Shore Paul M, Thomas Neal J, Clark Robert S B, Adelson P David, Wisniewski Stephen R, Janesko Keri L, Bayir Hülya, Jackson Edwin K, Kochanek Patrick M
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
J Neurotrauma. 2004 Sep;21(9):1113-22. doi: 10.1089/neu.2004.21.1113.
Drainage of cerebrospinal fluid (CSF) is routinely used in the treatment of severe traumatic brain injury (TBI), either continuously or intermittently in response to increases in intracranial pressure (ICP). There has been little study of the effect of CSF drainage method on the biochemistry, pathophysiology or outcome of TBI in adults or children. Having previously reported that a variety of markers of injury or repair increase in CSF after severe TBI, we chose to evaluate directly the effect of CSF drainage method on the biochemistry and volume of CSF drained as well as ICP. We hypothesized that concentrations of these markers would be similar in CSF drained continuously vs intermittently. We compared CSF levels of markers of neuronal injury (neuron specific enolase, [NSE]), glial injury (s100B), inflammation (interleukin-6 [IL-6]), and regeneration (vascular endothelial growth factor [VEGF]) (measured by ELISA) in 80 CSF samples from 19 severely injured children whose CSF was drained continuously (n = 13) versus intermittently (n = 6) as part of standard care in two institutions. Compared to continuous CSF drainage, intermittent drainage of CSF was associated with twofold greater CSF concentrations of NSE, s100B, IL-6 and VEGF (p < 0.05) and with about half the volume of CSF removal than continuous drainage (p = 0.002). The resulting elimination (concentration x volume) of these biochemicals, however, was not influenced by drainage method. Patients treated with continuous drainage had lower mean ICPs than those with intermittent drainage (13.6 +/- 0.69 vs. 21.8 +/- 0.95 mm Hg, p < 0.0001). We conclude that the method of CSF drainage greatly affects concentrations of CSF markers after TBI and may influence ICP. The influence of method on CSF marker concentration must be kept in mind when interpreting studies of CSF biomarkers. The striking difference in biomarker concentration, CSF volume drained, and ICP suggests the need for a randomized trial directly comparing these two approaches in infants and children with severe TBI.
脑脊液(CSF)引流常用于治疗重度创伤性脑损伤(TBI),根据颅内压(ICP)升高情况,可连续或间断进行。关于脑脊液引流方法对成人或儿童TBI的生物化学、病理生理学或预后影响的研究很少。此前我们曾报道,重度TBI后脑脊液中多种损伤或修复标志物会升高,因此我们选择直接评估脑脊液引流方法对脑脊液生物化学、引流脑脊液量以及颅内压的影响。我们假设连续引流与间断引流的脑脊液中这些标志物的浓度相似。我们比较了19名重度受伤儿童的80份脑脊液样本中神经元损伤标志物(神经元特异性烯醇化酶,[NSE])、胶质细胞损伤标志物(s100B)、炎症标志物(白细胞介素-6 [IL-6])和再生标志物(血管内皮生长因子[VEGF])(通过酶联免疫吸附测定法[ELISA]测量)的脑脊液水平,这些儿童来自两个机构,作为标准治疗的一部分,其脑脊液分别进行连续引流(n = 13)和间断引流(n = 6)。与连续脑脊液引流相比,间断引流的脑脊液中NSE、s100B、IL-6和VEGF浓度高出两倍(p < 0.05),且脑脊液排出量约为连续引流的一半(p = 0.002)。然而,这些生化物质的排出量(浓度×体积)不受引流方法的影响。接受连续引流治疗的患者平均颅内压低于间断引流患者(13.6 +/- 0.69 vs. 21.8 +/- 0.95 mmHg,p < 0.0001)。我们得出结论,脑脊液引流方法对TBI后脑脊液标志物浓度有很大影响,可能会影响颅内压。在解释脑脊液生物标志物研究时,必须考虑引流方法对脑脊液标志物浓度的影响。生物标志物浓度、脑脊液排出量和颅内压的显著差异表明,有必要进行一项随机试验,直接比较这两种方法在重度TBI婴幼儿中的效果。