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Sivelestat attenuates postoperative pulmonary dysfunction after total arch replacement under deep hypothermia

Division of Cardiovascular Surgery, Kobe University, Graduate School of Medicine, Kobe, Hyogo, Japan

Received 17 November 2007; received in revised form 22 May 2008; accepted 2 July 2008.

^_* Corresponding author. 7-5-1 Kusunoki-cho, Chuuo-ku, Kobe, Hyogo, 650-0017, Japan. Tel.: +81 78 382 5942; fax: +81 78 382 5959. (Email: naotom{at}med.kobe-u.ac.jp).

Background: Total arch replacement necessitating deep hypothermia with circulatory arrest has a greater effect on pulmonary function than other cardiac surgery using cardiopulmonary bypass (CPB). Since April 2004, 100 mg of sivelestat sodium hydrate was administrated by bolus injection into pulp circuit at the initiation of CPB in every case performed total arch replacement. We investigated the hypothesis that prophylactic use of the drug attenuates post-pump pulmonary dysfunction. Methods: A retrospective analysis of 120 consecutive patients who underwent total arch replacement from August 2001 to December 2006 was conducted. Patients were divided into two groups according to the date of surgery, April 2004, when we started sivelestat administration. Group A (n = 60), operated after April 2004, was administrated sivelestat at the initiation of CPB. Group B (n = 60), before April 2004, was not administrated. Time courses of hemodynamic variables were evaluated until 24 h after surgery and those of respiratory variables and inflammatory markers until 48 h after surgery. Results: There were no significant differences in patient age, sex, prevalence of chronic obstructive lung disease, preoperative lung function, time of operation and CPB, minimum temperature, and aprotinin usage. Hospital mortality occurred in two patients in the group B (3.3%) and no patient in group A (0%). Postoperative hemodynamic variables were not different between the two groups. Respiratory index, oxygenation index were significantly better in patients pretreated with sivelestat (respiratory index; p < 0.001, oxygenation index; p < 0.001, respectively). CRP was significantly lower in patients pretreated with sivelestat (p = 0.022). Except for patients who required tracheostomy or re-exploration for bleeding, patients pretreated with sivelestat were extubated significantly shorter (group A: 12.6 ± 10.8 h, group B: 25.5 ± 12.9 h, p = 0.033). No patient with postoperative respiratory failure requiring tracheostomy was noted in sivelestat group. Conclusion: Prophylactic administration of sivelestat at the initiation of CPB results in better postoperative pulmonary function, leading to earlier extubation time. Our study suggests that sivelestat was effective in facilitating postoperative respiratory management in total arch replacement.

Key Words: Cardiopulmonary bypass • Total arch replacement • Postperfusion pulmonary dysfunction