Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia*

Continuing Medical Education Articles Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia* Pedro Caruso, MD, PhD; Silvia Denari, PhD; Soraia A. L. Ruiz, RT; Sergio E. Demarzo, MD, PhD; Daniel Deheinzelin, MD, PhD LEARNING OBJECTIVES On completion of this article, the reader should be able to: 1. Describe technique for tracheal installation of saline. 2. Explain benefits and outcomes of tracheal installation of saline. 3. Use this information in a clinical setting. The authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationship with, or financial interests in, any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objectives: To compare the incidence of ventilator-associated pneumonia (VAP) with or without isotonic saline instillation before tracheal suctioning. As a secondary objective, we compared the incidence of endotracheal tube occlusion and atelectasis. Design: Randomized clinical trial. Setting and Patients: The study was conducted in a medical surgical intensive care unit of an oncologic hospital. We selected consecutive patients needing mechanical ventilation for >72 hrs. Patients were allocated into two groups: a saline group that received instillation of 8 mL of saline before tracheal suctioning and a control group which did not. VAP was diagnosed based on clinical suspicion and confirmed by bronchoalveolar lavage quantitative culture. The incidence of atelectasis on daily chest radiography and endotracheal tube occlusions were recorded. The sample size was calculated to a power of 80% and a type I error probability of 5%. Measurements and Main Results: One hundred thirty patients were assigned to the saline group and 132 to the control group. V The baseline demographic variables were similar between groups. The rate of clinically suspected VAP was similar in both groups. The incidence of microbiological proven VAP was significantly lower in the saline group (23.5% ⴛ 10.8%; p ⴝ 0.008) (incidence density/1.000 days of ventilation 21.22 ⴛ 9.62; p < 0.01). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p ⴝ 0.02, log-rank test). The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval, 18%– 74%) and the number needed to treat was eight (95% confidence interval, 5–27). The incidence of atelectases and endotracheal tube occlusion were similar between groups. Conclusions: Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP. (Crit Care Med 2009; 37:32–38) KEY WORDS: pneumonia; ventilator-associated pneumonia; prevention; respiratory therapy entilator-associated pneumonia (VAP) is a frequent mechanical ventilation (MV) complication associated to high mortality, morbidity, and cost (1–3). Management of airway and its secretions, such as subglottic suctioning (4), manipulations or changes of the ventilator circuit (5, 6), and drainage of ventilator circuit condensate (7) may affect the incidence of VAP. *See also p. 330. Medical Doctor (PC, SED), Hospital A C Camargo, Sao Paulo, SP, Brazil; Medical Doctor (DD), Núcleo Avançado do Tórax, Hospital Sírio-Libanês, Sao Paulo, SP, Brazil; and Respiratory Therapist (SD, SR), Hospital A C Camargo, Sao Paulo, SP, Brazil. The authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: pedro.caruso@hcnet.usp.br Copyright © 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins 32 DOI: 10.1097/CCM.0b013e3181930026 The isotonic saline instillation before tracheal suctioning (ISIBTS) represents an option to dilute and mobilize pulmonary secretions (8) and is a common practice in airway management. A national survey in the United States revealed that 74% of centers have airway management policies incorporating instillation of isotonic saline (9). Although its use before tracheal suctioning is a common practice, it remains controversial (10). Considering VAP incidence, ISIBTS is a double-edged sword. ISIBTS could inCrit Care Med 2009 Vol. 37, No. 1 crease the incidence of VAP because it dislodges more viable bacterial colonies from the endotracheal tube than the insertion of a suctioning catheter without previous saline instillation (11). Such dislodgement could lead to contamination of the lower airways. However, ISIBTS could decrease VAP incidence because it increases the amount of secretions removed (12), stimulates coughing (13) that can bring secretions to the trachea for subsequent suctioning, and also thins secretions. Another reason for decreased VAP incidence upon ISIBTS is hypothetical. Given that some authors consider the endotracheal biofilm as a reservoir for VAP (14 –16), the frequent rinsing of the endotracheal tube by saline instillation could potentially decrease it, thereby lessening VAP incidence. In the above context, we hypothesized that instillation of isotonic saline before tracheal suctioning could decrease the incidence of VAP. Since the accumulation of secretions in the endotracheal tube leads to its obstruction, improved removal of secretions by ISIBTS could avoid tube obstruction. Similarly, better airway secretion removal by ISIBTS could decrease the incidence of atelectasis stemming from secretion. The primary objective of this study was to compare the incidence of VAP with or without tracheal ISIBTS. As a secondary objective, we compared the incidence of both endotracheal tube obstruction due to secretion and atelectasis. MATERIALS AND METHODS Patients and Study Design. We designed a randomized clinical trial in a closed medical surgical intensive care unit (ICU) of a tertiary oncologic hospital. We included consecutive patients expected to receive MV for ⬎72 hrs through an orotracheal or tracheotomy tube, who were older than 18 yrs and had next of kin agreement. Exclusion criteria were previous MV within the last month, MV for ⬎6 hrs before study enrollment, contraindication to bronchoscopy and being expected to die or undergo withdrawal of treatment within 48 hrs. Patients were allocated into two groups. In the first group, tracheal suctioning was performed without prior saline instillation (control group) whereas in the second group there was instillation of 8 mL of isotonic saline before each tracheal suctioning (saline group). The following variables that could interfere in the incidence of VAP were recorded: airway humidification, stress ulcer prophylaxis, antibiotic use, immunosuppression (leukocytes ⬍ Crit Care Med 2009 Vol. 37, No. 1 1.000/mm3, continuous use of corticosteroids or chemotherapy in the last month), type of admission, cause of MV, and gastroenteral feeding tube. All patients used a closed tracheal suctioning system (Trach-Care 14F, Kimberley-Clark, Neenah, WI) changed weekly or upon mechanical failure or visible soiling (17). Patients used heat and moisture exchangers (HME) (Hydrobac II-Hudson-Gibeck-Durham) changed every 72 hrs (18), except for copious airway secretion, thick tenacious secretion, hypothermia, hemoptysis (5), or weaning failure attributed to increased airway resistance (19). In the cases when HME was contraindicated, humidification was performed with a heated water humidifier. Patients’ bed heads were instructed to be kept at an angle of 45 degree from the horizontal. Ventilator circuits were changed only if the circuits were soiled or mechanically disrupted (20). Selective decontamination of the digestive tract, oral decontamination with antiseptics or continuous aspiration of subglottic contents were not performed in any patients. The attending physicians and nurses were blinded to the study group. Only respiratory therapists performed and recorded the type or number of tracheal suctions. If nurses or physicians asked for tracheal suctioning of a patient, those were evaluated and performed by the respiratory therapist. This was possible because in our intensive care unit (ICU) there are respiratory therapists on hand around the clock. Physicians were asked to order a bronchoscopy with bronchoalveolar lavage upon clinical suspicion of VAP. The study was approved by the hospital ethics committee and an informed consent was obtained from next of kin. Tracheal Suctioning Routine and Method. Aspirations were carried out when any one of the following situations occurred: visible airway secretion into the endotracheal tube, discomfort or ventilator-patient asynchrony, noisy breathing, increased peak inspiratory pressures or decreased tidal volume during ventilation attributed to airway secretion (8). Before aspirations, patients were preoxygenated at 100% oxygen for 2 mins (8). In the saline group, 8 mL of isotonic saline was instilled through the lavage/instillation port of the closed tracheal suctioning system located close to the junction with the endotracheal tube. Aspirations were performed at a negative pressure of 200 cm H2O for 20 secs, during which the catheter was gently rotated and withdrawn. Aspirations in the control group were identical, except for the absence of saline instillation. Diagnosis of Ventilator-Associated Pneumonia. VAP was confirmed only after 48 hrs of MV. The clinical suspicion of VAP was established when otherwise unexplained new or worsening pulmonary infiltrates on chest radiograph developed in conjunction with at least one of the following alterations: fever (⬎37.8°C), leukocytosis (⬎12.000) or leuko- penia (⬍4.000) or appearance of purulent tracheal secretion (21). Bronchoalveolar lavage was performed in the wedge position with 120 mL of sterile saline in six aliquots, of which the first recovered aliquot was rejected. VAP was considered only if bronchoalveolar lavage fluid presented ⱖ104 CFU/mL (22, 23). To avoid VAP diagnostic misclassification because of fungal colonization, we considered fungal VAP only in immunosuppressed patients who responded to antifungal treatment (24 –26). The indication, type, and duration of antibiotics were according to the attending physician decisions. If a patient had more than one episode of VAP only the first was considered. Chest Radiograph Analysis. For the first 176 patients, daily bed chest radiography was performed while patients were included in the protocol. Two pulmonologists with expertise in intensive care medicine analyzed the chest radiography and recorded the incidence of pulmonary, lobar, and segmental atelectasis. They independently analyzed the chest radiography and both were blinded to the study group. Tube obstruction, Change of Heat And Moisture Exchangers, and Closed Tracheal Suctioning System. The orotracheal or tracheostomy tubes were considered obstructed by secretion if they have been clinically suspected and the substitution of the tube would have reverted the clinical picture. Macroscopical examination was used to confirm the suspicion. Endotracheal tube obstruction was considered only if diagnosed by the attending physician. We recorded the number of HME and closed tracheal suctioning system changes due to secretion. Programmed changes were not considered. Statistical Analysis. Based on a 50% reduction of VAP incidence (from 30% to 15%), a significance level of 5% and a power of 80% to reject the null hypothesis, the ideal number of patients in each group was 133. Comparisons between groups were performed using the Student’s t test for continuous variables and the chi-square statistic (␹2) for categorical variables. The time to occurrence of VAP was analyzed by the Kaplan-Meier method and tested by the log-rank test (27, 28). We performed a logistic regression analysis to prevent treatment effect from being influenced by covariate imbalances. The dependent variable was microbiological proven VAP and five independent variables were elected based on a p ⬍ 0.2 at univariate analysis: age, immunosuppression, antibiotics at admission, antibiotics during ICU stay and study group. Agreement regarding chest radiograph analysis between both physicians was measured with Cohen’s kappa (␬-statistic). A value of 1 indicates perfect agreement whereas a value of 0 indicates that agreement is no better than chance (29). Relative risk reduction and the number needed for treatment were calculated according to standard formulas. 33 Values are expressed in mean ⫾ SD for continuous variables. All reported p values are two sided. Statistical analysis was performed using SPSS software (SPSS, Chicago, IL). RESULTS Patients. From August 2001 through December 2004, 493 patients were eligible for the study. One hundred thirty patients in the saline group, and 132 in the control group completed the study (Fig. 1). Patient characteristics at the study enrollment were similar (Table 1). The ICU mortality (51.9% for saline and 49.6% for control group; p ⫽ 0.71), MV (11.2 ⫾ 11.2 for saline and 11.1 days ⫾ 9.0 for control group; p ⫽ 0.92), and ICU (17.2 ⫾ 12.3 for saline and 17.6 days ⫾ 12.8 for control group; p ⫽ 0.77) length of stay were similar between groups. However, ICU mortality, MV, and ICU length of stay were statistically higher in patients with VAP (Table 2). After study enrollment, tracheotomy was performed in 20 patients from each group (p ⫽ 1.0) and the time to tracheotomy was similar for both groups (12 ⫾ 7.6 for saline and 11 ⫾ 7.4 days for control group; p ⫽ 0.89). Ventilator-Associated Pneumonia. In the control group, 3 patients had more than 1 episode of VAP (2 with 2 episodes and 1 with 3 episodes) and in the saline group 1 patient had 2 episodes of VAP. The incidence density and proportion of microbiological proven VAP were significantly higher in the control group (Table 3). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p ⫽ 0.02, log-rank test) (Fig. 2). The rate of clinically suspected VAP was similar in both groups. The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval [CI] 18%–74%) and the number needed to treat was 8 (95% CI 5–27). In the logistic regression analysis, the only independent variable associated to microbiological proven VAP was allocation into the control group (Odds ratio 2.48 关95% CI 1.24 – 4.96兴; p ⫽ 0.010). The proportion of monomicrobial and polymicrobial VAP were similar between groups. Also, the proportions of VAP caused by Gram-positive cocci, Gramnegative bacilli, and yeast were similar between groups (Table 4). Since all fungal VAP (n ⫽ 3) occurred in the control group, we analyzed data excluding these 34 Figure 1. Patients eligible, excluded and included in the study. Table 1. Patients’ characteristics at study enrollment Number of patients (%) Age (yrs) Male (%) Causes of mechanical ventilation Pneumonia (%) Hypoxemic respiratory failure (%) Coma (%) Shock (%) Neuromuscular disease (%) Others (%) PaO2/FIO2 Simplified acute physiologic score II at intensive care unit admission Simplified acute physiologic score II at intubation Immunosuppression (%) Leucopenia (⬍1.000/mm3) (%) Gastric ulcer prophylaxis (%) Type of gastric ulcer prophylaxis H2 blocker (%) Proton pump inhibitor (%) Nasogastric tube (%) Chronic obstructive pulmonary disease (%) Type of airway humidification Heat and moisture exchange (%) Heated humidifier (%) Tracheotomy (%) p Total Saline Control 262 64.1 ⫾ 15.3 136 (51.9) 130 (49.6) 65 ⫾ 14 66 (50.8) 132 (50.4) 63 ⫾ 16 70 (53.0) 73 (28.0) 76 (29.1) 57 (21.8) 26 (10) 5 (1.9) 24 (9.2) 228 ⫾ 105 52.5 ⫾ 15.6 43 (33.3) 34 (26.4) 26 (20.2) 16 (12.4) 2 (1.6) 8 (6.2) 233 ⫾ 102 52.4 ⫾ 15.0 30 (22.7) 42 (31.8) 31 (23.5) 10 (7.6) 3 (2.3) 16 (12.1) 223 ⫾ 109 52.6 ⫾ 16.1 0.42 0.92 55.1 ⫾ 15.3 55.5 ⫾ 15.0 54.7 ⫾ 15.7 0.65 78 (29.8) 11 (4.2) 208 (80.0) 36 (27.7) 6 (4.6) 102 (79.7) 42 (31.8) 5 (3.8) 106 (80.3) 0.50 0.77 1.00 0.87 74 (35.4) 135 (64.6) 112 (42.9) 49 (18.7) 37 (35.9) 66 (64.1) 56 (43.4) 23 (17.7) 37 (34.9) 69 (65.1) 56 (42.4) 26 (19.7) 257 (98.1) 5 (1.9) 13 (5.0) 128 (98.5) 2 (1.5) 8 (6.2) 129 (97.7) 3 (2.3) 5 (3.8) 0.14 0.85 0.17 0.90 0.75 1.00 0.41 Hypoxemic respiratory failure means hypoxemic respiratory failure excluding pneumonia. Values are n (%). patients. This exclusion did not change the result that ISIBTS decreased the incidence of VAP (␹2 p ⫽ 0.02 and log-rank p ⫽ 0.04). There were two cases of VAP caused by coagulase-negative Staphylococcus, both as polymicrobial VAP, one associated with Pseudomonas aeruginosa and the other with Stenotrophomonas maltophilia. Tube Obstruction, Heat And Moisture Exchangers, and Closed Tracheal Suctioning System Changes. Four patients presented endotracheal tube obstruction in the control group (one episode each) and one patient in the saline group (one episode). However, the difference did not reach statistical significance (Table 5). The number of tracheal suctions per day, HME changes due airway secretions and tracheal closed system suctioning changes due airway secretions were similar between groups (Table 5). Chest Radiograph Analysis. Agreement regarding chest radiograph analysis between physicians was high (for pulmonary atelectasis ␬-statistic ⫽ 0.80, p ⬍ 0.01; for lobar atelectasis ␬-statistic ⫽ 0.41, p ⬍ 0.01, and for segmental atelectasis ␬-statistic ⫽ 0.74, p ⬍ 0.01). The incidence of pulmonary, lobar, and Crit Care Med 2009 Vol. 37, No. 1 Table 2. Characteristics of patients with and without VAP Number of patients (%) Age (years) Male (%) Causes of MV Pneumonia (%) Hypoxemic respiratory failure (%) Coma (%) Shock (%) Neuromuscular disease (%) Others (%) Simplified acute physiologic score II at ICU admission Simplified acute physiologic score II at intubation Immunosuppression (%) Leucopenia (⬍1.000/mm3) (%) Gastric ulcer prophylaxis (%) Type of gastric ulcer prophylaxis H2 blocker (%) Proton pump inhibitor (%) Nasogastric tube (%) Chronic obstructive pulmonary disease (%) Type of airway humidification Heat and moisture exchange (%) Heated humidifier (%) Tracheotomy at admission (%) Antibiotics at ICU admission (%) Antibiotics during ICU stay (%) Mechanical ventilation length (days) ICU length (days) ICU mortality Total VAP⫹ VAP⫺ p 262 64 ⫾ 15 136 (51.9) 45 (17.2) 60 ⫾ 14 217 (82.8) 65 ⫾ 15 0.043 73 (28) 76(29.1) 57 (21.8) 26 (10) 5 (1.9) 24 (9.2) 52.5 ⫾ 15.6 55.1 ⫾ 15.3 78 (29.8) 11 (4.2) 208 (80.0) 12 (27.3) 17 (38.6) 5 (11.4) 6 (13.6) 1 (2.1) 3 (6.8) 51.3 ⫾ 15.8 54.2 ⫾ 15.6 17 (37.8) 4 (8.9) 33 (73.3) 61 (28.1) 59 (27.2) 52 (24.0) 20 (9.2) 4 (1.8) 21 (9.7) 52.7 ⫾ 15.5 55.2 ⫾ 15.3 61 (28.1) 7 (3.2) 175 (81.4) 74 (35.4) 135 (64.6) 112 (42.9) 49 (18.7) 12 (36.4) 21 (63.6) 16 (36.4) 11 (24.4) 62 (35.2) 114 (64.8) 96 (44.2) 38 (17.5) 257 (98.1) 5 (1.9) 13 (5.0) 187 (71.4) 258 (98.5) 11.1 ⫾ 10.1 17.4 ⫾ 12.1 132 (50.8) 44 (97.8) 1 (2.2) 3 (6.7) 30 (66.7) 45 (100) 18.2 ⫾ 10.8 25.4 ⫾ 14.9 30 (66.7) 213 (98.2) 4 (1.8) 10 (4.6) 157 (72.4) 213 (98.2) 9.7 ⫾ 9.4 15.7 ⫾ 10.7 104 (47.9) 0.37 0.57 0.69 0.21 0.1 0.22 1.0 0.40 0.29 1.0 0.47 0.47 1.0 ⬍0.01 ⬍0.01 0.032 VAP⫹, patients who developed ventilator-associated pneumonia; VAP⫺, patients who did not develop ventilator-associated pneumonia. Hypoxemic respiratory failure means hypoxemic respiratory failure excluding pneumonia. Values are n (%). Table 3. Incidence of VAP and use of antibiotics Number of patients (%) Clinically suspected VAP events (%) Microbiological proven VAP (%) Incidence density/1.000 MV days Early-onset VAP (2–5 days of MV) (%) VAP between 5 and 10 days of MV) (%) VAP after 10 days of MV (%) Patients using antibiotics at intensive unit care admission (%) Patients using antibiotics at the day of clinically suspected VAP (%) Patients that used antibiotics during intensive unit care stay (%) Total Saline Control p 262 74 (28.2) 45 (17.2) 15.44 13 (5.0) 16 (6.1) 16 (6.1) 188 (72.0) 130 (49.6) 32 (24.6) 14 (10.8) 9.62 4 (3.1) 7 (5.4) 3 (2.3) 98 (76.0) 132 (50.4) 42 (31.8) 31 (23.5) 21.22 9 (6.8) 9 (6.8) 13 (9.8) 90 (68.2) 0.22 0.008 0.011 0.98 0.17 0.31 0.17 74 (28.2) 31 (23.8) 38 (28.8) 0.38 258 (98.5) 130 (100) 128 (97) 0.12 VAP, ventilator-associated pneumonia, MV, mechanical ventilation. Values are n (%). segmental atelectasis was similar between groups (Table 5). DISCUSSION In the present study, the instillation of isotonic saline before tracheal suctioning decreased the incidence of microbiological proven VAP. The incidence of endotracheal tube occlusion and atelectasis were similar between groups. Crit Care Med 2009 Vol. 37, No. 1 We speculate two reasons upon the decrease in VAP incidence due to ISIBTS. The first reason was a probable airway secretion removal improvement, mainly due to cough stimulation. The second reason was a probable decrease in endotracheal tube biofilm. In patients with VAP, tracheal colonization precedes pneumonia in the majority of patients (30, 31), and microorganisms present in tracheal aspirate and protected specimen bush are concordant (32). Trachea can be considered as an inert passage for microorganisms or as a reservoir of microorganisms. We consider trachea a significant VAP reservoir because the mucosal surface area, volume of pooled secretions, and clearance difficulties are equal or higher in the trachea than in the oropharynx. Considering trachea as a VAP reservoir, ISIBTS may decrease the incidence of VAP because it increases tracheal secretion removal (12). The reasons for secretion removal improvement after saline instillation are speculative. Among them, one probable reason is cough stimulation. The increase in coughing associated to saline instillation was reported in three previous studies (13, 33, 34). Because of in our ICU we avoid deep levels of sedation, cough stimulation could have been an important determinant of VAP incidence decrease. Many authors consider the endotracheal tube biofilm as a reservoir for VAP (14 –16). We can speculate that the frequent rinsing of the endotracheal tube by ISIBTS may have decreased the endotracheal tube biofilm, thereby lessening VAP incidence. However, one study showed that ISIBTS increased viable bacterial dis35 Figure 2. Kaplan-Meier curve. Probability of remaining free from ventilator-associated pneumonia (VAP). Log-rank ⫽ 0.02. Table 4. Microorganisms causing VAP Number of patients (%) Type of infection Monomicrobial VAP (%) Polymicrobial VAP (%) Gram-positive cocci Methicillin-resistant Staphylococcus aureus Coagulase-negative Staphylococci Gram-negative bacilli Pseudomonas aeruginosa Acinetobacter species Stenotrophomonas maltophilia Enterobacteriaceae Burkholderia cepacia Candida species Total Saline Control 262 130 (49.6) 132 (50.4) 35 (13.4) 10 (3.8) 11 (8.5) 3 (2.3) 24 (18.2) 7 (5.3) 6 2 1 0 5 2 16 6 8 10 1 3 7 1 3 4 0 0 9 5 5 6 1 3 p 0.99 0.54 0.59 0.25 VAP, ventilator-associated pneumonia. Values are n (%). Table 5. Atelectasis, tracheal suctions per day, endotracheal tube obstruction, Heat and moisture exchange and closed tracheal suction system changes Number of patients (%) Endotracheal tube occlusion (%) Heat and moisture exchange change due to secretion/100 days of MV Closed tracheal suctioning system change due to secretion/100 days of MV Tracheal suctions per day Chest radiograph analysis Number of patients (%) Pulmonary atelectasis/100 days of MV Lobar atelectasis/100 days of MV Segmental atelectasis/100 days of MV Total Saline Control p 262 5 (1.9) 9 ⫾ 18 130 (49.6) 1 (0.8) 9 ⫾ 19 132 (50.4) 4 (3.0) 10 ⫾ 18 0.37 0.97 2⫾5 1⫾4 2⫾5 0.41 4.8 ⫾ 1.2 4.7 ⫾ 0.9 4.9 ⫾ 1.4 0.14 174 0.21 ⫾ 2.1 0.39 ⫾ 1.9 39.8 ⫾ 39.6 88 (50.6) 0.13 ⫾ 1.3 0.23 ⫾ 1.6 41.2 ⫾ 40.8 86 (49.4) 0.30 ⫾ 2.8 0.55 ⫾ 2.1 38.4 ⫾ 38.5 0.61 0.26 0.64 MV, mechanical ventilation. Chest radiograph films for two patients, one from each group, were lost. Values are n (%). 36 lodgement (11). Nevertheless, authors used a very simple in vitro model that did not consider the anatomical complexity of the airways, especially its branching. In addition, saline instillation was applied once, and it is possible that subsequent instillations would dislodge less viable bacteria than successive suctioning without saline instillation. An interesting result of the present study was the proportional decrease in VAP type (monomicrobial or polymicrobial) and pathogens. This finding corroborates the above hypotheses that a decrease in the microbiological burden in trachea and/or endotracheal biofilm constitutes the mechanism of VAP decrease. Further studies are necessary to elucidate the mechanisms of the benefit of ISIBTS. We believe that a clinical randomized study with a control and saline group and quantification of the bacterial tracheal tube biofilm and cough intensity is necessary. Although the incidence of microbiological proven VAP was higher in the control group, the incidence of clinically suspected VAP was similar between the groups. It was not an unexpected result because we adopted a criterion of low specificity to the diagnosis of clinically suspected VAP (radiographic abnormality plus one of three criteria) leading to many false-positive results (21) that probably diluted any significant difference between groups. Higher airway secretion removal in the saline group could lead to a decrease in the incidence of atelectases due to secretion plugging. Pulmonary or lobar atelectases are usually obstructive. In our study, the incidence of pulmonary and lobar atelectasis in the control group was more than twice that in the saline group, but the difference did not reach statistical significance, probably because the number of events was small. The incidence of segmental atelectasis was similar between groups. This was expected, because segmental atelectasis, especially at the lower lobes, have causes other than secretion plugging, such as increased abdominal pressure, hypoventilation, diaphragm dysfunction, sedation, and the presence of pleural effusion (35). As previously speculated, saline instillation could prevent encrustations in the endotracheal tube (36). Since this speculation sounds plausible, one could expect a significant decrease in the endotracheal tube obstruction in the saline group. There was one episode of endotracheal Crit Care Med 2009 Vol. 37, No. 1 tube obstruction in the saline group and four in the control group. However, the difference did not reach statistical significance, probably because of the small number of events. There are concerns about the safety of ISIBTS, especially the occurrence of hypoxemia. The results are controversial (37) because some studies did not reveal hypoxemia in infants (38) or adults (12, 33) subjected to ISIBTS, whereas another did (39). However, in the latter study the decrease in arterial hemoglobin saturation, while statistically significant, was clinically irrelevant given the difference in saturation was around 1%. Two previous studies have revealed that saline instillation did not cause alterations in blood pressure or heart rate (33, 38). In the present study, there was an apparent lack of impact on patient outcomes such as mortality, MV, and ICU length of stay. Although one could expect an impact on these outcomes because of VAP incidence decrease, it did not occur because our simple size was calculated to compare VAP incidence and not mortality attributed to VAP between groups. In Table 2, we compared the above-mentioned outcomes between patients with and without VAP whereby the occurrence of VAP negatively affected these outcomes. In the present study, there was a high ICU mortality, a expected finding because most of our patients were cancer patients submitted to MV, a known risk factor for ICU death in cancer patients (40). Other studies with similar populations have found a similar or higher mortality (41, 42). A limitation of the present study is its single-center design. Nevertheless, the incidence (1, 3, 43, 44) and microbiology (43, 45) of VAP were similar to other studies. This appraisal is important because, as an oncologic hospital, the presence of immunosuppressed patients was elevated. Notwithstanding, we did not expect that a high percentage of immunosuppressed would affect our results because VAP has been considered a category distinct from pneumonia in immunosuppressed patients, given that pathogenesis differs (46). Besides, the prevalence of immunosuppression was similar between groups. It is worthy of note that the present study was conducted in an ICU with high incidence of VAP and in patients with long MV length of stay using HME, so our study requires confirmation in ICU patients with shorter MV length of stay, use of heated water humidifiers or lower incidence of VAP. Another limitaCrit Care Med 2009 Vol. 37, No. 1 tion is the lack of blinding of the respiratory therapists, but we believe that this did not bias the results, because the ICU physicians were unaware of the patient group. CONCLUSIONS Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP. The incidence of endotracheal tube obstruction, pulmonary, and lobar atelectasis did not differ. ACKNOWLEDGMENTS We thank all Respiratory Therapists of the Hospital A C Camargo Intensive Care Unit: Areta Agostinho, Ana Carolina S. de Oliveira, Ana Cristina Moura Santos, Ana Luiza Arévalo, Anderson Vendramine de Lima, Angela Martins Fernandes, Adriana Larios Nobrega, Celena Freire Friederich, Christiane Costa, Daniela Maia, Denise Simão Carnieli, Diego Brito Ribeiro, Fernanda Dal’maso, Eliana Louzada, Flávia C. Leite, Karla F. G. Bernal, Flávio Carlos Cardoso, Gabriela M. Manfrim, Jackeline S. Segarra, Maina Morales, Juliana Franzotti, Juliana Mesti Mendes, Milena Trudes de Oliveira, Marcelo Colucci, Luciana Nunes Titton, Luciane Sato Anitelli, Valéria Lourença Borba and Mariana R. Gazzotti. We also thank Suelene Aires Franca. REFERENCES 1. Cook DJ, Walter SD, Cook RJ, et al: Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 1998; 129:433– 440 2. Safdar N, Dezfulian C, Collard HR, et al: Clinical and economic consequences of ventilator-associated pneumonia: A systematic review. Crit Care Med 2005; 33:2184 –2193 3. Vincent JL, Bihari DJ, Suter PM, et al: The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA 1995; 274:639 – 644 4. Valles J, Artigas A, Rello J, et al: Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995; 122:179 –186 5. Branson RD: The ventilator circuit and ventilator-associated pneumonia. Respir Care 2005; 50:774 –785; discussion 785–777 6. Kollef MH, Shapiro SD, Fraser VJ, et al: Mechanical ventilation with or without 7-day circuit changes. A randomized controlled trial. Ann Intern Med 1995; 123:168 –174 7. Craven DE, Goularte TA, Make BJ: Contaminated condensate in mechanical ventilator circuits. A risk factor for nosocomial pneumonia? Am Rev Respir Dis 1984; 129:625– 628 8. AARC clinical practice guideline. Endotracheal suctioning of mechanically ventilated adults and children with artificial airways. American Association for Respiratory Care. Respir Care 1993; 38:500 –504 9. Sole ML, Byers JF, Ludy JE, et al: A multisite survey of suctioning techniques and airway management practices. Am J Crit Care 2003; 12:220 –230; quiz 231–222 10. Raymond SJ: Normal saline instillation before suctioning: helpful or harmful? A review of the literature. Am J Crit Care 1995; 4:267–271 11. Hagler DA, Traver GA: Endotracheal saline and suction catheters: Sources of lower airway contamination. Am J Crit Care 1994; 3:444 – 447 12. Bostick J, Wendelgass ST: Normal saline instillation as part of the suctioning procedure: Effects on PaO2 and amount of secretions. Heart Lung 1987; 16:532–537 13. Demers RR, Saklad M: Minimizing the harmful effects of mechanical aspiration. Heart Lung 1973; 2:542–545 14. Adair CG, Gorman SP, Feron BM, et al: Implications of endotracheal tube biofilm for ventilator-associated pneumonia. Intensive Care Med 1999; 25:1072–1076 15. Inglis TJ, Millar MR, Jones JG, et al: Tracheal tube biofilm as a source of bacterial colonization of the lung. J Clin Microbiol 1989; 27:2014 –2018 16. Sottile FD, Marrie TJ, Prough DS, et al: Nosocomial pulmonary infection: Possible etiologic significance of bacterial adhesion to endotracheal tubes. Crit Care Med 1986; 14:265–270 17. Kollef MH, Prentice D, Shapiro SD, et al: Mechanical ventilation with or without daily changes of in-line suction catheters. Am J Respir Crit Care Med 1997; 156:466 – 472 18. Dreyfuss D, Djedaini K, Gros I, et al: Mechanical ventilation with heated humidifiers or heat and moisture exchangers: Effects on patient colonization and incidence of nosocomial pneumonia. Am J Respir Crit Care Med 1995; 151:986 –992 19. Girault C, Breton L, Richard JC, et al: Mechanical effects of airway humidification devices in difficult to wean patients. Crit Care Med 2003; 31:1306 –1311 20. Hess DR, Kallstrom TJ, Mottram CD, et al: Care of the ventilator circuit and its relation to ventilator-associated pneumonia. Respir Care 2003; 48:869 – 879 21. Fabregas N, Ewig S, Torres A, et al: Clinical diagnosis of ventilator associated pneumonia revisited: Comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54:867– 873 22. Chastre J, Fagon JY, Bornet-Lecso M, et al: Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med 1995; 152:231–240 23. Mayhall CG: Ventilator-associated pneumo- 37 24. 25. 26. 27. 28. 29. 30. 31. 38 nia or not? Contemporary diagnosis. Emerg Infect Dis 2001; 7:200 –204 Pound MW, Drew RH, Perfect JR: Recent advances in the epidemiology, prevention, diagnosis, and treatment of fungal pneumonia. Curr Opin Infect Dis 2002; 15:183–194 el-Ebiary M, Torres A, Fabregas N, et al: Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. An immediate postmortem histologic study. Am J Respir Crit Care Med 1997; 156:583–590 Rello J, Esandi ME, Diaz E, et al: The role of Candida sp isolated from bronchoscopic samples in nonneutropenic patients. Chest 1998; 114:146 –149 Bland JM, Altman DG: Survival probabilities (the Kaplan-Meier method). BMJ 1998; 317: 1572 Bland JM, Altman DG: The logrank test. BMJ 2004; 328:1073 Chmura Kraemer H, Periyakoil VS, Noda A: Kappa coefficients in medical research. Stat Med 2002; 21:2109 –2129 de Latorre FJ, Pont T, Ferrer A, et al: Pattern of tracheal colonization during mechanical ventilation. Am J Respir Crit Care Med 1995; 152:1028 –1033 George DL, Falk PS, Wunderink RG, et al: Epidemiology of ventilator-acquired pneu- 32. 33. 34. 35. 36. 37. 38. monia based on protected bronchoscopic sampling. Am J Respir Crit Care Med 1998; 158:1839 –1847 Torres A, el-Ebiary M, Gonzalez J, et al: Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. Am Rev Respir Dis 1993; 148:352–357 Gray JE, MacIntyre NR, Kronenberger WG: The effects of bolus normal-saline instillation in conjunction with endotracheal suctioning. Respir Care 1990; 35:785–790 Jablonski RS: The experience of being mechanically ventilated. Qual Health Res 1994; 4:186 –207 Maffessanti M, Berlot G, Bortolotto P: Chest roentgenology in the intensive care unit: an overview. Eur Radiol 1998; 8:69 –78 O’Neal PV, Grap MJ, Thompson C, et al: Level of dyspnoea experienced in mechanically ventilated adults with and without saline instillation prior to endotracheal suctioning. Intensive Crit Care Nurs 2001; 17:356 –363 Blackwood B: Normal saline instillation with endotracheal suctioning: Primum non nocere (first do no harm). J Adv Nurs 1999; 29:928 –934 Shorten DR, Byrne PJ, Jones RL: Infant responses to saline instillations and endotracheal suctioning. J Obstet Gynecol Neonatal Nurs 1991; 20:464 – 469 39. Ackerman MH: The effect of saline lavage prior to suctioning. Am J Crit Care 1993; 2:326 –330 40. Maschmeyer G, Bertschat FL, Moesta KT, et al: Outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period. Eur J Cancer 2003; 39:783–792 41. Soares M, Salluh JI, Spector N, et al: Characteristics and outcomes of cancer patients requiring mechanical ventilatory support for ⬎24 hrs. Crit Care Med 2005; 33: 520 –526 42. Kress JP, Christenson J, Pohlman AS, et al: Outcomes of critically ill cancer patients in a university hospital setting. Am J Respir Crit Care Med 1999; 160:1957–1961 43. Chastre J, Fagon JY: Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:867–903 44. Rello J, Ollendorf DA, Oster G, et al: Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002; 122:2115–2121 45. Park DR: The microbiology of ventilatorassociated pneumonia. Respir Care 2005; 50: 742–763; discussion 763–745 46. Wunderink RG: Nosocomial pneumonia, including ventilator-associated pneumonia. Proc Am Thorac Soc 2005; 2:440 – 444 Crit Care Med 2009 Vol. 37, No. 1