Date Published: October 7, 2017
Publisher: Springer Vienna
Author(s): Frederick A. Zeiler, Eric Peter Thelin, Adel Helmy, Marek Czosnyka, Peter J. A. Hutchinson, David K. Menon.
To perform a systematic review on commonly measured cerebral microdialysis (CMD) analytes and their association to: (A) patient functional outcome, (B) neurophysiologic measures, and (C) tissue outcome; after moderate/severe TBI. The aim was to provide a foundation for next-generation CMD studies and build on existing pragmatic expert guidelines for CMD.
We searched MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016). Strength of evidence was adjudicated using GRADE.
(A) Functional Outcome: 55 articles were included, assessing outcome as mortality or Glasgow Outcome Scale (GOS) at 3–6 months post-injury. Overall, there is GRADE C evidence to support an association between CMD glucose, glutamate, glycerol, lactate, and LPR to patient outcome at 3–6 months. (B) Neurophysiologic Measures: 59 articles were included. Overall, there currently exists GRADE C level of evidence supporting an association between elevated CMD measured mean LPR, glutamate and glycerol with elevated ICP and/or decreased CPP. In addition, there currently exists GRADE C evidence to support an association between elevated mean lactate:pyruvate ratio (LPR) and low PbtO2. Remaining CMD measures and physiologic outcomes displayed GRADE D or no evidence to support a relationship. (C) Tissue Outcome: four studies were included. Given the conflicting literature, the only conclusion that can be drawn is acute/subacute phase elevation of CMD measured LPR is associated with frontal lobe atrophy at 6 months.
This systematic review replicates previously documented relationships between CMD and various outcome, which have driven clinical application of the technique. Evidence assessments do not address the application of CMD for exploring pathophysiology or titrating therapy in individual patients, and do not account for the modulatory effect of therapy on outcome, triggered at different CMD thresholds in individual centers. Our findings support clinical application of CMD and refinement of existing guidelines.
The online version of this article (10.1007/s00701-017-3338-2) contains supplementary material, which is available to authorized users.
Cerebral microdialysis (CMD) has seen broad application across neurocritical care [19, 24, 46]. By sampling brain parenchymal extracellular fluid, CMD provides insights into cellular metabolism and injury to guide clinical therapy, and provide characterization of the host response (currently only as a research tool) during pathologic states. To date, the largest application of CMD is within the traumatic brain injury (TBI) population [19, 46].
A systematic review was conducted using the methodology outlined in the Cochrane Handbook for Systematic Reviewers . Data were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . The review questions and search strategy were decided upon by the primary author (FAZ) and supervisors (AH and DKM).
We believe that this three-stage systematic review includes the major available studies documenting the relationship between common CMD analytes and Patient Functional Outcome (55 studies), Neurophysiologic Measures (59 studies), and Tissue Outcome (four studies). In broad terms, this systematic review replicates the pragmatic summary of literature that underpinned the previous consensus statements on CMD [41, 49, 50]. Our analysis strengthens the evidence for many of these associations by identifying a significantly larger number of studies than were cited in recent consensus statements [49, 50]. Further, we document the level of evidence based on conventional evaluation frameworks for evidence based medicine. This assessment found the following evidence:Patient Functional Outcome – GRADE level C evidence to support an association between CMD measured glucose, glutamate, glycerol, lactate, LPR and patient functional outcome as assessed by mortality and GOS at 3–6 months post-injury. These CMD measures have over ten studies in support of this relationship, with the majority documenting overwhelming statistical significance. Furthermore, there exists GRADE D level of evidence identified to support a relationship (positive or “nil”) between CMD measured pyruvate, potassium, sodium, and patient outcome. These CMD measures had much less robust literature to support an association with outcome.Neurophysiologic Measures – GRADE C evidence for a relationship between elevated LPR and elevated ICP and/or low CPP. We also judged that there was GRADE C evidence supporting an association between elevated glutamate and glycerol with elevated ICP and/or low CPP, and between elevated mean LPR and low PbtO2. All remaining CMD measures displayed either GRADE D evidence, or occasionally no evidence, to support a relationship with physiologic measures.Tissue Outcome – GRADE D of evidence to suggest an association between LPR in the acute/subacute phase of illness and frontal lobe atrophy at 6 months. The available literature reports no consistent association between CMD measures and MRS or ADC can be made at this time, other than the literature is “unclear”.
There currently exists GRADE C evidence to support an association between low CMD measured glucose and poor patient functional outcome at 3–6 months in severe TBI. Similarly, there exists GRADE C evidence to support an association between high CMD measured glutamate, glycerol, lactate, LPR and poor patient functional outcome at 3–6 months in severe TBI. Furthermore, there currently exists GRADE C level of evidence supporting an association between CMD measured LPR, glutamate and glycerol with ICP and/or CPP. In addition, there currently exists GRADE C evidence to support an association between LPR and PbtO2. All remaining CMD measures displayed either GRADE D evidence, or occasionally no evidence, to support a relationship with physiologic measures. Finally, there currently exists GRADE D evidence to suggest a potential association between elevated CMD measured LPR and frontal lobe atrophy at 6 months post-severe TBI.