Simulation-based Assessment of the Management of Critical Events by Board-certified Anesthesiologists.

BACKGROUND: We sought to determine whether mannequin-based simulation can reliably characterize how board-certified anesthesiologists manage simulated medical emergencies. Our primary focus was to identify gaps in performance and to establish psychometric properties of the assessment methods. METHODS: A total of 263 consenting board-certified anesthesiologists participating in existing simulation-based maintenance of certification courses at one of eight simulation centers were video recorded performing simulated emergency scenarios. Each participated in two 20-min, standardized, high-fidelity simulated medical crisis scenarios, once each as primary anesthesiologist and first responder. Via a Delphi technique, an independent panel of expert anesthesiologists identified critical performance elements for each scenario. Trained, blinded anesthesiologists rated video recordings using standardized rating tools. Measures included the percentage of critical performance elements observed and holistic (one to nine ordinal scale) ratings of participant's technical and nontechnical performance. Raters also judged whether the performance was at a level expected of a board-certified anesthesiologist. RESULTS: Rater reliability for most measures was good. In 284 simulated emergencies, participants were rated as successfully completing 81% (interquartile range, 75 to 90%) of the critical performance elements. The median rating of both technical and nontechnical holistic performance was five, distributed across the nine-point scale. Approximately one-quarter of participants received low holistic ratings (i.e., three or less). Higher-rated performances were associated with younger age but not with previous simulation experience or other individual characteristics. Calling for help was associated with better individual and team performance. CONCLUSIONS: Standardized simulation-based assessment identified performance gaps informing opportunities for improvement. If a substantial proportion of experienced anesthesiologists struggle with managing medical emergencies, continuing medical education activities should be reevaluated.

Embryonic development of circadian oscillations in the mouse hypothalamus.

Circadian rhythms in mammals are regulated by the hypothalamic suprachiasmatic nucleus (SCN). The generation of circadian oscillations is a cell-autonomous property, and coupling among cells is essential for the SCN to function as a pacemaker. The development of SCN anatomy and cytology has been extensively studied, but the point in development when the SCN first has the capacity to generate circadian oscillations has not been established. We therefore examined the development of circadian oscillations using per2::luc mice in which bioluminescence tracks the expression of the circadian clock protein, PER2. In vitro, hypothalamic explants first expressed consistent oscillations when isolated between 15 and 16 days postfertilization (e15). Oscillations were more robust at later ages. Explants from other brain areas did not express oscillations, indicating that the development of oscillations is not a general property of embryonic tissue. SCN explants obtained on e14 did not initially express oscillations but developed them in vitro over 4 to 6 d. Although coupling among cells is required for the long-term expression of tissue-level oscillations, explants from mice lacking the coupling peptide vasoactive intestinal peptide still developed oscillations. In the mouse, the capacity to generate molecular oscillations on e15 coincides with the completion of neurogenesis and SCN-specific transcription factor expression. Thus, within a day of its genesis at an age approximately equivalent to the end of the first trimester in humans, the SCN develops the capacity to express circadian oscillations and autonomously develops mechanisms sufficient to couple and synchronize its cells.

Chronic stimulation of the hypothalamic vasoactive intestinal peptide receptor lengthens circadian period in mice and hamsters.

Evidence suggests that circadian rhythms are regulated through diffusible signals generated by the suprachiasmatic nucleus (SCN). Vasoactive intestinal peptide (VIP) is located in SCN neurons positioned to receive photic input from the retinohypothalamic tract and transmit information to other SCN cells and adjacent hypothalamic areas. Studies using knockout mice indicate that VIP is essential for synchrony among SCN cells and for the expression of normal circadian rhythms. To test the hypothesis that VIP is also an SCN output signal, we recorded wheel-running activity rhythms in hamsters and continuously infused the VIP receptor agonist BAY 55-9837 in the third ventricle for 28 days. Unlike other candidate output signals, infusion of BAY 55-9837 did not affect activity levels. Instead, BAY 55-9837 lengthened the circadian period by 0.69 +/- 0.04 h (P < 0.0002 compared with controls). Period returned to baseline after infusions. We analyzed the effect of BAY 55-9837 on cultured SCN from PER2::LUC mice to determine if lengthening of the period by BAY 55-9837 is a direct effect on the SCN. Application of 10 muM BAY 55-9837 to SCN in culture lengthened the period of PER2 luciferase expression (24.73 +/- 0.24 h) compared with control SCN (23.57 +/- 0.26, P = 0.01). In addition, rhythm amplitude was significantly increased, consistent with increased synchronization of SCN neurons. The effect of BAY 55-9837 in vivo on period is similar to the effect of constant light. The present results suggest that VIP-VPAC2 signaling in the SCN may play two roles, synchronizing SCN neurons and setting the period of the SCN as a whole.

Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters.

The growth factor, transforming growth factor-alpha (TGF-alpha) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-alpha is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-alpha suppresses activity. TGF-alpha suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-alpha is correlated with some cancers, and it is possible the TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), mediate fatigue and weight loss associated with cancer. If true for cancers outside of the brain, then systemic TGF-alpha should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-alpha. Both treatments suppressed activity and infusions caused reduced food consumption and weight loss. To identify areas of the brain that might mediate these effects of systemic TGF-alpha, we used immunohistochemistry to localize cells with an activated MAP kinase signaling pathway (phosphorylated ERK1). Cells were activated in two hypothalamic areas, the paraventricular nucleus and a narrow region surrounding the third ventricle. These sites could not only be targets of TGF-alpha produced in the SCN but could also mediate effects of elevated TGF-alpha from tumors both within and outside the central nervous system.

Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signalling.

The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive daily rhythms of behaviour by secreting factors that act locally within the hypothalamus. In a systematic screen, we identified transforming growth factor (TGF)alpha as a likely SCN inhibitor of locomotion. TGFalpha is expressed rhythmically in the SCN, and when infused into the 3rd ventricle it reversibly inhibits locomotor activity and disrupts circadian sleep-wake cycles. These actions are mediated by epidermal growth factor (EGF) receptors, which we identified on neurons in the hypothalamic subparaventricular zone. Mice with a hypomorphic EGF receptor mutation exhibit excessive daytime locomotor activity and fail to suppress activity when exposed to light. These results implicate EGF receptor signalling in the daily control of locomotor activity, and they identify a neural circuit in the hypothalamus that likely mediates the regulation of behaviour both by the SCN and the retina.