Online supplement 2: Characteristics of included studies, data extraction table
Bent et al., 2012 Mahmoodpoor et al.,
2012
Saito et al., 2013 Philippart et al., 2015 Monsel et al., 2016 Jailette et al., 2017
Methods
Design RCT RCT RCT RCT RCT RCT
Location USA Iran Japan France and Tunesia France France
Type of randomisation
NR Individual Individual Clustered randomisation
(clusters of 9-10 people)
Allocation table in permuted blocks (block size 10)
Custer randomized cross- over study on ICU level
# centres 1 1 1 4 (3 in France and 1 in
Tunesia)
1 10
Study period April 2012 – May 2013
July 2011 – March 2012 April 2010 – March 2012 July 2010 – November 2012
October 2011 – September 2013
June 2014 – October 2015
Participants
n 80 64 289 604 109 326
Setting NR Medical-surgical ICU NR Medical-surgical ICUs Multidisciplinary ICU Medical patients
Inclusion criteria
a See table in the bottom of this appendix
18-65y
Expected duration of MV ≥ 96h
> 18y
Expected duration of MV ≥ 48h
Adults
Requiring intubation in the ICU
Expected duration of MV ≥ 48h
> 18y
Scheduled to undergo major thoracic, thoracoabdominal or abdominal aorta surgery without pulmonary exclusion requiring intubation with a bouble- lumen ET
Justifying systematic admission to the ICU for postoperative care
> 18y
Requiring intubation in the ICU
Expected duration of MV ≥ 48h
Exclusion criteria
a See table in the bottom of this appendix
Previous history of immunosuppression or pneumonia and intubation before admission to intensive care unit
Patients who are transferred from another hospital and received mechanical ventilation.
Patients who received tracheostomy within 72h from admission.
Patients that it was judged that nasal intubation was
MV for > 24h preceeding ICU admission
Lung surgery within the preceding month Documented
bronchiectasis or cystic fibrosis
Tracheostomy at ICU admission
History of pneumonia < 1 month before planned surgery
Already enrolled in another trial
Pregnant
Contraindication for enteral feeding Intubated for > 72h at screening for eligibility Tracheostomy at ICU admission
Inclusion in another study that may interfere with
necessary.
Patients who judged that a medical attendant was inappropriate.
this trial
Baseline characteristics
Taper ed
Stand ard
P Tapered Standar d
P Tapered Standard P Tapered Standar d
P Tapered Standar d
P Tapere d
Standa rd
P
% men 75.7% 62.8% NR 68.8% 62.5% NS NR NR NR 59,9% 59,9% NR 73% 68% NR 60.5% 67.7% 0.18
Age (y) 53.5
±14.7 58.2
±12.7
NR 54.0
±19.49
57.31
±19.77
NS NR NR NR PVC:
63.2 (53.4- 76.4) PU: 64.7 (51.1- 78.0)
PVC:
65.6 (53.0- 77.2) PU: 65.3 (55.2- 75.6)
NR 64 (58- 70)
66 (59- 73)
NR 63.5±1 4.5
61.1±1 5.1
0.14
SAPS II NR NR NR NR NR NR NR NR NR PVC: 45
(33-58) PU: 45 (33-57)
PVC: 42 (33-58) PU: 41 (33-58)
NR 29 (21–
42)
31 (24–
40)
NR 51.8 ± 17.4
51.7 ± 16.9
0.96
APACHE II NR NR NR 23 (17- 32)
23 (17- 33)
NS NR NR NR NR NR NR NR NR NR NR NR NR
COPD NR NR NR NR NR NR NR NR NR NR NR NR 35% 35% NR 19.8% 18.3% 0.74
Other sign. diff.
betw. groups
None reported None reported None reported None reported None reported “Patient characteristics at
ICU admission were similar in the two groups.
No significant difference was found in patient characteristics at randomization, during the 48h following
randomization, or during ICU stay between the two groups.”
Standard care for infection prevention
NR Manual Pcuff-regulation,
every 3h with a manometer (20-30 cmH2O)
SSD 1x/h
Head of bed elevation (30°-40°)
Manual Pcuff-regulation, every 6h with a manometer (20-30 cmH2O)
SSD
Manual Pcuff-regulation, every 6h with a
manometer (25-30mmHg) CHX 0.12% mouthwash every 6h
PEEP of at least 5 cmH2O Head of bed elevation,
Manual Pcuff-regulation, every 6h with a manometer (25 cmH2O) IV cefamandole (initial dose: 1.5g, and 750mg every 2h) intraoperatively and stopped at the end of
Manual Pcuff-regulation, every 8h with a manometer (25 cmH2O) Head of bed elevation checked every 3h CHX 0.10% mouthwash every 3h
5 cmH2O PEEP except for patients requiring prone positioning for acute respiratory distress syndrome
Low-dose erythromycin (200mg/12h) in case of gastric residual greater than 250 ml
No SSD
surgery
Head of bed elevation (30°-45°)
Enteral nutrition with quantification of residual gastric volume every 6h Hexetidine mouthwash every 6h
End-expiratory-pressure level set by treating physician (mean: 5.6 and 5.0 cmH2O in intervention and control group respectively (P=0.03))
PEEP of at least 5 cmH2O Open tracheal suctioning every 3h
No SSD
Stress ulcer prophylaxis
NR Proton-pump inhibitor or
H2 blockers
NR Proton-pump inhibitor in
case of hypocoagulability (39,9% of patients)
Proton-pump inhibitor Not routinely administered
Intervention
Tube PVC, taper-shaped (TaperGuard, Covidien, Dublin, Ireland)
PVC, taper-shaped (TaperGuard, Covidien, Dublin, Ireland)
PVC, taper-shaped (TaperGuard Evac, Covidien, Dublin, Ireland)
PVC, taper-shaped (TaperGuard, Covidien, Astlone, Ireland) PU, taper-shaped (SealGuard, Covidien, Astlone, Ireland)
PVC, taper-shaped (TaperGuard, Covidien, Astlone, Ireland)
PVC, taper-shaped (TaperGuard, Covidien, Astlone, Ireland)
Control
Tube PVC, cylindrical (Hi- Lo, Covidien, Dublin, Ireland)
PU, cylindrical (SealGuard, Covidien, Astlone, Ireland)
PVC, cylindrical (Hi-Lo Evac, Covidien, Dublin, Ireland)
PVC, cylindrical (Hi-Lo, Covidien, Astlone, Ireland) PU, cylindrical (Microcuff, Kimberly-Clark, Irving, TX)
PVC, spherical (High Contour, Brandt, Mallinckrodt Medical, USA)
PVC, cylindrical (Hi-Lo, Covidien, Astlone, Ireland)
Outcomes
Primary Number of
participants with dye leakage
VAP-incidence VAP-incidence Tracheal colonization Incidence of first
postoperative pneumonia episodes
Microaspiration of gastric contents during 48h following inclusion Secondary Hospital-LOS
Postoperative pneumonia incidence Incidence of
unanticipated ICU admission
NR Rate of achieving an
appropriate cuff pressure Time to VAP onset MV-duration ICU-LOS 28d-mortality Adverse events
VAP-incidence Incidence of
postextubational stridor
Time from intubation to postoperative pneumonia diagnosis
Rate of second pneumonia episodes
Microaspiration Cuff-pressure variations
Oropharyngeal Microaspiration during 48h following inclusion Tracheobronchial colonization VAP-incidence VAE-incidence
Data reported as median (25%-75% interquartile range) or mean ± standard deviation, depending on what authors reported
RCT, randomized controlled trial; NR, not reported; NS, authors only reported that P-value was non-significant; ICU, intensive care unit; MV, mechanical ventilation; SSD, subglottic secretion drainage; PEEP, positive end-expiratory-pressure; h, hours; CHX, chlorhexidine; PVC, polyvinylchloride; PU polyurethane; VAP, ventilator-associated pneumonia; LOS, length-of-stay; HAP, hospital acquired pneumonia; CXR, chest x-ray; US, ultrasound; BAL, broncho-alveolar lavage
a In- and exclusion criteria for Bent et al., 2012 (omitted from main table for legibility purposes) Inclusion criteria > 18y
Scheduled for an elective surgical procedure under general anesthesia for no less than 2hr and no more than 12hr with planned endotracheal intubation via the oral route
Willing and able to give informed consent for participation in the study
Anticipated extubation at the conclusion of general anesthesia in the operating room and prior to admission to the PACU
Expected hospital stay of greater than or equal to 23h
Exclusion criteria Preexisting acute respiratory illness requiring antibiotic treatment within the two weeks prior to surgery
Duration of MV ICU-LOS 28d-mortality
ICU-acquired infection Antimicrobial-free days Invasive MV-free days ICU-LOS
ICU-mortality (up to day 28 after inclusion or discharge, whatever happens first) HAP diagnostic criteria
Time frame NR NR From 48h post intubation 48h post intubation – 48h
post extubation
Intubation – 5d post extubation
48h post intubation – 48h post extubation
Clinical NR “Pneumonia was defined
based on clinical,
radiological and laboratory findings based on clinically pulmonary infection score (CPIS).”
NR New and persistent
infiltrate on CXR
New or persistent infiltrate on CXR and/or new bedside lung-US patterns highly evocative of lung infection
New and persistent infiltrate on CXR
Radiological NR NR ≥ 1 of the following:
1) Temperature > 38.4°C or < 36.6°C
2) Leucocytosis > 11*109/l 3) Purulent tracheal aspirates
≥ 2 of following:
1) Temperature > 38.4°C or < 36.5°C
2) Leucocytosis > 11*109/l 3) Purulent tracheal aspirates
≥ 2 of following:
1) Temperature > 38°C or
< 36°C
2) Leucocytosis > 10*109/l or < 1.5*109/l
3) Purulent tracheal aspirates
Microbiological NR “Semiquantitative BAL
fluid culture of 3+ or phagocytosis on Gram staining.”
tracheobronchial aspirate:
≥ 105 CFU/ml or BAL: ≥ 104 CFU/ml
BAL: ≥ 104 CFU/ml or mini- BAL: ≥ 103 CFU/ml)
tracheobronchial aspirate:
≥ 106 CFU/ml or BAL: ≥ 104 CFU/ml
Temperature of over 38.3°C at time of scheduled surgery
Surgical requirement for naso-tracheal intubation
Patients undergoing surgical procedures directly on the lungs, trachea, or airways
Presence of tracheostomy
History of allergic reaction to methylene blue
Methemoglobinemia, glucose-6-phosphate (G6PD) deficiency
Renal insufficiency or failure
Requirement for prolonged intubation and/or ventilation beyond the point of PACU admission
Intraoperative use of nitrous oxide, to avoid the increase in cuff pressure due to diffusion of gas over time
Psychiatric drugs of the following classifications: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).
Prone positioning during surgery
Pregnant or lactating women based on standardized preoperative screening protocols
Legally detained prisoner status
Unwilling or unable to give informed consent for participation in the study
