A clinical trial of silver-coated and tapered cuff plus supraglottic suctioning endotracheal tubes in preventing ventilator-associated pneumonia

Journal Pre-proof A clinical trial of silver-coated and tapered cuff plus supraglottic suctioning endotracheal tubes in preventing ventilator-associated pneumonia

Ata Mahmoodpoor, Sarvin Sanaie, Rukma Parthvi, Kamran Shadvar, Hadi Hamishekar, Afshin Iranpour, Hamidreza Nuri, Sama Rahnemayan, Nader D. Nader PII:

S0883-9441(19)31545-X

DOI:

https://doi.org/10.1016/j.jcrc.2019.12.024

Reference:

YJCRC 53454

To appear in:

Journal of Critical Care

Please cite this article as: A. Mahmoodpoor, S. Sanaie, R. Parthvi, et al., A clinical trial of silver-coated and tapered cuff plus supraglottic suctioning endotracheal tubes in preventing ventilator-associated pneumonia, Journal of Critical Care(2019), https://doi.org/10.1016/j.jcrc.2019.12.024

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© 2019 Published by Elsevier.

Journal Pre-proof A clinical trial of silver-coated and tapered cuff plus supraglottic suctioning endotracheal tubes in preventing ventilator-associated pneumonia Ata Mahmoodpoor, MD FCCM1 [email protected], Sarvin Sanaie, MD, Ph.D.1 [email protected], Rukma Parthvi, MD2 [email protected], Kamran Shadvar, MD1 [email protected], Hadi Hamishekar, Ph.D.4 [email protected], Afshin Iranpour, MD3 [email protected], Hamidreza Nuri, MD1 [email protected], Sama Rahnemayan, MD1 [email protected], Nader D. Nader, MD, Ph.D., FCCP, FACC, FAHA2,* [email protected] 1

Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran University at Buffalo, Jacob’s School of Medicine and Biomedical Sciences, Buffalo, NY 3 Dept. of Anesthesiology, Al-Garhoud Hospital, Dubai, United Arab Emirates, Dubai, UAE 4 Drug Applied research center, Tabriz University of Medical Sciences, Tabriz, Iran * Corresponding author at: Professor of Anesthesiology, UB-Anesthesia, 77 Goodell Street, Suite 550, Buffalo, NY 14203;

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1. Abstract:

Purpose: Novel designs of the endotracheal tube (ETT) are emerged to reduce the risk of

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ventilator-associated pneumonia (VAP). We evaluated the effect of two different types, namely

VAP in critically- ill patients.

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silver-coated (Bactiguard) and subglottic suctioning (Taperguard) ETTs, on the incidence of

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Methods: A total of 90 patients, mechanically ventilated for more than 72 hours, were randomly

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assigned to Bactiguard and Taperguard groups. They otherwise received routine care, including VAP prevention measures during their intensive care unit (ICU) stay. Subglottic suctioning was performed in Taperguard group. Statistical analyses were performed using SPSS 25 for iMacs. Results: Both groups had similar demographics and did not differ in the prevalence of comorbidities and the severity of underlying illness. There was no difference in the frequency of reintubation (P=0.565), the duration of ventilation, ICU and total hospital length of stay.

VAP

developed in 31% of the Bactiguard group and 20% of the Taperguard group (P=0.227). Nearly

Journal Pre-proof twice the number of patients died in the Bactiguard group compared to the Taperguard group. This difference was not significant either (P=0.352). Conclusions: The use of Bactiguard or Taperguard ETTs was not associated with any difference in the incidence of VAP or ICU mortality.

Keywords: Endotracheal tubes; Mortality; Ventilator-associated Pneumonia; Silver-coated

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Bactiguard; Subglottic suctioning; Taperguard Evac

Journal Pre-proof 2. Introduction Ventilator-associated

pneumonia

(VAP)

is

the most common acquired

infection

worldwide affecting almost 10-30% of ventilated patients in intensive care units (ICU) [1]. Based on the Center for Disease Control and Prevention (CDC) definition, VAP occurs after 48 hours from initiation of mechanical ventilation [2]. Several reports link the incidence of VAP to both crude and adjusted mortality in an ICU setting [3-5]. Although a few studies attribute this

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association between VAP and hospital mortality to the severity of underlying condition at the

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time of admission to the ICU [3]. Since it is associated with significant mortality and morbidity,

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several preventive measures are recommended by the CDC. One of the main risk factors for the

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development of VAP is presence of an endotracheal tube (ETT) and it also depends on the different designs and structures of the ETT [6]. A literature review of various ETTs shows that

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polyurethane cuffed ETTs equipped with subglottic secretion drainage port can decrease the

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incidence of VAP in critically ill patients [7-10]. However, a systematic review by Dezfulian and colleagues has reported conflicting results regarding the impact of these ETTs on the duration of

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mechanical ventilation [11]. Using subglottic secretion drainage port appears to be a cost-

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effective method and improving its compliance among healthcare workers can decrease the incidence of VAP. Hence, it is a part of standard practices in critical care setting [12]. A recently performed meta-analysis supported the use of ultrathin polyurethane-cuffed ETTs in high-risk surgical patients intubated for a short period, but its role in preventing VAP is unclear in patients on prolonged ventilation where microaspiration of subglottic secretions could increase pneumonia related to intubation [13]. Taperguard Evac ETTs have a conical cuff that is combined with continuous subglottic secretion drainage system (Figure 1). Both characteristics of these endotracheal tubes have been shown to reduce the risk of VAP [8, 10]. By reducing the

Journal Pre-proof number of microaspiration events past the cuff, the Taperguard evac oral tracheal tube may further reduce the risk of pulmonary complications associated with microaspiration, compared to the cylindrical cuffed ETTs [10]. Biofilm

formation

around

the

ETT

surface

that

facilitates

the

migration

of

microorganisms into the pulmonary epithelium, is one of the leading causes of VAP. Animal and preliminary studies have shown that silver-coated ETTs can reduce the occurrence of VAP by

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preventing biofilm formation and microbial colonization [14-17]. The galvanic effect of silver

Kollef et al have reported that silver-coated ETTs can

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decreases the risk for biofilm formation.

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alloy creates a micro current that reduces microbial adhesion to the catheter material, which

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reduce the incidence of VAP, especially early-onset VAP [18]. In a systematic review by Pneumatikos et al. indicate that silver-coated ETTs seem to be a useful measure in reducing the

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risk of VAP [19]. Most studies do not have adequate power; hence, future studies with a larger

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patient population who are at risk for VAP and who require mechanical ventilation for a more extended time are needed. VAP is a nosocomial lung infection that is more likely to be

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secondary to an endotracheal tube in the patient's airway than due to the ventilator per se [19].

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Based on the conflicting results of previous trials, we performed a study to compare the effect of two different types of ETT on the incidence of VAP in mechanically-ventilated patients. The null hypothesis was that the use of silver-coated or tapered-cuff ETTs was associated with comparable incidence of VAP in ICU patients.

3. Materials and Methods The study design, protocol, and the informed consent process were reviewed and approved for their merit by the Institutional Review Board. The research ethics and good clinical

Journal Pre-proof research guidelines published by the National Institute of Health were followed. The study was registered with the National Registry for Clinical Trials at http://www.IRCT.ir. (Trial ID: IRCT201601242582N13). Informed consent was obtained from patients or their surrogates before entering the study. 3.1. Sample size calculation Power and sample size version 3.2 was used for sample size calculation in this

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randomized controlled trial with a ratio of 1:1. Our study design was close to Dezfulian et al.

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(2005) who reported Taperguard Evac ETTs to decrease VAP up to 50% (P0: 0.5) with

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hypothesis of decreasing VAP by silver-coated ETTs up to 70% (P1: 0.7) and considering

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α=0.05 and power = 0.85, sample size for each group calculated as 40 [11]. Considering the loss

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to follow up and missing data, we increased the samples to 45 in each group.

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3.2. Inclusion/exclusion criteria and randomization Patients aged between 18 and 80 years who required mechanical ventilation for more

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than 48 hours with the placement of an ETT were enrolled in this study from March 2016 to

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March 2019. Exclusion criteria were patients transferred from other hospitals, urgent intubation performed on the medical wards other than ICU, recent mechanical ventilation (<30 days), pregnancy, HIV, immunosuppression, leukopenia, patient refusal, acute respiratory distress syndrome and patients receiving antibiotics. After initial screening for eligibility, 93 patients were enrolled in the study after an informed consent form was signed by their next of kin or health care proxy (Figure 1). Patients were randomized (block randomization) into two groups, each comprising 45 patients. Randomization was performed with Web-based software. In Taperguard group, patients

Journal Pre-proof were intubated with a supraglottic suctioning Evac ETT (Covidien, USA), and in Bactiguard group,

a

silver-coated

ETT

(Bactiguard®,

Tullinge,

Sweden)

was

used.

Practicing

anesthesiologists with experience in placing ETTs performed the intubation through direct laryngoscopy. Male patients were intubated with an 8.0 to 8.5 mm internal diameter ETT, and female patients were intubated with 7.0 to 7.5 mm internal diameter ETTs.

VAP prevention

bundle was performed as followings: maintaining head elevation 30-45, monitoring and keeping

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cuff pressure at almost 25 cmH2O every 6 hours, using enteral nutrition, daily oral mouthwash

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with 0.2% chlorhexidine, hand-washing, Richmond Agitation-Sedation Scale (RASS) 0/-1 for

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sedation. Ventilator circuit lines or tubes only if they were grossly spoiled and/or caused extra

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resistance toward the work of breathing. Gastric secretions were aspirated 2 hours after enteral feeding through an indwelling nasogastric tube and the residual volumes were recorded and

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reported daily. Suction was performed as needed in both groups via a closed suction system.

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Drainage of subglottic secretion was performed every 6 hours for patients in Taperguard group. Diagnosis of VAP was suspected in patients receiving mechanical ventilation for more

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than 48 hours by clinical pulmonary infection score (CPIS). The CPIS is a value of 0 to 12 based

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on the following 6 variables: body temperature, leukocyte count, volume and character of tracheal secretions, arterial oxygenation, and chest radiograph findings with a sensitivity of 72% to 80% and a specificity of 85% to 95% in detection of VAP [20]. Bronchoalveolar lavage (BAL) was performed for every patient with CPIS values more than six. Microbial analyses included gram staining, quantitative culture counts of colony-forming units, and antibiotic sensitivity of the bronchial aspirate specimens obtained during BAL. Any growth of any bacterial pathogens (Table 1) over 10,000 colony-forming units in quantitative cultures was required to confirm the diagnosis of VAP in patients who were mechanically ventilated for at

Journal Pre-proof least 48 hours. The incidence of VAP was the primary outcome measure of the study and presented as VAPs/1000 ventilator days. Secondary outcome measures were ICU length of stay, ventilator-free days, and hospital length of stay.

The mortality rate was also recorded for all

patients during their hospital stay. 3.3. Statistical analysis All obtained data were analyzed using SPSS 25.0 software (IBM, Chicago, Ill).

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Kolmogorov-Smirnov test was performed to test the normality of distribution for continuous

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variables. Continuous variables were reported as mean ± SD in case of a normal distribution, or

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median and interquartile range in case normality was rejected. Categorical variables were

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presented as frequency (%), and Fisher's Exact tests were used for their comparison. Multivariable regression analyses were performed, and the odds ratios (OR) were reported along C statistics was performed for the multivariable regression

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with 95% confidence intervals (CI).

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4. Results

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considered significant.

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model and the area under the curve (AUC) was provided with its standard error. P <0.05 was

Regarding demographic characteristics like age, sex, comorbidities, and APACHE (Acute Physiology and Chronic Health Evaluation)-II, there was no difference between the two groups (Table 1). The most common comorbidity was hypertension followed by diabetes mellitus. The frequency of suctioning subglottic secretion in Taperguard group was 12 (8–14) per day. CPIS values ≥ 6 was present in 12 (26.7%) of patients in Taperguard group, while 16 (35.6%) of patients in Bactiguard group had CPIS values ≥6. The microbiological findings of patients in the two groups are shown in Table 2. The duration of mechanical ventilation, ICU length of stay,

Journal Pre-proof and hospital length of stay did not differ between the two groups. Among the respiratory variables, the frequency of intraluminal suctioning, the rate of reintubation, and PaO2 /FiO2 values were similar between the two groups (Table 3). The tracheal cuff pressure was 25 (23-27) cmH2 O in Bactiguard group, which was significantly less than 27 (25-28) cmH2 O in Taperguard group, while both were in the normal range. The residual volume of the stomach was also comparable in both groups. The frequencies of VAP were 31% in Bactiguard group and 20% in

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Taperguard group, which did not have a significant difference between the two groups

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(P=0.227). Eight patients (17.8%) died in Bactiguard group, while only four patients (8.9%) died

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in Taperguard group, however, this difference does not reach a statistical significance (P =

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0.353).

Multivariable binary logistic regression analysis performed for the occurrence of VAP

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and the model included, age, duration of mechanical ventilation, gastric residual volume, the

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frequency of intraluminal suctioning, tracheal cuff pressure, length of ICU stay, and the type the endotracheal tube as the independent variables in predicting VAP which occurred in 23 patients.

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Our results showed that one day increase in mechanical ventilation increased the chance of VAP

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by 65% (P= 0.045). The AUC for this prediction model was 0.778 ± 0.054; P <0.001. OR values for the occurrence of the endpoint with various independent variables are shown in Table 4. No adverse effect was reported with the use of either of the ETT types.

5. Discussion The results of this study fail to show any difference between Bactiguard and Taperguard ETTs regarding the occurrence VAP and mortality. Aspiration of oral/nasopharyngeal secretions is one of the most important reasons for the development of VAP in critically ill patients [21,

Journal Pre-proof 22]. Taperguard ETTs have the advantage of continuous/intermittent suction of subglottic secretions, and the polyurethane material of their cuff reduces the production of folds to achieve a clinical seal. With less formation of channels, a smaller amount of subglottic secretions passes over the cuff folds toward the lower respiratory system, which in turn decreases the risk of VAP. Prevention of microbial adhesion and biofilm formation by generating galvanic micro current is the main mechanism of action for silver-coated ETTs. Previous studies have shown that silver-

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coated Bactiguard ETTs can decrease colonization and biofilm formation which is the leading

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risk factor for VAP development with 37% lower P aeruginosa tube concentrations in dogs [17],

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40% fewer days of tube colonization in the feasibility study [14, 17].

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Cuff pressures were higher in group of patients who were intubated with Taperguard Evac ETTs compared to those who were intubated with silver-coated Bactiguard tubes. We

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believe that the observed difference is due to their different cuff design. Silver-coated Bactiguard

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ETTs use Hi-Lo (high-volume/low-pressure) technology. One of the main advantages of this design is its minimal compression over the tracheal mucosa and preserving tracheal blood

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perfusion which may indeed contribute to its protective effect against formation of tracheal

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necrosis and fistula formation. However, on a negative note these designs lead to creations of several longitudinal wrinkles and channels along the folded edges of the cuff that may ultimately provide passages for various bacteria and microaspiration. On the other hand, Taperguard Evac ETTs by design, have less compliant cuff that closely mimics low-volume/ high pressure technology. The conical shape of the cuff as opposed to the cylindrical shape along with the high-pressure technology minimize the redundancy of the cuff membrane and decrease channeling and migration of the bacterial pathogens to distal airways.

Journal Pre-proof Silver has a broad-spectrum antimicrobial activity, decreases bacterial adhesion in vitro, and blocks biofilm formation in animal models [21]. Results of the NASCENT trial have shown that silver-coated Bactiguard ETTs can decrease colonization of high resistance pathogens like methicillin-resistant

Staphylococcus

aureus,

Pseudomonas

aeruginosa,

Acinetobacter

baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia in the lower respiratory tract [18]. Furthermore, silver-coated Bactiguard ETTs was less likely to have mucus covering

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the surface or obstructing the lumen [17]. Berra and colleagues (2008) showed that silver-coated

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Bactiguard ETTs were effective in decreasing bacterial colonization in critically-ill ventilated

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patients [23]. Shorr et al reported that although the cost of silver-coated Bactiguard ETTs was

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more than conventional ETTs but this difference was offset by decreasing the VAP incidence using silver-coated Bactiguard ETTs in his study [24]. Mucus accumulation can reduce the

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antibacterial activity of silver-coated Bactiguard ETTs by isolating bacterial colonies from the

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silver surface [14].

Most of the studies performed on silver-coated Bactiguard ETTs were preclinical trials

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that have some limitations. These studies were not always representative of clinical situations

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and did not include most of the routine clinical risk factors. On the other hand, these studies were designed to evaluate the endpoints during a short period. More studies are needed to determine whether these findings translate to reduce biofilm formation in humans and to elucidate the exact link between preclinical and clinical findings. Results of a recent meta-analysis showed that there were no statistically significant differences between groups in hospital mortality, device-related adverse events, duration of intubation; and length of hospital and ICU stay, especially during the first ten days of mechanical ventilation [25].

Journal Pre-proof Unlike the early-onset (<4 days) variation, the late-onset VAP carries a higher mortality rate that ranges between 30% to 50% [26, 27]. Methicillin-resistant Staphylococcus aureus is the most common bacterial pathogen isolated from the cases of late-onset VAP [28]. Although it is not statistically different, the duration of mechanical ventilation has been slightly longer in the Bactiguard group. Additionally, in the multivariate analysis (Table 4), we have demonstrated that the duration of mechanical ventilation is the most important factor that increases the risk of

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developing VAP. The duration of mechanical ventilation may therefore contribute some of our

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findings that differ from those by others. In most of our cases a late-onset VAP developed. Based

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on previous trials, silver-coated Bactiguard ETTs can prevent the occurrence of early-onset VAP,

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especially in cases with less than ten days of mechanical ventilation [20]. Therefore, we have used 10 days in the definition to be able to compare our results to these trials. According to

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worldwide observational data, many patients require 10 or more days of mechanical ventilation.

added ICU care [24].

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Thus, delaying the occurrence of VAP may have important clinical implications such as cost Based on the original classification by the American Thoracic Society,

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some of these cases of VAP are classified as early- or late-onset. As the distribution and the

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pattern of adverse events were comparable between treatment groups, we found no overt safety issues with the silver-coated Bactiguard ETTs. 6. Limitation of study: A modest number of participants in a single study center limited our research, and therefore its findings need to be verified by more extensive future trials. This study is also limited by not examining other secondary endpoints such as initiation of post-BAL antibiotic therapy for VAP. Many different diagnostic criteria for VAP are used in clinical practice, but we chose the definition criteria by CDC, as triggers for further evaluation that required

Journal Pre-proof microbiological confirmation of VAP.

In addition, we did not perform a microscopic

examination to evaluate for the presence of a biofilm. 7. Strengths of the study: This is the first study in human subjects which compared the effect of silver-coated Bactiguard ETTs and Taperguard ETT in prevention of VAP in mechanically ventilated patients who were exposed to routine clinical risk factors. Implementation of these expensive ETTs

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requires not only requires assessment of cost effectiveness of these tubes but also incorporating

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the VAP incidence and comparing with less expensive variations of the airway devices. It is

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important to note that the type of ETT is not the only method of reducing incidence of VAP

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hence all components of the VAP prevention bundle need to be implemented.

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8. Conclusions

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Our results show that silver-coated ETTs are safe to be used in critically ill patients. There is no significant difference between Taperguard Evac and silver-coated Bactiguard ETTs. In view of abundant historical evidence and previous research,

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regarding VAP development.

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tapered-cuff tube prototypes with supraglottic suctioning prevail to be an effective design to decrease the incidence of VAP. We conclude that the use of silver-coated ETTs was comparable and not inferior to the currently accepted design and therefore, future trials with silver-coated ETTs or utilizing a hybrid design of both ETT devices may offer some hope on the prevention of VAP. Conflict of Interest: None was declared by the authors. Funding Source: No funding was requested for this study. Author Statement: Ata Mahmoodpoor:

Journal Pre-proof Conceptualization; Data curation; Investigation; Methodology; Project administration; Writing – original draft Sarvin Sanaie: Data curation; Investigation; Resources Rukma Parthvi: Writing – original draft; Writing – review & editing Kamran Shadvar: Data curation; Investigation; Methodology; Project administration

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Afshin Iranpour : Funding acquisition ; Investigation ; Methodology

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Hamidreza Nuri: Data curation; Project administration Sama Rahnemayan: Conceptualization; Data curation;

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Hadi Hamishekar: Software; Supervision; Validation; Visualization

Batra P, Mathur P, John NV, Nair SA, Aggarwal R, Soni KD, et al. Impact of

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[1]

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References

na

Nader D. Nader: Formal analysis; Software; Supervision; Validation; Visualization; Writing – Original draft; Review & editing

multifaceted preventive measures on ventilator-associated pneumonia at a single surgical centre. Intensive Care Med 2015;41(12):2231-2. [2]

Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002;165(7):867-903.

[3]

Forel JM, Voillet F, Pulina D, Gacouin A, Perrin G, Barrau K, et al. Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lungprotective strategy. Crit Care 2012;16(2):R65.

Journal Pre-proof [4]

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the

prevalence

and

outcomes of infection in intensive care units.

JAMA

2009;302(21):2323-9. [5]

American Thoracic S, Infectious Diseases Society of A. 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. [6]

Rouze A, Jaillette E, Poissy J, Preau S, Nseir S. Tracheal Tube Design and Ventilator-

Walaszek M, Gniadek A, Kolpa M, Wolak Z, Kosiarska A. The effect of subglottic

ro

[7]

of

Associated Pneumonia. Respir Care 2017;62(10):1316-23.

-p

secretion drainage on the incidence of ventilator associated pneumonia. Biomed Pap Med

Mahmoodpoor A, Hamishehkar H, Hamidi M, Shadvar K, Sanaie S, Golzari SE, et al. A prospective randomized subglottic

suctioning

in

trial of tapered-cuff endotracheal tubes with intermittent

lP

[8]

re

Fac Univ Palacky Olomouc Czech Repub 2017;161(4):374-80.

preventing ventilator-associated

pneumonia in critically ill

[9]

na

patients. J Crit Care 2017;38:152-6.

Hubbard JL, Veneman WL, Dirks RC, Davis JW, Kaups KL. Use of endotracheal tubes

ur

with subglottic secretion drainage reduces ventilator-associated pneumonia in trauma

[10]

Jo

patients. J Trauma Acute Care Surg 2016;80(2):218-22. Mahmoodpoor A, Peyrovi-far A, Hamishehkar H, Bakhtyiari Z, Mirinezhad MM, Hamidi M, et al. Comparison of prophylactic effects of polyurethane cylindrical or tapered cuff and polyvinyl chloride cuff endotracheal tubes on ventilator-associated pneumonia. Acta Med Iran 2013;51(7):461-6. [11]

Dezfulian C, Shojania K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med 2005;118(1):11-8.

Journal Pre-proof [12]

Lacherade JC, Azais MA, Pouplet C, Colin G. Subglottic secretion drainage for ventilator-associated pneumonia prevention: an underused efficient measure. Ann Transl Med 2018;6(21):422.

[13]

Blot SI, Rello J, Koulenti D. The value of polyurethane-cuffed endotracheal tubes to reduce microaspiration and

intubation-related

pneumonia: a systematic review of

laboratory and clinical studies. Crit Care 2016;20(1):203. [14]

Pirrone M, Imber DA, Marrazzo F, Pinciroli R, Zhang C, Bry L, et al. Silver-Coated

of

Endotracheal Tubes Cleaned With a Mechanism for Secretion Removal. Respir Care

Rello J, Afessa B, Anzueto A, Arroliga AC, Olson ME, Restrepo MI, et al. Activity of a

-p

[15]

ro

2019;64(1):1-9.

silver-coated endotracheal tube in preclinical models of ventilator-associated pneumonia

Rello J, Kollef M, Diaz E, Sandiumenge A, del Castillo Y, Corbella X, et al. Reduced

lP

[16]

re

and a study after extubation. Crit Care Med 2010;38(4):1135-40.

burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a

Olson ME, Harmon BG, Kollef MH. Silver-coated endotracheal tubes associated with reduced

bacterial burden

ur

[17]

na

randomized multiple-center feasibility study. Crit Care Med 2006;34(11):2766-72.

in the lungs of mechanically ventilated

dogs.

Chest

[18]

Jo

2002;121(3):863-70.

Kollef MH, Afessa B, Anzueto A, Veremakis C, Kerr KM, Margolis BD, et al. Silvercoated

endotracheal tubes and

incidence of ventilator-associated pneumonia: the

NASCENT randomized trial. JAMA 2008;300(7):805-13. [19]

Pneumatikos IA, Dragoumanis CK, Bouros DE. Ventilator-associated pneumonia or endotracheal tube-associated

pneumonia? An approach to

the pathogenesis and

preventive strategies emphasizing the importance of endotracheal tube. Anesthesiology 2009;110(3):673-80.

Journal Pre-proof [20]

Zilberberg MD, Shorr AF. Ventilator-associated pneumonia: the clinical pulmonary infection score as a surrogate for diagnostics and outcome. Clin Infect Dis 2010;51 Suppl 1:S131-5.

[21]

Valles J, Pobo A, Garcia-Esquirol O, Mariscal D, Real J, Fernandez R. Excess ICU mortality attributable to ventilator-associated pneumonia: the role of early vs late onset. Intensive Care Med 2007;33(8):1363-8.

[22]

Ramirez P,

Ferrer M,

Torres A.

Prevention measures for ventilator-associated

of

pneumonia: a new focus on the endotracheal tube. Curr Opin Infect Dis 2007;20(2):190-

Berra L, Kolobow T, Laquerriere P, Pitts B, Bramati S, Pohlmann J, et al. Internally

-p

[23]

ro

7.

coated endotracheal tubes with silver sulfadiazine in polyurethane to prevent bacterial

Shorr AF, Zilberberg MD, Kollef M. Cost-effectiveness analysis of a silver-coated

lP

[24]

re

colonization: a clinical trial. Intensive Care Med 2008;34(6):1030-7.

endotracheal tube to reduce the incidence of ventilator-associated pneumonia. Infect

[25]

na

Control Hosp Epidemiol 2009;30(8):759-63. Tokmaji G, Vermeulen H, Muller MC, Kwakman PH, Schultz MJ, Zaat SA. Silver-

ur

coated endotracheal tubes for prevention of ventilator-associated pneumonia in critically

[26]

Jo

ill patients. Cochrane Database Syst Rev 2015(8):CD009201. Blot S, Koulenti D, Dimopoulos G, Martin C, Komnos A, Krueger WA, et al. Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old, and very old critically ill patients*. Crit Care Med 2014;42(3):601-9. [27]

Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005;128(6):3854-62.

[28]

Kollef MH, Silver P, Murphy DM, Trovillion E. The effect of late-onset ventilatorassociated pneumonia in determining patient mortality. Chest 1995;108(6):1655-62.

Journal Pre-proof Figure 1: The schematic display of the silver-coated Bactiguard endotracheal tubes (A) and Taperguard endotracheal tube with supraglottic suctioning (Evac) (B).

Figure 2: CONSORT flow diagram of the clinical trial

Table 1. Study variables between Silver-coated BactiGuard group and TaperGuard group endotracheal tubes.

Age (years)

59 (43 – 69)

APACHE-II Score

21 (20 – 24)

Hypertension

16 (35.6%)

13 (28.9%)

0.499

Diabetes Mellitus

11 (24.4%)

11 (24.4%)

1.000

8(17.8%)

10(22.2%)

0.598

9 (20.0%)

7 (15.6%)

0.581

7(15.6%)

8(17.8%)

0.777

4(8.9%)

4(8.9%)

1.000

Ischemic Heart Diseases

na

Congestive Heart Failure Cerebrovascular Event

ur

Admission type

Trauma Medical Diagnosis

Jo

Post-op/Surgical

P value 1.000

61 (44 – 69)

0.812

22 (19 – 26)

0.621

ro

-p

re

lP

Dyslipidemia

Bactiguard N = 45 30/15

of

Variables Sex (Male/Female)

Taperguard N = 45 30/15

0.818 14 (30.1%)

11 (24.4%)

10 (22.2%)

9 (20.0%)

21 (46.7%)

25 (55.6%)

Table 2. Bacterial pathogens isolated from the patients with ventilator-associated pneumonia during study Bactiguard Taperguard N = 45 N = 45 P value Pseudomonas Aeruginosa 2 4 0.102 Enterobacteriaceae

1

2

0.236

Acinetobacter Baumannii

3

4

0.715

Methicillin-resistant Staph. Aureus

2

3

0.564

Methicillin-sensitive Staph. Aureus

1

1

1.000

Journal Pre-proof Total

9

14

0.227

Table 3. Respiratory variables and clinical outcome between Silver-coated Bactiguard and Taperguard Evac endotracheal tubes. Variables Frequency of intraluminal suctioning

TaperGuard N = 45 12 (11-13)

BactiGuard N = 45 12 (9-14)

P value 0.360

27 (25-28)

25 (23-27)

0.005

Cuff pressures (cmH2O)

15.9 ± 0.9

17.8 ± 0.8

0.105

177.8 ± 4.3

165.6 ± 4.1

0.039

Ventilator-associated Pneumonia

9 (20.0%)

Tracheostomy

8 (17.8%)

Death rate

4 (8.9%)

of

Duration of mechanical ventilation (Days) PaO2 / FiO2 (mmHg)

0.227

5 (11.1%)

0.368

8 (17.8%)

0.353

23 ± 6

24 ± 5

0.188

19.5 ± 5.8

21.2 ± 5.3

0.147

-p

ro

14 (31.1%)

Hospital Length of Stay (Days)

re

ICU Length of Stay (Days)

lP

Table 4. Multivariable logistic regression for the occurrence of ventilator-associated pneumonia S.E. 0.019

Wald P-Value 0.463 0.496

OR 0.987

Lower 0.950

Upper 1.025

0.124

0.562

0.048

0.826

1.132

0.376

3.405

0.002

0.006

0.093

0.760

1.002

0.990

1.014

Suctioning frequency (freq/day)

-0.030

0.035

0.719

0.396

0.971

0.906

1.040

Duration of Mechanical Ventilation (Days) ICU Length of Stay (Days)

0.504

0.262

3.707

0.045

1.655

1.001

2.765

-0.309

0.252

1.502

0.220

0.734

0.447

1.204

Constant

-2.734

1.982

1.902

0.168

0.065

na

Coefficient -0.013

Age (years)

Jo

Gastric Volume (mL)

ur

BactiGuard/TaperGuard

Area-under-the-Curve= 0.778 ± 0.054; P-value for this model was < 0.001. Highlights:  Several prototypes of the endotracheal tubes are used to decrease the risk of VAP.  Subglottic suctioning (TaperGuard) tubes have been credited to decrease the prevalence of VAP.  Silver-coated tubes (BactiGurad) are manufactured to reduce the risk of bacterial VAP.  BactiGuard tubes were comparable to TaperGuard tubes for the risk of VAP.