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

Jonathan Dugernier; Déborah Le Pennec; Guillaume Maerckx; Laurine Allimonnier; Michel Hesse; Diego Castanares-Zapatero; Virginie Depoortere; Laurent Vecellio; Gregory Reychler; Jean-Bernard Michotte; Pierre Goffette; Marie-Agnes Docquier; Christian Raftopoulos; François Jamar; Pierre-François Laterre; Stephan Ehrmann; Xavier Wittebole

doi:10.1186/s13613-023-01220-y

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

Ann Intensive Care. 2023 Dec 11;13(1):125. doi: 10.1186/s13613-023-01220-y.

Authors

Jonathan Dugernier^#^{1

2

3

4}, Déborah Le Pennec^#⁵, Guillaume Maerckx^#^{6

7

8}, Laurine Allimonnier⁵, Michel Hesse⁹, Diego Castanares-Zapatero⁶, Virginie Depoortere⁹, Laurent Vecellio⁵, Gregory Reychler^{7

8

10}, Jean-Bernard Michotte¹¹, Pierre Goffette¹², Marie-Agnes Docquier¹³, Christian Raftopoulos¹⁴, François Jamar⁹, Pierre-François Laterre¹⁵, Stephan Ehrmann^#^{5

16

17}, Xavier Wittebole^#⁶

Affiliations

¹ Soins Intensifs, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium. [email protected].
² Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Université Catholique de Louvain, 1200, Brussels, Belgium. [email protected].
³ Physiothérapie, Département des Thérapies, Hôpital Pourtales, Réseau Hospitalier Neuchâtelois, 2000, Neuchâtel, Switzerland. [email protected].
⁴ Haute École Arc Santé, HES-SO, University of Applied Sciences and Arts of Western Switzerland, 2000, Neuchâtel, Switzerland. [email protected].
⁵ Centre d'Etude des Pathologies Respiratoires, INSERM U1100, Faculté de médecine, Université de Tours, Tours, France.
⁶ Soins Intensifs, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
⁷ Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Université Catholique de Louvain, 1200, Brussels, Belgium.
⁸ Secteur de Kinésithérapie et Ergothérapie, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
⁹ Médecine Nucléaire, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
¹⁰ Pneumologie, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
¹¹ School of Health Sciences (HESAV), HES-SO, University of Applied Sciences and Arts of Western Switzerland, 1011, Lausanne, Switzerland.
¹² Radiologie Interventionnelle, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
¹³ Anesthésiologie, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
¹⁴ Neurochirurgie, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
¹⁵ Soins Intensifs, CHR Mons-Hainaut, 7000, Mons, Belgium.
¹⁶ CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS-TriggerSep F-CRIN Research Network, Tours, France.
¹⁷ Université de Tours, Tours, France.

^# Contributed equally.

Abstract

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.

Keywords: Aerosol delivery; Invasive mechanical ventilation; Nebulizer.