Background The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. Methods Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. Results Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. Conclusions We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.
Perioperative fluid management impacts outcomes and plays a pivotal role in enhanced recovery pathways (ERPs). There have been major advances in understanding the effects of fluid therapy and administration during the perioperative period. Improving fluid management during this period leads to a decrease in complications, decrease in length of stay (LOS), and enhanced patient outcomes. It is important to consider preoperative and postoperative fluid management to be just as critical as intraoperative management given multiple associated benefits to the patients. Preoperative hydration with (complex) carbohydrate drinks up until 2 h before surgery is safe and should be encouraged, as this helps improve metabolism, decrease insulin resistance, reduce anxiety, and reduce nausea and vomiting. During the intraoperative period, the goals of fluid management are to maintain euvolemia using an individualized plan for fluid and haemodynamic management, matching the needs for monitoring with patient and surgical risk through goal-directed therapy (GDT). By combining the use of fluids and inotropes, GDT uses measurements and indicators of cardiac output and stroke volume to improve blood flow intraoperatively, and ultimately reduce LOS and complications. In the postoperative period, an early transition to oral hydration helps to enhance the conditions for healing and recovery from surgery. I.V. fluid therapy should be kept at a minimum, and urine output should not be the driving force for fluid administration. The optimization of perioperative fluid management is critical to ERPs as it helps improve pulmonary function, tissue oxygenation, gastrointestinal motility, and wound healing.
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