Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Surgical ICU (I): Cointervention: Polyurethane- Patients transferred from other TaperGuard EVACTM tubes: cone shape cuff (I): hospitals, urgent intubation in equipped with SSD port,

APACHE II: 22.6 ± 5.1 MV>48h, clinical wards other than ICU, history polyurethane and cone shape VAP bundle: ICU LOS: 15 ± 5 features (CPIS) and Age between 18 and of MV, pregnancy, HIV, cuff. - Head elevation of 45º. Duration MV: 11.6 ± 7.1 bacterial pathogens 80 yr requiring immunosuppression, Method of SSD: Intermittent Mahmoodpoor - Protocolized enteral feeding. 276 ≥104 CFU/ml in leukopenia, patient refusal, and every 6h et al, 2017 - Sedation with washout periods. quantitative culture for more than 72 hours acute respiratory distress - Oral hygiene with (C): from bronchoalveolar with placement of an syndrome. Patients who were (C): chlorhexidine. APACHE II: 21.4 ± 4.4 lavage. endotracheal tube receiving at the time Conventional high-volume - Hand washing. ICU LOS: 18 ± 10 of intubation, and those who low-pressure endotracheal - Pantoprazol for Duration MV: 12.3 ± 10.5 need a PEEP>5cm H2O. tubes prophylaxis.

ICUs at Harborview Cointervention: Polyurethane- Medical Center. (I): cuffed 1) a polyurethane-conical

(I): Patients with out-of-hospital shaped cuffed tube VAP bundle: SAPS II: 60 ± 12 cardiac arrest. 2) a polyurethane- conical - Head elevation of 45º. ICU LOS: N/A Adults (>18 yr of age) Use of a non–study-designated shaped cuffed tube with - Protocolized enteral feeding. Duration MV: 6.5 ± 12.7 Modified Criteria of requiring emergency intubation device. a port for SSD Deem et al, 66 - Oral care every 8h with 0.12% CDC orotracheal intubation Nasal intubation or Method of SSD: 2016 chlorhexidine. and critical care. tracheostomy. Continuous - Hand washing. (C): Children (age < 18 yr), (C): - Stress ulcer prophylaxis. SAPS II: 60 ± 14 pregnant women, and prisoners. Standard polyvinylchloride- - Endotracheal tube cuff ICU LOS: N/A cylindrical cuffed tube pressure measured and Duration MV: 4.5 ± 4.3 adjusted every 8h.

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Neurological ICU (I): Cointervention: None specified Portex Blue Line (I): Patients with Patients who arrived to ICU endotracheal tube (suction APACHE/SAPS II: N/A MV>48h, clinical VAP bundle: neurological illnesses already intubated or reintubated above cuff endotracheal ICU LOS: 29.8 ± 20.1 features and - Oral intubation. aged > 18 years and during the study period, tube). Duration MV: 21.5 ± 17.6 microbiological - Use of nasogastric tubes. Jena et al, 2016 50 requiring endotracheal patients with a tracheostomy, Method of SSD: Intermittent confirmation of VAP - Early enteral nutrition. intubation and VM > and patients intubated for every 2h. by bronchoalveolar - Semi-recumbent position. 48 h were cardiac arrest or ventilated for (C): lavage fluid. - Stress ulcer prophylaxis. <48 h (C): APACHE/SAPS II: N/A - Maintenance of cuff pressure Standard endotracheal tube ICU LOS: 24.4 ± 14.2 between 20-30 cm H2O.

Duration MV: 17.2 ± 11.5

Cointervention: Tracheal seal Cardiothoracic monitor that allow continuous ICU cuff inflation pressures (I): (I): monitorization and maintenance. EuroSCORE: 6.4 ± 2.2 Venner-PneuXTM

ICU LOS: N/A Hospital in Europe Age over 70 years and/ endotracheal tube. VAP bundle: Duration MV: N/A Link for Infection or left ventricular Method of SSD: N/A Gopal et al, - Semi-recumbent position. 240 Control through ejection function N/A 2015 - Change of circuits Surveillance <50% and urgent when soiled or at 7 days. (C): (HELICS) cardiac surgery. (C): - Mouthwash every 6h with 2% EuroSCORE: 6.4 ± 2.6 Standard endotracheal tube chlorhexidine. ICU LOS: N/A (Portex tracheal tube) - Appropriate hand hygiene. Duration MV: N/A Intermitent every 6h - Stress ulcer prophylaxis with

50mg I.V every 8h.

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

5 ICUs in a tertiary Cointervention: None specified hospital

(I): VAP bundle: I): Teleflex IsisTM endotracheal - Semi-recumbent position of at SAPS III: 70 ± 14.5 Clinical features and Expected MV>48h, tube that allow the SSD least 30º. ICU LOS: 16.2 ± 13.5 Patient participating in another Damas et al, quantitative bacterial age over 18 years and Method of SSD: N/A - Oral care and teeth brushing 352 Duration MV: 11.7 ± 11.9 study or having already 2015 culture ≥ 106 CFU/ml intubation with a with 0.2% chlorhexidine and participated in this study. from bronchoalveolar Teleflex Isis TM (C): application of 1%

lavage. Teleflex IsisTM endotracheal chlorhexidine gel. (C): tube without SSD technique - Daily assessment of sedation. SAPS III: 69 ± 16.6 - Control of cuff pressure ICU LOS: 15.8 ± 13.2 between 20-30 cm H2O. Duration MV: 10.9 ± 9.8

N/A

I): (I): SAPS III: N/A 1) Intermitent SSD every 4h ICU LOS: N/A MV>48h, clinical 2) Continuous SSD Expected MV>48h Duration MV: N/A features and culture of Lung infection when MV Tao et al, 2014 149 and APACHE score Cointervention: None specified endotracheal aspirate, beginning 20-30 reduction of oxygen. (C): (C): Not SSD SAPS III: N/A ICU LOS: N/A Duration MV: N/A

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

ICU of Hospital of Tehran

I): (I): SAPS/APACHE: N/A Special tracheal tube for SSD ICU LOS: N/A Method of SSD: Intermittent Cointervention: N/A Duration MV: N/A Clinical features every 1-2h Seyfi et al, 2013 80 N/A N/A (CPIS) VAP bundle: N/A (C): (C): Ordinary tracheal tube SAPS/APACHE: N/A ICU LOS: N/A Duration MV: N/A

Medical-surgical ICU

Cointervention: none specified. (I): I): Clinical features and Specific tracheal tube for SAPS III: 51 [40–64] c quantitative bacterial VAP bundle: SSD (HI-Lo Evac tube) c culture ≥104 CFU/ml Intubated before ICU and/ or - Semi-recumbent body position. ICU LOS: 11 [7–19] Expected MV>48h, Method of SSD: Intermittent from bronchoalveolar with a tube different than Hi-Lo - Oral route of insertion of the Lacherade et al, Duration MV: 8 [5–13] c older than 18 years, every 1h. 333 lavage or quantitative Evac tube, tracheostomy, tracheal and gastric tubes. 2010 intubated with HI-Lo culture ≥ 103 CFU/ml physhotropic drug overdose, - Enteral delivery of nutritional Evac tube (C): from protected acute drunkenness, cardiac support. (C): Conventional tracheal tube telescoping arrest. - Maintenance of cuff pressure c and/or HI-Lo Evac tube SAPS III: 52 [39–63] sample. between 20-30 cm H2O. without SSD technique. ICU LOS: 11 [6–20] c

Duration MV: 7 [3–15] c

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Medical-surgical ICU

Cointervention: N/A I): (I): APACHE II: 17.6 ± 2.9 Criteria of United Special tracheal tube for SSD VAP bundle: ICU LOS: 9.3 ± 2.9 States of VAP clinical Method of SSD: Continuous - Semi-recumbent body position. Zheng et al, Duration MV: 7.9 ± 2.6 Age over 18 years and 61 standard diagnosis of N/A - Body position changes every 2008 expected MV>48h infection (C): 4h.

system (NNIS) Standard tracheal tube - Maintenance of cuff pressure (C): between 25-30 cm H2O. APACHE II: 17.6 ± 3.5

ICU LOS: 12.3 ± 5.7 Duration MV: 10.4 ± 0.9

Cointervention: N/A Medical-surgical ICU

VAP bundle: I): - Peptic ulcer prophylaxis with SAPS/APACHE: N/A (I): . ICU LOS: N/A SSD Clinical features or - Endotracheal tube cuff control Duration MV: N/A Age over 18 years and Method of SSD: Continuous Yang et al, 2008 91 positive tracheal/blood Intubated before ICU twice a day. expected MV>48h cultures or CPIS ≥ 5 - Head elevated (C): - Open system single-use (C): Not SSD SAPS/APACHE: N/A - Weekly circuit changes ICU LOS: N/A - Oral decontamination Duration MV: N/A

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Cardiothoracic surgery ICU

MV>48h, Clinical Cointervention: None specified I): (I): features (CDC criteria) APACHE II: 10.2 ± 2.4 Special tracheal tube for SSD and quantitative VAP bundle: c (HI-Lo Evac) ICU LOS: 7 [3-27] bacterial culture ≥104 - Tracheal aspiration. Bouza et al, Method of SSD: Continuous 690 Duration MV: 3 [2-9] c CFU/ml from Major Heart Surgery N/A - Maintenance of cuff pressure 2008 endotracheal between 20-30 mm Hg. (C): aspiration and ≥103 - Pantoprazol for stress ulcer Standard tracheal tube (Hi- (C): CFU/ml from prophylaxis. Contour) APACHE II: 10.4 ± 3.3 telescopic brushing.

ICU LOS: 16.5 [6.5-39.5] c Duration MV: 7 [3-11] c

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Cointervention: Polyurethane- cuffed

VAP bundle: - Verification every 4h of semi- recumbent body position 40º Medical-surgical ICU - Nasogastric tubes. (I): - Continuous enteric nutrition. I): Special tracheal tube with - Ranitidine for stress ulcer

APACHE II: 14.9 ± 6.6 polyurethane cuff and SSD prophylaxis. Age less than 18 years, ICU LOS: 14.1 ± 17.9 Clinical features and (SealGuard Evac) - Verification every 4h of cuff pregnancy, infection with Duration MV: 10.5 ± 15.9 quantitative culture of Method of SSD: Intermittent pressure to maintain a pressure Lorente et al, human immunodeficiency 280 respiratory secretions Expected MV>24h every 1 h of 25 cm H2O. 2007 virus, blood leukocyte count by endotracheal - Oral cleaning with less than 1,000 cells/mm3, solid (C): aspirate >106 CFU/ml (C): chlorhexidine every 8h. or hematological tumor, and/or APACHE II: 15.1 ± 6.3 Conventional endotracheal - Protocol of sedation. immunosuppressive therapy. ICU LOS: 15.5 ± 19.9 tube with polyvinyl cuff - Protocol for MV weaning. Duration MV: 11.1 ± 15.2 without SSD (Hi-Lo) - No selective digestive decontamination. - Verification of gastric volume every 6h. - Tracheal suction when necessary. - No routine change of ventilator circuits.

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

N/A

I): SAPS/APACHE: N/A (I): ICU LOS: N/A Expected death within 48h; Special tracheal tube for SSD Cointerventions: Semi-recumbent Clinical features and Duration MV: N/A Age over 18 years and Expected weaning within 48h; Method of SSD: Continuous position and mosapride citrate Liu et al, 2006 86 culture of endotracheal expected MV>48h existing lung infection when aspirate. MV beginning (C): VAP bundle: N/A (C): Standard endotracheal tube SAPS/APACHE: N/A ICU LOS: N/A Duration MV: N/A

Respiratory ICU

I): MV >48 h, the chest I): SAPS/APACHE: N/A radiograph showed Special tracheal tube for SSD ICU LOS: N/A pulmonary new or Method of SSD: Intermittent Duration MV: N/A progressive infiltrates, Age over 60 years and Cointervention: N/A Liu et al, 2006 98 N/A and excluding expected MV>48h VAP bundle: N/A (C): atelectasis, pulmonary Standard tracheal tube (C): edema, and pleural

SAPS/APACHE: N/A effusion ICU LOS: N/A Duration MV: N/A

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

10-bed medical ICU Cointervention: Semi-recumbent position 30º. I): Clinical features and (I): APACHE II: 27 [20-40] c quantitative culture of Special tracheal tube for SSD VAP bundle: ICU LOS: N/A protected specimen (HI-Lo Evac) - Sucralfate for stress ulcer Duration MV: N/A brush or Semi-recumbent position prophylaxis. Girou et al, Patients intubated within the 15 18 bronchoalveolar Expected MV>5 days Method of SSD: Continuous - Verification every 8h of cuff 2004 days preceding ICU admission. lavage specimen with pressure to maintain between (C): more than 5% of cells (C): 20-30 mm Hg. APACHE II: 27 [24-33] c containing Standard tracheal tube - Verification every 4h of ICU LOS: N/A intracellular bacteria Supine position permeability of drainage Duration MV: N/A system.

12- bed general ICU Cointervention: None specified

I): VAP bundle: APACHE II: 23.1 ± 7.6 (I): - Sucralfate for stress ulcer ICU LOS: 9.3 ± 7.4 Adaptation of the Special endotracheal tube for prophylaxis. Duration MV: 5.8 ± 4.4 American College of MV<72 h SSD (HI-Lo Evac) Smulders et al, - Changes of body position from 105 Chest Physicians. Expected MV>72 h developed within Method of SSD: Intermittent 2002 the right to the left decubitus Clinical features and 72h. every 4h. (C): culture of endotracheal (C): - Endotracheal suction every 4h APACHE II: 22.3 ± 8.6 aspirate. Standard endotracheal tube or according to need. ICU LOS: 12.3 ± 3.6 - Control of cuff pressure every Duration MV: 7.1 ± 5.4 4h.

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Surgical ICU

Cointervention: None specified I):

SAPS/APACHE: N/A I): VAP bundle: ICU LOS: N/A Quantitative bacterial Intubated outside Special tracheal tube for SSD - Intra-cuff pressure monitored Duration MV: N/A culture of secretions hospital; high-risk surgery Method of SSD: Continuous Bo et al, 2000 68 Expected MV>72 h every 4h. obtained by protected or trauma; pre-existing (C): - Stress ulcer prophylaxis with specimen brush infection Standard tracheal tube histamine-2 receptor or proton (C): pump inhibitor. SAPS/APACHE: N/A

ICU LOS: N/A

Duration MV: N/A

Cardiothoracic ICU

I): (I): APACHE II: 11.1 ± 3.7 Cointervention: None specified Special endotracheal tube for ICU LOS: 3.7 ± 4.6 Adaptation of the Age >18 years and SSD (HI-Lo Evac) Duration MV: 1.5 ± 3.3 American College of required MV in the Patients transferred from an VAP bundle: Kollef et al, Method of SSD: Continuous 343 Chest Physicians. cardiothoracic ICU outside hospital and had - Head elevated 1999 Clinical features and after undergoing already received MV - Circuit change (C): (C): culture of endotracheal cardiac surgery - Stress ulcer prophylaxis (not Standard endotracheal tube APACHE II: 11.0 ± 3.6 aspirate. specific drug data) without SSD ICU LOS: 3.2 ± 4.5

Duration MV: 1.9 ± 5.1

Table S5. Studies included in the systematic reviews with meta-analysis

Diagnosis of Inclusion Intervention (I) and Cointerventions a Study n Characteristic of Exclusion criteria VAP criteria Control (C) groups and VAP Bundle b ICU/ patients

Medical-surgery ICU Clinical features after Cointervention: None specified 72h of MV and I): (I): protected specimen APACHE II: 20.5 ± 7.0 Special tracheal tube for SSD VAP bundle: brush culture ICU LOS: N/A Expected MV>72h, Patients intubated in other areas (HI-Lo Evac) - Intra-cuff pressure monitored containing >103 Valles et al, Duration MV: N/A intubation in ICU or in of the hospital, tracheostomy, Method of SSD: Continuous every 4h. 153 CFU/ml or 1995 the emergency develop pneumonia during the - Stress ulcer prophylaxis with bronchoalveolar department. first 72 hours of MV (C): sucralfate. lavage culture with (C): HI-Lo Evac with SSD lumen - No selective decontamination >104CFU/mlor good APACHE II: 18.9 ± 7.1 closed regimen or response to antibiotic ICU LOS: N/A prophylaxis. agents. Duration MV: N/A

Medical-surgical ICU (I): Cointervention: Stress ulcer

Special tracheal tube for SSD prophylaxis: I): New and persistent (HI-Lo Evac) with/without (aluminum hydroxide) SAPS/APACHE: N/A infiltrate on the chest stress ulcer prophylaxis 20ml/6h or cytoprotective agent ICU LOS: N/A X-ray after 2 days of No intubation, tracheostomy, Method of SSD: Intermittent (sucralfate) 1g/6h. Mahul et al, Duration MV: N/A intubation and aerobic intubated <3 days, vital risk for 145 Expected MV>3 days every 1h 1992 microorganism on new intubation, intubated VAP bundle: bronchoalveolar before ICU, gastric bleeding, (C): - Intra-cuff pressure monitored (C): lavage culture ≥ 105 oesogastrectomy HI-LO EVAC tube without every 8h and kept up to 30mm SAPS/APACHE: N/A CFR/ml. SSD technique with/without Hg. ICU LOS: N/A stress ulcer prophylaxis Duration MV: N/A

MV, mechanical ventilation; ICU, ; I, intervention; C, control; CPIS, Clinical infection pulmonary score; SSD, subglottic secretion drainage; PEEP, positive end-expiratory pressure; CFU, colony-forming units; CDC, Centers for Disease Control and Prevention; APACHE II, Acute Physiology and Chronic Health Evaluation; SAPS II, Simplified Acute Physiologic Score; LOS, length of stay. a Cointervention only in intervention group. b VAP bundle carried out in both groups: control and intervention. c Median [IQR]