Thiopental attenuates energetic impairment but fails to normalize cerebrospinal fluid glutamate in brain-injured patients

OBJECTIVES: Brain-injured patients are susceptible to secondary brain damage related to decreased cerebral perfusion pressure associated with edema formation and increased intracranial pressure (ICP). Whenever conventional therapy fails to reduce elevated ICP, barbiturate coma represents an additional intervention that may control ICP. In patients suffering from severe traumatic brain injury, cerebrospinal fluid levels of glutamate, hypoxanthine, and lactate were measured during barbiturate coma and correlated to electroencephalographic recordings and ICP. DESIGN: Prospective, descriptive study. SETTING: Ten-bed surgical intensive care unit in a university hospital. PATIENTS: Twenty-one patients with severe traumatic brain injury (Glasgow Coma Scale score < or = 9); 11 required barbiturate coma because of refractory intracranial hypertension, and 10 were manageable with continuous administration of fentanyl and midazolam. INTERVENTIONS: Thiopental was administered continuously for increased ICP within the first 24 hrs after trauma and adjusted to the burst-suppression pattern (four to six bursts per minute) on continuous electroencephalographic monitoring. MEASUREMENTS AND MAIN RESULTS: Glutamate and hypoxanthine were analyzed using high-performance liquid chromatography, whereas lactate was measured enzymatically. Patients requiring thiopental presented with significantly higher ICP, glutamate, and hypoxanthine levels than patients receiving fentanyl and midazolam (p < .05). Within the first 24 hrs, thiopental significantly reduced cerebrospinal fluid glutamate and hypoxanthine levels in all patients, i.e., the burst-suppression pattern was successfully induced (p < .001). Interestingly, in five patients cerebrospinal fluid glutamate increased to initial values again despite unchanged neuronal activity. In these patients, ICP, hypoxanthine, and lactate remained significantly elevated compared with the six patients with steadily decreasing cerebrospinal fluid glutamate, hypoxanthine, lactate, and ICP values (p < .02). CONCLUSIONS: Barbiturate coma does not unequivocally preserve energetic stability despite successful suppression of neuronal activity. Despite the use of barbiturate coma in patients with refractory intracranial hypertension, persistent release or impaired uptake of glutamate may be associated with continuous anaerobic metabolism, as shown by increases in cerebrospinal fluid hypoxanthine and lactate levels

Thiopental and midazolam do not seem to impede metabolism of glutamate in brain-injured patients

Increased extracellular glutamate levels are related to glial and neuronal damage. Glutamate-mediated toxicity is limited by glial uptake and metabolic transformation of glutamate to glutamine and the energetic compounds alanine and lactate which are utilized by surrounding neurons. Under in vitro conditions, barbiturates have been shown to reduce glutamate uptake and its further metabolism, possibly impeding metabolic coupling between astrocytes and neurons. The aims were to investigate if under clinical conditions, the barbiturate thiopental reduces important detoxification of glutamate, resulting in lower CSF glutamine, alanine and lactate levels as opposed to patients receiving midazolam. During long-term administration of thiopental and midazolam, pathologically elevated ventricular CSF glutamate levels were associated with significantly increased glutamine and alanine levels up to 14 days after trauma. CSF lactate, however, remained normal. These data suggest that long-term administration of thiopental and midazolam under clinical conditions does not impede enzymatic activities responsible for detoxification and metabolism of glutamate

Neurotransmitters in cerebrospinal fluid reflect pathological activity

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood-brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meningitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents

Humanistic Bildung: regulative idea or empty concept?

The article focuses on the notion and humanistic ideal of self-cultivation and self-transformation, for which the term Bildung is/was traditionally used in German educational thought. It is argued that the idea of Bildung, understood as human development and end-in-itself, is not a German exclusivity. However, to understand the specificity of the notion, it may be necessary to consider that German Enlightenment—Aufklärung—in which the term gained a lot of importance, came later in history than French, English, and Scottish Enlightenment. Whereas in the early Western Enlightenment period, freedom was understood as an outward, definitely political concept, in later German Enlightenment the predominant understanding of freedom was characterized by a rather aesthetic dimension, not outward but internal freedom. The shift from a political understanding of Enlightenment—like in France, and also England or Scotland—to German inwardness (“Innerlichkeit”), as realized by the concept of Bildung, can be—at least to a certain degree—interpreted as a desire of German intellectuals at the time to escape from a brutal and on the whole disappointing post-revolutionary world to a place where man could seek secular perfection: an escape toward inwardness

Civil society in Central and Eastern Europe: The ambivalent legacy of accession

Civil society organisations in Central and Eastern Europe (CEE) have remained weak players compared to their counterparts in established democracies. Given the particular incentives that the EU offered for the empowerment of non-state actors during pre-accession, it has often been assumed that EU intervention improved this situation. We argue that, instead, the EU's impact was highly ambivalent. Although the EU aid and EU-induced policy reform levelled the way for established actors' involvement in multilevel politics, it reinforced some of the barriers to development that the civil society organisations face in CEE. In particular, EU measures have failed to address the lack of sustainable income, of formalised interactions with the state and of grassroot support. Drawing on the experiences of trade unions and environmental groups, we show that this ambivalent 'legacy of accession' is due to an unfortunate interrelation between various, often implicit mechanisms of the EU's enlargement regime on one hand, and particular problems inherited from state socialism and transition on the other. Acta Politica (2010) 45, 41-69. doi: 10.1057/ap.2009.1