Aerosol delivery during invasive mechanical ventilation: a systematic review.
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ABSTRACT: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed.In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias.Twenty-six clinical and ten experimental studies were included. Between 30% and 43% of nominal drug dose was lost to the circuit in ventilated patients. Whole lung deposition of up to 16% and 38% of nominal dose (proportion of drug charged in the device) were reported with nebulizers and metered-dose inhalers, respectively. A penetration index inferior to 1 observed in scintigraphic studies indicated major proximal deposition. However, substantial concentrations of antibiotics were measured in the epithelial lining fluid (887 (406-12,819) ?g/mL of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 ?g/g of amikacin) dissected from infected piglets, suggesting a significant distal deposition. The administration technique varied among studies and may explain a degree of the variability of deposition that was observed.Lung deposition was lower than 20% of nominal dose delivered with nebulizers and mostly occurred in proximal airways. Further studies are needed to link substantial concentrations of antibiotics in infected pulmonary fluids to pulmonary deposition. The administration technique with nebulizers should be improved in ventilated patients in order to ensure an efficient but safe, feasible and reproducible technique.
<h4>Background</h4>This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed.<h4>Methods</h4>In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently a ...[more]
Project description:BACKGROUND:Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction. Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed. The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation, with two modes: pressure support ventilation and volume-controlled ventilation. METHODS:Seventeen postoperative neurosurgery patients without pulmonary disease were randomly ventilated in pressure support or volume-controlled ventilation. Diethylenetriaminepentaacetic acid labeled with technetium-99m (2 mCi/3 mL) was administrated using a vibrating-mesh nebulizer (Aerogen Solo(®), provided by Aerogen Ltd, Galway, Ireland) connected to the endotracheal tube. Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy. RESULTS:Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation, respectively (p < 0.05). Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation (27.4 ± 6.6 vs. 20.7 ± 6.0 %, p < 0.05). A similar penetration index was observed for the right (p = 0.210) and the left lung (p = 0.211) with both ventilation modes. A high intersubject variability of lung deposition was observed with both modes regarding lung doses, aerosol penetration and distribution between the right and the left lung. CONCLUSIONS:In the specific conditions of the study, volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation. The clinical benefit of this effect warrants further studies. Clinical trial registration NCT01879488.
Project description:Acinetobacter baumannii is a nosocomial pathogen associated with severe illness and death. Glucocorticoid aerosol is a common inhalation therapy in patients receiving invasive mechanical ventilation. We conducted a prospective cohort study to analyze the association between glucocorticoid aerosol therapy and A. baumannii isolation from ventilator patients in China. Of 497 enrolled patients, 262 (52.7%) received glucocorticoid aerosol, and A. baumannii was isolated from 159 (32.0%). Glucocorticoid aerosol therapy was an independent risk factor for A. baumannii isolation (hazard ratio 1.5, 95% CI 1.02-2.28; p = 0.038). Patients receiving glucocorticoid aerosol had a higher cumulative hazard for A. baumannii isolation and analysis showed that glucocorticoid aerosol therapy increased A. baumannii isolation in most subpopulations. Glucocorticoid aerosol was not a direct risk factor for 30-day mortality, but A. baumannii isolation was independently associated with 30-day mortality in ventilator patients. Physicians should consider potential A. baumannii infection when prescribing glucocorticoid aerosol therapy.
Project description:Invasive mechanical ventilation is a frequent therapy in critically ill patients in critical care units. To achieve favorable outcomes, patient and ventilator interaction must be adequate. However, many clinical situations could attempt against this principle and generate a mismatch between these two actors. These asynchronies can lead the patient to worst outcomes; that is why it is vital to recognize and treat these entities as soon as possible. Early detection and recognition of the different asynchronies could favor the reduction of the days of mechanical ventilation, the days of hospital stay, and intensive care and improve clinical results.
Project description:PurposeA systematic review and meta-analysis was conducted to answer the question 'In adults with respiratory failure requiring invasive ventilation for more than 24 h, does a weaning strategy with early extubation to non-invasive ventilation (NIV) compared to invasive ventilation weaning reduce all-cause hospital mortality?'MethodsWe included randomised and quasi-randomised controlled trials that evaluated the use of non-invasive ventilation, compared to invasive ventilation, as a weaning strategy in adults mechanically ventilated for at least 24 h. The EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) bibliographic databases were searched from inception to February 2018. Bayesian hierarchical models were used to perform the meta-analysis. The primary outcome was mortality at hospital discharge. Secondary outcomes included mortality (30, 60, 90 and 180 days), quality of life, duration of invasive ventilation, weaning failure, length of stay [intensive care unit (ICU) and hospital] and adverse events.ResultsTwenty-five relevant studies involving 1609 patients were included in the quantitative analysis. Studies had moderate to high risk of bias due to risk of performance and detection bias. Mortality at hospital discharge was lower in the NIV weaning group compared to the invasive weaning group [pooled odds ratio (OR) 0.58, 95% highest density interval (HDI) 0.29-0.89]. Subgroup analyses showed lower pooled mortality at hospital discharge rates in NIV weaning than those in the control group in chronic obstructive pulmonary disease (COPD) patients (pooled OR 0.43, 95% HDI 0.13-0.81) and the effect is less certain in the mixed ICU population (pooled OR 0.88, 95% HDI 0.25-1.48). NIV weaning reduced the duration of invasive ventilation in patients [standardised mean difference (SMD) - 1.34, 95% HDI - 1.92 to - 0.77] and ICU length of stay (SMD - 0.70, 95% HDI - 0.94 to - 0.46). Reported rates of ventilator associated pneumonia (VAP) were lower in the NIV group. NIV weaning did not reduce overall hospital length of stay or long-term mortality. There were insufficient data to compare other adverse events and health-related quality of life.ConclusionsThe use of NIV in weaning from mechanical ventilation decreases hospital mortality, the incidence of VAP and ICU length of stay. NIV as a weaning strategy appears to be most beneficial in patients with COPD.
Project description:ObjectiveThere are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation.Data sourcePubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation.Study selectionWe included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion.Data extractionTwo investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated.Data synthesisA total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%).ConclusionsBarotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.
Project description:IntroductionAerosol therapy is often prescribed concurrently during invasive mechanical ventilation (IMV). This study determines the effects of nebuliser position, circuit humidification source, and most importantly, lung health on the delivery of aerosol in simulated adult and paediatric IMV patients. Furthermore, the influence of closed suction catheters on aerosol delivery is also addressed.MethodsA vibrating mesh nebuliser was used to deliver Albuterol to simulated adult and paediatric IMV patients with differing states of lung health. Four different nebuliser positions and two types of humidification were analysed. Closed suction catheter mounts, a mainstay in IMV therapy, were incorporated into the circuits. The mean ± SD dose of aerosol (%) was assayed from a filter at the distal end of the endotracheal tube.ResultsNebuliser placement and circuit humidification source had no effect on the delivered dose (%) in adults, yet both significantly did in the simulated paediatric patients. The use of closed suction catheter mounts significantly reduced the delivered dose (%) in adults but not in paediatric patients. A simulated healthy lung state generated the largest delivered dose (%), irrespective of nebuliser position in the adult. However, different lung health and nebuliser positions yielded higher delivered doses (%) in paediatrics.ConclusionLung health and respiratory circuit composition significantly affect aerosol delivery in both adult and paediatric IMV patients. Nebuliser placement and respiratory circuit humidification source do not affect the delivered dose in adult but do in paediatric IMV patients.
Project description:Background. The prevalence of patients supported with home mechanical ventilation (HMV) for chronic respiratory failure has increased. However, the clinical outcomes associated with HMV are largely unknown. Methods. We performed a systematic review of studies evaluating patients receiving HMV for indications other than obstructive lung disease, reporting at least one clinically relevant outcome including health-related quality of life (HRQL) measured by validated tools; hospitalization requirements; caregiver burden; and health service utilization. We searched MEDLINE, EMBASE, CINAHL, the Cochrane library, clinical trial registries, proceedings from selected scientific meetings, and bibliographies of retrieved citations. Results. We included 1 randomized control trial (RCT) and 25 observational studies of mixed methodological quality involving 4425 patients; neuromuscular disorders (NMD) (n = 1687); restrictive thoracic diseases (RTD) (n = 481); obesity hypoventilation syndrome (OHS) (n = 293); and others (n = 748). HRQL was generally described as good for HMV users. Mental rather than physical HRQL domains were rated higher, particularly where physical assessment was limited. Hospitalization rates and days in hospital appear to decrease with implementation of HMV. Caregiver burden associated with HMV was generally high; however, it is poorly described. Conclusion. HRQL and need for hospitalization may improve after establishment of HMV. These inferences are based on relatively few studies of marked heterogeneity and variable quality.
Project description:BackgroundUncertainty remains around the benefit of home non-invasive ventilation (NIV) for stable chronic obstructive pulmonary disease (COPD) patients and those with a recent exacerbation (post-hospital). The aim of this systematic review was to: (1) update the evidence base with studies published in any language, including Chinese language studies not indexed in standard medical databases, and (2) explore the impact of additional studies on the evidence base.MethodsStandard systematic review methodology was used for identifying and appraising studies. Randomized controlled trials (RCTs) and non-randomized studies reporting mortality, hospitalizations, exacerbations, quality of life, adverse events, or adherence were included. Random effects meta-analysis was undertaken for mortality and hospitalizations, with studies sub-grouped by population and study design. Sensitivity analysis was performed to explore the effect of including studies from Western and non-Western countries.ResultsA total of 103 studies were included, substantially more than in previous reviews. There was no significant effect on mortality for the stable population. There was a benefit from NIV for the post-hospital population based on non-randomized studies, or RCTs from non-Western countries. There was a small but significant reduction in hospital admissions (1-2/year) with NIV across all sub-groups, and a variable reduction in duration of stay with greater reductions in studies from China.ConclusionsThe evidence base on home NIV is considerably larger than previously presented. While NIV may reduce hospital admissions and improve quality of life, there is still little evidence of a reduction in mortality, regardless of country. Individual participant data analysis may clarify which patients would benefit most from NIV.
Project description:Non-invasive ventilation (NIV) is external support for respiration to assist breathing in case of respiratory failure (either hypercapnic or hypoxemic) without patient intubation. Nowadays, medicated aerosols are normally delivered to mechanically ventilated patients by nebulizers and pressurized metered-dose inhaler (pMDI) attached to adapter or spacer that fit into the ventilated circuit. Studies with obstructive lung disease patients have shown that aerosol delivery during mechanical ventilation is possible and of benefit. There are several models for investigating the aerosol delivery and deposition during mechanical ventilation such as in vitro, in vivo, and ex vivo models, these models depend on the technique used for quantitative or qualitative measurement of the deposited aerosol. In vitro models could be used for calculating the total emitted doses from different aerosol-generating devices or for aerodynamic characterization of the deposited inhaled medications. In vivo models dependents of extracting drugs from biological samples for measuring its concentration and bioavailability (pharmacokinetic model) or be dependent on the imaging technique of the radioactive aerosol. Applying different methods to predict aerosol efficiency before starting NIV and to quantify aerosol delivery during NIV are promising approaches that guide clinicians to avoid treatment failure before and during patient therapy.
Project description:INTRODUCTION: Mechanical ventilation (MV) is commonly regarded as a risk factor for acute kidney injury (AKI) in the critically ill. We investigated the strength of this association and whether settings of tidal volume (Vt) and positive end-expiratory pressure (PEEP) affect the risk for AKI. METHODS: We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included studies reporting on a relation between the use of invasive MV and subsequent onset of AKI, or comparing higher with lower Vt or PEEP and subsequent onset of AKI. All studies clearly stating that MV was initiated after onset of AKI were excluded. We extracted the proportion with and without MV and AKI. We included 31 studies on invasive MV. RESULTS: The pooled odds ratio (OR) for the overall effect of MV on AKI was 3.16 (95% CI 2.32 to 4.28, P<0.001). Nearly all subgroups showed that MV increases the risk for AKI. The pooled OR for studies with a multivariate analysis including MV as a risk factor for AKI was 3.58 (95% CI 1.85 to 6.92; P<0.001). Different settings of Vt and PEEP showed no effect. CONCLUSIONS: Invasive MV is associated with a threefold increase in the odds of developing AKI and various Vt or PEEP settings do not modify this risk. The latter argues in favour of a haemodynamic origin of AKI during MV.
