Journal of Critical Care 29 (2014) 1123

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Noninvasive mechanical ventilation and neutrophil elastase inhibitor: Is it a new potential approach to acute hypoxemic failure?☆ To the Editor: Oxygenation impairment shown by a decreasing PaO2/FiO2 ratio is one of the most well-documented predictor of noninvasive mechanical ventilation (NIV) failure in acute lung injury (ALI)–acute respiratory distress syndrome (ARDS) [1]. Mechanisms are developed by complex inflammatory pathways triggered by releasing inflammatory neutrophils [2]. Tsushima et al [3] described effects on oxygenation index of neutrophil elastase inhibitor (NEI) during NIV, and main conclusions were that baseline PaO2/FiO2 greater than 150 mm Hg and the lung injury score improved significantly. We want to congratulate them for this interesting new combined approach of 2 therapies, pharmacology and NIV approach, to improve oxygenation in ARDSALI. However, some methodological aspects need remarks for a proper practical extrapolation. First of all, we need more precise interpretation of baseline PaO2/ FiO2 greater than 150 mm Hg, and trends could be influenced by other uncontrolled factors during NIV [1,4,5]. Second, there are some controversial methodology and timing for NEI therapy during NIV [6,7]. This aspect is crucial because some previous studies consider that nearly 65% of NIV failures occur within 1 to 48 hours during NIV [5]. Third, there are unresolved questions derived of application during neutropenic ARDS-ALI and NIV [8]. Summarized factors influence NIVNEI approach (Table). Although this is an original and emergent approach to improve hypoxemic conditions during NIV in ARDS-ALI, further prospective clinical trials need to explore these methodology aspects to consolidate NIV-NEI as solid practical tool.

Antonio M. Esquinas, MD, PhD Intensive Care Unit and Noninvasive Ventilatory Unit, Murcia, Spain Corresponding author at: Avenida Marques Vélez s/n Murcia, Spain, 30008 Tel.: +34 968360900; fax: +34 968232484 E-mail address: [email protected] Javier Muñoz Bono, MD Miguel Salguero Piedras, MD Intensive Care Unit, Hospital Carlos Haya, 29010, Málaga, Spain References [1] Antonelli M, Conti G, Moro ML, Esquinas A, Gonzalez-Diaz G, Confalonieri M, et al. Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive Care Med 2001;27:1718–28. [2] Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med 2011;17:293–307. [3] Tsushima K, Yokoyama T, Matsumura T, Koizumi T, Kubo K, Tatsumi K, et al. Acute Lung Injury Group in Nagano. The potential efficacy of noninvasive ventilation with administration of a neutrophil elastase inhibitor for acute respiratory distress syndrome. J Crit Care 2014;29(3):420–5. [4] Hoshi K, Kurosawa S, Kato M, Andoh K, Satoh D, Kaise A. Sivelestat, a neutrophil elastase inhibitor, reduces mortality rate of critically ill patients. Tohoku J Exp Med 2005;207:143–8. [5] Agarwal R, Handa A, Aggarwal AN, Gupta D, Behera D. Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a respiratory intensive care unit in north India. Respir Care 2009;54:1679–87. [6] Hoelz C, Negri EM, Lichtenfels AJ, Conceção GM, Barbas CS, Saldiva PH, et al. Morphometric differences in pulmonary lesions in primary and secondary ARDS. A preliminary study in autopsies. Pathol Res Pract 2001;197:521–30. [7] Lee SK, Son BS, Hwang JJ, Kim KD, Kim DH. The use of neutrophil elastase inhibitor in the treatment of acute lung injury after pneumonectomy. J Cardiothorac Surg 2013;8(8(1)):69. [8] Ognibene FP, Martin SE, Parker MM, et al. Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med 1986;9:547–51.

Table Factors and relationships during NIV-NEI therapy ARDS-ALI [1,4-6] (a) Causes and severity (b) Underlying ARDS-ALI (c) Patterns and time of clinical progress (d) Rate and morphological lung neutrophils infiltration (e) Baseline and trends index PaO2/FiO2 (f) Alveolar recruitment that may influence PaO2/FiO2 ratio NIV interface factors [1,5] (a) Interface (b) Leakages (c) Positive pressure (IPAP/EPAP) setting and variations Timing for use of NIV-NEI [7,8] (a) NEI pharmacokinetics and ALI-ARDS stage (b)Variability NIV indication ☆ Authors declare no conflict of interest. 0883-9441/© 2014 Elsevier Inc. All rights reserved.

Abbreviations: IPAP, inspiratory positive airway pressure; EPAP, end positive airway pressure.

Noninvasive mechanical ventilation and neutrophil elastase inhibitor: is it a new potential approach to acute hypoxemic failure?

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