Fragmented Sleep Enhances Postoperative Neuroinflammation but Not Cognitive Dysfunction.

Vacas, S. et al. Anesthesia & Analgesia. Published online: October 11 2016
Image source: Tim Ellis – Wellcome Images // CC BY-NC-ND 4.0

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-[alpha] (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-[alpha] (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.

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Postoperative Cognitive Dysfunction and the Change of Regional Cerebral Oxygen Saturation in Elderly Patients Undergoing Spinal Surgery

Kim, J. et al. Anesthesia & Analgesia. 2016. 123(2). pp. 436–444

B0005916 The brain and Prozac
Image source: Rowena Dugdale – Wellcome Images // CC BY-NC-ND 4.0

Background: In this study, we examined the relationship between postoperative cognitive dysfunction (POCD) and intraoperative regional cerebral oxygen saturation (rSO2) in elderly patients undergoing spinal surgery.

Methods: We enrolled 87 patients older than 65 years. All patients were tested using a battery of cognitive function tests (Korean Mini-Mental State Examination and visuomotor test of Dynamic Lowenstein Occupational Therapy Cognitive Assessment–Geriatric Version) the day before their surgical operation and on the seventh postoperative day. Our threshold for defining POCD for a given patient was a Reliable Change Index score of <−1.96 occurring on 2 tests.

Results: POCD was detected in 20 patients (23%) at the seventh postoperative day. Between-patient baseline characteristics, surgical data, and baseline cognitive function were similar for both those who developed POCD and those who did not. A univariate analysis that included age, female sex, education level, presence of diabetes, and duration of intraoperative decline in rSO2 to a level of <60% of baseline revealed that only diabetes and duration of rSO2 <60% (odds ratio, 1.01; 95% confidence interval [CI], 1.005–1.010) were found to be risk factors for POCD. After multivariate logistic regression analysis of these 2 variables, only the duration of rSO2 <60% (odds ratio, 1.006; 95% CI, 1.00–1.01, P = 0.014) remained as an independent risk factor for POCD. The area under the receiver operation characteristic of the duration of rSO2 <60% was 0.70 (95% CI, 0.57–0.82; P = 0.008). The optimal cutoff value was 157 minutes with a sensitivity of 75% and specificity of 72%.

Conclusions: This study showed that the duration of decline in rSO2 <60% during lumbar spinal surgery was correlated with the development of POCD at the seventh postoperative day in elderly patients.

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Persistent Postoperative Cognitive Decline?: The Pyramid of Evidence

Avidan, M. S. & Evers, A. S. 2016; 124:255–8

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Image source: Anesthesiology


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