Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of
neutrophil elastase (NE) and is effective in reducing
acute lung injury associated with
systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of
sivelestat sodium hydrate to prevent postoperative
acute lung injury in patients undergoing thoracoscopic
esophagectomy and radical
lymphadenectomy. Twenty-two patients with thoracic
esophageal cancer underwent video-assisted thoracoscopic
esophagectomy with extended
lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received
sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (
sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given
methylprednisolone immediately before surgery. Postoperative
clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed
pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial
oxygen pressure/fraction of inspired
oxygen ratio, white blood cell count, serum
C-reactive protein level, plasma
cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the
sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the
sivelestat-treated group than in the control group (P= 0.007). The median arterial
oxygen pressure/fraction of inspired
oxygen ratio of the
sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum
C-reactive protein levels, plasma
interleukin-1beta,
tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6,
surfactant protein-A, or
surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of
lung injury. Plasma
interleukin-8 levels were significantly lower in the
sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of
sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative
hypoxia, partially suppressed postoperative
hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic
esophagectomy.