Aerosol delivery during invasive mechanical ventilation: a systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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) µg/mL of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 µg/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. CONCLUSIONS: 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.

Effects of Neurally Adjusted Ventilatory Assist (NAVA) levels in non-invasive ventilated patients: titrating NAVA levels with electric diaphragmatic activity and tidal volume matching.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) delivers pressure in proportion to diaphragm electrical activity (Eadi). However, each patient responds differently to NAVA levels. This study aims to examine the matching between tidal volume (Vt) and patients' inspiratory demand (Eadi), and to investigate patient-specific response to various NAVA levels in non-invasively ventilated patients. METHODS: 12 patients were ventilated non-invasively with NAVA using three different NAVA levels. NAVA100 was set according to the manufacturer's recommendation to have similar peak airway pressure as during pressure support. NAVA level was then adjusted ±50% (NAVA50, NAVA150). Airway pressure, flow and Eadi were recorded for 15 minutes at each NAVA level. The matching of Vt and integral of Eadi (ʃEadi) were assessed at the different NAVA levels. A metric, Range90, was defined as the 5-95% range of Vt/ʃEadi ratio to assess matching for each NAVA level. Smaller Range90 values indicated better matching of supply to demand. RESULTS: Patients ventilated at NAVA50 had the lowest Range90 with median 25.6 uVs/ml [Interquartile range (IQR): 15.4-70.4], suggesting that, globally, NAVA50 provided better matching between ʃEadi and Vt than NAVA100 and NAVA150. However, on a per-patient basis, 4 patients had the lowest Range90 values in NAVA100, 1 patient at NAVA150 and 7 patients at NAVA50. Robust coefficient of variation for ʃEadi and Vt were not different between NAVA levels. CONCLUSIONS: The patient-specific matching between ʃEadi and Vt was variable, indicating that to obtain the best possible matching, NAVA level setting should be patient specific. The Range90 concept presented to evaluate Vt/ʃEadi is a physiologic metric that could help in individual titration of NAVA level.

NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

Clinical review: Update on neurally adjusted ventilatory assist--report of a round-table conference.

Conventional mechanical ventilators rely on pneumatic pressure and flow sensors and controllers to detect breaths. New modes of mechanical ventilation have been developed to better match the assistance delivered by the ventilator to the patient's needs. Among these modes, neurally adjusted ventilatory assist (NAVA) delivers a pressure that is directly proportional to the integral of the electrical activity of the diaphragm recorded continuously through an esophageal probe. In clinical settings, NAVA has been chiefly compared with pressure-support ventilation, one of the most popular modes used during the weaning phase, which delivers a constant pressure from breath to breath. Comparisons with proportional-assist ventilation, which has numerous similarities, are lacking. Because of the constant level of assistance, pressure-support ventilation reduces the natural variability of the breathing pattern and can be associated with asynchrony and/or overinflation. The ability of NAVA to circumvent these limitations has been addressed in clinical studies and is discussed in this report. Although the underlying concept is fascinating, several important questions regarding the clinical applications of NAVA remain unanswered. Among these questions, determining the optimal NAVA settings according to the patient's ventilatory needs and/or acceptable level of work of breathing is a key issue. In this report, based on an investigator-initiated round table, we review the most recent literature on this topic and discuss the theoretical advantages and disadvantages of NAVA compared with other modes, as well as the risks and limitations of NAVA.

Ventilatory management during routine general anaesthesia.

Intraoperative hypoxaemia and postoperative respiratory complications remain the challenges of modern anaesthetic practice. Anaesthesia causes both depression of respiratory centres and profound changes of respiratory mechanics. Most anaesthetized patients consequently require mechanical ventilation and supplemental oxygen. Recent data suggest that intraoperative respiratory management of a patient can affect postoperative outcome. In this review, we briefly describe the mechanisms responsible for the impairment of intraoperative gas exchange and provide guidelines to prevent or manage hypoxaemia. Moreover, we discuss several aspects of mechanical ventilation that can be employed to improve patients' outcome.

Pressure-controlled ventilation does not improve gas exchange in morbidly obese patients undergoing abdominal surgery.

BACKGROUND: Morbid obesity results in marked respiratory pathophysiologic changes that may lead to impaired intraoperative gas exchange. The decelerating inspiratory flow and constant inspiratory airway pressure resulting from pressure-controlled ventilation (PCV) may be more adapted to these changes and improve gas exchanges compared with volume-controlled ventilation (VCV). METHODS: Forty morbidly obese patients scheduled for gastric bypass were included in this study. Total intravenous anesthesia was given using the target-controlled infusion technique. During the first intraoperative hour, VCV was used and the tidal volume was adjusted to keep end-tidal PCO(2) around 35 mmHg. After 1 h, patients were randomly allocated to 30-min VCV followed by 30-min PCV or the opposite sequence using a Siemens Servo 300. FiO(2) was 0.6. During PCV, airway pressure was adjusted to provide the same tidal volume as during VCV. Arterial blood was sampled for gas analysis every 15 min. Ventilatory parameters were also recorded. RESULTS: Peak inspiratory airway pressures were significantly lower during PCV than during VCV (P < 0.0001). The other ventilatory parameters were similar during the two periods of ventilation. PaO(2) and PaCO(2) were not significantly different during PCV and VCV. CONCLUSION: PCV does not improve gas exchange in morbidly obese patients undergoing gastric bypass compared to VCV.

Evaluation of the Roche® Elecsys and the Diasorin® Liaison S100 kits in the management of mild head injury in the emergency room.

INTRODUCTION: The aim of this single-center prospective study is to compare two commercially available S100ß kits (the Roche® Elecsys and the Diasorin® Liaison S100 kits) in terms of analytical and clinical performances in a population admitted in the emergency room for mild traumatic brain injury (mTBI). MATERIAL AND METHOD: 110 patients were enrolled from September 2014 to May 2015. Blood sample draws were performed within 3h after head trauma and the study population was split into pediatric and adult subpopulations (>18years of age). RESULTS: Although both kits correlated well, we observed a significant difference in terms of S100ß levels (P value<0.05) in both subpopulations. In the pediatric subpopulation, both kits showed elevated S100ß levels for the only patient (3.5%) who displayed abnormal findings on a CT-scan. However, we observed a poor agreement between both kits (Cohen's kappa=0.345, P value=0.077). In the adult subpopulation, a total of 10 patients (12.2%) had abnormal head computed tomography scans. Using the Roche® (cut off=0.1µg/L) and the Diasorin® (cut off=0.15µg/L) S100ß kits, brain injuries were detected with a sensitivity of 100% (95% CI: 65-100%) and 100% (95% CI: 63-100%) and a specificity of 15.28% (95% CI: 7.9-25.7%) and 24.64% (95% CI: 15-36.5) respectively. Finally, a moderate agreement was concluded between both kits (Cohen's kappa=0.569, P value=0.001). CONCLUSION: Although a good correlation could be found between both kits, emergency physicians should be aware of discrepancies observed between both methods, making those immunoassays not interchangeable. Furthermore, more studies are still needed to validate cut off used according to technique and to age, especially in the population below the age of 2years.

Impact of a VAP bundle in Belgian intensive care units.

BACKGROUND: In order to decrease the incidence of ventilator-associated pneumonia (VAP) in Belgium, a national campaign for implementing a VAP bundle involving assessment of sedation, cuff pressure control, oral care with chlorhexidine and semirecumbent position, was launched in 2011-2012. This report will document the impact of this campaign. METHODS: On 1 day, once a year from 2010 till 2016, except in 2012, Belgian ICUs were questioned about their ventilated patients. For each of these, data about the application of the bundle and the possible treatment for VAP were recorded. RESULTS: Between 36.6 and 54.8% of the 120 Belgian ICUs participated in the successive surveys. While the characteristics of ventilated patients remained similar throughout the years, the percentage of ventilated patients and especially the duration of ventilation significantly decreased before and after the national VAP bundle campaign. Ventilator care also profoundly changed: Controlling cuff pressure, head positioning above 30° were obtained in more than 90% of cases. Oral care was more frequently performed within a day, using more concentrated solutions of chlorhexidine. Subglottic suctioning also was used but in only 24.7% of the cases in the last years. Regarding the prevalence of VAP, it significantly decreased from 28% of ventilated patients in 2010 to 10.1% in 2016 (p ≤ 0.0001). CONCLUSION: Although a causal relationship cannot be inferred from these data, the successive surveys revealed a potential impact of the VAP bundle campaign on both the respiratory care of ventilated patients and the prevalence of VAP in Belgian ICUs encouraging them to follow the guidelines.

Consequences of under- and over-humidification.

Respiratory mucosal and lung structures and functions may be severely impaired in mechanically ventilated patients when delivered gases are not adequately conditioned. Although under- and over-humidification of respiratory gases have not been defined clearly, a safe range of temperature and humidity may be suggested. During mechanical ventilation, gas entering the trachea should reach at least physiologic conditions (32 degrees C-34 degrees C and 100%relative humidity) to keep the ISB at its normal location. Clinicians must keep in mind that relative humidity is more important than absolute humidity: the warmer the gas, the higher the risk of tracheal mucosa dehydration and proximal airway obstruction. Practical assessment of the adequacy of the humidification system in use is not easy. The consistency (thin, moderate, or thick) of the patient's sputum should be evaluated regularly [47]. Full saturation of inspiratory gases is likely when water condensation is observed in the flex tube [91,92]. Nevertheless, no clinical parameter is accurate enough to detect all the effects of inadequate conditioning [45]. When mechanical ventilation is extended beyond several days, adequate conditioning of respiratory gases becomes increasingly crucial to prevent retention of secretions and to maximize mucociliary function; a requirement that respiratory gases reach at least physiologic conditions is appropriate.

Closed-loop ventilation mode (IntelliVent®-ASV) in intensive care unit: a randomized trial.

BACKGROUND: Closed-loop modes automatically adjust ventilation settings, delivering individualized ventilation over short periods of time. The objective of this randomized controlled trial was to compare safety, efficacy and workload for the health care team between IntelliVent®-ASV and conventional modes over a 48-hour period. METHODS: ICU patients admitted with an expected duration of mechanical ventilation of more than 48 hours were randomized to IntelliVent®-ASV or conventional ventilation modes. All ventilation parameters were recorded breath-by-breath. The number of manual adjustments assesses workload for the healthcare team. Safety and efficacy were assessed by calculating the time spent within previously defined ranges of non-optimal and optimal ventilation, respectively. RESULTS: Eighty patients were analyzed. The median values of ventilation parameters over 48 hours were similar in both groups except for PEEP (7[4] cmH2O versus 6[3] cmH2O with IntelliVent®-ASV and conventional ventilation, respectively, P=0.028) and PETCO2 (36±7 mmHg with IntelliVent®-ASV versus 40±8 mmHg with conventional ventilation, P=0.041). Safety was similar between IntelliVent®-ASV and conventional ventilation for all parameters except for PMAX, which was more often non-optimal with IntelliVent®-ASV (P=0.001). Efficacy was comparable between the 2 ventilation strategies, except for SpO2 and VT, which were more often optimal with IntelliVent®-ASV (P=0.005, P=0.016, respectively). IntelliVent®-ASV required less manual adjustments than conventional ventilation (P<0.001) for a higher total number of adjustments (P<0.001). The coefficient of variation over 48 hours was larger with IntelliVent®-ASV in regard of maximum pressure, inspiratory pressure (PINSP), and PEEP as compared to conventional ventilation. CONCLUSIONS: IntelliVent®-ASV required less manual intervention and delivered more variable PEEP and PINSP, while delivering ventilation safe and effective ventilation in terms of VT, RR, SpO2 and PETCO2.

Aerosol delivery with two ventilation modes during mechanical ventilation: a randomized study.

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.

Influence of inspiratory flow pattern and nebulizer position on aerosol delivery with a vibrating-mesh nebulizer during invasive mechanical ventilation: an in vitro analysis.

BACKGROUND: Aerosol delivery during invasive mechanical ventilation (IMV) depends on nebulizer type, placement of the nebulizer and ventilator settings. The purpose of this study was to determine the influence of two inspiratory flow patterns on amikacin delivery with a vibrating-mesh nebulizer placed at different positions on an adult lung model of IMV equipped with a proximal flow sensor (PFS). METHODS: IMV was simulated using a ventilator connected to a lung model through an 8-mm inner-diameter endotracheal tube. The impact of a decelerating and a constant flow pattern on aerosol delivery was evaluated in volume-controlled mode (tidal volume 500 mL, 20 breaths/min, inspiratory time of 1 sec, bias flow of 10 L/min). An amikacin solution (250 mg/3 mL) was nebulized with Aeroneb Solo(®) placed at five positions on the ventilator circuit equipped with a PFS: connected to the endotracheal tube (A), to the Y-piece (B), placed at 15 cm (C) and 45 cm upstream of the Y-piece (D), and placed at 15 cm of the inspiratory outlet of the ventilator (E). The four last positions were also tested without PFS. Deposited doses of amikacin were measured using the gravimetric residual method. RESULTS: Amikacin delivery was significantly reduced with a decelerating inspiratory flow pattern compared to a constant flow (p<0.05). With a constant inspiratory flow pattern, connecting the nebulizer to the endotracheal tube enabled similar deposited doses than these obtained when connecting the nebulizer close to the ventilator. The PFS reduced deposited doses only when the nebulizer was connected to the Y-piece with both flow patterns or placed at 15 cm of the Y-piece with a constant inspiratory flow (p<0.01). CONCLUSIONS: Using similar tidal volume and inspiratory time, a constant flow pattern (30 L/min) delivers a higher amount of amikacin through an endotracheal tube compared to a decelerating inspiratory flow pattern (peak inspiratory flow around 60 L/min). The optimal nebulizer position depends on the inspiratory flow pattern and the presence of a PFS.

Respiratory muscle workload in intubated, spontaneously breathing patients without COPD: pressure support vs proportional assist ventilation.

OBJECTIVE: To compare the respiratory muscle workload associated with pressure support ventilation (PSV) and proportional assist ventilation (PAV) in intubated and spontaneously breathing patients without COPD. DESIGN AND SETTING: Prospective study, intensive care unit university hospital. INTERVENTIONS: Twenty intubated patients, during early weaning, PSV settings made by clinician in charge of the patient, and two levels of PAV, set to counterbalance 80% (PAV 80) and 50% (PAV 50) of both elastic and resistive loads, respectively. The patients were ventilated in the following order: 1) PSV; 2) PAV 50 or PAV 80; 3) PSV; 4) PAV 80 or PAV 50; 5) PSV. PSV settings were kept constant. MEASUREMENTS: Arterial blood gases, breathing pattern and respiratory effort parameters at the end of each of the five steps. MAIN RESULTS: PSV and PAV 80 had the same effects on work of breathing (WOB). The pressure-time product (PTP) was significantly higher during PAV 80 than during PSV (90+/-76 and 61+/-56 cmH(2)O.s.min(-1), respectively, P <0.05). Tidal volume was comparable, albeit more variable with PAV 80 than with PSV (variation coefficient, 43% vs 25%, respectively, P <0.05). PAV 50 entailed a higher respiratory rate, lower tidal volume, and higher WOB and PTP than PSV and PAV 80. PaO(2)/FiO(2) and SaO(2) were lower with PAV 50 than with PSV and PAV 80. CONCLUSION: In a group of intubated spontaneously breathing non-COPD patients, PAV 80 and PSV were associated with comparable levels WOB, whereas PTP was higher during PAV 80. PAV 50 provided insufficient respiratory assistance.

Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator interaction during non-invasive ventilation delivered by face mask.

PURPOSE: To determine if, compared to pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces patient-ventilator asynchrony in intensive care patients undergoing noninvasive ventilation with an oronasal face mask. METHODS: In this prospective interventional study we compared patient-ventilator synchrony between PS (with ventilator settings determined by the clinician) and NAVA (with the level set so as to obtain the same maximal airway pressure as in PS). Two 20-min recordings of airway pressure, flow and electrical activity of the diaphragm during PS and NAVA were acquired in a randomized order. Trigger delay (T(d)), the patient's neural inspiratory time (T(in)), ventilator pressurization duration (T(iv)), inspiratory time in excess (T(iex)), number of asynchrony events per minute and asynchrony index (AI) were determined. RESULTS: The study included 13 patients, six with COPD, and two with mixed pulmonary disease. T(d) was reduced with NAVA: median 35 ms (IQR 31-53 ms) versus 181 ms (122-208 ms); p = 0.0002. NAVA reduced both premature and delayed cyclings in the majority of patients, but not the median T(iex) value. The total number of asynchrony events tended to be reduced with NAVA: 1.0 events/min (0.5-3.1 events/min) versus 4.4 events/min (0.9-12.1 events/min); p = 0.08. AI was lower with NAVA: 4.9 % (2.5-10.5 %) versus 15.8 % (5.5-49.6 %); p = 0.03. During NAVA, there were no ineffective efforts, or late or premature cyclings. PaO(2) and PaCO(2) were not different between ventilatory modes. CONCLUSION: Compared to PS, NAVA improved patient ventilator synchrony during noninvasive ventilation by reducing T(d) and AI. Moreover, with NAVA, ineffective efforts, and late and premature cyclings were absent.

Neurally adjusted ventilatory assist improves patient-ventilator interaction.

PURPOSE: To determine if, compared with pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces trigger delay, inspiratory time in excess, and the number of patient-ventilator asynchronies in intubated patients. METHODS: Prospective interventional study in spontaneously breathing patients intubated for acute respiratory failure. Three consecutive periods of ventilation were applied: (1) PS1, (2) NAVA, (3) PS2. Airway pressure, flow, and transesophageal diaphragmatic electromyography were continuously recorded. RESULTS: All results are reported as median (interquartile range, IQR). Twenty-two patients were included, 36.4% (8/22) having obstructive pulmonary disease. NAVA reduced trigger delay (ms): NAVA, 69 (57-85); PS1, 178 (139-245); PS2, 199 (135-256). NAVA improved expiratory synchrony: inspiratory time in excess (ms): NAVA, 126 (111-136); PS1, 204 (117-345); PS2, 220 (127-366). Total asynchrony events were reduced with NAVA (events/min): NAVA, 1.21 (0.54-3.36); PS1, 3.15 (1.18-6.40); PS2, 3.04 (1.22-5.31). The number of patients with asynchrony index (AI) >10% was reduced by 50% with NAVA. In contrast to PS, no ineffective effort or late cycling was observed with NAVA. There was less premature cycling with NAVA (events/min): NAVA, 0.00 (0.00-0.00); PS1, 0.14 (0.00-0.41); PS2, 0.00 (0.00-0.48). More double triggering was seen with NAVA, 0.78 (0.46-2.42); PS1, 0.00 (0.00-0.04); PS2, 0.00 (0.00-0.00). CONCLUSIONS: Compared with standard PS, NAVA can improve patient-ventilator synchrony in intubated spontaneously breathing intensive care patients. Further studies should aim to determine the clinical impact of this improved synchrony.