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CHAPTER 59: Ventilator-Associated Pneumonia 523

to our data on 567 ventilated patients, those who had received antimi-
TABLE 59-2 Independent Factors for VAP Identified by Multivariate Analysis
in Selected Studies crobial therapy within the 15 days preceding lung infection were not
at higher risk for development of VAP, but 65% of the lung infections
Host Factors Intervention Factors Other that occurred in patients who had received broad-spectrum antimi-
Serum albumin <2.2 g/dL H blockers ± antacids Season crobial drugs versus only 19% of those developing in patients who had
2 not received antibiotics were caused by Pseudomonas or Acinetobacter
Age ≥60 years Paralytic agents, continuous intravenous spp. 12,59,88,93-95 In a 1988 investigation on mechanically ventilated baboons
sedation
treated with a variety of regimens of intravenous and topical antibiotics
ARDS >4 units of blood products or no antibiotics at all polymicrobial pneumonia occurred in almost all
COPD, pulmonary disease Intracranial pressure monitoring untreated animals. 95,96 However, baboons that had received prophylactic
topical polymycin had only a slightly lower incidence of pneumonia, and
Coma or impaired consciousness MV >2 days
the prevalence of drug-resistant microorganisms in the tracheal secre-
Burns, trauma Positive end-expiratory pressure tions was very high: 60% and 78% after 4 and 8 days of MV, respectively.
Organ failure Frequent ventilator circuit changes Therefore, strong arguments suggest that the prophylactic use of antibi-
otics in the ICU increases the risk of superinfection with multiresistant
Severity of illness Reintubation
pathogens while only delaying the occurrence of nosocomial infection.
Large-volume gastric aspiration Nasogastric tube
Gastric colonization and pH Supine head position ■ STRESS ULCER PROPHYLAXIS
Upper respiratory tract colonization Transport out of the ICU In theory, patients receiving stress-ulcer prophylaxis that does not
change gastric acidity, such as sucralfate, should have lower rates of gas-
Sinusitis Prior antibiotic or no antibiotic therapy
tric bacterial colonization and, consequently, a lower risk for nosocomial
pneumonia, than those receiving antacids or H -blockers. 97,98
2
According to meta-analyses of the efficacy of stress-ulcer prophylaxis
authors stated that the development of pneumonia was closely associated in ICU patients, respiratory tract infections were significantly less fre-
with preoperative markers of severity of the underlying disease, such as quent in patients treated with sucralfate than those receiving antacids
low serum albumin concentration and a high score on the American or H -blockers. 99,100 This conclusion, however, was not fully confirmed
2
Society of Anesthesiologists preanesthesia physical status classification. in a very large, multicenter, randomized, blinded, placebo-controlled
A history of smoking, longer preoperative stays, longer surgical proce- trial that compared sucralfate suspension (1 g every 6 hours) with the
dures and thoracic or upper abdominal surgery were also significant risk H -receptor antagonist ranitidine (50 mg every 8 hours) for the preven-
2
factors for postsurgical pneumonia. Another study comparing adult ICU tion of upper gastrointestinal bleeding in 1200 ventilated patients.
101
populations demonstrated that postoperative patients had consistently Clinically relevant gastrointestinal bleeding developed in 10 of the 596
higher rates of nosocomial pneumonia than did medical ICU patients, (1.7%) patients receiving ranitidine, as compared with 23 of the 604
with a risk ratio of 2.2. Multiple regression analysis was performed to (3.8%) receiving sucralfate (relative risk [RR], 0.44; 95% confidence
82
identify independent predictors of nosocomial pneumonia in the two interval [CI], 0.21-0.92; p = 0.02). In the ranitidine group, 114 of 596
groups; for surgical ICU patients, mechanical ventilation (>2 days) and (19.1%) patients had VAP, as diagnosed by an adjudication committee
acute physiology and chronic health evaluation score (APACHE) were using a modified version of the CDC criteria, versus 98 of 604 (16.2%)
retained by the model; for the medical ICU population, only mechanical in the sucralfate group (RR, 1.18; 95% CI, 0.92-1.51; p = 0.19). VAP,
ventilation (>2 days) remained significant. It has been suggested that however, occurred significantly less frequently in patients receiving
different surgical ICU patient populations may have different risks for sucralfate when the diagnosis of pneumonia was based on Memphis
nosocomial pneumonia: cardiothoracic surgery and trauma (particu- VAP Consensus Conference criteria (if there was radiographic evidence
larly the head) patients were more likely to develop VAP than medical of abscess and a positive needle aspirate, or histologic proof of pneumo-
or other types of surgical patients. 29 nia at biopsy or autopsy) (p = 0.03). 101
■ ANTIMICROBIAL AGENTS because stress-ulcer prophylactic medications that raise the gastric
Sucralfate appears to have a small protective effect against VAP

The use of antibiotics in the hospital setting has been associated with an pH might themselves increase the incidence of pneumonia. 102,103 This
increased risk of nosocomial pneumonia and selection of resistant patho- contention is supported by direct comparisons of trials of H -receptor
2
gens. 13,36,59,85-89 In a cohort study of 320 patients, prior antibiotic adminis- antagonists versus no prophylaxis, which showed a trend toward higher
tration was identified by logistic regression analysis to be one of the four pneumonia rates among the patients receiving H -receptor antagonists
2
99
variables independently associated with VAP along with organ failure, age (OR, 1.25; 95% CI, 0.78-2.00). Furthermore, the comparative effects of
>60 years, and the patient’s head positioning (ie, flat on his back or supine sucralfate and no prophylaxis are unclear. Among 226 patients enrolled
36
vs head and thorax raised 30°-40° or semirecumbent). Other investiga- in two randomized trials, those receiving sucralfate tended to develop
tors, however, found that antibiotic administration during the first 8 days pneumonia more frequently than those given no prophylaxis (OR, 2.11;
was associated with a lower risk of early-onset VAP. For example, Sirvent 95% CI, 0.82-5.44). 104,105
90
prophylactically was associated with a lower rate of early-onset VAP in ■ ENDOTRACHEAL TUBE—REINTUBATION—TRACHEOSTOMY
et al showed that a single dose of a first-generation cephalosporin given
patients with structural coma. Moreover, multiple logistic regression The presence of an endotracheal tube by itself circumvents host defenses,
91
analysis of risk factors for VAP in 358 medical ICU patients identified the causes local trauma and inflammation, and increases the probability of
absence of antimicrobial therapy as one of the factors independently asso- aspiration of nosocomial pathogens from the oropharynx around the
92
ciated with VAP onset. Finally, the results of the multicenter Canadian cuff. Scanning electron microscopy of 25 endotracheal tubes revealed
study on the incidence of and risk factors for VAP indicated that antibiotic that 96% had partial bacterial colonization and 84% were completely
29
treatment conferred protection against VAP. This apparent protective coated with bacteria in a biofilm or glycocalyx. The authors hypoth-
106
effect of antibiotics disappears after 2 to 3 weeks, suggesting that a higher esized that bacterial aggregates in biofilm dislodged during suctioning
risk of VAP cannot be excluded beyond this point. might not be killed by antibiotics or effectively cleared by host immune
Prolonged antibiotic administration to ICU patients for primary defenses. Clearly, the type of endotracheal tube may also influence the
infection is thought to favor selection and subsequent colonization with likelihood of aspiration. Use of low-volume, high-pressure endotra-
resistant pathogens responsible for superinfections. 12,59,88,93-95 According cheal cuffs reduced the rate to 56% and the advent of high-volume,

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