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      The use of neutrophil elastase inhibitor in the treatment of acute lung injury after pneumonectomy

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          Abstract

          Background

          The prognosis of acute lung injury (ALI) after pneumonectomy is poor, with reported mortality rates of 30-100%. Neutrophil elastase inhibitor (NEI) is known to prevent lung injury caused by neutrophil elastase and improve lung function in ALI. We evaluated the effect of NEI on ALI after pneumonectomy.

          Methods

          We analyzed nine patients who required ventilator care due to ALI after pneumonectomy. Five of these patients underwent conventional ventilator care (group I), and four patients underwent ventilator care and were administrated NEI (group II). We retrospectively analyzed the lung injury score (LIS) for 10 days after intubation.

          Results

          The LIS before intubation satisfied the diagnostic criteria of ALI or acute respiratory distress syndrome (ARDS) in all patients. After intubation, the LIS improved in both groups. But, as times went on, the mean value of the LIS in group II was lower compared to group I. In group I, only one patient underwent extubation. In group II, extubation was possible in three patients. Mortality rates were 80% in group I and 25% in group II.

          Conclusions

          We conclude that NEI may improve the lung function, shorten the duration of mechanical ventilation, and reduce mortality in patients with ALI after pneumonectomy.

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          Most cited references14

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          An expanded definition of the adult respiratory distress syndrome.

          J F Murray, M Matthay, J Luce … (1988)
          Article 0 comments Cited 363 times – based on 0 reviews     Review now
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            High-dose corticosteroids in patients with the adult respiratory distress syndrome.

            G R Bernard, J Luce, C. L. Sprung … (1987)
            Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.
            Article 0 comments Cited 147 times – based on 0 reviews     Review now
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              Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.

              Bernhardt Zeiher, , Alexei Dmitrienko … (2004)
              Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury. Multiple-center, double-blind, placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg.kg(-1)hr(-1). One hundred and five institutions in the United States, Canada, Belgium, Spain, Australia, and New Zealand. A total of 492 mechanically ventilated patients with acute lung injury. Patients were randomized in a 1:1 fashion to sivelestat or placebo. Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days. All patients were managed using low tidal volume mechanical ventilation. The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board, which noted a negative trend in long-term mortality rate. Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days (day 1-day 28) or 28-day all-cause mortality. There were 64 deaths in each treatment group within the 28-day study period, and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups, respectively (p =.536). There was no evidence of effect on measures of pulmonary function, including Pao2/Fio2, static lung compliance, and time to meeting weaning criteria. There was no difference in adverse events or serious adverse events between treatment groups. A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups (p =.102), but there was an increase in 180-day all-cause mortality in the sivelestat treatment group compared with the placebo group (p =.006). Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.
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                Author and article information

                Contributors
                Sang Kwon Lee
                Bong Soo Son
                Jung Joo Hwang
                Kil Dong Kim
                Do Hyung Kim
                Journal
                Journal ID (nlm-ta): J Cardiothorac Surg
                Journal ID (iso-abbrev): J Cardiothorac Surg
                Title: Journal of Cardiothoracic Surgery
                Publisher: BioMed Central
                ISSN (Electronic): 1749-8090
                Publication date Collection: 2013
                Publication date (Electronic): 8 April 2013
                Volume: 8
                Page: 69
                Affiliations
                [1 ]Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
                [2 ]Department of Thoracic and Cardiovascular Surgery, Eulji University Hospital, Daejeon, South Korea
                Article
                Publisher ID: 1749-8090-8-69
                DOI: 10.1186/1749-8090-8-69
                PMC ID: 3680002
                PubMed ID: 23566653
                SO-VID: 456552b8-c322-4314-abf8-922bc95d3308
                Copyright © Copyright ©2013 Lee et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 8 November 2012
                Date accepted : 6 March 2013
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Surgery
                Data availability:
                ScienceOpen disciplines: Surgery

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