A pharmacokinetic-pharmacodynamic real-time display may change anesthesiologists' behavior.

We have developed a real-time graphical display that presents anesthetic pharmacology data (drug effect site concentrations (Ce) and probability of anesthetic effects including hypnosis, loss of response to tracheal intubation), improving a previous prototype. We hypothesized that the use of the display alters (1) clinical behavior of anesthesiologists (i.e., Ce of isoflurane and fentanyl at the end of anesthesia), (2) fentanyl dose during the first 30 min of recovery in the post anesthesia care unit (PACU), and that the response of clinicians to the display in terms of workload and utility is favorable. The display was evaluated in a two-group, non-randomized prospective observational study of 30 patients undergoing general anesthesia using isoflurane and fentanyl. The isoflurane-predicted Ce was lower in the display group (without-display: 0.64% ± 0.06%; with-display: 0.42 ± 0.04%; t23.9 = 3.17, P = 0.004 < adjusted alpha 0.05/2). The difference in fentanyl-predicted Ce did not achieve statistical significance (without-display: 1.5 ± 0.1 ng/ml; with-display: 2.0 ± 0.2 ng/ml; t25.5 = 2.26, P = 0.03 > adjusted alpha 0.05/2) (means ± standard error). A joint test of isoflurane and fentanyl Ce with respect to the display condition rejected the null hypothesis of no differences (Hotelling T2, P = 0.01), supporting our primary hypothesis. The total fentanyl per patient during the first 30 min in the PACU with the display was 75.0 ± 62.7 µg and that without the display was 83.0 ± 74.7 µg. There was no significant difference between the groups (means ± standard deviation, P = 0.75). There were no differences in perceived workload. Use of the display does not appear to be cognitively burdensome and may change the anesthesiologist's dosing regimen.

Novel broad-spectrum inhibitors of bacterial methionine aminopeptidase.

With increasing emergence of multi-drug resistant infections, there is a dire need for new classes of compounds that act through unique mechanisms. In this work, we describe the discovery and optimization of a novel series of inhibitors of bacterial methionine aminopeptidase (MAP). Through a high-throughput screening campaign, one azepinone amide hit was found that resembled the native peptide substrate and possessed moderate biochemical potency against three bacterial isozymes. X-ray crystallography was used in combination with substrate-based design to direct the rational optimization of analogs with sub-micromolar potency. The novel compounds presented here represent potent broad-spectrum biochemical inhibitors of bacterial MAP and have the potential to lead to the development of new medicines to combat serious multi-drug resistant infections.

Evaluation of graphic cardiovascular display in a high-fidelity simulator.

UNLABELLED: "Human error" in anesthesia can be attributed to misleading information from patient monitors or to the physician's failure to recognize a pattern. A graphic representation of monitored data may provide better support for detection, diagnosis, and treatment. We designed a graphic display to show hemodynamic variables. Twenty anesthesiologists were asked to assume care of a simulated patient. Half the participants used the graphic cardiovascular display; the other half used a Datex As/3 monitor. One scenario was a total hip replacement with a transfusion reaction to mismatched blood. The second scenario was a radical prostatectomy with 1.5 L of blood loss and myocardial ischemia. Subjects who used the graphic display detected myocardial ischemia 2 min sooner than those who did not use the display. Treatment was initiated sooner (2.5 versus 4.9 min). There were no significant differences between groups in the hip replacement scenario. Systolic blood pressure deviated less from baseline, central venous pressure was closer to its baseline, and arterial oxygen saturation was higher at the end of the case when the graphic display was used. The study lends some support for the hypothesis that providing clinical information graphically in a display designed with emergent features and functional relationships can improve clinicians' ability to detect, diagnose, manage, and treat critical cardiovascular events in a simulated environment. IMPLICATIONS: A graphic representation of monitored data may provide better support for detection, diagnosis, and treatment. A user-centered design process led to a novel object-oriented graphic display of hemodynamic variables containing emergent features and functional relationships. In a simulated environment, this display appeared to support clinicians' ability to diagnose, manage, and treat a critical cardiovascular event in a simulated environment. We designed a graphic display to show hemodynamic variables. The study provides some support for the hypothesis that providing clinical information graphically in a display designed with emergent features and functional relationships can improve clinicians' ability to detect, diagnosis, mange, and treat critical cardiovascular events in a simulated environment.