Handbook of Clinical Anesthesia

Chapter 13

Inflammation, Wound Healing and Infection

Despite major advances in the management of patients undergoing surgery (e.g., aseptic technique, prophylactic antibiotics) and advances in surgical approaches (e.g., laparoscopic surgery), surgical wound infection and wound failure remain common complications of surgery (Hopf W, Chapman CR, Cochran A, et al: Inflammation, wound healing and infection. InClinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 271–289). Along with aseptic technique and prophylactic antibiotics, maintaining perfusion and oxygenation of surgical wounds is paramount.

  1. Infection Control
  2. Hand Hygiene(Table 13-1)
  3. Perhaps the most crucial component of infection prevention is frequent and effective hand hygiene. (In 1847, Ignaz Semmelweis instituted the use of hand washing between patient examinations.)
  4. Despite our current knowledge of the germ theory, hand hygiene remains an inexplicably neglected component of infection control.
  5. Even “clean” activities such as taking a patient's pulse or applying monitors can lead to hand contamination.
  6. 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.
  7. Plain (not antiseptic) soap and water are generally the least effective at

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reducing hand contamination. Soap and water are, however, the most effective at removing spores (Clostridium difficile or Bacillus anthracis).

Table 13-1 Hand Hygiene Technique

Decontaminating hands with an alcohol-based hand rub: Apply the recommended volume of product to the palm of one hand.
Rub the hands together, covering all surfaces of the hands and fingers until the hands are dry.
When washing hands with soap and water:
Wet the hands first with water.
Apply an amount of product recommended by the manufacturer to the hands.
Rub the hands together vigorously for at least 15 seconds, covering all surfaces of the hands and fingers.
Rinse the hands with water and dry thoroughly them with a disposable towel.
Use a 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 non-antimicrobial soap and water.
When bar soap is used, soap racks that facilitate drainage and small bars of soap should be used.

  1. Antiseptics containing 60% to 95% ethanol with a water base are germicidal and effective against gram-positive and gram-negative bacteria and lipophilic viruses (herpes simplex, human im-munodeficiency, influenza, respiratory syncytial, vaccinia viruses, hepatitis B and C viruses).
  2. Chlorhexidine is a cationic bisbiguanide that is germicidal against gram-positive bacteria and lipophilic viruses. It has substantial persistence on the skin, and the Centers for Disease Control and Prevention has identified it as the topical agent of choice for skin preparation in central venous catheter insertion. Chlorhexidine 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.
  3. Iodine and iodophors (iodine with a polymer carrier) are bactericidal against gram-positive,

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gram-negative, and some spore-forming bacteria. Allergies to this class of topical agent are common.

  1. Wearing gloves does not reduce the need for hand hygiene. Hand hygiene should be practiced both before putting on gloves and immediately after removal.
  2. Wearing rings 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.
  3. Antisepsis
  4. Masks have long been advocated as preventing surgical site infection (SSI); however, data suggest that wearing a head cover is useful for preventing SSIs but wearing a mask is not.
  5. Masks do 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 and at other times when protection from body fluids is appropriate.
  6. Most postoperative surgical infections are caused by flora that are endogenous to the patient; environmental and airborne contaminants may also play a causative role.
  7. An important but frequently overlooked consideration is the role that traffic patterns into an operating room can play in patient exposure to airborne organisms. Current recommended practices are that traffic patterns should limit the flow of people through an operating room that is in use and that no more people than necessary should be in an operating room during a procedure.
  8. Gowning, gloving, careful aseptic technique, and use of a wide sterile field should be routine for placement of central venous lines.
  9. Epidural abscess formation is an extremely rare but potentially catastrophic complication of neuraxial anesthesia and epidural catheter placement. The most important consideration is preventing contamination of the needle and catheter.
  10. Hand washing, skin preparation, and draping and maintenance of a sterile field should be used.
  11. Gowning and wearing a mask, however, are unlikely to reduce the risk of infection.

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  1. Epidurals should probably be avoided in patients known or suspected to have bacteremia or should be deferred until after appropriate antibiotics have been administered.
  2. Antibiotic Prophylaxis(Tables 13-2 and 13-3)
  3. Antibiotic prophylaxis is standard for surgeries in which there is more than a minimum risk of infection.
  4. Recommendations published in 2004 by the National Surgical Infection Prevention Project emphasize timing and choice of appropriate agents.
  5. The agent selected for antibiotic prophylaxis must cover the most likely spectrum of bacteria pre-sented in the surgical field.
  6. The most commonly used antibiotic for surgical prophylaxis is cefazolin, a first-generation cephalosporin, because the potential pathogens for the vast majority of surgeries are gram-positive cocci from the skin.
  7. The exact timing for the administration of the antibiotic depends on the pharmacology and half-life of the drug. Ideally, administration of the prophylaxis should be within 30 minutes to 1 hour of incision. In general, it is considered acceptable if the infusion is started before incision. When a tourniquet is used, the infusion must be complete before inflation of the tourniquet.
  8. Administration of antibiotics is uncomplicated when the drug can be given as a bolus dose (e.g., cephalosporins) or as an infusion over a few minutes (e.g., clindamycin) and thus provides tissue levels within minutes.
  9. For drugs such as vancomycin that require infusion over an hour, coordination of administration is more complex.
  10. Depending on half-life, antibiotics should be repeated during long operations or operations with large blood loss. (Cefazolin is normally dosed every 8 hours, but the dose should be repeated every 4 hours intraoperatively.)
  11. Prophylactic antibiotics should be discontinued by 24 hours after surgery because prolonging the course of prophylactic antibiotics does not reduce the risk of infection but does increase the risk of adverse consequences of antibiotic administration.

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Table 13-2 Guidelines for Prophylactic Antibiotics in Adult Patients

Hip and Knee Arthroplasty, Extradural Spine Surgery, Cardiothoracic, Vascular Surgery, and Kidney Transplantation

Drug

Dose

Timing

Additional Dose

Cefazolin

<80 kg: 1 g
≥80 kg: 2 g

<60 min before incision as a bolus over 3–5 min; with bolus dose, tissue levels are adequate in a few minutes

Every 4 hours
Exclude kidney transplants

Neurosurgery (Cranial and Intradural Spine)

Ceftriaxone

<80 kg: 1 g

<60 min before incision as a bolus over
3–5 min

Every 12 hours

Liver Transplantation

Ceftriaxone

<80 kg: 1 g
≥80 kg: 2 g

<60 min before incision as a bolus over 3–5 min

Every 12 hours

Liver Transplantation: β-Lactam Allergy

Vancomycin

1 g

Start infusion on arrival in the operating room (after monitors are attached); infuse over 30–60 min

Every 12 hours

Clindamycin

<100 kg:
600 mg

<60 min before incision as infusion over 10–15 min

Every 6 hours

Colon Surgery

Cefotetan

<80 kg: 1 g
≥80 kg: 2 g

<60 min before incision as a bolus over 3–5 min

Every 6 hours

Colon Surgery: β-Lactam Allergy

Ciprofloxacin and

400 mg

<60 min before incision as infusion over 30 min

Every 6 hours

Metronidazole

500 mg

Vaginal and Abdominal Hysterectomy

Cefazolin or

<80 kg: 1 g

<60 min before incision as a bolus over 3–5 min

Every 4 hours
Every 6 hours

Cefotetan (if bowel involved)

≥80 kg: 2 g

Vaginal and Abdominal Hysterectomy: β-Lactam Allergy

Ciprofloxacin and

400 mg

<60 min before incision as infusion over 30 min

Every 6 hours

Metronidazole or

500 mg

Clindamycin and

600 mg

<60 min before incision as infusion over 10–15 minutes

Every 6 hours

Gentamicin

1.5 mg/kg

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Table 13-3 Guidelines for Prophylactic Antibiotics in Pediatric Patients

Drug

Dose

Cefazolin

20–30 mg/kg

Ceftriaxone

25 mg/kg

Cefotetan

20–30 mg/kg

Cefuroxime

50 mg/kg

Vancomycin

15 mg/kg (as an infusion over 30–60 min)

Gentamicin

2 mg/kg

Clindamycin

15 mg/kg

Metronidazole

10 mg/kg

Ciprofloxacin

Not recommended

  1. Methicillin-resistant Staphylococcus aureus(MRSA) is becoming a more common pathogen. Hand hygiene is among the most effective means of preventing development

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of MRSA because when used properly, alcohol-based gel kills more than 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.

  1. Anesthesiologists should work in consultation with surgeons to use guidelines determined by the local infection control committee to take initiative for administering prophylactic antibiotics.
  2. Mechanisms of Wound Repair
  3. Many factors may impair wound healing (Table 13-4).
  4. Initial Response to Injury
  5. Wound healing has traditionally been described in four separate phases: hemostasis, inflammation, proliferation, and remodeling. Each phase is composed of complex interactions between host cells, contaminants, cytokines, and other chemical mediators that, when functioning properly, lead to repair of injury. These processes are highly conserved across species, indicating the critical importance of the inflammatory response that directs the process of cellular and tissue repair.
  6. In wounds, local blood supply is compromised at the same time that metabolic demand is increased. (The wound environment becomes hypoxic and acidotic.) Hypoxia acts as a stimulus to repair but also leads to poor healing and increased susceptibility to infection.

Table 13-4 Factors That May Impair Wound Healing

Oxygen supply to the wound (most important element)
Systemic Factors
Medical comorbidities
Nutrition
Sympathetic nervous system activation
Age
Local Environmental Factors
Bacterial load
Degree of inflammation
Moisture content
Oxygen tension
Vascular perfusion

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  1. Resistance to Infection
  2. After a disruption of the normal skin barrier, successful wound healing requires the ability to clear foreign material and resist infection. Neutrophils provide nonspecific immunity and prevent infection. In the absence of infection, neutrophils disappear by about 48 hours after surgery.
  3. Resistance to infection is critically impaired by hypoxia and wound healing becomes more efficient as PO2increases even to very high levels (500–1,000 mm Hg as produced by hyperbaric oxygenation).
  4. Proliferation.The proliferative phase (granulation and epithelization) normally begins approximately 4 days after injury, concurrent with a waning of the inflammatory phase.
  5. Neovascularizationin wounds proceeds both by angiogenesis (vessel growth via budding from existing vessels) and vasculogenesis.
  6. Collagen and Extracellular Matrix Deposition
  7. New blood vessels grow into the matrix that is produced by fibroblasts.
  8. Wound strength, which results from collagen deposition, is highly vulnerable to wound hypoxia.
  9. Epithelizationis characterized by replication and migration of epithelial cells across the skin edges in response to growth factors. Topical oxygen applied in a manner that does not dry out epithelial cells has been advocated as a method of increasing the rate of epithelization.
  10. Maturation and Remodeling
  11. The final phase of wound repair is maturation, which involves ongoing remodeling of the granulation tissue and increasing wound tensile strength.
  12. Contraction is inhibited by the use of high doses of corticosteroids (even steroids given several days after injury have this effect). In wounds in which contraction is detrimental, this effect can be beneficial.
  13. Some wounds heal to excess. Hypertrophic scar (most common after burn injury) and keloids are common forms of abnormal scar tissue caused by abnormal responses to healing. Keloids likely have a genetic predisposition.

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III. Wound Perfusion and Oxygenation

  1. Complications of wounds include failure to heal, infection, and excessive scarring or contracture.
  2. All surgical procedures lead to some degree of contamination that must be controlled by local host defenses. The initial hours after contamination represent a decisive period during which inadequate local defenses may allow an infection to become established.
  3. Normally, wounds on the extremities and trunk heal more slowly than those on the face. The major difference in these wounds is the degree of tissue perfusion and thus the wound tissue oxygen tension.
  4. Ischemic or hypoxic tissue is highly susceptible to infection and heals poorly, if at all. A high PO2is needed to force oxygen into injured and healing tissues, particularly in subcutaneous tissue, fascia, tendon, and bone, the tissues at highest risk for poor healing.
  5. In surgical patients, the rate of wound infections is inversely proportional and collagen deposition is directly proportional to postoperative subcutaneous wound tissue oxygen tension.
  6. High oxygen tensions (>100 mm Hg) can be reached in wounds, but only if perfusion is rapid and arterial PO2is high. Oxygen-carrying capacity (hemoglobin concentration) is not particularly important to wound healing, provided that perfusion is normal.
  7. Peripheral vasoconstriction, which results from central sympathetic control of subcutaneous vascular tone, is probably the most frequent and clinically the most important impediment to wound oxygenation (Table 13-5).
  8. Prevention or correction of hypothermia and blood volume deficit decreases wound infections and increases collagen deposition in patients undergoing major abdominal surgery.
  9. Preoperative systemic (forced air warmer) or local warming decrease wound infections.
  10. Delivery of antibiotics also depends on perfusion.
  11. Patient Management
  12. Preoperative Preparation(Table 13-6)
  13. Intraoperative Management(Table 13-7)

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Table 13-5 Causes of Sympathetically Induced Peripheral Vasoconstriction

Hypothermia (anesthetic drugs, exposure to cold, redistribution of body heat from core to the periphery)
Pain
Fear
Blood volume deficit
Pharmacologic agents
   Nicotine
   β-Adrenergic antagonists
   α-1 Agonists

  1. Careful surgical technique is fundamental to optimal wound healing.
  2. Delicate handling of the tissue, adequate hemostasis, and surgeon experience lead to healthier wounds.
  3. Volume Management
  4. Surgical stress results in increased intravenous fluid requirements.
  5. The major complications associated with hypervolemia include pulmonary edema, congestive heart failure, edema of the gut with prolonged ileus, and possibly an increase in cardiac arrhythmias.
  6. Aside from hemodynamic instability, the major complications of hypovolemia include decreased oxygenation of surgical wounds (which predisposes to wound infection), decreased collagen formation, impaired wound healing, and increased wound breakdown.
  7. Intraoperative transesophageal echocardiography has been advocated as a more useful monitor of intraoperative volume status than pulmonary artery catheters.

Table 13-6 Preoperative Checklist

Assess and optimize cardiopulmonary function (correct hypotension).
Treat vasoconstriction (blood volume, pain, anxiety).
Assess recent nutrition and treat as appropriate.
Treat existing infection (clean and treat skin infections).
Improve or maintain blood sugar control.

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Table 13-7 Intraoperative Management

Administer appropriate prophylactic antibiotics at the start of any procedure in which infection is highly probable or has potentially disastrous consequences. Antibiotic levels should be maintained during long operations.
Keep patients warm.
Observe gentle surgical technique with minimal use of ties and cautery.
Keep wounds moist.
Use antibiotic irrigation in contaminated cases.
Elevate PaO2.
Use delayed closure for heavily contaminated wounds.
Use appropriate sutures (and skin tapes).
Use appropriate dressings.

  1. Current recommendations include replacing fluid losses based on standard guidelines for the type of surgery, replacement of blood loss, and replacement of other ongoing fluid losses (Table 13-8).
  2. Postoperative Management(Table 13-9)
  3. Wounds are most vulnerable in the early hours after surgery. Although antibiotics lose their effectiveness after the first few hours, oxygen-mediated natural wound immunity lasts longer.

Table 13-8 Standard Volume Management Guidelines for Surgical Patients

Fluid Requirement = Deficit + Maintenance (baseline plus replacement) + Estimated blood Loss (and other sensible fluid losses)
Deficit = Maintenance (1.5 mL/kg) × hours NPO
Adjust for fever, high nasogastric output, bowel preps
Replace estimated blood loss with 3:1 crystalloid and 1:1 with colloid
Maintenance Requirements for Different Surgeries
Superficial surgical trauma (peripheral surgery): 1–2 mL/kg/hr
Minimal surgical trauma (head and neck, hernia, knee surgery): 3–4 mL/kg/hr
Moderate surgical trauma (major surgery without exposed abdominal contents): 5–6 mL/kg/hr
Severe surgical trauma (major abdominal with exposed abdominal contents): 8–10 mL/kg/hr

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Table 13-9 Postoperative Management

Keep the patient warm.
Provide analgesia to keep the patient comfortable, if not pain free.
Patient report and the ability to move freely are the best signs of adequate pain relief.
Only use one more doses of antibiotic unless an infection is present or contamination continues.
Keep up with third-space losses (fever increases fluid losses).
Assess perfusion and react to abnormalities.
Avoid diuresis until pain is gone and the patient is warm.
Assess losses (including thermal losses) if the wound is open.
Assess the need for parenteral or enteral nutrition and respond.
Continue to control hypertension and hyperglycemia.

From Hunt T: Fundamentals of wound management in surgery, Wound Healing:
Disorders of Repair. South Plainfield, NJ, Chirugecom, Inc, 1976, with permission.

  1. Even a short period of vasoconstriction during the first day after surgery is sufficient to reduce oxygen supply and increase the risk of infection. Correction and prevention of vasoconstriction in the first 24 to 48 hours after surgery has significant beneficial effects.
  2. Strict glycemic control is also important, although the best method to achieve this in the non-intensive care unit setting has not yet been established.
  3. Local perfusion is not assured until patients have a normal blood volume, are warm and pain free, and are receiving no vasoconstrictive drugs.
  4. Warming should continue until patients are thoroughly awake and active and can maintain their own thermal balance.
  5. Low output may indicate decreased renal perfusion, but normal or even high urine output has little correlation to wound or tissue PO2.
  6. Physical examination (capillary return, eye turgor, warm and dry skin) of the patient is a better guide to hypovolemia and vasoconstriction.
  7. Vasoconstrictive drugs (nicotine, beta-blockers) should be avoided.
  8. Maintenance of tissue PO2requires attention to pulmonary function after surgery. Administration of supplemental oxygen via a face mask or nasal cannulae may increase safety in patients receiving systemic opioids. Pain control also appears

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important because it favorably influences both pulmonary function and vascular tone.

  1. Summary
  2. During surgery, appropriate antibiotic use, prevention of vasoconstriction through volume and warming, and maintenance of a high PaO2(300–500 mm Hg) are key.
  3. After surgery, the focus should remain on prevention of vasoconstriction through pain relief, warming, and adequate volume administration in the postanesthesia care unit.

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine

Title: Handbook of Clinical Anesthesia, 6th Edition

Copyright ©2009 Lippincott Williams & Wilkins

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