Effects of sevoflurane on cytokine balance in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: The effects of sevoflurane on proinflammatory cytokines related to ischemic-reperfusion injury are not clear. The hypothesis was tested that sevoflurane decreases myocardial ischemic-reperfusion injury by suppressing proinflammatory cytokines. DESIGN: Prospective, randomized study. SETTING: A medical university heart center. PARTICIPANTS: Twenty-three patients undergoing coronary artery bypass surgery allocated randomly into 2 groups. INTERVENTIONS: Anesthesia for 23 patients undergoing coronary artery bypass surgery was maintained using either fentanyl (30 microg/kg) with propofol (2-8 mg/kg/h) in the control group (n = 10) or fentanyl (30 microg/kg) with 0.5% to 1.0% sevoflurane in the sevoflurane group (n = 13). MEASUREMENTS AND MAIN RESULTS: Interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) were measured by enzyme-linked immunosorbent assay. Troponin-T and creatine kinase-MB isoenzyme (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry, respectively. Serum IL-6 and IL-8 concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta (p < 0.001). The increases were greater in the control group than in the sevoflurane group (p < 0.05). Serum IL-10 and IL-1ra concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta (p < 0.001). There were no differences between the two groups. Serum troponin-T and CK-MB concentrations increased significantly in both groups from 60 minutes after declamping the aorta (p < 0.001); the increases were greater in the control group (p < 0.05). CONCLUSION: Sevoflurane suppressed the production of IL-6 and IL-8, but not IL-10 and IL-1ra. Changes in the balance between pro- and anti-inflammatory cytokines may be one of the most important mechanisms of myocardial protection caused by sevoflurane.

Sivelestat, a neutrophil elastase inhibitor, reduces mortality rate of critically ill patients.

Many studies have suggested that neutrophil elastase (NE) may contribute to multiple organ failure (MOF) and acute injury of lung endothelial cells. It is therefore conceivable that NE inhibitors may improve the outcome of MOF patients. A synthetic NE inhibitor, sivelestat, which was developed and released in Japan, inhibited inflammatory reactions in various animal models. We examined the medical records of patients requiring more than two days of respiratory care in four intensive care units to investigate whether sivelestat contributed to improvement of their conditions. A total of 110 patients were divided into two groups (sivelestat treated group of 57 patients and untreated group of 53 patients). The conditions and age of the patients were similar in both groups. Sivelestat (0.2 mg/kg/hr) was administered continuously for 14 days beginning on the day of the intensive care unit (ICU) admission or for less than 14 days until discharge from the ICU. Hospital mortality differed significantly between the two groups (treated: 19% and untreated: 40%, p < 0.05). The severity of acute lung injury is defined by the ratio of arterial oxygen partial pressure (PaO2)/fraction concentration of oxygen in the inspired air (FiO2). When the PaO2/FiO(2) ratio is more than 200 mmHg, the morbidity is lower. In patients with PaO2/FiO2 ratio more than 200 mmHg, the hospital mortality was 33.3% (7/21) in the untreated group and 6.0% (1/18) in the treated group (p = 0.0236). We conclude that administration of sivelestat reduces mortality of critically ill patients.