Abstract
Cerebral microdialysis (CMD) is used in severe traumatic brain injury (TBI) in order to recover metabolites in brain extracellular fluid (ECF). To recover larger proteins and avoid fluid loss, albumin supplemented perfusion fluid (PF) has been utilized, but because of regulatory changes in the European Union, this is no longer practicable. The aim with this study was to see whether fluid, absolute (AR), and relative (RR) recovery for the novel carrier, Dextran 500, was better than conventional PF for a range of cytokines and chemokines. An in vitro setup mimicking conditions observed in the neurocritical care of TBI patients was used, utilizing 100-kDa molecular-weight cut-off CMD catheters inserted through a triple-lumen bolt cranial access device into an external solution with diluted cytokine standards in known concentrations for 48 h (divided into 6-h epochs). Samples were run on a 39-plex Luminex (Luminex Corporation, Austin, TX) assay to assess cytokine concentrations. We found that fluid recovery was inadequate in 50% of epochs with conventional PF, whereas Dextran PF overcame this limitation. The AR was higher in the Dextran PF samples for a majority of cytokines, and RR was significantly increased for macrophage colony-stimulating factor and transforming growth factor-alpha. In summary, Dextran PF improved fluid and cytokine recovery as compared to conventional PF and is a suitable alternative to albumin supplemented PF for protein microdialysis.
Highlights
Cerebral microdialysis (CMD) is a technique enabling sampling from the extracellular fluid (ECF) in vivo, providing a unique opportunity to study underlying metabolic and inflammatory processes that occur in traumatic brain injury (TBI).[1,2] Microdialysis sampling is based on the free diffusion of analytes across a semipermeable membrane with a nominal molecularweight cutoff (MWCO)
Vials perfused with the standard perfusion fluid (PF) demonstrated inadequate fluid recovery in certain epochs over the three experiments and needed intermittent flushing in the initial phase of the epoch (Fig. 2)
This procedure did not alter the absolute recovery (Table 1), but for some, notably IL-6, regulated on activation, normal T cell expressed and secreted (RANTES), and TNF, the necessary flushing sequences resulted in a significantly lower recovery in the fluid collected during the remaining of the epoch in the conventional CNS PF (Fig. 2A)
Summary
Cerebral microdialysis (CMD) is a technique enabling sampling from the extracellular fluid (ECF) in vivo, providing a unique opportunity to study underlying metabolic and inflammatory processes that occur in traumatic brain injury (TBI).[1,2] Microdialysis sampling is based on the free diffusion of analytes across a semipermeable membrane with a nominal molecularweight cutoff (MWCO). The membrane is attached to inlet and outlet tubing through which perfusion fluid (PF) is slowly pumped and collected.[3] To measure metabolites in clinical practice, such as glucose, lactate, and pyruvate, a 20-kDa MWCO is adequate and an isotonic solution, mimicking cerebrospinal fluid, is used as a carrier.[4] Microdialysis of proteins is limited by both lower absolute concentrations within the brain ECF, as well as the larger molecular weight, necessitating the use of larger MWCO membranes This causes a number of problems, including non-specific adsorption to the device materials, clogging of membranes, and protein-protein interactions, which all negatively affect recovery.[5,6,7] A further issue with increased MWCO catheters (e.g., 100 kDa) is loss by convection of fluid within the catheter.[8] This is attributed to the hydrostatic pressure differences (with a relatively low osmotic pressure in the PF) and referred to as ultrafiltration. In order to mitigate this phenomenon, addition of colloid to the PF to increase the oncotic pressure has been recommended, typically albumin.[6,9] a regulatory reclassification of albumin within
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