Abstract
BackgroundNeuromuscular 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.MethodsWe 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 cm3/kg) and by an initial arterial oxygen tension (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio of 120.ResultsA 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.ConclusionNBM 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.
Highlights
Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS)
Compared with the original 902 patients, there were no significant differences in age, gender, treatment arm, initial Arterial oxygen tension (PaO2) to FiO2 (P/F) ratio, Acute Physiology and Chronic Health Evaluation (APACHE) III score, etiology of ARDS, or ventilator settings after Bonferroni correction in this study group
There was no significant difference in the number of NMB days between groups (p = 0.62). After adjusting for these baseline differences in a multivariable regression model, each day of NMB was associated with a decrease in Surfactant protein D (SP-D) (−23.7 ng/ml/day of NMB, 95% Confidence interval (CI) −44.8 to −2.5; p = 0.028), Von Willebrand Factor (VWF) (−33.5% of control/day of NMB, 95% CI −60.5 to −6.4; p = 0.015), and IL-8 (−362.6 pg/ml/day of NMB, 95% CI −689.3 to −35.9; p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving Low tidal volume ventilation (LTVV) (Table 3)
Summary
Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). 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. Despite significant advances in ventilator management, acute respiratory distress syndrome (ARDS) mortality remains unacceptably high. ARDS is characterized by the disruption of the alveolar capillary membrane and the subsequent accumulation of noncardiogenic pulmonary edema. Both alveolar epithelium and pulmonary vascular endothelium are injured in ARDS [1]. Neuromuscular blockade (NMB) has been investigated as a therapy for ARDS in conjunction with LTVV to reduce VILI. NMB reduced markers of systemic inflammation in patients with ARDS [6, 7]
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