Ventriculostomy for control of raised ICP in acute traumatic brain injury.

UNLABELLED: The aim of this study was to evaluate the effect of ventriculostomy on intracranial pressure (ICP), and related parameters, including cerebrospinal compensation, cerebral oxygenation (PbtO2) and metabolism (microdialysis) in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: Twenty-four patients with parenchymal ICP sensors were prospectively included in the study. Ventriculostomy was performed after failure to control ICP with initial measures. Monitoring parameters were digitally recorded before and after ventriculostomy and compared using appropriate tests. RESULTS: In all patients ventriculostomy led to rapid reduction in ICP. Pooled mean daily values of ICP remained < 20mmHg for 72h after ventriculostomy and were lower than before (p < 0.001). In 11 out of 24 patients during the initial 24-h period following ventriculostomy an increase in ICP to values exceeding 20mmHg was observed. In the remaining 13 patients ICP remained stable, allowing reduction in the intensity of treatment. In this group ventriculostomy led to significant improvement in craniospinal compensation (RAP index), cerebral perfusion pressure and PbtO2. Improvement in lactate/pyruvate ratio, a marker of energy metabolism, was correlated with the increase in PbtO2. CONCLUSION: Ventriculostomy is a useful ICP-lowering manoeuvre, with sustained ICP reduction and related physiological improvements achieved in > 50% of patients.

Microdialysis in the management of hepatic encephalopathy.

INTRODUCTION: Fulminant hepatic encephalopathy has a high mortality. METHODS: This case report describes the role of cerebral microdialysis as an adjunct to the management of a 49 - year-old woman with hepatic encephalopathy secondary to a paracetamol overdose. RESULTS: The application of the microdialysis technique, by detecting a very low cerebral glucose concentration in the presence of a normal plasma glucose, assisted in clinical decision making. CONCLUSIONS: Cerebral microdialysis, by enabling continuous on-line monitoring of substrate delivery and metabolism, may have a role in the management of patients with fulminant hepatic failure.

Cerebral microdialysis methodology--evaluation of 20 kDa and 100 kDa catheters.

Microdialysis monitoring of cerebral metabolism is now performed in several neuro-intensive care units. Conventional microdialysis utilizes CMA70 catheters with 20 kDa molecular weight cut-off membranes enabling the measurement of small molecules such as glucose, lactate, pyruvate and glutamate. The CMA71 100 kDa molecular weight cut-off microdialysis catheter has recently been introduced to allow detection of larger molecules such as cytokines. The objective of this study was to perform in vitro and in vivo testing of the CMA71 microdialysis catheter, comparing its performance with the CMA70. In vitro comparison studies of three of each catheter using reference analyte solutions, demonstrated equivalent recovery for glucose, lactate, pyruvate and glutamate (range 94-97% for CMA70 and 88-103% for CMA71). In vivo comparison involved intracranial placement of paired CMA70 and CMA71 catheters (through the same cranial access device) in six patients with severe traumatic brain injury. Both catheters were perfused with CNS Perfusion Fluid without dextran at 0.3 microl min-1 with hourly sampling and bedside analysis on a CMA600 microdialysis analyser. The two catheters yielded equivalent results for glucose, lactate, pyruvate, glutamate and lactate/pyruvate ratio. CMA71 microdialysis catheters can, therefore, be used for routine clinical monitoring of extracellular substances, as well as for their intended research role of larger molecular weight protein sampling.

Extracellular amino acid changes in patients during reversible cerebral ischaemia.

This study investigated the changes in extracellular chemistry during reversible human cerebral ischaemia. Delayed analysis was performed on samples taken from a subgroup of patients during aneurysm surgery previously reported. Frozen microdialysis samples from 14 patients who had all undergone temporary clipping of the ipsilateral internal carotid artery (ICA) were analysed for another 15 amino acids with HPLC and for glycerol with CMA-600. Changes were characterised according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients was not associated with changes in amino acids or glycerol. Cerebral ischaemia, defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA occlusion, occurred in 3 patients. None of whom developed an infarct in the monitored region. This prolonged reversible ischaemia was associated with transient delayed increases in gamma-amino butyric acid (GABA) as well as glutamate and glycerol, each by two-to-three folds. This study demonstrates detectable transient increases in human extracellular glutamate, GABA and glycerol during identified periods of reversible cerebral ischaemia, maximal 30-60 minutes after onset of ischaemia, but not in other amino acids detected by HPLC.

Cerebral blood flow augmentation in patients with severe subarachnoid haemorrhage.

Following aneurysmal subarachnoid haemorrhage (SAH), cerebral blood flow (CBF) may be reduced, resulting in poor outcome due to cerebral ischaemia and subsequent stroke. Hypertonic saline (HS) is known to be effective in reducing intracranial pressure (ICP). We have previously shown a 20-50% increase in CBF in ischaemic regions after intravenous infusion of HS. This study aims to determine the effect of HS on CBF augmentation, substrate delivery and metabolism. Continuous monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), brain tissue oxygen (PbO2), middle cerebral artery flow velocity (FV), and microdialysis was performed in 14 poor grade SAH patients. Patients were given an infusion of 23.5% HS, and quantified xenon computerised tomography scanning (XeCT) was carried out before and after the infusion in 9 patients. The results showed a significant increase in ABP, CPP, FV and PbO2, and a significant decrease in ICP (p < 0.05). Nine patients showed a decrease in lactate-pyruvate ratio at 60 minutes following HS infusion. These results show that HS safely and effectively augments CBF in patients with poor grade SAH and significantly improves cerebral oxygenation. An improvement in cerebral metabolic status in terms of lactate-pyruvate ratio is also associated with HS infusion.

Glucose metabolism in traumatic brain injury: a combined microdialysis and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) study.

Following traumatic brain injury, as a consequence of ionic disturbances and neurochemical cascades, glucose metabolism is affected. [18F]-2-Fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (FDG-PET) provides a measure of global and regional cerebral metabolic rate of glucose (rCMRglc), but only during the time of the scan. Microdialysis monitors energy metabolites over extended time periods, but only in a small focal volume of the brain. Our objective in this study is to assess the association of parameters derived from these techniques when applied to patients with traumatic brain injury. Eleven sedated, ventilated patients receiving intracranial pressure monitoring and managed using Addenbrooke's Neurosciences Critical Care Unit protocols were monitored. Dialysate values for glucose, lactate, pyruvate, and glutamate, and the lactate to glucose (L/G), lactate to pyruvate (L/P) and pyruvate to glucose (P/G) ratios were determined and correlated with rCMRglc. FDG-PET scans were performed within 24 hours (five patients), or between 1 and 4 days (two patients) or after 4 days (six patients). Two patients were rescanned 4 and 7 days after their initial scan. A 20 mm region of interest (ROI) was defined on co-registered CT scan on two contiguous slices around the microdialysis catheter. Mean (+/-sd) for rCMRglc was 19.1 +/- 5.5 micromol/100 g/min, and the corresponding microdialysis values were: glucose 1.4 +/- 1.4 mmol/ L; lactate 5.3 +/- 3.6 mmol/L; pyruvate 164.1 +/- 142.3 micromol/L; glutamate 15.0 +/- 14.7 micromol/L; L/G 11.0 +/- 16.0; L/P 27.3 +/- 7.9 and P/G 381 +/- 660. There were significant relations between rCMRglc and dialysate lactate (r = 0.58, P = 0.04); pyruvate (r = 0.57, P = 0.04), L/G (r = 0.55, P = 0.05), and the P/G (r = 0.56, P = 0.05) but not between rCMRglc and dialysate glucose, L/P or glutamate in this data set. The results suggest that increases in glucose utilization as assessed by FDG-PET in these patients albeit in mainly healthy tissue are associated with increases in dialysate lactate, pyruvate, L/G and the P/G ratio perhaps indicating a general rise in metabolism rather than a shift towards non-oxidative metabolism. Further observations are required with regions of interest (microdialysis catheters positioned) adjacent to mass lesions notably contusions.

Near infrared spectroscopy in brain injury: today's perspective.

The technique of near infrared spectroscopy (NIRS) is based on the principle of light attenuation by the chromophores oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and cytochrome oxidase. Changes in the detected light levels can therefore represent changes in concentrations of these chromophores. Clinical use of NIRS in the brain has been well established in neonates where transillumination is possible. While it has become a useful research tool for monitoring the adult brain, clinical application has been hampered by the fact that it must be applied in reflectance mode. This has resulted in a number of concerns, most significantly the issue of signal contamination by the extracranial tissue layers. Algorithms have been applied to try to overcome this problem, and techniques such as time resolved, phase resolved and spatially resolved spectroscopy have been developed. There has been renewed interest in NIRS as an easy to use, non-invasive technique for measuring tissue oxygenation in the adult brain. Recent technical advances have led to the development of compact, portable instruments that detect changes in optical attenuation of several wavelengths of light. Near infrared spectroscopy is an evolving technology that holds significant potential for technical advancement. In particular, NIRS shows future promise as a clinical tool for bedside cerebral blood flow measurements and as a cerebral imaging modality for mapping structure and function.

Effects of propofol on cerebral oxygenation and metabolism after head injury.

BACKGROUND: Flow-metabolism coupling is thought to be deranged after traumatic brain injury, while the effects of propofol on flow-metabolism coupling are controversial. We have used a step increase in target plasma propofol concentration in head injured patients to explore flow-metabolism coupling in these patients. METHODS: Ten patients with a moderate to severe head injury received a step increase in propofol target controlled infusion of 2 microg x ml(-1). Cerebral tissue gas measurements were recorded using a multimodal sensor, and regional chemistry was assessed using microdialysis. Arterial-jugular venous oxygen differences (AVDO(2)) were measured and all patients had cortical function monitoring (EEG). RESULTS: The step increase in propofol led to a large increase in EEG burst-suppression ratio (0% (range 0-1.1) to 46.1% (range 0-61.7), P<0.05); however, this did not significantly change tissue gas levels, tissue chemistry, or AVDO(2). CONCLUSIONS: Flow-metabolism coupling remains intact during a step increase in propofol after traumatic brain injury. The EEG burst-suppression induced by propofol after traumatic brain injury does not appear to be a useful therapeutic tool in reducing the level of regional ischaemic burden.

Clinical cerebral microdialysis--determining the true extracellular concentration.

Current monitoring of the cerebral extracellular chemistry of neurosurgical patients using microdialysis does not provide the true extracellular concentration because full equilibration across the membrane is not achieved. By varying the flow rate and extrapolating to zero flow, the relative recovery i.e. the concentration of the substance in the microdialysate as a proportion of the true concentration in the extracellular space may be calculated. The disadvantage of this method is that it depends on the underlying baseline chemistry being constant during measurements for the calculations, which is not the case in the changing environment of a neuro-intensive unit. We have therefore designed a modification of the extrapolation to zero flow method using an adjacent constant flow rate catheter to monitor the baseline. The results demonstrate that the relative recovery varies considerably with flow rate, and for the CMA70 10 mm membrane catheter, is approximately 70% at a rate of 0.3 microliter/min and 30% at a rate of 1.0 microliter/min for glucose, lactate, pyruvate and glutamate.

Extracellular lactate/pyruvate and glutamate changes in patients during per-operative episodes of cerebral ischaemia.

OBJECTIVE: Temporary Internal Carotid Artery (ICA) clipping necessary during aneurysm surgery was used as a model to investigate metabolic changes in the human brain during defined episodes of ischaemia. DESIGN: An observational study using intracerebral monitors: PBO2 (Neurotrend) and microdialysis (CMA, Sweden). SUBJECTS: 16 patients monitored during complex aneurysm surgery. OUTCOME MEASURES: Changes in extracellular concentrations of glucose, lactate, and glutamate and lactate/pyruvate ratio (L/P). RESULTS: Mean age was 55. 10 patients presented with subarachnoid haemorrhage and 6 with mass effect (4 giant). Temporary ICA occlusion was required for dissection (n = 9), intraoperative rupture (n = 5) or aneurysmal thrombectomy (n = 2). The mean total duration was 15 minutes (range 4-52 minutes). No infarcts developed in the monitored regions. Microdialysis was unsuccessful in 3 patients and Neurotrend in 1. Patients were grouped according to the degree and duration of fall in PBO2: minimal brief falls were not associated with microdialysis changes (n = 5). More pronounced falls were associated with increases in L/P (n = 4). Only prolonged occlusions averaging 42 minutes (n = 3) with PBO2 sustained below 1 kPa were associated with rises in glutamate. CONCLUSIONS: Brief temporary ICA occlusion caused an initial increased L/P. Glutamate increases were only seen after occlusion that was prolonged with PBO2 below 1.0 kPa.

Effect of hypothermia on brain tissue oxygenation in patients with severe head injury.

BACKGROUND: There is renewed interest in the use of induced hypothermia as a method of neuroprotection both intraoperatively and in the intensive care management of severe brain injury. In this study we have investigated the effects of hypothermia on brain tissue oxygenation in patients with severe head injury. METHODS: Thirty patients with severe head injury (Glasgow coma score <8) were monitored with a multimodal sensor inserted into the brain which measures tissue PO2, PCO2, pH and temperature in addition to routine monitoring. Patients were cooled to a minimum of 33 degrees C when clinically indicated. RESULTS: For all 30 patients brain and systemic temperature correlated well (r=0.96). Brain temperature was consistently higher than systemic temperature by 0.41 +/- 0.26 degrees C (confidence limits). Brain tissue PO2 decreased with hypothermia, with a significant reduction below 35 degrees C (P<0.05). CONCLUSIONS: These results emphasize the advantage of measuring brain temperature directly, and suggest that decreasing brain temperature below 35 degrees C may impair brain tissue oxygenation.

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids.

OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.

Evaluation of a near-infrared spectrometer (NIRO 300) for the detection of intracranial oxygenation changes in the adult head.

BACKGROUND AND PURPOSE: The clinical application of intracranial near-infrared spectroscopy in adults has been hampered by concerns over contamination from extracranial tissues. The NIRO 300 (Hamamatsu Photonics) provides continuous online measurements of hemoglobin and cytochrome oxidase concentrations and a calculated tissue oxygen index (TOI). The present study seeks confirmation of the anatomic source of TOI in the adult cranium. METHODS: Sixty patients undergoing carotid endarterectomy were studied. The NIRO 300 was incorporated into an established multimodal monitoring system. TOI, oxyhemoglobin, and deoxyhemoglobin changes were assessed and compared with (1) frontal cutaneous laser-Doppler flowmetry and (2) transcranial Doppler measurement of the ipsilateral middle cerebral artery flow velocity. RESULTS: Changes in TOI were seen during cross-clamping of the carotid vessels in 49 patients (mean DeltaTOI=-9.4%, SD=7.1). Significant correlation was seen between TOI and flow velocity (r=0.56) but not with laser-Doppler flowmetry (r=0.13). In 31 patients, oxyhemoglobin and deoxyhemoglobin concentrations were recorded, showing significant changes during both external carotid artery and internal carotid artery clamping. A change in TOI was predominantly associated with internal carotid artery clamping (n=41). When TOI changed during external carotid artery clamping (n=8), significant blood pressure changes occurred, or extracranial-to-intracranial anastomosis was evident. In the absence of such variables, the sensitivity of TOI to intracranial and extracranial changes was 87.5% and 0%, respectively, and specificity was 100% and 0%, respectively. CONCLUSIONS: The NIRO 300 reflects changes in cerebral tissue oxygenation when TOI is calculated, with a high degree of sensitivity and specificity.

Multiparameter brain tissue monitoring--correlation between parameters and identification of CPP thresholds.

Continuous monitoring of brain interstitial gas concentrations allows direct regional evaluation of the pathophysiology of cerebral tissues. We have incorporated the Paratrend 7 (P7) multiparameter sensor into our established multimodal monitoring of head injured patients, to investigate the relationship between brain and arterial pO2, pCO2, and pH, as well as defining thresholds for cerebral perfusion pressure (CPP). A P7 sensor was inserted into the brain tissue of 40 adult head injured patients via a modified Camino bolt or triple lumen bolt. A second sensor was placed in the femoral artery for continuous monitoring of blood gases. Data signals from 19 monitored parameters were collected onto computer at the bedside for up to 14 days. No complications were seen. For individual patients the changes in brain tissue parameters showed large variations over 24 hours and the relationship between parameters varied considerably both between patients and during the period of monitoring any one individual. Changes related to periods of arterial desaturation, cerebral hypoperfusion and therapeutic manoeuvres could be seen. Good correlation was seen between brain pCO2 and arterial pCO2 (r = 0.58). Poor correlation was seen between CPP and brain pO2, and between brain pO2 and ICP. However, by grouping values for intracranial pressure (ICP) and CPP, thresholds for brain tissue pO2 were identified in 16 patients where CPP fell below 60 mmHg. No patients where CPP was always > 60 mmHg showed a significant threshold for a drop in brain pO2 (n = 16). In conclusion, the P7 shows potential as a monitor of regional brain oxygenation and for detection of potentially damaging secondary insults. The results must be interpreted whilst considering catheter position, autoregulation and systemic arterial changes for each individual.

Head injury monitoring using cerebral microdialysis and Paratrend multiparameter sensors.

INTRODUCTION: Following head injury complex pathophysiological changes occur in brain metabolism. The objective of the study was to monitor brain metabolism using the Paratrend multiparameter sensor and microdialysis catheters. PATIENTS, MATERIAL AND METHODS: Following approval by the Local Ethics Committee and consent from the relatives, patients with severe head injury were studied using a triple bolt inserted into the frontal region, transmitting an intracranial pressure monitor, microdialysis (10 mm or 30 mm membrane; glucose, lactate, pyruvate, glutamate) catheter and Paratrend multiparameter (oxygen, carbon dioxide, pH and temperature) sensor. A Paratrend sensor was also inserted into the femoral artery for continuous blood gas analysis. RESULTS: 21 patients were studied with cerebral microdialysis for a total of 91 monitoring days (range 19 hours to 12 days). Of these, 14 patients were also studied with cerebral and arterial Paratrend sensors. The mean (+/- 95% confidence intervals) arterial and cerebral oxygen levels were 123 +/- 10.9 mmHg and 27.9 +/- 5.71 mmHg respectively. The arterial and cerebral carbon dioxide levels were 34.3 +/- 2.35 mmHg and 45.3 +/- 3.07 mmHg respectively. Episodes of systemic hypoxia and hypotension resulting in falls in cerebral oxygen and rises in cerebral carbon dioxide were rapidly detected by the arterial and cerebral Paratrend sensors. Systemic pyrexia was reflected in the brain with the cerebral Paratrend sensor reading 0.17 degree C (mean) higher than the arterial sensor. Elevations of cerebral glucose were detected, but the overall cerebral glucose was low (mean 1.57 +/- 0.53 mM 10 mm membrane; mean 1.95 +/- 0.68 mM 30 mm membrane) with periods of undetectable glucose in 6 patients. Lactate concentrations (mean 5.08 +/- 0.73 mM 10 mm membrane; mean 8.27 +/- 1.31 mM 30 mm membrane) were higher than glucose concentrations in all patients. The lactate/pyruvate ratio was 32.1 +/- 5.16 for the 10 mm membrane and 30.6 +/- 2.17 for the 30 mm membrane. Glutamate concentrations varied between patients (mean 15.0 +/- 10.5 microM 10 mm membrane; mean 28.8 +/- 17.8 microM 30 mm membrane). CONCLUSION: The combination of microdialysis catheters and Paratrend sensors enabling the monitoring of substrate delivery and brain metabolism, and the detection of secondary metabolic insults has the potential to assist in the management of head-injured patients.

Clinical cerebral microdialysis: a methodological study.

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

OBJECTIVE AND IMPORTANCE: The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. CLINICAL PRESENTATION: A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. INTERVENTION: During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. CONCLUSION: The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

On-line monitoring of substrate delivery and brain metabolism in head injury.

Head injury is associated with complex pathophysiological changes in metabolism. The objective of the study was to investigate these changes by applying on-line bedside monitoring of cerebral metabolism using microdialysis. Following approval by the Local Ethics Committee and consent from the next of kin, a microdialysis catheter was inserted into the frontal cortex of patients with severe head injury. Twenty-one patients were studied for 102.3 +/- 26.9 hours (mean +/- 95% confidence interval; total 89.4 patient monitoring days). The overall cerebral glucose (mean of means) was 1.63 +/- 0.31 mM with periods of undetectable glucose recorded. The cerebral lactate and lactate/pyruvate ratio were 4.69 +/- 0.61 mM and 29.9 +/- 3.73 respectively. Patients who died (n = 4) or who were severely disabled (not proceeding to rehabilitation, n = 5) had a tendency towards lower glucose (1.39 +/- 0.35 mM), higher lactate (5.10 +/- 1.02 mM) and higher lactate/pyruvate ratios (35.5 +/- 7.67) compared to patients with good outcome (home or proceeding to rehabilitation, n = 12, glucose 1.80 +/- 0.49 mM, lactate 4.38 +/- 0.85 mM, lactate/pyruvate ratio 27.9 +/- 4.33). Trends in these metabolic parameters relating to outcome were identifiable. In the majority of patients, cerebral glutamate levels (overall mean of means 9.47 +/- 4.59 microM) were initially high and then declined to stable levels. Patients in whom the glutamate level remained elevated or in whom secondary rises in glutamate were seen had a poor outcome. The application of bedside analysis of microdialysis enables the progress of the patient to be monitored on-line. In addition to establishing trends of improving and deteriorating metabolism, the technique has the potential to monitor the effects of therapeutic manoeuvres on the biochemistry.