Alexandra Nagel

INTRODUCTION: Hyperglycaemia following aneurysmal subarachnoid hemorrhage (SAH) is associated with complications and impaired neurological recovery. The aim of this study was to determine the effect of insulin treatment for glucose control on cerebral metabolism in SAH patients. METHODS: This prospective, nonrandomized study was conducted in 31 SAH patients in an intensive care unit (age 52 +/- 10 years, World Federation of Neurological Surgeons grade 2.9 +/- 1.6). A microdialysis catheter was inserted into the vascular territory of the aneurysm after clipping. Blood glucose levels above 140 mg/dl were treated with intravenous insulin and the microdialysates were analyzed hourly for the first 12 hours of infusion. RESULTS: No hypoglycaemia occurred. Twenty-four patients were treated with insulin for glucose control. Higher age and World Federation of Neurological Surgeons score were risk factors for need for insulin treatment (P < 0.05). Although blood glucose remained stable after initiation of insulin infusion, insulin induced a significant decrease in cerebral glucose at 3 hours after onset of the infusion until the end of the observation period (P < 0.05), reflecting high glucose utilization. The lactate:pyruvate ratio and glutamate did not increase, excluding ischaemia as possible cause of the decrease in glucose. Glycerol tended toward higher values at the end of the observation period (9 to 12 hours), reflecting either tissue damage after SAH or the beginning of cellular distress after insulin infusion. CONCLUSION: Higher SAH grade was among the risk factors for need for insulin. Intensive glycaemic control using insulin induced a decrease of cerebral glucose and a slight increase in glycerol, though blood glucose remained normal. Future studies might detect relevant metabolic derangements when insulin treatment starts at low cerebral glucose levels, and may allow us to design a strategy for avoidance of insulin-induced metabolic crisis in SAH patients.

BACKGROUND AND PURPOSE: We studied the dynamics of extracellular brain tissue concentrations of glucose, lactate, pyruvate, and glutamate during the occurrence of spreading depolarizations (SDs) in patients with aneurysmal subarachnoid hemorrhage. METHODS: In this prospective observational study, patients with aneurysmal subarachnoid hemorrhage received multimodal cerebral monitoring, including intracranial pressure, cerebral microdialysis, and subdural electrocorticography. RESULTS: Seven of the 17 recruited patients had intracerebral hemorrhage, acute ischemia and severe brain oedema leading to acute ischemic neurological deficits associated with early disturbance of metabolism at the recording site. They displayed a total of 130 SDs. The remaining 10 patients without acute ischemic neurological deficits exhibited 138 single SDs and 68 SDs in clusters. In patients without acute ischemic neurological deficits, clustered SDs were associated with a significant transient decrease in glucose and increase in lactate compared with baseline during the first 140 minutes after SDs. Moreover, the number of clustered SDs correlated with the outcome (R=-0.659; P<0.01). CONCLUSIONS: SDs can propagate in nonischemic human brain tissue. Clusters of SDs are related to metabolic changes suggestive of ongoing secondary damage in primarily nonischemic brain tissue.

OBJECT: Intracranial hypertension, defined as intracranial pressure (ICP) >/= 20 mm Hg, is a complication typically associated with head injury. Its impact on cerebral metabolism, ICP therapy, and outcome has rarely been studied in patients with aneurysmal subarachnoid hemorrhage (aSAH); such an assessment is the authors' goal in the present study. METHODS: Cerebral metabolism was prospectively studied in 182 patients with aSAH. The database was retrospectively analyzed with respect to ICP. Patients were classified into 2 groups based on ICP. There were 164 with low ICP (<20 mm Hg) and 18 with high ICP (>or=20 mm Hg, measured>6 hours/day). Cerebral microdialysis parameters of energy metabolism, glycerol, and glutamate levels were analyzed hourly from the brain parenchyma of interest for 7 days. The 12-month outcome in these patients was evaluated. RESULTS: In the high ICP group, extended ICP therapy including decompressive craniectomy was necessary in 7 patients (39%). Cerebral glycerol levels and the lactate/pyruvate ratio were pathologically increased on Days 1-7 after aSAH (p<0.001). The excitotoxic neurotransmitter glutamate and glycerol, a marker of membrane degradation, further increased on Days 5-7, probably reflecting the development of secondary brain damage. An ICP>or=20 mm Hg was shown to have a significant influence on the 12-month Glasgow Outcome Scale (GOS) score (p=0.001) and was a strong predictor of mortality (OR=24.6; p<0.001). Glutamate (p=0.012), the lactate/pyruvate ratio as a marker of anaerobic metabolism (p=0.028), age (p<0.001), and Fisher grade (p=0.001) also influenced the GOS score at 12 months. CONCLUSIONS: The authors confirmed the relevance of intracranial hypertension as a severe complication in patients with aSAH. Because high ICP is associated with a severely deranged cerebral metabolism and poor outcome, future studies focusing on metabolism-guided, optimized ICP therapy could help minimize secondary brain damage and improve prognosis in patients with aSAH.

OBJECTIVE: There is a rising debate about the role of inflammation in the pathogenesis of complications after aneurysmal subarachnoid hemorrhage (SAH) such as intracranial hypertension (intracranial pressure, ICP >20 mmHg). This study aimed to analyse the origin of interleukin-6 (IL-6) in respect to ICP and cerebral metabolism in SAH patients. METHODS: Prospectively, IL-6 was measured in three compartments, the extracellular fluid (ECF) monitored by cerebral microdialysis (MD), cerebrospinal fluid (CSF) and plasma for 10 days after SAH (days 0-4, three times daily; days 5-10, two times daily). Patients were classified having intracranial hypertension (n=7) or normal ICP (n=17) during 10 days after bleeding. Glasgow outcome scale (GOS) was assessed after 3 and 6 months. RESULTS: Patient groups were comparable for age, WFNS and Fisher grade. Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome. The data suggest the ECF but not the CSF as main origin of IL-6 in the systemic circulation in the presence of intracranial hypertension in SAH. DISCUSSION: Intracranial hypertension is associated with a strong activation of the inflammatory cascade in the brain and systemic circulation, and might be underestimated as proinflammmatory trigger in the pathogenesis of complications after SAH. Future therapies targeting anti-inflammatory response in plasma may help to reduce the inflammatory cascade responsible for development of intracranial hypertension.