Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effects of antibiotics delivered via the respiratory tract in preventing ventilator-associated pneumonia (VAP). DATA SOURCES: We searched PubMed, Scopus, the Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 25, 2023. STUDY SELECTION: Adult patients with mechanical ventilation of over 48 h and receiving inhaled or instilled antibiotics (with control group) to prevent VAP were included. DATA EXTRACTION: Two independent groups screened studies, extracted the data, and assessed the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty/quality of the evidence. Results of a random-effects model were reported for overall and predefined subgroup meta-analyses. The analysis was primarily conducted on randomized controlled trials, and observational studies were used for sensitivity analyses. DATA SYNTHESIS: Seven RCTs with 1445 patients were included, of which six involving 1283 patients used nebulizers to deliver antibiotics. No obvious risk of bias was found among the included RCTs for the primary outcome. Compared with control group, prophylactic antibiotics delivery via the respiratory tract significantly reduced the risk of VAP (risk ratio [RR], 0.69 [95% CI, 0.53-0.89]), particularly in subgroups where aminoglycosides (RR, 0.67 [0.47-0.97]) or nebulization (RR, 0.64 [0.49-0.83]) were used as opposed to other antibiotics (ceftazidime and colistin) or intratracheal instillation. No significant differences were observed in mortality, mechanical ventilation duration, ICU and hospital length of stay, duration of systemic antibiotics, need for tracheostomy, and adverse events between the two groups. Results were confirmed in sensitivity analyses. CONCLUSIONS: In adult patients with mechanical ventilation for over 48 h, prophylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides.

Survey of Ventilator Waveform Interpretation Among ICU Professionals.

BACKGROUND: The interpretation of ventilator waveforms is essential for effective and safe mechanical ventilation but requires specialized training and expertise. This study aimed to investigate the ability of ICU professionals to interpret ventilator waveforms, identify areas requiring further education and training, and explore the factors influencing their interpretation skills. METHODS: We conducted an international online anonymous survey of ICU professionals (physicians, nurses, and respiratory therapists [RTs]), with ≥ 1 y of experience working in the ICU. The survey consisted of demographic information and 15 multiple-choice questions related to ventilator waveforms. Results were compared between professions using descriptive statistics, and logistic regression (expressed as odds ratios [ORs; 95% CI]) was performed to identify factors associated with high performance, which was defined by a threshold of 60% correct answers. RESULTS: A total of 1,832 professionals from 31 countries or regions completed the survey; 53% of respondents answered ≥ 60% of the questions correctly. The 3 questions with the most correct responses were related to waveforms that demonstrated condensation (90%), pressure overshoot (79%), and bronchospasm (75%). Conversely, the 3 questions with the fewest correct responses were waveforms that demonstrated early cycle leading to double trigger (43%), severe under assistance (flow starvation) (37%), and early/reverse trigger (31%). Factors significantly associated with ≥ 60% correct answers included years of ICU working experience (≥ 10 y, OR 1.6 [1.2-2.0], P < .001), profession (RT, OR 2.8 [2.1-3.7], P < .001), highest degree earned (graduate, OR 1.7 [1.3-2.2], P < .001), workplace (teaching hospital, OR 1.4 [1.1-1.7], P = .008), and prior ventilator waveforms training (OR 1.7 [1.3-2.2], P < .001). CONCLUSIONS: Slightly over half respondents correctly identified ≥ 60% of waveforms demonstrating patient-ventilator discordance. High performance was associated with ≥ 10 years of ICU working experience, RT profession, graduate degree, working in a teaching hospital, and prior ventilator waveforms training. Some discordances were poorly recognized across all groups of surveyed professionals.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

Aerosol Delivery to Simulated Spontaneously Breathing Tracheostomized Adult Model With and Without Humidification.

BACKGROUND: Optimal aerosol delivery methods for spontaneously breathing patients with a tracheostomy remain unclear. Thus, we aimed to assess the impact of nebulizer placement, flow settings, and interfaces on aerosol delivery by using a vibrating mesh nebulizer and a jet nebulizer in line with unheated humidification. METHODS: An 8.0-mm tracheostomy tube was connected to the lung model that simulates adult breathing parameters via a collecting filter. Albuterol sulfate (2.5 mg/3 mL) was administered via a vibrating mesh nebulizer and a jet nebulizer, which was placed in line with unheated humidification provided by a large-volume nebulizer, with FIO2 set at 0.28, with gas flows of 2 L/min versus 6 L/min. Nebulizers were placed in line distal and proximal to the lung model by using a tracheostomy collar and a T-piece. Conventional nebulization was tested using a vibrating mesh nebulizer and a jet nebulizer directly connected to the tracheostomy tube bypassing the humidification device. The drug was eluted from the collecting filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: During in-line nebulizer placement with unheated humidification, the inhaled dose was 2-4 times higher with a gas flow of 2 L/min than 6 L/min, regardless of nebulizer type, placement, or interface (all P < .05). At 6 L/min, the inhaled dose was higher with proximal than distal placement when using both interfaces, but, at 2 L/min, the inhaled dose was lower with proximal placement. With a jet nebulizer, the tracheostomy collar generated a higher inhaled dose at proximal placement compared with the T-piece, whereas the T-piece resulted in a higher inhaled dose than the tracheostomy collar with distal placement, regardless of the flow settings. Compared with conventional nebulization using a vibrating mesh nebulizer, an in-line vibrating mesh nebulizer with a large-volume nebulizer at 2 L/min had a similar inhaled dose, regardless of nebulizer placement and interface. In contrast, the in-line jet nebulizer was influenced by both placement and interface. CONCLUSIONS: Aerosol delivery with an in-line vibrating mesh nebulizer and jet nebulizer with unheated humidification was affected by nebulizer placement, interface, and gas flow settings.

The effects of flow settings during high-flow nasal cannula support for adult subjects: a systematic review.

BACKGROUND: During high-flow nasal cannula (HFNC) therapy, flow plays a crucial role in the physiological effects. However, there is no consensus on the initial flow settings and subsequent titration. Thus, we aimed to systematically synthesize the effects of flows during HFNC treatment. METHODS: In this systematic review, two investigators independently searched PubMed, Embase, Web of Science, Scopus, and Cochrane for in vitro and in vivo studies investigating the effects of flows in HFNC treatment published in English before July 10, 2022. We excluded studies that investigated the pediatric population (< 18 years) or used only one flow. Two investigators independently extracted the data and assessed the risk of bias. The study protocol was prospectively registered with PROSPERO, CRD42022345419. RESULTS: In total, 32,543 studies were identified, and 44 were included. In vitro studies evaluated the effects of flow settings on the fraction of inspired oxygen (FIO2), positive end-expiratory pressure, and carbon dioxide (CO2) washout. These effects are flow-dependent and are maximized when the flow exceeds the patient peak inspiratory flow, which varies between patients and disease conditions. In vivo studies report that higher flows result in improved oxygenation and dead space washout and can reduce work of breathing. Higher flows also lead to alveolar overdistention in non-dependent lung regions and patient discomfort. The impact of flows on different patients is largely heterogeneous. INTERPRETATION: Individualizing flow settings during HFNC treatment is necessary, and titrating flow based on clinical findings like oxygenation, respiratory rates, ROX index, and patient comfort is a pragmatic way forward.