Ever since Bedford’s seminal Lancet case series in 1955, we have known that perioperative care is sometimes followed by significant cognitive dysfunction (1). Although the safety of perioperative care has improved dramatically since 1955, the descriptions of cognitive dysfunction in that case series are eerily similar to the complaints of current patients suffering from post-operative cognitive dysfunction (POCD). POCD remains a common post-operative complication associated with significant morbidity and even mortality, especially among elderly patients. There has been a great deal of interest in and controversy about POCD, from how it is measured, to how long it lasts, to its precise implications for patients. This interest and controversy is reflected partly in the increasing number of papers published on this subject recently (shown in Figure 1). Recent work has also suggested surgery may be associated with cognitive improvement in some patients (2–4), termed Post-Operative Cognitive Improvement (POCI). As the number of surgeries performed worldwide approaches 250 million per year (5) (with an increasing number elderly patients), optimizing postoperative cognitive function and preventing/treating POCD are major public health issues. In this article we review the literature on POCD and POCI, and discuss current research challenges in this area.

Background Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer’s disease (AD)-associated markers tau, phosphorylated tau (p-tau)and amyloid-β (Aβ). Objective We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers. Methods Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time. Results The CSF tau/Aβ ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24h after drain placement (p = 2.002 × 10−6 and p = 1.985 × 10−6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations). Conclusion Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/Aβ ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/Aβ ratio was largely driven by increases in tau levels. Futurework should determine the functional/prognostic significance of these perioperative CSF tau elevations.

IntroductionAside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states.Materials and methodsTo examine whether propofol and isoflurane differentially modulate neuroinflammation in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with , identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients.ResultsAfter Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery.DiscussionThese data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

We sought to determine predictive factors for selective laser trabeculoplasty (SLT) outcome. 252 eyes from 198 adult patients with open-angle glaucoma who underwent SLT between July 2016 and February 2018 with a minimum 6 month follow up were reviewed. We defined success as ≥20% IOP reduction or ≥1 medication reduction without an IOP lowering procedure. We also evaluated the relationship of these factors to postoperative iop elevation >5 mmHg (IOP spikes). Our primary outcome measure was association between age, type and severity of glaucoma, pigmentation of the trabecular meshwork (PTM), total energy delivered, and baseline intraocular pressure (IOP) with success. At 2 and 6 months, 33.6% (76/226) and 38.5% (97/252) of eyes met success criteria respectively. Baseline IOP > 18 mmHg was significantly associated with success both at 2 and 6 months, reducing IOP by 5.4 ± 5.3 mmHg (23.7% reduction), whereas those with lower baseline remained at −0.7 ± 4.6 mmHg (4.9% increase) at 6 months (P < 0.001). No other baseline characteristics significantly predicted success or IOP spikes. Patients with higher baseline IOPs had greater success rates and mean IOP reduction at both 2 and 6 months following SLT. Age, type and severity of glaucoma, PTM, or total energy delivery had no association with procedural success or IOP spikes. Patients with higher baseline IOP may experience greater lowering of IOP after SLT. However, SLT may be equally successful for patients with a variety of other characteristics.