Intravenous glutamine supplementation to head trauma patients leaves cerebral glutamate concentration unaffected.

OBJECTIVE: There is reluctance to use glutamine-containing i.v. nutrition for neurosurgical patients, as this may result in elevated intracerebral glutamate levels, which are thought to be associated with neuronal injury and cell swelling, causing an increase in ICP and an unfavourable outcome. As general ICU patients benefit from i.v. glutamine supplementation in terms of reduced mortality and morbidity, neurosurgical patients might also be candidates for such treatment, if the possible relation between i.v. glutamine supplementation and a possible increase in cerebral glutamate could be sorted out. DESIGN AND SETTING: The study protocol had a crossover design with a 24h treatment period and a 24h placebo period in random order. Treatment was a glutamine containing dipeptide, L-alanyl-L-glutamine 200mg/ml, for 20h; placebo was saline. The rate of infusion was 0.125ml/kg/h, which is equal to 0.34g/kg of glutamine over the 20h period. Microdialysate was collected for analysis in 120min portions. The flow through the microdialysis catheter was 0.3microl/min. SUBJECTS: Patients with severe head trauma (GCS

Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after non-complicated gastrointestinal surgery.

OBJECTIVE: Visceral ischemia is an early event in the development of shock and organ failure. Microdialysis has been presented as a promising method for detection of visceral hypoxia and ischemia. The aim of this study was to investigate differences in the metabolic response measured by microdialysis between intraperitoneal and subcutaneous locations and to estimate normal values of lactate/pyruvate ratio, glucose and glycerol. MATERIAL AND METHODS: Intraperitoneal and subcutaneous metabolic responses were compared regarding lacate/pyruvate ratio, glucose and glycerol, during 45 postoperative hours in 33 patients undergoing various non-complicated elective major gastrointestinal surgery. RESULTS: Intraperitoneal lactate/pyruvate ratio started around 15 and decreased over time, while subcutaneous levels were stable around 9. Glucose levels were higher intraperitoneally and increased rapidly during the first 9 h to 8.6 mM, while the subcutaneous levels increased during 21 h to 7.5 mM. Intraperitoneal glycerol levels were stable around 100 microM, while subcutaneous values started around 230 microM and then increased. CONCLUSIONS: In a non-complicated postoperative course the lactate/pyruvate ratio and glucose levels are higher intraperitoneally, suggesting a higher postoperative intraperitoneal metabolism. Glycerol levels are higher and increase subcutaneously, suggesting increased postoperative energy demand, particularly in the visceral organs, as being responsible for the lipolysis seen in the subcutaneous tissue.

Subcutaneous microdialysis before and after an oral glucose tolerance test: a method to determine insulin resistance in the subcutaneous adipose tissue in diabetes mellitus.

AIMS: Subcutaneous microdialysis has been used for continuous glucose monitoring in patients with diabetes mellitus (DM) to facilitate tight regulation of blood glucose levels. The aims of this study were therefore to investigate (i) the relationship between capillary and interstitial glucose in patients with type 1 or 2 DM and healthy subjects and (ii) the feasibility of using microdialysis to assess local insulin sensitivity in adipose tissue. METHODS: Using subcutaneous microdialysis, interstitial glucose, lactate, pyruvate and glycerol were determined as measures of glucose and lipid metabolism in adipose tissue, before and after an oral glucose tolerance test (OGTT) in 14 patients and seven controls. The results were correlated to whole-body insulin sensitivity and insulin sensitivity in liver estimated from the levels of insulin-like growth factor-binding protein 1 (IGFBP-1). RESULTS: Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and in type 1 DM but not in type 2 DM. In fasting state, the glycerol levels were higher in both type 1 and type 2 DM compared with controls. After the OGTT, the insulin levels were sufficient to suppress lipolysis in type 1 but not in type 2 DM. The glucose/lactate ratio was higher at fasting in type 1 DM and after OGTT in type 1 and 2 DM. In type 1 DM, basal interstitial glycerol levels correlated to whole-body glucose utilization. In type 2 DM, correlations were found between the basal glycerol levels and whole-body insulin sensitivity and between glucose/lactate and per cent decrease in IGFBP-1 levels 120 min after OGTT. CONCLUSION: Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and patients with type 1 DM. Correlations were also found between insulin sensitivity in whole body and in adipose tissue in both type 1 and type 2 DM and between insulin sensitivity in subcutaneous adipose tissue and liver in type 2 DM. This study shows that microdialysis technique can be used to study in vivo insulin sensitivity in adipose tissue over time and may be useful in the evaluation of, for example, the effects of new drugs on insulin sensitivity.

Measurement of glucose and metabolites in subcutaneous adipose tissue during hyperglycemia with microdialysis at various perfusion flow rates.

BACKGROUND: Microdialysis-based glucose sensors have recently been introduced for monitoring glucose levels in diabetic patients. The flow rate by which the fluid sample is pumped through the microdialysis catheter varies in different studies. AIM: To study the effects of various flow rates on glucose and its metabolites sampled by microdialysis during an oral glucose tolerance test. MATERIAL, METHODS: Glucose, lactate, pyruvate and glycerol were measured with microdialysis in interstitial fluid of subcutaneous adipose tissue in twelve healthy young subjects before and during an oral glucose tolerance test using four different flow rates (0.3, 1, 2 and 5 microL/min) and a 30 mm dialysis membrane. RESULTS: At the basal fasting state the dialysate glucose obtained by 0.3 microL/min was equal to capillary glucose concentration. A decrease in dialysate glucose levels during the basal state was observed for higher flow rates but not for 0.3 microL/min, which indicates a depleting effect. The relative increase after OGTT was similar for capillary glucose and flow rate 0.3 microL/min but not for higher flow rates. CONCLUSION: The low microdialysis flow rate (0.3 microL/min) facilitates the capture of true interstitial glucose concentrations during glucose fluctuations. Thus this low flow rate is preferred in studies of local tissue metabolism.

Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema.

BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI2 in an experimental model of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h before the LPS injection and was constant during the study period. RESULTS: Intracranial pressure increased significantly in animals treated with PGI2. The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of low-dose PGI2 caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.

Postoperative on-line monitoring with intraperitoneal microdialysis is a sensitive clinical method for measuring increased anaerobic metabolism that correlates to the cytokine response.

BACKGROUND: Visceral ischaemia and cytokine release are early stages in the development of shock and multiorgan failure. Because of lack of methods to measure anaerobic metabolism or visceral hypoxia in the early phase, diagnosis is not usually established until shock and organ failure are evident. METHODS: Nineteen patients were studied postoperatively after major abdominal gastrointestinal surgery. A microdialysis catheter was placed intraperitoneally before closure of the abdomen. Analysis of glucose, pyruvate and lactate was performed every second hour and the ratio between lactate and pyruvate was calculated. Peritoneal fluid was collected from a peritoneal drainage for analysis of tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10). RESULTS: Sixteen of the patients had a normal postoperative course; the lactate/pyruvate ratio started at the level of 20 immediately postoperatively and decreased significantly during the first 45 postoperative hours (P = 0.007). A similar pattern was recorded for peritoneal TNF-alpha, which decreased correspondingly (P = 0.003). A correlation coefficient of 0.303 (P < 0.001 ) between lactate/pyruvate ratio and TNF-alpha was found. After an initial short increase, IL-10 decreased over time (P < 0.001). Three of the patients had abnormalities in the microdialysis results, cytokines and clinical outcome. These patients are presented separately. CONCLUSIONS: A normal postoperative course results in a decrease in the intraperitoneal lactate/pyruvate ratio, TNF-alpha and IL-10. A correlation between the intraperitoneal lactate/pyruvate ratio and TNF-alpha was found which suggests that intraperitoneal microdialysis is a sensitive, indirect method in analysing the postoperative intraperitoneal inflammatory response. A complicated postoperative course was preceded by increase of the peritoneal lactate/pyruvate ratio interpreted as splanchnic hypoxia and also an increased TNF-alpha level.

Results of intraperitoneal microdialysis depend on the location of the catheter.

BACKGROUND AND OBJECTIVE: Intraperitoneal microdialysis was recently described as a method for early detection of visceral ischemia. The method seems safe and accurate. The intra-abdominal catheter used may imply variations in results depending on the location of the catheter. The aim of the study was to investigate possible differences in metabolic parameters obtained depending on various locations of the intra-abdominal catheter, compared with using the subcutaneous reference catheter. METHOD: After right-sided hemicolectomy in 12 patients, three catheters were placed and fixed intraperitoneally: one at the anastomosis, one in the omentum and one embedded between the small intestinal loops. A subcutaneous catheter placed in the pectoral region was used as reference. Analyses of lactate/pyruvate ratio and glucose and glycerol levels were done during a period of 45 hours postoperatively. RESULTS: Lactate/pyruvate ratio decreased numerically at all three intraperitoneal locations during the study while the subcutaneous lactate/pyruvate ratio increased slightly. Significant differences between intraperitoneal and subcutaneous locations were found as well as differences between the three intraperitoneal locations. Highest values of the lactate/pyruvate ratio were found at the anastomosis, while the widest range was found at the small intestine. Subcutaneous glucose levels were lower while glycerol levels were higher compared with intraperitoneal values. CONCLUSIONS: In evaluating postoperative metabolism, intraperitoneal microdialysis is influenced by the location of the microdialysis catheter. The same pattern is, however, recorded over time. The juxta-anastomotic region and the small intestinal loop area seem to be the most reasonable locations for measurements.

Human intraperitoneal microdialysis: increased lactate/pyruvate ratio suggests early visceral ischaemia. A pilot study.

BACKGROUND: Previous studies suggest that visceral ischaemia precedes shock and multiple organ failure, though methods for studying humans are lacking. We aimed to evaluate intraperitoneal microdialysis, a new technique for detecting splanchnic ischaemia in clinical practice. METHODS: Right-sided hemicolectomy was performed in eight patients who were studied by microdialysis postoperatively for glucose, lactate, pyruvate and glycerol levels. RESULTS: Six of the eight patients showed a normal postoperative course and had lactate/pyruvate ratios between 7.1 and 21.7, glucose between 4.5 and 14.3 mmol/L and glycerol between 10.4 and 296 micromol/L. In one patient, intraperitoneal lactate/pyruvate ratio and glycerol increased and glucose decreased 5 h before low oxygenation appeared. Another patient exhibited a period of increased lactate/pyruvate ratio before a period of atrial fibrillation. CONCLUSION: Intraperitoneal microdialysis was performed safely. Two out of the eight patients exhibited changes of metabolic markers followed by clinical symptoms that were probably related to transient visceral ischaemia. Our findings suggest that intraperitoneal microdialysis may become a useful tool for monitoring splanchnic ischaemia in clinical practice.

Bedside biochemical monitoring of the penumbra zone surrounding an evacuated acute subdural haematoma.

We describe a penumbra zone with increased biochemical vulnerability in cerebral cortex underlying an evacuated acute subdural haematoma. Two microdialysis catheters were placed in this zone and one catheter was placed in the opposite, less injured hemisphere. The microdialysis perfusates were analysed bedside for glucose, pyruvate, lactate, glutamate, and glycerol. In the penumbra zone, but not in the opposite hemisphere, energy metabolism was seriously disturbed with signs of cell membrane degradation. During an adverse event (decrease in haemoglobin level, systemic blood pressure and cerebral perfusion pressure) the perturbation of energy metabolism increased in this zone. Energy metabolism recovered and the signs of cell membrane degradation disappeared after normalization of the physiological parameters. We use the term biochemical penumbra zone to describe an area with signs of energy failure and cell membrane degradation, which has a capacity to regain a normal metabolic pattern but also an increased vulnerability to secondary insults.

Regional differences in glutamine synthetase inhibition by L-methionine sulfoximine: a microdialysis study in the rabbit brain.

Elevated levels of glutamate, an endogenous excitatory amino acid, contribute to the development of neuronal injury in various cerebral diseases. Using a microdialysis approach, the response of extracellular levels of amino acids and metabolic parameters to glutamine synthetase inhibition by l-methionine sulfoximine was monitored simultaneously in the hippocampal formation and in the frontal cortex of the rabbit brain. In the hippocampal formation the decrease of glutamine levels during l-methionine sulfoximine treatment was more pronounced than in the frontal cortex, and was accompanied by a delayed decline of extracellular glutamate concentrations. Furthermore, l-methionine sulfoximine diminished the increase of lactate and pyruvate concentrations in the hippocampal formation, but not in the frontal cortex. Neither l-methionine sulfoximine treatment nor microdialysis probe insertion caused neuronal apoptosis, as measured by in situ tailing. An impaired function of hippocampal astrocyte glutamate uptake mechanisms or a higher functional capacity of the cortical glutamine synthetase may be possible explanations for the differences demonstrated. The present data are in accordance with regional differences in glutamine synthetase activation during bacterial meningitis and may explain, in part, the higher susceptibility of certain areas of the hippocampal formation (i.e., the dentate gyrus) to neuronal injury.

Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care.

BACKGROUND: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. METHODS: The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 microl/min) with a Ringer solution from a microinfusion pump and analyzed for glucose, lactate, and glycerol. The study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. RESULTS: The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The correlation was relatively poor for 1-6 h after insertion of the probes. During this period, a continuous increase in the subcutaneous level of glucose and decreases in lactate and glycerol were noted. CONCLUSIONS: The correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6 h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.

Cerebral physiological and biochemical changes during vasogenic brain oedema induced by intrathecal injection of bacterial lipopolysaccharides in piglets.

BACKGROUND: The objective of the study was to evaluate biochemical and physiological changes in an experimental model of vasogenic brain oedema utilising techniques also used in routine neurointensive care. METHOD: 32 piglets were randomised to control or experimental group. The latter received an intrathecal injection of lipopolysaccharide (LPS) from E. coli (LPS group). Intracranial pressure (ICP)and mean arterial pressure (MAP) were measured continuously. Intracerebral microdialysis was used for analysing interstitial levels of glucose, pyruvate, lactate, glutamate, glycerol and urea every 30 min. Repeated calculations of mean hemispheric CBF were performed utilising an extracranial scintillation detector and Intra-carotid injection of (133)Xe. Cerebral specific gravity was measured and the brains were fixed for histological examinations. FINDINGS: After LPS injection ICP increased reaching a plateau phase after 4-7 hours and CBF increased by 46%. Histological examination showed inflammation with pronounced extravasation of granulocytes. A significant decrease in brain specific gravity (p =0.022) was obtained. LPS caused a significant decrease in cerebral interstitial concentration of glucose (p = 0.0035), and significant increases in lactate concentration (p = 0.002) and lactate/pyruvate ratio (p = 0.0017). A small but significant increase in glutamate was obtained (p = 0.0219). Glycerol did not change significantly. INTERPRETATION: Intrathecal LPS caused an inflammatory reaction with extravasation of granulocytes, increased blood-brain barrier permeability and cerebral oedema. Biochemical analyses indicate increased glycolysis but no signs of cell membrane degradation.

Clinical experience in continuous graft monitoring with microdialysis early after liver transplantation.

BACKGROUND: Early detection of impaired graft function after transplantation is essential. Microdialysis permits continuous monitoring of metabolic changes by mimicking the passive function of a capillary blood vessel by perfusion of a tubular semipermeable membrane introduced into the tissue. Based on the results of animal experiments, a clinical pilot study was undertaken. METHODS: Ten consecutive patients undergoing whole-organ orthotopic liver transplantation were studied. Intrahepatic implantation of a microdialysis catheter was performed at the end of the operation. A reference catheter was placed in the subcutaneous tissue over the right pectoral area immediately after abdominal closure. Consecutive serial samples were collected at 1-h intervals for 3 days after the operation. Glucose, lactate, pyruvate and glycerol concentrations were measured. RESULTS: During the first 24 h, the glucose level was higher in the liver than in reference tissue. Initially, increased mean(s.e.m.) levels of lactate (7.0(1.9) mmol/l) were observed in the liver, with a rapid decrease (to 2.7(0.3) mmol/l) over 24 h. A decrease in, and later stabilization of, the lactate : pyruvate ratio in the liver, from 18.7(4.2) to 10.0(1.1), was observed within 24 h after transplantation. Liver glycerol levels decreased from 62.3(7.4) to 24.3(7.5) micro mol/l within the first 16 h after reperfusion and remained stable thereafter. CONCLUSION: Microdialysis allows continuous monitoring of tissue metabolism in the transplanted liver. The procedure is easy to perform and safe. The specific detection and monitoring of pathological changes in the liver graft (e.g. arterial and portal vein thrombosis, or early rejection) with microdialysis should be addressed in further studies.

Local changes in cerebral energy metabolism due to brain retraction during routine neurosurgical procedures.

PATIENTS AND INTERVENTIONS: Tissue damage caused by brain retraction was evaluated utilizing intracerebral microdialysis in six patients operated on subfrontally for pituitary adenoma. The microdialysis probes (membrane length 10 mm, cut-off 20 kDalton) were placed in cerebral cortex beneath the brain retractor and perfused with Ringer solution at 0.3 microl/min. The microdialysis vials were changed at intervals of 30 minutes and analysed for glucose, pyruvate, lactate, glutamate and glycerol. RESULTS: During brain retraction regional intracerebral glucose was within normal range in cortical tissue and the levels of lactate, glutamate, and glycerol as well as the lactate/pyruvate ratio were considerably above normal range. CONCLUSION: The biochemical analysis shows a pronounced incomplete cerebral ischemia due to brain retraction. The increases in glutamate and glycerol indicate tissue damage and degradation of cell membranes. Intracerebral microdialysis may be a valuable tool in the development of optimal techniques for brain retraction during neurosurgical procedures.

Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia.

BACKGROUND: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol. METHODS: Fourteen patients who underwent major abdominal or thoraco-abdominal surgery were studied postoperatively over 3 days. For postoperative analgesia the patients were prospectively randomized to receive either thoracic epidural analgesia with a bupivacaine/morphine infusion (EPI-group, n=6) or a continuous i.v. infusion of morphine (MO-group, n=8). The concentration of glycerol, glucose and lactate in the abdominal and deltoid subcutaneous adipose tissue were measured using a microdialysis technique. RESULTS: The abdominal glycerol levels were equal in both groups. In the deltoid region of the EPI-group, glycerol concentrations started to increase on Day 2, and reached significantly higher levels on Day 3 compared with the MO-group. The glucose and lactate levels showed no differences between groups in the two regions. CONCLUSION: The uniform glycerol levels in abdominal subcutaneous adipose tissue in conjunction with the difference in glycerol levels in the deltoid area indicate that the local lipolysis is different in the two study groups. This might be explained by a regional metabolic influence of thoracic epidural analgesia, possibly via the sympathetic nervous system.

Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and rats.

The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats (n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats (P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.

Lactate concentrations in human skeletal muscle biopsy, microdialysate and venous blood during dynamic exercise under blood flow restriction.

The intramuscular microdialysate lactate concentration during dynamic exercise with various degrees of blood flow restriction and its relation to lactate concentration in skeletal muscle biopsy and venous blood were studied. Nine healthy males performed three one-legged knee extension exercises (Ex 1-3). Blood flow was restricted stepwise by applying supra-atmospheric pressure over the working leg. Microdialysate mean (range) lactate concentrations at the end of the exercise periods were 3.2 (0.5-6.6), 4.4 (1.1-9.8) and 7.9 (1.1-11.6) mmol.l(-1)during unrestricted, moderately restricted and severely restricted blood flow respectively. There was a significant correlation between microdialysate and venous lactate concentrations at the end of all three exercise periods. Microdialysate lactate concentration correlated significantly to skeletal muscle biopsy lactate concentration at the end of Ex 1. In conclusion, microdialysate lactate concentration in the working muscle increased step-wise with increasing blood flow restriction. It showed a better correlation to venous than to muscle biopsy lactate, which is possibly partly explained by the characteristics of diffusion between body compartments and differences in time resolution between the methods used.

Microdialysis in human skeletal muscle: effects of adding a colloid to the perfusate.

Microdialysis catheters (CMA-60 with a polyamide dialysis membrane; 20,000-molecular wt cutoff) were either immersed in an external medium or were inserted in the quadriceps femoris muscle of healthy subjects, using perfusate with or without dextran 70. Varying the position of the outflow tubing induced changes in hydrostatic pressure. The sample volumes were significantly smaller in catheters perfused without a colloid compared with those perfused with a colloid [11-50% (in vitro) and 8-59% (in vivo) lower than in colloid-perfused catheters with the same position of the outflow tubing]. The sample volumes were also significantly smaller when the dialysis membrane was influenced by maximal hydrostatic pressure (above position) compared with minimal hydrostatic pressure (below position) [7-38% (in vitro) and 3-46% (in vivo) lower than in catheters in the below position with the same perfusion fluid]. In vivo, glucose concentration at a perfusion flow rate of 0.33 microl/min was higher when the catheters were perfused without a colloid [18-28% higher than in colloid-perfused catheters with the same position of the outflow tubing (P < 0.001)] than with a colloid. A corresponding difference also tended to occur with lactate, glycerol, and urea. At 0.16 microl/min, the glucose concentration was the same irrespective of whether fluid loss had been counteracted by colloid inclusion or by lowering of outlet tubing. The mechanism behind the observed concentration difference is thought to be a higher effective perfusion flow rate when fluid loss is prevented at low-perfusion flows. This study shows that fluid imbalances can have important implications for microdialysis results at low-perfusion flow rates.

Spinal cord metabolism during thoracic aortic cross-clamping in pigs with special reference to the effect of allopurinol.

OBJECTIVE: investigate the metabolic response of the spinal cord and the effect of allopurinol following cross clamping of the descending thoracic aorta in a porcine model. DESIGN: experimental animal study. MATERIALS: twelve domestic swine. Six pigs were pre-treated with allopurinol, while six pigs served as controls. METHODS: measurement of extracellular concentrations of glucose, pyruvate, lactate, glycerol and glutamate using microdialysis in the lumbar spinal cord. Measurement of lumbar spinal blood flow using laser Doppler technique. RESULTS: for all animals there was a significant decrease in concentrations of glucose and pyruvate together with a significant increase in the lactate-pyruvate ratio during aortic cross clamping. There was also a significant increase in glycerol concentrations 60 min after cross clamping, and a significant decrease in glutamate concentrations after 50 min. No differences in concentrations of glucose, pyruvate, lactate and glutamate or the glutamate-pyruvate ratio were observed between animals used as controls and those treated with allopurinol. The laser Doppler flux decreased to 40% of pre cross-clamp level, returning to normal values at declamping. CONCLUSION: the changes in energy-related metabolites reflect a considerable ischaemia in the spinal cord tissue but there was no convincing effect of allopurinol on the lumbar spinal cord metabolism during thoracic aortic cross clamping in this model.

Intracerebral microdialysis and bedside biochemical analysis in patients with fatal traumatic brain lesions.

BACKGROUND: Microdialysis with bedside biochemical analysis was used to monitor cerebral biochemical alterations that precede and accompany increase in intracranial pressure (ICP), resulting in a complete cessation of cerebral blood flow. METHODS: Seven patients, who died due to an untreatable increase in ICP, were included. The patients originate from a large, consecutive series of severely head injured patients (n: 95) monitored with intracerebral microdialysis (perfusion rate 0.3 microl/min). One microdialysis catheter was inserted via a separate burr hole frontally to that used for the intraventricular catheter ("better" position) and one catheter was inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated haematoma ("worse" position). Biochemical analyses of glucose, lactate, glycerol, urea, glutamate, and pyruvate were performed at the bedside. All samples were frozen for subsequent HPLC (high-performance liquid chromatography) analyses of amino acids and ions. RESULTS: Decreases in glucose and pyruvate and increases in lactate, glycerol, glutamate, and lactate/pyruvate (la/py) ratio characterized cerebral ischaemia. The measured markers give information regarding substrate availability (glucose), redox state of the tissue (la/py ratio), degradation of glycerophospholipids in cell membranes (glycerol), and extracellular concentration of excitatory amino acids (glutamate). In the "worse" position biochemical deterioration occurred before the increase in ICP. In the "better" position biochemical deterioration was usually observed after the increase in ICP. CONCLUSION: Changes of cerebral energy metabolism that accompany cerebral ischaemia follow a certain pattern and may be detected at the bedside by intracerebral microdialysis before the secondary damage causes an increase in ICP.