Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH. (J Neurol Neurosurg Psychiatry 2001;70:534-537) Keywords: subarachnoid haemorrhage; inflammatory cytokines; cerebral blood flow; vasospasm; cerebral ischaemia Subarachnoid haemorrhage (SAH) most commonly occurs when an aneurysm in a basal cerebral artery ruptures. Among patients who survive this event, the leading cause of death and disability is subsequent constriction of the large cerebral arteries causing delayed cerebral ischaemia, the "second stroke". 1 2 Monitoring of cerebral blood flow velocities (CBFVs) in the large pial arteries identifies patients with SAH with raised risk for ischaemic complications. [3][4][5][6] In SAH, it has been shown in multiple studies that CBFVs on transcranial Doppler sonography are inversely related to vessel diameters on angiography. [3][4][5][6] The noninvasive character of this technique enables serial investigations of developing haemodynamic abnormalities in an individual patient.Earlier studies described inflammatory changes in SAH-that is, subarachnoidal and perivascular leucocytic infiltrates in the subarachnoidal space 7-9 in relation to development of cerebral vasospasms. 8 9 Moreover, the proinflammatory cytokines interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-that orchestrate the cascade of inflammatory host response to infection and tissue damage 10 11 have been detected in the CSF of patients with SAH. [12][13][14][15][16] These earlier findings suggest an inflammatory pathogenesis of vasospasms in SAH. In this study, we tested the hypothesis that the extent and pattern of secretion of key mediators of inflammation IL-1 , IL-6, and TNFare associated with development of haemodynamic abnormalities in basal cerebral arteries and with clinical outcome. Patients and methods PATIENTS AND CONTROL SUBJECTSThirty five patients (21 women and 14 men), aged between 23 and 76 (median 56) years with SAH caused by aneurysmal rupture and presenting within 48 hours after onset of first symptoms were studied. Hunt and Hess scores to classify disease severity were 1 in 9%, 2 in 11%, 3 in 32%, 4 in 29%, and...

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Sleep is an integral part of human existence and is now, more than ever, the subject of clinical and research interest. Why do we spend approximately one third of our lives asleep? Sleep probably has a recovery function, especially for the brain. Throughout rapid eye movement sleep, neuronal connections in the catecholamine system are created, and this activity is essential to maintain cognitive function.w1 During rapid eye movement sleep in particular, the body is at its most relaxed state, and a three dimensional collapse of muscle (musculus genioglossus and musculus geniohyoideus) and fatty tissue around the upper airway may cause obstruction.1 When a pre-existent narrowing and slackening of the upper airway is also present, 2 apnoeas (complete cessation of breathing for 10 seconds or more) or hypopnoeas ( > 50% diminishing of airflow or oxygen desaturations > 3% for 10 seconds or more) may result. The prevalence of obstructive sleep apnoea in middle age is 2% for women and 4% for men.3 In practice, obstructive sleep apnoea seems to be under-reported; obstructive sleep apnoea is undiagnosed in an estimated 80% of patients. 4 Patients with obstructive sleep apnoea are particularly vulnerable during anaesthesia and sedation. w2This is not only the case for operations or other invasive interventions aiming at alleviation of obstructive sleep apnoea through reduction of the obstructive upper airway; even after surgery not related to obstructive sleep apnoea, such as hip and knee operations, patients with obstructive sleep apnoea are at risk of developing respiratory and cardiopulmonary complications postoperatively. Serious complications include reintubations and cardiac events.6 Anaesthetic management must focus on and deal with the increased likelihood of morphological alterations of the upper airway leading to an increased rate of difficulties in securing and maintaining a patent airway. 7In this review we discuss the various anaesthetic aspects of obstructive sleep apnoea, including preoperative, perioperative, and postoperative points of special interest. We also cover the various management options.

Background and Purpose-The most potent vasoconstrictor known, endothelin-1, is currently considered to mediate cerebral vasospasm in subarachnoid hemorrhage (SAH), which can cause delayed cerebral ischemia. In our study, we performed clinical and in vitro experiments to investigate the origin and the mechanisms of the secretion of endothelin-1 in SAH. Methods-Endothelin-1 and markers of inflammatory host response (interleukin [IL]-1␤, IL-6, and tumor necrosis factor-␣) were comparatively quantified in the cerebrospinal fluid (CSF) of SAH patients and control subjects, and concentrations were related to clinical characteristics. Furthermore, mononuclear leukocytes isolated from the CSF of SAH patients and control subjects were analyzed regarding their mRNA expression of endothelin-1 and inflammatory cytokines. Finally, complementary in vitro experiments were performed to investigate whether coincubation of blood and CSF can trigger leukocytic mRNA expression and release of these factors. Results-Activated mononuclear leukocytes in the CSF of SAH patients synthesize and release endothelin-1 in parallel with known acute-phase reactants (IL-1␤, IL-6, and tumor necrosis factor-␣). Complementary in vitro experiments not only further confirmed this leukocytic origin of endothelin-1 but also showed that aging and subsequent hemolysis of blood is sufficient to induce such endothelin-1 production. Conclusions-The demonstration that endothelin-1 is produced by activated CSF mononuclear leukocytes suggests that subarachnoid inflammation may represent a therapeutic target to prevent vasospasm and delayed cerebral ischemia after SAH. (Stroke. 2000;31:2971-2975.)