Avoid intubation and reintubation if possible

1. 1. Use high-flow nasal oxygen or non-invasive positive pressure ventilation (NIPPV) as appropriate whenever safe and feasible (Quality of Evidence: HIGH).

   1. a. High-flow nasal oxygen may help avert intubation in patients with hypoxemic respiratory failure and prevent reintubation after extubation of critically ill patients and postoperative patients compared to conventional oxygen therapy. ^{Reference Rochwerg, Granton and Wang91–Reference Yasuda, Okano and Mayumi94} High-flow nasal oxygen has also been associated with a trend toward less nosocomial pneumonia in patients with hypoxemic respiratory failure. ^{Reference Frat, Thille and Mercat95}

   2. b. NIPPV is associated with lower rates of intubation, reintubation, VAP, and mortality compared to conventional oxygen therapy in patients with acute hypercapnic or hypoxemic respiratory failure. ^{Reference Osadnik, Tee, Carson-Chahhoud, Picot, Wedzicha and Smith96–Reference Vaschetto, Pecere and Perkins100} Use caution when considering NIPPV to manage patients with impaired consciousness, acute lung injury, acute respiratory distress syndrome, severe hypoxemia, severe acidemia, or when continuing NIPPV for patients whose dyspnea or gas exchange fails to rapidly respond to NIPPV. Helmet ventilation may be associated with better outcomes than face-mask ventilation. ^{Reference Ferreyro, Angriman and Munshi99,Reference Grieco, Menga and Cesarano101}

   3. c. High-flow nasal oxygen and NIPPV appear to be similar in their capacity to prevent intubation, reintubation, and postextubation respiratory failure. Some meta-analyses suggest that high-flow nasal cannula may reduce ICU and hospital length of stay compared to NIPPV, while others do not. ^{Reference Granton, Chaudhuri and Wang92,Reference Sang, Nong and Zheng102}

   4. d. Combining high-flow nasal oxygen with NIPPV immediately after extubation may further decrease the risk of reintubation in patients at high risk for extubation failure compared to using high-flow nasal oxygen alone. ^{Reference Thille, Muller and Gacouin103}

2. 2. Placing nonintubated patients with COVID-19 acute hypoxemic respiratory failure in the prone position may lower the risk of intubation compared to standard care (Quality of Evidence: MODERATE). ^{Reference Ehrmann, Li and Ibarra-Estrada104}

Minimize sedation

1. 1. Minimize sedation of ventilated patients whenever possible (Quality of Evidence: HIGH). ^{Reference Shehabi, Bellomo and Kadiman105,Reference Devlin, Skrobik and Gelinas106}

2. 2. Preferentially use multimodal strategies and medications other than benzodiazepines to manage agitation (Quality of Evidence: HIGH). ^{Reference Devlin, Skrobik and Gelinas106}

   1. a. Examples include analgesics for pain, reassurance for anxiety, and antipsychotics, dexmedetomidine, and/or propofol for agitation. ^{Reference Devlin, Skrobik and Gelinas106} Dexmedetomidine and propofol are associated with shorter duration of mechanical ventilation and ICU length of stay compared to benzodiazepines. ^{Reference Fraser, Devlin and Worby107} A randomized trial of light sedation with dexmedetomidine versus propofol found no difference in ventilator-free days or mortality. ^{Reference Hughes, Mailloux and Devlin108} Dexmedetomidine may decrease need for intubation in patients on noninvasive ventilation. ^{Reference Lewis, Piticaru and Chaudhuri109}

3. 3. Utilize a protocol to minimize sedation (Quality of Evidence: HIGH). ^{Reference Ouellette, Patel and Girard110}

   1. a. Potential strategies to minimize sedation include nurse-driven protocols for targeted light sedation and daily sedative interruptions (ie, spontaneous awakening trials) for patients without contraindications. ^{Reference Devlin, Skrobik and Gelinas106,Reference Ouellette, Patel and Girard110}

   2. b. A meta-analysis of 6 randomized trials reported that protocols to minimize sedation were associated with significantly shorter ICU length of stay compared to managing patients without protocols. ^{Reference Ouellette, Patel and Girard110} There was no significant association between the use of protocols to minimize sedation and duration of mechanical ventilation or short-term mortality. There was insufficient evidence to recommend one protocol over another.

   3. c. A small, single-center, randomized trial ^{Reference Strom, Martinussen and Toft111} suggested that patients managed with no sedation (but morphine as needed) versus propofol or midazolam may be extubated sooner and have shorter ICU length of stay, but a subsequent multicenter randomized trial of no sedation versus light sedation with daily sedative interruptions reported no difference in ventilator-free days, ICU-free days, or 90-day mortality. ^{Reference Olsen, Nedergaard and Strom112}

4. 4. Implement a ventilator liberation protocol (Quality of Evidence: HIGH) ^{Reference Girard, Alhazzani and Kress113}

   1. a. Assess readiness to extubate daily in patients without contraindications (i.e., conduct spontaneous breathing trials). ^{Reference Ely, Baker and Dunagan114–Reference Lellouche, Mancebo and Jolliet117}

   2. b. Ventilator liberation protocols are associated with extubating patients an average of 1 day earlier compared to managing patients without a protocol. ^{Reference Girard, Alhazzani and Kress113}

   3. c. Protocols to minimize sedation, mobilize patients, and liberate them from mechanical ventilation may be synergistic. ^{Reference Girard, Kress and Fuchs118,Reference Hsieh, Otusanya and Gershengorn119}

Maintain and improve physical conditioning

1. 1. Provide early exercise and mobilization (Quality of Evidence: MODERATE).

   1. a. Early exercise and mobilization programs may shorten duration of mechanical ventilation, reduce ICU length of stay, lower VAP rates, and increase the rate of return to independent function. ^{Reference Girard, Alhazzani and Kress113,Reference Zhang, Hu and Cai120–Reference Zang, Chen and Wang123} There is no consistent association between early mobilization and hospital length of stay or mortality.

   2. b. Financial modeling suggests that early mobility programs may be cost saving. ^{Reference Hsieh, Otusanya and Gershengorn119,Reference Lord, Mayhew and Korupolu124}

Elevate the head of the bed

1. 1. Elevate the head of the bed to 30–45° (Quality of Evidence: LOW).

   1. a. A meta-analysis of 8 randomized trials reported that elevating the head of the bed was associated with a significant reduction in VAP rates but no difference in duration of mechanical ventilation or mortality. ^{Reference Wang, Li, Yang, Tang, Yuan and Deng125} The data on outcomes other than VAP, however, were sparse (combined sample size <500 patients); thus, the impact on these outcomes is uncertain. Given the simplicity, ubiquity, minimal risk, lack of cost, and potential benefit of this intervention, we nonetheless classify it as an essential practice while we await further data.

Provide oral care with toothbrushing but without chlorhexidine

1. 1. Provide daily oral care with toothbrushing but without chlorhexidine (Quality of Evidence: MODERATE).

   1. a. Daily toothbrushing is associated with significantly lower VAP rates, shorter duration of mechanical ventilation, and shorter ICU length of stay. ^{Reference Zhao, Wu, Zhang, Li, Worthington and Hua126,Reference Sozkes and Sozkes127}

   2. b. Meta-analyses of randomized trials and observational studies allow for the possibility that oral care with chlorhexidine may increase mortality rates. ^{Reference Klompas, Li, Kleinman, Szumita and Massaro75,Reference Price, MacLennan and Glen128–Reference Deschepper, Waegeman, Eeckloo, Vogelaers and Blot130} This is further discussed below.

Provide early enteral rather than parenteral nutrition

1. 1. Provide early enteral rather than parenteral nutrition (Quality of Evidence: HIGH).

   1. a. Early enteral nutrition is associated with a lower risk of nosocomial pneumonia, shorter ICU length of stay, and shorter hospital length of stay compared to early parenteral nutrition. ^{Reference Singer, Blaser and Berger131}

Maintain ventilator circuits

1. 1. Change the ventilator circuit only if visibly soiled or malfunctioning (Quality of Evidence: HIGH).

   1. a. Changing the ventilator circuit as needed rather than on a fixed schedule has no impact on VAP rates or patient outcomes but decreases costs. ^{Reference Han and Liu132}

   2. b. Follow manufacturers’ instructions for use if they differ from this recommendation.

   3. c. Follow CDC/Healthcare Infection Control Practices Advisory Committee guidelines and manufacturers’ instructions for use of sterilization and disinfection of respiratory care equipment. ^{Reference Rutala and Weber133}

Approaches that definitively are not recommended for VAP or VAE prevention

Good-quality evidence suggests that the following interventions neither lower VAP/VAE rates nor decrease duration of mechanical ventilation, length of stay, or mortality.

1. 1. Stress-ulcer prophylaxis (Quality of Evidence: MODERATE)

   1. a. Stress-ulcer prophylaxis lowers the risk of gastrointestinal bleeding, but a meta-analyses of randomized trials suggested no impact on nosocomial pneumonia, length of stay, or mortality. ^{Reference Barbateskovic, Marker and Granholm188–Reference Deliwala, Hamid and Goyal192} A large, multicenter randomized trial of pantoprazole versus placebo in ICU patients reported no difference in pneumonia rates or mortality rates. ^{Reference Krag, Marker and Perner193}

   2. b. Stress-ulcer prophylaxis may be indicated for reasons other than VAP prevention.

2. 2. Monitoring residual gastric volumes (Quality of Evidence: MODERATE)

   1. a. Monitoring patients for regurgitation and vomiting alone is as effective as monitoring patients for regurgitation, vomiting, and residual gastric volumes with regard to VAP rates, duration of mechanical ventilation, and mortality. ^{Reference Reignier, Mercier and Le Gouge194}

3. 3. Early versus late parenteral nutrition (Quality of Evidence: MODERATE)

   1. a. Early parenteral nutrition (within 48 hours of ICU admission) is associated with increased mortality and nosocomial infections compared to late parenteral nutrition (initiated on or after ICU day 8). ^{Reference Casaer, Mesotten and Hermans195}

Avoid intubation

1. 1. Avoid intubation if possible (Quality of Evidence: HIGH).

   1. a. Nasal continuous positive airway pressure (CPAP) ventilation (with or without nasal intermittent mechanical ventilation) and high-flow oxygen via nasal cannula are viable alternatives to intubation in most preterm infants, but success rates are greatest for those delivered at >28 weeks gestation. ^{Reference Bhandari, Finer and Ehrenkranz204–Reference Hong, Li, Li and Zhang208}

   2. b. Many premature neonates (especially those with a gestational age >28 weeks) can be successfully supported with noninvasive positive pressure ventilation in the delivery room and subsequently in the NICU.

Minimize duration of mechanical ventilation

1. 1. Manage patients without sedation whenever possible ^{Reference Hamid, Malik, Masood, Zia and Ahmad209,Reference Ng, Taddio and Ohlsson210} (Quality of Evidence: LOW).

2. 2. Use caffeine therapy for apnea of prematurity within 72 hours after birth to facilitate extubation ^{Reference Murner-Lavanchy, Doyle and Schmidt211} (Quality of Evidence: HIGH).

3. 3. Assess readiness to extubate daily (Quality of Evidence: LOW).

4. 4. Take steps to minimize unplanned extubations and reintubations ^{Reference Veldman, Trautschold, Weiss, Fischer and Bauer212,Reference Merkel, Beers, Lewis, Stauffer, Mujsce and Kresch213} (Quality of Evidence: LOW).

   1. a. Use nasal CPAP or nasal NIPPV in the postextubation period to help prevent the need for reintubation. ^{Reference Ramaswamy, Bandyopadhyay and Nanda214}

5. 5. Provide regular oral care with sterile water (extrapolated from practice in infants and children, no data in preterm neonates) (Quality of Evidence: LOW).

6. 6. Change the ventilator circuit only if visibly soiled or malfunctioning or per manufacturers’ instructions for use (extrapolated from studies in adults and children, no data in preterm neonates) (Quality of Evidence: LOW).

Avoid intubation if possible

1. 1. Use noninvasive positive pressure ventilation (NIPPV) or high flow oxygen by nasal cannula whenever safe and feasible (Quality of Evidence: MODERATE).

   1. a. Risks of NIPPV in pediatric patients mirror those for adults with the added issue that pediatric patients often need sedation to tolerate NIPPV. ^{Reference Javouhey, Barats, Richard, Stamm and Floret240,Reference Yanez, Yunge and Emilfork241}

   2. b. CPAP may be superior to high flow oxygen by nasal cannula to avoid intubation in infants with bronchiolitis. ^{Reference Milesi, Essouri and Pouyau242}

Minimize duration of mechanical ventilation

1. 1. Assess readiness to extubate daily in patients without contraindications ^{Reference Ferguson, Walsh, Munhall and Arnold243–Reference Faustino, Gedeit and Schwarz247} (Quality of Evidence: MODERATE).

   1. a. Randomized controlled trials suggest that daily spontaneous breathing trials can decrease mean duration of ventilation and PICU length of stay in postoperative cardiac surgery patients. ^{Reference Foronda, Troster and Farias245,Reference Ferreira, Sugo, Aragon, Carmona and Carlotti248} There is no consensus on the most effective technique for spontaneous breathing trials in pediatric patients. ^{Reference Ferguson, Walsh, Munhall and Arnold243,Reference Newth, Hotz and Khemani246}

2. 2. Take steps to minimize unplanned extubations and reintubations ^{Reference Lucas da Silva and de Carvalho249,Reference Klugman, Melton and Maynord250} (Quality of Evidence: LOW)

   1. a. A multicenter, quality-improvement initiative tested a bundle of measures to reduce unplanned extubations. ^{Reference Klugman, Melton and Maynord250} The bundle included standardized anatomic reference points and securement methods, protocols for high-risk situations, and multidisciplinary apparent-cause analyses. The bundle was associated with significant reductions in unplanned extubations and episodes of cardiovascular collapse.

3. 3. Avoid fluid overload (Quality of Evidence: MODERATE).

   1. a. Meta-analysis of the association between fluid balance and outcomes in critically ill children suggests that fluid overload is associated with increased risk for prolonged mechanical ventilation (>48 hours). ^{Reference Alobaidi, Morgan and Basu251}

   2. b. Interventional studies on fluid management in critically ill children are sparse. One of the few available studies assessed infants at risk for acute kidney injury and fluid overload following cardiac surgery. These infants were randomized to peritoneal dialysis versus furosemide; those randomized to peritoneal dialysis were less likely to develop fluid overload and less likely to have prolonged ventilator use. ^{Reference Kwiatkowski, Goldstein, Cooper, Nelson, Morales and Krawczeski252} The generalizability of these findings to other populations is unknown.

   3. c. The Pediatric Surviving Sepsis Campaign and the Pediatric Acute Lung Injury Consensus Conference recommend limiting fluid intake, starting diuretics, and/or early renal replacement therapy for children with ARDS and for children in the postresuscitation phase of sepsis. ^{Reference Weiss, Peters and Alhazzani253,254}

Provide regular oral care

1. 1. Provide regular oral care (Quality of Evidence: LOW).

   1. a. Four before-and-after studies of VAP bundles that emphasized oral care reported significant decreases in VAP rates following bundle implementation. ^{Reference Bigham, Amato and Bondurrant234,Reference Curley, Schwalenstocker and Deshpande255–Reference McBeth, Montes, Powne, North and Natale257}

   2. b. The American Dental Association recommends beginning oral hygiene a few days after birth in term infants. Wipe the gums with a gauze pad after each feeding to remove plaque and residual formula that could harm erupting teeth.

   3. c. For children aged <3 years, the ADA recommends brushing children’s teeth as soon as they begin to come into the mouth using fluoride toothpaste in an amount no more than a smear the size of a grain of rice. ²⁵⁸ A pea-sized amount of fluoride toothpaste is recommended for children aged 3–6 years. ²⁵⁸

   4. d. After oral hygiene, rinse and suction the mouth. Keep the oral mucosa and lips clean, moist, and intact using sponge-tipped applicators dipped in non-alcohol, non-peroxide mouth rinse. ^{Reference Curley, Schwalenstocker and Deshpande255}

Elevate the head of the bed

1. 1. Elevate the head of the bed unless medically contraindicated (Quality of Evidence: LOW).

   1. a. Three before-and-after studies of VAP bundles that included head of bed elevation reported lower VAP rates. ^{Reference Bigham, Amato and Bondurrant234,Reference De Cristofano, Peuchot, Canepari, Franco, Perez and Eulmesekian256,Reference McBeth, Montes, Powne, North and Natale257}

   2. b. Many hospital cribs do not have inbuilt angle-measuring devices. Alternative measuring devices are required in these circumstances.

Maintain ventilator circuits

1. 1. Change ventilator circuits only when visibly soiled or malfunctioning or per manufacturers’ instructions (Quality of Evidence: MODERATE).

   1. a. A meta-analysis of 6 studies reported no difference in VAP rates or mortality with 3-day versus 7-day circuit changes. ^{Reference Abiramalatha, Ramaswamy, Thanigainathan, Pullattayil and Kirubakaran259} Circuit changes are therefore recommended only when the circuit is soiled or malfunctioning to minimize costs. ^{Reference Samransamruajkit, Jirapaiboonsuk and Siritantiwat260,Reference Hsieh, Hsia, Wu, Lin, Chang and Wong261}

   2. b. Follow manufacturers’ instructions for use if they differ from this recommendation.

2. 2. Remove condensate from the ventilator circuit frequently (Quality of Evidence: LOW).

   1. a. Avoid draining the condensate toward the patient. ^{Reference Bigham, Amato and Bondurrant234}

Endotracheal tube selection and management

1. 1. Use cuffed endotracheal tubes (Quality of Evidence: LOW).

   1. a. Pediatric intensivists have historically favored uncuffed tubes due to concern that cuffs may induce subglottic stenosis in pediatric airways. Cuffing has proven safe, however, and may decrease the risk of microaspiration. ^{Reference Gopalareddy, He and Soundar262,Reference Weiss, Dullenkopf, Fischer, Keller and Gerber263} Cuffed tubes are now recommended for term newborns and children. ^{Reference Topjian, Raymond and Atkins264}

2. 2. Maintain cuff pressure and volume at the minimal occlusive settings to prevent clinically significant air leaks around the endotracheal tube, typically 20–25 cm H₂O. ^{Reference Nseir, Zerimech and Fournier171,Reference Gopalareddy, He and Soundar262,Reference Schneider, Mulale, Yamout, Pollard and Silver265} This “minimal leak” approach is associated with lower rates of post-extubation stridor ^{Reference Schneider, Mulale, Yamout, Pollard and Silver265} (Quality of Evidence: LOW).

   1. a. The potential merits of automated manometers for VAP prevention have not been studied in pediatric patients.

3. 3. Suction oral secretions before each position change (Quality of Evidence: LOW). ^{Reference Tsai, Lin and Chang266}

No impact on VAP rates for pediatric patients

These interventions may be indicated for reasons other than VAP prophylaxis.

1. 1. Oral care with chlorhexidine (Quality of Evidence: MODERATE)

   1. a. Chlorhexidine appears to be safe for developing teeth, ^{Reference Wan, Seow, Purdie, Bird, Walsh and Tudehope279} but randomized controlled trials have found no difference in VAP rates, length of stay, or mortality in infants and children. ^{Reference Jacomo, Carmona, Matsuno, Manso and Carlotti280–Reference Karakaya, Duyu and Yersel285}

2. 2. Stress-ulcer prophylaxis (Quality of Evidence: LOW)

   1. a. Two small studies found no impact on VAP rates. ^{Reference Yildizdas, Yapicioglu and Yilmaz286,Reference Lopriore, Markhorst and Gemke287} A larger, multicenter, cohort study and a meta-analysis reported that acid-suppressive medications were associated with higher VAP rates. ^{Reference Albert, Zurakowski and Bechard288,Reference Yao, Ong, Eales, Sultana, Wong and Lee289}

Lowers VAP rates but no impact on duration of mechanical ventilation, length of stay, or mortality

1. 1. Silver-coated endotracheal tubes (Quality of Evidence: LOW)

   1. a. These tubes have not been studied in children and are only feasible for children aged ≥10 years since the smallest available size is 6.0.

No recommendation

These interventions have limited data from pediatric studies, no impact on VAP rates or outcomes in adults, and unclear impact on costs.

1. 1. Closed/in-line suctioning (Quality of Evidence: LOW)

   1. a. Closed suctioning may be associated with fewer transient decreases in oxygenation and increases in heart rate and blood pressure compared to open suctioning, but the clinical significance of these findings is unclear. ^{Reference Evans, Syddall, Butt and Kinney290–Reference Tume, Baines and Guerrero292}

   2. b. An observational study of open versus closed suctioning in children did not find any difference in VAP rates, length of stay, or mortality, but the significance of these findings are unclear given the lack of blinding and randomization. ^{Reference Morrow, Mowzer, Pitcher and Argent293}

Provide regular oral care

1. 1. Oral care is the most commonly studied strategy to prevent NV-HAP. Before-and-after series suggest a possible benefit. ^{Reference Chick and Wynne294–Reference Baker, Quinn, Ewan and Giuliano297} Two large, cluster randomized trials conducted in nursing homes did not show a benefit, but their generalizability to acute-care hospitals is unknown. ^{Reference Juthani-Mehta, Van Ness and McGloin298,Reference Zimmerman, Sloane and Ward299} Most randomized trials in acute-care hospitals have focused on ICU patients, most of whom were on mechanical ventilation, making it difficult to discern their effect on NV-HAP. ^{Reference Kaneoka, Pisegna, Miloro, Lo, Saito and Riquelme300,Reference Satheeshkumar, Papatheodorou and Sonis301}

   1. a. Uncertainty remains regarding the most effective protocols, including types of staff involved (eg, dentistry professionals versus nondentistry professionals), frequency of oral care, whether to include an antiseptic, and if so, what type of antiseptic to use (eg, chlorhexidine gluconate, sodium bicarbonate, hydrogen peroxide, cetylpyridinium chloride, povidone-iodine).

   2. b. Notwithstanding the gaps in current evidence, we recommend toothbrushing daily given its benefits for oral health and the possible positive impact on objective outcomes observed in before-and-after studies in nonventilated patients and meta-analyses of randomized trials in ventilated patients. ^{Reference Zhao, Wu, Zhang, Li, Worthington and Hua126,Reference Sozkes and Sozkes127,Reference Chick and Wynne294–Reference Baker, Quinn, Ewan and Giuliano297}

Diagnose and manage dysphagia

1. 1. Early diagnosis and treatment of dysphagia may prevent NV-HAP, especially among neurologically impaired post-stroke patients. ^{Reference Cipra302–Reference Passaro, Harbarth and Landelle304}

2. 2. Potential approaches to diagnose dysphagia include nurse-administered risk assessment tools, bedside functional evaluations of swallowing, video fluoroscopic study, and fiberoptic endoscopic examination.

3. 3. Potential options to manage dysphagia include changes in method of pill administration, adjustments in consistencies of liquids and solids, supervision or assistance with meals, use of straws, and elevation of the head of bed while eating.

Provide early mobilization

1. 1. Data for early mobilization to prevent NV-HAP among hospitalized patients are sparse. ^{Reference Passaro, Harbarth and Landelle304,Reference Lacerna, Patey and Block305} One quasi-experiment found that bundling mobilization with other interventions reduced NV-HAP, attributable mortality, and antibiotic utilization, but the relative contribution of mobilization to these benefits is unclear. ^{Reference Lacerna, Patey and Block305} A randomized trial of engaging families to provide turning plus passive mobilization to post-stroke patients versus turning by nursing staff alone reported a significant decrease in pneumonia rates but did not report impact on length of stay or mortality. ^{Reference Cuesy, Sotomayor and Pina306} A nonrandomized controlled trial reported that mobilizing patients in 2 geriatric and respiratory wards was associated with a significant decrease in pneumonia rates compared to usual care in matched wards, although falls were significantly more frequent in the intervention group than in the control group and data were not provided on length of stay or mortality. ^{Reference Stolbrink, McGowan and Saman307} In a quasi-experimental study, intensified postoperative physical therapy for elderly patients undergoing hip fracture surgery was associated with less pneumonia and shorter length of stay compared to historical controls. ^{Reference Stahl and Westerdahl308}

2. 2. Additional trials are needed to better quantify the possible benefits versus fall-related harms of mobility programs. Implementation strategies are needed to increase the feasibility, frequency, and safety of mobilizing acute-care patients. In the meantime, early mobilization of patients should take into the account the risk of falls.

Implement multimodal interventions to prevent viral infections

1. 1. Approximately 20%–40% of NV-HAP is attributable to viral pathogens, and the ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the risk and morbidity of within-hospital transmission of respiratory viruses. ^{Reference Klompas, Baker and Rhee25,Reference Ambrosch, Rockmann, Klawonn and Lampl309–Reference Pagani, Thomas and Huttner311}

2. 2. Possible strategies to prevent nosocomial viral transmission include symptom screening of patients and healthcare workers, surveillance testing of all admitted patients, transmission-based precautions for patients with suspected and confirmed respiratory viral infections, universal masking when respiratory virus transmission rates are high in the hospital or in the community, assuring adequate ventilation, and vaccination of healthcare personnel and patients. ^{Reference Klompas, Milton, Rhee, Baker and Leekha312,Reference Klompas313}

Bundles

1. 1. Multiple observational studies have reported lower NV-HAP rates after implementing prevention bundles. ^{Reference Lacerna, Patey and Block305,Reference Kazaure, Martin, Yoon and Wren314,Reference de Assis, Macedo and Martins315} Effective bundles have included heterogeneous combinations of oral hygiene, bed positioning, dysphagia diagnosis and management, mobilizing patients, nasal hygiene, sedation restrictions, incentive spirometry, education for physicians and nurses, and/or electronic order-set bundles. One small randomized trial of usual care versus a bundle comprising dysphagia screening, oral care with chlorhexidine, placing the bed in the reverse Trendelenburg position, and vaccination against influenza and pneumococcus reported no difference in NV-HAP rates, length of stay, or mortality but did report a lower 1-year risk of readmission for respiratory infection. ^{Reference Rosario, Shafi and Yii316}

2. 2. The respective contribution of each bundle component, the extent to which bundle components are synergistic versus additive, and the most effective combination of interventions to include in bundles remains unknown.

Bed positioning

1. 1. Elevating the head of the bed is recommended to prevent VAP and VAE despite sparse evidence because some studies suggest benefit, it is simple, economical, and associated with minimal risk of harm in ventilated patients. Even fewer data, however, are available to inform whether and to what extent this applies to NV-HAP.

2. 2. One randomized trial among critically ill patients with tetanus in Vietnam found that semirecumbent position was associated with no difference in pneumonia rates but more frequent complications including the need for tracheostomy. ^{Reference Loan, Parry and Nga317} The generalizability of these findings to nontetanus patients in other settings is unknown.

Stress-ulcer prophylaxis

1. 1. Observational studies suggest an association between stress-ulcer prophylaxis and risk for NV-HAP but we are not aware of any randomized trials assessing the impact of acid-suppressing medications on NV-HAP outside the ICU setting. ^{Reference Herzig, Howell, Ngo and Marcantonio318}

Systemic antibiotic prophylaxis

1. 1. Randomized trials of prophylactic antibiotics in acute stroke patients show no impact on pneumonia rates, functional outcome, or mortality. ^{Reference Vermeij, Westendorp, Dippel, van de Beek and Nederkoorn319}

Monitoring and reporting

1. 1. Regular monitoring and internal reporting of patient outcomes and adherence rates to recommended prevention strategies (“process measures”) are important quality improvement strategies.

2. 2. Both outcome and process-measure reporting are likely beneficial: improving outcomes is the primary goal of care improvement programs but process of care surveillance can help identify specific processes to target for improvement.

3. 3. Report outcome measures to key organizational stakeholders including frontline care providers, service leaders (medical, nursing, respiratory therapy), and senior hospital administrators. Reporting these data back to providers and leaders has been associated with improvements in both performance rates and outcomes. ^{Reference Hatler, Mast and Corderella320–Reference Berenholtz, Pham and Thompson325}

4. 4. Report process measures internally only. External reporting of process measure data is not appropriate given substantial variability in the ways different organizations define, collect, analyze, and present process measure data.

Process measures

1. 1. Process-measure definitions and measurement strategies vary widely.

2. 2. For organizations that collect and report process measures:

   1. a. Clearly define measures including data sources, inclusion and exclusion criteria, frequency of monitoring, and numerator and denominator criteria.

   2. b. Develop a formal system to document compliance.

      1. i. Compliance can be measured via direct observations or via audits of patient charts, bedside checklists, and/or electronic medical records. Periodically validate the accuracy of paper and/or electronic documentation.

   3. c. Perform assessments regularly.

      1. i. The optimal frequency of assessments (eg, once daily, twice daily, or weekly) is not known but can likely be adjusted based on compliance rates and unit size.

      2. ii. An analysis of a large collaborative quality improvement effort suggests that the following approach can be used to determine the frequency of process measure assessments. ^{Reference Diehl, Yang and Speck326}

         1. 1. Start by measuring processes daily. If compliance is consistently high for a given process, then decrease the frequency of measures (ie, once every 2–3 days or once per week, and if compliance continues to be high, then decrease to once per month). If compliance is low or variable, then continue with daily measurements.

         2. 2. For units with at least 30 ventilator days per month, measuring compliance on 7 consecutive days per month provides accurate performance estimates

         3. 3. For units with <30 ventilator days per month, daily data collection is required to achieve accurate performance estimates.

   4. d. There is no consensus on how best to define adherence to different process measures and definitions for measuring adherence vary widely.

      1. i. Several published studies provide examples of how process measures were defined. ^{Reference Girard, Kress and Fuchs118,Reference Berenholtz, Pham and Thompson325,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327–329} These approaches can be used as starting points to come up with local strategies to define adherence.

Prevention bundles

1. 1. Prevention bundles are widespread in critical care and have been associated with decreases in VAP, VAE, NV-HAP, and in some cases, length of stay and mortality.

2. 2. A meta-analysis of 13 observational studies in adults found that implementation of ventilator bundles was associated with a 10% decrease in mortality, less time to extubation, and shorter length of stay. ^{Reference Pileggi, Mascaro, Bianco, Nobile and Pavia330} All the studies included in this analysis, however, were before-and-after or time-series analyses. It is therefore difficult to discern the extent to which lower VAP rates and better outcomes were due to prevention bundles versus changes in patient mix or unrelated changes in care. ^{Reference Klompas and Kalil331} Observational analyses of pediatric bundles have reported significant decreases in VAP rates, but few data are available on other outcomes. ^{Reference de Neef, Bakker, Dijkstra, Raymakers-Janssen, Vileito and Ista332}

3. 3. Prevention bundles have only been tested in 1 randomized trial. Researchers in Brazil randomized 188 ICUs to a multifaceted intervention including checklists for the prevention of VAP, daily goal assessments, and clinician prompts. There were no significant differences between intervention versus control units in VAP rates or mortality rates. ³²⁹ These results should be interpreted with caution, however, given that baseline adherence with some process measures was already high (eg, head of bed elevation), adherence with other measures did not improve (eg, light sedation, low tidal volume ventilation), and the intervention period may have been too brief to achieve significant changes. ^{Reference Nunez, Perdomo and Chavez333}

4. 4. There is no consensus on which processes to include in VAP/VAE prevention bundles. Bundles vary widely among different centers. ^{Reference Pileggi, Mascaro, Bianco, Nobile and Pavia330,Reference Klompas334}

5. 5. Ventilator bundle components potentially associated with lower mortality rates include staff education, performance feedback, and in adults, elevating the head of the bed, minimizing sedation, and assessing readiness for extubation. ^{Reference Ouellette, Patel and Girard110,Reference Girard, Alhazzani and Kress113,Reference Pileggi, Mascaro, Bianco, Nobile and Pavia330,Reference Stephens, Dettmer and Roberts335} Additional promising strategies include conservative fluid management, low tidal volume ventilation, and early mobility. ^{Reference Klompas, Anderson and Trick77,Reference Hsieh, Otusanya and Gershengorn119,Reference Pun, Balas and Barnes-Daly336}

6. 6. Compliance can be reported for each process measure individually and/or as ‘all or none’ compliance with a bundle of process measures. For ‘all or none’ compliance, credit is given only if all components have been accomplished and documented; if any components were not performed and/or were not documented, no credit is given.

Outcome measures

1. 1. Conduct surveillance for all VAEs including VAC, IVAC, and PVAP in adult ICUs. ^54,337 Report PedVAE rates in pediatric and neonatal ICUs. Report location-stratified rates for all events included in VAE and PedVAE algorithms. Report standardized infection ratios (SIRs) for all events included in VAE algorithms. ⁵⁴

   1. 1. VAE and PedVAE incidence density.

      1. i. Numerator: total number of VAEs (including VAC+IVAC+PVAP) or PedVAEs

      2. ii. Denominator: total ventilator days

      3. iii. Multiply by 1,000 and express as VAEs or PedVAEs per 1,000 ventilator days

   2. 2. IVAC incidence density (adults)

      1. i. Numerator: total number of IVACs and PVAPs

      2. ii. Denominator: total ventilator days

      3. iii. Multiply by 1,000 and express as the IVAC rate per 1,000 ventilator days

   3. 3. PVAP incidence density (adults)

      1. i. PVAP rate

      2. ii. Numerator: total number of PVAPs

      3. iii. Denominator: total ventilator days

      4. iv. Multiply by 1,000 and express as the overall PVAP rate per 1,000 ventilator days

   4. 4. Total VAE SIR (adults)

      1. i. Numerator: total number of VAEs, including VAC, IVAC, and PVAP

      2. ii. Denominator: total number of predicted VAEs

   5. 5. IVAC plus SIR (adults)

      1. i. Numerator: total number of IVACs (including PVAPs)

      2. ii. Denominator: total number of predicted IVACs (including PVAPs)

   6. 6. Note that the combined outcome of IVAC including PVAPs is sometimes referred to as “IVAC-plus.”

External reporting

1. 1. VAE is a potentially appropriate metric for public reporting, interfacility comparison, and pay-for-performance programs. Better data on the responsiveness of VAE to quality-improvement programs are necessary, however, before recommending VAEs for interfacility comparisons or pay-for-performance programs. Suitable risk adjustment strategies are also needed.

2. 2. PVAP is not suitable for external reporting because substantial variability in clinical and laboratory practices in the acquisition, processing, and interpretation of culture data preclude meaningful comparisons of PVAP rates between institutions.

3. 3. VAP rates generated using former NHSN surveillance definitions are not appropriate for external reporting in light of their considerable subjectivity.

4. 4. Hospitals in states that have mandatory reporting laws must collect and report data as required by their state. Pennsylvania and South Carolina are currently the only 2 states that require hospitals to report VAEs. Local and state health departments can provide specific information on public reporting requirements.

Develop a multidisciplinary team

1. 1. Multidisciplinary teams set goals, define each step in the implementation process, and monitor progress in reaching goals. ^{Reference Rawat, Yang and Ali79,Reference Seaver, Grant, Lunn, Sandor, Moran and Shapiro83,Reference Bigham, Amato and Bondurrant234,Reference Aragon and Sole339–Reference Michelangelo, Angriman and Pizarro341} Programs developed by team consensus are more effective and increase guideline adherence. ^{Reference Bigham, Amato and Bondurrant234,Reference Aragon and Sole339,Reference Brierley, Highe, Hines and Dixon342} Multidisciplinary teams include representatives from all disciplines that care for ventilated patients, including, at a minimum, unit directors, physicians, nurses, and respiratory therapists. Other partners that can strengthen the team include infection preventionists, pharmacists, nutritionists, physical therapists, occupational therapists, family members, and patient advocates. ^{Reference Klompas, Anderson and Trick77,Reference Seaver, Grant, Lunn, Sandor, Moran and Shapiro83,Reference Berenholtz, Pham and Thompson325,Reference Weireter, Collins, Britt, Reed, Novosel and Britt343–Reference Lim, Kuo and Ko347}

Involve local champions

1. 1. Identify local champions, including formal (eg, medical director, nursing director, charge nurses, director of respiratory therapy) and informal leaders (eg, engaged frontline staff). ^{Reference Pronovost, Berenholtz and Needham321,Reference Berenholtz, Pham and Thompson325,Reference Bloos, Muller and Harz328,Reference Burns, Earven, Fisher, Lewis, Merrell and Schubart340,Reference Weireter, Collins, Britt, Reed, Novosel and Britt343–Reference Rello, Afonso and Lisboa345,Reference Heimes, Braxton and Nazir348,Reference Danckers, Grosu and Jean349}

2. 2. Local champions are important to success because they engage stakeholders, educate peers, encourage ongoing improvement, and increase buy-in and ownership by both staff and administrators. ^{Reference Bigham, Amato and Bondurrant234,Reference Pronovost, Berenholtz and Needham321,Reference Berenholtz, Pham and Thompson325,Reference Brierley, Highe, Hines and Dixon342,Reference Khan, Al-Dorzi and Al-Attas346,Reference Heimes, Braxton and Nazir348,Reference Craven350}

3. 3. Local champions should know their hospital’s interests and needs and should be able to shape strategies to match local unit culture, monitor progress, and facilitate necessary changes during implementation. ^{Reference Hatler, Mast and Corderella320,Reference Miller, Briody and Casey351–Reference Khan, Al-Juaid and Al-Mutairi353} Early and continual communication between local champions and frontline staff allows providers to ask questions, resolve concerns, prepare for action, and sustain improvements. ^{Reference Hatler, Mast and Corderella320,Reference Craven350,Reference Robinson, Hoze, Hevener and Nichols352}

Utilize peer networks

1. 1. Horizontal networking of peers across hospitals can promote and increase compliance with evidence-based best practices. Voluntary peer networks encourage collaboration, analysis of performance, accountability, and commitment to specific goals. ^{Reference Klompas, Anderson and Trick77,Reference Rawat, Yang and Ali79,Reference Berenholtz, Pham and Thompson325,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Rello, Afonso and Lisboa345,Reference Mangino, Peyrani and Ford354,Reference Scales, Dainty and Hales355} Comparing progress and benchmarks between ICUs can help units better understand their local strengths and weaknesses, learn from best practices, brainstorm solutions to common problems, and promulgate local successes. ^{Reference Klompas, Anderson and Trick77,Reference Rawat, Yang and Ali79,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Pun, Balas and Barnes-Daly336,Reference Rello, Afonso and Lisboa345,Reference Khan, Al-Juaid and Al-Mutairi353}

Provide education sessions

1. 1. The introduction of evidence-based practices in the clinical setting should be supported by active and multifaceted education programs. ^{Reference Klompas, Anderson and Trick77,Reference Pileggi, Mascaro, Bianco, Nobile and Pavia330,Reference Jansson, Kaariainen and Kyngas356}

2. 2. Education sessions help summarize evidence, explain new processes, set expectations, and encourage staff to adopt recommended practices. ^{Reference Hatler, Mast and Corderella320,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Grimshaw, Eccles and Thomas357,Reference Talbot, Carr and Lee Parmley358}

3. 3. Education sessions can include workshops, hands-on training, conferences, slide presentations, and/or interactive discussions; employing multiple teaching modalities can help meet diverse learning styles. ^{Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Michelangelo, Angriman and Pizarro341,Reference Craven350,Reference Bouadma, Mourvillier and Deiler359,Reference Rosenthal, Desse and Maurizi360} Both local champions and topic experts (eg, infection preventionists) can lead staff education. ^{Reference Bigham, Amato and Bondurrant234,Reference Miller, Briody and Casey351,Reference Scales, Dainty and Hales355,Reference Al-Abdely, Khidir Mohammed and Rosenthal361}

4. 4. Education sessions must be informative and relevant for the learner; therefore it is important to have multidisciplinary educational programs customized for different levels of training and different specialties. ^{Reference Chumpia, Ganz, Chang and de Peralta81,Reference Pronovost, Berenholtz and Needham321,Reference Krimsky, Mroz and McIlwaine322,Reference Aragon and Sole339}

5. 5. Ongoing staff education helps maintain high levels of compliance with recommended practices. ^{Reference Hawe, Ellis, Cairns and Longmate323,Reference Rello, Afonso and Lisboa345,Reference Lim, Kuo and Ko347,Reference Bouadma, Mourvillier and Deiler359,Reference Parisi, Gerovasili and Dimopoulos362}

6. 6. Implementation of experiential learning strategies (simulation models, play activities, knowledge and attitude competencies, role-playing and feedback) may improve bundle adherence. ^{Reference Michelangelo, Angriman and Pizarro341}

7. 7. Educating patients and family members may help them better engage with and support the medical team’s plan of care. ^{Reference Pun, Balas and Barnes-Daly336,Reference Kellie, Scott and Cavallazzi363}

Provide educational materials

1. 1. Provide educational materials to staff that summarize the evidence, support self-study, and remind staff about new practices. ^{Reference Bassi, Ferrer, Saucedo and Torres364}

2. 2. Examples of educational materials include smartphone applications, interactive websites, pocket cards, brochures, posters, fact sheets, daily guides, guideline summaries, flow sheets and 1-page bulletins. ^{Reference Bigham, Amato and Bondurrant234,Reference Hawe, Ellis, Cairns and Longmate323,Reference Berenholtz, Pham and Thompson325,Reference Rello, Afonso and Lisboa345,Reference Parisi, Gerovasili and Dimopoulos362–Reference Lyerla366}

Standardize care processes

1. 1. Standardize care processes through the implementation of guidelines, bundles, protocols or pathways. Standardization helps establish new care processes as “normal behaviors” for staff. ^{Reference Klompas, Anderson and Trick77,Reference Rawat, Yang and Ali79,Reference Chumpia, Ganz, Chang and de Peralta81,Reference Seaver, Grant, Lunn, Sandor, Moran and Shapiro83,Reference Hatler, Mast and Corderella320,Reference Lim, Kuo and Ko347,Reference Danckers, Grosu and Jean349,Reference Khan, Al-Juaid and Al-Mutairi353,Reference Talbot, Carr and Lee Parmley358}

2. 2. Interventions to improve adherence with best practices in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care. ^{Reference Sinuff, Muscedere and Cook367}

3. 3. Daily multidisciplinary rounds are widely recommended. ^{Reference Weled, Adzhigirey and Hodgman368,Reference Balas, Weinhouse and Denehy369} Rounds should follow a structured format and include discussion about the patients’ goals for the day, consideration of what resources and actions are necessary to achieve these goals, and identification of potential barriers and/or safety issues. ^{Reference Krimsky, Mroz and McIlwaine322,Reference Berenholtz, Pham and Thompson325,Reference Johnson, Mangram, Mitchell, Lorenzo, Howard and Dunn344,Reference Kellie, Scott and Cavallazzi363,Reference Kim, Barnato, Angus, Fleisher and Kahn370,Reference Stone, Snetman and O’Neill371}

Create redundancy

1. 1. Build redundancy or independent checks into care delivery processes to increase the likelihood that best practices are followed. ^{Reference Hatler, Mast and Corderella320,Reference Pronovost, Berenholtz and Needham321,Reference Lim, Kuo and Ko347,Reference Kellie, Scott and Cavallazzi363,Reference Sinuff, Muscedere and Cook367,Reference Youngquist, Carroll and Farber372}

2. 2. Redundancy includes reminders about best practice and can take the form of posters, bulletins, pens, stamps, pocket cards, 1-page signs, daily goal lists in patient rooms, checklists, and preprinted order sets, text messages, and screensavers on clinical computers. ^{Reference Chumpia, Ganz, Chang and de Peralta81,Reference Pronovost, Berenholtz and Needham321,Reference Hawe, Ellis, Cairns and Longmate323,Reference Miller, Briody and Casey351,Reference Scales, Dainty and Hales355,Reference Lyerla366,Reference Youngquist, Carroll and Farber372–Reference Ladbrook, Bouchoucha and Hutchinson378}

3. 3. Engage family members to assist with preventive care as appropriate and/or to discuss prevention practices with the care team daily. This provides an external prompt for the performance of best practices and can help increase patient acceptance of practices such as oral care, mobilization, and delirium prevention. ^{Reference Berenholtz, Pham and Thompson325,Reference Kellie, Scott and Cavallazzi363}

4. 4. The combination of education and reminders significantly improves process of care performance rates. ^{Reference Grimshaw, Eccles and Thomas357}

Measure performance

1. 1. Measure performance using frequent formal and informal audits of clinical practice. ^{Reference Klompas, Anderson and Trick77,Reference Chumpia, Ganz, Chang and de Peralta81,Reference Seaver, Grant, Lunn, Sandor, Moran and Shapiro83,Reference Pronovost, Berenholtz and Needham321,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Kellie, Scott and Cavallazzi363,Reference Westwell379}

2. 2. Measuring process and outcome measures enhances awareness, establishes expectations, creates urgency, and rewards changes in behavior. ^{Reference Hatler, Mast and Corderella320,Reference Rosenthal, Desse and Maurizi360–Reference Parisi, Gerovasili and Dimopoulos362}

3. 3. Evaluating performance provides an ongoing, real-time image of actual implementation rates. Areas of poor compliance can be rapidly identified and rectified. ^{Reference Pronovost, Berenholtz and Needham321,Reference Michelangelo, Angriman and Pizarro341,Reference Khan, Al-Dorzi and Al-Attas346,Reference Miller, Briody and Casey351,Reference Talbot, Carr and Lee Parmley358,Reference Omrane, Eid and Perreault374,Reference Westwell379,Reference Eom, Lee and Chun380} If compliance remains poor in one area, the improvement team should walk the process with staff to gain additional insights into barriers to implementation. ^{Reference Pronovost, Berenholtz and Needham321,Reference Michelangelo, Angriman and Pizarro341,Reference Khan, Al-Dorzi and Al-Attas346,Reference Miller, Briody and Casey351,Reference Robinson, Hoze, Hevener and Nichols352}

4. 4. Analyze all or a representative sample of VAEs for etiology and preventability. Pneumonia, pulmonary edema, acute respiratory distress syndrome, and atelectasis are the precipitants for most VAEs. ^{Reference Klompas, Khan and Kleinman17,Reference Hayashi, Morisawa and Klompas19,Reference Klein Klouwenberg, van Mourik and Ong22,Reference Boyer, Schoenberg, Babcock, McMullen, Micek and Kollef58,Reference Nakahashi, Yamada, Ogura, Nakajima, Suzuki and Imai60,Reference Chao, Chang, Wu and Chan61} Use these analyses to select and refine prevention strategies that address the most frequent and preventable causes of VAEs in the specific unit of interest. ^{Reference Seaver, Grant, Lunn, Sandor, Moran and Shapiro83,Reference Miller, Briody and Casey351}

Provide feedback to staff

1. 1. Provide regular feedback on process and/or outcome data to staff. ^{Reference Klompas, Anderson and Trick77,Reference Rawat, Yang and Ali79,Reference Hatler, Mast and Corderella320,Reference Krimsky, Mroz and McIlwaine322,Reference Scales, Dainty and Hales355,Reference Rosenthal, Desse and Maurizi360,Reference Youngquist, Carroll and Farber372,Reference Zaydfudim, Dossett and Starmer375} Feedback can be provided via dashboards, wall displays, or during meetings. ^{Reference Chumpia, Ganz, Chang and de Peralta81,Reference Bigham, Amato and Bondurrant234,Reference Hatler, Mast and Corderella320,Reference Miller, Briody and Casey351,Reference Talbot, Carr and Lee Parmley358,Reference Bassi, Ferrer, Saucedo and Torres364,Reference Berenholtz and Pronovost365}

2. 2. Providing feedback helps staff appreciate how their efforts to improve are affecting performance rates and patients’ outcomes. This helps maintain staff motivation and can boost adherence to new processes. ^{Reference Rawat, Yang and Ali79,Reference Pronovost, Berenholtz and Needham321,Reference Alvarez-Lerma, Palomar-Martinez and Sanchez-Garcia327,Reference Miller, Briody and Casey351,Reference Pinto, Burnett and Benn381}

3. 3. Feedback is also important for future efforts because feedback helps pinpoint new areas for improvement and marks successful transitions to new standards of care. ^{Reference Hatler, Mast and Corderella320,Reference Pronovost, Berenholtz and Needham321,Reference Miller, Briody and Casey351,Reference Westwell379,Reference Pinto, Burnett and Benn381}