable pharmacokinetics?^131,132 Should daptomycin be tried, because it is rapidly bactericidal against staphylococci? (Many infectious-disease specialists might prefer daptomycin for themselves in this situation but would question routine prophylactic daptomycin use: daptomycin is currently a drug of last resort for life-threatening MRSA infection, and daptomycin-nonsusceptible S. aureus strains are becoming more prevalent. A MEDLINE search revealed no studies of daptomycin for prophylaxis in cardiac and thoracic surgery.) In summary, the optimal choices of agents, doses, and dosage schedules for prophylactic antibiotic therapy necessitate ongoing scrutiny.

Minimizing Intraoperative Risk Factors

In minimizing intraoperative risk factors, considerations include a sterile operating room with adequate ventilation, because airborne pathogens such as Aspergillus and Legionella species can cause outbreaks in cardiac surgery patients^21,133–136; hygienic operating-room practices, including limited traffic flow; and adherence to basic surgical principles, as expressed in particular by William Stewart Halsted. These last include control of bleeding, accurate anatomic dissection, the use of completely sterile equipment, strict adherence to aseptic operative technique, exact approximation of tissue in wound closures without excessive tightness, and gentle handling of tissues. The control of bleeding is especially important. Excessive bleeding and hematoma formation creates a culture medium or locus minoris resistentiae that is a major risk factor for mediastinitis. Intraoperative risk factors predisposing patients to hemorrhage include prolonged perfusion time, the use of a ventricular assist device or intra-aortic balloon pump, and aortic dissection.²³ In one study, 71 of 136 patients (52%) who had been supported with an intra-aortic balloon pump during cardiac surgery developed a postoperative infection.¹³⁷ Blood transfusion also seems to increase the risk of infection^138–141 and could be the major preventable intraoperative risk factor for mediastinitis.²⁷ The benefits of transfusing leukocyte-reduced blood are unclear.^142,143

The use of internal mammary artery grafts in high-risk patients, specifically bilateral grafts in patients with diabetes mellitus,^10,144,145 continues to be controversial. The effects on infection rates of off-pump CABG and of minimally invasive surgical techniques such as mini-sternotomy are not yet clear.^146,147 Inadvertent paramedian sternotomy, which reduces sternal stability, might increase the risk of infection.¹⁴⁸ In a multicenter study of 815 patients at high risk of sternal instability and infection, external reinforcement with use of the method described by Robicsek did not reduce the complication rates.¹⁴⁹ A reinforced sternal-closure system in elderly patients with osteoporosis yielded no benefit¹⁵⁰; however, rigid-plate sternal fixation in high-risk patients reduced the incidence of postoperative infection.¹⁵¹ Studies examining techniques of sternal wiring (figure-of-8 vs interrupted wires, and number of wires) and skin closure (intracutaneous vs transcutaneous) have yielded somewhat conflicting results.^36,152–154 A multicenter trial of the Posthorax® support vest (Posthorax GmbH; Vienna, Austria) showed a significant lowering of sternal complications, including the need for reoperation¹⁵⁵; however, further experience is needed before this device can be endorsed as standard-of-care. Levels of concern have varied in regard to the risks of mediastinitis and sternal osteomyelitis from the liberal application of bone wax. Animal studies showed that lower numbers of S. aureus organisms (inocula size) were needed to cause infection,¹⁵⁶ but a prospective, randomized study of 400 patients¹⁵⁷ showed no detrimental effect; the authors concluded that bone wax is “obviously safe but not particularly beneficial.”¹⁵⁷

Control of Hyperglycemia

Hyperglycemia promotes pathogen proliferation, impairs neutrophil function, and possibly has other effects on host defenses. Most but not all retrospective studies indicate that poor glucose control promotes CABG-related complications and increases mortality rates.^158,159 Investigators at the Mayo Clinic concluded that intraoperative hyperglycemia is an independent risk factor for complications: a 20-mg/dL increase in the mean intraoperative glucose level correlated with an increase of more than 30% in adverse outcomes (a composite of death, infections, or major organ-system complications).¹⁶⁰ Investigators with the Portland Diabetic Project, a large prospective study of diabetic patients undergoing cardiac surgery, confirmed that hyperglycemia was an independent risk factor for death, length of hospital stay, and infection rates, and showed that continuous insulin infusions eliminated these risks.^161,162 The danger of tight glucose control is inadvertent hypoglycemia. Literature from the late 2000s emphasizes continuous infusion protocols with frequent blood-glucose monitoring during surgery and the immediate postoperative period, supplemented by a multidisciplinary approach that incorporates nursing education, feedback, and ongoing audits of procedures.^163–167

Novel Approaches to Infection Control

In regard to deep sternal infections, efforts continue worldwide to examine variables and try novel approaches. In a prospective study of more than a thousand patients, Spanish investigators could not show a relationship between infection rates and the inspired oxygen fraction during surgery.¹⁶⁸ Italian investigators reviewed randomized, double-blinded trials of intraoperative steroids that have been used in cardiac surgery, with the rationale that the acute inflammatory response might contribute to postoperative morbidity. Steroid prophylaxis had no effect on mortality rates, the duration of mechanical ventilation, re-exploration for bleeding, or postoperative infection.¹⁶⁹ Japanese investigators claimed to reduce infection rates by spraying an antibiotic solution containing cefazolin and gentamicin into the operative field.¹⁷⁰ In a Swedish study, carbon dioxide insufflation into the cardiothoracic wound cavity—a technique for preventing arterial air embolism—reduced the risk of airborne contamination and postoperative infection when the insufflation was performed with a gas-diffuser. Conversely, insufflation with an open-ended tube substantially increased the risk of airborne contamination and wound infection.¹⁷¹

There is no consensus about the effectiveness of topical agents with antimicrobial activity. Sutures coated with triclosan, a phenolic compound used in toothpaste, attracted initial interest¹⁷² that subsided after results of a large observational study and a randomized trial showed no benefit.^173,174 In a single randomized trial, applying topical vancomycin to the cut sternal edges reduced infection rates.¹⁷⁵ Swedish and Finnish investigators generated enthusiasm for leaving a gentamicin-collagen sponge in the sternotomy wound^176–179; however, a large multicenter trial conducted in the United States in patients with diabetes, high BMI, or both failed to show a benefit from implanting 2 gentamicin-collagen sponges during cardiac surgery.¹⁸⁰ In 2012, it was reported that the routine use of a gentamicin-collagen sponge reduced the incidence of infection from 3.5% to 0.6%,¹⁸¹ but 2 systematic reviews showed no clear benefit.^182,183 Applying topical bacitracin to the sternotomy incision after closure seemed to be effective.¹⁸⁴ Applying a platelet gel reportedly promoted wound-healing and reduced the incidence of superficial and deep sternal wound infections; however, the mechanisms of action were unclear.^185,186 Also unresolved is the use of the skin adhesive InteguSeal® (Kimberly-Clark Worldwide, Inc.; Roswell, Ga), which contains a cyanoacrylate-based antimicrobial skin sealant. Observations in Brazil, Turkey, Germany, the United Kingdom, and Chile suggested clinical and experimental benefit^187–193; conversely, a subsequent large, nonrandomized study from Germany revealed no reduction in the incidence of postoperative mediastinitis.¹⁹⁴

Minimizing Postoperative Risk Factors

Aggressive environmental cleaning of the intensive care unit (ICU) and cardiovascular recovery room is important, because patients admitted to a room previously occupied by a carrier of MRSA or a vancomycin-resistant Enterococcus have as much as a 40% increased risk of acquisition.¹⁹⁵ Early extubation is desirable.²⁶ Daily attention should be given to whether patients' indwelling urinary and central venous catheters continue to be necessary. In a large case-control study, central venous catheter-related infection was found to increase wound infection by 5-fold.¹⁹⁶ Peripherally inserted vascular-access devices, including radial artery catheters for pressure-monitoring, can also cause sternal wound infections.¹⁹⁷ Postoperative S. aureus bacteremia can be a cause or a consequence of deep sternal wound infection. In one study, a positive blood culture for S. aureus within 60 days of surgery had a 68% sensitivity, 98% specificity, 87% positive predictive value, and 95% negative predictive value for S. aureus mediastinitis.¹⁹⁸ Protocols for insulin administration and glucose monitoring should be implemented for patients with diabetes. A negative study¹⁹⁹ has partially allayed concerns that infection rates are increased by intravenous iron that is used to promote red blood cell production as part of blood-conservation programs.

Clinical evaluations of sternal and vein-harvest wounds should be documented daily.²⁰⁰ Sound scientific evidence is scanty in regard to wound-dressing choices. Australian investigators found no differences in rates of post-sternotomy healing or rates of infection among 3 types of dressing: PRIMAPORE®, a dry absorbent dressing (Smith & Nephew, Inc.; St. Petersburg, Fla); DuoDERM® Extra Thin, a hydrocolloid dressing (ConvaTec Professional Services; Skillman, NJ); and Opsite®, a hydroactive dressing (Smith & Nephew). PRIMAPORE was the most comfortable for patients.²⁰¹ An incision-care program that involved a sterile, impermeable adhesive drape performed no better than an absorbent dressing.²⁰² After conducting a prospective study that compared a silver nylon dressing to a standard gauze dressing, the investigators suggested that a large randomized trial might settle the issue.²⁰³

The chief postoperative contributors to deep surgical wound infection after CABG are prolonged treatment in the ICU and reoperation for bleeding (Table I). Although the causes of postoperative bleeding remain poorly understood, related deaths might be declining because of more aggressive management.²⁰⁴ Early reoperation for bleeding might substantially reduce risks of infection and other complications, such as renal failure and prolonged mechanical ventilation.^205,206 Re-exploring the chest in the ICU for bleeding or tamponade might be a safe alternative to returning to the operating room.²⁰⁷ Few systematic studies have dealt with the choice and duration of prophylactic antibiotic therapy for repeat operations, which are important but unresolved issues. Because standard preoperative antibiotics substantially alter the patient's flora, there is a high likelihood of wound contamination by drug-resistant organisms: gram-positive bacteria that are resistant to the β-lactam antibiotics, gram-negative bacilli, and even yeasts. It was concluded from a best-evidence topic review that, although it is common practice to administer additional antibiotics, no well-conducted studies appear to support the practice.²⁰⁸

Vigilance, Audits, and Periodic Policy Reviews

Reducing the risk of CABG-related infection requires constant vigilance and attention to detail, both in caring for individual patients and in ensuring that policies conform with up-to-date knowledge and experience. Every case of life-threatening infection, such as mediastinitis, should be reviewed and the root cause considered. Clusters or outbreaks of infection should prompt an epidemiologic investigation. These investigations occasionally pinpoint a specific source, such as chemical solutions, equipment, or an individual involved in the patient's care. More often, these efforts foster better adherence to standard practices, with the result that infection rates decline with no clear explanation other than the Hawthorne effect (behavioral change that occurs when subjects know that they are being watched). Ideally, cardiac surgery programs should supplement ongoing vigilance with process audits and periodic, multidisciplinary reviews of best-practice standards (Table III).^26,209–213

TABLE III. Proposed Checklist for Scheduled Institutional Reviews of Experiences, Policies, and Procedures

Deep infections will continue to complicate CABG procedures, chiefly because so many patients have severe comorbidities. However, to paraphrase football coach Vince Lombardi (“in chasing perfection we catch excellence”), scrupulous attention to the details of preoperative, intraoperative, and postoperative care should enable all programs to keep rates at an irreducible minimum.