Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion.

Background: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality?

Method: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma.

Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published.

Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA).

Traumatic brain injury (TBI) is an important cause of death and disability. Safety and pharmacodynamics of 4-amino-tetrahydrobiopterin (VAS203), a nitric oxide (NO)-synthase inhibitor, were assessed in TBI in an exploratory Phase IIa study (NOSynthase Inhibition in TRAumatic brain injury=NOSTRA). The study included 32 patients with TBI in six European centers.

Red blood cell transfusion affects microdialysis-assessed interstitial lactate/pyruvate ratio in critically ill patients with late sepsis.

Purpose: The aim of this study was to explore the effect of red blood cell (RBC) transfusion on microdialysis-assessed interstitial fluid metabolic parameters in septic patients.

Methods: We conducted a retrospective study of 37 patients with severe sepsis/septic shock requiring transfusion of one to two RBC units. Interstitial fluid metabolic alterations were monitored by a microdialysis catheter inserted in the subcutaneous adipose tissue.

Microdialysis-assessed interstitium alterations during sepsis: relationship to stage, infection, and pathogen.

Purpose: More than a disorder of macrocirculation, sepsis is a disease affecting the microcirculation and the tissue metabolism. In vivo microdialysis (MD) is a bedside technique that can monitor tissue metabolic changes. We conducted this study aiming (1) to assess whether patients at different sepsis stages present with different MD-assessed tissue metabolic profiles and (2) to determine if different underlying types of infections and implicated pathogens are associated with dissimilar metabolic alterations.

Kinetics of adipose tissue microdialysis-derived metabolites in critically ill septic patients: associations with sepsis severity and clinical outcome.

Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes. This study aimed to describe the kinetics of MD-derived metabolites during the course of critical sepsis, to assess whether these metabolites are useful in grading sepsis severity, and to investigate their prognostic use. To this end, 54 mechanically ventilated septic patients were prospectively studied, out of which 39 had shock.

Analyte flux at a biomaterial-tissue interface over time: implications for sensors for type 1 and 2 diabetes mellitus.

Objective: The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

Method: Microdialysis was used to model implanted sensors.

The rotational model and microdialysis: Significance for dopamine signalling, clinical studies, and beyond.

The detailed anatomy of the monoamine pathways of the rat by the students of Nils-Ake Hillarp provided the basis for a neurocircuitry targeting pharmacology. Further progress was achieved by the introduction of 6-hydroxydopamine as a tool for performing specific lesions, leading to the first stereotaxic mapping of the monoamine pathways in the rat brain by Urban Ungerstedt at the Karolinska Institutet, Stockholm, Sweden. Unilateral intracerebral injections with 6-hydroxydopamine led to the proposal of 'Rotational Behaviour', as a classical model for screening drugs useful for alleviating Parkinson's disease and other neuropathologies.

Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.

Objective: The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase.

Study Design: Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord.

Microdialysis monitoring of porcine liver metabolism during warm ischemia with arterial and portal clamping.

Early detection of vascular complications following liver surgery is crucial. In the present study, intrahepatic microdialysis was used for continuous monitoring of porcine liver metabolism during occlusion of either the portal vein or the hepatic artery. Our aim was to assess whether microdialysis can be used to detect impaired vascular inflow by metabolic changes in the liver.

AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives.

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment.

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.

Are primary supratentorial intracerebral hemorrhages surrounded by a biochemical penumbra? A microdialysis study.

Objective: Opinions vary regarding the indications for surgical evacuation of spontaneous intracerebral hemorrhages (ICH) and whether or not penumbra zones surround them.

Methods: We performed intracerebral microdialysis (mean duration, 3.5 d) after surgical evacuation of ICH in 22 patients.

Microdialysis for myocardial metabolic surveillance: developing a clinical technique.

Metabolic surveillance of the myocardium is of great interest in cardiac surgery. Microdialysis allows sampling of chemical substances from the interstitial fluid for immediate analysis. The two objectives of this study were to develop a technique for simple and safe implantation of a commercially available microdialysis probe (CMA-70) into the myocardium and to obtain reference data for further use and metabolic control.

Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).

Objectives: To study the metabolic effects in vivo of L-2, 4 diaminobutyric acid (DAB) administered by retrograde microdialysis in glioblastoma and to evaluate the feasibility of the technique.

Methods: In 10 patients with glioblastoma, a stereotactic biopsy was performed followed by implantation of microdialysis catheters. One or two catheters were implanted in tumor tissue and two reference catheters were implanted in normal brain tissue and subcutaneous abdominal tissue, respectively.

Screening of microdialysates taken before and after induced liver damage; on-line solid phase extraction-electrospray ionization-mass spectrometry.

A novel method is described to follow known and unknown compounds in biological processes using microdialysis sampling and mass spectrometric detection. By implementation of internal standard, desalting/enrichment for the sample work-up, and multivariate data analysis, this methodology is a basis for future applications in early diagnosis of diseases and organ damage, as a complement to the routinely used clinical methods for biological samples. The present study includes screening without specific target analytes, of samples collected by microdialysis from liver of anaesthetized rats before and after local damage to this organ.

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.

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 ketogenic diet influences the levels of excitatory and inhibitory amino acids in the CSF in children with refractory epilepsy.

The ketogenic diet (KD) is an established treatment for medically refractory pediatric epilepsy. Its anticonvulsant mechanism is still unclear. We examined the influence of the KD on the CSF levels of excitatory and inhibitory amino acids in 26 children (mean age 6.

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.

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

Object: Intracerebral microdialysis has attracted increasing interest as a monitoring technique during neurological/neurosurgical intensive care. The purpose of this study was to compare cerebral energy metabolism, an indicator of secondary excitotoxic injury and cell membrane degradation close to focal traumatic lesions ("penumbra zones") and in remote and apparently intact brain regions of the ipsilateral and contralateral hemispheres.

Methods: The study included 22 consecutive patients with a mean age 44 +/- 17 years and an estimated postresuscitation Glasgow Coma Scale motor score less than 5.