New techniques are being tested to stop nosocomial infections in hospitalized, ventilator-dependent patients.
Pneumonia is the second most common nosocomial infection (after urinary tract infection) in the United States, and is the leading cause of death as a result of nosocomial infection.1 Intubation and mechanical ventilation greatly increase the risk of bacterial pneumonia.1 In fact, nosocomial pneumonia that occurs in association with mechanical ventilation has become a clinical entity so well recognized that a relatively new term used to describe it-ventilator-associated pneumonia (VAP)-has gained widespread acceptance.
Placement of an endotracheal tube allows bacteria to enter the lower respiratory tract directly, and it promotes colonization through any of three mechanisms: interference with the cough reflex, inhibition of mucociliary clearance, and stimulation of excessive mucus secretion. VAP is a significant problem because it causes considerable morbidity and mortality, adds substantially to the length of hospitalization, and adds billions of dollars to health care costs each year.2 According to the American Lung Association,1 nosocomial pneumonia occurs at a rate of 5 to 10 cases per 1,000 hospital admissions (0.5 percent to 1 percent), with the incidence increasing by as much as 6 to 20 times in patients receiving mechanical ventilatory support. An understanding of pathogenic mechanisms and risk factors will facilitate the implementation of preventive strategies.
Any patient in the hospital can develop nosocomial pneumonia by either aspirating contaminated substances or inhaling airborne particles. Such contaminants and particles can come from various respiratory and medical devices, the hospital environment, other patients, and even hospital staff. Aspiration occurs when food, fluid, or gastric contents enter the patient’s lungs. The signs and symptoms of aspiration may be insidious; they include fever, confusion, agitation, lethargy, and a productive cough that evolves over several days.
In hospitals, aspiration occurs most frequently in patients who cannot swallow normally or who have altered levels of consciousness, mechanical ventilatory support, or gastric or endotracheal tubes. A patient who is fed by someone else or who has dementia is also at increased risk. Inhalation of airborne particles occurs when contaminated droplets enter the patient’s lungs through respiratory or anesthesia equipment, ventilation systems, humidifiers, showers, faucets, or the coughing and sneezing of others. Pathogens may then proliferate in the patient’s respiratory tract and lead to infection.
Another possible mechanism promoting the development of nosocomial pneumonia is translocation, a poorly understood process through which bacteria cross from the intestine to the blood vessels or lymph nodes. Once this happens, the intestinal bacteria can spread to other parts of the body, such as the lung. Several factors may contribute to bacterial translocation. These include excessive bleeding, the presence of systemic endotoxins, bacterial overgrowth in the intestine, immunosuppression, and total parenteral nutrition. Patients may become colonized with nosocomial pathogens within 48 to 72 hours of hospital admission.
According to the National Nosocomial Infections Surveillance system of the Centers for Disease Control and Prevention,3 the pathogens most commonly responsible for nosocomial pneumonia and VAP are Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter species, Klebsiella pneumoniae, and Haemophilus influenzae (Table 1, page 88). In fact, these species account for approximately 60 percent of all cases of nosocomial pneumonia. Viruses are not an important cause of nosocomial pneumonia. Fungal causes of nosocomial pneumonia, such as Aspergillus species and Candida albicans, are usually seen only in immunocompromised patients.
Risk factors and host defenses that are altered by the placement of an artificial airway contribute to the development of VAP once colonization occurs.
These include underlying illness (particularly chronic obstructive pulmonary disease), immunosuppression, coma, prolonged hospitalization, thoracic or ab- dominal surgery, and being age 65 or older.
Hand washing is important in reducing the incidence of VAP. The administration of antibiotics in the intensive care unit (ICU) is also an important factor in the development of VAP. Prior antibiotic therapy can lead to the emergence of antibiotic-resistant strains of bacteria. Patients who previously have been treated with antibiotics are more likely than those who have not to be infected by high-risk pathogens such as P aeruginosa.4 In addition, the incidence of sepsis, septic shock, and death may be increased in patients infected by resistant strains of bacteria.2
Endotracheal Tube Factors
Direct effects of an endotracheal tube include mucosal injury, impaired mucociliary function, and a reduction in upper-
airway defenses due to an ineffective cough mechanism. The presence of an endotracheal tube may contribute indirectly to the risk of VAP by creating binding sites for bacteria in the bronchial tree and by increasing mucus secretion. Stagnation of secretions promotes the growth and proliferation of bacterial pathogens. In addition, the endotracheal tube may serve as a reservoir for bacteria that are inaccessible to host defense systems and antibiotic treatment.
Bacterial colonization of the oropharynx may also contribute to the risk of VAP. Endotracheal intubation allows leakage around the tube of oropharyngeal secretions laden with bacteria. For this reason, continuous aspiration of subglottic secretions may reduce the incidence of VAP.1
The risk of VAP caused by contaminated respiratory equipment is low.1 The internal machinery of mechanical ventilators is not considered an important source of bacterial contamination. Most ventilators have either bubble-through or wick humidifiers that produce little or no aerosol for humidification; therefore, the risk of their causing pneumonia is low. Bacteria from the patient’s oropharynx, however, can contaminate the inspiratory circuit, and spillage of contaminated condensate into the patient’s tracheobronchial tree may increase the risk of VAP.
Several gastrointestinal factors are believed to increase the risk of VAP. These include the presence of a nasogastric tube, gastric alkalinization, and use of enteral feedings.4 Gastric alkalinization with antacids and/or histamine2-receptor antagonists may be performed to prevent stress-induced gastritis, but it has been implicated as a risk factor for VAP.3 Alkalinizing agents increase the pH of the gastric secretions; this allows bacteria to grow in the stomach and may affect the normal flora of the entire gastrointestinal tract. Pathogens that proliferate in gastric secretions may increase the likelihood of VAP. The alkalinized stomach is a particularly attractive breeding ground for gram-negative enteric bacteria. A gastric pH of more than 3.5 is associated with increased bacterial colonization of the lower respiratory tract.5,6
The supine position may predispose some intubated patients to aspirate gastric contents. This can occur even if the endotracheal tube cuff is inflated. Some authorities6 believe that the risks of aspiration and VAP can be reduced by keeping the head of the patient’s bed at an angle of 45 degrees or more. In addition, continuous lateral rotational therapy (use of a bed that rotates the patient continuously from side to side) has been purported to improve mucociliary clearance and facilitate the drainage of pulmonary secretions.6,7
Based on an understanding of the pathogenic mechanisms and risk factors for VAP, several preventive strategies can be recommended. These can be divided into methods used to reduce bacterial colonization, techniques used to reduce the aspiration of oropharyngeal secretions, and strategies used to reduce the aspiration of gastric secretions. In addition, the use of noninvasive positive-pressure ventilation (NPPV) in patients for whom endotracheal intubation is not mandatory may reduce the risk of VAP. The initiation of appropriate empiric antibiotic therapy in patients who have developed the signs and symptoms of VAP may also prevent the progression of pneumonia.
REDUCTING BACTERIAL COLONIZATION
Perhaps the most effective means of preventing VAP caused by exogenous microorganisms is consistent and thorough hand washing. All health care personnel should wash their hands before and after contact with patients. Hands should also be washed before and after contact with a patient’s respiratory equipment and after contact with respiratory secretions. Hand washing should be performed whether or not gloves are worn.
In addition to hand washing, universal precautions should be observed. Gloves should be worn if contact with respiratory secretions or contaminated objects is anticipated. Gowns are useful if it is expected that the health care worker’s clothes may become soiled. The cornerstone of the successful implementation of universal precautions is the regular changing of gloves and gowns. Gloves and gowns should be changed, and hands should be washed, after any contaminating event and before touching any other patient, object, or environmental surface.
Maintenance of oral and nasal hygiene is another useful means of reducing bacterial colonization. Instead of just swabbing the patient’s mouth, caregivers should brush the patient’s teeth and apply a mouthwash solution to the oral cavity. In addition, oral secretions should be adequately removed through suction. Regular oral assessment should be a part of the routine care of all intubated patients.
Meticulous nasal care and cleansing of the nasopharynx may also reduce bacterial colonization. Nasal hygiene is a frequently neglected component of the overall care of the intubated patient. If a nasoenteric or nasotracheal tube has been in place for a prolonged period, secretions may accumulate in the nares. Nasopharyngeal secretions should be removed using suction regularly.
Because stagnating lower-pulmonary secretions create a nourishing environment for bacterial pathogens, routine turning and positioning of the patient are often recommended to promote mobilization of secretions and reduce the likelihood of colonization. The use of beds that provide continuous lateral rotation therapy is currently being evaluated in clinical trials to determine whether they are associated with a true reduction in the incidence of VAP. Even in the absence of conclusive data, however, frequent postural changes make good clinical sense.
An issue that is constantly undergoing reevaluation is how frequently endotracheal suction should be used. Many institutional ICU protocols call for suction to be performed only when there is an apparent need for it. The rationale for this approach is that infrequent suction reduces trauma to the airways. Applying this rationale, however, means that patients who have only minimal secretions may remain without suction for many hours. Because stagnating mucus and the lack of an adequate cough reflex are risk factors for the development of VAP, suction may be needed periodically. Although no uniform guidelines exist regarding this issue, it is probably beneficial to perform suction on all intubated patients on at least a semiregular basis.
If prophylaxis for stress ulcers is warranted (as for patients who remain intubated for long periods of time), then the use of agents that do not alter the gastric pH, such as sucralfate, may be preferred. Unfortunately, it is not always feasible to use sucralfate because it must pass through the stomach to be therapeutically effective, and many critically ill patients have jejunostomy tubes. For such cases, protocols should be developed that stipulate precise clinical indications for stress ulcer prophylaxis.
A new approach to the reduction of bacterial colonization (and hence VAP risk) is selective digestive decontamination. This procedure has been evaluated in mechanically ventilated patients in Europe.8,9 In selective digestive decontamination, a nonabsorbable antibiotic paste is applied locally to the oropharynx and is administered via nasogastric tube three or four times daily. Unfortunately, the results of clinical trials investigating the usefulness of selective digestive decontamination in reducing the risk of VAP have been mixed.
Because the aspiration of oropharyngeal secretions is a primary mechanism for the development of VAP, strategies that reduce aspiration may significantly decrease the risk of VAP. Perhaps the simplest method for reducing risk is to extubate patients as soon as possible. The longer an endotracheal tube remains in place, the greater the amount of stagnant lower pulmonary secretions and the greater the chance for bacterial colonization. In addition, it is important to take precautions to prevent accidental extubation (because reintubation increases the risk of VAP).5 Endotracheal cuff pressures should be checked periodically to make sure that a pressure of at least 20 cm H2O is maintained. The incidence of VAP may increase when endotracheal cuff pressures fall below that level. It is also important to perform thorough oral suction whenever endotracheal tubes are repositioned in order to reduce the pooling of secretions above the tube.
The use of a special dual-lumen endotracheal tube to facilitate the continuous suction of subglottic secretions has been evaluated in Europe as a means of reducing the risk of VAP.10 Clinical trials of the effectiveness of the dual-lumen tube are under way in the United States.
Several strategies can be used to reduce the potential for the introduction of gastrointestinal contents and microorganisms into the respiratory tract. Elevating the head of the patient’s bed 30 degrees to 45 degrees, particularly if he/she is being fed enterally, helps avoid gastric reflux and reduces the risk of aspiration. Nasogastric tubes, if used, should be removed as soon as possible. If long-term enteral feedings are required, then patients should be evaluated for placement of a gastrostomy or jejunostomy feeding tube. If nasogastric tubes must be used, then the verification of postpyloric placement is essential. Whatever feeding method is used, bowel sounds should be assessed regularly to ensure that the rate and volume of enteral feeding are appropriate for the patient’s gastrointestinal function; feeding too much or too rapidly can increase the risk of regurgitation and aspiration.
The use of NPPV instead of endotracheal intubation for patients with acute respiratory failure is controversial. It may, however, offer several advantages, not the least of which is a reduced risk of VAP. According to Umberto Meduri, MD, associate professor of pulmonology at the University of Tennessee School of Medicine and a pulmonologist at Bowld Hospital in Memphis, “NPPV offers several potential advantages over endotracheal intubation. These include flexibility of use, avoidance of complications associated with the use of endotracheal tubes such as pneumonia and sinusitis, preservation of the ability to speak and swallow, and improved patient comfort. Patient selection is very important,” Meduri adds. “Not all patients are candidates for noninvasive ventilation. The patient must be alert and cooperative. Contraindications include cardiovascular hypotension and significant arrhythmia, or anything that puts the patient at high risk of aspiration. If a patient has any contraindications for noninvasive ventilation, the physician should use intubation instead.”
According to Meduri, NPPV and endotracheal intubation have roughly equal mortality rates. In addition, NPPV appears to be effective in ameliorating pulmonary edema. The use of NPPV is being investigated in several ongoing clinical trials. Numerous questions about the procedure remain unanswered, including which patients it suits best.
Severe, established VAP is usually treated with a combination empiric regimen. Traditionally, this has included an antipseudomonal penicillin plus an aminoglycoside. Any of the drugs suitable for monotherapy may be substituted for the antipseudomonal penicillin. Several different regimens may be employed for patients with significant penicillin allergy. These include: a quinolone plus an aminoglycoside; aztreonam (a nonpenicillin, noncephalosporin beta-lactam antibiotic) plus an aminoglycoside; and aztreonam plus a quinolone.
Systemic antibiotic therapy is inappropriate for the prophylaxis of VAP because the indiscriminate use of antibiotics can lead to the development of resistant bacterial strains. Antibiotics, however, are the cornerstone in the management of established disease. Antibiotic therapy for VAP should be specific for known microorganisms with established susceptibilities. In cases in which the causative pathogen cannot be isolated, empiric therapy usually includes coverage against the most common agents. In many cases, this is achieved through the use of combination therapy.
In choosing antibiotics, the specific pharmacologic features of the antibiotics should be considered in addition to the cost of therapy. The penetration of antibiotics to the site of infection is important. Some agents penetrate into respiratory secretions better than others. For example, aminoglycosides have relatively poor penetration, while quinolones can achieve concentrations in bronchial secretions that equal or exceed serum levels. Because of these considerations, an aminoglycoside should never be used alone in the treatment of a gram-negative lung infection.
Consideration of bactericidal mechanisms may also be important in antibiotic selection and dosing. Agents such as the quinolones and the aminoglycosides are bactericidal in a dose-dependent fashion, killing more rapidly at high concentrations. In addition, these agents have a prolonged postantibiotic effect, allowing them to suppress bacterial growth even after the antibiotic concentration becomes low. Other antibiotics, such as vancomycin and the cephalosporins, are bactericidal but in a time-dependent fashion: the killing effect depends on how long the treatment lasts, not the dose used.
Nosocomial pneumonia remains an important cause of morbidity and mortality in hospitalized, ventilator-dependent patients. By implementing a variety of strategies proven to reduce the risk of VAP, health care personnel may be able to decrease the occurrence of VAP and improve patient outcomes. Simple and effective strategies are available to reduce bacterial colonization and prevent the aspiration of oropharyngeal and gastric secretions. The application of newer preventive techniques (such as NPPV, continuous lateral rotation therapy, and dual-lumen endotracheal tubes that facilitate subglottic suction) is undergoing rigorous clinical testing to determine whether these techniques play a role in reducing the risk of VAP. N
John D. Zoidis, MD, is a contributing writer for RT.
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