A compromise for closed system anesthesia.

Closed system anesthesia is economical, minimally, polluting, and conserves a patient's airway heat and moisture. Yet this method of anesthesia is not widely used because it is considered dangerous by many clinicians. We review the origins of that belief and then test the application of 2 schemes for administering potent agents in a closed system with CO2 absorption. We 1st employed Lowe's square-root-of-time uptake model in 30 patients, using halothane or enflurane. We found that the model provided a good starting point for learning to use the closed system. However, anesthetic concentrations were not accurately predicted. Based on our experience with that model, we examined a simpler approach. We began each of 10 anesthetics using a semiclosed system, then closed the system. Only sufficient O2 for metabolic demand and halothane were added to the closed system. The rate of halothane administration was the same for each patient. This approach proved clinically satisfactory, and the measured halothane concentration remained relatively constant during 45 minutes using the closed system. Changing from a semiclosed to a closed system affords the advantages of the closed system 75 percent of the time, yet requires no extra tasks or equipment.

Sex differences in anaesthetic toxicity: fluroxene and trifluoroethanol in mice.

A sex difference in postanaesthetic mortality after fluroxene anaesthesia was found in Swiss Webster mice. More males succumbed than females. This toxicity was biotransformation-dependent and could be reversed by pretreatment with "opposite" sex hormones. The toxicity of the fluroxene metabolite trifluoroethanol also was more marked in male mice, but was only partially influenced by microsomal enzyme inhibitors or stimulators, or by sex hormones.

Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity.

Glucocorticoids (GCs) are the mainstay of asthma therapy; however, major side effects limit their therapeutic use. GCs influence the expression of genes either by transactivation or transrepression. The antiinflammatory effects of steroids are thought to be due to transrepression and the side effects, transactivation. Recently, a compound, RU 24858, has been identified that demonstrated dissociation between transactivation and transrepression in vitro. RU 24858 exerts strong AP-1 inhibition (transrepression), but little or no transactivation. We investigated whether this improved in vitro profile results in the maintenance of antiinflammatory activity (evaluated in the Sephadex model of lung edema) with reduced systemic toxicity (evaluated by loss in body weight, thymus involution, and bone turnover) compared with standard GCs. RU 24858 exhibits comparable antiinflammatory activity to the standard steroid, budesonide. However, the systemic changes observed indicate that transactivation events do occur with this GC with similar potency to the standard steroids. In addition, the GCs profiled showed no differentiation on quantitative osteopenia of the femur. These results suggest that in vitro separation of transrepression from transactivation activity does not translate to an increased therapeutic ratio for GCs in vivo or that adverse effects are a consequence of transrepression.