Elsevier

The Annals of Thoracic Surgery

Volume 96, Issue 6, December 2013, Pages 2184-2191
The Annals of Thoracic Surgery

Original article
Congenital heart surgery
Sivelestat Attenuates Lung Injury in Surgery for Congenital Heart Disease With Pulmonary Hypertension

https://doi.org/10.1016/j.athoracsur.2013.07.017Get rights and content

Background

Pulmonary hypertension associated with congenital heart disease increases the risk of surgery using cardiopulmonary bypass. Sivelestat is a neutrophil elastase inhibitor thought to have a prophylactic effect against lung injury after surgery using bypass. We elucidated that Sivelestat had the protective effect on lung in patients with congenital heart disease and pulmonary hypertension who underwent surgery using bypass.

Methods

This study was a controlled prospective randomized trial and enrolled 13 neonates or infants with ventricular septal defect and pulmonary hypertension. The patients were assigned to either sivelestat with the dose of 0.2 mg/kg per hour (sivelestat group, n = 7) or saline (placebo group, n = 6) from the start of bypass until 6 hours after bypass. Proinflammatory cytokines and adhesion molecules on leukocytes were measured at 10 time points during the above period. Pulmonary function was assessed perioperatively.

Results

Compared with the placebo group, the sivelestat group had significantly lower values of alveolar-arterial oxygen tension gradient at 24 hours (p = 0.038) and at 48 hours (p = 0.028) after bypass, and significantly better balance of hydration at 48 hours after bypass (p = 0.012). The sivelestat group also showed significantly lower plasma levels of interleukin-8 immediately after bypass (p = 0.041) and interleukin-10 at 15 minutes after removal of the aortic cross-clamp (p = 0.048), and immediately after bypass (p = 0.037).

Conclusions

Administration of sivelestat during bypass prevented pulmonary damage and activities of proinflammatory cytokines at the cardiac operation in neonates or infants. Our results show that sivelestat may be considered to protect pulmonary function against the injury by bypass.

Section snippets

Patient and Study Design

This study was a randomized, double-blind, placebo-controlled trial in two parallel treatment groups of neonates or infants, and was approved by the Institutional Review Board of Nagoya City University Hospital. Informed consent was obtained from the parents of each patient. All subjects had congenital heart disease and PH and underwent cardiac surgery using CPB from July 2004 to January 2009.

Eligible patients were neonates or infants with ventricular septal defect (VSD) and pulmonary

Results

The preoperative demographic characteristics and intra- and postoperative clinical data are summarized in Tables 1 and 2, respectively. Pulmonary blood flow was excessive in all patients (mean Qp/Qs, 3.60 ± 1.19; range, 2.30 to 6.20). No patient had high pulmonary vascular resistance (mean Rp/Rs, 0.27 ± 0.07; range, 0.15 to 0.40). No restrictive VSD was confirmed in all patients. The two groups were similar in terms of baseline characteristics. No patient died in either group. Treatment with

Comment

Pulmonary hypertension is a poor prognostic factor in patients undergoing surgery for congenital heart disease, and hence its management is important. The pulmonary vascular condition of patients, operative stress, and the initiation of CPB may increase pulmonary vascular damage after surgery in patients with congenital heart disease and PH. Dilution of blood, contact between blood and the artificial surfaces of the perfusion circuit, and ischemia and reperfusion during CPB activates

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