Appropriate sleep hygiene is crucial for repair in states of disease and injury and in restoring function especially in the central nervous and immune systems. Anesthetics have different action targets and ultimately different consequences. The effects of anesthetics on circadian rhythm possibly also lead to immune deregulation. α2-adrenergic agonists converge on sleep pathways within the brainstem and are associated with changes in neuronal activity similar to those seen in deeper stages of NREM sleep. Thoughtful attention must be made in selecting an anesthetic agent that best mimics natural sleep. Future studies will further elucidate the benefits of dexmedetomidine as a good anesthetic/sedative candidate. © 2013 Elsevier Inc.

Background

Sleep is integral to biologic function, and sleep disruption can result in both physiological and psychologic dysfunction including cognitive decline. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. Because surgical patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium, an acute form of cognitive decline, we investigated the contribution of perioperative sleep fragmentation (SF) to the neuroinflammatory and cognitive responses of surgery.

Methods

The effects of 24-hour SF and surgery were explored in adult C57BL/6J male mice. The SF procedure started at 7 AM with cages being placed on a large platform orbital shaker that cycled every 120 seconds (30 seconds on/90 seconds off) for 24 hours. In separate cohorts, stabilized tibial fracture was performed either before or after the 24-hour SF procedure and assessed for systemic and hippocampal inflammation and cognition.

Results

SF-induced nonhippocampal memory dysfunction (mean ± standard deviation [SD] of the difference in time spent between novel and familiar object for control was 4.7 ± 1.4 seconds, n = 8 versus SF -0.5 ± 0.2 seconds, n = 11, yielding an estimated treatment effect of 5.2 seconds [95% confidence interval {CI}, 2.6-7.7]; P < .001) and increased systemic interleukin-6 (median [25%-75% quartile] for control 0.0 [0.0-2.4] pg/mL versus 9.7 [6.3-12.9] pg/mL, n = 8/group, yielding an estimated treatment effect of 9.7 pg/mL [95% CI, 5.8-11.8]; P < .0001). SF reduced freezing time in hippocampal-dependent memory test (mean ± SD for control 49.3% ± 5.8% versus for SF 32.9% ± 5.8%, n = 10/group, estimated treatment effect = 16.4% [95% CI, 11.0-21.8]; P < .0001). Although surgery also reduced freezing time (mean ± SD for control 49.3% ± 5.8% versus for surgery 30.3% ± 3.3%, n = 10/group, estimated treatment effect = 19.0% [95% CI, 14.6-23.4]; P < .0001), memory impairment was not further exacerbated by combining SF with surgery. One day after SF, there was an increase in hippocampal messenger RNA expression of tumor necrosis factor-α (relative quantitation [RQ] 5.12-fold, n = 5/group [95% CI, 1.64-15.97]; P < .01), and 1 day after surgery, there was an increase in messenger RNA interleukin-6 (RQ 4.64-fold, n = 5 [95% CI, 1.48-14.56]; P < .05) and tumor necrosis factor-α (RQ 5.54-fold, n = 5 [95% CI, 2.92-10.51]; P < .01). These increments were more pronounced when either pre- or postoperative SF was combined with surgery.

Conclusions

Although SF and surgery can independently produce significant memory impairment, perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. The dissociation between neuroinflammation and cognitive decline may relate to the use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.

An increasing number of patients require precise intraoperative hemodynamic monitoring due to aging and comorbidities. To prevent undesirable outcomes from intraoperative hypotension or hypoperfusion, appropriate threshold settings are required. These setting can vary widely from patient to patient. Goal-directed therapy techniques allow for flow monitoring as the standard for perioperative fluid management. Based on the concept of personalized medicine, individual assessment and treatment are more advantageous than conventional or uniform interventions. The recent development of minimally and noninvasive monitoring devices make it possible to apply detailed control, tracking, and observation of broad patient populations, all while reducing adverse complications. In this manuscript, we review the monitoring features of each device, together with possible advantages and disadvantages of their use in optimizing patient hemodynamic management.

Background

Aseptic surgical trauma provokes a homeostatic neuroinflammatory response to promote healing and protect the organism from further injury. When this response is dysregulated, harmful consequences can follow, including postoperative cognitive decline.

Sources of data

We performed a comprehensive search on PubMed related to postoperative cognitive dysfunction (POCD).

Areas of agreement

Although the precise pathogenic mechanisms for POCD remain unclear, certain risk factors are known.

Areas of controversy

The mechanisms that lead to exaggerated and persistent neuroinflammation and the best way to counteract it are still unknown. AREAS FOR DEVELOPING RESEARCH: It is imperative that we identify the underlying processes that increase the risk of cognitive decline in elderly surgical patients. In this review we explore non-resolution of inflammation as an underlying cause of developing exaggerated and persistent POCD. If interventions can be developed to promote resolution of neuroinflammation, the patient's postoperative recovery will be enhanced and long-term consequences can be prevented.

While people 65 years of age and older represent 16% of the population in the United States, they account for >40% of surgical procedures performed each year. Maintaining brain health after anesthesia and surgery is not only important to our patients, but it is also an increasingly important patient safety imperative for the specialty of anesthesiology. Aging is a complex process that diminishes the reserve of every organ system and often results in a patient who is vulnerable to the stress of surgery. The brain is no exception, and many older patients present with preoperative cognitive impairment that is undiagnosed. As we age, a number of changes occur in the human brain, resulting in a patient who is less resilient to perioperative stress, making older adults more susceptible to the phenotypic expression of perioperative neurocognitive disorders. This review summarizes the current scientific and clinical understanding of perioperative neurocognitive disorders and recommends patient-centered, age-focused interventions that can better mitigate risk, prevent harm, and improve outcomes for our patients. Finally, it discusses the emerging topic of sleep and cognitive health and other future frontiers of scientific inquiry that might inform clinical best practices.

Background

Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain.

Methods

The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated.

Results

A single injection of HMGB1 caused memory decline, as evidenced by a decrease in freezing time (52 ± 11% vs. 39 ± 5%; n = 16-17); memory decline was prevented when bone marrow-derived macrophages were depleted (39 ± 5% vs. 50 ± 9%; n = 17). Disabling HMGB1 with a blocking monoclonal antibody, before surgery, reduced postoperative memory decline (52 ± 11% vs. 29 ± 5%; n = 15-16); also, hippocampal expression of monocyte chemotactic protein-1 was prevented by the neutralizing antibody (n = 6). Neither the systemic nor the hippocampal inflammatory responses to surgery occurred in mice pretreated with anti-HMGB1 neutralizing antibody (n = 6).

Conclusion

Postoperative neuroinflammation and cognitive decline can be prevented by abrogating the effects of HMGB1. Following the earlier characterization of the resolution of surgery-induced memory decline, the mechanisms of its initiation are now described. Together, these data may be used to preoperatively test the risk to surgical patients for the development of exaggerated and prolonged postoperative memory decline that is reflected in delirium and postoperative cognitive dysfunction, respectively.

Study objectives

Obstructive sleep apnea (OSA) is accompanied by sleep fragmentation and altered sleep architecture, which can potentially hinder the glymphatic system, increasing risks for Alzheimer's disease (AD), but the status is unclear in OSA. Our aim was to investigate the glymphatic system in OSA subjects and examine the relationships between OSA disease severity, sleep symptoms, and glymphatic system indices in OSA using diffusion tensor imaging (DTI).

Methods

We acquired DTI data from 59 OSA and 62 controls using a 3.0-Tesla MRI and examined OSA disease severity and sleep symptoms with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Diffusivity maps in the x-axis (D_xx), y-axis (D_yy), and z-axis (D_zz), as well as in x-y axis (D_xy), y-z axis (D_yz), and x-z axis (D_xz) were calculated, diffusion values for the projection and association fibers extracted, and the DTI analyses along the perivascular space (DTI-ALPS index) were performed. The glymphatic system indices were compared between groups and correlated with disease severity and sleep symptoms in OSA subjects.

Results

D_zz values, derived from projection fiber areas, D_yy and D_zz values from association fiber areas, as well as ALPS and D_yzmean values were significantly reduced in OSA over controls. Significant correlations emerged between disease severity, sleep symptoms, and D_xy, D_xx, and D_zz values in OSA subjects.

Conclusion

OSA patients show abnormal glymphatic system function that may contribute to increased risks for AD. The findings suggest that the APLS method can be used to assess the glymphatic system in OSA patients.