Monitoring in Neurointensive Care - The Challenge to Detect Delayed Cerebral Ischemia in High-Grade Aneurysmal SAH.

Delayed cerebral ischemia (DCI) is a feared and significant medical complication following aneurysmal subarachnoid hemorrhage (aSAH). It occurs in about 30% of patients surviving the initial hemorrhage, mostly between days 4 and 10 after aSAH. Clinical deterioration attributable to DCI is a diagnosis of exclusion and especially difficult to diagnose in patients who are comatose or sedated. The latter are typically patients with a high grade on the World Federation of Neurosurgical Societies scale (WFNS grade 4-5), who represent approximately 40-70% of the patient population with ruptured aneurysms. In this group of patients, the incidence of DCI is often underestimated and higher when compared to low WFNS grade patients. To overcome difficulties in diagnosing DCI, which is especially relevant in sedated and comatose patients, the article reports the most recent recommendation for definition of DCI and discusses their advantages and problematic issues in neurocritical care practice. Finally, appropriate neuromonitoring techniques and their clinical impact in high-grade SAH patients are summarized.

Intracranial hypotension after trauma.

INTRODUCTION: Intracranial hypotension (IH) occurs typically spontaneous and is a potentially life-threatening condition characterized by symptoms varying from postural headache to coma, with classical magnetic resonance imaging (MRI) findings. CASE DESCRIPTION: We report two cases of clinically relevant trauma-related IH and review of the literature. One patient with a cerebral trauma presented unilateral mydriasis and coma resolved by the Trendelenburg position (-20°) as urgency intervention. In the second patient, IH was caused by a lesion of the brachial plexus after a motor vehicle accident. DISCUSSION AND CONCLUSION: A history of mild or moderate trauma in association with prolonged postural or permanent headache may indicate IH. Posttraumatic IH is rare, nevertheless life-threatening in case of misdiagnosis. Intracranial hypotension in a trauma context is rarely described and difficult to diagnose. The change from tipical supine 30° to Trendelenburg position (0-20°) can be a life-saving manoeuver in these patients.

Clusters of spreading depolarizations are associated with disturbed cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage.

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.

Severe traumatic brain injury in children--a single center experience regarding therapy and long-term outcome.

OBJECT: The impact of intracranial pressure (ICP), decompressive craniectomy (DC), extent of ICP therapy, and extracranial complications on long-term outcome in a single-center pediatric patient population with severe traumatic brain injury (TBI) is examined. METHODS: Data of pediatric (≤16 years) TBI patients were retrospectively reviewed using a prospectively acquired database on neurosurgical interventions between April 1996 and March 2007 at the Charité Berlin. The patients' records, neuroimages, admission Glasgow Coma Scale (GCS) score, the time to craniectomy for hematoma evacuation/DC, and the extent of ICP therapy were reviewed. Twelve-month and long-term outcome was evaluated (Glasgow Outcome Scale). RESULTS: Fifty-three pediatric TBI patients [mean age 8.41 (0-16) years] were studied. Patients were categorized into two groups, with DC (n = 14) and without DC (n = 39). DC was performed 3 ± 3.98 median, quartiles 2 (0-3.75) days post-trauma. In the majority of children (n = 9; 64%), surgical decompression was performed early within 2 days post-trauma. (0.8 ± 0.9 days). The DC group tended to be older (median age 12 vs. 7 years, p = 0.052), had a lower GCS (3 vs. 6.5, p < 0.01), and had a 3-fold longer stay on the ICU (20 vs. 6.5 days, p < 0.03) compared to the conservatively treated group. Mean follow-up duration (n = 30) was 5.2 ± 2.4 years (range 1-10.5). At the most recent follow-up examination, 92% of survivors had returned to school. CONCLUSION: Though initial GCS was worse in pediatric TBI patients who underwent decompressive craniectomy compared to the conservatively treated patients, long-term outcome was comparable. In children, decompressive craniectomy might be favored early in the management of uncontrollable ICP.

Imaging of hypoxic-ischemic penumbra with (18)F-fluoromisonidazole PET/CT and measurement of related cerebral metabolism in aneurysmal subarachnoid hemorrhage.

This study aimed to characterize hypoxic, but salvageable, tissue imaged by (18)F-fluoromisonidazole ((18)F-FMISO), combining with perfusion-computed tomography (PCT) for regional cerebral blood flow (rCBF) measurement and metabolism by microdialysis (MD) in aneurysmal subarachnoidal hemorrhage (SAH) patients. (18)F-FMISO positron-emission tomography (PET)/CT was performed within the period of possible vasospasm (day 6.8+/-3 after SAH) in seven SAH patients. In parallel, rCBF was determined within the MD region of interest (MD-ROI) (n=5). The MD catheter was inserted into the brain parenchyma with highest risk for ischemia; extracellular levels of glutamate and energy metabolites were registered at time of PET and hourly for 10 days. Twelve-month outcome was evaluated. In asymptomatic patients (n=3) no hypoxia was detected and glutamate levels were low (<10 mmol/L), whereas symptomatic patients had higher glutamate concentrations (P<0.001). Increased (18)F-FMISO uptake within the MD-ROI (n=3) was related to higher glutamate levels, while rCBF was above the ischemic range. Hypoxia (increased (18)F-FMISO uptake) was present in symptomatic patients and associated with relevant metabolic derangement of extracellular glutamate levels, whereas energy metabolism and rCBF were preserved. This technique has the potential to improve our understanding of the role of cellular hypoxia in aneurysmal SAH.

Decompressive craniectomy in aneurysmal subarachnoid hemorrhage: relation to cerebral perfusion pressure and metabolism.

INTRODUCTION: Outcome is poor in aneurysmal subarachnoid hemorrhage (SAH) patients with intracranial hypertension. As one treatment option for increased intracranial pressure (ICP), decompressive craniectomy (DC) is discussed. Its impact on cerebral metabolism and outcome in SAH patients is evaluated in this pilot study. METHODS: A prospectively collected database of cerebral metabolism in SAH patients was analyzed retrospectively for individuals developing high ICP (>20 mmHg > 6 h/day, n = 18). Patients with intracranial hypertension were classified into groups with (n = 7) and without DC (n = 11). An age-matched control group was established (n = 89). Cerebral perfusion pressure (CPP) and high ICP treatment were analyzed for 7 days after SAH (or 72 h after craniectomy, respectively). Cerebral microdialysates were analyzed hourly. Twelve-month outcome was evaluated. RESULTS: Groups were comparable for age, WFNS grade, and outcome. ICP was significantly reduced by DC (P < 0.01), however, in 43% of patients the effect was transient. An increase in the lactate/pyruvate ratio (P < 0.001) and glycerol levels (>200 muM) was observed before DC. In the DC group, glucose (P = 0.005) and pyruvate (P = 0.04) were higher, while glycerol levels were lower (P = 0.007) compared to the non-DC group, reflecting better aerobic glucose utilization and reduced cellular stress. CONCLUSION: Outcome was poor in all SAH patients with intracranial hypertension. Although glucose utilization was improved after DC, no improvement in outcome could be shown for this small patient population. Future studies will have to demonstrate whether markers of cerebral crisis may support the decision for DC in aneurysmal SAH patients.

Preliminary evidence that ketamine inhibits spreading depolarizations in acute human brain injury.

BACKGROUND AND PURPOSE: Spreading depolarizations, characterized by large propagating, slow potential changes, have been demonstrated with electrocorticography in patients with cerebral hemorrhage and ischemic stroke. Whereas spreading depolarizations are harmless under normal conditions in animals, they cause or augment damage in the ischemic brain. A fraction of spreading depolarizations is abolished by N-methyl-d-aspartate receptor antagonists. Summary of Case- In 2 patients with severe acute brain injury (traumatic and spontaneous intracranial hemorrhage), spreading depolarizations were inhibited by the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine. This restored electrocorticographic activity. CONCLUSIONS: These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future neuroprotective trials.

Cerebral microdialysis for detection of bacterial meningitis in aneurysmal subarachnoid hemorrhage patients: a cohort study.

INTRODUCTION: Bacterial meningitis (BM) is a severe complication in patients with aneurysmal subarachnoid haemorrhage (SAH). Clinical signs of meningitis are often masked by SAH-related symptoms, and routine cerebrospinal fluid (CSF) analysis fails to indicate BM. Microdialysis (MD) is a technique for monitoring cerebral metabolism in patients with SAH. A cohort study was performed to investigate the value of MD for the diagnosis of BM. METHODS: Retrospectively, 167 patients with SAH in an ongoing investigation on cerebral metabolism monitored by MD were analysed for the presence of BM and related MD changes. Diagnosis of BM was based on microbiological CSF culture or clinical symptoms responding to antibiotic treatment, combined with an increased CSF cell count and/or fever. Levels of MD parameters before and after diagnosis of BM were analysed and compared with the spontaneous course in controls. RESULTS: BM developed in 20 patients, of which 12 underwent MD monitoring at the time of diagnosis. A control group was formed using 147 patients with SAH not developing meningitis. On the day BM was diagnosed, cerebral glucose was lower compared with the value three days before (p = 0.012), and the extent of decrease was significantly higher than in controls (p = 0.044). A decrease in cerebral glucose by 1 mmol/L combined with the presence of fever >or= 38 degrees C indicated BM with a sensitivity of 69% and a specificity of 80%. CSF chemistry failed to indicate BM, but the cell count increased during the days before diagnosis (p < 0.05). CONCLUSIONS: A decrease in MD glucose combined with the presence of fever detected BM with acceptable sensitivity and specificity, while CSF chemistry failed to indicate BM. In patients with SAH where CSF cell count is not available or helpful, MD might serve as an adjunct criterion for early diagnosis of BM.

Is continuous insulin treatment safe in aneurysmal subarachnoid hemorrhage?

OBJECTIVES: To investigate the long-term effect of continuous insulin infusion for glucose control on cerebral metabolism in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: Prospective, nonrandomized study of 31 SAH patients in the ICU (52 +/- 10 years, WFNS Grade 2.9 +/- 1.6). A microdialysis catheter was inserted into the vascular territory of the aneurysm. Metabolic changes during 4 days after onset of insulin infusion were analyzed. Blood glucose levels >140 mg/dL after clinical stabilization were treated with intravenous insulin. RESULTS: 24 patients were treated with intravenous insulin. Though no insulin-induced hypoglycemia occurred, cerebral glucose decreased on days 1-4 after insulin onset without reaching critical levels. Glycerol, a marker of membrane degradation, showed a reversible increase on day 1 while the lactate/pyruvate ratio remained stable and glutamate even decreased indicating absence of severe cerebral crisis following insulin infusion and excluding ischemia as a cause for cerebral glucose depletion. CONCLUSIONS: Concerning cerebral metabolism, long-term continuous insulin infusion appears to be safe as long as cerebral glucose levels do not fall below the physiological range. In view of the high incidence of hyperglycemia and need for insulin treatment, future studies on the effect of insulin on cerebral metabolism in SAH patients are desirable.

Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine whether hyperglycemia exerts deleterious effects via cerebral energy metabolism and to illuminate the effects of cerebral high/low glucose in patients with aneurysmal subarachnoid hemorrhage. DESIGN AND SETTING: Prospective, nonrandomized single-center study over a 2-year period in an intensive care unit at a primary-level university hospital. PATIENTS: 28 subarachnoid hemorrhage patients (age 53 +/- 10 years, WFNS grade 2.8 +/- 1.5) classified as asymptomatic (n = 5) or symptomatic with acute focal or delayed ischemic neurological deficits (n = 23). MEASUREMENTS AND RESULTS: Hyperglycemia (> 7.8 mmol/l; >140 mg/dl) was more frequent in symptomatic patients and was reflected in higher glycerol concentrations than in asymptomatic patients. In all patients a microdialysis catheter was inserted into the tissue at risk; dialysates were collected hourly for 10 days. Cerebral low-glucose episodes (0.6 mmol/l) and high-glucose episodes (>2.6 mmol/l) occurred independently of blood glucose levels. During high-glucose episodes cerebral microdialysate levels were normal, while cerebral low glucose, occurring more frequently in symptomatic patients, was associated with severe cellular distress (increase in lactate/pyruvate ratio, glutamate, glycerol) and with unfavorable outcome if combined with hyperglycemia. CONCLUSIONS: Although hyperglycemia was more frequent in symptomatic patients and associated with high glycerol levels, hyperglycemia was not related to cerebral high glucose. It appears that the association of adverse outcome with acute-phase hyperglycemia is not mediated by cerebral glucose metabolism. Cerebral low glucose was associated with severe metabolic distress and may present a target for therapy to improve clinical outcome.

Insulin-related decrease in cerebral glucose despite normoglycemia in aneurysmal subarachnoid hemorrhage.

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.

Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients.

BACKGROUND: Osmotic agents are widely used to lower elevated intracranial pressure (ICP). However, little data are available regarding cerebral oxygenation and metabolism in the traumatized brains studied under clinical conditions. The present prospective, open-labeled clinical study was designed to investigate whether administration of mannitol, with the aim of reducing moderate intracranial hypertension, improves cerebral metabolism and oxygenation in patients after severe traumatic brain injury (TBI). METHODS: Multimodal cerebral monitoring (MCM), consisting of intraparenchymal ICP, tissue oxygenation (ptiO2), and micro dialysis measurements was initiated in six male TBI patients (mean age 45 years; Glasgow Coma Scale score <9). A total of 14 mannitol boli (20%, 0.5g/kg, 20 minutes infusion time) were administered to treat ICP exceeding 20 mm Hg (2.7 kPa). Temporal alterations determined by MCM after mannitol infusions were recorded for 120 minutes. Microdialysates were assayed immediately for extracellular glucose, lactate, pyruvate, and glutamate concentrations. RESULTS: Elevated ICP was successfully treated in all cases. This effect was maximal 40 minutes after start of infusion (25 +/- 6 mm Hg [3.3 +/- 0.8 kPa] to 17 +/- 3 mm Hg [2.3 +/- 0.4 kPa], p < 0.05) and lasted up to 100 minutes. Cerebral ptiO2 remained unaffected (21 +/- 5 mm Hg [2.8 +/- 0.7 kPa] to 23 +/- 6 mm Hg [3.1 +/- 0.8 kPa], n.s.). Microdialysate concentrations of all analytes rose unspecifically by 10% to 40% from baseline, reaching maximum concentrations 40 to 60 minutes after start of the infusion. CONCLUSIONS: Mannitol efficiently reduces increased ICP. At an ICP of up to 30 mm Hg [4 kPa] it does not affect cerebral oxygenation. Unspecific increases of extracellular fluid metabolites can be explained by transient osmotic dehydration. Additional mechanisms, such as increased cerebral perfusion and blood volume, might explain an accelerated return to baseline.

Cerebral ischemia in aneurysmal subarachnoid hemorrhage: a correlative microdialysis-PET study.

BACKGROUND AND PURPOSE: Cerebral microdialysis (MD) is discussed as a technique for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical data on cerebral blood flow (CBF) are limited in these patients. The main objective of this study was to investigate whether pathological MD parameters reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET. METHODS: Thirteen subarachnoid hemorrhage patients (age, 48.7+/-15.0 years; World Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels were analyzed hourly. rCBF was determined in the volume of interest of the MD catheter and all vascular territories. MD values were correlated to rCBF on the day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day medians) were analyzed. RESULTS: In symptomatic patients (n=10), rCBF was significantly lower compared with controls (n=3, P=0.048). Glutamate correlated best with rCBF (r=-0.66; P=0.014), followed by glycerol (r=-0.62; P=0.021). The L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of ischemia, but only during longer periods of ischemia. CONCLUSIONS: rCBF correlates best with glutamate, followed by glycerol, whereas the L/P ratio is sensitive only after longer periods of ischemia. Clinically relevant regional metabolic derangements occur already above an rCBF of 20 mL x 100 g(-1).min(-1). Future research should focus on identifying alternative causes of metabolic derangement in subarachnoid hemorrhage patients and optimal treatment management in these patients.

Neuromonitoring: brain oxygenation and microdialysis.

Patients with cerebral lesions run a high risk of developing cerebral hypoxic and ischemic damage due to secondary insults. To minimize the risk of secondary cerebral hypoxia and ischemia, new monitoring techniques of cerebral oxygenation and metabolism have been developed and may help to understand the pathophysiology of secondary brain damage for a better treatment and outcome in critical patients. Cerebral microdialysis is a relatively new technique for measuring brain molecules of the extracellular space. The technical aspects, the interpretation of the commonly measured parameters, the use of the two commonly used oxygenation parameters (jugular venous oxygen saturation and monitoring of brain tissue PO(2) and the microdialysis technique to monitor cerebral metabolism in patients with head injury), subarachnoid hemorrhage, and ischemic stroke are considered. Pitfalls of the techniques and their future potential are discussed.

Bedside microdialysis: a tool to monitor cerebral metabolism in subarachnoid hemorrhage patients?

OBJECTIVE: To analyze the time course and changes of cerebral microdialysis parameters after aneurysmal subarachnoid hemorrhage (SAH) in respect to the clinical course (asymptomatic, delayed, and acute ischemic neurologic deficits) to evaluate the method of bedside microdialysis in these patients. DESIGN: Prospective, controlled study during a 3-yr period. SETTING: Neurosurgical intensive care unit at a primary level university hospital, supervised and staffed by members of both the department of neurosurgery and the department of anesthesiology and intensive care medicine. PATIENTS: Ninety-seven patients (51 females/21 males; 52 +/- 13 yrs; World Federation of Neurological Surgeons Scale grades 0-5) after aneurysmatic SAH. MEASUREMENTS AND MAIN RESULTS: A microdialysis catheter (CMA 100) was inserted into the region most likely to be affected by vasospasm directly after aneurysm clipping, connected to a pump, and perfused with Ringer solution (0.3 microL/min). The dialysates were collected hourly and analyzed at the bedside for glucose, lactate, lactate-pyruvate ratio, glutamate, and glycerol (CMA 600). Patients were classified according to clinical presentation as being asymptomatic or having acute (AIND) or delayed (DIND) ischemic neurologic deficits. DIND patients (n = 18) had significantly higher lactate and glutamate concentrations on days 1-8 post-SAH and a higher lactate-pyruvate ratio on days 3-8 post-SAH compared with asymptomatic patients (n = 57; p <.025). Glucose and glycerol levels did not differ in asymptomatic and DIND patients. AIND patients (n = 22) had the worst metabolic pattern: the extracellular glucose concentration was low, whereas the lactate, lactate-pyruvate ratio, glutamate, and glycerol levels were significantly elevated compared with asymptomatic and DIND patients. In 83% of the DIND patients, the changes in metabolites indicative of cerebral ischemia preceded the onset of symptomatic vasospasm. All DIND patients clinically improved in their Glasgow Coma Scale scores with induced hypertension, intentional hypervolemia, and/or hemodilution therapy (p =.01). CONCLUSION: Cerebral bedside microdialysis is a safe and promising technique for monitoring (impending) regional cerebral ischemia. The dialysate changes can indicate early the onset of delayed neurologic deterioration and are in good accordance with the clinical course of SAH patients. In the future, this technique may be used to monitor the efficacy of the intensive care therapy of these patients.