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In situ gentamicin concentrations in cortical bone: an experimental study using microdialysis in bone.

We used microdialysis to study gentamicin in cortical bone and compared these results to values obtained in bone specimens. 10 healthy pigs were given an intravenous bolus of 160 mg of gentamicin. We measured reproducibility by inserting two microdialysis catheters into the cortex of tibial diaphyses and by taking samples of serum, dialysates and bone specimens during 6 hours and measuring the concentrations of this antibiotic. The peak concentrations in the two microdialysis probes and bone specimens were 3 mg/L, 2.9 mg/L and 2.6 mg/L (Anova, p = 0.3). Similarly, the areas under the curve from 0 to 6 hours (AUC6h) were 704 mg/min/L, 661 mg/min/L and 569 mg/min/L (Anova, p = 0.07). The reproducibility of the measurements of the microdialysates was evaluated with the mean AUC(6h/catheter no.1)/AUC(6h/catheter no. 2) ratio, which was 1.12. It seems that microdialysis is a suitable method for making dynamic and quantitative measurements of gentamicin in bone.

Animals↗

Technical aspects of microdialysis of human breast.

In this study a technique for insertion of microdialysis catheters and the influence of the position of the catheters within normal human breast tissue were evaluated by measuring amino acids. Moreover, to assess variability over time, the levels of amino acids were measured during a period of 3 h. In nine healthy women two parallel microdialysis catheters were implanted, guided by a catheter for intravenous use, into the breast tissue. All insertions were successful and there were no complications. The levels of amino acids were equal in the two parallel catheters and varied less than 10% over a period of 3 h. Insertion of the microdialysis catheter via an intravenous catheter is suitable for the dense breast tissue. The position of the microdialysis catheter within the same breast seems to be of minor importance for measurements of amino acids. Thus, the described technique is a safe and reproducible way of investigating the human breast in vivo.

Adult↗

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.

Adipose Tissue↗

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.

Aged↗

Validation of microdialysis probes for studying nitrosative chemistry within localized regions of the human upper gastrointestinal tract.

BACKGROUND: We have examined the suitability of microdialysis probes for examining nitrosative chemistry within localized regions of the lumen of the gastrointestinal tract. Chemical nitrosation occurs maximally at pH 2.5 in the presence of nitrite and thiocyanate and absence of ascorbic acid. Nitrite and thiocyanate are delivered into the stomach in saliva and ascorbic acid is secreted in gastric juice. METHODS: We used a benchtop model to reproduce the nitrosative chemistry occurring in the human upper GI tract and assessed the ability of the microdialysis probes to measure it. RESULTS: The microdialysis probes were reliable at measuring nitrite ascorbic acid, total vitamin C and thiocyanate in both aqueous solutions and human gastric juice over the full range of intragastric pH, i.e. 1.5, 2.5, 3.5, 5.0 and 7.0. The probes were also reliable at measuring these chemicals under conditions simulating the active interaction between nitrite and ascorbic acid. Under such conditions with ascorbic acid in excess the probes gave a more accurate assessment of the nitrite level than that obtained by directly sampling the gastric juice. This was due to the probes not being subject to artefactual measurement of nitric oxide as nitrite. This was prevented by the rapid diffusion of nitric oxide through the probe collecting tube. CONCLUSION: Microdialysis probes provide a reliable means of examining nitrosative chemistry within the lumen of the upper GI tract. In addition, they have the advantage of measuring this chemistry in very local regions and of simultaneously comparing the chemistry in different regions of the upper GI tract.

Ascorbic Acid↗

Validation of intramural intestinal microdialysis as a detector of intestinal ischaemia.

BACKGROUND: The purpose of this study was to validate intestinal microdialysis as a detector of intestinal ischaemia using measurements of glucose, lactate and glycerol from the jejunal wall. METHODS: Based on a previous study, the cut-off levels for the presence of regional intestinal ischaemia were defined for microdialysis glucose, lactate, glycerol and the lactate/glucose ratio. Changes of 60% in the metabolic compounds measured after 100 min were defined as the cut-off level for ischaemia. The cut-off levels were tested in a randomized, single-blinded study. Ten pigs were used; occlusive ischaemia was performed by clamping a segment of the mesentery to the intestine. Four catheters were inserted per pig, two in the ischaemic segment and two in the non-ischaemic segment. All catheters were numbered, randomly allocated and inserted in the intestine by the staff at the institute and unknown to the investigators. RESULTS: One pig was excluded because the clamping was insufficient. Technical problems with the catheters were registered in 15% of cases owing to damage of the microdialysis membrane, dislocation, or incorrect placement. The predictive values of presence of ischaemia for glucose, lactate, glycerol and the lactate/glucose ratio were: 0.91, 1,0.85 and 0.92, respectively. CONCLUSION: Using a 60% cut-off limit measured after 100 min, intestinal ischaemia can be detected and excluded using intestinal microdialysis, but some technical problems remain that need further investigation.

Animals↗

Surveillance of triazole susceptibility of colonizing yeasts in patients with haematological malignancies.

The species distribution and antifungal susceptibility of yeasts isolated from colonization cultures, and the contribution of previous fluconazole prophylaxis to the emergence of resistance, was prospectively studied in 87 neutropenic patients treated for haematological malignancies. Minimal inhibition concentrations (MICs) to fluconazole, itraconazole and voriconazole for 123 yeast isolates (65 Candida albicans, 22 Candida glabrata, 15 Saccharomyces cerevisiae, 5 Candida krusei, 5 Candida norvegensis, 11 other Candida spp.) were determined by E-test. Fluconazole MICs for Candida species and S. cerevisiae isolated from patients given prophylaxis were > or =2 mg/l in 24 of 40 (60%) isolates compared with 26 of 83 (31%) isolates from patients in the non-prophylaxis group (p =0.002). Among the non-albicans yeast species reduced susceptibility was common against itraconazole but was rarely found against voriconazole. Cross resistance between fluconazole and itraconazole was observed in 14 of all isolates, 4 of them also showing reduced susceptibility to voriconazole (MICs 4-8 mg/l). Fluconazole prophylaxis may contribute to emergence of less susceptible yeast strains also in patients with haematological malignancies not treated with allogeneic bone marrow transplantation.

Adult↗

A multi-sample microdialysis apparatus for proteins and nucleic acids.

A multiposition microdialysis system suitable for simultaneous microsample applications (between 10 microL and 500 microL), has been developed. Each sample, contained in a specially designed microfuge dialysis tube (mDT), is dialysed independently from the other samples. Each mDT has its own membrane, and this feature allows the use of different membranes and dialysis times for different samples. The microdialysis apparatus is kept at constant temperature by an external thermostat, avoiding the use of a cold box. The dialysis release time for small ions, a parameter used for quantitation of microdialysis efficiency, decreases from 22.9 min (for a 200 microL sample) to 7 min (for a 50 microL sample). The sample is efficiently recovered by centrifugation. Quantitative recoveries (90%) of different proteins and DNA were achieved after microdialysis by mDT.

Microdialysis↗

The role of cerebral microdialysis in predicting the outcome after experimental hypothermic circulatory arrest.

OBJECTIVE: To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. DESIGN: Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20 degrees C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. RESULTS: Brain glucose concentrations were higher in animals that survived (p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period (p=0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. CONCLUSION: Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Animals↗

Monitoring of porcine myocardial ischemia and reperfusion by intravasal microdialysis.

OBJECTIVE: A novel application of microdialysis is studied where myocardial metabolism is semi-continuously monitored in the myocardial venous outflow during ischemia and reperfusion. DESIGN: Microdialysis catheters were introduced into the great cardiac vein, the pulmonary artery, and the right external jugular vein in 20 anesthetized pigs. The left anterior descending artery was occluded in four separate groups of pigs for 0, 10, 15, and 60 min, respectively. Ischemia was followed by 120 min of reperfusion. Microdialysis samples were collected every 10-20 min and analyzed for lactate, pyruvate, glycerol, glutamate, and glucose. RESULTS: Myocardial infarction was observed after 15 min of ischemia. Metabolic changes were observed only in the great cardiac vein. Lactate increased early during ischemia. After 60 min of ischemia an increase of the lactate/pyruvate ratio and glutamate was observed. Glycerol was progressively released during prolonged ischemia. Myocardial infarction resulted in an additional release of glycerol early in reperfusion. CONCLUSION: Intravasal microdialysis is a semi-continuous method to monitor myocardial metabolism and tissue damage during ischemia and reperfusion.

Animals↗

Evaluation of myocardial metabolism with microdialysis after protection with cold blood- or cold crystalloid cardioplegia. A porcine model.

OBJECTIVES: There has been a considerable change in the patient population referred for cardiac surgery in the last decade. More complex and marginal patients require optimized myocardial protection. An insufficient cardioplegic procedure results in anaerobic metabolism during cardiac arrest with subsequent lactate accumulation. Increased lactate level is regarded as a predictor for low cardiac output syndrome. In an acute porcine model we examined two standard cardioplegic methods. Myocardial microdialysis was used to investigate the metabolism during cardioplegic arrest and in the reperfusion period. METHODS: Twelve domestic pigs were randomly chosen to receive either cold blood-or cold crystalloid cardioplegia. After midline sternotomy two microdialysis probes were implanted in two different regions of the heart. Cardiopulmonary bypass was initiated, aorta was clamped, and antegrade cardioplegia was delivered. These conditions were maintained for 90 min. Subsequent to myocardial reperfusion the animals were observed for 180 min. Microdialysis and plasma markers to characterize myocardial metabolism, and plasma markers for myocardial failure and necrosis were obtained every 30 min. RESULTS: Lactate concentrations were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group, in tissue dialysate (p < 0.001) as well as in serum (p = 0.018). Pyruvate concentrations in the dialysate were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group (p = 0.008). There were no significant differences in dialysate concentrations of glycerol. Plasma markers for myocardial failure (Brain Natriuretic Peptide) and for myocardial necrosis (Cardiac Troponin T) showed no differences between the groups. CONCLUSION: The results indicate that cold blood cardioplegia offers superior protection of the heart, in terms of more rapid normalization of myocardial metabolism. The microdialysis technique seems to have a high sensitivity and ability to detect even minor metabolic changes. This enhances the possibility of designing a myocardial protection, which might lower morbidity and mortality risk.

Animals↗

Microdialysis: a new technique to monitor perioperative human peritoneal mediator production.

BACKGROUND: Standardized methods to measure peritoneal cytokine production do not exist. This feasibility study examines the use of microdialysis to monitor perioperative peritoneal mediator production in patients following abdominal surgery for infective or non-infective conditions. MATERIALS AND METHODS: At the beginning of the operation, a microdialysis catheter was placed between the patient's parietal peritoneum and the muscular fascia of the abdominal wall in the connective tissue bed. The device was irrigated (18 microL/h, Ringer's solution/0.05% albumin) for up to 7 days. Samples of the dialysate were collected at least twice a day, and concentrations of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 were measured by an ELISA technique. Four of the nine patients included had proved intra-abdominal infections. RESULTS: In uninfected patients, IL-6 concentrations peaked 8 h after skin incision (mean +/- SEM): 1696 +/- 1292 pg/mL and dropped rapidly to significantly lower concentrations (less than 400 pg/mL) thereafter. MCP-1 concentrations also peaked at 8 h (12787 +/- 6893 pg/mL). In the following days, MCP-1 concentrations were variable between 1000 and 5000 pg/mL. In infected patients, early IL-6 production tended to be higher and that of MCP-1 tended to be lower than in uninfected patients. Catheters were removed between day four and day seven when the system failed or when the patients became mobile without any clinical symptoms of complications. CONCLUSION: The samples derived from microdialysis were suitable to measure sub-peritoneal mediator profiles during surgery and up to 7 days postoperatively. Microdialysis data should be validated for a potential correlation with the clinical course.

Abdomen↗

Effects of microdialysis catheter insertion into the subcutaneous adipose tissue assessed by the SCGM1 system.

To monitor glucose in patients with diabetes continuously a microdialysis-based glucose sensor system (SCGM1 System, Roche Diagnostics GmbH, Mannheim, Germany) is under clinical development. This system allows monitoring of glucose levels in the subcutaneous interstitial fluid of patients with diabetes for a maximum duration of up to 120 h. The aim of the study was to determine the effect of microdialysis catheter insertion on the stability of the SCGM1 System glucose sensor signal. At four study sites, 47 experiments with the prototype of the novel SCGM1 System were performed in 42 patients with type 1 diabetes; two additional experiments were performed in two healthy volunteers. The microdialysis catheter was inserted in the subcutaneous adipose tissue of the patients in order to measure the glucose concentration in the interstitial fluid continuously. The catheter was perfused with a pump rate of 0.3 microL/min. For method comparison capillary blood glucose measurements were performed as reference values. In addition, the skinfold thickness was measured. Out of the total of 49 experiments 34 were usable. The average monitoring time in these experiments was 106.0 +/- 14.3 h (mean +/- SD). However, for this study the data from the first study day were evaluated in more detail. The analysis showed that during the first 12 h after catheter insertion the sensor signal increased 20% in comparison with the capillary blood glucose values (normalized calibration factor). This leads to a lower normalized calibration factor compared with the following study days. It remains stable in the time thereafter. The skinfold thickness showed no significant effect on the sensor signal. The observed increase in sensor signal in the first hours after insertion of the microdialysis catheter was probably due to a local trauma, which can induce an inflammation reaction. Thereafter, the signal registered by the SCGM1 System was stable and free of drift to the end of the experiment.

Adult↗

Cerebral microdialysis: research technique or clinical tool.

Cerebral microdialysis is a well-established laboratory tool that is increasingly used as a bedside monitor to provide on-line analysis of brain tissue biochemistry during neurointensive care. This review describes the principles of cerebral microdialysis and the rationale for its use in the clinical setting, including discussion of the most commonly used microdialysis biomarkers of acute brain injury. Potential clinical applications are reviewed and future research applications identified. Microdialysis has the potential to become an established part of mainstream multi-modality monitoring during the management of acute brain injury but at present should be considered a research tool for use in specialist centres.

Biomarkers↗

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

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

Adult↗

Advanced monitoring in the neurology intensive care unit: microdialysis.

Cerebral microdialysis is a relatively new technique for measuring the levels of brain extracellular chemicals, which to date has predominantly been used as a research tool. This review considers the technical aspects of microdialysis, the importance of the commonly measured chemicals, and the use of microdialysis to monitor patients with ischemic stroke, head injury, and subarachnoid hemorrhage. The advantages and disadvantages of microdialysis are discussed, as is its future potential.

Brain Chemistry↗

Treatment of extreme hyperglycemia monitored with intracerebral microdialysis.

OBJECTIVE: Description of a pediatric patient with hyperosmolar hyperglycemic nonketotic syndrome where the treatment was monitored with intracerebral microdialysis. DESIGN: Case report. SETTING: Intensive care unit at a university hospital. PATIENT: An 11-yr-old boy with new-onset diabetes who presented with a blood glucose concentration of 100 mmol/L (1800 mg/dL) and a serum osmolality of 448 mOsm/kg. INTERVENTIONS: Interventions included intracerebral and subcutaneous microdialysis as well as intracranial pressure monitoring during correction of the hyperosmolar condition. The strategy was to decrease osmolality by 1 mOsm.kg(-1).hr(-1) and blood glucose by 1.5 mmol.L(-1).hr(-1) (27 mg/dL). MEASUREMENTS AND MAIN RESULTS: The concentrations of glucose in the subcutaneous dialysates corresponded to the blood glucose concentrations. The brain/subcutaneous glucose ratio varied between 0.20 and 1.28 (mean, 0.43; median, 0.4). When the blood glucose decreased quickly after steady state, the brain/subcutaneous ratio increased sharply, demonstrating that the normalization of glucose in the brain was slower than that in blood. CONCLUSIONS: Microdialysis can be used to monitor the brain/subcutaneous glucose ratio in patients with extreme hyperglycemia. A rapid decrease in blood glucose increases the brain/subcutaneous glucose ratio, which may be a potential risk factor for osmotic brain edema. Microdialysis may prove to be a valuable tool in treatment management. The child made a full recovery.

Blood Glucose↗

Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison of intradermal injections with an atraumatic intraprobe drug delivery system.

BACKGROUND: The skin microdialysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injections and following skin challenge by a novel atraumatic delivery technique. OBJECTIVE: The purpose of the study was to compare histamine release in human skin by codeine, delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, correlations between histamine release and skin responses, and reproducibility. METHODS: Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subject, six fibres in each arm. Each fibre was perfused at a rate of 3 microM/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm, and ICTs were done on the other arm. RESULTS: Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant dose-related histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak histamine release was linearly correlated with cumulative release of the 20 min sampling period, and histamine release correlated with weal size. The coefficient of variation on peak histamine release was 18.9% and 4.8% for codeine ICT and IPD, respectively. CONCLUSION: We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumatically to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of inflammatory mediators release in normal and diseased skin, and it will be possible to deliver immunopharmacologically active drugs to the skin by intraprobe delivery.

Adult↗