Inhaled drug delivery: a randomized study in intubated patients with healthy lungs.

BACKGROUND: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. METHODS: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. RESULTS: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0-24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001). CONCLUSION: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings.

Impact of additional HEPA filter on APAP performance and CPAP pressure level in simulated sleep apnea events.

Background: CPAP is the first line treatment of obstructive sleep apnea. Recently, the use of added filters has been debated following the field safety notice of Philips Respironics™ on potential health risks due to foam degradation used in their ventilators. However, the added resistance of filters has never been analyzed. Objectives: The primary aim was to investigate the impact of four different filters on APAP mode performance with and without added unintentional air leaks (UIAL) with two simulated respiratory events. The secondary aim was to assess the pressure drop due to the increased filter resistance at different fixed CPAP pressure levels. Method: This is a bench study. Performance tests were performed on a breathing simulator (ASL 5000™) with a DreamStation™ device. To assess the combined effect of UIAL, a controlled valve was added to the setup. Results: Without UIAL, the algorithm was able to detect respiratory events and increase pressure level consequently. In the presence of UIAL, the device's response to simulated events was affected. In fixed CPAP mode, the median measured end-expiratory pressure was 6.2 to 10.0% (p < 0.001) below the set pressure with the additional filters. Additional UIAL severely impacted the delivered pressure with a median reduction up to 28.3% (p < 0.001) to the set pressure. Conclusion: Despite a slight pressure drop, the APAP algorithm still performed with additional filters when UIAL were avoided. However, the combined effect of added filter resistance and UIAL severely impacted APAP performance and effectively delivered set pressure.

Role of Non-Invasive Respiratory Supports in COVID-19 Acute Respiratory Failure Patients with Do Not Intubate Orders.

The current gold-standard treatment for COVID-19-related hypoxemic respiratory failure is invasive mechanical ventilation. However, do not intubate orders (DNI), prevent the use of this treatment in some cases. The aim of this study was to evaluate if non-invasive ventilatory supports can provide a good therapeutic alternative to invasive ventilation in patients with severe COVID-19 infection and a DNI. Data were collected from four centres in three European countries. Patients with severe COVID-19 infection were included. We emulated a hypothetical target trial in which outcomes were compared in patients with a DNI order treated exclusively by non-invasive respiratory support with patients who could be intubated if necessary. We set up a propensity score and an inverse probability of treatment weighting to remove confounding by indication. Four-hundred patients were included: 270 were eligible for intubation and 130 had a DNI order. The adjusted risk ratio for death among patients eligible for intubation was 0.81 (95% CI 0.46 to 1.42). The median length of stay in acute care for survivors was similar between groups (18 (10-31) vs. (19 (13-23.5); p = 0.76). The use of non-invasive respiratory support is a good compromise for patients with severe COVID-19 and a do not intubate order.

[Place of the respiratory physiotherapist in the Covid-19 crisis: Neuchâtel experience]. / Place du physiothérapeute respiratoire dans la crise Covid-19 : expérience neuchâteloise.

The physiotherapy service became an important player in the care of patients with COVID-19 at Pourtalès hospital (Neuchâtel, Switzerland), illustrating its important role in the organization of acute care units. The workforce was increased, and the diaries extended (7/7d, 24/24h). Respiratory physiotherapists were largely involved in the initiation and the adaptation of the respiratory therapy in the units dedicated to Covid-19 patients (emergency, intensive care and pulmonology units), such as oxygen therapy and both invasive and non-invasive ventilation. Rehabilitation was also early initiated in order to limit the risk of intensive care unit-acquired polyneuromyopathy and to prevent physical deconditioning.

Le Service de physiothérapie s'est inscrit comme un acteur important dans la prise en charge des patients Covid-19 à l'Hôpital Pourtalès (Neuchâtel, Suisse), illustrant son rôle important dans l'organigramme des unités de soins aigus. L'effectif a été augmenté et les horaires étendus (7 j/7, 24 h/24). Les physiothérapeutes spécialisés dans le domaine respiratoire ont activement participé à la mise en route des traitements respiratoires et à leur adaptation dans les unités dédiées aux patients Covid-19 (urgences, soins intensifs et pneumologie), tels que l'oxygénothérapie et l'assistance ventilatoire invasive et non invasive. Une réhabilitation a par ailleurs été initiée précocement afin de limiter le risque de polyneuromyopathie acquise aux soins intensifs et de prévenir le déconditionnement physique.

Acute Effects of Sitting Out of Bed and Exercise on Lung Aeration and Oxygenation in Critically Ill Subjects.

BACKGROUND: Early mobilization during critical illness is safe and has beneficial effects on functional outcomes. However, its impact on pulmonary function has not been thoroughly explored. We hypothesized that a sitting position out of bed coupled with exercise could result in an improvement in oxygenation and lung aeration. METHODS: The study was conducted on a cohort of adult subjects within a week of their admission to an ICU. Subjects were transferred to a chair and undertook a 15-min session of exercise, either active or passive. Subjects in the control group were only transferred to a chair. Electrical impedance tomography, a reliable bedside technique monitoring regional lung aeration and the distribution of ventilation, was continuously performed, and blood gases were assessed at baseline and 20 min post-exercise. RESULTS: The cohort included 40 subjects, 17 of whom were mechanically ventilated and 23 spontaneously breathing. The control group for each modality consisted of 5 mechanically ventilated or 5 spontaneously breathing subjects. Mild hypoxemia was present in 45% of the spontaneously breathing cohort, whereas the mechanically ventilated subjects demonstrated moderate (50%) or severe (12%) hypoxemia. Compared with the control group, early mobilization induced a significant increase in lung aeration. In mechanically ventilated subjects, lung aeration increased, especially in the anterior lung regions (mean impedance [95% CI]: T1 (baseline in bed) = 1,265 [691-1,839]; T2 (chair sitting) = 2,003 [1,042-2,963]; T3 (exercise) = 1,619 [810 2,427]; T4 (post exercise in chair) = 2,320 [1,186-3,455]). In spontaneously breathing subjects, lung aeration increased mainly in the posterior lung regions (mean impedance [95% CI]: T1 = 380 [124-637]; T2 = 655 [226-1,084]; T3 = 621 [335-906]; T4 = 600 [340-860]). [Formula: see text] increased, especially in subjects with lower [Formula: see text] at baseline (< 200) (133 ± 31 to 158 ± 48, P = .041). CONCLUSIONS: For critically ill subjects, a sitting position and exercise increased lung aeration and were associated with an improvement in [Formula: see text] in the more severely hypoxemic subjects.

Nasal High-Flow Nebulization for Lung Drug Delivery: Theoretical, Experimental, and Clinical Application.

The use of nasal high-flow (NHF) therapy is rapidly spreading across acute care facilities. This raises the question of optimal delivery of inhaled medication to patients undergoing this noninvasive ventilatory support consisting in delivering heated and humidified high gas flow rates through nasal cannulas. In this article, we review experimental and clinical work evaluating the delivery of inhaled medication within the NHF circuit to target the lung without interrupting the ventilatory support. Using vibrating mesh nebulizers placed immediately upstream or downstream of the humidification chamber, with flow rates of 30-45 L/min in adults and 2-6 L/min in children and infants, about 1%-10% of the drug charged in the nebulizer may be delivered to the lungs. Compared with conventional facemask aerosol interfaces, this amount is significantly lower than amounts delivered to adults (i.e., up to 25% of the nominal dose), but similar to amounts delivered to children and infants, the latter having a predominantly nasal breathing. However, significant clinical effects have been shown in both populations when delivering bronchodilators through NHF. This interface is particularly well tolerated and may be useful to improve aerosol therapy tolerance in the pediatric setting. Thus, among patients undergoing NHF therapy, bronchodilators may be delivered through this route. Whereas other drugs may be delivered this way or if there is a patient-centered benefit to specifically use NHF for aerosol therapy among patients without ongoing ventilatory support, requires further evaluation and technological development.

Pulmonary Drug Delivery Following Continuous Vibrating Mesh Nebulization and Inspiratory Synchronized Vibrating Mesh Nebulization During Noninvasive Ventilation in Healthy Volunteers.

BACKGROUND: A breath-synchronized nebulization option that could potentially improve drug delivery during noninvasive positive pressure ventilation (NIPPV) is currently not available on single-limb circuit bilevel ventilators. The aim of this study was to compare urinary excretion of amikacin following aerosol delivery with a vibrating mesh nebulizer coupled to a single-limb circuit bilevel ventilator, using conventional continuous (Conti-Neb) and experimental inspiratory synchronized (Inspi-Neb) nebulization modes. MATERIALS AND METHODS: A crossover clinical trial involving 6 noninvasive ventilated healthy volunteers (mean age of 32.3 ± 9.5 y) randomly assigned to both vibrating mesh nebulization modes was conducted: Inspi-Neb delivered aerosol during only the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. All subjects inhaled amikacin solution (500 mg/4 mL) during NIPPV using a single-limb bilevel ventilator (inspiratory positive airway pressure: 12 cm H2O, and expiratory positive airway pressure: 5 cm H2O). Pulmonary drug delivery of amikacin following both nebulization modes was compared by urinary excretion of drug for 24 hours post-inhalation. RESULTS: The total daily amount of amikacin excreted in the urine was significantly higher with Inspi-Neb (median: 44.72 mg; interquartile range [IQR]: 40.50-65.13) than with Conti-Neb (median: 40.07 mg; IQR: 31.00-43.73), (p = 0.02). The elimination rate constant of amikacin (indirect measure of the depth of drug penetration into the lungs) was significantly higher with Inspi-Neb (median: 0.137; IQR: 0.113-0.146) than with Conti-Neb (median: 0.116; IQR: 0.105-0.130), (p = 0.02). However, the mean pulmonary drug delivery rate, expressed as the ratio between total daily urinary amount of amikacin and nebulization time, was significantly higher with Conti-Neb (2.03 mg/min) than with Inspi-Neb (1.09 mg/min) (p < 0.01). CONCLUSIONS: During NIPPV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization may improve pulmonary drug delivery compared with conventional continuous vibrating mesh nebulization.

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.

Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

BACKGROUND: High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). METHODS: Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo®; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer®; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow®; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. RESULTS: Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. CONCLUSIONS: In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PURPOSE: To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. METHODS: Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). RESULTS: Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. CONCLUSIONS: This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Teamwork enables high level of early mobilization in critically ill patients.

BACKGROUND: Early mobilization in critically ill patients has been shown to prevent bed-rest-associated morbidity. Reported reasons for not mobilizing patients, thereby excluding or delaying such intervention, are diverse and comprise safety considerations for high-risk critically ill patients with multiple organ support systems. This study sought to demonstrate that early mobilization performed within the first 24 h of ICU admission proves to be feasible and well tolerated in the vast majority of critically ill patients. RESULTS: General practice data were collected for 171 consecutive admissions to our ICU over a 2-month period according to a local, standardized, early mobilization protocol. The total period covered 731 patient-days, 22 (3 %) of which met our local exclusion criteria for mobilization. Of the remaining 709 patient-days, early mobilization was achieved on 86 % of them, bed-to-chair transfer on 74 %, and at least one physical therapy session on 59 %. Median time interval from ICU admission to the first early mobilization activity was 19 h (IQR = 15-23). In patients on mechanical ventilation (51 %), accounting for 46 % of patient-days, 35 % were administered vasopressors and 11 % continuous renal replacement therapy. Within this group, bed-to-chair transfer was achieved on 68 % of patient-days and at least one early mobilization activity on 80 %. Limiting factors to start early mobilization included restricted staffing capacities, diagnostic or surgical procedures, patients' refusal, as well as severe hemodynamic instability. Hemodynamic parameters were rarely affected during mobilization, causing interruption in only 0.8 % of all activities, primarily due to reversible hypotension or arrhythmia. In general, all activities were well tolerated, while patients were able to self-regulate their active early mobilization. Patients' subjective perception of physical therapy was reported to be enjoyable. CONCLUSIONS: Mobilization within the first 24 h of ICU admission is achievable in the majority of critical ill patients, in spite of mechanical ventilation, vasopressor administration, or renal replacement therapy.

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.

In Vitro Comparison of a Vibrating Mesh Nebulizer Operating in Inspiratory Synchronized and Continuous Nebulization Modes During Noninvasive Ventilation.

UNLABELLED: Backround: Coupling nebulization with noninvasive ventilation (NIV) has been shown to be effective in patients with respiratory diseases. However, a breath-synchronized nebulization option that could potentially improve drug delivery by limiting drug loss during exhalation is currently not available on bilevel ventilators. The aim of this in vitro study was to compare aerosol delivery of amikacin with a vibrating mesh nebulizer coupled to a single-limb circuit bilevel ventilator, using conventional continuous (Conti-Neb) and experimental inspiratory synchronized (Inspi-Neb) nebulization modes. METHODS: Using an adult lung bench model of NIV, we tested a vibrating mesh device coupled with a bilevel ventilator in both nebulization modes. Inspi-Neb delivered aerosol only during the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. The nebulizer was charged with amikacin solution (250 mg/3 mL) and placed at two different positions: between the lung and exhalation port and between the ventilator and exhalation port. Inhaled, expiratory wasted and circuit lost doses were assessed by residual gravimetric method. Particle size distribution of aerosol delivered at the outlet of the ventilator circuit during both nebulization modes was measured by laser diffraction method. RESULTS: Regardless of the nebulizer position, Inspi-Neb produced higher inhaled dose (p < 0.01; +6.3% to +16.8% of the nominal dose), lower expiratory wasted dose (p < 0.05; -2.7% to -42.6% of the nominal dose), and greater respirable dose (p < 0.01; +8.4% to +15.2% of the nominal dose) than Conti-Neb. The highest respirable dose was found with the nebulizer placed between the lung and exhalation port (48.7% ± 0.3% of the nominal dose). CONCLUSIONS: During simulated NIV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization improves respirable dose and reduces drug loss of amikacin compared with continuous vibrating mesh nebulization.

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients.

PURPOSE: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. METHODS: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. RESULTS: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. CONCLUSIONS: Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.

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.

Neurally adjusted ventilatory assist during weaning from respiratory support in a case of guillain-barré syndrome.

We report a case of Guillain-Barré syndrome complicated by respiratory failure requiring mechanical ventilation. Neurally adjusted ventilatory assist (NAVA) allowed proper patient-ventilator synchronization by pressure support proportional to the electrical activity of the diaphragm (Edi). Prolonged ventilation with NAVA seems feasible in patients with neuromuscular impairment, but the weaning process conducted by a continuous monitoring of Edi for pressure support titration needed to be assessed in a Guillain-Barré syndrome patient. Beginning on day 12 after hospital admission, the patient was ventilated with NAVA for 8 d. The NAVA level (pressure support per unit of Edi) was decreased from 1.2 cm H2O/µV to zero over the 8-d period. A simultaneous decrease in the tidal volume/Edi ratio was interpreted as a sign of recovery. A spontaneous breathing trial was successfully performed on day 20, followed by decannulation 4 d later. In conclusion, NAVA should be further investigated in patients with Guillain-Barré syndrome, particularly during the weaning period.