The effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells.

BACKGROUND: Acute renal failure is a frequent complication of sepsis. Hydroxyethyl starch (HES) is widely used in the treatment of such patients. However, the effect of HES on renal function during sepsis remains controversial. We established an in vitro model of tumor necrosis factor-alpha (TNF-alpha)-stimulated human proximal tubular epithelial (HK-2) cells to assess the possible effects of HES 130/0.42 and HES 200/0.5 on these activated cells. METHODS: HK-2 cells were stimulated with TNF-alpha in the presence or absence of HES 130/0.42 or 200/0.5. After 4, 10, and 18 h of incubation, monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was measured. In addition, viability and cytotoxicity assays were performed. RESULTS: MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200/0.5 in 98% (96%) medium over a stimulation time period of 10 h and 18 h, the MCP-1 concentration was decreased between 26% and 56% (P < 0.05). TNF-alpha stimulation resulted in a significant decrease of viability by 53%-63%, whereas viability decreased by only 32%-40% in coincubation with HES 130/0.42 (P < 0.005) and remained even less affected by TNF-alpha in the presence of HES 200/0.5 (P < 0.001). The TNF-alpha-induced cell death rate was attenuated in the presence of HES 200/0.5 (P < 0.05). CONCLUSIONS: This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types.

Anesthetic-induced improvement of the inflammatory response to one-lung ventilation.

BACKGROUND: Although one-lung ventilation (OLV) has become an established procedure during thoracic surgery, sparse data exist about inflammatory alterations in the deflated, reventilated lung. The aim of this study was to prospectively investigate the effect of OLV on the pulmonary inflammatory response and to assess possible immunomodulatory effects of the anesthetics propofol and sevoflurane. METHODS: Fifty-four adults undergoing thoracic surgery with OLV were randomly assigned to receive either anesthesia with intravenously applied propofol or the volatile anesthetic sevoflurane. A bronchoalveolar lavage was performed before and after OLV on the lung side undergoing surgery. Inflammatory mediators (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, monocyte chemoattractant protein 1) and cells were analyzed in lavage fluid as the primary endpoint. The clinical outcome determined by postoperative adverse events was assessed as the secondary endpoint. RESULTS: The increase of inflammatory mediators on OLV was significantly less pronounced in the sevoflurane group. No difference in neutrophil recruitment was found between the groups. A positive correlation between neutrophils and mediators was demonstrated in the propofol group, whereas this correlation was missing in the sevoflurane group. The number of composite adverse events was significantly lower in the sevoflurane group. CONCLUSIONS: This prospective, randomized clinical study suggests an immunomodulatory role for the volatile anesthetic sevoflurane in patients undergoing OLV for thoracic surgery with significant reduction of inflammatory mediators and a significantly better clinical outcome (defined by postoperative adverse events) during sevoflurane anesthesia.

A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic.

OBJECTIVE: To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion. BACKGROUND: In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial. METHODS: Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system. RESULTS: Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P = 0.05) were also lowered by preconditioning. CONCLUSION: This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.