Table 1 List of recommendations
Number | Recommendation | Round 1 | Round 2 | Round 3 | 1st and 2nd online meetings | Level of consensus and recommendation | Final results |
|---|---|---|---|---|---|---|---|
1–1.1 | During invasive ventilation, VMN is more efficient in aerosol delivery than continuous JN, with no influence on flows or fraction of inspired oxygen. VMN is preferred over continuous JN | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation I: During mechanical ventilation, VMN or pMDI with spacer are recommended for aerosol delivery, with no preference between the devices. The use of an inline continuous JN results in changes in tidal volume, inspiratory flow patterns, and fraction of inspired oxygen, and aerosol delivery efficiency is low, thus continuous JN is not preferred for aerosol delivery in this setting |
1–1.2 | During high-frequency oscillatory ventilation, VMN is more efficient in aerosol delivery than continuous JN, with no influence on flows or fraction of inspired oxygen. When available, VMN is recommended over continuous JN | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.3 | Based on variation of the reported inhaled doses and lack of definitive clinical outcomes, there is no recommendation for pMDI and spacer versus VMN | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.4 | When placed close to the ventilator, the VMN is more efficient in aerosol delivery than ultrasonic nebulizer. When nebulizer is placed at the inspiratory limb before Y-piece, the VMN is as efficient as ultrasonic nebulizer in aerosol delivery | Revise | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.5 | During high frequency oscillatory ventilation with nebulizer placed between Y-piece and endotracheal tube, VMN is more efficient in aerosol delivery than ultrasonic nebulizer. When available, VMN is recommended over ultrasonic nebulizer | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.6 | When placed at the inspiratory limb before Y-piece, pMDI with a spacer is more efficient in aerosol delivery than the continuous JN, with no influence on flows or fraction of inspired oxygen. When available, pMDI with spacer actuated at beginning of inspiration is recommended over continuous JN | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.7 | When placed at 12–15 cm from the Y-piece in the inspiratory limb, ultrasonic nebulizer is more efficient in aerosol delivery than the continuous JN, with no influence on flows or fraction of inspired oxygen. When available, ultrasonic nebulizer is recommended over continuous JN | NC | Withdrawn | Withdrawn | Withdrawn | NA | Recommendation II: When a VMN or JN is utilized during invasive ventilation with bias flow, it is recommended to place the nebulizer in the inspiratory limb, away from the Y-piece and towards the ventilator |
1–1.8 | When VMN is utilized during invasive ventilation with bias flow, it is recommended to be placed close to ventilator | Revise | Revise | Controversy | Revise and include | Very good consensus, strong recommendation | |
1–1.9 | When JN is utilized during invasive ventilation, it is recommended to be placed near the ventilator | NC | Revise | Controversy | Revise and include | Very good consensus, strong recommendation | |
1–1.10 | When ultrasonic nebulizer is utilized during invasive ventilation without bias flow, it is recommended to be placed at 15 cm from Y-piece at inspiratory limb; With bias flow, ultrasonic nebulizer is recommended to be placed proximal to ventilator | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.11 | When ultrasonic nebulizer is placed at the inspiratory limb before Y-piece, adding a spacer is recommended | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.12 | When pMDI is utilized during invasive ventilation, it is recommended to be used with a spacer with volume > 150 mL | NC | Revise | Include | Include | Perfect consensus, strong recommendation | Recommendation III: When pMDI is utilized during invasive ventilation, it is recommended to be used with a spacer with a volume > 150 mL and placed in the inspiratory limb before the Y-piece. The pMDI is recommended to be actuated at the beginning of inspiratory flow from the ventilator |
1–1.13 | During invasive ventilation, pMDI and spacer are recommended to be placed in the inspiratory limb before the Y-piece | NC | Revise | Include | Include | Perfect consensus, strong recommendation | |
1–1.14 | During high-frequency oscillatory ventilation, nebulizers are recommended to be placed between the Y-piece and the endotracheal tube | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.15 | The efficiency of aerosol delivery in dry ventilator circuits is higher than that in humidified ventilator circuits. Considering the potential harms of dry gas on patient airway, and the time lapse required for a humidifier and circuits to cool down, turning off humidifier is not recommended for routine aerosol therapy | NC | Revise | Controversy | Revise and include | Very good consensus, strong recommendation | Recommendation IV: For patients using an active heated humidifier, turning off the humidifier is not recommended for routine aerosol therapy; for patients using a heat–moisture exchanger, removing or bypassing the heat moisture exchanger is recommended for aerosol therapy |
1–1.16 | When aerosol device is placed in the inspiratory limb, removing or bypassing the heat moisture exchanger is recommended | NC | Include | Include | Include | Perfect consensus, strong recommendation | |
1–1.17 | In ventilated patients, using a continuous JN means adding compressed gas independent of the ventilator. The effect on tidal volume, FiO2 etc. makes this practice unacceptable. The empirical compensations on ventilator settings may be dangerous and should be avoided. If no integrated inspiration-synchronized JN is available, the use of continuous jet neb in ventilated patients is not recommended | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation I |
1–1.18 | The influence of ventilator integrated breath-actuated JN on ventilator function and aerosol delivery efficiency varies between ventilators | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.19 | Metered-dose inhaler should be primed, shaken, with actuation at the beginning of inspiration, with a minimum of 15 s between puffs | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation III |
1–1.20.1 | For the jet or ultrasonic nebulizer with a residual volume > 0.5 mL, aerosol delivery efficiency is improved with a higher fill volume, but changing fill volume for the sole purpose of improving aerosol delivery efficiency is not recommended for FDA approved inhaled medication | Revise | Revise | Controversy | Revise and include | Very good consensus, strong recommendation | Recommendation V: When a nebulizer is utilized, changing fill volume or diluent volume for the sole purpose of improving aerosol delivery efficiency is not recommended |
1–1.20.2 | Increasing diluent volume in VMN to improve aerosol delivery efficiency is not recommended | Add | Revise | Include | Include | Perfect consensus, strong recommendation | |
1–1.20.3 | For viscous formulations, increasing diluent volume in VMN to improve aerosol delivery efficiency is recommended | NC | Add | Controversy | Withdrawn | NA | |
1–1.21 | Aerosol delivery efficiency varies between endotracheal tube and tracheotomy tube. Changing tubes for the sole purpose of improving aerosol delivery efficiency is not recommended | NC | Include | Include | Include | Perfect consensus, strong recommendation | Recommendation VI: It is not recommended to change the endotracheal tube or tracheostomy tube to increase the internal diameter of the airway for the sole purpose of improving aerosol delivery efficiency |
1–1.22 | Aerosol delivery efficiency is higher with a large size of endotracheal tube, but changing endotracheal tube for the sole purpose of improving aerosol delivery efficiency is not recommended | NC | Include | Include | Include | Perfect consensus, strong recommendation | |
1–1.23 | When heliox is utilized for invasive ventilation, aerosol delivery efficiency can improve. However, adding heliox for the sole purpose of improving aerosol delivery efficiency is not recommended | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation VII: Adding heliox for the sole purpose of improving aerosol delivery efficiency is not recommended |
1–1.24 | When heliox is substituted for oxygen to drive continuous JN at the same driving flow, nebulizer output is reduced. If driving nebulizer with heliox, it is recommended to set at 15 L/min | NC | Revise | Controversy | Revise and include | Very good consensus, strong recommendation | |
1–1.25 | It is not recommended to change the ventilator mode for the sole purpose of improving aerosol delivery efficiency | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendations IX: It is not recommended to change the ventilator mode and parameter settings for the sole purpose of improving aerosol delivery efficiency during routine nebulization in invasive ventilation |
1–1.26 | When metered-dose inhaler is utilized during invasive mechanical ventilation, there is no recommendation on flow trigger versus pressure trigger solely for aerosol delivery | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.27 | It is not recommended to change tidal volume and respiratory rate for the sole purpose of improving aerosol delivery efficiency | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.28 | Increasing inspiratory time and lowering inspiratory flows solely for aerosol delivery is not recommended | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.29 | It is not recommended to change the inspiratory flow patterns solely for aerosol delivery | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.30 | It is not recommended to apply end-inspiratory pause when pMDI is used during invasive mechanical ventilation | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.31 | It is not recommended to change the positive end-expiratory pressure (PEEP) for the sole purpose of improving aerosol delivery efficiency | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
1–1.32 | With nebulizer placed proximal to patient, higher bias flow is associated with lower aerosol delivery efficiency. With nebulizer placed proximal to ventilator, adding bias flow up to 5 L/min improves delivery. It is recommended to set bias flow up to 5 L/min when nebulizer is placed proximal to ventilator | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
1–1.33 | Placing a filter on the expiratory limb reduces fugitive aerosols and protects the expiratory sensors. Use of an expiratory filter with frequent changes is recommended | NC | Add | Include | Include | Very good consensus, strong recommendation | Recommendation VIII: Placing a filter on the expiratory limb reduces fugitive aerosols and protects the ventilator expiratory sensors. Use of an expiratory filter with frequent changes (daily or more frequent based on aerosol administered and effect on filter resistance) is recommended |
1–2.1 | For antibiotics or other cost-prohibitive medications, changing to a dry circuit immediately before nebulization is recommended | Add | Revise | Controversy | Withdrawn | NA | No consensus |
1–2.2 | When delivering inhaled antibiotics for invasively ventilated patients, spontaneous breathing ventilator modes may reduce aerosol delivery efficiency, thus spontaneous breathing should be avoided and volume-controlled mode is preferred, and assessing overall benefit/risk ratio especially related to sedation | Add | Revise | Include | Withdrawn | NA | |
1–2.3 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to set tidal volume of 8 mL/kg of patient’s predicted body weight, and the clinician must weigh the benefit/risk ratio of increasing tidal volume for improving aerosol delivery with the risk of high tidal volume | Add | Revise | Include | Withdrawn | NA | |
1–2.4 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to keep respiratory rates at 12–15 breaths/min | Add | Revise | Controversy | Withdrawn | NA | |
1–2.5 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to keep inspiratory flow below 40L/min | Add | Revise | Include | Withdrawn | NA | |
1–2.6 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to use inspiratory to expiratory ratio of 50% | Add | Revise | Controversy | Withdrawn | NA | |
1–2.7 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to use a constant inspiratory flow | Add | Revise | Controversy | Withdrawn | NA | |
1–2.8 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to set end-inspiratory pause at 20% | Add | Revise | Controversy | Withdrawn | NA | |
1–2.9 | When delivering inhaled antibiotics for invasively ventilated patients, it is recommended to set a positive end-expiratory pressure (PEEP) at 5–10 cmH2O | Add | Revise | Controversy | Withdrawn | NA | |
2.1 | Placing the nebulizer inline with NIV has similar or higher aerosol delivery efficiency than using the nebulizer with a mask or mouthpiece. Interrupting or discontinuing NIV to administer aerosol via a mask or mouthpiece is unnecessary and not recommended | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation X: Placing the nebulizer inline with NIV has similar or higher aerosol delivery efficiency than using the nebulizer with a mask or mouthpiece. Interrupting or discontinuing NIV to administer aerosol via a mask or mouthpiece is not recommended |
2.2 | During NIV using single limb circuit, placing pMDI with spacer between exhalation valve and mask, with actuation at the beginning of inspiration is recommended. There is no recommendation on the placement orientation (toward or away from patient) of the spacer | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation XI: During NIV placing a pressurized metered-dose inhaler with a spacer between exhalation valve and mask, with actuation at the beginning of inspiration is recommended |
2.3 | When placing the continuous nebulizer inline with NIV, VMN is more efficient in aerosol delivery than JN, with no influence on flows or fraction of inspired oxygen. When available, VMN is recommended over JN | NC | Revise | Include | Include | Perfect consensus, strong recommendation | Recommendation XII: During NIV using a single-limb circuit, the continuous nebulizer is recommended to be placed between the exhalation valve and the mask. When available, VMN is preferred over JN |
2.4 | During NIV using single limb circuit, the continuous nebulizer is recommended to be placed between the exhalation valve and the mask | NC | Include | Include | Include | Very good consensus, strong recommendation | |
2.5 | During NIV using a single limb circuit, with the continuous nebulizer placed between mask and exhalation valve, there is no recommendation on the type of exhalation valve | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
2.6 | During aerosol delivery via NIV, turning off the humidifier is not recommended | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation XIV: During aerosol delivery via NIV, turning off the humidifier is not recommended |
2.7 | The aerosol delivery efficiency is less affected by the fill volume in the VMN than the continuous JN. For continuous JNs, more dilution is associated with greater aerosol delivery. Increasing fill volume for the sole purpose to improve aerosol delivery efficiency is not recommended | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation XV: When a continuous nebulizer is utilized during NIV, increasing the fill volume for the sole purpose of improving aerosol delivery efficiency is not recommended |
2.8 | The aerosol delivery efficiency is similar between CPAP and NIV, changing the mode for the sole purpose of increasing aerosol delivery is not recommended | NC | Revise | Include | Include | Perfect consensus, strong recommendation | Recommendation XVI: During aerosol delivery via NIV, changing the mode or parameters for the sole purpose to improve aerosol delivery efficiency is not recommended |
2.9 | When continuous nebulizer is placed between the mask and the exhalation valve during NIV with a single limb circuit, the aerosol delivery efficiency increases as IPAP increases or EPAP decreases. Changing the parameters for the sole purpose to improve aerosol delivery efficiency is not recommended | NC | Revise | Include | Include | Very good consensus, strong recommendation | |
2.10 | When a continuous nebulizer is placed inline with NIV, the aerosol delivery efficiency is higher with a non-vented mask than a vented mask. Aerosol administration with a vented mask is not recommended | NC | Revise | Include | Include | Perfect consensus, strong recommendation | Recommendation XIII: When a continuous nebulizer is placed inline with NIV, aerosol administration with a non-vented mask is preferred over a vented mask. When a non-vented mask is used, there is no recommendation for the use of single versus dual limb circuits for aerosol delivery |
2.11 | When non-vented mask is used during NIV, the aerosol delivery efficiency with optimal position is similar with the single limb and dual limb circuits. There is no recommendation for the use of single versus dual limb circuits for aerosol delivery | NC | Revise | Include | Include | Perfect consensus, strong recommendation | |
3.1 | The aerosol delivery efficiency with a nebulizer via HFNC at flow ≤ 35 L/min is similar to that with a nebulizer and a mask or mouthpiece. Discontinuing HFNC treatment to administer nebulizer with a mask or mouthpiece is not recommended | Revise | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation XVII: The aerosol delivery efficiency with a nebulizer via HFNC is similar to that with a nebulizer and a mask or mouthpiece. Discontinuing HFNC treatment to administer a nebulizer with a mask or mouthpiece is not recommended. Placing a nebulizer with a mask or mouthpiece with concurrent HFNC treatment should be avoided |
3.2 | Placing a nebulizer with a mask or mouthpiece on a patient who is using concurrent HFNC treatment is not recommended | NC | Include | Include | Include | Very good consensus, strong recommendation | |
3.3 | During aerosol delivery via HFNC, VMN is more efficient in aerosol delivery than JN, with no influence on flows or fraction of inspired oxygen. VMN is recommended for trans-nasal aerosol delivery | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation XVIII: During aerosol delivery via HFNC, a VMN is preferred over a JN. The nebulizer is recommended to be placed at the inlet of the humidifier |
3.4 | Nebulizers are recommended to be placed at the inlet of humidifier at HFNC flows ≥ 10 L/min | Revise | Revise | Include | Include | Perfect consensus, strong recommendation | |
3.5 | When pMDI is placed inline with HFNC, it is recommended to be used with a spacer and placed close to nasal cannula with the aerosol plume directed toward the patient | NC | Revise | Include | Include | Very good consensus, strong recommendation | Recommendation XIX: When pMDI is placed inline with HFNC, it is recommended to be used with a spacer and placed close to the nasal cannula with the aerosol plume directed toward the patient |
3.6 | To optimize aerosol delivery via HFNC, gas flow is recommended to be titrated below the patient’s peak inspiratory flow if tolerated | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
3.7 | Using heliox via HFNC for the sole purpose of improving aerosol delivery is not recommended | NC | Revise | Include | Include | Perfect consensus, strong recommendation | Appendix 10 |
3.8 | Using dry gas to deliver aerosol via HFNC has been shown to improve aerosol delivery efficiency, however, considering the discomfort and the potential harms, routine use of dry gas to deliver aerosol via HFNC is not recommended | NC | Include | Include | Include | Very good consensus, strong recommendation | Recommendation XX: During aerosol delivery via HFNC, turning off the humidifier is not recommended |
3.9 | When gas flow exceeds patient inspiratory flow, open mouth breathing reduces inhaled dose. Discontinuing aerosol via HFNC to mouth breathing patients is not recommended | NC | Withdrawn | Withdrawn | Withdrawn | NA | |
3.10 | For trans-nasal aerosol delivery, Optiflow is preferred over Airvo2 with VMN placed at the inlet of humidifier. Aerosol delivery via Vapotherm should be avoided | Revise | Withdrawn | Withdrawn | Withdrawn | NA |