Journal of Critical Care (2011) 26, 482488

An open-labelled randomized controlled trial comparing costs and clinical outcomes of open endotracheal suctioning with closed endotracheal suctioning in mechanically ventilated medical intensive care patients,,,
Deepu David MD a,, Prasanna Samuel MSc b , Thambu David MD, DNB a , Shyamkumar Nidugala Keshava MBBS, DMRD, DNB, FRCR, FRANZCR c , Aparna Irodi MBBS, DMRD, MD, FRCR c , John Victor Peter MD, DNB, FRACP, FJFICM, FCICM d
a

Department of Medicine II, Christian Medical College & Hospital, Vellore, 632004, Tamil Nadu, India Department of Biostatistics, Christian Medical College and Hospital, Vellore, India c Department of Radiodiagnosis, Christian Medical College and Hospital, Vellore, India d Medical Intensive Care Unit, Christian Medical College and Hospital, Vellore, India
b

Keywords:
Endotracheal; Suctioning; Ventilator-associated pneumonia; Mortality; Outcome

Abstract Purpose: Closed endotracheal suctioning (CES) may impact ventilator-associated pneumonia (VAP) risk by reducing environmental contamination. In developing countries where resource limitations constrain the provision of optimal bed space for critically ill patients, CES assumes greater importance. Materials and Methods: In this prospective, open-labeled, randomized controlled trial spanning 10 months, we compared CES with open endotracheal suctioning (OES) in mechanically ventilated patients admitted to the medical intensive care unit (ICU) of a university-affiliated teaching hospital. Patients were followed up from ICU admission to death or discharge from hospital. Primary outcome was incidence of VAP. Secondary outcomes included mortality, cost, and length of stay. Results: Two hundred patients were recruited, 100 in each arm. The incidence of VAP was 23.5%. Closed endotracheal suctioning was associated with a trend to a reduced incidence of VAP (odds ratio,

Institution where study was done: Christian Medical College and Hospital, Vellore, India. Name, date, and location of any meeting or forum: This study was awarded the Hansraj Nayyar award for the best paper at the 16th Annual Conference of the Indian Society of Critical Care Medicine, February 2010. Financial support: The study was supported by the Fluid Research Grant, Christian Medical College & Hospital, Vellore, India, and funded partly by Tyco Health Care, who provided the closed suction catheters. There was no conflict of interest for any of the authors, nor did the funding agencies have any role in the data collection, analysis, or write-up of the study. Contributions: Study conceived and designed by J.V.P; data abstraction form by D.D. and J.V.P.; data collection by D.D.; statistical expertise by P.S.; coordinating the study, planning, literature review, and overall direction by T.D. and J.V.P.; and radiological aspects by S.N.K. and A.I. All authors have reviewed the final version of the manuscript and have approved for submission. Corresponding author. Tel.: +91 416 228 2031(Office), +91 99940 68478(Mobile). E-mail address: deepudavid@gmail.com (D. David).

0883-9441/$ see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2010.10.002

Costs and clinical outcomes of OES vs CES in ICU patients

483

1.86; 95% confidence interval, 0.91-3.83; P = .067). A significant benefit was, however, observed with CES for late-onset VAP (P = .03). Mortality and duration of ICU and hospital stay were similar in the 2 groups. The cost of suction catheters and gloves was significantly higher with CES (Rs 272 [US $5.81] vs Rs 138 [US $2.94], P b .0001). Nine patients need to be treated with CES to prevent 1 VAP (95% confidence interval, 0.7 to 22). Conclusions: In the ICU setting in a developing country, CES may be advantageous in reducing the incidence of VAP, particularly late-onset VAP. These results mandate further studies in this setting before specific guidelines regarding the routine use of CES are proposed. 2011 Elsevier Inc. All rights reserved.

1. Introduction
In recent years, there has been a trend to use closed endotracheal suctioning (CES) over the traditional open endotracheal suctioning (OES) system [1]. Closed endotracheal suctioning is postulated to decrease the risk of ventilator-associated pneumonia (VAP) by limiting environmental contamination and preventing spread of infection [2]. However, this potential advantage has not translated into clinically meaningful improvements, with recent metaanalyses [1,3,4] of randomized controlled trials failing to demonstrate a benefit of CES over OES for clinical outcomes that include VAP incidence, mortality, and length of hospital stay. Although these results are important for the implementation of evidence-based clinical practice, they cannot be considered conclusive because the meta-analyses were underpowered to detect a true difference between suctioning systems [5]. Furthermore, most trials were conducted in firstworld environments limiting its application to intensive care units (ICUs) in developing countries. Interestingly, the relevant guidelines on this issue, published before the meta-analyses, also are inconclusive. The American Association for Respiratory Care recommends closed suctioning as a strategy to prevent VAP [6]. The European Task Force on VAP suggested that the limited evidence of CES in reducing VAP was at the expense of increased cost [7]. The Canadian Critical Care Society concluded that the type of suctioning had no effect on VAP incidence [8]. The Centers for Disease Control and Prevention stated that the preferential use of either the closed or the open tracheal suctioning for VAP prevention was an unresolved issue [9]. In developing countries, additional challenges may contribute to the development of VAP. These include inadequate staffing and patient overcrowding that could increase cross-contamination between patients and an increased burden of infectious diseases, particularly pulmonary tuberculosis. Thus, ICU beds in close proximity may impact VAP, given that studies on postsuction colony counts have demonstrated organisms up to 1 m from the suction site with open suctioning but not with closed suctioning [2]. Closed endotracheal suctioning may also impact VAP rates by reducing cross-contamination between the bronchial

system and gastric juices [10]. However, until clinical benefit of CES is demonstrated, its use cannot be justified in developing nations [5]. This study was thus done to compare clinical outcomes and cost of OES with CES in medical ICU patients. The primary objective was to assess if CES and OES resulted in an equivalent incidence of VAP in mechanically ventilated ICU patients. Secondary outcomes included mortality, duration of hospitalization, and cost.

2. Materials and methods

2.1. Study design and eligibility criteria
This randomized controlled equivalence trial was performed for 10 months (June 2007-March 2008) in the Medical ICU of a tertiary care universityaffiliated teaching hospital in South India. The study was approved by the institutional research and ethics committees. All adult patients (N18 years) admitted to the ICU and needing invasive mechanical ventilation within the first 24 hours were considered for inclusion. Patients were excluded if they required high positive end expiratory pressure and were deemed to require CES by the clinician. Patients admitted following cardiac arrest, those needing mechanical ventilation after 24-hours of ICU admission, and patients whose relatives did not agree to participate in the trial were excluded. Patients were randomized either to OES or to CES using computer-generated random numbers with blocks of varying size. Allocation concealment was ensured with the use of sealed envelopes. Blinding was not possible in view of the nature of the study. However, the radiologists assessing the x-rays were blinded. Relevant data were collected in data abstraction forms. Patients were followed up till death or hospital discharge.

2.2. Study outcomes

The primary outcome measure was VAP incidence. Ventilator-associated pneumonia was diagnosed using clinical criteria and the clinical pulmonary infection score (CPIS). The clinical criteria constitute the presence of at least

484 2 of the following in association with a new and persistent radiographic infiltrate: (i) body temperature higher than 38C or lower than 36C without obvious extrapulmonary infectious source, (ii) white blood cells more than 10 000 or less than 4000/cu mm, and (iii) macroscopically purulent tracheal aspirate. This criteria, with a sensitivity of 69% and specificity of 75% [11], as per the American Thoracic Society statement, represents the most accurate clinical criteria for starting empiric antibiotic therapy [12]. The more stringent CPIS score, with a sensitivity of 60% to 77% and a specificity of 42% to 85%, was also used independently to diagnose VAP [11,13]. Ventilator-associated pneumonia was classified as early or late depending on whether it developed within or after 4 days of ventilation [14]. Secondary outcomes considered were in-hospital mortality, duration of hospital stay, and cost of suctioning (suction catheters and gloves).

D. David et al. between CES and OES arms. We calculated 95% confidence interval (CI) around this difference in VAP incidence to determine whether it met our definition of equivalence (14%). If the 95% CI for the difference lies entirely within our equivalence margin (14% and +14%), then CES is considered equivalent to the OES. 2 Test and MannWhitney U test was used for all other exploratory analysis (testing for superiority). Odds ratio and CIs were calculated, and a P value less than .05 was considered significant. Data were analyzed using SPSS version 15 (SPSS, Chicago, Ill).

3. Results
Of the 693 patients admitted to the ICU during the study period, 448 required mechanical ventilation. Two-hundred forty-eight patients were excluded (Fig. 1). The remaining were randomized into CES (n = 100) or OES (n = 100). Baseline characteristics were comparable except for a higher (P = .02) incidence of ischemic heart disease in the CES group (Table 1). Poisoning and drug overdose constituted 22% of the patients. The mean (SD) Acute Physiology and Chronic Health Evaluation II scores of 21.05 (6.16) and 20.82 (6.33) in the OES and CES groups, respectively (P = .79), correspond to a predicted mortality of about 40% in both the groups. Elective intubation was performed in

2.3. Statistical methods

Although VAP incidence ranges from 6.8% to 44%, a recent meta-analysis showed an incidence of 18.6% with open and 19.8% with closed suctioning [3]. An equivalence study with 80% power, 5% error and a sample size of 100 in each arm was planned so that a difference of less than 14% between the groups would be considered equivalent. The primary end point was the difference in the incidence of VAP

Fig. 1

Schematic representation of patient flow in the trial.

Costs and clinical outcomes of OES vs CES in ICU patients

Table 1 Baseline characteristics of the participants Open suction 44 50 16 17 4 1 2 3 4 11 9 3 7 5 6 3 11 1 73 14 49 35 2 6 21.05 40% Closed suction 42 54 20 16 1 9 1 5 4 12 7 0 6 5 5 0 13 9 67 0.15 5 51 50 4 4 20.82 40% .54 .79 P

485 17% randomized to the OES group and 22% randomized to the CES group (P = .37). Mechanical ventilation was required for more than 4 days in 60% of the patients in CES group and 56% in OES group. Outcome measures are summarized in Table 2. The overall incidence of VAP was 23.5% when clinical criteria were used and 14% with the CPIS score. Using the clinical criteria, the incidence of VAP was higher with OES than with CES. The absolute difference in the incidence of VAP was 11%, with a 95% CI ranging from 0.6% to 22%. For OES to be considered equivalent with CES, the limits of 95% CI could not exceed 14%. Thus, according to our prespecified definition of equivalence (14%), the OES and CES were not found to be equivalent. When tested for superiority, CES was associated with a trend to a reduced incidence of VAP (odds ratio, 1.86; 95% CI, 0.91-3.83; P = .067). The number needed to treat with CES to prevent 1 VAP was 9 (95% CI, 0.7 to 22.7). A significant benefit was observed with CES for late-onset VAP (P = .03) but not for early VAP (P = .82). The median time to develop VAP was similar in the 2 groups (OES 4 days vs CES 3 days, P = .08). No association between the type of suctioning and VAP incidence was observed when the CPIS was used (P = .1). The duration of ventilation, ICU stay, and hospital stay were similar (Table 2) in the 2 groups. Overall in-hospital mortality of the study cohort was 52.5%, with mortality of 57% in the OES group and 48% in the CES group (P = .2). The Kaplan-Meier survival graph is presented in Fig. 2. In-hospital mortality for patients with VAP was 48.9%. Of the 47 patients diagnosed with VAP, endotracheal aspirates from 5 patients did not grow organisms. Ten patients had a monomicrobial infection, and the rest had polymicrobial growth. The isolates were similar in both groups (Table 3) and included Pseudomonas (63.8%), nonfermenting gram-negative bacilli other than Pseudomonas (36.2%), Klebsiella (32%), and staphylococcus (19.1%).

Baseline characteristics Demographic data Age (y) Male Comorbidities Diabetes Hypertension Dyslipidemia Ischemic heart disease Cerebrovascular accident COPD Smoking Malignancy Chronic renal failure HIV status Other respiratory diseases Previous medications Steroids Aspirin HAART Immunosuppressive Others None Place of intubation ICU Emergency department Wards Previous hospital Prior NIV use Prior NIV use Admission APACHE II score Score Predicted mortality

.31 .57 .46 .85 .17 .02 .56 .47 .99 .83 .60 .08 .77 0.13

COPD indicates chronic obstructive pulmonary disease; HAART, highly active antiretroviral therapy; NIV, noninvasive ventilation; HIV, human immunodeficiency virus; APACHE, Acute Physiology and Chronic Health Evaluation.

Table 2

Outcome measures Open suction 29 18 11 18 (29%) (18%) (11%) (32%) Closed suction 18 10 10 8 (18%) (10%) (10%) (13%) Odds ratio (95% CI) 1.86 1.98 1.11 3.08 (0.91-3.83) (0.81 - 4.91) (0.41-3.0) (1.12-8.70) P .07 .15 .82 .03 .48 .20 .99 .48 .65 .0001

Outcome measure VAP Clinical criteria CPIS Early VAP Late VAP (%) Mortality ICU Hospital Duration of stay a ICU Hospital Duration of ventilation a Cost of suction b
a b

47 (47%) 57 (57%) 6 12 6 138 (1-35) (1-80) (1-39) (2.94)

42 (42%) 48 (48%) 6 11.5 5 272 (1-25) (1-98) (1-29) (5.81)

1.22 (0.67-2.23) 1.44 (0.79-2.61)

Median duration in days (range). Cost of suction per day in Rs (US $).

486

D. David et al. for the superiority of CES over OES and would justify a large superiority trial to conclusively address this issue. When tested for superiority, we found a trend to having a benefit (P = .07) in terms of reduction of VAP rates with CES, particularly for late-onset VAP (P = .03) It is recognized that the incidence of VAP varies depending on the type of ICU, the population admitted, and the criteria used for the diagnosis of VAP. Although clinical criteria have been found to be less specific than other diagnostic methods, we chose this over the CPIS due to its simplicity. Furthermore, we preferred to use a tool that might overdiagnose VAP rather than one that could potentially miss the diagnosis. Closed endotracheal suctioning catheters, in our study, were used for a maximum period of 1 week, since trials have shown that although the prolonged use of closed suctioning system was associated with increased colonization of the device [15], there was no documented increase in the incidence of VAP [16-18], and its use was considered safe and cost-effective [15-18]. There was no difference between the 2 groups with adherence to other measures of VAP prevention like weaning protocols, oral disinfection, and elevation of the head of the bed. The incidence of VAP of 23.5% in our study, although comparable with reports from systematic analysis [1,3,19], is higher than previous unpublished data (17% in 1999, 8.5 in 2005-2006) from our institution (personal communication). These changing trends could be partly attributed to changing patient case mix and the diagnostic tools used. In 2 other studies from India, VAP rates were found to be 16.7% [20] and 45.4% [21]. The median duration to develop VAP in our study of 4 days was similar to other studies [22]. Using clinical criteria to diagnose VAP, we observed a trend (P = .07) favoring CES over OES. This finding contrasts the results of meta-analysis that did not show any difference in VAP rates [1,4]. Late VAP was significantly higher with OES in our study compared with CES (P = .03). Considering that 58% of the patients enrolled into our study stayed beyond 4 days, CES may be worth considering for patients expected to stay long in the ICU. The predominance of gram-negative bacilli implicated in VAP in our study is consistent with other studies [23,24]. However, in contrast to other studies that reported a preponderance of methicillin-sensitive Staphylococcus aureus, Staphylococcus pneumoniae, and Haemophilus influenza in early VAP and methicillin-resistant S aureus, Pseudomonas aeruginosa, Acinetobacter baumannii. and Stenotrophomonas maltophilia in late VAP [24,25], we observed that P aeruginosa was the commonest pathogen for both early and late VAP. The crude mortality rates in patients with VAP in previous studies have ranged from 23.7% [26] to 65.0% [27]. Our mortality rate of 48.9% lies in between. There was no differential treatment effect of type of suctioning on mortality and length of stay in our study, and this is consistent with the findings of a previous meta-analysis [4]. Although trials have shown a lower duration of mechanical

Fig. 2 This graph compares the survival probabilities of both the groups over time. Median survival time in open suction group was 18 days (95% CI, 11.6-24.4) and closed group was 27 days (95% CI, 17.2-36.8). There was no significant difference between the 2 groups with regard to patient survival (P = .14).

Suctioning costs were calculated by including the cost of gloves as well as the suction catheters and compared for CES and OES. The median cost of suctioning per day was Rs 272 (US $5.81) for CES and Rs 138 (US $2.94) for OES (P b .0001).

4. Discussion
Although several trials have been performed on CES vs OES in developed countries, there is paucity of trials from developing countries where other unique factors may play a role. In this randomized trial of 200 patients admitted to the medical ICU, we observed an incidence of VAP of 23.5% using the clinical criteria. The 95% CI for differences in VAP partially overlapped with their respective predefined equivalence margins. Our data thus provide promising evidence

Table 3 Organism

Organisms isolated in each group in patients with VAP Open suction (n = 56) 4 (7.1) 20 (35.71) 11 (19.64) 2 (3.5) 1 (1.7) 3 (5.6) 5 (8.9) 10 (17.85) Closed suction (n = 35) 4 (11.42) 10 (28.57) 6 (17.14) 2 (5.7) 1 (2.8) 1 (2.8) 4 (11.42) 7 (20) P .22 .36 .71 .57 .65 .3 .49 .72

Escherichia coli Pseudomonas NFGNB Enterococcus Pneumococcus H influenza Staphylococcus aureus Klebsiella

Values in parentheses indicate percentages; the total number of organisms adds up to more than the total numbers of patients in each group, as multiple organisms were isolated in some situations. *NFGNB indicates nonfermenting gram-negative bacilli.

Costs and clinical outcomes of OES vs CES in ICU patients ventilation in patients randomized to OES [4], we did not observe a difference (P = .65). In resource-constrained developing countries like India, cost-effectiveness is an important factor that needs to be considered before implementation of a new intervention, particularly when clinical benefits may be marginal. Studies from developed countries on the type of suctioning device have been inconclusive with 2 studies [28,29] reporting higher costs for CES and with 1 study [30] reporting lower costs. One other study [31] showed that the cost of CES was higher when length of mechanical ventilation was less than 4 days and lower when longer duration of ventilation was required. The higher cost of CES in our study was primarily due to the use of an additional catheter to clear oral secretions. However, further cost issues need to be considered. If we assume a number needed to treat with CES to prevent 1 VAP as 9 patients, in patients ventilated for a median duration of 6 days, the additional suctioning cost would be Rs 7236 (around US $157). This cost is small considering the cost of a 10-day course of an antibiotic (Piperacillin/Tazobactam or Meropenem) to treat VAP (US $513-1030) as well as costs of other medications and additional hospital stay due to VAP. Thus, CES may be worthwhile in ICUs in a developing country. The study has the following limitations. The intervention was not blinded except for the radiologic diagnosis of pneumonia and, hence, was at risk for bias for outcomes dependent on the clinician's discretion, such as duration of ventilation and days in the ICU. A higher proportion of patients with ischemic heart disease were randomized to CES; its impact is uncertain. The high rate of emergency intubation of about 80% reflects the case mix of the study, which was done in the medical ICU and did not include postoperative patients who are managed in the surgical ICU. Although emergency intubation may have impacted VAP rates by increasing aspiration risk, the proportion of patients requiring emergency intubations in both treatment arms was similar, and it is likely that aspiration risk would have been equal in both arms. Patients who were intubated in the wards may have experienced delays of up to 3 to 4 hours before shifting to ICU that could have resulted in the use of OES before randomization. Finally, costing issues were not all inclusive and did not incorporate nursing time, among others.

487 this setting before specific guidelines regarding the routine use of CES is proposed.

References
[1] Jongerden IP, Rovers MM, Grypdonck MH, et al. Open and closed endotracheal suction systems in mechanically ventilated intensive care patients: a meta-analysis. Crit Care Med 2007;35(1):260-70. [2] Cobley M, Atkins M, Jones PL. Environmental contamination during tracheal suction. A comparison of disposable conventional catheters with a multiple-use closed system device. Anaesthesia 1991;46(11): 957-61. [3] Peter JV, Chacko B, Moran JL. Comparison of closed endotracheal suction versus open endotracheal suction in the development of ventilator-associated pneumonia in intensive care patients: an evaluation using meta-analytic techniques. Indian J Med Sci 2007;61 (4):201-11. [4] Siempos II, Vardakas KZ, Falagas ME. Closed tracheal suction systems for prevention of ventilator-associated pneumonia. Br J Anaesth 2008;100(3):299-306. [5] Morrow BM. Closed-system suctioning: why is the debate still open? Indian J Med Sci 2007;61(4):177-8. [6] Hess DR, Kallstrom TJ, Mottram CD, et al. Care of the ventilator circuit and its relation to ventilator-associated pneumonia. Respir Care 2003;48(9):869-79. [7] Torres A, Carlet J. Ventilator-associated pneumonia. European Task Force on ventilator-associated pneumonia. Eur Respir J 2001;17(5): 1034-45. [8] Dodek P, Keenan S, Cook D, et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med 2004;141(4):305-13. [9] Tablan OC, Anderson LJ, Arden NH, et al. Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol 1994;15(9):587-627. [10] Rabitsch W, Kostler WJ, Fiebiger W, et al. Closed suctioning system reduces cross-contamination between bronchial system and gastric juices. Anesth Analg 2004;99(3):886-92. [11] 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(10):867-73. [12] Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171(4):388-416. [13] Papazian L, Thomas P, Garbe L, et al. Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med 1995;152(6):1982-91. [14] Langer M, Cigada M, Mandelli M, et al. Early onset pneumonia: a multicenter study in intensive care units. Intensive Care Med 1987;13 (5):342-6. [15] Freytag CC, Thies FL, Konig W, et al. Prolonged application of closed in-line suction catheters increases microbial colonization of the lower respiratory tract and bacterial growth on catheter surface. Infection 2003;31(1):31-7. [16] Darvas JA, Hawkins LG. The closed tracheal suction catheter: 24 hour or 48 hour change? Aust Crit Care 2003;16(3):86-92. [17] Stoller JK, Orens DK, Fatica C, et al. Weekly versus daily changes of in-line suction catheters: impact on rates of ventilator-associated pneumonia and associated costs. Respir Care 2003;48(5):494-9. [18] 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(2):466-72. [19] Vonberg RP, Eckmanns T, Welte T, et al. Impact of the suctioning system (open vs. closed) on the incidence of ventilation-associated

5. Conclusions
In this randomized control trial of CES vs OES, a benefit of reduction in VAP rates was evident for late-onset VAP. Although the cost of CES was higher, reduction in VAP is likely to translate to cost savings overall, given the high costs of treating VAP. Closed endotracheal suctioning catheters should be considered in patients expected to need ventilation for more than 4 days. These results mandate further studies in

488
pneumonia: meta-analysis of randomized controlled trials. Intensive Care Med 2006;32(9):1329-35. Merchant M, Karnad DR, Kanbur AA. Incidence of nosocomial pneumonia in a medical intensive care unit and general medical ward patients in a public hospital in Bombay, India. J Hosp Infect 1998;39 (2):143-8. Dey A, Bairy I. Incidence of multidrug-resistant organisms causing ventilator-associated pneumonia in a tertiary care hospital: a nine months' prospective study. Ann Thorac Med 2007;2(2):52-7. Tejerina E, Frutos-Vivar F, Restrepo MI, et al. Incidence, risk factors, and outcome of ventilator-associated pneumonia. J Crit Care 2006;21 (1):56-65. Richards MJ, Edwards JR, Culver DH, et al. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999;27(5):887-92. Alp E, Voss A. Ventilator associated pneumonia and infection control. Ann Clin Microbiol Antimicrob 2006;5:7. Rello J, Torres A. Microbial causes of ventilator-associated pneumonia. Semin Respir Infect 1996;11:24-31.

D. David et al.
[26] Heyland DK, Cook DJ, Griffith L, et al. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group. Am J Respir Crit Care Med 1999;159:1249-56. [27] Alp E, Guven M, Yildiz O, et al. Incidence, risk factors and mortality of nosocomial pneumonia in intensive care units: a prospective study. Ann Clin Microbiol Antimicrob 2004;3:17. [28] Lorente L, Lecuona M, Martin MM, et al. Ventilator-associated pneumonia using a closed versus an open tracheal suction system. Crit Care Med 2005;33:115-9. [29] Adams DH, Hughes M, Elliott TS. Microbial colonization of closedsystem suction catheters used in liver transplant patients. Intensive Crit Care Nurs 1997;13:72-6. [30] Johnson KL, Kearney PA, Johnson SB, et al. Closed versus open endotracheal suctioning: costs and physiologic consequences. Crit Care Med 1994;22:658-66. [31] Lorente L, Lecuona M, Jimenez A, et al. Tracheal suction by closed system without daily change versus open system. Intensive Care Med 2006;32:538-44.

[20]

[21]

[22]

[23]

[24] [25]

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.