Study on Perioperative Administration of a Neutrophil Elastase Inhibitor for Interstitial Pneumonias.

BACKGROUND: Although acute exacerbation of idiopathic interstitial pneumonias (IIPs) is a lethal complication after pulmonary resection for lung cancer with IIPs, there are no established methods to prevent its occurrence. This prospective randomized study was conducted to evaluate whether perioperative administration of the neutrophil elastase inhibitor sivelestat prevents acute exacerbation after surgery. METHODS: The IIP patients with suspected lung cancers were randomly assigned to two groups before surgery: in group A (n = 65), sivelestat was perioperatively administered for 5 days; in group B (n = 65), no medications were administered. The primary endpoint was the frequency of acute exacerbation of IIPs. The secondary endpoints were perioperative changes in the lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, surfactant protein D and surfactant protein A values, and the safety of preoperative administration of sivelestat. Multivariate analyses were performed using a logistic regression model to identify the factors that predicted acute exacerbation. RESULTS: Acute exacerbation developed in 2 patients in group A and 1 patient in group B (p = 0.559). Administration of sivelestat did not contribute to decreasing the acute exacerbation as well as short- and long-term mortality. The differences were not statistically significant in perioperative lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, and surfactant protein D and A levels. No subjective adverse events were observed. A preoperative partial pressure oxygen level of less than 70 mm Hg was the only predictive factor identified in the logistic analysis (p = 0.019, hazard ratio 19.2). CONCLUSIONS: Perioperative administration of neutrophil elastase inhibitor appeared to be safe; however, it could not prevent the development of acute exacerbation after surgery in lung cancer patients with IIPs.

Prophylaxis for acute exacerbation of interstitial pneumonia after lung resection.

BACKGROUND AND PURPOSE: Acute exacerbation of interstitial pneumonia is a life-threatening complication after lung cancer surgery. Dorsal subpleural fibrotic changes occupying 3 or more segments of both lower lobes on high-resolution computed tomography indicate a very high risk. We conducted a prospective phase II study to assess the efficacy of prophylactic treatment. METHODS: Patients with lung cancer underwent high-resolution computed tomography preoperatively to assess the risk of acute exacerbations of interstitial pneumonia. Before induction of general anesthesia, high-risk patients received 125 mg of methylprednisolone as an intravenous bolus and sivelestat sodium hydrate 300 mg ·day(-1) as a continuous intravenous infusion. From January 2010 through August 2011, a total of 327 patients underwent surgery for lung cancer, and 31 (9.5%) were enrolled. RESULTS: There was no case of acute exacerbation. No adverse events were associated with prophylaxis. Usual interstitial pneumonia was confirmed histopathologically in 25 (80.6%) patients. Four (12.9%) patients had major complications. Usual interstitial pneumonia was diagnosed postoperatively in 4 (1.4%) of 327 patients who did not meet the inclusion criteria, and 1 of these patients died due to acute exacerbation of occult interstitial pneumonia. CONCLUSION: Perioperative use of sivelestat sodium hydrate and low-dose methylprednisolone may be useful as prophylaxis for acute exacerbation of interstitial pneumonia.

[A nationwide survey concerning lung surgery for lung cancer associated with idiopathic interstitial pneumonia].

Acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) is a near-fatal condition with especially high risk following lung surgery. We conducted a nationwide survey concerning prophylactic therapy to prevent possible AE following lung surgery in Japan. We sent a questionnaire concerning prophylactic therapy immediately before and after lung surgery to a total of 701 institutions, including specific questions about anesthesia. Some prophylactic medication was applied in 128 institutions (prophylactic group : P group). In contrast, no prophylactic therapy was utilized in the remaining 92 institutions (non-prophylactic group : N group). In 1 year, 744 operations were performed for lung cancer associated with IIP. In the P group, the prevalence of AE following surgery was 7.8%, and the mortality rate was 48.4%. In the N group, the prevalence was 9.6%, and the mortality rate was 32.2%. In 204 departments (92.7%), certain specific settings for ventilation or surgery were applied. In conclusion, it is necessary to further evaluate the feasibility of such prophylactic therapy, and standard guidelines should be established.