Introduction
Methods
Discussion
Advances since the 2004 consensus statement
2004 consensus statement [4] | Current consensus statement | |
---|---|---|
Microdialysis methodology | Monitoring of small molecules using standard 10-mm 20-kDa catheter | |
Focus on microdialysis metabolites as a marker of ischemia and cell damage | Novel applications of microdialysis for monitoring and understanding brain pathology following TBI and SAH | |
Core data reporting information | Not defined | Details are given of the essential information required to interpret and compare microdialysis data |
Reference values | Not defined | |
Tiered approach to microdialysis metabolites for clinical application | Not defined | Glucose and LP ratio more clinically useful than glutamate and glycerol in TBI and SAH patients |
Guidance for microdialysis-directed management | Not given | Suggested therapeutic interventions for when glucose is low (<0.2 mM) and for when the LP ratio indicates ischemia ± tissue hypoxia |
Monitoring in TBI | Guidance on catheter placement in focal or diffuse injury | Guidance on single or multiple catheter placement based on whether the injury is focal or diffuse and based on the aims of microdialysis monitoring |
Monitoring in SAH | Guidance on catheter placement in the tissue at risk | Two principal indications for microdialysis monitoring are defined: |
1. As a primary monitoring device in mechanically ventilated patients | ||
2. As a monitor of patients with a secondary neurological deterioration |
How microdialysis monitoring can be used in neurocritical care | Traumatic brain injury | Subarachnoid hemorrhage |
---|---|---|
Outcome and prognostication | ||
Early warning system of secondary insults | ||
Monitoring and treatment of low cerebral glucose; guiding systemic glucose management and insulin use | ||
Monitoring during CPP-augmentation/reduction | ||
Monitoring during neurological wake-up test (tolerating moderate rises in ICP) | ||
Deciding on transfusion thresholds | [89] | |
Evaluating the effect of body temperature on cerebral chemistry | [90] | [91] |
Monitoring after decompressive craniectomy | [92] | [93] |
Investigating the concept of lactate as a substrate as opposed to a metabolic by-product in select patients | |
Use of 100-kDa microdialysis membranes to measure larger molecules including cytokines | |
Use of 13C-labelled substrates to interrogate metabolic pathways in more detail, e.g., the fate of glucose metabolism (glycolysis vs. pentose phosphate pathway) and the fate of lactate as a substrate | |
Monitoring drug penetration across the blood–brain barrier and the effect of drugs on brain chemistry | |
Clinical use in pediatric practice | |
Monitoring of the ionic component of the interstitial space | [103] |
Monitoring of biomarkers | |
Development of microfluidic based on-line assays that give continuous neurochemical information in real time |
Advances in microdialysis methodology
Clinical application in intensive care
Safety profile
Cost-benefit analysis
Recommendations from the 2014 International Forum on Microdialysis––the 2014 consensus statement
Methodology
-
Catheters should be inserted according to local institutional protocols either by twist drill hole, transcranial bolt, or at craniotomy.
-
The first hour of microdialysate collected should not be used for clinical monitoring due to unreliable results caused by insertion trauma and the pump flush sequence.
-
To monitor glucose, pyruvate, lactate, glycerol and glutamate catheters with a 20- or 100-kDa cut-off are available (100-kDa catheters are not yet FDA-approved, although they are CE marked for use in Europe).
-
A flow rate of 0.3 μL/min with hourly sampling is recommended, which is the flow rate most commonly used in the cerebral microdialysis literature.
-
Publication of microdialysis data should include the following information (core data reporting):
-
catheter type
-
catheter location based on post-insertion imaging
-
flow rate
-
membrane length
-
perfusion fluid composition
-
time from ictus to monitoring
-
Interpretation of cerebral microdialysis
-
Microdialysis monitors substrate delivery and metabolism at the cellular level. Chemistry should be interpreted in the context of the clinical condition of the patient and in conjunction with other monitored parameters including ICP, CPP, PbtO2, cerebrovascular pressure reactivity (PRx) and systemic parameters, in order to determine the likely cause of perturbed metabolism. For example, a rise in LP ratio associated with a fall in CPP and loss of cerebrovascular reactivity (i.e., a high PRx) indicates that the likely cause of disordered chemistry is ischemia.
-
Microdialysis is a focal technique. The heterogeneity of brain injury means that brain chemistry varies in different regions of the brain. In TBI, peri-lesional brain demonstrates more perturbed chemistry, in particular a higher LP ratio, compared to other areas of brain [47‐52]. Therefore, brain chemistry should be interpreted according to catheter location in relation to focal injury based on CT/MRI imaging.
Glucose
-
Glucose is the main substrate for brain metabolism.
-
Periods of low glucose (<0.8 mM) are observed in TBI and SAH.
Lactate/pyruvate ratio
-
The LP ratio is a marker of cellular redox status.
-
The LP ratio is a quantitative measure (independent of relative recovery).
-
The absolute lactate and pyruvate concentrations should be considered when interpreting a high LP ratio.
-
Ischemia and mitochondrial dysfunction are two ends of a spectrum of factors that increase the LP ratio.
-
An increase in the LP ratio in the presence of low pyruvate (and low oxygen) indicates ischemia.
-
An increase in LP ratio in the presence of normal or high pyruvate (and normal oxygen) indicates mitochondrial dysfunction.
Glutamate
-
Glutamate is an excitatory amino acid and neurotransmitter. Excess levels are thought to be an additional injurious mechanism and may exacerbate injury in TBI and SAH.
-
Measuring cerebral glutamate is an option and may be useful in estimating prognosis.
Glycerol
-
Glycerol is a marker of cell membrane breakdown. It is a potential marker of oxidative stress.
-
Glycerol has limited specificity; brain glycerol concentrations are influenced by systemic concentrations. Systemic glycerol concentrations reflect a stress response and/or administration of glycerol-containing substances.
-
There is no definitive evidence of a relationship between glycerol and outcome.
-
Cerebral glycerol is an option as a marker of cerebral injury.
Guidance for use of microdialysis in traumatic brain injury and subarachnoid hemorrhage—catheter location, reference values and interventions
Traumatic brain injury
-
In diffuse TBI, we recommend placing the catheter in the right (non-dominant) frontal lobe.
-
In focal TBI, there are different options for catheter placement that depend on whether the goal is to monitor tissue at risk or normal brain, e.g., to guide systemic glucose treatment.
-
Where there is a focal lesion, we recommend, if feasible, catheter placement ipsilateral to the lesion and in radiographically normal brain.
-
Multiple catheters are an option in focal TBI.
-
E.g., placed at craniotomy for a focal lesion into peri-lesional brain with a contralateral ‘bolt’ catheter in radiographically normal brain.
-
Stereotactic placement is an option but rarely practical.
-
Subarachnoid hemorrhage
-
There are two principal indications for the insertion of microdialysis in SAH patients:1.As a primary monitoring device in mechanically ventilated (‘poor-grade’) patients.2.As a monitor of patients with a secondary neurological deterioration.
-
As a primary monitoring device, we recommend catheter location in the watershed anterior cerebral artery–middle cerebral artery (ACA–MCA) territory (frontal lobe) on the same side as the maximal blood load seen on CT or the ruptured aneurysm. If the blood load is symmetrical, we recommend non-dominant frontal lobe placement.
-
In patients with a secondary neurological deterioration, catheter location should be guided by local practice to identify tissue at risk (e.g., CT perfusion scanning or trans-cranial Doppler).
-
Multiple catheters are an option in SAH.
Reference values and interventions
-
It is currently difficult to define absolute normal or abnormal values based on the literature. Different groups have used different threshold values to relate microdialysate values to outcome. Furthermore, some authors have used a combination of values to relate microdialysis to clinical outcomes.
-
The trend is as important or possibly more important than point values or threshold values.
-
It is important to distinguish between normal values, which have been reported in the awake and anesthetised brain of patients undergoing surgery for benign intracranial lesions, and values that characterize pathophysiological disturbance of brain chemistry.
-
We propose the following pathological thresholds (one or two stages), for microdialysis at 0.3 µl/min, based on observational studies that have explored statistical differences in outcomes in relation to thresholds of microdialysate values. Microdialysate values observed beyond these thresholds indicate that the area of brain being monitored is ‘at risk’. We propose clinical interventions that may be appropriate in response to disturbed brain chemistry. Further research is needed to elucidate whether these thresholds can be applied to both peri-lesional and to radiographically normal brain and to identify whether interventions directed by these thresholds improve clinical outcomes.
-
If brain glucose is low (<0.2 mM), a trial of increasing serum glucose (by intravenous or enteral administration and/or loosening glycemic control) should be considered. Factors to consider when deciding whether this is an appropriate intervention include baseline serum glucose concentration and whether other parameters indicate cerebral ischemia. If baseline serum glucose concentration is high, further increasing the glucose concentration is likely to increase the risk of both neurological and systemic complications from hyperglycemia. The precise definition of blood sugar thresholds for safety is beyond the scope of this manuscript, but frank hyperglycemia should be avoided. If other parameters, such as the LP ratio and PbtO2, indicate ischemia, interventions directed at improving cerebral perfusion should be considered first-line.
-
If the LP ratio indicates ischemia, i.e. an increase in the LP ratio in the presence of low pyruvate, CPP augmentation is a therapeutic option.
-
If the LP ratio is increased in the presence of low brain tissue oxygen, interventions that improve oxygen delivery, such as judiciously increasing the cerebral perfusion pressure, increasing PaCO2, increasing inspired concentration of oxygen and/or correcting anemia, should be considered. However, all of these interventions have potential side effects, and the choice of intervention will depend on the pre-intervention levels of any given variable, and a consideration of the side effects of the intervention. Thus, for example, in patients with significant hypocarbia, an increase in PaCO2 might be the most appropriate intervention, but may be difficult to achieve due to increases in intracranial pressure.
Tiered approach to the clinical value of substances
-
Accumulating evidence since the last consensus statement indicates that the value of the metabolites can now be considered in a tiered fashion (tier 1 being most robust and useful) for their clinical application as follows. This hierarchy is based on the larger volume of observational data linking glucose and LP ratio with outcome compared to glutamate and glycerol and on the greater potential for glucose and LP ratio to direct clinical interventions.
-
Tier 1: glucose and LP ratio.
-
Tier 2: glutamate.
-
Tier 3: glycerol.