Dataset Information

Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome.

ABSTRACT:

Objectives

Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.

Design

Preclinical study.

Setting

Research laboratory.

Subjects

Anesthetized pigs.

Intervention

In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao₂/Fio₂ <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.

Measurements and main results

Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao₂/Fio₂ (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao₂/Fio₂ less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.

Conclusions

Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

SUBMITTER: DiBlasi RM

PROVIDER: S-EPMC7886457 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: The acute respiratory distress syndrome (ARDS) is a common, devastating complication of critical illness that is characterized by pulmonary injury and inflammation. The clinical diagnosis may be improved by means of objective biological markers. Electronic nose (eNose) technology can rapidly and non-invasively provide breath prints, which are profiles of volatile metabolites in the exhaled breath. We hypothesized that breath prints could facilitate accurate diagnosis of ARDS in intubated and ventilated intensive care unit (ICU) patients. METHODS: Prospective single-center cohort study with training and temporal external validation cohort. Breath of newly intubated and mechanically ventilated ICU-patients was analyzed using an electronic nose within 24 hours after admission. ARDS was diagnosed and classified by the Berlin clinical consensus definition. The eNose was trained to recognize ARDS in a training cohort and the diagnostic performance was evaluated in a temporal external validation cohort. RESULTS: In the training cohort (40 patients with ARDS versus 66 controls) the diagnostic model for ARDS showed a moderate discrimination, with an area under the receiver-operator characteristic curve (AUC-ROC) of 0.72 (95%-confidence interval (CI): 0.63-0.82). In the external validation cohort (18 patients with ARDS versus 26 controls) the AUC-ROC was 0.71 [95%-CI: 0.54 - 0.87]. Restricting discrimination to patients with moderate or severe ARDS versus controls resulted in an AUC-ROC of 0.80 [95%-CI: 0.70 - 0.90]. The exhaled breath profile from patients with cardiopulmonary edema and pneumonia was different from that of patients with moderate/severe ARDS. CONCLUSIONS: An electronic nose can rapidly and non-invasively discriminate between patients with and without ARDS with modest accuracy. Diagnostic accuracy increased when only moderate and severe ARDS patients were considered. This implicates that breath analysis may allow for rapid, bedside detection of ARDS, especially if our findings are reproduced using continuous exhaled breath profiling. TRIAL REGISTRATION: NTR2750, registered 11 February 2011.