Each year over 16 million older Americans undergo general anesthesia for surgery, and up to 40% develop postoperative delirium and/or cognitive dysfunction (POCD). Delirium and POCD are each associated with decreased quality of life, early retirement, increased 1-year mortality, and long-term cognitive decline. Multiple investigators have thus suggested that anesthesia and surgery place severe stress on the aging brain, and that patients with less ability to withstand this stress will be at increased risk for developing postoperative delirium and POCD. Delirium and POCD risk are increased in patients with lower preoperative cognitive function, yet preoperative cognitive function is not routinely assessed, and no intraoperative physiological predictors have been found that correlate with lower preoperative cognitive function. Since general anesthesia causes alpha-band (8–12 Hz) electroencephalogram (EEG) power to decrease occipitally and increase frontally (known as “anteriorization”), and anesthetic-induced frontal alpha power is reduced in older adults, we hypothesized that lower intraoperative frontal alpha power might correlate with lower preoperative cognitive function. Here, we provide evidence that such a correlation exists, suggesting that lower intraoperative frontal alpha power could be used as a physiological marker to identify older adults with lower preoperative cognitive function. Lower intraoperative frontal alpha power could thus be used to target these at-risk patients for possible therapeutic interventions to help prevent postoperative delirium and POCD, or for increased postoperative monitoring and follow-up. More generally, these results suggest that understanding interindividual differences in how the brain responds to anesthetic drugs can be used as a probe of neurocognitive function (and dysfunction), and might be a useful measure of neurocognitive function in older adults.

Changes in heart transplantation (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society for Heart & Lung Transplantation (ISHLT)-defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time-trend analysis was performed over the study period. Three-hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD, or both, were observed in 99 patients (31%). Risk factors independently associated with PGD included ischemic time, recipient African American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence; however, there was an increase in the recipient pretransplantation use of amiodarone. The rate of 30-day mortality was significantly elevated in those with PGD versus those without PGD (6.06% vs 0.92%, P = .01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions.

Background Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. Methods The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. Results The median postoperative nadir platelet count was 121 × 109/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 109/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). Conclusion The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.

Background Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice. Methods Adult male C57BL/6 ( n =111) and Ccr2 RFP/+ Cx3cr1 GFP/+ ( n =54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery. Systemic inflammatory changes, bone healing, neuroinflammation, and cognition were assessed at different time points. MaR1 protective effects were also evaluated using bone marrow derived macrophage cultures. Results MaR1 exerted potent systemic anti-inflammatory effects without impairing fracture healing. Prophylaxis with MaR1 prevented surgery-induced glial activation and opening of the blood–brain barrier. In Ccr2 RFP/+ Cx3cr1 GFP/+ mice, fewer infiltrating macrophages were detected in the hippocampus after surgery with MaR1 prophylaxis, which resulted in improved memory function. MaR1 treatment also reduced expression of pro-inflammatory cell surface markers and cytokines by in vitro cultured macrophages. MaR1 was detectable in the cerebrospinal fluid of older adults before and after surgery. Conclusions MaR1 exerts distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-κB signalling, and cytokine release after surgery. Future studies on the use of pro-resolving lipid mediators may inform novel approaches to treat neuroinflammation and postoperative neurocognitive disorders.

Background: Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients. Methods: We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression. Results: The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56e3.45; P<0.001), less than the 6.47% MAC decrease per decade that we found in a meta-regression analysis of published studies of age-dependent changes in MAC (P<0.001), and less than the age-dependent decrease in MAC-awake. The BIS values correlated positively with age (r¼0.15; 95% CI: 0.12e0.17; P<0.001), and inversely with the age-adjusted endtidal MAC (aaMAC) fraction (r¼ e0.13; 95% CI: e0.16, e0.11; P<0.001). Conclusions: The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults.

BackgroundIn this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970.MethodsPatient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without “E” status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures.ResultsAs reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort (p < 0.0001). Additionally, the overall mortality rate at 48 h was significantly higher among patients undergoing emergent compared to elective procedures in the large contemporary cohort (1.27 versus 0.03 %, p < 0.0001). In the comparative analysis with the historical cohort that focused on adult males, we found the overall 48-h mortality rate was significantly lower among patients undergoing elective procedures in the contemporary cohort (0.05 % now versus 0.24 % in 1970, p < 0.0001) but not significantly lower among those undergoing emergent procedures (1.88 % now versus 1.22 % in 1970, p < 0.0001).ConclusionsThe association between increasing ASA PS designation (1–5) and mortality within 48 h of surgery is significant for patients undergoing both elective and emergent procedures in a contemporary dataset consisting of over 700,000 patient encounters. Emergency surgery was associated with a higher risk of patient death within 48 h of surgery in this contemporary dataset. These data trends are similar to those observed nearly five decades ago in a landmark study evaluating the association between ASA PS and 48-h surgical mortality on adult men at US naval hospitals. When a comparison cohort was created from the contemporary dataset and compared to this landmark historical cohort, the absolute 48-h mortality rate was significantly lower in the contemporary cohort for elective procedures but n...

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.

Background and objectivesThere are few prospective studies providing comprehensive assessment of risk factors for acute and persistent pain after breast surgery. This prospective observational study assessed patient-related, perioperative, and genetic risk factors for severe acute pain and persistent pain following breast cancer surgery.MethodsWomen presenting for elective breast cancer surgery completed State Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale questionnaires preoperatively. Diffuse noxious inhibitory control and mechanical temporal summation were assessed. A blood sample was obtained for genetic analysis. Analgesic consumption and pain scores were collected in the post-anesthesia care unit, and at 24 and 72 hours. Patients were contacted at 1, 3, 6, and 12 months to assess persistent pain. Primary outcome was maximum acute pain score in first 72 hours and secondary outcome was persistent pain.ResultsOne hundred twenty-four patients were included in analysis. Increased duration of surgery, surgeon, and higher pain catastrophizing scores were associated with increased severity of acute pain, while preoperative radiotherapy was associated with reduced severity. Persistent pain was reported by 57.3% of patients. Postdischarge chemotherapy (OR 2.52, 95% CI 1.13 to 5.82), postdischarge radiation (OR 3.39, 95% CI 1.24 to 10.41), severe acute pain (OR 5.39, 95% CI 2.03 to 15.54), and moderate acute pain (OR 5.31, 95% CI 1.99 to 15.30) were associated with increased likelihood of persistent pain.ConclusionsIncreased duration of surgery, higher pain catastrophizing score, and surgeon were associated with increased severity of acute pain. Preoperative radiation was associated with lower acute pain scores. Postsurgery radiation, chemotherapy, and severity of acute pain were associated with increased likelihood of persistent pain.Trial registration NCT03307525.