Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AI rho) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AI rho values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AI rho offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.     

Effect of bacterial meningitis complicating severe head trauma upon brain microdialysis and cerebral perfusion

Introduction: This article describes changes in regional cerebral perfusion and brain metabolism in a case of bacterial meningitis complicating severe traumatic brain injury. Case report: As part of clinical monitoring of patients with severe head injury, cerebral microdialysis was performed and extracellular concentration of glucose, lactate, glutamate, and pyruvate was determined. A thermal diffusion probe was used for bedside monitoring of cerebral blood flow. A cinetobacter meningitis complicated the clinical course on the seventh post-admission day and dramatically altered the neurochemistry. Microdialy sate analysis showed glucose under the detection limit, lactate at moderately high levels, and a marked increase in glutamate and pyruvate levels. A reduction of cerebral perfusion was detected in the early phase of meningitis, probably secondary to vascular complications related to the inflammatory process. Discussion: This case describes an emerging area of study and practice in patients with brain injury. It demonstrates how cerebral perfusion monitoring and study of brain metabolism can provide an early detection of secondary events that complicate severe head injury and can contribute to a better understanding of the complex pathogenetic mechanisms responsible for neuronal damage.     

Assessment of prognostic factors in severe traumatic brain injury patients treated by mild therapeutic cerebral hypothermia therapy

Abstract

This study analyzed the predictable factors of outcome such as neuro-parameters and systemic complications to elucidate the indications for therapeutic hypothermia. In our institute, 35 patients with severe head injury (Glasgow Coma Scale 3-7) were treated with mild hypothermia therapy (33° - 35°C). Twenty-two of these 35 patients underwent complete neuromonitoring and outcome assessments by Glasgow Outcome Scale (GOS) at three months after injury. GOS of hypothermia group was significantly better than another patient group which was treated without mild hypothermia therapy. The hypothermia group was divided into two groups: good outcome (GOOD) (good recovery or moderate disability; n = 9, 40.9%) and poor outcome (POOR) (severe disability, vegetative state, or death; n = 13, 59.1%). The mean age (mean 30.2 years, range 9-46) was significantly lower in GOOD than in POOR (mean 45.2 years, range 17-62). Patients aged over 50 years had poor outcome. CPP was significantly higher in GOOD during hypothermia. All patients with thrombocytopenia had poor outcome. Hypothermia therapy can improve outcome in patients with traumatic brain injury who are younger than 50 years old, without severe brain damage, and if improvement of cerebral perfusion is expected. Systemic complications must be prevented as far as possible by combination with other therapies.     

Increased intracranial pressure is associated with elevated cerebrospinal fluid ADH levels in closed-head injury

Abstract

Objectives: Head injury frequently results in increased intracranial pressure and brain edema. Investigators have demonstrated that ischemic injury causes an increase in cerebrospinal fluid (CSF) levels of antidiuretic hormone (ADH); increased CSF ADH levels exacerbate cerebral edema, and inhibition of the ADH system with specific ADH antagonists reduces cerebral edema. The current study was designed to test the hypothesis that elevated levels of ADH are present in the CSF of subjects with head injury.

Methods: Ventricular CSF and blood samples were taken from 11 subjects with head injury and 12 subjects with no known head trauma or injury. ADH levels were analyzed using radioimmunoassay. Severity of increased intracranial pressure (ICP) was rated in head-injured subjects using a four-point ordinal scale, based on which treatments were necessary to reduce ICP.

Results: Subjects with head injury had higher CSF (3.2 versus 1.2 pg/ml; P<0.02) and plasma (4.1 versus 1.4 pg/ml; P<0.02) levels of ADH than did control subjects. In head-injured subjects, CSF ADH levels positively correlated with severity of ICP.

Discussion: The results of this study suggest that ADH plays a role in brain edema associated with closed head injury.     

Association between intracranial,arterial pulse pressure amplitudes and cerebral autoregulation in head injury patients

Abstract

Objective: To explore whether intracranial pulse pressure amplitudes relate to arterial pulse pressure amplitudes and whether correlations between time-related changes in intracranial and arterial pulse pressure amplitudes associate with indices of cerebral autoregulation.

Methods: A total of 257 continuous and simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and middle cerebral artery (MCA) blood velocity recordings were obtained 1–14 days after ictus in 76 traumatic head injury patients and analysed retrospectively. Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse pressure amplitudes of corresponding single ICP and ABP waves were correlated in consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and mean and systolic MCA blood flow velocities, were computed in consecutive 6 second time windows. The indices of cerebral autoregulation PRx (moving correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation between mean and systolic MCA blood velocity and cerebral perfusion pressure) were calculated over 4 minute periods and averaged over each recording.

Results: Intracranial pulse pressure amplitudes were not related to arterial pulse pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome was related to mean ICP, PRx and Sx (p ≤ 0.04, multiple regression analysis). Correlations between intracranial and arterial pulse pressure amplitudes were weakly related to PRx (Pearson's correlation coefficient: 0.16; p=0.01), but were not related to the indices of cerebral autoregulation Mx (Pearson's correlation coefficient: 0.07) and Sx (Pearson's correlation coefficient: 0.04).

Conclusions: In this cohort of pressure recordings, we found no evidence of a correlation between intracranial and arterial blood pressure amplitudes. The correlation appeared not to be related to the state of cerebral autoregulation, although a weak correlation was found with pressure reactivity index PRx.     

Influence of cerebral oxygenation following severe head injury on neuropsychological testing

Abstract

Despite recent advances in the management of severe head injury the mortality and morbidity remains high. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are crucial parameters for the correct management at the intensive care unit, due to their therapeutic and prognostic importance. In addition, regional brain tissue oxygenation (p_tiO₂) seems to be of importance. While different studies demonstrated the impact of cerebral hypoxia on outcome (mortality), no data are available focusing on morbidity (neuropsychological deficits). Therefore, our study is carried out to demonstrate a possible relationship between amount of cerebral oxygenation during acute stage after severe head injury and neuropsychological outcome. Besides ICP and CPP, p_tiO₂ was monitored in 40 severely head injured patients during the ICU stay from the day of admission until day 10. Monitoring data were stored and amount of hypoxic episodes were calculated. Besides outcome using the Glasgow Outcome Scale neuropsychological testing was performed 2–3 years after injury. Analysing the quality of brain tissue oxygenation, a relationship to the performance in neuropsychological tests could be found. Patients with low brain tissue oxygenation had a worse outcome in neuropsychological testing, especially concerning intelligence and memory. Associated with these deficits patients showed a reduced performance in their profession. Our data suggest a possible predictive value of brain tissue oxygen on morbidity analysing neurocognitive function after head injury. This may implicate monitoring and treatment of cerebral hypoxia.     

Quantitative electroencephalography in a swine model of cerebral arterial gas embolism

ObjectiveCerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE.Methods0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4 h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF₉₀), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated.ResultsMAMP and tBSI but not ADR, SEF₉₀ and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4 h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4 h.ConclusionsMAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE.SignificanceThis study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients.     

Early Cerebral Metabolic Crisis After TBI Influences Outcome Despite Adequate Hemodynamic Resuscitation

Background

Optimal resuscitation after traumatic brain injury (TBI) remains uncertain. We hypothesize that cerebral metabolic crisis is frequent despite adequate resuscitation of the TBI patient and that metabolic crisis negatively influences outcome.

Methods

We assessed the effectiveness of a standardized trauma resuscitation protocol in 89 patients with moderate to severe TBI, and determined the frequency of adequate resuscitation. Prospective hourly values of heart rate, blood pressure, pulse oximetry, intracranial pressure (ICP), respiratory rate, jugular venous oximetry, and brain extracellular values of glucose, lactate, pyruvate, glycerol, and glutamate were obtained. The incidence during the initial 72?h after injury of low brain glucose <0.8?mmol/L, elevated lactate/pyruvate ratio (LPR) >25, and metabolic crisis, defined as the simultaneous occurrence of both low glucose and high LPR, were determined for the group.

Results

5 patients were inadequately resuscitated and eight patients had intractable ICP. In patients with successful resuscitation and controlled ICP (n?=?76), within 72?h of trauma, 76?% had low glucose, 93?% had elevated LPR, and 74?% were in metabolic crisis. The duration of metabolic crisis was longer in those patients with unfavorable (GOSe????6) versus favorable (GOSe????7) outcome at 6?months (P?=?0.011). In four multivariate models the burden of metabolic crisis was a powerful independent predictor of poor outcome.

Conclusions

Metabolic crisis occurs frequently after TBI despite adequate resuscitation and controlled ICP, and is a strong independent predictor of poor outcome at 6?months.     

Heterogeneous regional and temporal energetic impairment following controlled cortical impact injury in rats

Abstract

Objectives: Following traumatic brain injury metabolic stability is impaired. Duration and reversibility of these changes might be important to guide specific interventions.

Methods: To characterize temporal and regional changes in cerebral metabolism, 68 male Sprague–Dawley rats were subjected to a focal cortical contusion. Lesion progression and mitochondrial impairment were determined by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride (TTC) staining, respectively. Metabolic alterations were determined at hours 6 and 24 and day 7 by measuring extracellular glucose, lactate and hypoxanthine levels with microdialysis catheters placed adjacent and distant to the contusion and by quantifying changes in tissue ATP, lactate and glucose using bioluminescence imaging.

Results: The cortical lesion reached its maximal extent at hour 24 and remained confined to the ipsilateral hemisphere. In microdialysate, at hour 6, extracellular hypoxanthine and lactate reached maximal values, thereafter hypoxanthine normalized while lactate remained increased. Extracellular glucose reached the highest values at hour 24 and remained elevated. Bioluminescence imaging revealed heterogeneous changes in areas distant to the contusion. No significant changes were found in ATP content. Slightly elevated tissue glucose until 24 hours in the ipsilateral hemisphere was observed. Following a continuous increase, lactate levels were the highest by 6 hours in the ipsilateral cortex and hippocampus.

Discussion: CCI is associated with disturbances in energetic metabolism. Metabolic perturbation is not restricted to the early phase and the contusional region following focal cortical contusion, but also involves hippocampus and primarily uninjured parts of the hemisphere.     

Effect of hypothermia on serum electrolyte, inflammation, coagulation, and nutritional parameters in patients with severe traumatic brain injury

Introduction: We evaluated the effect of induced hypothermia on biochemical parameters in patients with severe traumatic brain injury. Methods: We obtained hemoglobin, hematocrit, white blood count, lymphocyte count, platelet count, and serum concentrations of sodium, potassium, glucose, albumin, and C-reactive protein, and prothrombin time, hepaplastin test, activated partial thromboplastin time, antithrombin-III, α2PI, and nitrogen excretion on the day of admission, and on days 1, 3, 5, 7, 14, and 21 after the injury in 31 patients with severe head injury who were treated with hypothermia of 33°ranging from 48 to 72 hours. We selected 33 normothermic patients as a control group; these patients were selected from patients who had been treated before hypothermia was used as a treatment modality, by the same criteria for hypothermia therapy. We compared the biochemical markers and rectal temperature and intracranial pressure in the hypothermia group with those in the normothermia group. Outcome was assessed using the Glasgow Outcome Scale at 6 months after injury. Results: The demographic characteristics, severity, and outcome were similar in the hypothermia and normothermia group. Intracranial pressure was significantly decreased by hypothermia. Serum potassium concentration decreased significantly during hypothermia. White blood cell counts and C-reactive protein levels were higher after rewarming in the hypothermia group, and these were also higher in the patients with infectious complications, although the incidence of infectious complications did not differ between the hypothermia and normothermia groups. There were no statistically significant prolongations of activated partial thromboplastin time and no decline in prothrombin time with hypothermia. Platelet count, antithrombin-III, and α2PI did not differ significantly between the two groups. Conclusion: Hypothermia of 33° for 48–72 hours does not appear to increase the risk for coagulopathy and infections, although hypothermic patients exhibited significant increments in inflammatory markers such as C-reactive protein and white blood counts after rewarming.     

Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

Background

Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis.

Methods

Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO₂) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O₂ and CO₂. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection.

Results

After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO₂ or ICP was registered. No changes in physiological variables were observed.

Conclusions

The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO₂, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.

     

Cerebrospinal fluid lactate and pH in patients with acute severe head injury.

Cerebral ventricular fluid (CSF) lactate and pH were measured repeatedly in 21 comatose patients with severe head injury during the first three weeks after trauma. In addition, regional cerebral 133Xe blood flow (rCBF) was measured two to four times in each patient at various time intervals, depending on the indications for carotid angiography, and the pressure in the cerebral ventricular system (IVP) was measured continuously. The series was divided into three groups: (1) patients with local cortical cerebral lesions, (2) patients with brain-stem symptoms, and (3) patients with both local cortical lesions and brain-stem symptoms. The results showed that a high CSF lactate level in patients with severe acute brain injury suggested severe and extensive brain lesions and predicted a poor outcome of the injury. In the individual patients, increasing CSF lactate foreboded clinical deterioration, whereas decreasing CSF lactate indicated recovery. The CSF pH was decreased in most patients, but very low pH levels (below 7.20) were seen only in three patients who all had a poor outcome. Correlation was not observed between CSF lactate and rCBF or between CSF pH and rCBF. It is concluded that repeated determination of CSF lactate and pH during the post-traumatic period may be a valuable tool in the assessment of the course and outcome of the brain injury.     

Significance of a reduced cerebral blood flow during the first 12 hours after traumatic brain injury

Background: It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain’s injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF. Methods: We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed. Results: Average global CBF for the 77 patients was 36±16 mL/100g/minutes. Nine patients had an average global CBF <18 (average 12±5). The remaining 68 patients had a global CBF of 39±15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF≥18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury. Conclusion: In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.     

Cerebrospinal compensation of pulsating cerebral blood volume in hydrocephalus

Abstract

Objective: The aim of the study was to develop a computational method for the assessment of brain pressure compensation of cerebrospinal arterial blood inflow. The method was verified using clinical recordings performed during infusion studies in a group of patients diagnosed with hydrocephalus.

Materials and methods: We studied 27 patients suspected of having normal pressure hydrocephalus. The infusion test was used to measure the resistance to cerebrospinal fluid outflow, and the elastance coefficient was performed together with recording of the blood flow velocity in the middle cerebral artery. From the blood flow velocity waveform, the pulsatile pattern of increasing cerebral blood volume during one heart cycle was evaluated as a time integral of the arterial blood flow velocity minus the mean arterial blood flow. Cerebrospinal 'compliance index' (C _i) was calculated as the amplitude of change in blood volume divided by the amplitude of intracranial pressure pulse waveform.

Results: Compliance index C _i decreased during the infusion test, proportionally inverse to the rise in intracranial pressure controlled by the external infusion of saline (R=?0·76; p<0·005). A relative change in compliance (from baseline to the plateau phase of the study) was positively associated with greater brain elasticity (R=0·61; p<0·005) and poorer compensatory reserve at the phase of infusion (R=0·51; p=0·009)

Conclusion: C _i decreases during the infusion study and seems to well replicate the relative changes in cerebrospinal compensatory reserve in hydrocephalus.     

高原地区91例重型颅脑损伤不同治疗方法疗效分析

目的探讨高原地区急性颅脑损伤不同治疗方法,特别是不同手术方式的疗效,提高临床治疗水平。方法分析本院2002年12月至2012年12月收治的91例急性重型颅脑损伤患者,根据采用的新式治疗方案,尤其是标准大骨瓣减压术的时间,91例患者分为两组:早期组(48例,2006年前),后期组(43例,2006年后),对比早期组与后期组不同治疗方法效果总结临床治疗方法。结果术后早期组1、3、7、15 d GCS评分均低于后期组(P0.05);术后15 d内早期组死亡18例,后期组死亡7例,早期组死亡率高于后期组(P0.05);术后15 d内早期组发生大面积脑梗塞10例,而后期组2例,早期组发生大面积脑梗塞率高于后期组(P0.05);6月良好功能恢复率后期组高于早期组(P0.05)。结论高原地区急性重型颅脑损伤患者采用标准大骨瓣减压术式,可以降低致死率、脑梗率和提高功能恢复良好率。     

Plasma glucose level in Nigerian Africans with head injury

Trauma is often associated with increased plasma glucose concentrations. This prospective study was designed to determine random plasma glucose concentrations in patients with head injury in our center and to determine if this is related to injury severity and outcome. Patients with head injury in whom the plasma glucose concentration could be determined at our accident and emergency unit during the study period were included. We obtained information on demographic data, diagnosis, injury severity using Glasgow Coma Scale scores, treatment with glucose-containing fluid prior to presentation in our center, plasma glucose on admission, 24 hours later and 72 hours later and outcome at discharge using the Glasgow Outcome Scale score. Hyperglycemia was defined as glucose concentrations above 11.1 mmol/L. Fifty eight patients were included in the study from October 2004 to December 2005. There were 46 males and 12 females (4:1). The mean age (± standard deviation [SD]) was 31.3 (16.4) years. Fourteen patients (24.1%) had mild head injury, 21 patients (36.2%) had moderate head injury and 23 patients (39.7%) had severe head injury. The outcome was good in 29 patients (50%), moderate disability in five patients (8.6%), severe disability in one (1.7%) and death in 10 (17.2%). Eighty percent of the patients who died had severe head injury. Most of the patients had a plasma glucose in the normal range irrespective of the severity of the head injury. Only one patient had a plasma glucose in the hyperglycemic range and that patient had a severe head injury. Fifty percent of the patients who died had a plasma glucose concentration in the normal range; none in the hyperglycemic range. This study shows that the plasma glucose is generally below hyperglycemic concentration in our patients irrespective of the severity of head injury.     

Influence of inspired oxygen on glucose-lactate dynamics after subdural hematoma in the rat

The mechanisms causing brain damage after acute subdural hematoma (SDH) are poorly understood. A decrease in cerebral blood flow develops immediately after the hematoma forms, thus reducing cerebral oxygenation. This in turn may activate mitochondrial failure and tissue damage leading to ionic imbalance and possibly to cellular breakdown. The purpose of this study was to test whether a simple therapeutic measure, namely increased fraction of inspired oxygen (FiO2 100), and hence increased arterial and brain tissue oxygen tension, can influence brain glucose and lactate dynamics acutely after subdural hematoma in the rat. Twenty-five male Sprague-Dawley anesthetized rats were studied before, during and after induction of the SDH in two separate groups. The Oxygen group (n = 10) was ventilated with 100% oxygen immediately after induction of the SDH. The Air group (n = 10) was ventilated during the entire study with 21% oxygen. Brain microdialysate samples were analyzed for glucose and lactate. All rats were monitored with femoral arterial blood pressure catheters, arterial blood gas analysis, arterial glucose, lactate and end tidal CO2 (EtCO2). Five male Sprague-Dawley rats were sham operated to measure the effect of oxygen challenge on glucose-lactate dynamics without injury. Arterial oxygen tension in the Oxygen group was 371 +/- 30 mmHg and was associated with significantly greater increase in dialysate lactate in the first 30 min after induction of SDH. Dialysate glucose initially dropped in both groups, after SDH, but then reverted significantly faster to values above baseline in the Oxygen group. Changes in ventilatory parameters had no significant effect on dialysate glucose and lactate parameters in the sham group. Extracellular dialysate lactate and glucose are influenced by administration of 100% O2 after SDH. Dialysate glucose normalizes significantly quicker upon 100% oxygen ventilation. We hypothesize that increased neural tissue oxygen tension, in presence of reduced regional CBF, and possibly compromised mitochondrial function, after acute SDH results in upregulation of rate-limiting enzyme systems responsible for both glycolytic and aerobic metabolism. Similar changes have been seen in severe human head injury, and suggest that a simple therapeutic measure, such as early ventilation with 100% O2, may improve cerebral energy metabolism, early after SDH. Further studies to measure the generation of adenosine triphosphate (ATP) are needed to validate the hypothesis.     

Nω-nitro-L-arginine methyl ester (L-NAME) attenuates the acute inflammatory responses and brain injury during the early phase of experimental Escherichia coli meningitis in the newborn piglet

Abstract

We evaluated the anti-inflammatory and neuroprotective effect of nonselective NOS inhibitor, N^ω-nitro-Larginine methyl ester (L-NAME), in experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10⁸ colony forming units of Escherichia coli. L-NAME 10 mg kg^-1 was given intravenously 30 min before induction of meningitis. L-NAME significantly attenuated the increase in intracranial pressure and decrease in cerebrospinal fluid glucose concentration observed in the meningitis group. Systemic and cerebral perfusion pressure were even higher compared to the control and meningitis groups. However, the meningitis-induced increase in tumor necrosis factor- α level, leukocyte numbers and lactate level in the cerebrospinal fluid was not significantly attenuated with L-NAME administration. Reduced cerebral cortical cell membrane Na⁺ ,K⁺-ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were significantly improved with L-NAME treatment. Decreased brain glucose and ATP levels were also significantly improved with L-NAME treatment. These findings suggest that L-NAME was effective in attenuating the acute inflammatory responses and brain injury in neonatal bacterial meningitis. [Neurol Res 2001; 23: 862-868]     

Influence of body position on tissue-pO2, cerebral perfusion pressure and intracranial pressure in patients with acute brain injury

Abstract

ft is a common practice to position head-injured patients in bed with the head elevated above the level of the heart in order to reduce intracranial pressure OCP). This practice has been in vivid discussion since some authors argue a horizontal body position will increase the cerebral perfusion pressure (CPP) and therefore improve cerebral blood flow (CBF). However, ICP is generally significantly higher in the horizontal position. The aim of this study was to evaluate changes in regional microcirculation using tissue pO ² (ti-p0₂), as well as changes in cerebral perfusion pressure (CPP) and intracranial pressure induced by changes in body position in patients with head injury. The effect of 0° and 30° head elevation on ti-p0₂, CPp, ICP and arterial blood pressure (MABP) was studied in 22 head injured patients during day 0-12 after trauma. The mean ICP was significantly lower at 30° head elevation than at 00 (74.1 + 8.6 vs. 19.9+8.3 mmHg). While MABP was unaffected by head elevation, CPP was slightly higher at 300 than at 0° (76.5+ -13.5 vs. 71.5+ 13.2 mmHg). However, regional ti-p0₂ was unaffected by body position (30° vs. 0°: 24.9+73.1 vs. 24.7 + 12.9 mmHg). fn add~tion, there was no change in the time course after trauma concerning these findings in the individLfal pati,ents. The data indicate that a moderate head elevation of 300 reduces ICP without jeopardizing regional cerebral microcirculation as monitored using a polarographic ti-p0₂ microcatheter. [Neural Res 1997; 19: 249-253]     

Regional analyses of CNS microdialysate glucose and lactate in seizure patients

PURPOSE: To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures. METHODS: We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region. RESULTS: Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels. CONCLUSIONS: We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.