Use of bispectral index to monitor the depth of sedation in mechanically ventilated patients in the prehospital setting.

BACKGROUND: Sedative drug administration is a challenging aspect of the management of mechanically ventilated patients in the out-of-hospital critical care medicine. We hypothesised that the bispectral index of the EEG (BIS) could be a helpful tool in evaluating the depth of sedation in this difficult environment. The main objective of the present study was to assess the agreement of BIS with the clinical scales in the out-of-hospital setting. METHODS: This prospective study included mechanically ventilated patients. BIS values were blindly recorded continuously. A Ramsay score was performed every 5 min. The main judgement criterion was the correlation between BIS values and the Ramsay score. RESULTS: 72 patients were included, mostly presenting with toxic coma (36%) or neurological coma (21%). The median (IQR) BIS value was 85 (84-86) when the Ramsay score was 3, 80 (76-84) when the Ramsay score was 4, 61 (55-80) when the Ramsay score was 5 and 45 (38-60) when the Ramsay score was 6. According to Receiver operating characteristic (ROC) curves, BIS was categorised into three classes (BIS<54 corresponding to Ramsay score 6, 54≤BIS<72 for Ramsay score 5 and BIS≥73 for Ramsay score ≤4). Based on these categories, the proportion of appropriate BIS values was 67% (217/323). The concordance correlation coefficient for repeated measurements was 0.54 (0.43-0.64). The agreement between BIS and the Ramsay score is moderate. CONCLUSIONS: Prehospital measured BIS values appear poorly correlated with clinical assessment of the depth of sedation. For this reason, the use of BIS to guide prehospital sedation cannot be recommended.

Neurosphere-derived neural cells show region-specific behaviour in vitro.

Neurosphere cultures provide a useful model to study neural stem/progenitor cells (NSC/NPCs). The degree to which neurospheres (NS) retain their regional identity in vitro has, however, been questioned. Here, NS obtained from mouse embryonic cortex, striatum or spinal cord were compared after differentiation. Neurons from cortical NS formed well ordered clusters containing astrocytes, those from striatal NS formed an external ring at the borderof the astrocyte layer, whereas those from spinal cord NS spread radially like the astrocytes. Such in-vitro neural behaviour was region-specific and persisted in clonal conditions, providing evidence of the maintenance of positional cues in NS cultures.

Exogenous and fibroblast growth factor 2/epidermal growth factor-regulated endogenous cytokines regulate neural precursor cell growth and differentiation.

Neurospheres (NSs) are clonal cellular aggregates composed of neural stem cells and progenitors. A comprehensive description of their proliferation and differentiation regulation is an essential prerequisite for their use in biotherapies. Cytokines are essential molecules regulating cell precursor fate. Using a gene-array strategy, we conducted a descriptive and functional analysis of endogenous cytokines and receptors expressed by spinal cord-derived NSs during their growth or their differentiation into neuronal and glial cells. NSs were found to express approximately 100 receptor subunits and cytokine/secreted developmental factors. Several angiogenic factors and receptors that could mediate neural precursor cell-endothelial cell relationships were detected. Among them, receptor B for endothelins was highly expressed, and endothelins were found to increase NS growth. In contrast, NSs express receptors for ciliary neurotrophic factor (CNTF), bone morphogenetic protein (BMP), interferon (IFN)-gamma, or tumor necrosis factor (TNF)-alpha, which, when added in the growth phase, led to a dramatic growth reduction followed by a reduction or a loss of oligodendrocyte formation on differentiation. In addition, NSs synthesize fibroblast growth factor 2/epidermal growth factor (FGF2/EGF)-regulated endogenous cytokines that participate in their growth and differentiation. Notably, BMP-7 and CNTF were expressed during expansion, but upon differentiation there was a remarkable switch from BMP-7 to BMP-4 and -6 and a sharp increase of CNTF. Reintroduction of growth factors reverses the BMP expression profile, indicating growth factor-BMP cross-regulations. The role of endogenous CNTF was investigated by deriving NSs from CNTF knockout mice. These NSs have an increased growth rate associated with reduction of apoptosis and generate astrocytes with a reduced glial fibulary acidic protein (GFAP) content. These results demonstrate the combined role of endogenous and exogenous cytokines in neural precursor cell growth and differentiation.