Ischemia-reperfusion-induced unmeasured anion generation and glycocalyx shedding: sevoflurane versus propofol anesthesia.

INTRODUCTION: Vascular leakage after ischemia-reperfusion (IR) is largely attributed to the destruction of the endothelial barrier and its associated negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes. Therefore, we compared sevoflurane with propofol with regard to the protection of the glycocalyx and the release of negatively charged substances in vivo. METHODS: After surgical preparation under midazolam-fentanyl, nine pigs each received either propofol or sevoflurane. Ischemia of 90 min was induced by a balloon catheter in the thoracic aorta. After 120 min of reperfusion, the anesthetics were changed back to midazolam-fentanyl. Five animals, each without aortic occlusion, served as time controls. Blood electrolyte parameters were measured, from which the strong ion gap (SIG) was calculated. Serum heparan sulfate concentrations and immunohistology served as a marker of glycocalyx destruction. RESULTS: Immediately after reperfusion, SIG increased significantly only in the propofol group (+6.7 mEq/l versus baseline; p < .05), remaining stable in sevoflurane and both time-controlled groups. Initially, heparan sulfate concentration increased comparably in both experimental groups, but after 120 min, it became stable in sevoflurane-anesthetized animals, while increasing further in the propofol group (p < .05). CONCLUSIONS: Unmeasured anions, predictive of negative outcome in previous studies, did not increase significantly in sevoflurane-anesthetized animals. Additionally, there was less heparan sulfate shedding over time, signaling less destruction of the glycocalyx. Therefore, in this in-vivo situation, sevoflurane proves to be superior to propofol in protecting the endothelium from IR injury.

Methylnaltrexone, a new peripheral mu-receptor antagonist for the prevention and treatment of opioid-induced extracerebral side effects.

Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.

Sevoflurane provides greater protection of the myocardium than propofol in patients undergoing off-pump coronary artery bypass surgery.

BACKGROUND: Sevoflurane, like other halogenated anesthetics, has been shown to have a protective effect on the myocardium at risk after an ischemic injury. The current study tested the hypothesis that such beneficial effects, so far mainly seen in the laboratory, are reproducible in humans. METHODS: After institutional review board approval, 20 patients scheduled to undergo elective off-pump coronary artery bypass surgery were randomized to receive general anesthesia with either sevoflurane or propofol. Except for this, anesthetic and surgical management was the same in both groups. For assessing myocardial injury, troponin I and myocardial fraction of creatine kinase were determined during the first 24 postoperative hours. Systemic hemodynamic variables were measured before, during, and after completion of coronary artery bypass. RESULTS: Troponin I concentrations increased significantly more in propofol-anesthetized patients than in patients anesthetized with sevoflurane. CONCLUSION: Patients receiving sevoflurane for off-pump coronary artery surgery had less myocardial injury during the first 24 postoperative hours than patients receiving propofol. The results further support cardioprotective effects of sevoflurane.

Halogenated inhalational anaesthetics.

The halogenated inhalational anaesthetics halothane, enflurane, isoflurane and desflurane can produce metabolic hepatocellular injury in humans to a variable extent. During metabolism of these anaesthetics, tissue acetylation occurs due to the formation of reactive intermediates. Proteins modified by acetylation may constitute neo-antigens with a potential for triggering an antibody-mediated immune response. The likelihood of suffering post-operative immune hepatitis depends on the amount of the anaesthetic metabolized and is thereby considerably less with enflurane, isoflurane or desflurane compared with halothane. Plasma inorganic fluoride concentrations are regularly increased after sevoflurane. Elevated inorganic fluoride concentrations have been associated with nephrotoxicity following methoxyflurane anaesthesia but not after sevoflurane. Another source of concern is the products of degradation from reactions with carbon dioxide absorbents. Most important is compound A, which has been shown to exhibit nephrotoxicity in rodents. However, no significant changes in renal function parameters have been reported in surgical patients.

Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency.

BACKGROUND: Sevoflurane is degraded to compound A (CpA) by carbon dioxide absorbents containing strong base. CpA is nephrotoxic in rats. Patient exposure to CpA is increased with low fresh gas flow rates, use of Baralyme, and high sevoflurane concentrations. CpA formation during low-flow and closed circuit sevoflurane anesthesia had no significant renal effects in surgical patients with normal renal function. Preexisting renal insufficiency is a risk factor for postoperative renal dysfunction. Although preexisting renal insufficiency is not affected by high-flow sevoflurane, the effect of low-flow sevoflurane in patients with renal insufficiency is unknown. METHODS: After obtaining institutional review board approval, 116 patients with a stable preoperative serum creatinine concentration 1.5 mg/dl or greater were assessable. Patients were randomized to receive either sevoflurane (n = 59, 0.8-2.5 vol%) or isoflurane (n = 57, 0.5-1.4 vol%) at a fresh gas flow rate of 1 l/min or less. Use of opioids was restricted to a minimum, and Baralyme was used to increase CpA exposure. Inspiratory and expiratory CpA concentrations were measured during anesthesia. Renal function (serum creatinine and blood urea nitrogen, urine protein and glucose, creatinine clearance) was measured preoperatively and 24 and 72 h after induction. RESULTS: Demographic patient data did not differ between groups. Patients received 3.1 +/- 2.4 minimum alveolar concentration-hours sevoflurane or 3.8 +/- 2.6 minimum alveolar concentration-hours isoflurane (mean +/- SD). Durations of low flow were 201.3 +/- 98.0 and 213.6 +/- 83.4 min, respectively. Maximum inspiratory CpA with sevoflurane was 18.9 +/- 7.6 ppm (mean +/- SD), resulting in an average total CpA exposure of 44.0 +/- 30.6 ppm/h. There were no statistically significant changes from baseline to 24- and 72-h values for serum creatinine or blood urea nitrogen, creatinine clearance, urine protein, and glucose, nor were there significant differences between both anesthetics. CONCLUSION: There were no statistically significant differences in measured parameters of renal function after low-flow sevoflurane anesthesia compared with isoflurane. These results suggest that low-flow sevoflurane anesthesia is as safe as low-flow isoflurane and does not alter kidney function in patients with preexisting renal disease.