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Acs0817 Postoperative And Ventilator Associated Pneumonia

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  • 1. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 1 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA Craig M. Coopersmith, M.D., F.A.C.S., and Marin H. Kollef, M.D. Pulmonary complications are common after surgical procedures, Incidence and Risk Factors accounting for nearly one of every four deaths that occur in the For an accurate assessment of the incidence of and risk factors first postoperative week.1 Overall, pneumonia is the third most for pneumonia in postoperative patients, it is helpful to consider common postoperative infection, after urinary tract infection and postoperative pneumonia separately from VAP. Postoperative VAP, surgical site infection.2 In critically ill patients, however, the respi- by definition, occurs in a patient who has undergone a surgical ratory tract is the most common site of nosocomial infection3: in procedure and is on mechanical ventilation for longer than 48 to the intensive care unit, pneumonia accounts for 28% to 47% of all 72 hours; however, not every patient who acquires pneumonia nosocomial infections.4,5 after an operation is on a ventilator or in the ICU. The severity of In discussing pneumonia occurring in surgical patients after an episode of pneumonia and its ultimate outcome are at least par- operation, it is useful to distinguish between postoperative pneu- tially related to the comorbid conditions present; therefore, a sur- monia and ventilator-associated pneumonia (VAP). Throughout gical ICU patient with multiple organ dysfunction typically has a this chapter, we make this distinction where appropriate [see worse prognosis than a patient who acquires pneumonia while Incidence and Risk Factors and Diagnosis, below]. recovering from an operation on the surgical ward. POSTOPERATIVE PNEUMONIA A wide-ranging assessment of pneumonia in the postoperative Pathogenesis setting was provided by a retrospective review of 160,805 patients Under basal conditions, the lower respiratory tract is sterile. who underwent major noncardiac surgical procedures at 100 Thus, for pneumonia to develop, bacteria must be introduced into Veterans Affairs Medical Centers between 1997 and 1999.2 Pneu- the lungs, typically by being aspirated from either the upper respi- monia was diagnosed in a total of 2,466 (1.5%) of the 160,805 ratory tract or the gastrointestinal tract. This introduction of bac- patients. The 30-day mortality was 21% in patients who experi- teria is generally associated with impairment of host defenses, both enced postoperative pneumonia and 2% in those who did not. locally and systemically. Multivariate analysis identified several risk factors that led to an A leading hypothesis regarding the pathogenesis of VAP is that increased risk of postoperative pneumonia, including type of sur- the oropharynx is overgrown by microbes, which subsequently are gery, age, functional status, recent weight loss, chronic obstructive aspirated into the lungs and colonize the airway.6 This hypothesis pulmonary disease (COPD), type of anesthesia, impaired sensori- is supported by the observation that whereas enteric gram-nega- um, history of a cerebrovascular accident, blood urea nitrogen tive bacteria are absent from the oropharynx under basal condi- (BUN) level, substantial transfusion, emergency surgical interven- tions, they can be detected in the oropharynx in nearly 75% of tion, long-term steroid use, recent smoking, and significant recent critically ill patients.7 Upper airway colonization by enteric bacte- alcohol use [see Table 1]. This review represents by far the most ria occurs in 45% to 100% of intubated patients. Besides being substantial effort yet made to quantify the incidence and risk fac- colonized by aspirated endogenous flora, the airways may be col- tors of postoperative infections. However, it has two major limita- onized by exogenous flora as a result of cross-contamination from tions: (1) it was retrospective rather than prospective, and (2) more other ICU patients (through inadvertent transmission by health than 95% of the patients involved in the study were male. care workers). A complementary hypothesis is that the upper GI tract plays a VENTILATOR-ASSOCIATED PNEUMONIA critical role in the pathogenesis of VAP. According to this view, the In contrast to postoperative pneumonia,VAP has been the subject stomach is a primary site of colonization that may subsequently in- of a good deal of epidemiologic study, though to date, surgical pa- fect the lung through retrograde movement of bacterial overgrowth, tients have made up only a subset of the patients studied.The report- followed by aspiration of organisms from the oropharynx.The small ed overall incidence of VAP in ICU patients varies widely among decrease in mortality seen in certain ICU patient populations who published studies, ranging from 1 to more than 20 cases per 1,000 undergo selective decontamination of the digestive tract (SDD) sup- ventilator days4,10; the average incidence across the various studies is ports the possibility that endogenous gut flora plays a role in the approximately 7 cases per 1,000 ventilator days.6 Although VAP can pathogenesis of VAP, though this possibility remains controversial.8 occur in any patient undergoing mechanical ventilation, it is substan- Chronic infection of biofilms in an endotracheal tube may also play a tially more common in surgical ICU patients than in medical ICU role in the pathogenesis of VAP.9 Either suctioning or performing patients, reaching its highest prevalences in trauma, neurosurgical, bronchoscopy in a patient with a biofilm may result in distal em- surgical, and burn ICUs. As an example of how VAP disproportion- bolization of bacteria. The importance of biofilms in this setting, ately affects surgical patients, ventilator usage in trauma ICUs is however, remains to be fully determined. nearly identical to that in respiratory ICUs (0.58 versus 0.57 ventila-
  • 2. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 2 Table 1 Preoperative Predictors of tality associated with VAP has not been determined with certain- Postoperative Pneumonia2 ty: estimates range from no increased risk of death to a relative risk increase of 3.6.6,13,15 Attributable mortality is especially difficult to establish in patients with ARDS, though one study of 11 predom- Predictor Odds Ratio (95% CI) inantly medical ICUs in France found that mortality in ARDS Type of surgical procedure patients was not appreciably affected by whether they had VAP.16 AAA repair 4.29 (3.34–5.50) Studies that demonstrate an increased relative risk of death with Thoracic 3.92 (3.36–4.57) VAP frequently also demonstrate an increased prevalence of resis- Upper abdominal 2.68 (2.38–3.03) tant organisms (e.g., Pseudomonas aeruginosa and Acinetobacter Neck 2.30 (1.73–3.05) baumanii).17 VAP patients as a group remain in the ICU approxi- Neurologic 2.14 (1.66–2.75) mately 6 days longer than comparable patients without VAP and Vascular 1.29 (1.10–1.52) incur more than $40,000 in additional charges.13,15 When the sub- Other 1.00 (referent) group of surgical patients is considered on its own, however, the Age increase in length of stay in the ICU is closer to 1 day,13 and the ≥ 80 yr 5.63 (4.62–6.84) increase in hospital charges is almost certainly smaller (though still 70–79 yr 3.58 (2.97–4.33) substantial). 60–69 yr 2.38 (1.98–2.87) 50–59 yr 1.49 (1.23–1.81) < 50 yr 1.00 (referent) Diagnosis Functional status Pneumonia is commonly defined as distal air-space inflamma- Totally dependent 2.83 (2.33–3.43) tion caused by microorganisms or products of microorganisms.6 Partially dependent 1.83 (1.63–2.06) Although this definition is simple, diagnosis of pneumonia is often Independent 1.00 (referent) complex, for two reasons. First, it is frequently difficult to isolate Weight loss > 10% in past 6 mo 1.92 (1.68–2.18) microorganisms from the lower respiratory tract, even if the patient has an active infection. Second, in the unlikely circum- History of COPD 1.72 (1.55–1.91) stance that a patient undergoes an open lung biopsy that demon- Type of anesthesia strates inflammation, this finding does not indicate that pneumo- General 1.56 (1.36–1.80) nia is present, because there are a number of noninfectious insults Spinal, monitored, or other 1.00 (referent) that can result in both local and systemic inflammation. Impaired sensorium 1.51 (1.26–1.82) DIAGNOSTIC CRITERIA History of cerebrovascular accident 1.47 (1.28–1.68) Postoperative Pneumonia BUN level < 2.86 mmol/L (< 8 mg/dl) 1.47 (1.26–1.72) Most postoperative fevers are of noninfectious origin, and even 2.86–7.50 mmol/L (8–21 mg/dl) 1.00 (referent) when an elevated temperature and an increased white blood cell 7.85–10.70 mmol/L (22–30 mg/dl) 1.24 (1.11–1.39) (WBC) count result from an infection, pneumonia still is not the ≥ 10.70 mmol/L (≥ 30 mg/dl) 1.41 (1.22–1.64) most likely diagnosis. It is therefore critical to establish objective Transfusion > 4 units 1.35 (1.07–1.72) criteria for diagnosing pneumonia after a surgical procedure. Of the several different diagnostic approaches that have been formu- Emergency operative intervention 1.33 (1.16–1.54) lated, one of the more popular uses a combination of clinical and Use of steroids for chronic condition 1.33 (1.12–1.58) radiographic criteria to diagnose pneumonia in nonventilated postoperative patients [see Table 2].2,18 Typically, in a surgical ward Current smoker within 1 yr 1.28 (1.17–1.42) patient, the diagnosis requires either new onset of purulent spu- Alcohol intake > 2 drinks/day in past 2 wk 1.24 (1.08–1.42) tum or a change in the character of the sputum in combination with a worsening chest x-ray that demonstrates either new or pro- gressive infiltrate or consolidation. Ventilator-Associated Pneumonia tor days/patient days), but VAP develops nearly four times as often in the former as in the latter (15.1 versus 4.2 cases per 1,000 ventilator Diagnosing VAP is more complicated than diagnosing postopera- days).11 It should be remembered, however, that patients in respira- tive pneumonia in a patient on the surgical ward, though with inva- tory ICUs may have already had an episode of pneumonia while in sive quantitative cultures, it may be possible to make the diagnosis the hospital, which may make diagnosis of secondary VAP more dif- more accurately in a ventilated patient. In ICU patients, as in surgi- ficult in this population. cal ward patients, fever and leukocytosis are very common and are The single greatest risk factor for VAP is related to the duration frequently of noninfectious origin. Unlike surgical ward patients, of mechanical ventilation. The risk peaks at day 5 on the ventila- however, ICU patients often have chronically purulent secretions tor, plateaus after day 15, and then declines significantly, with the and abnormal chest x-rays that are not representative of pneumo- result that VAP is uncommon in patients on long-term mechani- nia.19 There is no absolute gold standard for diagnosing VAP, and at- cal ventilation.6,12 Other risk factors associated with the develop- tempts to define VAP objectively for surveillance purposes have so far ment of VAP are trauma, thermal injury, male gender, increased failed to reach any resolution.6 In addition to fever, leukocytosis, in- age, acute lung injury, and greater severity of illness.12,13 creased or changed sputum production, and an abnormal chest x- The absolute mortality in VAP patients ranges from 12% to ray, indicators used to diagnose VAP may include sputum culture, more than 50%, with a substantially lower crude mortality in sur- the clinical pulmonary infection score (CPIS), and (less commonly) gical patients than in medical patients.14,15 The attributable mor- pleural fluid culture or open lung biopsy.20,21
  • 3. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 3 still essentially tracheal aspiration, not BAL. As noted (see above), pneumonia is defined as the presence of microorganisms in the Table 2 Criteria* for Definition of distal airways; thus, obtaining a sample from the proximal airways Postoperative Pneumonia2 (even if access is obtained with a bronchoscope), though it can provide information about the microbial content of the proximal Rales or dullness to percussion on physical examination of chest AND airways, suffers from the same limitations that obtaining a culture any of the following: with a catheter placed down the endotracheal tube does. New onset of purulent sputum or change in character of sputum Techniques for performing BAL vary somewhat among institu- Isolation of organism from blood culture tions. Generally, however, the bronchoscope is wedged in the most Isolation of pathogen from specimen obtained by transtracheal aspiration, bronchial brushing, or biopsy distal airway in the lobe of interest before cultures are obtained, Chest radiography showing new or progressive infiltrate, consolidation, and a 20 or 50 ml aliquot of normal saline is lavaged, returned, cavitation, or pleural effusion AND any of the following: and discarded. Another aliquot of normal saline is then lavaged, New onset of purulent sputum or change in character of sputum and the returned fluid is sent off for quantitative culture. Isolation of organism from blood culture Using invasive sampling techniques to obtain a diagnosis is espe- Isolation of pathogen from specimen obtained by transtracheal cially important in trauma patients, who often have fever, leukocyto- aspiration, bronchial brushing, or biopsy sis, purulent sputum, and radiographic abnormalities as a conse- Isolation of virus or detection of viral antigen in respiratory secretions quence of the systemic inflammatory response syndrome (SIRS). A Diagnostic single antibody titer (IgM) or fourfold increase in paired study of 43 trauma patients exhibiting all these symptoms and signs serum samples (IgG) for pathogen Histopathologic evidence of pneumonia who underwent BAL found that 20 had culture results consistent with VAP, whereas 23 had bacterial growth amounting to fewer than *Only one criterion need be fulfilled to establish the diagnosis. 105 cfu/ml.26 Antibiotics were stopped after culture results in all pa- tients with low or no bacterial growth (average, 3.3 days); 65% of pa- tients showed improvement after discontinuance of antibiotics, and there was no difference in mortality between the SIRS group and the INVASIVE AND NONINVASIVE CULTURES VAP group.These findings highlight the need to obtain invasive cul- Samples for sputum culture may be obtained either noninva- tures in the trauma setting, in that a high percentage of the patients sively, via tracheal aspiration, or invasively, via bronchoscopy with in this study would have been incorrectly diagnosed as having pneu- either bronchoalveolar lavage (BAL) or a protected specimen monia on clinical grounds alone. brush (PSB). Tracheal cultures, though commonly employed, Several nonbronchoscopic quantitative sampling techniques are overestimate the rate of VAP and fail to diagnose some occur- now available, including mini-BAL and blind sampling PSB.27,28 rences of pneumonia documented by postmortem pathologic These techniques involve blind passage of a catheter or telescop- study of the lung20,22; these failings persist even when quantitative ing catheters to a wedged position in the lung.20 Both mini-BAL cultures are used. Moreover, the threshold used for documenting and blind sampling PSB are slightly less accurate than their bron- VAP with tracheal cultures changes both the sensitivity and the choscopic counterparts, with sensitivities ranging from 58% to specificity of the test. In one study, reducing this threshold from 100% and specificities ranging from 66% to 100%.6 In addition, 106 to 105 colony-forming units (cfu)/ml increased sensitivity from these techniques may miss unilateral left-side pneumonia, pre- 55% to 63% while decreasing specificity from 85% to 75%, as sumably because blind insertion is more likely to result in wedg- determined by comparison with postmortem specimens in a sam- ing of the catheter in the right lung. ple of 28 patients who died within 3 days after culture.23 Regardless of the culture technique used, previous antibiotic ther- Invasive sampling is significantly more accurate than tracheal apy can reduce the chances of obtaining a positive culture.The de- aspiration in diagnosing VAP. Both BAL and PSB have sensitivi- termining factor appears to be the duration of such therapy. Initia- ties and specificities higher than 80% [see Table 3].23,24 A study tion of antibiotic therapy within the preceding 24 hours decreases involving 22 patients with suspected VAP who had five samples the chances of obtaining a positive culture and reduces the number taken from the same site during the same bronchoscopy proce- of microorganisms recovered, though these effects are less pro- dure found that the two techniques yielded similar results.25 In this nounced with BAL than with other diagnostic techniques6; however, study, PSB isolated the same organisms each time, but quantita- in patients who have been receiving antibiotics for more than 72 tion with BAL varied within one log 59% of the time, leading to a hours, the sensitivity and specificity of BAL and PSB for the diagno- change in diagnosis (from presence to absence of pneumonia or sis of pneumonia are largely unaffected.29,30 These findings have clear vice versa) in 13% of cases. implications for treating pneumonia in postoperative patients. It must be noted that simply placing a bronchoscope through Specifically, cultures should be accurate in a patient who is in the an endotracheal tube or a tracheostomy and obtaining a sample is middle of a 1-week antibiotic course for complicated intra-abdomi- Table 3 Diagnostic Techniques Used in Diagnosis of VAP20 Positive Negative Diagnostic Technique Sensitivity (%) Specificity (%) Predictive Value Predictive (%) Value (%) PSB cultures (≥ 103 cfu/ml) 82 89 90 89 BAL cultures (≥ 104 cfu/ml) 91 78 83 87 Microscopic examination of BAL fluid 91 89 91 89 (≥ 5% intracellular organisms)
  • 4. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 4 nal infection, but starting antibiotic therapy immediately before ob- Table 4 Calculation of Clinical taining a culture for suspected VAP will adversely affect the ability of Pulmonary Infection Score6 the surgeon to diagnose this condition. CLINICAL PULMONARY INFECTION SCORE Variable Finding Points The CPIS quantifies a number of clinical findings suggestive of ≥ 36.5 and ≤ 38.4 0 pneumonia—temperature, WBC count, tracheal secretions, tra- Temperature (ºC) ≥ 38.5 and ≤ 38.9 1 cheal cultures, oxygenation, chest x-rays, and the presence of and ≥ 39 or ≤ 36 2 progression of infiltrates on x-rays—in an attempt to diagnose ≥ 4,000 and ≤ 11,000 0 pneumonia noninvasively [see Table 4].21 A CPIS higher than 6 is Blood leukocytes < 4,000 or > 11,000 1 associated with a high likelihood of pneumonia, and there is a clear (No./mm3) Plus band forms ≥ 50% Add 1 correlation between a high CPIS and a high concentration of bac- teria found with invasive culture techniques.31 The main use of the Absent 0 CPIS is as a method of defining the probability of pneumonia in a Tracheal secretions Nonpurulent secretions present 1 given patient that is more objective than clinical judgment alone. Purulent secretions present 2 A patient with a low CPIS probably need not be treated for pneu- Oxygenation > 240 or ARDS* 0 monia, whereas one with a high CPIS is likely to benefit from inva- (PaO2/FIO2) ≤ 240 and no ARDS 2 sive culturing, followed by rapid institution of broad-spectrum No infiltrate 0 antibiotic therapy.The main drawbacks of the CPIS are (1) that all Pulmonary Diffuse (or patchy) infiltrate 1 of its elements are weighted equally (for example, the presence of radiography Localized infiltrate 2 an infiltrate is given the same weight as a WBC count of 11,000/mm3, even though it is substantially more suggestive of No radiographic progression 0 Progression of pneumonia) and (2) that assessment of chest x-rays and sputum pulmonary infiltrate Radiographic progression (after CHF and 2 ARDS excluded) production is necessarily subjective, meaning that an equivocal CPIS could lead to an inappropriate treatment decision. Pathogenic bacteria cultured in very low to 0 low quantity or not at all Culture of tracheal Pathogenic bacteria cultured in moderate or 1 OTHER MODALITIES FOR DIAGNOSING VAP aspirate high quantity Although the use of invasive culture methods in conjunction with Same pathogenic bacteria seen on Gram Add 1 clinical judgment is the most common approach to diagnosing VAP, stain there are rare circumstances in which other diagnostic modalities *Defined as PaO2/FIO2 ≥ 200 and PAWP ≤ 18 mm Hg, with acute bilateral infiltrates. may be useful.20 The most likely surgical situation in which pneumo- ARDS—acute respiratory distress syndrome CHF—congestive heart failure FIO2—fraction of inspired oxygen PaO2—arterial oxygen tension PAWP—pulmonary arterial wedge nia might be diagnosed without invasive cultures involves a patient pressure with empyema in whom a positive purulent fluid culture is obtained at the time of either chest tube placement or thoracocentesis. Histopathologic examination of tissue obtained at open lung biopsy respectively).13 In more than 50% of VAP cases, more than one or- that demonstrates the presence of both bacteria and inflammation is ganism is isolated.24 Isolation of an organism, in itself, does not es- diagnostic of VAP. Rapid cavitation of a pulmonary infiltrate in a pa- tablish the diagnosis of pneumonia, and colonization can occur at tient who has a negative workup for both cancer and tuberculosis, any time during the course of mechanical ventilation. It is crucial to though extremely uncommon after operation, is likely to represent distinguish infection from colonization: the former calls for aggres- pneumonia when it does occur in this setting. sive antimicrobial therapy, and the latter need not be treated at all— in fact, inappropriate use of antibiotics to treat colonization may ad- versely affect outcome.A study of 26 patients undergoing mechanical Management ventilation demonstrated that 22 were colonized by at least a single bacterial strain during their ICU stay, with 16 being colonized with- IDENTIFICATION OF PATHOGENS in 5 days after intubation.33 Of these 22 patients, 21 were colonized For effective treatment of pneumonia in the postoperative by aerobes and 15 by anaerobes, and five went on to acquire VAP patient, it is critical to know which organism or organisms are (three with aerobic pathogens, two with anaerobic pathogens). causing the disease. Overall, pneumonia in ICU patients is more The role of anaerobes in VAP is controversial33,34: although they frequently caused by gram-negative bacteria than by gram-positive may represent as many as 23% of the isolated strains in patients bacteria [see Table 5]. The most commonly isolated gram-negative with VAP (typically in early-onset cases in which aspiration was pathogen is P aeruginosa, and the most commonly isolated gram- . witnessed), their presence is not associated with an increase in positive pathogen is Staphylococcus aureus.13,32 mortality,35 and there is no evidence that antianaerobic therapy It is important to note that the microbes isolated in the first 3 to 4 changes outcomes in patients with VAP. days of an ICU stay are dramatically different from those isolated lat- The role played by so-called commensal bacteria in the nor- er.6 The pathogens found early (e.g., S. aureus, Haemophilus influen- mally sterile lower respiratory tract is also unclear. Approximately zae, and Streptococcus pneumoniae) are typically sensitive to many 50% of isolates from ventilated patients are from bacterial species classes of antibiotics, whereas the pathogens identified later (e.g., P . that are believed to be nonpathogenic except in immunocompro- aeruginosa, A.baumanii, methicillin-resistant S.aureus [MRSA], and mised patients; however, the significance of commensal bacteria in Stenotrophomonas maltophilia) are more likely to be resistant. In a the airways of immunocompetent patients is unknown.The possi- large United States database, S. aureus was the most commonly iso- ble importance of commensal bacteria in the lower respiratory lated organism in patients whose VAP was identified during the first tract was highlighted by a study of 369 patients with VAP, a group 4 days of mechanical ventilation, P .aeruginosa in patients whose VAP comprising all patients diagnosed with the disease over a 10-year was identified after the first 4 days of ventilation (23.7% and 19.7%, period in a mixed medical/surgical ICU.36 The investigators iden-
  • 5. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 5 tified 23 cases of VAP (through a combination of PSB and clini- At present, there are no data from surgical populations on the cal signs) as resulting from a monomicrobial infection involving an impact of delayed initiation of appropriate antimicrobial therapy; organism typically considered to be commensal (most commonly, however, the findings of one study from a medical ICU suggest non–β-hemolytic Streptococcus, Neisseria species, and coagulase- that this is not an effective strategy for preventing mortality caused negative S. aureus). Because the idea that commensal bacteria by initial selection of inadequate antibiotics.40 In this study, 107 could cause VAP was, and is, controversial, the diagnosis was consecutive ICU patients with VAP, all of whom were treated with reported only if agreed on by three independent experts. Mortality appropriate antimicrobial therapy, were followed prospectively. Of in these patients was not different from that in patients without these patients, 31% experienced delays longer than 24 hours in VAP. At present, the importance of commensal bacteria in the receiving antimicrobial therapy, almost always because of delays in pathogenesis of VAP remains undetermined. order writing.The mean time to initiation of antibiotic therapy was 28.6 hours in this group, compared with 12.5 hours in the control ANTIMICROBIAL THERAPY group (in whom antimicrobial therapy was initiated in a timely manner). Even though all of the patients in this study received Importance of Rapid Initial Treatment appropriate antimicrobial treatment, mortality differed dramati- The cornerstone of therapy for hospital-acquired pneumonia is cally between the delayed-initiation group and the control group. rapid institution of an appropriate broad-spectrum antibiotic reg- VAP-attributable mortality was 39.4% in the former group, com- imen. Appropriate initial antimicrobial treatment is typically de- pared with 10.8% in the latter. Logistic regression analysis identi- fined as an antibiotic regimen that is known to possess in vitro fied delayed initiation of antibiotics as a major independent risk activity against the identified bacterial species. factor for hospital mortality. The importance of rapid institution of appropriate antibiotic therapy has been highlighted in a number of trials involving post- Choice of Appropriate Antibiotic operative patients. In one such trial, a group of 65 patients in a When pneumonia is suspected on the basis of clinical and radi- medical/surgical ICU who had positive BAL cultures and were ographic signs, there is no way of knowing precisely which bacte- diagnosed with VAP were retrospectively subdivided into a group ria are causing the disease, and culture results usually are not avail- that received adequate antibiotic therapy at the time of broncho- able until 2 to 3 days after a specimen is obtained. In the current scopy and a group that received inadequate therapy.37 Mortality in era of increasing antibiotic resistance, it is critical to provide broad the adequate-therapy group was 38%, but that in the inadequate- initial coverage of both sensitive and resistant microorganisms. therapy group was 91%. Similar results, albeit with substantially Because resistance patterns vary among countries, among institu- lower mortalities, were obtained in a study from a different med- tions, and even among ICUs within a single hospital, what consti- ical/surgical ICU involving 113 patients with VAP diagnosed by tutes adequate initial antibiotic therapy may be country specific, means of either PSB or BAL.38 Patients receiving inadequate ini- institution specific, or even ICU specific. tial antimicrobial therapy had a mortality of 37%, whereas those The makeup of the flora causing nosocomial infection tends to receiving adequate therapy had a mortality of only 15%. evolve as a patient’s hospitalization proceeds, with bacterial resis- A link between adequate initial antimicrobial therapy and mortal- tance increasing in the later stages, and this evolution must be taken ity was also documented in a study of 2,000 consecutive ICU pa- into account in prescribing the initial antibiotic regimen. Several oth- tients, including 793 surgical ICU patients.39 In more than 60% of er factors must be considered as well: (1) the hospital-specific (or, if the 655 patients with documented infections, the respiratory tract available, ICU-specific) antibiogram documenting antibiotic resis- was the source of the infection. Of the 655 infected patients, 210 had tance, (2) key patient-specific characteristics (for example, an im- previously been operated on. Infection-related mortality was 42% in munosuppressed liver transplant patient may be susceptible to mi- infected patients who initially received inadequate antimicrobial croorganisms that a previously healthy trauma patient would not be), therapy, compared with 18% in those who received adequate thera- and (3) the efficacy, toxicity, and lung penetration of the antibiotics. py. Using a logistic regression model, the investigators found inade- If an antibiotic has poor lung penetration (as is the case with van- quate institution of antibiotic therapy to be the single most impor- comycin and the aminoglycosides), a higher dosage may be needed tant independent determinant of hospital mortality. for treatment of VAP than for treatment of other conditions. In addi- Table 5 Most Common Pathogens Isolated from Pneumonia Patients in Different Types of ICUs32 Type of ICU Pathogen Burn Cardiothoracic Medical/Surgical Neurosurgical General Surgical Trauma [No. (%)] [No. (%)] [No. (%)] [No. (%)] [No. (%)] [No. (%)] Enterobacter species 51 (8.0) 375 (13.1) 1,022 (10.6) 257 (10.5) 1,557 (12.8) 281 (13.4) Escherichia coli 21 (3.4) 139 (4.8) 402 (4.1) 112 (4.6) 593 (4.9) 93 (4.4) Klebsiella pneumoniae 34 (5.3) 169 (5.9) 720 (7.4) 182 (7.5) 878 (7.2) 146 (7.0) Haemophilus influenzae 42 (6.6) 165 (5.8) 340 (3.5) 181 (7.4) 532 (4.4) 155 (7.4) Pseudomonas aeruginosa 137 (21.5) 375 (13.1) 1,507 (15.5) 294 (12.1) 2,087 (17.2) 360 (17.1) Staphylococcus aureus 157 (24.7) 326 (11.3) 1,750 (18.0) 527 (21.6) 2,065 (17.0) 379 (18.1) Enterococcus species 12 (1.9) 66 (2.3) 177 (1.8) 32 (1.3) 215 (1.8) 24 (1.1) Candida albicans 18 (2.8) 180 (6.3) 592 (6.1) 104 (4.3) 468 (3.9) 32 (1.5) All others 164 (25.8) 1,073 (37.4) 3,197 (33.0) 749 (30.7) 3,759 (30.9) 626 (29.9)
  • 6. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 6 Table 6 Initial Empirical Therapy for Hospital-Acquired Pneumonia, VAP, and Health Care–Associated Pneumonia in Patients with Late-Onset Disease or Risk Factors for Multidrug-Resistant Pathogens41 Potential Pathogens Combination Antibiotic Regimen Initial Dosage* Streptococcus pneumoniae Antipseudomonal cephalosporin Cefepime, 1–2 g q. 8–12 hr Haemophilus influenzae Ceftazidime, 2 g q. 8 hr or Methicillin-sensitive Staphylococcus aureus Antibiotic-sensitive enteric gram-negative bacilli Antipseudomonal carbapenem Imipenem, 500 mg q. 6 hr or 1 g q. 8 hr Escherichia coli Meropenem, 1 g q. 8 hr Klebsiella pneumoniae or Enterobacter species β-Lactam/β-lactamase inhibitor Piperacillin-tazobactam, 4.5 g q. 6 hr Proteus species Serratia marcescens plus Multidrug-resistant pathogens Antipseudomonal fluoroquinolone Levofloxacin, 750 mg/day Pseudomonas aeruginosa Ciprofloxacin, 400 mg q. 8 hr or K. pneumoniae (ESBL+)† Acinetobacter species† Aminoglycoside Gentamicin, 7 mg/kg/day¶ Tobramycin, 7 mg/kg/day¶ Amikacin, 20 mg/kg/day|| plus MRSA Vancomycin or linezolid§ Vancomycin, 15 mg/kg q. 12 hr** Legionella pneumophila‡ Linezolid, 600 mg q. 12 hr * Dosage recommendations assume normal renal and hepatic function. Initial dosages should be adjusted or streamlined in accordance with microbiologic data and clinical response to therapy. † If an ESBL+ strain or Acinetobacter is suspected, a carbapenem is recommended. ‡ If Legionella is suspected, a macrolide or a fluoroquinolone is preferable to an aminoglycoside § Indicated if there are risk factors for MRSA or local incidence of MRSA is high. ¶ Trough levels should be < 1 µg/ml. || Trough levels should be < 4–5 µg/ml. **Trough levels should be 15–20 µg/ml. ESBL—extended-spectrum β-lactamase MRSA—methicillin-resistant S. aureus tion, when different classes of drugs possess similar efficacy, those microbiologic success rates in all of the patients studied, suggest- with higher side-effect profiles (e.g., aminoglycosides) should not be ing that these agents will be equally effective in the typical patient used as primary monotherapy. with gram-positive nosocomial pneumonia.42,43 As a rule, initial antibiotic treatment decisions must be tailored to Two retrospective analyses pooled patients from the two trials local antibiograms. In 2005, however, the American Thoracic Soci- just mentioned (see above), comparing vancomycin to linezolid in ety and the Infectious Diseases Society of America published con- a subset of patients with MRSA nosocomial pneumonia44 and in sensus recommendations that outlined an evidence-based strategy a smaller subset comprising patients with VAP from MRSA.45 for initiating antimicrobial therapy in patients with suspected VAP.41 Both analyses demonstrated significantly improved survival and Patients with early-onset postoperative pneumonia or VAP who have clinical cure rates in patients treated with linezolid. In the 160 no risk factors for multidrug-resistant pathogens may be treated with patients with MRSA nosocomial pneumonia, treatment with lin- ceftriaxone, a quinolone (ciprofloxacin, levofloxacin, or moxiflox- ezolid was associated with an increase in the Kaplan-Meier sur- acin), ampicillin-sulbactam, or ertapenem. In contrast, patients with vival rate from 63.5% to 80.0% and an increase in the clinical cure late-onset postoperative pneumonia or VAP and those with risk fac- rate from 35.5% to 59.0%.44 In the 91 patients with VAP from tors for multidrug-resistant organisms must be treated more aggres- MRSA, logistic regression analysis showed that treatment with sively.They should be started on combination therapy for gram-neg- linezolid was an independent predictor of survival (odds ratio, 4.6) ative infections and should receive agents that provide broad and clinical cure (odds ratio, 20.0). In contrast, a study comparing coverage of gram-positive infections [see Table 6]. vancomycin with quinupristin-dalfopristin found the two drugs to have similar cure rates both in nosocomial pneumonia patients as Gram-positive infections The optimal initial antibiotic a whole and in a subset of patients with MRSA pneumonia.46 regimen for gram-positive infections has not been established. A Although the favorable linezolid results are obviously limited by number of antibiotics can effectively treat infections caused by the fact that they derive from retrospective analyses of data pooled sensitive gram-positive organisms, but the options for treating from two studies, they do raise the question of whether linezolid infections caused by MRSA are limited. Historically, MRSA infec- should be the antibiotic of choice in patients with MRSA pneu- tion has been treated with vancomycin because no other common- monia. If vancomycin is used to treat MRSA, it should be given in ly used antibiotic has been effective. Unfortunately, vancomycin an initial dose of 15 mg/kg, and trough levels should be main- has relatively poor lung penetration. For this reason, linezolid has tained between 15 and 20 µg/ml.41 been proposed as an alternative therapy for nosocomial pneumo- nia. Two prospective, randomized, multicenter trials comparing Gram-negative infections The optimal initial antibiotic regi- vancomycin with linezolid for the treatment of nosocomial pneu- men for gram-negative infection involves starting the patient on monia found the two agents to have similar clinical cure rates and combination therapy until culture results can be obtained. Options
  • 7. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 7 commonly employed include an antipseudomonal penicillin with a an antibiotic protocol with infection-related mortality during a 1- β-lactamase inhibitor, an antipseudomonal cephalosporin, or an an- year period in which antibiotics were rotated on a quarterly basis.49 tipseudomonal carbapenem combined with either an antipseudo- Antibiotic rotation reduced infection-related mortality from 9.6 to monal fluoroquinolone or an aminoglycoside. If the patient has re- 2.9 deaths per 100 admissions; in addition, it reduced the rates of cently received antimicrobial therapy, the initial antibiotic regimen resistant gram-positive coccus infection (from 14.6 to 7.8 infec- for VAP should employ a different class of antibiotic so as to avoid tions per 100 admissions) and resistant gram-negative bacillus the risk of microbial resistance induced by previous antibiotic use. infection (from 7.7 to 2.5 infections per 100 admissions). A prospective study of 156 patients with VAP in two medical/sur- A follow-up study examined 2,088 patients both in a surgical gical ICUs showed that treatment with antipseudomonal penicillin ICU and in the ward they were transferred to, using a study design with β-lactamase inhibitors yielded better outcomes than treatment in which ICU patients (but not floor patients) were treated for 1 with cephalosporins, fluoroquinolones, or aminoglycosides (car- year without an antibiotic rotation protocol and for 1 year with such bapenems were not given as first-line therapy).47 The concept that a protocol.50 In the first quarter of the year, patients received even within the bounds of what constitutes appropriate initial antibi- ciprofloxacin with or without clindamycin for pneumonia; in the otic therapy there may be a single “most appropriate” antibiotic is in- second, piperacillin-tazobactam; in the third, carbapenem; and in triguing and worthy of further study. At present, however, no single the fourth, cefepime with or without clindamycin. The study antibiotic class can be recommended over the others as optimal demonstrated that the overall number of hospital-acquired infec- treatment of gram-negative infections. tions was decreased on the surgical ward in the year that antibiotic rotation was instituted in the ICU [see Table 7]. Similarly, the inci- Rotation of Antibiotics dence of resistant gram-positive and resistant gram-negative infec- VAP developing later in a patient’s ICU stay is more likely to be tions was reduced on the surgical ward when antibiotic rotation was caused by resistant organisms. An increase in resistant organisms practiced in the ICU. Perhaps surprisingly, the decrease in resis- is associated with an increased relative risk of death in patients tance came from patients who were not transferred from the ICU. with VAP.17 Furthermore, patients who are isolated for infection Although antibiotic cycling has not been definitively proved to control purposes because of MRSA experience more preventable be useful in postoperative patients, antibiotic cycling for VAP in adverse events and receive less documented care.48 Accordingly, the surgical ICU appears to be a strategy that is relatively easy to scheduled rotation of antibiotics on a protocol basis has been pro- implement and that may not only decrease the incidence of resis- posed as a technique for hindering the emergence of resistant tant infection but also, possibly, decrease the overall incidence of organisms by manipulating prevailing antibiotic pressures in the infection. hospital environment.49,50 Antibiotic rotation has been studied in both surgical ICUs and Deescalation of Antibiotic Therapy surgical wards. A study of 1,456 patients in a surgical ICU com- Although early initiation of adequate antimicrobial therapy has pared infection-related mortality during a 1-year period without been demonstrated to reduce mortality in patients with pneumo- Table 7 Differences in Infection-Related Outcomes for Non–ICU Ward Patients with and without ICU Antibiotic Rotation50 Outcome Nonrotation ICU Rotation P Infections 407 213 — Infected patients 333 161 — Infections/infected patient 1.3 ± 0.04 1.2 ± 0.05 0.1 Infections/100 admissions 19.7 9.8 < 0.0001 Infected patients/100 admissions 15.9 7.4 < 0.0001 Infections by service [No. (%)] Transplantation 95 (23) 39 (18) 0.2 General surgery 292 (72) 155 (73) 0.8 Trauma 21 (5) 19 (9) 0.1 rGPC infections 52 34 — rGPC infections/100 admissions 2.5 1.6 0.04 rGNR infections 20 8 — rGNR infections/100 admissions 1.0 0.4 0.03 Time from intervention to discharge (days) 11.3 ± 0.8 13.5 ± 1.0 0.1 Total utilization of antibiotics (days) 11.2 ± 0.9 8.7 ± 0.5 0.02 Length of stay (days) 18.8 ± 1.3 26.4 ± 1.7 0.0004 Deaths 28 23 — Deaths/100 admissions 1.3 1.1 0.5 rGPC deaths 6 5 — rGPC deaths/100 admissions 0.3 0.2 0.9 rGNR deaths 4 3 — rGNR deaths/100 admissions 0.2 0.1 1.0 rGNR—resistant gram-negative rod rGPC—resistant gram-positive coccus
  • 8. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 8 Table 8 Effect of Duration of Antibiotic Therapy for VAP on Outcomes 28 Days after Bronchoscopy54 8-Day Regimen 15-Day Regimen Risk Difference Outcome (N = 197) (N = 204) between Groups [No./Total (%)] [No./Total (%)] (90% CI) (%) Death from all causes All patients 37/197 (18.8) 35/204 (17.2) 1.6 (–3.7 to 6.9) Nonfermenting GNB 15/64 (23.4) 19/63 (30.2) –6.7 (–17.5 to 4.1) MRSA 6/21 (28.6) 5/21 (23.8) 4.8 (–13.9 to 23.4) Other bacteria 16/112 (14.3) 11/120 (9.2) 5.1 (–0.7 to 10.9) Recurrence of pulmonary infection All patients 57/197 (28.9) 53/204 (26.0) 2.9 (–3.2 to 9.1) Superinfection 39/197 (19.8) 38/204 (18.6) 1.2 (–4.3 to 6.6) Relapse 33/197 (16.8) 23/204 (11.3) 5.5 (0.7 to 10.3) Nonfermenting GNB 26/64 (40.6) 16/63 (25.4) 15.2 (3.9 to 26.6) Superinfection 13/64 (20.3) 8/63 (12.7) 7.6 (1.1 to 14.2) Relapse 21/64 (32.8) 12/63 (19.0) 13.8 (7.8 to 19.7) MRSA 7/21 (33.3) 9/21 (42.9) –9.5 (–30.1 to 11.1) Superinfection 6/21 (28.6) 5/21 (23.8) 4.8 (–8.8 to 18.3) Relapse 3/21 (14.3) 4/21 (19.0) –4.8 (–9.9 to 0.4) Other bacteria 24/112 (21.4) 28/120 (23.3) –1.9 (–9.5 to 5.6) Superinfection 20/112 (17.9) 25/120 (20.8) –3.0 (–8.2 to 2.2) Relapse 9/112 (8.0) 7/120 (5.8) 2.2 (–1.3 to 5.7) Mean No. (SD) Mean Difference (95% CI) (%) Antibiotic-free days All patients 13.1 (7.4) 8.7 (5.2) 4.4 (3.1 to 5.6) Nonfermenting GNB 12.0 (7.4) 7.5 (5.4) 4.5 (2.2 to 6.7) MRSA 12.9 (7.0) 4.9 (5.7) 8.0 (4.6 to 12.1) Other bacteria 13.7 (7.5) 10.0 (4.6) 3.7 (2.1 to 5.3) GNB—gram-negative bacillus nia, it is inappropriate to continue broad-spectrum agents for the MRSA is fairly easy to culture; thus, if invasive cultures are neg- entire treatment period. Instead, antibiotic therapy should be ative for this organism, vancomycin or linezolid that was started reassessed 2 to 3 days after initiation, when culture results become for coverage of resistant gram-positive organisms can be available, and specifically tailored in accordance with these results. stopped. If there is good evidence of VAP (i.e., CPIS > 6 with If a single pathogen is identified in a culture, all antibiotics may be both radiographic and sputum evidence of pneumonia), it is rea- stopped except for a single agent to which the microbe is sensitive. sonable to continue gram-negative coverage for an appropriate The exception to this rule is P aeruginosa infection, which many . period (see below). In the second group, treatment must be indi- experts recommend treating with two synergistic agents.41 vidualized. Repeat cultures should be obtained, and a search for Although there is little evidence that dual-agent therapy changes nonpulmonary sources of infection, particularly those related to outcome, except in cases where VAP is accompanied by bac- the patient’s surgical procedure or to an indwelling central teremia,51 the recommendation is made because resistance fre- venous catheter, should be initiated. Depending on the clinical quently develops if a patient is treated with a single agent.There is situation, all antibiotics may be discontinued, the current antimi- no evidence that maintaining broad-spectrum antibiotic therapy crobial regimen may be continued, or a switch to a different class after a positive culture has been obtained improves outcome; how- of antibiotic may be made. ever, there is abundant evidence that inappropriate antibiotic use breeds resistant organisms, which are a potential threat not only to Optimal Duration of Antibiotic Therapy the infected patient but also to nearby patients, who may become The length of the treatment period for VAP has long been a mat- infected secondarily. ter of controversy, thanks largely to the paucity of data on the sub- Unfortunately, even invasive quantitative cultures do not iden- ject. Historically, 7 to 10 days of treatment has been recommended tify all pneumonia-causing organisms. How best to tailor antibi- for sensitive organisms and 14 to 21 days for multiresistant organ- otic therapy in a patient with suspected VAP whose cultures are isms that may be difficult to eradicate from the respiratory tract.52,53 negative remains somewhat controversial. A common approach Expert opinion also has suggested treating either multilobar or cavi- divides such patients into two broad groups: (1) those whose tary pneumonia for 14 to 21 days.52 To date, few recommendations condition is improving with broad-spectrum therapy and (2) have been published regarding postoperative pneumonia in surgical those whose condition is staying the same or becoming worse. In patients who are not in an ICU. Given that these patients are health- the first group, antibiotic therapy should be tailored to cover ier than critically ill patients, the duration of antibiotic therapy in this gram-negative (and, possibly, sensitive gram-positive) bacteria. population should be similar to or shorter than that in patients with
  • 9. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 9 VAP, though many surgeons treat any pneumonia for 10 to 14 days, In another study, 102 consecutive patients with VAP were pros- regardless of the initiating organism. pectively evaluated before and after the implementation of a clini- In an attempt to resolve this issue, a prospective, randomized cal guideline restricting the total duration of antibiotics to 7 days trial was undertaken that assessed mortality in 401 patients (in- in selected patients who became afebrile under therapy and were cluding surgical patients) treated for VAP with antibiotics in 51 dif- neither bacteremic nor neutropenic.57 Implementation of the ferent ICUs.54 All patients received adequate antimicrobial therapy guideline reduced the average duration of antibiotic therapy from within 24 hours of the diagnosis of VAP. Antibiotics were with- 14.8 days to 8.6 days. As in the study mentioned earlier (see drawn after either 8 or 15 days, regardless of the patient’s clinical above),54 no differences in either hospital mortality or length of condition, except in the case of a documented pneumonia recur- stay were noted. However, VAP recurrence rates were actually rence that occurred before the conclusion of the study. At 28 days, lower in patients restricted to 7 days of antibiotics than in patients mortality in patients treated with antibiotics for 8 days (18.8%) receiving physician-directed therapy. was comparable to that in patients treated for 15 days (17.2%) [see On the basis of the evidence currently available in the literature, Table 8]. In addition, the two groups were comparable with respect it is possible to formulate a treatment approach that is generally to the overall recurrent infection rate (28.9% and 26.0%, respec- appropriate for the treatment of postoperative pneumonia and tively). The only exception to this latter finding arose in patients VAP [see Figure 1]. with infections caused by nonfermenting gram-negative bacilli TREATMENT FAILURE (e.g., P aeruginosa), in whom 8-day therapy was associated with a . recurrence rate of 40.6%, compared with 25.4% for 15-day ther- A 2004 study of 71 patients with ICU-acquired pneumonia in apy; this increase in recurrence was not associated with excess five medical and surgical ICUs found that 62% of patients did not mortality. Overall number of mechanical ventilation–free days and respond 3 days after therapy was initiated.58 No cause of treatment organ failure–free days, length of stay, and 60-day mortality were failure could be identified in one third of the cases; in the remain- also similar in the two groups. Not surprisingly, patients receiving ing two thirds, the most common causes were inappropriate treat- 8-day therapy had significantly more antibiotic-free days (13.1) ment (23%); concomitant infection (27%); misdiagnosis of infec- than those receiving 15-day therapy (8.7).This increase was asso- tion, with the pulmonary disease being of noninfectious origin ciated with a decrease in resistant organisms in patients who (16%); and superinfection (14%). When treatment fails, the acquired recurrent infections: recurrence was associated with a patient should be reevaluated to look for a nonpulmonary source 42.1% incidence of multiresistant pathogens in the 8-day group of fever, a noninfectious causative condition, or a pneumonia but a 62.0% incidence in the 15-day group. Such results are con- caused by organisms that are resistant to the empirical antibiotic sistent with other observational studies documenting an increase regimen. Aerosolized antibiotics may have a role to play as adjunc- in resistant organisms that is directly related to the duration of tive therapy in patients with multidrug-resistant pneumonia who antimicrobial therapy.55,56 do not respond to I.V. antibiotics. Discussion Prevention of Pneumonia after Operation tentially decreasing postoperative pneumonia, a meta-analysis of Before undergoing elective surgical procedures, patients should 14 published studies assessing the usefulness of this modality after be instructed about taking deep breaths and ambulating postop- upper abdominal procedures did not support its routine use.62 eratively (unless there is a medical contraindication to doing so).59 Like many other infections in critically ill patients, VAP is often Such instruction is especially important in patients who are at high preventable.63 Well-designed studies have found numerous interven- risk for pneumonia after operation. This group includes patients tions to be effective in lowering the incidence of VAP. Some of these scheduled for abdominal aortic aneurysm repair or thoracic pro- interventions are as simple as positioning the patient appropriately or cedures, those older than 60 years, those undergoing general anes- educating health care workers about risk factors for VAP. thesia, those whose functional status is poor, those with greater HAND HYGIENE than 10% weight loss, those on long-term steroid therapy, those with COPD, smokers, those with abnormally low or high BUN Appropriate hand hygiene is a simple but underutilized method levels, and those receiving more than 4 units of blood preopera- of preventing nosocomial infection [see 1:1 Prevention of Postoperative tively.2,60 Patients who are also at high risk but are not candidates Infection]. Lack of attention to hand hygiene has been a persistent for preoperative respiratory instruction include those undergoing problem worldwide for decades, and physicians often have the poor- emergency surgical intervention, those with impaired sensoria, est compliance.64 The alcohol foams and gels currently available are and those with a history of cerebrovascular accident with residual more effective than handwashing in killing the bacteria present on neurologic deficit (though, depending on the type of deficit, this the hands and take substantially less time to use, improving compli- patient population may benefit from preoperative teaching as well). ance with hand hygiene in the ICU.65 Such preparations now rep- Incentive spirometry is valuable for preventing pneumonia after resent the hand hygiene method of choice in most cases and should operation and is a cost-effective adjunct to early ambulation. It be readily available throughout the ICU. Hands that are visibly dirty benefits a wide range of patients but is especially effective in mod- or are soiled with blood or body fluids should still be washed with erate-risk and high-risk patients, who should receive extra atten- antimicrobial soap and water, however.59 Appropriate hand hygiene tion in ensuring compliance with this simple intervention.61 Al- practices should be followed both before and after contact with a though chest physiotherapy has been proposed as a means of po- patient who has an endotracheal tube or tracheostomy in place,
  • 10. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 10 tory tract or any portion of the ventilator circuit on the same Pneumonia is suspected after operation patient.59 Gowns are also recommended when soiling with respi- ratory secretions is anticipated; they should be removed after the Obtain chest x-ray. soiling occurs and before any contact with other ICU patients.66 Postoperative pneumonia: obtain microbiologic samples for culture and staining. PATIENT POSITIONING VAP: perform invasive microbiologic sampling with BAL or PSB for culture and staining. Aspiration of upper airway secretions occurs in healthy adults as well as in ill ones. It is, however, a matter of much greater concern in critically ill patients with decreased host defenses, who are at increased risk for VAP. Maneuvers to reduce aspiration of gastric Antibiotic therapy is initiated contents therefore have the potential to decrease the incidence of Select combination of antibiotics to treat most VAP. Because the supine position is associated with an increased common pathogens, as determined by local risk of aspiration (especially if the patient is receiving tube feedings antibiograms. via a nasoenteric tube), placing the patient in a semirecumbent Follow clinical paramenters: T˚, WBC count, position—via the simple expedient of raising the head of the bed chest x-ray, CPIS, PaO2/FIO2. to an angle of 30° to 45° or greater—is recommended as a means of possibly preventing VAP (if not medically contraindicated). A prospective, randomized trial involving 86 patients in two Antibiotic therapy is deescalated ICUs (neither of them surgical) was stopped at the first interim analysis because of the significant difference in the incidence of Reassess antibiotic requirements in 2–3 days, when culture results are VAP between semirecumbent patients and supine patients.67 The available. incidence of both clinically suspected VAP and microbiologically proven VAP was drastically reduced in patients positioned with the head of the bed at a 45° angle (from 34% to 8% and from 23% to 5%, respectively). Enteral feeding was also independently asso- Culture results Culture results are negative ciated with the risk of VAP: supine patients receiving enteral feed- identify pathogen(s) ings had a 50% chance of acquiring VAP. Patient is improving with initial broad- The supine position has been identified as an independent risk Tailor antibiotic therapy spectrum treatment: tailor antibiotic factor for VAP in other observational studies of ICU patients as to cover identified therapy to cover gram-negative well.68 In addition, patients who require transport from the ICU pathogen(s). (and, possibly, sensitive gram-positive) are at substantially higher risk for VAP than those who do not Continue to follow organisms; discontinue resistant gram- clinical parameters. positive coverage (e.g., vancomycin (24.2% versus 4.4%).69 It is possible that the VAP rate is increased or linezolid). because patients requiring transport are sicker at baseline, but it is Patient is not improving with initial broad- also possible that the rate is higher in this group partly because spectrum treatment: obtain repeat patients are supine for much or all of their transport time. cultures and look for nonpulmonary sources of infection; individualize Because static bed rest is known to increase the risk of pulmonary treatment according to clinical situation. (and nonpulmonary) complications, it has been theorized that pos- Continue to follow clinical parameters. tural oscillation and rotation may prevent VAP. Specialized kinetic beds are available that provide continuous movement and are capa- ble of reducing pulmonary complications in surgical patients. A study of 106 blunt trauma patients in a surgical ICU demonstrated a significant decrease in VAP in patients randomly selected to undergo continuous postural oscillation.70 A study of 65 surgical patients im- Patient shows improvement Patient does not show mobilized because of head injury or traction showed a nonstatistical after 7–8 days total antibiotic improvement after 7–8 days therapy (?14–15 for total antibiotic therapy trend toward a decreased risk of pneumonia in patients treated with P. aeruginosa) (?14–15 for P. aeruginosa) kinetic beds.71 Finally, a study of 69 liver transplant patients random- ly assigned to either continuous lateral rotation or a conventional bed Discontinue antibiotics. Search for superinfection or found that the incidence of lower respiratory tract infections was de- noninfectious causes of fever. creased in the study group, as was length of time to development of infection; however, duration of mechanical ventilation and length of Figure 1 Algorithm outlines recommended approach to antibi- stay were unchanged.72 otic treatment of suspected pneumonia after operation.40 Overall, there appears to be a trend toward decreased VAP in surgical patients treated with kinetic beds. In addition, there are various accompanying nonpulmonary complications that can also regardless of whether gloves are worn. In addition, hand decontam- be prevented by this treatment (e.g., decubitus ulcers). According- ination is required before and after contact with any respiratory ly, kinetic beds should be used in surgical patients who are expect- device that is used on a mechanically ventilated patient.66 ed to have a prolonged ICU course. Gloves should be worn for handling respiratory secretions or objects contaminated with such secretions.66 They should be CHOICE OF FEEDING ROUTE changed between contacts with different patients, after handling Although elevation of the head of the bed reduces aspiration, it respiratory secretions. In addition, gloves should be changed does not prevent gastroesophageal reflux.73 Because gastric between contacts with a contaminated body site and the respira- overdistention is also associated with an increased risk of aspira-
  • 11. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 11 tion, there has been considerable interest in identifying a route of it is clear that the number is not zero.The decision to extubate is, feeding that is associated with a decreased incidence of VAP. This in a way, comparable to the decision to perform an appendecto- issue is directly relevant to the postoperative setting, in which my. If every patient on whom an appendectomy is done has many patients, as a consequence of the surgical procedure, expe- appendicitis, it is likely that too few operations are being done and rience ileus, which is often exacerbated by narcotics given for pain that some patients are being allowed to experience a ruptured relief. The generally appropriate reluctance to feed a patient with appendix needlessly. Similarly, if every patient who is extubated a large gastric residuum in the ICU setting should be balanced postoperatively does well, it is likely that too few extubations are against the desire to provide adequate nutrition as soon as is prac- being done and that some patients are being kept intubated inap- ticable after an operation, as well as against the multiple advan- propriately and thus experiencing preventable morbidity. tages of enteral feeding over parenteral feeding. Accordingly, the Nasal intubation increases the risk of sinusitis, which, even though timing for initiating feedings postoperatively must be individual- only 10% of patients with opacified sinuses have recoverable bacte- ized on the basis of each patient’s situation and condition. In addi- ria, is associated with an increased incidence of VAP.81 It is not clear tion, whereas feeding a supine patient greatly increases the risk of whether sinusitis causes VAP or merely represents a marker of pa- VAP,67 there is no documented benefit to postpyloric feeding or to tients who are at higher risk for pneumonia. In either case, given the using smaller nasogastric tubes,74,75 and no clear recommenda- association between nasotracheal intubation and increased infection tions can be made regarding how best to feed a postoperative rate and mortality, nasotracheal intubation should not be considered patient enterally. a first-line method of obtaining airway control. MINIMIZATION OF ENDOTRACHEAL INTUBATION MANAGEMENT OF VENTILATOR Extended mechanical ventilation is a major risk factor for VAP; Although in theory, ventilator tubing, suction catheters, and it follows, then, that decreasing or eliminating the need for an humidification systems could all play a role in the development of endotracheal tube has the potential to lower the incidence of VAP. pneumonia, none of them have been convincingly shown to have There are two major strategies by which this goal can be accom- an impact on VAP rates. Condensate in the ventilator tubing can plished: (1) earlier extubation (i.e., removing an endotracheal tube become contaminated, but multiple randomized trials have when it is no longer needed) and (2) noninvasive ventilation (i.e., demonstrated that routinely changing ventilator circuits in continuing ventilatory support without the presence of an endo- patients with respiratory failure does not lower the VAP rate.82-84 tracheal tube). In addition, the route of intubation (oral versus Circuits should be changed when they are visibly soiled with vomit nasal) can influence the development of pneumonia.76 or blood or are malfunctioning. In addition, condensate should Although the optimal mode of weaning has not been definitive- periodically be drained and discarded. ly determined, it is clear that many patients are kept intubated Heat moisture exchangers (HMEs) are frequently used instead even when they no longer require mechanical ventilation.The use of heated water humidification systems, because HMEs are rela- of a weaning protocol, a sedation protocol, or both has been shown tively inexpensive and require neither electricity nor active heating to reduce the duration of mechanical ventilation.69 In addition, elements. HMEs minimize the formation of condensate within daily interruption of sedation until a patient is awake has been ventilator circuits, thereby, in theory, potentially decreasing VAP demonstrated to decrease the number of ventilator days in a med- rates. One study found HMEs to yield lower infection rates than ical ICU population77; however, this approach has not been stud- humidification systems,85 but at present, there is no clear consen- ied in the surgical ICU, where the issue is complicated by the sus in favor of either type of device.8,59 greater need for postoperative narcotics. Regardless of the tech- Either an open single-use catheter system or a closed multiuse nique or protocol employed, patients should be assessed daily to catheter system may be used for suctioning. Although open sys- determine whether ventilatory support is still necessary. Extubated tems are associated with increased environmental contamination, patients have a substantially lower incidence of postoperative current evidence suggests that the incidence of VAP is not signifi- pneumonia than patients with an endotracheal tube in place. cantly affected by the type of suctioning system used.14,86 In addi- The presence of an endotracheal tube in itself, independent of tion, when closed systems are used, routine changing of inline suc- the need for mechanical ventilation, also appears to be a risk fac- tion catheters does not reduce the incidence of VAP,87 nor is there tor for VAP. The tube hinders both airway reflexes and coughing, convincing evidence that more frequent suctioning prevents VAP. allowing secretions that accumulate above the tube to enter the PREVENTION OF OROPHARYNGEAL COLONIZATION airways over time and serve as a nidus of infection. This problem is eliminated in patients who are ventilated noninvasively with Oropharyngeal colonization can be decreased by means of bilevel positive airway pressure (BiPAP). Multiple studies have either antiseptic therapy or a comprehensive oral hygiene pro- found noninvasive ventilation to be associated with lower pneu- gram. Oral chlorhexidine gluconate (0.12%), given before and monia rates and mortalities than conventional ventilation.78,79 after cardiac procedures, has proved effective in preventing post- However, these studies were done in medical ICUs, predominant- operative pneumonia.88 In a prospective, randomized, blinded ly on patients with COPD exacerbations, and it is unclear whether trial, patients receiving a chlorhexidine rinse, which has docu- similar results are achievable in patients with postoperative respi- mented activity against both aerobes and anaerobes, experienced ratory failure. a 69% decrease in the incidence of postoperative pneumonia.This Reintubation is also an independent risk factor for the develop- decrease was not associated with a change in antibiotic resistance ment of VAP.80 However, fear of the potential adverse conse- patterns after operation and was accompanied by a reduction in quences of reintubation should not prevent an awake patient who postoperative antibiotic use.The effect of a chlorhexidine rinse on passes a spontaneous breathing trial from being extubated. Many the development of postoperative pneumonia in a general surgical postoperative patients who are extubated and have unexpected population, however, has not yet been adequately studied. ventilatory problems can be managed without reintubation on A comprehensive oral hygiene program includes daily oral BiPAP. In addition, although it is unclear what the correct per- assessment, frequent tooth brushing, readily available dental care, centage of extubation attempts that require reintubation would be, mouth swabs, and, possibly, a chlorhexidine rinse.These measures
  • 12. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 12 18 have proved effective in preventing pneumonia in nursing-home patients.89 One retrospective study examining the application of a 16 VAP Cases /1,000 Ventilator Days comprehensive oral care protocol in medical/surgical ICU patients demonstrated a decrease in the VAP rate after the initiation of such 14 a program.90 12 DRAINAGE OF SUBGLOTTIC SECRETIONS 10 Secretions that pool above an inflated endotracheal cuff may be 8 a source of aspirated material that results in VAP. Specially de- signed endotracheal tubes are available that have a separate open- 6 ing above the cuff of the tube to allow either continuous suction- 4 ing or intermittent irrigation and drainage of secretions that accu- mulate in the subglottic space. 2 Three prospective, randomized trials have evaluated the role of 0 subglottic secretion drainage. A study of 190 patients in a med- O N D J F M A M J J A S O N D J F M A M J J A S ical/surgical ICU demonstrated a decrease in the VAP rate from 39.6 to 19.9 episodes per 1,000 ventilator days.91 VAP developed 1999 2000 2001 later in the subglottic-drainage group (12.0 versus 5.9 days). A Figure 2 Illustrated is the influence of an education program for study of 150 patients in a general ICU reported similar results, health care workers on the monthly rate of VAP per 1,000 ventila- with the VAP rate decreasing from 16% in the control group to 4% tor days between October 1999 and 2001.100 (Dotted line represents in patients receiving intermittent subglottic drainage.92 However, the VAP rate cited by the National Nosocomial Infection continuous aspiration of subglottic secretions does not appear to Surveillance system for ICUs in the United States; arrow repre- reduce the VAP rate significantly in cardiac surgical patients. A sents the point at which the education program was initiated. prospective, randomized trial of 343 cardiac surgical patients demonstrated that pneumonia developed in 5.0% of patients who received subglottic suctioning, compared with 8.2% of control ated pneumonia59 or by the Fourth International Consensus patients.93 As in other studies of subglottic drainage, pneumonia Conference in Critical Care on ICU-Acquired Pneumonia.6 developed later in patients who received the intervention (5.6 Another pharmacologic approach that has been proposed as a days) than in those who did not (2.9 days). means of preventing VAP is avoidance of drugs that raise stomach At present, utilization of subglottic secretion drainage is hin- pH, on the assumption that these agents may lead to bacterial over- dered by logistical difficulties. Not only must these specialized growth and eventually to VAP.The available data, however, indicate tubes and the expertise required to care for them be readily avail- that this assumption is incorrect. A prospective, randomized trial able in the ICU, but the decision to place the tubes must also be involving 1,200 patients in 16 ICUs that compared the H2 receptor made preoperatively and communicated to the anesthesiologist antagonist ranitidine with sucralfate found no difference in VAP rate before the patient is intubated. between the ranitidine group and the sucralfate group.97 Notably, the rate of clinically important GI bleeding was higher in the sucral- PHARMACOLOGIC APPROACHES fate group. On the basis of this definitive study, drugs that raise Widely varying study results and significant infection control stomach pH should not be avoided for infection control reasons. concerns have made SDD an extremely controversial practice. COMPLIANCE WITH EVIDENCE-BASED GUIDELINES FOR The term selective decontamination of the digestive tract is actu- PREVENTION ally a misnomer, in that successful SDD protocols employ a com- bination of systemic antibiotics and nonabsorbable antibiotics Pneumonia in the postoperative setting cannot be eliminated, given both orally and via a nasogastric tube. This is an important but its incidence can be substantially decreased by following evi- point: meta-analyses of SDD studies show that SDD is not effec- dence-based prevention guidelines. Unfortunately, compliance with tive if systemic antibiotics are not included.94,95 such guidelines is far from uniform. A prospective, randomized, unblinded trial of 934 patients in a In an attempt to understand why guidelines for preventing VAP mixed medical/surgical ICU who received either 4 days of SDD or are not more widely implemented, a study was performed in standard treatment reported that hospital mortality decreased which a questionnaire was sent to 110 opinion leaders from 22 from 31% to 24% in SDD patients.8 The treatment protocol con- countries to ascertain whether 33 practices with the potential to sisted of intravenous cefotaxime and oral and enteral polymyxin E, prevent VAP63 were instituted in their ICUs.98 If respondents did tobramycin, and amphotericin B. The results mirrored those of not follow these practices, they were asked to indicate why not. two meta-analyses that documented decreases in both VAP rate The overall nonadherence rate among the 62 physicians who and mortality in patients given SDD,94,95 with surgical patients returned the survey was 37.0%. For strategies clearly recom- deriving greater benefit than medical patients.94 mended for clinical use, the nonadherence rate was 25.2%; for less Nearly all of the studies supporting the value of SDD were per- effective strategies, the rate rose to 45.6%. Self-reported compli- formed in ICUs with low baseline levels of resistant organisms.The ance ranged from 11.7% for continuous subglottic suctioning to effectiveness of SDD in ICUs where basal antimicrobial resistance 100% for removal of endotracheal tubes as soon as clinically fea- is moderate or high is unknown. For instance, a 6-year study of 360 sible and avoidance of unnecessary reintubation. The most com- trauma patients receiving SDD reported a moderate increase in the mon reasons for nonadherence were disagreement with the inter- development of resistant organisms.96 Owing to infection control pretation of the clinical trials (35%), unavailability of the necessary concerns, SDD is not widely accepted in the United States. It is note- resources (31.3%), and high cost (16.9%). worthy that routine use of SDD to prevent VAP is not recommend- The findings of this study complement those of a separate sur- ed either by the CDC guidelines for preventing health care–associ- vey of 103 ICU directors in France and Canada on strategies to
  • 13. © 2005 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 17 POSTOPERATIVE AND VENTILATOR-ASSOCIATED PNEUMONIA — 13 prevent VAP, which cited lack of convincing evidence (e.g., for 114 respiratory therapists and 146 nurses took a 20-question subglottic secretion drainage) and high cost (e.g., of kinetic beds) pretest to determine their level of knowledge about methods of as reasons for nonadherence with published recommendations.99 preventing VAP. They then received a 10-page self-study module Notably, semirecumbent positioning was used more commonly in that provided information about VAP and outlined prevention France than in Canada, and the convenience for the nursing staff strategies. Both immediately after the intervention and 6 months was given as the reason for this difference. later, participants took a posttest that was identical to the original test.Test scores improved at both time points, demonstrating that EDUCATION OF HEALTH CARE WORKERS the information taught was both learned and retained. Obviously, to implement interventions that prevent VAP, In the 12 months before implementation of the education pro- health care workers must be aware that such interventions exist. gram, 191 episodes of VAP were identified (12.6 per 1,000 venti- Although ICU directors clearly play a major role in the overall lator days). In the 12 months following completion of the pro- direction of care, direct daily care of patients undergoing gram, however, only 81 episodes of VAP (5.7 per 1,000 ventilator mechanical ventilation is provided by respiratory therapists and days) were identified [see Figure 2]. The greatest success in VAP nurses, and it is these professionals who stand to benefit most prevention was achieved in the surgical/trauma/burn ICU, where from educational efforts. VAP rates decreased from 18.1 to 6.6 per 1,000 ventilator days. To test the effect of education in reducing VAP rates, a program These results highlight the importance of disseminating informa- was initiated that was directed toward respiratory care practition- tion on VAP prevention to the health care workers who are pro- ers and nurses in five ICUs at a single academic center.100 Initially, viding the day-to-day care for patients at risk for VAP. References 1. Brooks-Brunn JA: Postoperative atelectasis and pneu- 13. Rello J, Ollendorf DA, Oster G, et al: Epidemiology 24. Chastre J, Fagon JY, Bornet-Lecso M, et al: Evalua- monia. Heart Lung 24:94, 1995 and outcomes of ventilator-associated pneumonia in tion of bronchoscopic techniques for the diagnosis of 2. 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