Microdialysis patterns in subarachnoid hemorrhage patients with focus on ischemic events and brain interstitial glutamine levels

Background  This observational microdialysis (MD) study of 33 subarachnoid hemorrhage patients explores brain interstitial levels of glutamine, glutamate, lactate and pyruvate, and their relationship to clinical status and clinical course at the neurointensive care unit. Methods  The focus was on ischemic events, defined by clinical criteria or by radiology, and the significance of brain interstitial glutamine levels and lactate/pyruvate (L/P) ratio. Results  Eleven out of 12 periods with an ischemic MD pattern, defined as lactate/pyruvate (L/P) ratios exceeding 40, were either related to delayed ischemic neurological deficits (DIND) or CT-verified infarcts, confirming that L/P above 40 is a specific ischemic and pathological MD measure. Poor admittance WFNS grade (WFNS 4–5) patients had lower glutamine at the onset of monitoring than what good admittance WFNS grade (WFNS 1–3) patients had (P < 0.05). Interstitial glutamine increased over time in most patients. A “glutamine surge” was defined as a period where the interstitial glutamine concentration increased at least 150 μM over 12 h. Fifteen patients had a DIND and associated MD patterns were glutamine surges (n = 12) and/or L/P>40 (n = 6). Seven patients received vasospasm treatment; in five of these the only DIND-associated MD pattern was a glutamine surge. Seventy percent of the glutamine surges occurred during ongoing propofol sedation, and there was no association between extubations and glutamine surges. There was no difference in mean glutamine levels during the monitoring period between patients with favorable 6-month outcome and patients with poor 6-month outcome. Conclusion  We suggest that an increasing interstitial glutamine trend is a dynamic sign of augmented astrocytic metabolism with accelerated glutamate uptake and glutamine synthesis. This pattern is presumably present in metabolically challenged, but yet not overt ischemic tissue.     

Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients

BACKGROUND: Using cerebral microdialysis, baseline values for energy-related chemical markers have been reported in awake patients. Radionuclide studies have demonstrated a locally decreased metabolism, thought to be the result of brain retraction. These baseline values, however, may not be applicable to patients after surgical aneurysm repair following a subarachnoid hemorrhage (SAH). We assessed metabolic chemical marker levels in World Federation of Neurological Surgeons Committee (WFNS) grade I SAH patients after aneurysm surgery and compared them with previously reported baseline values. METHODS: In 5 WFNS grade I SAH patients, energy-related chemical marker levels were obtained using microdialysis in the area of brain retraction after aneurysm surgery. In addition, an [(18)F]2-deoxy-d-glucose positron emission tomography (FDG-PET) was performed. RESULTS: The FDG-PET showed a decrease of glucose metabolism in the frontotemporal area. Comparing the mean values for chemical markers of this study with reported baseline values, the most striking difference was a mild decrease of pyruvate and an increase of the lactate/pyruvate ratio. In individual patients, some markers indicated possible ischemia. A consistent pattern or ischemic profile for all markers, however, was not found. CONCLUSION: FDG-PET scanning confirmed postoperative metabolic changes found in previous studies. Mean interstitial chemical marker levels ranged from normal to mildly deviant compared with reference chemical marker levels for awake patients and are likely to be applicable in SAH patients after aneurysm repair.     

Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolisms in patients with aneurysmal subarachnoid hemorrhage

OBJECT: The success of treatment for delayed cerebral ischemia is time dependent, and neuronal monitoring methods that can detect early subclinical levels of cerebral ischemia may improve overall treatment results. Cerebral microdialysis may represent such a method. The authors' goal was to characterize patterns of markers of energy metabolism (glucose, pyruvate, and lactate) and neuronal injury (glutamate and glycerol) in patients with subarachnoid hemorrhage (SAH), in whom ischemia was or was not suspected. METHODS: By using low-flow intracerebral microdialysis monitoring, central nervous system extracellular fluid concentrations of glucose, pyruvate, lactate, glutamate, and glycerol were determined in 46 patients suffering from poor-grade SAH. The results in two subgroups were analyzed: those patients with no clinical or radiological signs of cerebral ischemia (14 patients) and those who succumbed to brain death (five patients). Significantly lower levels of energy substrates and significantly higher levels of lactate and neuronal injury markers were observed in patients with severe and complete ischemia when compared with patients without symptoms of ischemia (glucose 0 compared with 2.12+/-0.15 mmol/L; pyruvate 0 compared with 151+/-11.5 micromol; lactate 6.57+/-1.07 compared with 3.06+/-0.32 mmol/L; glycerol 639+/-91 compared with 81.6+/-12.4 micromol; and glutamate 339+/-53.4 compared with 14+/-3.33 micromol). Immediately after catheter placement, glutamate concentrations declined over the first 4 to 6 hours to reach stable values. The remaining parameters exhibited stable values after 1 to 2 hours. CONCLUSIONS: The results confirm that intracerebral microdialysis monitoring of patients with SAH can be used to detect patterns of cerebral ischemia. The wide range from normal to severe ischemic values calls for additional studies to characterize further incomplete and possible subclinical levels of ischemia.     

Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage

OBJECT: In the treatment of patients with aneurysmal subarachnoid hemorrhage (SAH), early occlusion of the aneurysm is necessary as well as monitoring and treatment of complications following the primary bleeding episode. Monitoring with microdialysis has been studied for its ability to indicate and predict the occurrence of delayed ischemic neurological deficits (DINDs) in patients with SAH. METHODS: In 42 patients with aneurysmal SAH microdialysis monitoring of metabolites was performed using a 0.3-microl/minute perfusion flow over several days, and the results were correlated to clinical events and to brain infarction observed on computerized tomography scans. The microdialysis probe was inserted into the territory of the parent artery of the aneurysm. The authors defined an ischemic pattern as increases in the lactate/glucose (L/G) and lactate/pyruvate (L/P) ratios that were greater than 20% followed by a 20% increase in glycerol concentration. This ischemic pattern was found in 17 of 18 patients who experienced a DIND and in three of 24 patients who did not experience a delayed clinical deterioration. The ischemic pattern preceded the occurrence of a DIND by a mean interval of 11 hours. Maximum L/G and L/P ratios did not correlate with the presence of DIND or outcome, and there was no association between the glycerol level and subsequent brain infarction. CONCLUSIONS: Microdialysis monitoring of the cerebral metabolism in patients with SAH may predict with high sensitivity and specificity the occurrence of a DIND. Whether an earlier diagnosis results in better treatment of DINDs and, therefore, in overall better outcomes remains to be proven, as it is linked to an efficacious treatment of cerebral vasospasm.     

Ultra-early surgery for aneurysmal subarachnoid hemorrhage: outcomes for a consecutive series of 391 patients not selected by grade or age

OBJECT: This study was undertaken to determine the outcomes in an unselected group of patients treated with semiurgent surgical clipping of aneurysms following subarachnoid hemorrhage (SAH). METHODS: A clinical management outcome audit was conducted to determine outcomes in a group of 391 consecutive patients who were treated with a consistent policy of ultra-early surgery (all patients treated within 24 hours after SAH and 85% of them within 12 hours). All neurological grades were included, with 45% of patients having poor grades (World Federation of Neurosurgical Societies [WFNS] Grades IV and V). Patients were not selected on the basis of age; their ages ranged between 15 and 93 years and 19% were older than 70 years. The series included aneurysms located in both anterior and posterior circulations. Eighty-eight percent of all patients underwent surgery and only 2.5% of the series were selectively withdrawn (by family request) from the prescribed surgical treatment. In patients with good grades (WFNS Grades I-III) the 3-month postoperative outcomes were independence (good outcome) in 84% of cases, dependence (poor outcome) in 8% of cases, and death in 9%. In patients with poor grades the outcomes were independence in 40% of cases, dependence in 15% of cases, and death in 45%. There was a 12% rate of rebleeding with all cases of rebleeding occurring within the first 12 hours after SAH; however, outcomes of independence were achieved in 46% of cases in which rebleeding occurred (43% mortality rate). Rebleeding was more common in patients with poor grades (20% experienced rebleeding, whereas only 5% of patients with good grades experienced rebleeding). CONCLUSIONS: The major risk of rebleeding after SAH is present within the first 6 to 12 hours. This risk of ultra-early rebleeding is highest for patients with poor grades. Securing ruptured aneurysms by surgery or coil placement on an emergency basis for all patients with SAH has a strong rational argument.     

Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes

OBJECTIVE: A prospective observational study was conducted to investigate whether episodes of ischemia are detected by continuous cerebral monitoring and whether such episodes are related to clinical outcome. METHODS: Forty patients (35 after subarachnoid hemorrhage and 5 after complex aneurysm surgery) were monitored for a total of 174 days (mean, 4 d; range, 1-12 d). Brain tissue partial pressures of oxygen and carbon dioxide, pH, and temperature were measured continuously using Neurotrend sensors (Codman, Bracknell, England). Bedside analysis of extracellular chemistry was performed hourly using microdialysis. Glasgow Outcome Scale score was assessed at 3 to 6 months. RESULTS: Patients with poor World Federation of Neurosurgical Societies grades (4 and 5) or an unfavorable outcome (severe disability or death) had, on average, higher lactate and lactate/pyruvate ratio but lower glucose/lactate ratio (P < or = 0.05). Brain tissue partial pressure of oxygen decreased to below 1.1 kPa in 78% of the patients for 18% (95% confidence interval, 12-24%) of time monitored. There were 197 episodes in which brain tissue partial pressures of oxygen decreased to below 1.1 kPa for at least 30 minutes. Unfavorable outcome was associated with more of these episodes (8.8 episodes; 95% confidence interval, 4.4-13.2 episodes) than favorable outcome (2.2 episodes; 95% confidence interval, 1.1-3.3 episodes), as well as an episode of glutamate levels of more than 10 micromol/L or lactate/pyruvate ratio more than 40 (P < 0.05, chi(2) test). CONCLUSION: Intraparenchymal oximetry and microdialysis can detect but fail to predict the development of delayed cerebral ischemia. There were associations between episodes of low brain oxygen, abnormal microdialysis, and unfavorable outcome, but these associations were weak.     

Japanese Subarachnoid Aneurysm Trial of Neurosurgical Clipping versus Endovascular Coiling in 1863 Patients with Ruptured Intracranial Aneurysms

This is a post hoc multivariate analysis of the modified World Federation of Neurosurgical Societies (WFNS) grading project, multicenter prospective observational study including 38 neurosurgical institutions across Japan. Japan Neurosurgical Society WFNS grading committee conducted a modified WFNS grading project as a nationwide prospective registry study. We investigate the clinical outcome of both surgical and endovascular interventions after aneurysmal subarachnoid hemorrhage (SAH) in Japan. A total of 792 patients received surgical intervention and 417 patients received endovascular treatment. Eight hundred patients were female, and 409 patients were male. The mean age was 61.5 ± 13.7 years. At 3 month follow-up, there was no statistically significant difference in good clinical outcome between surgical (68.2%) and endovascular (60.9%) group (odds ratio, 0.89; 95% confidence interval, 0.68-1.16; p = 0.381). Unfavorable outcome rate was 31.8% (238 patients) in the surgical group and 39.1% (154 patients) in the endovascular group. Male, elderly people, modified Rankin scale condition before onset, high-grade modified WFNS clinical grading scale, intracerebral hematoma, posttreatment normal pressure hydrocephalus, and neurological deficit due to symptomatic vasospasm were risk factors for the clinical outcome. Treatment modality was not a statistical factor for clinical outcomes. Surgical clipping has still a major role in the management of SAH in Japan. The present study was not a randomized controlled study, but clinical outcome is not influenced by treatment modalities.     

The Stimulation of Vascular Smooth Muscle Oxidative Metabolism by CSF from Subarachnoid Haemorrhage Patients Increases with Fisher and WFNS Grades

Summary  The purpose of this paper is to present an in vitro method for examining cerebral vasospasm after subarachnoid haemorrhage (SAH) which correlates to the patients' condition. The O₂ consumption of the porcine carotid artery was monitored, using an oxygen electrode, after exposure to cerebrospinal fluid (CSF) from patients who had a SAH. The vessels were exposed to CSF from SAH patients at a 1 in 30 dilution. Force measurements were carried out using freeze-dried CSF, reconstituted in the organ bath equivalent to undiluted CSF. These observations were then compared to the patients' condition.  We divided the patient CSF samples into those that stimulated oxygen consumption above 0.4 μM/min/g dry wt, and those that did not. It was found that there was a correlation between the stimulation of oxygen consumption and the Fisher grade as well as the World Federation of Neurosurgeons Grading System (WFNS) for the patients. Of the CSF tested, 24 stimulated oxygen consumption above our cut off, and 8 did not (0.84±0.34, n=24 compared with the rate of 0.27±0.1 μmol/min/g dry wt, respectively; SD n=8) at 180 minutes. We then examined the Fisher Grades of these two groups, the results were 3.21±0.88 vs 2.25±0.83 respectively (SD p≤0.01). When examining the WFNS System we found a similar difference between the groups that stimulated respiration and those who did not (WFNS Grades of 2.64±1.1 vs. 1.43±0.53; p≤0.01). The observed stimulation of oxygen consumption also correlated with tension generation in vitro.  The CSF from subarachnoid haemorrhage patients stimulates the oxygen consumption of the porcine carotid artery. This stimulation correlated to the WFNS and Fisher Grades of the patients and can be performed using 1:30 dilution of CSF. We conclude that the metabolic changes that occur in the vessels during vasospasm are important parameters for assessing cerebral vasospasm.     

A combined microdialysis and FDG-PET study of glucose metabolism in head injury

Background  Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Positron emission tomography (PET) establishes metabolism of the whole brain but only for the scan’s duration. This study’s objective was to apply these techniques together, in patients with traumatic brain injury, to assess the relationship between microdialysis (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate (L/P) ratio as a marker of anaerobic metabolism) and PET parameters of glucose metabolism using the glucose analogue [¹⁸F]-fluorodeoxyglucose (FDG). In particular, we aimed to determine the fate of glucose in terms of differential metabolism to pyruvate and lactate. Materials and methods  Microdialysis catheters (CMA70 or CMA71) were inserted into the cerebral cortex of 17 patients with major head injury. Microdialysis was performed during FDG-PET scans with regions of interest for PET analysis defined by the location of the gold-tipped microdialysis catheter. Microdialysate analysis was performed on a CMA600 analyser. Findings  There was significant linear relationship between the PET-derived parameter of glucose metabolism (regional cerebral metabolic rate of glucose; CMRglc) and levels of lactate (r = 0.778, p < 0.0001) and pyruvate (r = 0.799, p < 0.0001), but not with the L/P ratio. Conclusion  The results suggest that in this population of patients, glucose was metabolised to both lactate and pyruvate, but was not associated with an increase in the L/P ratio. This suggests an increase in glucose metabolism to both lactate and pyruvate, as opposed to a shift towards anaerobic metabolism.     

Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study

OBJECT: The authors investigated the effects of hyperoxia on brain tissue PO2 and on glucose metabolism in cerebral and adipose tissue after traumatic brain injury (TBI). METHODS: After 3 hours of ventilation with pure O2, 18 tests were performed on different days in eight comatose patients with TBI. Lactate, pyruvate, glucose, glutamate, and brain tissue PO2 were measured in the cerebral extracellular fluid (ECF) by using microdialysis. Analytes were also measured in the ECF of abdominal adipose tissue. After 3 hours of increase in the fraction of inspired O2, brain tissue PO2 rose from the baseline value of 32.7 +/- 18 to 122.6 +/- 45.2 mm Hg (p < 0.0001), whereas brain lactate dropped from its baseline (3.21 +/- 2.77 mmol/L), reaching its lowest value (2.90 +/- 2.58 mmol/L) after 3 hours of hyperoxia (p < 0.01). Pyruvate dropped as well, from 153 +/- 56 to 141 +/- 56 micromol/L (p < 0.05), so the lactate/pyruvate ratio did not change. No significant changes were observed in glucose and glutamate. The arteriovenous difference in O2 content dropped, although not significantly, from a baseline of 4.52 +/- 1.22 to 4.15 +/- 0.76 m/100 ml. The mean concentration of lactate in adipose tissue fell significantly as well (p < 0.01), but the lactate/pyruvate ratio did not change. CONCLUSIONS: Hyperoxia slightly reduced lactate levels in brain tissue after TBI. The estimated redox status of the cells, however, did not change and cerebral O2 extraction seemed to be reduced. These data indicate that oxidation of glucose was not improved by hyperoxia in cerebral and adipose tissue, and might even be impaired.     

Relationship between intracranial pressure and other clinical variables in patients with aneurysmal subarachnoid hemorrhage

OBJECT: Increased intracranial pressure (ICP) is well known to affect adversely patients with head injury. In contrast, the variables associated with ICP following aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have been less intensely studied. METHODS: In this retrospective study the authors reviewed a prospective observational database cataloging the treatment details in 433 patients with SAH who had undergone surgical occlusion of an aneurysm as well as ICP monitoring. All 433 patients underwent postoperative ICP monitoring, whereas only 146 (33.7%) underwent both pre- and postoperative ICP monitoring. The mean maximal ICP was 24.9 +/- 17.3 mm Hg (mean +/- standard deviation). During their hospital stay, 234 patients (54%) had elevated ICP (> 20 mm Hg), including 136 of those (48.7%) with a good clinical grade (Hunt and Hess Grades I-III) and 98 (63.6%) of the 154 patients with a poor grade (Hunt and Hess Grades IV and V) on admission. An increased mean maximal ICP was associated with several admission variables: worse Hunt and Hess clinical grade (p < 0.0001), a lower Glasgow Coma Scale (GSC) motor score (p < 0.0001); worse SAH grade based on results of computerized tomography studies (p < 0.0001); intracerebral hemorrhage (p = 0.024); severity of intraventricular hemorrhage (p < 0.0001); and rebleeding (p = 0.0048). Both intraoperative cerebral swelling (p = 0.0017) and postoperative GCS score (p < 0.0001) were significantly associated with a raised ICP. Variables such as patient age, aneurysm size, symptomatic vasospasm, intraoperative aneurysm rupture, and secondary cerebral insults such as hypoxia were not associated with raised ICP. Increased ICP adversely affected outcome: 71.9% of patients with normal ICP demonstrated favorable 6-month outcomes postoperatively, whereas 63.5% of patients with ICP between 20 and 50 mm Hg and 33.3% with ICP greater than 50 mm Hg demonstrated favorable outcomes. Among 21 patients whose raised ICP did not respond to mannitol therapy, all experienced a poor outcome and 95.2% died. Among 145 patients whose elevated ICP responded to mannitol, 66.9% had a favorable outcome and only 20.7% were dead 6 months after surgery (p < 0.0001). According to results of multivariate analysis, however, ICP was not an independent outcome predictor (odds ratio 1.26, 95% confidence interval 0.28-5.68). CONCLUSIONS: Increased ICP is common after SAH, even in patients with a good clinical grade. Elevated ICP post-SAH is associated with a worse patient outcome, particularly if ICP does not respond to treatment. This association, however, may depend more on the overall severity of the SAH than on ICP alone.     

Transluminal balloon angioplasty improves brain tissue oxygenation and metabolism in severe vasospasm after aneurysmal subarachnoid hemorrhage: case report

OBJECTIVE AND IMPORTANCE: The effect of transluminal balloon angioplasty on cerebral biochemical monitoring during treatment of severe cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. CLINICAL PRESENTATION: In a 36-year-old man, an anterior communicating artery aneurysm caused an SAH (Hunt and Hess Grade IV, Fisher Grade III). After clipping, intraparenchymal monitoring (intracranial pressure, brain tissue oxygen tension [P(ti)O(2)], and microdialysis sampling of extracellular glucose, lactate, pyruvate, and glutamate) was initiated. Flow velocities obtained by transcranial Doppler sonography increased in the internal carotid artery (ICA)/middle cerebral artery bilaterally. INTERVENTION: After a decrease of P(ti)O(2) to less than 2 mm Hg and an increase of the lactate-to-pyruvate ratio to 44 in the territorial region of the left ICA, angiography demonstrated a 70 to 80% stenosis of the left ICA, which was dilated by a temporary occlusion balloon. This maneuver normalized the ICA diameter, P(ti)O(2) increased immediately from 1.5 to 40 mm Hg, the lactate-to-pyruvate ratio decreased from 44 to 30, and extracellular glucose increased from 0.4 to 0.9 mmol/L. No major changes in glutamate or intracranial pressure were seen. In the clinical follow-up, the patient showed a good recovery 6 months after SAH. CONCLUSION: Transluminal balloon angioplasty led to a continuous and effective resolution of cerebral vasospasm observed by sustained, improved cerebral biochemical parameters. Both P(ti)O(2) and lactate-to-pyruvate ratio might provide an early diagnosis of severe cerebral vasospasm after SAH and continuous surveillance of threatened tissue regions after transluminal balloon angioplasty.     

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

Objective： To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury （STBI） using clinical microdialysis. Methods：Thirty-one patients with STBI （ GCS ≤ 8 ） were randomly divided into hypothermic group （Group A ） and control group（ Group B）. Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA mlcrodialysis analyzer. Results. In comparison with the control group, lactate/glucose ratio （ L/G ）, lactate/pyruvate ratio （ L/P ） and glycerol（Gly） in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perileusional tissue was higher than that in relative normal brain. Conclusions： Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in ＂ normal brain＂ tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.     

Correlation of serum brain natriuretic peptide with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage

OBJECTIVE: Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and may exacerbate delayed ischemic neurological deficits. We examined the temporal relationship between serum BNP elevation, hyponatremia, and the onset of delayed ischemic neurological deficits and determined whether serum BNP levels correlated with the 2-week outcome after SAH. METHODS: Serum BNP and sodium were measured prospectively every 12 hours for 14 days in 40 consecutive patients admitted with SAH. All patients remained euvolemic, underwent transcranial Doppler assessment every 48 hours, and underwent angiography at the onset of delayed neurological deficits. New-onset neurological deficits were attributed to vasospasm only in the absence of other causes and when supported by transcranial Doppler or cerebral angiography. RESULTS: Sixteen patients (40%) experienced symptomatic cerebral vasospasm after SAH. A more than threefold increase in admission serum BNP was associated with the onset of hyponatremia (P < 0.05). Mean BNP levels were similar between vasospasm and nonvasospasm patients fewer than 3 days after SAH (126 +/- 39 pg/ml versus 154 +/- 40 pg/ml; P = 0.61) but were elevated in the vasospasm cohort 4 to 6 days after SAH (285 +/- 67 pg/ml versus 116 +/- 30 pg/ml; P < 0.01), 7 to 9 days after SAH (278 +/- 72 pg/ml versus 166 +/- 45 pg/ml; P < 0.01), and 9 to 12 days after SAH (297 +/- 83 pg/ml versus 106 +/- 30 pg/ml; P < 0.01). BNP level remained independently associated with vasospasm adjusting for Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval, 1.1-1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4-fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after vasospasm onset. Patients with increasing BNP levels from admission demonstrated no change (0 +/- 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 +/- 2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without increasing serum BNP levels. CONCLUSION: Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.     

Natural hypothermia immediately after transient global cerebral ischemia induced by spontaneous subarachnoid hemorrhage

OBJECT: Spontaneous subarachnoid hemorrhage (SAH) has an aspect of graded transient global cerebral ischemia. The purpose of the present study was the documentation of sequential changes in body temperature immediately after SAH-induced transient global cerebral ischemia in humans. METHODS: Patients admitted within 12 hours after the initial onset of SAH were examined retrospectively (426 patients). Patients with unruptured cerebral aneurysms served as a control group (73 patients). Body temperature measured at the axilla on admission was analyzed. The grade of SAH was established according to the Glasgow Coma Scale (GCS): Grade I, GCS Score 15; Grade II, GCS Score 11 to 14; Grade III, GCS Score 8 to 10; Grade IV, GCS Score 4 to 7; and Grade V, GCS Score 3. The mean body temperature of patients in the control group was 36.49 +/- 0.45 degrees C (mean +/- standard deviation). The mean body temperature of patients in the SAH group who had been admitted within 4 hours of onset for Grades I to V were significantly different (p < 0.001, analysis of variance [ANOVA]): 36.26 +/- 0.7 degrees C, 59 patients; 35.98 +/-0.85 degrees C, 73 patients; 35.52 +/- 0.79 degrees C, 25 patients; 35.9 +/- 1.09 degrees C, 108 patients; and 35.56 +/- 1.14 degrees C, 73 patients, respectively. These values were significantly lower than those in control volunteers, except for patients with Grade I SAH. The reduction in body temperature was unrelated to the location of the cerebral aneurysm and was not the product of circadian rhythm. The temperatures of patients in the SAH group who were admitted beyond 4 hours after onset for each grade were significantly different (p < 0.01, ANOVA): 36.8 +/- 0.91 degrees C, 36 patients; 36.74 +/- 0.68 degrees C, 31 patients; 36.73 +/- 0.38 degrees C, three patients; 37.41 +/- 1.37 degrees C, 17 patients; and 38.9 degrees C, one patient, respectively. These values were significantly higher than those in patients admitted within 4 hours of SAH onset for all grades except Grade V, and significantly higher than control values in patients with Grades I and IV SAH. CONCLUSIONS: These results indicate that body temperature falls and then rises immediately after the SAH-induced transient global cerebral ischemia without cardiac arrest in humans. The reduction in temperature may be a natural cerebral protection mechanism that is activated shortly after ischemic insult.     

Hypothermia reduces cytotoxic edema and metabolic alterations during the acute phase of massive SAH: a diffusion-weighted imaging and spectroscopy study in rats

Acute changes in cerebral perfusion and metabolism after subarachnoid hemorrhage (SAH) have been shown to contribute significantly to acute brain injury. The purpose of this study was to examine the effects of moderate hypothermia on the acute changes after massive experimental SAH as evaluated by diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS). SAH in rats was induced by injection of 0.5 mL of arterial blood. Normothermic animals (NT, n = 10) were kept at 37.0 +/- 0.2 degrees C, while temperature was lowered to 32.0 +/- 0.2 degrees C in the primary hypothermia group (pHT, n = 10) prior to SAH and in the secondary hypothermia group (sHT, n = 10) immediately after SAH. DWI and MRS were performed from 30 min prior up to 3 h after injury. The apparent diffusion coefficient (ADC) was measured in cortical and hippocampal regions of interest (ROIs). MRS included lactate, N-acetyl aspartate (NAA), and creatine in a central voxel. DWI showed a generalized, significant decline in ADC after SAH in NT. Significant change in ADC in pHT was absent, and accelerated recovery for animals in sHT was noted. MRS analysis revealed significant lactate accumulation to 204 +/- 40% from baseline only in NT, while sHT was characterized by a transient, less pronounced increase of lactate (159 +/- 11%) and lactate in pHT did not change significantly (117 +/- 11%). NAA did not change significantly when compared to baseline or between groups for NT, pHT, or sHT. Creatine rose significantly to 166 +/- 27% in NT after the insult, indicating increased metabolic stress which was absent in pHT (106 +/- 8%) and sHT (124 +/- 18%). Hypothermia can ameliorate early development of cytotoxic edema, lactate accumulation, and a general metabolic stress response after SAH, even when started after the insult. Our study indicates that a potentially beneficial influence on metabolism and cerebral perfusion in this crucial phase is practicable and might hold the key to further improve outcome in SAH.     

Neurochemical monitoring using intracerebral microdialysis during systemic haemorrhage

Summary Background. Intracerebral microdialysis is a sensitive tool to analyse tissue biochemistry, but the value of this technique to monitor cerebral metabolism during systemic haemorrhage is unknown. The present study was designed to assess changes of intracerebral microdialysis parameters both during systemic haemorrhage and after initiation of therapy. Methods. Following approval of the Animal Investigational Committee, 18 healthy pigs underwent a penetrating liver trauma. Following haemodynamic decompensation, all animals received a hypertonic-hyperoncotic solution and either norepinephrine or arginine vasopressin, and bleeding was subsequently controlled. Extracellular cerebral concentrations of glucose (Glu), lactate (La), glycerol (Gly), and the lactate/pyruvate ratio (La/Py ratio) were assessed by microdialysis. Cerebral venous protein S-100B was determined. Haemodynamic data, blood gases, S-100B, and microdialysis variables were determined at baseline, at haemodynamic decompensation, and repeated after drug administration. Results. Microdialysis measurements showed an increase of La, Gly, and La/Py ratio at BL Th compared to BL (mean ± SEM; La 2.4 ± 0.2 vs. 1.4 ± 0.2 mmol · l⁻¹, p < 0.01; Gly 37 ± 7 vs. 27 ± 6 μmol · l⁻¹, n.s.; La/Py ratio 50 ± 8 vs. 30 ± 4, p < 0.01), followed by a further increase during the therapy phase (La 3.4 ± 0.3 mmol · l⁻¹; Gly 69 ± 10 μmol · l⁻¹; La/Py ratio 58 ± 8; p < 0.001, respectively). Cerebral venous protein S-100B increased at decompensation and after therapy, but decreased close to baseline values after 90 min of therapy. Conclusions. In this model of systemic haemorrhage, changes of cerebral energy metabolism detected by intracerebral microdialysis indicated anaerobic glycolysis and degradation of cellular membranes throughout the study period.     

Hypomagnesemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypomagnesemia frequently occurs in hospitalized patients, and it is associated with poor outcome. We assessed the frequency and time distribution of hypomagnesemia after aneurysmal subarachnoid hemorrhage (SAH) and its relationship to the severity of SAH, delayed cerebral ischemia (DCI), and outcome after 3 months. METHODS: Serum magnesium was measured in 107 consecutive patients admitted within 48 hours after SAH. Hypomagnesemia (serum magnesium <0.70 mmol/L) at admission was related to clinical and initial computed tomographic characteristics by means of the Mann-Whitney U test. Hypomagnesemia at admission and during the DCI onset period (Days 2-12) was related to the occurrence of DCI and hypomagnesemia at admission, and hypomagnesemia that occurred any time during the first 3 weeks after SAH was related to outcome. RESULTS: Hypomagnesemia at admission was found in 41 patients (38%) and was associated with more cisternal (P = 0.006) and ventricular (P = 0.005) blood, a longer duration of unconsciousness (P = 0.007), and a worse World Federation of Neurosurgical Societies scale score at admission (P = 0.001). The crude hazard ratio for DCI with hypomagnesemia at admission was 2.4 (95% confidence interval, 1.0-5.6), and after multivariate adjustment it was 1.9 (95% confidence interval, 0.7-4.7). The hazard ratio of hypomagnesemia from Days 2 to 12 for patients with DCI was 3.2 (range, 1.1-8.9) after multivariate adjustment. The crude odds ratio for poor outcome (Glasgow Outcome Scale score, 1-3) with hypomagnesemia at admission was 2.5 (range, 1.1-5.5). Hypomagnesemia at admission did not contribute to the prediction of outcome in the multivariate model. CONCLUSION: Hypomagnesemia is frequently present after SAH and is associated with severity of SAH. Hypomagnesemia occurring between Days 2 and 12 after SAH predicts DCI.     

Microdialysis-based long-term measurements of energy-related metabolites in the rat brain following a fluid percussion trauma

The aim of the study was to evaluate an experimental approach based on a fluid percussion rat trauma model in combination with the microdialysis technique for the analysis of cerebral interstitial biochemical alterations following head trauma, and to test the hypothesis that the previously observed acute accumulation of lactate and increase in the lactate pyruvate ratio may persist for several days following trauma. We analyzed how lactate, pyruvate, and glucose were altered in the cortex adjacent to the contusion and in the contralateral side of the brain following a traumatic brain injury. The results were compared with those from sham-operated animals. The lactate concentration in the cortex adjacent to the contusion was 0.73 +/- 0.13 mmol/L and 0.71 +/- 0.08 mmol/L 24 and 48 h posttrauma, respectively, and 0.42 +/- 0.07 mmol/L in the sham group (p < 0.05). The lactate/pyruvate ratio of 18.3 +/- 2.3 in the cortex adjacent to the contusion 24 h posttrauma was higher than corresponding value of 10.3 +/- 1.5 in the sham group (p < 0.05). The lactate/pyruvate ratio 48 h posttrauma did not differ from that in the sham group. Interstitial glucose in the cortex adjacent to the contusion and the sham group were similar. Microdialysis measurements from the contralateral side did not differ from those in the sham group. We conclude that the previously observed acute alterations in brain metabolism persist for at least 48 h posttrauma. Further, the measured parameters from the contralateral side can be used as controls since they did not differ from the sham group. Combining microdialysis with a fluid percussion trauma model may be a tool to explore secondary brain injury mechanisms and evaluate new therapies for the treatment of traumatic brain injury.     

Intracerebral microdialysis in severe brain trauma: the importance of catheter location

OBJECT: Intracerebral microdialysis has attracted increasing interest as a monitoring technique during neurological/neurosurgical intensive care. The purpose of this study was to compare cerebral energy metabolism, an indicator of secondary excitotoxic injury and cell membrane degradation close to focal traumatic lesions ("penumbra zones") and in remote and apparently intact brain regions of the ipsilateral and contralateral hemispheres. METHODS: The study included 22 consecutive patients with a mean age 44 +/- 17 years and an estimated postresuscitation Glasgow Coma Scale motor score less than 5. Altogether 40 microdialysis catheters with radiopaque tips were inserted. Two catheters could not be localized on postoperative computerized tomography (CT) scans and were excluded from the analysis. The perfusates were analyzed at the patient's bedside for levels of glucose, pyruvate, lactate, glutamate, and glycerol with the aid of a CMA 600 Analyzer. The positions of eight (22%) of the 36 catheters were reclassified after a review of findings on CT scans. Except for pyruvate the values of all biochemical variables and the lactate/pyruvate (L/P) ratio were significantly different in the penumbra zone when compared with mean values found in "normal" tissue ipsilateral to the parenchymal damage and in contralateral normal tissue (p < 0.001). In the penumbra zone a slow normalization of the L/P ratio and levels of glutamate and glycerol were observed. In normal tissue these parameters remained within normal limits. CONCLUSIONS: Data obtained from intracerebral microdialysis can be correctly interpreted only if the locations of the catheters as they relate to focal brain lesions are visualized. A "biochemical penumbra zone" surrounds focal traumatic brain lesions. It remains to be proven whether therapeutic interventions can protect the penumbra zone from permanent damage.