Inflammation, Wound Healing, and Infection



Inflammation, Wound Healing, and Infection


Harriet W. Hopf

C. Richard Chapman

Amalia Cochran

Michael B. Dorrough

Randal O. Dull






Despite major advances in the management of patients undergoing surgery—including aseptic technique, prophylactic antibiotics, and advances in surgical approaches such as laparoscopic surgery—surgical wound infection and wound failure remain common complications of surgery (Fig. 13-1). Wound complications are associated with prolonged hospitalization, increased resource consumption, and even increased mortality. More than 300,000 surgical site infections (SSIs; Table 13-1) occur each year in the United States at an estimated cost of more than $1 billion.2 A growing body of literature supports the concept that patient factors are a major determinant of wound outcome following surgery. Comorbidities such as diabetes and cardiac disease clearly contribute, but environmental stressors as well the individual response to stress may be equally important. In particular, wounds are exquisitely sensitive to hypoxia, which is both common and preventable. Perioperative management can be adapted to promote postoperative wound healing and resistance to infection. Along with aseptic technique and prophylactic antibiotics, maintaining perfusion and oxygenation of the wound is paramount. This chapter discusses how knowledge of the principles of infection control and the biology and physiology of wound repair and resistance to infection can improve outcomes.






Figure 13.1. Thomas et al.1 reviewed the records of 15,000 nonpsychiatric patients discharged from a representative sample of Utah and Colorado hospitals in 1992 for adverse events. There were 17,912 adverse events identified, or 2.9 ± 0.2% of hospitalizations. Of these, almost half (45%) were related to operative care. The graph shows the distribution of adverse events within the subcategory of operative care (7,716 operative adverse events). Note that about 20% were infection related and about 15% were wound related. SSI, surgical site infection; HCAI, health care–associated infection; DVT, deep venous thrombosis; MI, myocardial infarction; PE, pulmonary embolus; CHF, congestive heart failure; CVA, cerebrovascular accident. (Data from: Thomas EJ, Studdert DM, Burstin HR, et al. Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care 2000;38:261–271.)


Infection Control


Hand Hygiene

Perhaps the most crucial component of infection prevention is frequent and effective hand hygiene. In 1847 Ignaz Semmelweis made the observation that women who delivered their babies in the First Clinic at the General Hospital of Vienna, staffed by medical students and physicians, had a mortality rate of 5% to 15%, largely the result of puerperal infections; this was substantially higher than the 2% rate of women who delivered at Clinic 2, which was staffed by midwife students and midwives.3 Students and physicians at Clinic 1 usually started the day performing autopsies (including on patients who died of puerperal fever) and then moved on to the clinic, where they performed examinations on women in labor. Semmelweis made the connection, and although germ theory was some years off, he insisted that physicians and medical students wash their hands in a chlorinated solution when leaving the pathology laboratory. This reduced the rate of puerperal fever to the same rate as at Clinic 2. Soon, Semmelweis identified cases of transmission from an infected to an uninfected patient, and instituted the use of chlorinated solution hand washing between cases as well. He also demonstrated that the chlorinated solution was more effective than soap and water. Unfortunately, his innovation was not widely adopted, resulting from a combination of his delay in publishing his results, the reluctance of his colleagues to accept that they might be responsible for transmitting disease, and his lack of tact in trying to convince health care workers to adopt his measures. Despite our current knowledge of germ theory, hand hygiene remains an inexplicably neglected component of infection control: Studies consistently demonstrate about a 40% rate of adherence (range, 5% to 81%) to hand hygiene guidelines.4

Bacteria are resident in the skin and can never be completely eliminated.4 Resident flora are embedded in the deeper folds of the skin and are more resistant to removal, but are also infrequently pathogenic. Coagulase-negative staphylococci and diphtheroids
are the most common. Transient flora colonize the superficial layers of the skin and thus are easier to remove with hand hygiene. Transient flora are also the source of most health care–associated infections, as health care worker skin can become contaminated from patient contact or contact with contaminated surfaces. Contamination from surfaces is most commonly with organisms such as staphylococci and enterococci, which are resistant to drying. Even “clean” activities such as taking a patient’s pulse or applying monitors can lead to hand contamination: 100 to 1,000 colony-forming units of Klebsiella species were measured on nurses’ hands following such activities in one study.5 No studies have related hand contamination to actual transmission of infection to patients; however, numerous studies, starting with those of Semmelweis, have demonstrated a reduction in health care–associated infections following institution of hand hygiene or improved adherence to hand hygiene.4








Table 13-1. Criteria for Defining A Surgical Site Infection (SSI)






Superficial Incisional SSI

  • Infection occurs within 30 days after the operation
    and
  • Infection involves only skin or subcutaneous tissue of the incision
    and
  • At least one of the following:

    1. Purulent drainage, with or without laboratory confirmation, from the superficial incision
    2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision
    3. At least one of the following signs or symptoms of infection: Pain or tenderness, localized swelling, redness, or heat and superficial incision is deliberately opened by the surgeon, unless the incision is culture-negative
    4. Diagnosis of superficial incisional SSI by the surgeon or attending physician

  • Do not report the following conditions as superficial incisional SSI:

    1. Stitch abscess (minimal inflammation and discharge confined to the points of suture penetration)
    2. Infection of an episiotomy or newborn circumcision site
    3. Infected burn wound
    4. Incisional SSI that extends into the facial and muscle layers (see “Deep Incisional SSI”)
Note: Specific criteria are used for identifying infected episiotomy and circumcision sites and burn wounds
Deep Incisional SSI

  • Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation
    and
  • Infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision
    and
  • At least one of the following:

    1. Purulent drainage from the deep incision but not from the organ/space component of the surgical site
    2. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or symptoms: Fever (>38°C), localized pain, or tenderness, unless site is culture-negative
    3. An abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination
    4. Diagnosis of a deep incisional SSI by a surgeon or attending physician
Notes:

  1. Report infection that involves both superficial and deep incision sites as deep incisional SSI
  2. Report an organ/space SSI that drains through the incision as a deep incisional SSI
Organ/Space SSI

  • Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation
    and
  • Infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation
    and
  • At least one of the following:

    1. Purulent drainage from a drain that is placed through a stab wound into the organ/space
    2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space
    3. An abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination
    4. Diagnosis of an organ/space SSI by a surgeon or attending physician
From: Mangram AJ, Horan TC, Pearson ML, et al. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27:97–132, with permission.

A number of products are available for hand hygiene. The ideal agent kills a broad spectrum of microbes, has antimicrobial
activity that persists for at least 6 hours after application, is simple to use, and has few side effects. The most commonly used and efficacious agents are reviewed here.

Plain (not antiseptic) soap and water are generally the least effective at reducing hand contamination.6 Although obvious dirt is removed by the detergent effect of soap and the mechanical action of washing, bacterial load is not greatly reduced. Further, soap and water hand hygiene is associated with high rates of skin irritation and drying, both of which are risk factors for an increased bacterial load. Soap and water are, however, the most effective at removing spores, and therefore should be used when contamination with Clostridium difficile or Bacillus anthracis is a concern.4

Alcohol-based rinses, gels, and foams denature proteins, and this confers their antimicrobial activity.4 Ethanol is most commonly used because it has more antiviral activity than isopropanol. Antiseptics containing 60% to 95% ethanol with a water base are germicidal and effective against gram-positive and gram-negative bacteria, lipophilic viruses such as herpes simplex, human immunodeficiency, influenza, respiratory syncytial, and vaccinia viruses, and hepatitis B and C viruses. They have little persistent activity, although regrowth of bacteria does occur slowly after use of alcohol-based products. Combination with low doses of other agents such as chlorhexidine, quaternary ammonium compounds, or triclosan can confer persistent activity. Efficacy depends on volume applied (3 mL is superior to 1 mL) and duration of contact (ideally, 30 seconds).

Chlorhexidine is a cationic bisbiguanide that disrupts cytoplasmic membranes, resulting in precipitation of cellular contents.4 It is germicidal against gram-positive bacteria and lipophilic viruses, with somewhat less activity against gram-negative bacteria and fungi, and minimal against tubercle bacilli. It has substantial persistence on the skin, and the Centers for Disease Control and Prevention (CDC) has identified it as the topical agent of choice for skin preparation in central venous catheter insertion. It may cause severe corneal damage after direct contact with the eye, ototoxicity after direct contact with the inner or middle ear, and neurotoxicity after direct contact with the brain or meninges. There are reports of bacteria that have acquired reduced susceptibility to chlorhexidine, but these are of questionable clinical pertinence since the concentrations at which resistance was found were substantially lower than that of commercially available products. Recent reports have identified immunoglobulin E–mediated allergic reactions to chlorhexidine.7 Cases are likely underreported because of the difficulty identifying the source of anaphylactic reactions perioperatively. Chlorhexidine is present in a wide range of medical and community based products, including wipes, impregnated central venous catheters, toothpaste, mouthwash, contact lens cleanser, and food preservatives. Therefore, potentially sensitizing exposures are common.

Iodine and iodophors (iodine with a polymer carrier) penetrate the cell wall and impair protein synthesis and cell membrane function.4 They are bactericidal against gram-positive, gram-negative, and some spore-forming bacteria including clostridia and Bacillus species, although inactive against spores. They also have activity against mycobacteria, viruses, and fungi. Their persistence is generally fairly poor. They cause more contact dermatitis than other commonly used agents, and allergies to this class of topical agent are common. Iodophors generally cause fewer side effects than iodine agents.

The choice of an antiseptic depends on the expected pathogens, acceptability by health care workers, and cost. In general, antiseptics cost about $1 per patient day, far less than the cost of health care–associated infections. In nine studies that examined the effect of improved hand hygiene adherence on health care–associated infections, the majority demonstrated that as hand hygiene practices improved, infection rates decreased.4

Barriers to hand hygiene include skin irritation and fear of skin irritation, inaccessibility, time, and health care worker acceptance (largely related to the other factors mentioned). Although alcohol-based agents have long been believed to cause more skin irritation, several recent trials have demonstrated less skin irritation and better acceptance with emollient-containing, alcohol-based hand rubs compared with either antimicrobial or nonantimicrobial soaps. The use of appropriate (glove-compatible) lotions twice a day also reduces skin irritation—as well as leading to a 50% increase in hand hygiene frequency in one study.4 Alcohol-based gels and foams are also generally more accessible than antiseptic soap and water, as the dispenser may be pocket-sized or placed conveniently near sites of patient care. It has been estimated that alcohol-based gels and foams require only about 25% of the time of going to a sink to wash one’s hands. However, soap and water should be used to remove particulate matter including blood and other body fluids or after five to ten applications of alcohol-based agent.

Adherence to hand hygiene guidelines (Tables 13-2 to 13-4) generally decreases as the frequency of indicated hand washing increases, as the workload increases, and as staffing decreases. CDC guidelines for health care providers traditionally focused on hand hygiene prior to entering and after leaving a patient room. More recently, the World Health Organization has developed a campaign highlighting the “5 Moments” of hand hygiene (Fig. 13-2). The campaign emphasizes the need to perform hand hygiene after each contact with a patient or their immediate environment.8

In an intensive care unit (ICU), hand hygiene for nurses is generally indicated about 20 times per hour, as compared with a normal ward where this number decreases to 8 times per hour.4 In the operating room (OR), frequent patient contact by the anesthesiologist requires frequent hand hygiene, probably at about the level of nurses in the ICU, while accessibility is often quite limited. Sinks are available only outside the OR. Therefore, alcohol-based agents should be available within hand’s reach of the anesthesia machine. Loftus et al.9 studied bacterial contamination of the anesthesia work area (adjustable pressure limiting valve complex and agent flowmeter) and cross-contamination of the sterile anesthesia stopcock during 61 first cases in their OR. They found an average increase in bacterial contamination of the work area of 115 colonies per surface area sampled during cases (95% confidence interval: 62–169; p < 0.001). Transmission of bacteria from the work area to the sterile stopcock in the patients’ intravenous tubing occurred in 32% of cases, including transmission of methicillin-resistant Staphylococcus aureus (MRSA) in two cases and vancomycin-resistant Enterococcus in one case. A high level of contamination of the work area (>100 colonies per surface area sampled) increased the risk of stopcock contamination 4.7 fold (95% confidence interval: 1.42–15.42; p = 0.011).

In a follow-up study, Koff et al.10 demonstrated that increased hand hygiene episodes (7–9 per hour compared to <0.5 per hour during the control period) triggered by an alarm and encouraged by education decreased work area contamination, decreased stopcock contamination from 32% to 8%, and decreased health care–associated infections significantly. Opportunities were not measured and hand hygiene episodes were not necessarily coordinated with one of the 5 Moments. Thus, transmission of bacterial contamination by the anesthesia provider appears to be common, a potential source of nosocomial infections, and largely preventable.9 Frequent hand hygiene by anesthesia providers has a direct and positive impact on patient outcomes.

Wearing gloves does not reduce the need for hand hygiene. Although gloves provide protection, bacterial flora from patients
may be cultured from up to 30% of health care workers who wear gloves during patient contact.4 Therefore, hand hygiene should be practiced both before putting on gloves and immediately after removal. Moreover, gloves should be removed or changed immediately after each procedure, including vascular access, intubation, and neuraxial anesthesia, because gloves become contaminated by patient contact just as hands do. Balancing hand hygiene with close attention to the patient during critical portions of the case (e.g., securing the airway) can be challenging. Double gloving and providing a convenient location for contaminated equipment have been suggested as effective approaches.11








Table 13-2. Indications for Hand Hygiene








  • When hands are visibly dirty or contaminated with proteinaceous material or are visibly soiled with blood or other body fluids, wash hands with either a nonantimicrobial soap and water or an antimicrobial soap and water.
  • If hands are not visibly soiled, use an alcohol-based hand rub for routinely decontaminating hands. Alternatively, wash hands with an antimicrobial soap and water.
  • Decontaminate hands before having direct contact with patients.
  • Decontaminate hands before donning sterile gloves when inserting a central intravascular catheter.
  • Decontaminate hands before inserting indwelling urinary catheters, peripheral vascular catheters, or other invasive devices that do not require a surgical procedure.
  • Decontaminate hands after contact with a patient’s intact skin (e.g., applying monitors, moving patient).
  • Decontaminate hands after contact with body fluids or excretions, mucous membranes, nonintact skin, and wound dressings if hands are not visibly soiled.
  • Decontaminate hands if moving from a contaminated-body site (e.g., mouth during tracheal intubation) to a clean-body site (e.g., adjusting gas flow, turning on ventilator, starting IV) during patient care.
  • Decontaminate hands after contact with inanimate objects (including medical equipment) in the immediate vicinity of the patient. Take care to reduce contamination of the anesthesia machine (e.g., after tracheal intubation) as well!
  • Decontaminate hands after removing gloves.
  • Before eating and after using a restroom, wash hands with a nonantimicrobial soap and water or with an antimicrobial soap and water.
  • Antimicrobial-impregnated wipes (i.e., towelettes) may be considered as an alternative to washing hands with nonantimicrobial soap and water. Because they are not as effective as alcohol-based hand rubs or washing hands with an antimicrobial soap and water for reducing bacterial counts on the hands of HCWs, they are not a substitute for using an alcohol-based hand rub or antimicrobial soap.
IV, intravenous (tube); HCW, health care worker.
Modified from: Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Am J Infect Control. 2002;30(8):S1.








Table 13-3. Hand Hygiene Technique








  • When decontaminating hands with an alcohol-based hand rub, apply the recommended volume of product to the palm of one hand and rub hands together, covering all surfaces of hands and fingers, until hands are dry.
  • When washing hands with soap and water, wet hands first with water, apply an amount of the product recommended by the manufacturer to hands, and rub hands together vigorously for at least 15 seconds, covering all surfaces of the hands and fingers. Rinse hands with water and dry thoroughly with a disposable towel. Use towel to turn off the faucet. Avoid using hot water because repeated exposure to hot water may increase the risk of dermatitis.
  • Liquid, bar, leaflet, or powdered forms of plain soap are acceptable when washing hands with a nonantimicrobial soap and water. When bar soap is used, soap racks that facilitate drainage and small bars of soap should be used.
Modified from: Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Am J Infect Control. 2002;30(8):S1.

Artificial and long fingernails, as well as chipped fingernail polish, are associated with higher concentrations of bacteria on the hands of health care workers. Artificial nails have been identified as a source in several hospital-associated outbreaks of infection with gram-negative bacilli and yeast, and CDC guidelines discourage wearing of artificial nails by health care workers in high-risk settings; many hospitals have banned wearing of artificial nails by any employee who has direct patient contact.4 It may also be appropriate to counsel patients scheduled for surgery that artificial nails may increase their risk of infection, although this has not been investigated. Large quantities of bacteria are

typically trapped under the fingernails, and 2002 CDC guidelines recommend that health care workers keep their nail tips trimmed to less than ¼ inch.4








Table 13-4. Skin Care








  • Provide health care workers with hand lotions or creams to minimize the occurrence of irritant contact dermatitis associated with hand antisepsis or hand washing.
  • Solicit information from manufacturers regarding any effects that hand lotions, creams, or alcohol-based hand antiseptics may have on the persistent effects of antimicrobial soaps being used in the institution, as well as on glove integrity. Select a combination of products that minimizes these effects.
Modified from: Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Am J Infect Control. 2002;30(8):S1.






Figure 13.2. World Health Organization schematic of the “5 Moments” for hand hygiene.

Bacteria may be cultured at higher concentrations from the skin beneath a ring. On the other hand, wearing a ring does not increase overall bacterial levels measured on the hands of health care workers. Therefore, it remains unclear whether transmission of infection could be reduced by prohibiting health care workers from wearing rings.4


Antisepsis

Masks have long been advocated as preventing SSI, and are used almost universally in the US operating rooms. Tunevall.12 studied the rate of wound infections in 3,088 patients over 115 weeks. In alternating weeks, OR personnel either wore masks or did not (personnel with active respiratory infections continued to wear masks). There was no difference in the rate of surgical wound infections (4.7% vs. 3.5%, respectively) in the two groups, nor in bacterial species cultured from the wounds. Friberg et al.13 demonstrated comparable air and surface contamination during sham surgery in a horizontal laminar airflow unit whether OR personnel wore a nonsterile hood and mask or a sterilized helmet aspirator system. When the head cover but not the mask was omitted, however, contamination increased three- to fivefold. These data suggest that wearing a head cover is useful for preventing SSI, while wearing a mask is not. Nonetheless, the study by Tunevall is a small one, and most hospital personnel continue to require a mask in the OR while surgical instruments are open. Moreover, the mask does serve the purpose of protecting the health care provider, particularly when combined with eye protection, and thus should most likely be used during tracheal intubation, emergence from anesthesia, and at other times when exposure to body fluids is likely.

Although the preponderance of postoperative surgical infections is caused by flora that are endogenous to the patient, environmental and airborne contaminants may also play a causative role. An important, but frequently overlooked, consideration is the role that traffic patterns into an OR can play in patient exposure to airborne organisms. A recent Israeli study of risk factors for surgical infection after total knee replacement demonstrated a trend toward increased infection rates within increased number of orthopedic surgeons or anesthetists present in the OR.14 This study reconfirmed a prior study showing a trend toward increased incidence of SSI as the number of people in the operating suite increases.15 However, it has been noted in one audit that physicians and nurses did little to limit the number of people through ORs during procedures.16 Current recommended practices are that traffic patterns should limit the flow of people through an OR that is in use, and that no more people than necessary should be in an OR during a procedure.17 The anesthesiologist is clearly in a position to play a leadership role in controlling human traffic through the OR.

Mermel et al.18 in 1991 demonstrated that central venous lines placed by the anesthesiologist in the OR became infected more often (relative risk [RR], 2.1; p = 0.03) than those placed by surgeons or other providers, whether in or out of the OR. Contributing factors appeared to be site of placement and the stringency of aseptic technique. Internal jugular vein insertion has a greater risk of infection (RR, 4.3; p < 0.01) compared with subclavian vein, although its other benefits may outweigh this risk. Raad et al.19 demonstrated that use of a maximal sterile barrier technique versus sterile gloves and small sterile drapes led to a significant reduction in central venous catheter-related infection from 7.2% to 2.2% (p = 0.03). Therefore, gowning and gloving, careful aseptic technique, and use of a wide sterile field should be routine.20 In anesthetized patients, the central line is ideally placed before the surgical site is draped in order to avoid contamination of the wire on the underside of the surgical drape.

Epidural abscess formation is an extremely rare but potentially catastrophic complication of neuraxial anesthesia and epidural catheter placement. Therefore, careful attention to aseptic technique and infection control is required. The most important consideration is to prevent contamination of the needle and catheter. Thus, hand washing, skin preparation, draping, and maintenance of a sterile field should be carefully observed. Gowning and wearing a mask likely play a smaller role, but are reasonable given the devastating consequences of infection. Finally, epidurals should probably be avoided in patients known or suspected to have bacteremia or deferred until after appropriate antibiotics are administered.


Antibiotic Prophylaxis

After antibiotics came into widespread use in the 1940s and 1950s, there was much debate over the possibility that antibiotic prophylaxis might prevent SSI. In 1957 Miles et al.21 used a guinea pig model for the proof of principle that administration of an antibiotic prior to contamination (incision) could reduce the risk of SSI. When appropriate antibiotics were given within 2 hours before or after intradermal injection of bacteria, they were effective in preventing invasive infection and necrosis. When given outside this window, they were not effective. This gave rise to the concept of a “decisive period” in which antibiotics will be effective, which remains a guiding principle of antibiotic prophylaxis. Miles et al. also demonstrated that injection of epinephrine intradermally prior to administration of antibiotics led to antibiotic failure, as demonstrated in an increased wound infection rate. This demonstrated the crucial role of local perfusion in delivering antibiotics to the site. Knighton et al.,22 using the same model, demonstrated that increased inspired oxygen was equally as effective as antibiotics in preventing infection, and that the two effects were additive (Fig. 13-3). Knighton et al.23 also delayed the administration of oxygen for up to 6 hours after inoculation and demonstrated no reduction in effect. Thus, the decisive period for oxygen is considerably longer than that of antibiotics.

Two surgeons at Washington University in St. Louis, Harvey Bernard and William Cole,24 reported on the first controlled clinical trial of the efficacy of antibiotic prophylaxis in 1964 and demonstrated a benefit in abdominal operations. Thereafter, numerous clinical trials were performed with somewhat variable results. Eventually these served to define the timing and population in which prophylactic antibiotics work. By the 1970s antibiotic prophylaxis for high-risk surgery—meaning clean-contaminated and contaminated cases—was becoming well accepted and widely used, although some skeptics remained. In 1992, Classen et al.25 published their prospective series including 2,847 patients undergoing clean or clean-contaminated surgical procedures at LDS Hospital in Salt Lake City, UT (Fig. 13-4). They demonstrated that the decisive period for SSI in humans undergoing surgery was essentially the same as for experimental infections in guinea pigs. That is, they found the lowest infection rate when antibiotics were given within 2 hours before or after incision and a rapid increase in SSI rate when they were given outside that range. The best results, though only by a small margin and not statistically significant, were within 0 to 60 minutes of surgery, and this subsequently became the clinical standard.

Antibiotic prophylaxis has now become standard for surgeries in which there is more than a minimum risk of infection.
Although not every surgery and situation has been studied, a strong rationale for the approach to prophylactic antibiotics has emerged. Several groups separately developed guidelines for use, culminating in recommendations published in 2004 by the National Surgical Infection Prevention Project.26 These guidelines emphasize timing and choice of appropriate agents. Guidelines generally do not specify antibiotic agents, although they give rationales for various choices.26 The agent for antibiotic prophylaxis must cover the most likely spectrum of bacteria presented in the surgical field (see Tables 13-5 and 13-6). The most commonly used antibiotic for surgical prophylaxis is cefazolin, a first-generation cephalosporin, as the potential pathogens for most surgeries are gram-positive cocci from the skin.26,27






Figure 13.3. The effect of oxygen and/or antibiotics on lesion diameter after intradermal injection of bacteria into guinea pigs. Note that at every level, oxygen adds to the effect of antibiotics and that increasing oxygen in the breathing mixture from 12% to 20% or from 20% to 45% exerts an effect comparable to that of appropriately timed antibiotics. (From: Rabkin J, Hunt TK. Infection and oxygen, Problem wounds: The Role of Oxygen. Edited by Davis J, Hunt TK. New York, Elsevier, 1988, pp 1, with permission.)

By definition, prophylactic antibiotics are given pre- or intraoperatively. The exact timing for the administration of the antibiotic depends on the pharmacology and half-life of the drug. It has been suggested that administration of prophylatic antibiotics is ideal within 30 minutes to 1 hour of incision.27,28 Drugs given by bolus administration (e.g., cefazolin) achieve adequate tissue concentration rapidly, so that giving these drugs within 0 to 30 minutes of incisions appears equally efficacious. Giving the antibiotics too early (so that the incision is more than 60 minutes after the dose) is a recurrent issue at many hospitals, especially for cases that require complex patient positioning. Giving the antibiotics closer to the incision time prevents this problem. Providing timely prophylactic antibiotics is relatively uncomplicated for antibiotics that can be given as a bolus dose (e.g., cephalosporins) or as an infusion over a few minutes (e.g., clindamycin) and thus provide tissue levels within minutes. For drugs like vancomycin that require infusion over an hour, coordination of administration is more complex. In general, it is considered acceptable if the infusion is started prior to incision. When a tourniquet is used, the infusion must be complete prior to inflation of the tourniquet. An appropriate dose based on body weight and volume of distribution should be given. Depending on the half-life, antibiotics should be repeated during long operations or operations with large blood loss.29 For example, cefazolin is normally dosed every 8 hours but the dose should be repeated every 4 hours intraoperatively.29 Finally, prophylactic antibiotics should be discontinued by 24 hours following surgery if postoperative dosing is selected at all. Prolonging the course of prophylactic antibiotics does not reduce the risk of infection but does increase the risk of adverse consequences of antibiotic administration,22 including resistance, Clostridium difficile infection, and sensitization.






Figure 13.4. The figure demonstrates rates of surgical wound infection corresponding to the temporal relation between antibiotic administration and the start of surgery. The number of infections and the number of patients for each hourly interval appear as the numerator and denominator, respectively, of the fraction for that interval. The trend toward higher rates of infection for each hour that antibiotic administration was delayed after the surgical incision was significant (z score = 2.00; p < 0.05 by the Wilcoxon test). (From: Classen DC, Evans RS, Pestotnik KS, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992:326;281, with permission.)

Unfortunately, MRSA is becoming a more common pathogen. Although it varies by country, region, and hospital, about 60% of S. aureus are MRSA. Independent risk factors identified for MRSA infection include prolonged use of prophylaxis, use of drains for more than 24 hours, and increasing number of procedures performed on the patient. Hand hygiene is among the most effective means of preventing development of MRSA since alcohol-based gel or foam used properly kills over 99.9% of all transient pathogens including MRSA. There does not appear to be a justification for using antibiotics effective against MRSA for prophylaxis in most clinical settings.

Because they have access to the patient during the 60 minutes prior to incision and can optimize timing of administration, anesthesiologists should work in consultation with the surgeon to use guidelines determined by the local infection control committee


to take initiative for administering prophylactic antibiotics. In this way, anesthesiologists can make a major contribution to preventing SSI. The Centers for Medicare and Medicaid Services has identified timely and appropriate antibiotic prophylaxis administration as a cornerstone of SSI prevention. Physician and hospital reimbursements are increasingly tied to such performance measures, meaning anesthesiologists also have an economic interest in ensuring adherence to guidelines.








Table 13-5. Recommended Drugs for Common Procedures

























































Procedure Primary Drug Alternate Drug (If Primary Contraindicated)
General orthopedics
Joint replacementsa
Spine surgery
Neurosurgery
Vascular surgery
Kidney transplant
Plastic surgery
Cefazolin Clindamycin
Cardiothoracica Cefazolin Cefuroxime
OR
Clindamycin
Colorectal Cefoxitin Ciprofloxacinb and metronidazole
Gynecology

Abdominal hysterectomy
Cefazolin Clindamycin and gentamicin
OR
Ciprofloxacinb and metronidazole
Open gastric and biliary—low risk Cefazolin Clindamycin
Open gastric and biliary—high risk

Biliary stent or other foreign body placement
Cefoxitin Clindamycin and gentamicin
OR
Clindamycin and ciprofloxacinb
Head and neck—low risk Cefazolin Clindamycin and gentamicin
Head and neck— high risk

Oral cavity involvement
Clindamycin Clindamycin and gentamicin
OR
Ertapenem
Genitourinary—low risk Cefazolin Clindamycin
Genitourinary— high risk
ESWL with nonsterile urine
Implant or other foreign body placement
Ciprofloxacinb  
Low-risk elective procedures without implants

  • Laparoscopic cholecystectomy
  • Breast biopsy
  • Inguinal hernia repair
  • Anorectal surgery
  • ESWL with sterile urine
  • Thyroidectomy
Cefazolin OR
No antibiotics
Clindamycin OR
No antibiotics
Cases in which therapeutic antibiotics have already been given in ER (e.g., appendicitis, acute cholecystitis) Continue antibiotics started in ER. Re-dose using guidelines for intraoperative re-dosing for the given antibiotic
NOTE:

  • Always confirm with surgeons at the time-out or earlier.

    • The surgeon may wish to delay antibiotics until after culture
    • Antibiotics may not be indicated (e.g., low risk, elective procedures such as laparoscopic cholecystectomy or breast biopsy where implants will not be used)
    • Make sure to record the reason for not giving antibiotics on the record

  • Ideally an antibiotic infusion should be completed before incision, but CMS guidelines consider starting the infusion before incision adequate. When possible, for drugs requiring slow (>30 min) infusion, the infusion should be initiated preoperatively.

    • When a tourniquet is used, the dose must be completed at least 5 minutes before the tourniquet is inflated.

  • Additional intraoperative doses should be given when there is significant blood loss (∼half to one blood volume). Use the recommended second dose for this purpose.
  • When therapeutic antibiotics are given for an infection or presumed infection (e.g., acute appendicitis), prophylactic antibiotics are not required. Each situation should be examined individually: When was the antibiotic given? Which antibiotic was used? In some cases, coverage of skin flora may be appropriate prior to skin incision, but often continuation of the therapeutic antibiotics is all that is required.
aVancomycin is indicated only for patients undergoing cardiothoracic or joint replacement surgery who are at high risk for MRSA (e.g. transferred from a skilled nursing facility, jail, or long-term care facility). Recent studies [Lee BY, Wiringa AE, Bailey RR, Goyal V, Tsui B, Lewis GJ, Muder RR, Harrison LH. The economic effect of screening orthopedic surgery patients preoperatively for methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2010 Nov;31(11):1130–1138.] suggest screening for MRSA may be a useful approach to identifying patients at high risk.
bNote that ciprofloxacin is infused over an hour. Ideally the infusion should be completed before incision, but CMS guidelines consider starting the infusion before incision adequate.
Used with permission from the University of Utah Health Care.








Table 13-6. Drugs and Doses Available Routinely for Antibiotic Prophylaxis



































































































































Drug Initial Dose (<80 kg) Initial Dose (≥80 kg) Timing Repeat Dosed (Interval) Interval for Serum Creatinine >3
Drugs to Be Given in the operating room (OR) by the Anesthesia Team
Cefazolin 1 g 2 g 0–60 min before incision 1 g (4 hr) 12 hr
Cefoxitin 2 g 2 g 0–60 min before incision 1 g Q3h 12 hr
Cefuroxime 1.5 g 1.5 g 0–60 min before incision 1.5 g Q4h
No repeat dose for serum creatinine >3
No re-dose
Clindamycin 600 mg 900 mg Infuse over 10–15 mina 600 mg Q6h 12 hr
Gentamicin 1.5 mg/kg 1.5 mg/kg Infuse over 10–15 mina 1 mg/kg Q6h 12 hr
Metronidazole 500 mg 500 mg Infuse over 30 mina 500 mg Q6h 12 hr
Aztreonamb 2 g 2 g Infuse over 30 mina 1 g Q4h 12 hr
Ertapenemc 1 g 1 g Infuse over 30 mina Q24h Q24h
Re-dose for Therapeutic Antibiotics Started Preoperatively
Piperacillin/Tazobactam (Zosyn)c 3.375 g 3.375 g Infuse over 30 mina Re-dose prior to incision if most recent dose >2 hr before incision; then re-dose Q4h 12 hr
Ampicillin/Sulbactam (Unasyn) 1.5 g 3 g Infuse over 30 mina Re-dose prior to incision if most recent dose >2 hr before incision; then re-dose Q4h 12 hr
Meropenemc 500 mg 500 mg Infuse over 30 mina Re-dose prior to incision if most recent dose >2 hr before incision; then re-dose Q4h 12 hr
Cefazolinc 1 g 2 g 0–60 min before incision Re-dose prior to incision if most recent dose >2 hr before incision; then re-dose 1 g Q4h 12 hr
Drug Initial Dose Timing Repeat Dose (Interval)
Drugs to be Given in the Preoperative Setting by a Ragistered Nurse
Vancomycine(<110 kg) 1.5 g Infuse over 1.5 hr;
Complete within 0–60 min prior to incision
Single re-dose at 8 hr
No repeat dose for serum creatinine >2
Vancomycine (≥ 110 kg) 2 g Infuse over 2 hr;
Complete within 0–60 min prior to incision
Single re-dose at 8 hr
No repeat dose for serum creatinine >2
Levofloxacin 500 mg Infuse over 60 min
Complete within 0–60 min prior to incision
500 mg Q12h
Ciprofloxacin (IV)f 400 mg Infuse over 60 min
Complete within 0–60 min prior to incision
400 mg Q6h
Ciprofloxacin (Oral)f 500 mg Take p.o. 60 min prior to OR 400 mg IV Q6h
aInfusion must begin prior to incision (CMS guidelines). Ideally, it should be completed before incision as well.
bAztreonam is indicated only for ventricular assist device placement; it is given in addition to vancomycin in those patients.
cProtocol used when therapeutic antibiotics are started preoperatively (e.g., in the Emergency Department) to treat actual or presumed infections, e.g., appendicitis or acute cholecystitis. Either the same drug can be continued or the usual prophylactic antibiotic agent for that procedure may be used. Note that, procedurally, these cases are not counted in our compliance monitoring, because these are therapeutic rather than prophylactic guidelines. These cases were created to provide guidance to providers in determining when to re-dose the antibiotics from the perspective of patient benefit.
dNote that dosing schedule is more frequent than for therapeutic use to maintain wound tissue levels throughout surgery and ongoing contamination.
Used with permission from the University of Utah Healthcare.
eVancomycin is indicated only for patients undergoing cardiac or joint replacement surgery who are at high risk of MRSA infection based on surveillance. These patients should be identified in the preoperative clinic. They should never be scheduled as first case, and should be asked to come in 3–4 hours before surgery so that vancomycin can be initiated in the preoperative setting.
fOral administration is acceptable for urology cases.


Mechanisms of Wound Repair

Wound healing is a complex process, requiring a coordinated repair response including inflammation, matrix production, angiogenesis, epithelization, and remodeling (Fig. 13-5). Many factors may impair wound healing. Systemic factors such as medical comorbidities, nutrition,30 sympathetic nervous system activation,31 and age32,33,34 have a substantial effect on the repair process. Local environmental factors in and around the wound including bacterial load,35 degree of inflammation, moisture content,36 oxygen tension,37 and vascular perfusion38 also have a profound effect on healing. Although all of these factors are important, perhaps the most critical element is oxygen supply to the wound. Wound hypoxia impairs each of the components of healing.39






Figure 13.5. Schematic of the processes of wound healing. (From Hunt T. Fundamentals of wound management in surgery, wound healing: Disorders of Repair. South Plainfield, NJ, Chirugecom, Inc., 1976, with permission.)

Although the role of oxygen is usually thought of in terms of aerobic respiration and energy production via oxidative phosphorylation, in wound healing oxygen is required as a cofactor for enzymatic processes and for cell-signaling mechanisms. Oxygen is a rate-limiting component in leukocyte-mediated bacterial killing and collagen formation because specific enzymes require oxygen at a partial pressure of at least 40 mm Hg.40,41 The mechanisms by which the other processes are oxygen-dependent are less clear, but these processes also require oxygen at a concentration much above that required for cellular respiration.42,43,44,45

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Jul 5, 2016 | Posted by in ANESTHESIA | Comments Off on Inflammation, Wound Healing, and Infection

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