Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome.
Pubmed ID: 29523157
Pubmed Central ID: PMC5845220
Journal: Critical care (London, England)
Publication Date: 03/10/2018
Affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 E. 19th Ave., RC2 9th Floor, C272, Aurora, CO, 80045, USA.
MeSH Terms: Humans, Male, Adult, Female, Aged, Cohort Studies, Middle Aged, Multivariate Analysis, Prospective Studies, Analysis of Variance, Tidal Volume, von Willebrand Factor, Interleukin-8, Biomarkers, Pulmonary Surfactant-Associated Protein D, Neuromuscular Blockade, Respiratory Distress Syndrome
Grants: R01 LM006910, UL1TR001082, LM06910, UL1 TR001082, HL069223
Authors: Sottile PD, Albers D, Moss MM
Cite As: Sottile PD, Albers D, Moss MM. Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome. Crit Care 2018 Mar 10;22(1):63.
- Acute Respiratory Distress Network (ARDSNet) Studies 01 and 03 Lower versus higher tidal volume, ketoconazole treatment and lisofylline treatment (ARMA/KARMA/LARMA)
- Acute Respiratory Distress Network (ARDSNet) Study 04 Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury (ALVEOLI)
BACKGROUND: Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. METHODS: We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm<sup>3</sup>/kg) and by an initial arterial oxygen tension (PaO<sub>2</sub>) to fractional inspired oxygen (FiO<sub>2</sub>) (P/F) ratio of 120. RESULTS: A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (-23.7 ng/ml/day, p = 0.029), VWF (-33.5% of control/day, p = 0.015), and IL-8 (-362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations. CONCLUSION: NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120.