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.

Comparison of amikacin lung delivery between AKITA® and eFlow rapid® nebulizers in healthy controls and patients with CF: A randomized cross-over trial.

INTRODUCTION: Nebulization plays a key role in the treatment of cystic fibrosis. The Favorite function couple to jet nebulizers (AKITA®) emerged recently. The aim of this study was to assess the efficiency of the lung delivery by the AKITA® by comparing the urinary concentration of amikacin after nebulization with the AKITA® and the eFlow rapid®, in healthy subjects and patients with CF (PwCF). METHOD: The two samples (healthy subjects and PwCF) were randomized (cross-over 1:1) for two nebulizations (500 mg of amikacin diluted in 4 mL of normal saline solution), with the AKITA® and with the eFlow rapid®. The primary endpoint was the amount of urinary excretion of amikacin over 24 h. The constant of elimination (Ke) was calculated based on the maximal cumulative urinary amikacin excretion plotted over time. RESULTS: The total amount of urinary amikacin excretion was greater when AKITA® was used in PwCF (11.7 mg (8.2-14.1) vs 6.1 mg (3.7-13.3); p = 0.02) but not different in healthy subjects (14.5 mg (11.7-18.5) vs 12.4 mg (8.0-17.1); p = 0.12). The duration of the nebulization was always shorter with eFlow rapid® than with AKITA® (PwCF: 6.5 ± 0.6 min vs 9.2 ± 1.8 min; p = 0.001 - Healthy: 4.7 ± 1.3 min vs 9.7 ± 1.6 min; p = 0.03). The constant of elimination was similar between the two modalities in CF subjects (0.153 (0.071-0.205) vs 0.149 (0.041-0.182); p = 0.26) and in healthy subjects (0.166 (0.130-0.218) vs 0.167 (0.119-0.210), p = 0.25). CONCLUSION: the Favorite inhalation is better to deliver a specific amount of drug than a mesh nebulizer (eFlow rapid®) in PwCF but not in healthy subjects.

Prone Positioning in Spontaneously Breathing Subjects With Moderate or Severe ARDS During Invasive Ventilation.

BACKGROUND: Prone positioning (PP) during invasive mechanical ventilation improves outcomes of patients with severe ARDS. Recent studies suggest that PP in spontaneously breathing, nonintubated patients with acute respiratory failure is well tolerated and improves oxygenation. However, little is known regarding patient triggered ventilation in intubated patients with ARDS undergoing PP. We conducted a retrospective review of our experience with placing patients in the prone position in 2 cohorts of subjects with moderate and severe ARDS (ie, one cohort with ARDS related to COVID-19, the other with ARDS unrelated to COVID-19), many of whom were receiving pressure support ventilation (PSV). METHODS: We conducted a retrospective analysis in a single 22-bed mixed ICU. The subjects included in the analysis were ≥ 18 y old, met the Berlin definition for moderate or severe ARDS (whether related COVID-19 or not), and underwent PP during invasive ventilation. RESULTS: 39 subjects were included in the analysis: 20 subjects had ARDS related to COVID-19, while 19 had ARDS related to other etiologies. A total of 113 PP episodes were analyzed: 84 during PSV and 29 during volume control continuous mandatory ventilation. PP during PSV was well tolerated and was effective in improving arterial oxygenation (ie, an increase of median [Formula: see text] from 100 mm Hg [interquartile range 75-120] before PP to 135 mm Hg [interquartile range 111-161] at the end of the PP session, P < .0001). No significant difference between continuous mandatory ventilation and PSV was noted regarding arterial oxygenation during PP. Compared with continuous mandatory ventilation mode, PP during PSV was associated with a significant decrease in the use of neuromuscular blocking agents (4% vs 69% of subjects, P < .001), while sedative requirements remained unchanged. CONCLUSIONS: In a retrospective analysis of consecutive intubated subjects with moderate or severe ARDS, related or not to COVID-19, spontaneous breathing during PP was well tolerated and achieved significant improvement in arterial oxygenation.