PEDIATRICS Vol. 122 No. 4 October 2008, pp. 770-774 (doi:10.1542/peds.2007-1826)
ARTICLE |
Randomized, Controlled Trial on Tracheal Colonization of Ventilated Infants: Can Gravity Prevent Ventilator-Associated Pneumonia?
a Department of Newborn Services, George Washington University and Children's National Medical Center, Washington, DC
b Department of Neonatology, Children's Hospital
c Department of Microbiology, School of Medicine, Cairo University, Cairo, Egypt
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The goal was to test the hypothesis that intubated infants positioned on their sides would be less likely to contract bacterial colonization in their tracheae, compared with those positioned supine.
METHODS. We conducted a prospective, randomized, controlled trial with 60 intubated infants; 30 infants were positioned supine (supine group), and 30 infants were maintained in the lateral position (lateral group). Tracheal aspirates were cultured and bacterial colony counts were recorded after 48 hours and after 5 days of mechanical ventilation.
RESULTS. After 2 days, the numbers of positive tracheal cultures in the supine group (67%) and in the lateral group (47%) showed no statistical difference. After 5 days of mechanical ventilation, tracheal cultures differed significantly between groups. Cultures were positive for 26 infants (87%) in the supine group and 9 infants (30%) in the lateral group. Compared with the lateral group, more infants in the supine group experienced increased colony counts or had new organisms in their tracheal aspirates over time (21 vs 8 infants). The most common organisms isolated from tracheal aspirates in both groups were Gram-negative rods.
CONCLUSIONS. Respiratory contamination is very common among ventilated infants. Therefore, judicious use of mechanical ventilation cannot be overemphasized. Gravitational force can ameliorate the onset of respiratory colonization. The mechanism and clinical applicability of such observations need to be explored further.
Key Words: endotracheal tube • ventilator-associated pneumonia • microbiology • infants • preterm • NICU
Abbreviations: VAP—ventilator-associated pneumonia
Ventilator-associated pneumonia (VAP) is the leading cause of death among nosocomial infections in ventilated patients. The diagnosis of VAP in neonates is difficult; therefore, the exact incidence cannot be estimated. In adult populations, however, the risk of pneumonia is increased threefold to 10-fold after intubation, and almost 90% of hospital-acquired pneumonia cases involve intubated patients.1 The causative pathogens and the hospitalization course are more benign when VAP occurs early after intubation (<5 days), compared with a late onset (
5 days).2 Each episode of VAP is associated with 7 to 9 days of additional hospital stay, with an estimated increase in costs of care that can exceed $40 000.3 In an effort to control VAP, several studies were conducted, with approaches such as oral and gastric decontamination with antibiotics, rotation of the patient, and local instillation of antibiotics through the endotracheal tube.4–7 Despite such efforts, VAP remains a major unsolved problem among intubated patients.
The effect of gravity on bacterial colonization of the respiratory system was explored in an animal study at the US National Institutes of Health.8 The study demonstrated significantly decreased tracheal colonization and decreased alveolar contamination in ventilated sheep when they were positioned on their sides, allowing for tracheal drainage through gravity.8 Such findings have not been validated in clinical practice, and clinical trials studying the effects of lateral positioning have been demanded.9 We embarked on a randomized, controlled trial to test the hypothesis that intubated infants positioned on their sides would be at lower risk for contracting microbes in their tracheae, compared with those in a supine position.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Setting
A prospective, randomized, controlled trial was conducted in the neonatal unit at Cairo University Children's Hospital (Cairo, Egypt). The trial was approved by the institutional review board at Cairo University, and parental consent was obtained. Recruitment of subjects started in 2005 and was completed in 13 months.
Patients
Infants were included in the study if all of the following criteria were fulfilled: (1) gestational age of 28 weeks, (2) tracheal intubation at postnatal age of <48 hours, (3) conventional mechanical ventilation for 5 days, and (4) parental consent obtained. Infants were not considered for the study if they were diagnosed as having congenital sepsis or pneumonia or congenital anomalies such as tracheoesophageal fistulae, thoracic cage deformities, or diaphragmatic hernias. Infants were excluded from the study if they could not be maintained on mechanical ventilation for 5 full days.
Eligible subjects were identified and assigned to 1 of 2 groups according to a predetermined randomization sequence. The investigators did not have control regarding the randomization sequence when recruiting a new subject.
In the supine group, infants were maintained on their backs at all times. The endotracheal tube was held upright in a vertical position at all times. The bed was kept horizontal without any angle or tilt.
In the lateral group, infants were maintained on their side with the back supported by a rolled soft towel. The endotracheal tube was oriented horizontal on the bed (Fig 1). Infants were expected to change position from one side to the other every 2 hours, when their clinical conditions allowed such manipulation; however, turning was accomplished less frequently because of the workload of the NICU staff. The bed was maintained flat, without tilt, at all times. Demographic and clinical data, including ventilatory management, blood gas measurements, and readings of chest radiographs, were documented routinely.
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Airway Care
Suction of the endotracheal tube was performed by using a sterile, open-circuit technique, with a single-use, disposable, suction catheter. Infants were preoxygenated and were ventilated manually with a self-inflating bag between suction catheter passes. Drops of sterile normal saline solution were instilled to liquefy tracheal secretions. Tracheal suctioning was performed during routine care according to unit policy for nurses (usually every 8 hours or as needed), without involvement or interference by any of the investigators. Ventilator circuits were not changed routinely in the NICU.
Respiratory Cultures
Respiratory cultures were obtained on days 2 and 5 after mechanical ventilation. Respiratory aspirates were obtained without previous installation of saline solution. The suction catheter was attached to a standard sputum trap, and all samples were processed within 30 minutes. Samples were qualitatively plated on blood, chocolate, and Sabouraud agar media in serial dilutions of 1:10, 1:100, and 1:1000. When results were negative, the plates were discarded after 3 days of resting for aerobic bacteria and 4 weeks for fungi. Positive culture results were expressed in colony-forming units per mL. All cultures were processed by the same microbiologist, who was not aware of the infants' group assignment.
Sample Size and Data Analysis
Previous microbiologic studies of tracheal aspirates reported 70% colonization of intubated infants.10 We hypothesized that gravity could account for 50% of microbial colonization in the tracheae of intubated infants. To demonstrate a difference in colonization from 70% to 20%, a sample size of 25 in each group was required (power of 90%, β of 10%, and 
of 5%). Five patients were added to each group to account for any differences in baseline colonization rates in the environment at our unit, compared with the values reported previously. Therefore, a total of 60 infants were required for this study.
Demographic data were expressed as mean ± SD for continuous variables and proportion for categorical variables. Microbiologic results and bacterial colony counts in the 2 tracheal aspirates (at 2 and 5 days) were charted for each subject. Routine laboratory results, blood gas values, and ventilator settings were recorded. Univariate and bivariate analyses were conducted to compare groups, using the 2-tailed Student's t test and the 
2 test for continuous and categorical variables, respectively.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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A total of 79 infants were initially enrolled in the trial; 19 infants dropped out of the study because of death (n = 15) or early extubation (n = 4). Therefore, 60 infants completed the study, 30 infants in the supine group and 30 infants in the lateral group. The 2 groups were similar in demographic and clinical characteristics, with the exception that more infants in the supine group were fed and required reintubation (Table 1). Because all infants were <1 week of age and had respiratory distress, they all began antibiotic treatment, according to unit policy, until sepsis could be ruled out. The values for blood gas measurements and ventilator settings during the study period (5 days) did not differ among groups (Table 2). Findings from chest radiographs after 5 days of ventilation differed significantly between groups. Twenty infants in the supine group had new or persistent infiltrates and/or opacities (14 on the right side, 4 on the left side, and 3 bilateral), compared with 6 infants in the lateral group (2 on the right side, 3 on the left side, and 1 bilateral) (P < .01).
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Cultures of tracheal aspirates at 48 hours yielded positive results for 20 infants (67%) in the supine group and 14 infants (47%) in the lateral group; the difference was not significant (P = .12). The number of colonies recovered in the supine group (n = 20; 1.1 x 106± 1.3 x 106 colony-forming units per mL) was significantly greater than that in the lateral group (n = 14; 4.4 x 105± 3.8 x 105 colony-forming units per mL; P = .03). Isolated organisms were mostly Gram-negative rods in both groups (13 of 20 isolates in the supine group and 11 of 14 isolates in the lateral group; P = .6) (Table 3).
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At 5 days, the number of positive tracheal cultures was significantly higher in the supine group (26 of 30 infants, 87%) than in the lateral group (9 of 30 infants, 30%;
= 19.8, P < .01) (Fig 2). Compared with the lateral group, there were more infants in the supine group who experienced increased colony counts and/or had new organisms in their tracheal aspirates over time (21 vs 8 infants; = 11.3, P < .001). The most common organisms recovered from both groups were Gram-negative rods (18 vs 6 isolates; P < .01) (Table 3).
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) and lateral (
) groups. a P < .01. |
DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our study demonstrated a significant decrease in tracheal colonization for infants who were placed in the lateral position during mechanical ventilation. After 5 days of mechanical ventilation, bacteria were detected in the tracheal aspirates of the majority of infants (87%) positioned on their backs, whereas only 30% of infants positioned on their sides grew organisms in their tracheal aspirates. Consistent with previous studies, Gram-negative rods were the most frequently cultured organisms from the trachea.11,12
It is difficult to diagnose neonates with pneumonia with certainty because of multiple factors, including the radiologic picture of pneumonia, which overlaps with other conditions such as atelectasis and hyaline membrane disease; the challenge of eliciting signs of pneumonia through auscultation of the chest in small premature infants; and the overall absence of sure signs of pneumonia, such as fever and chills, in premature infants.13 VAP can be diagnosed most accurately through quantitative culture and microscopic examination of lower respiratory tract secretions. This method was advocated even for patients who received antibiotics for <72 hours before sampling of tracheal secretions.14,15 There might be an overlap between VAP and tracheobronchitis, but tracheal aspirates still can serve as an objective surrogate for the incidence of VAP.16
Two days and 5 days are considered landmarks for infants treated with mechanical ventilation. Nosocomial pneumonia is attributed to ventilators only for patients treated with mechanical ventilation for >2 days.17 Therefore, baseline tracheal aspirates were evaluated at 48 hours. The second tracheal cultures were obtained after 5 days of mechanical ventilation, because the highest incidence of VAP is known to occur during the first 5 days of mechanical ventilation.1 Almost one half of VAP occurs before 5 days of continuous mechanical ventilation.
The presence of a tube in the trachea plays a primary role in the pathogenesis of VAP. It interferes with the clearance of respiratory secretions and organisms that is conducted by cilia of mucosal cells in a nonintubated trachea. It seems logical that keeping the breathing circuit and endotracheal tube in a vertical position at a level higher than the trachea would allow respiratory secretions, mixed with bacteria, to travel passively by gravity to the terminal airway and to alveoli. Therefore, eliminating the effect of gravity by maintaining the endotracheal tube and breathing circuit horizontal should make respiratory secretions less likely to move down the airway. The effect of gravity on bacterial colonization, VAP, and mobilization of secretions was first reported in an animal study by Panigada et al.8 Indeed, when the endotracheal tube was placed horizontal or just below horizontal, animals showed no altered bacterial colonization in their airways and distal alveoli after 72 hours of continuous ventilation.8 In addition, the authors noticed that such positioning of the trachea facilitated sliding of respiratory secretions along the endotracheal tube wall, so that the secretions drained by the force of gravity to the outside, eliminating the need for tracheal suctioning.18
The intubation procedure itself contributes to VAP. During intubation, the tube passes through the pharynx, which is heavily colonized with bacteria, and can facilitate the movement of organisms into the sterile lower respiratory tract.19 Therefore, repetitive reintubation increases the risk of a patient contracting VAP.19 In our study, there were fewer episodes of self-extubation and reintubation in the lateral group, which could be a confounding bias in our study for which we did not control. However, the decreased incidence of self-extubation in the lateral group provides added reassurance that positioning of ventilated infants on their sides could be safer and make it less likely that an infant would self-extubate. However, we speculate that having the breathing circuit hanging in the air may impose an increased risk for self-extubation.
This study was a single-blind, randomized trial. The microbiologist who performed all tracheal culturing was not aware of subject group identification. Group identification, however, could not be masked during sampling of the tracheal aspirates from subjects. To control for any bias in tracheal aspirate sampling, we ascertained that all sampling was performed by the same investigator. The fact that there were fewer episodes of self-extubation and reintubation in the lateral group also could be a bias, because it could reflect lower bacterial colonization, with reintubation being a major risk factor for translocation of bacteria from the upper airways.
Finally, it is alarming to find that tracheal aspirates, which should be naturally sterile, were colonized with bacteria in up to 87% of ventilated infants in our trial. Similar to previous reports, there is growing concern about the recent emergence of Gram-negative rods in neonatal units in general20 and in tracheal aspirates in particular.21 The source of Gram-negative rods is mainly environmental,22 primarily from the hands of staff members.23 Therefore, this study indirectly confirms the importance of hand-washing in the neonatal unit. Another lesson from this study is that mechanical ventilation for even a brief period is potentially harmful and can predispose fragile neonates to infections. Such risk should be addressed when debating whether to intubate routinely premature infants with hyaline membrane disease.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Tracheal aspirates are less likely to become colonized when ventilated infants are positioned on their sides. Also, infants placed on their sides are less likely to self-extubate. Whether these short-term benefits are associated with overall improvements, such as in the length of hospital stay and the incidence of chronic lung disease, needs to be explored further.
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ACKNOWLEDGMENTS |
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We thank Adenike Aniyikaiye for her efforts in data preparation and analysis, Pete van Riper for the medical illustration, and Cynthia Poindexter for editing.
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FOOTNOTES |
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Accepted Jan 9, 2008.
Address correspondence to Hany Aly, MD, 900 23rd St, NW, Suite G-2092, Washington, DC 20037. E-mail: haly{at}mfa.gwu.edu
This trial has been registered at www.clinicaltrials.gov (identifier NCT00491660).
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Pneumonia is a common complication of mechanical ventilation.
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| What This Study Adds Lateral positioning of intubated infants decreases the risk for bacterial colonization of the respiratory system.
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