Hypertonic Saline Versus Mannitol for Traumatic Brain Injury: A Systematic Review and Meta-Analysis With Trial Sequential Analysis Background: Mannitol and hypertonic saline are widely used to treat raised intracranial pressure (ICP) after traumatic brain injury (TBI), but the clinical superiority of one over the other has not been demonstrated. Methods: According to the PRISMA statement, this meta-analysis reports on randomized controlled trials investigating hypertonic saline compared with mannitol in the treatment of elevated ICP following TBI. The protocol for the literature searches (Medline, Embase, Central databases), quality assessment, endpoints (mortality, favorable outcome, brain perfusion parameters), and statistical analysis plan (including a trial sequential analysis) were prospectively specified and registered on the PROSPERO database (CRD42017057112). Results: A total of 12 randomized controlled trials with 464 patients were eligible for inclusion in this analysis. Although there was a nonsignificant trend in favor of hypertonic saline, there were no significant differences in mortality between the 2 treatments (relative risk [RR]: 0.69, 95% confidence interval [CI]: 0.45, 1.04; P=0.08). There were also no significant differences in favorable neurological outcome between hypertonic saline (HS) and mannitol (RR: 1.28, 95% CI: 0.86, 1.90; P=0.23). There was no difference in ICP at 30 to 60 minutes after treatment (mean difference [MD]: −0.19 mm Hg, 95% CI: −0.54, 0.17; P=0.30), whereas ICP was significantly lower after HS compared with mannitol at 90 to 120 minutes (MD: −2.33 mm Hg, 95% CI: −3.17, −1.50; P<0.00001). Cerebral perfusion pressure was higher between 30 to 60 and 90 to 120 minutes after treatment with HS compared with after treatment with mannitol (MD: 5.48 mm Hg, 95% CI: 4.84, 6.12; P<0.00001 and 9.08 mm Hg, 95% CI: 7.54, 10.62; P<0.00001, respectively). Trial sequential analysis showed that the number of cases was insufficient to produce reliable statements on long-term outcomes. Conclusion: There are indications that HS might be superior to mannitol in the treatment of TBI-related raised ICP. However, there are insufficient data to reach a definitive conclusion, and further studies are warranted. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Franz Schwimmbeck. E-mail: franz.schwimmbeck@med.uni-muenchen.de. Received November 12, 2018 Accepted August 12, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Site of Occlusion May Influence Decision to Perform Thrombectomy Under General Anesthesia or Conscious Sedation Background: Although mechanical thrombectomy has become the standard of care for large-vessel occlusion, the role of conscious sedation versus general anesthesia (GA) with intubation during thrombectomy remains controversial. Aphasia may increase patient agitation or apparent uncooperativeness/confusion and thereby lead to higher use of GA. The purpose of this study was to identify risk factors for GA and determine if the side of vessel occlusion potentially impacts GA rates. Materials and Methods: Patients who underwent mechanical thrombectomy of the middle cerebral artery (MCA) for acute ischemic stroke at our institution between April 2014 and July 2017 were retrospectively reviewed. Patient characteristics, procedural factors, and outcomes were assessed using multivariate regression analyses. Mediation analysis was utilized to investigate whether aphasia lies on the causal pathway between left-sided MCA stroke and GA. Results: Overall, 112 patients were included: 62 with left-sided and 50 with right-sided MCA occlusion. Patients with left-sided MCA occlusion presented with aphasia significantly more often those with right-sided occlusion (90.3% vs. 32.0%; P<0.001). GA rates were significantly higher for patients with left-sided compared with right-sided MCA occlusion (45.2% vs. 20.0%; P=0.028). Aphasia mediated 91.3% of the effect of MCA stroke laterality on GA (P=0.02). GA was associated with increased door-to-groin-puncture time (106.4% increase; 95% confidence interval, 24.1%-243.4%; P=0.006) and adverse discharge outcome (odds ratio, 1.04; 95% confidence interval, 1.01-1.07; P=0.019). Conclusions: Patients who had a stroke with left-sided MCA occlusion are more likely to undergo GA for mechanical thrombectomy than those with right-sided MCA occlusion. Aphasia may mediate this effect and understanding this relationship may decrease GA rates through modification of management protocols, potentially leading to improved clinical outcomes. Our study suggests that GA should preferentially be considered for the subset of patients with acute ischemic stroke undergoing mechanical thrombectomy for left-sided MCA occlusion. Supported the National Institutes of Health grant number TL1TR001443 awarded to M.G.B. J.A.S., M.G.B., K.M.K., A.R.W., and A.A.K.: designed the study and participated in initial data collection. J.A.S., R.C.R., D.R.S-D., S.E.O., J.S.P., and A.A.K.: monitored data collection. J.A.S., M.G.B., K.M.K., and A.W.: curated the existing data and completed additional data collection. J.A.S., M.G.B., A.R.W., R.C.R., D.R.S-D., S.E.O., J.S.P., and A.A.K.: wrote the statistical analysis plan. J.A.S., M.G.B., K.M.K., and A.R.W.: cleaned and analyzed the data. J.A.S., M.G.B., and K.M.K.: drafted and revised the paper. A.R.W., R.C.R., D.R.S-D., S.E.O., J.S.P., and A.A.K.: revised the paper. The authors have no conflicts of interest to disclose. Address correspondence to: Alexander A. Khalessi, MD, MS. E-mail: akhalessi@ucsd.edu. Received April 5, 2019 Accepted July 31, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Does Thoracolumbar Interfascial Plane Block Provide More Focused Analgesia Than Erector Spinae Plane Block in Lumbar Spine Surgery? No abstract available

Anesthesia-induced Recognition Deficit is Improved in Postnatally Gonadectomized Male Rats Background: Preclinical investigations of the effects of general anesthesia on the young brain show differences in vulnerability of males and females to anesthetic exposure at different times during development. However, the mechanism underlying this sex difference is poorly understood. Perinatal testosterone is the primary determinant of sexual differentiation and likely plays an important role in defining the period of susceptibility to anesthetic injury. We investigated whether the removal of testosterone through gonadectomy shortly after birth would improve cognitive outcomes in male rodents after early anesthesia exposure. Methods: Male Sprague Dawley rats underwent gonadectomy at postnatal day 2 (P2), followed by exposure to 6 hours of isoflurane at P7. A control cohort of gonad-intact male littermates was simultaneously exposed. All rats were subjected to a series of object recognition and association tasks beginning at P42. Cell death in the thalamus and hippocampus was assessed in a separate cohort. Results: All groups performed similarly on the Novel Object Recognition task; however, the gonad-intact isoflurane group exhibited decreased performance in the more difficult tasks. This deficit was ameliorated in the gonadectomized group. Cell death was similar between both isoflurane-exposed groups, regardless of gonadectomy. Conclusions: The absence of testosterone does not block cell death after anesthesia in specific brain regions of interest; however, does provide some neuroprotection as evidenced by the improved cognitive test performance during adulthood. These findings suggest that testosterone may be mechanistically involved in the sex-specific effects of anesthetic injury on the developing brain by extending the vulnerable period in male rats. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Jeffrey W. Sall, MD, PhD. E-mail: Jeffrey.Sall@ucsf.edu. Received May 12, 2019 Accepted July 23, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Anesthesia and Cognitive Outcome in Elderly Patients: A Narrative Viewpoint Better ways to manage preoperative, intraoperative and postoperative care of surgical patients is the bailiwick of anesthesiologists. Although we care for patients of all ages, protecting the cognitive capacity of elderly patients more frequently requires procedures and practices that go beyond routine care for nonelderly adults. This narrative review will consider current understanding of the reasons that elderly patients need enhanced care, and recommendations for that care based on established and recent empirical research. In that latter regard, unless and until we are able to classify anesthetic neurotoxicity as a rare complication, the first-do-no-harm approach should: (1) add anesthesia to surgical intervention on the physiological cost side of the cost/benefit ratio when making decisions about whether and when to proceed with surgery; (2) minimize anesthetic depth and periods of electroencephalographic suppression; (3) limit the duration of continuous anesthesia whenever possible; (4) consider the possibility that regional anesthesia with deep sedation may be as neurotoxic as general anesthesia; and (5) when feasible, use regional anesthesia with light or no sedation. Details of previous presentation of the work (or part thereof): Some sections of this manuscript are similar to sections of American Society of Anesthesiologists (ASA) Refresher Course Lecture (RCL) Outlines for RCL’s that Dr. Cottrell has presented at ASA Annual Meetings over the past 30+ years. Those RCL Outlines have been distributed to attendees of ASA Annual Meetings as part of the fee for attending the meetings (formerly in print, subsequently digital only). They have also been made available to ASA members that do not attend Annual Meetings at a substantial cost at the ASA “store,” and to nonmembers at a substantially higher cost at the ASA “store.” For examples, see: www.asahq.org/shop-asa#sort=%40fsearchdate77238%20descending Under the original meaning of “publish”—to make written material available to the public—given the limited distribution and cost of ASA Refresher Course Lecture Outlines, we do not consider those Outlines to have been “published” in the conventional sense. That view is supported by the ASA’s stipulation that authors of RCL Outlines retain copyright of their material. The authors have no funding or conflicts of interest to disclose. Address correspondence to: John Hartung, PhD. E-mail: john.hartung@downstate.edu. Received February 5, 2019 Accepted July 30, 2019 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

A Retrospective Observational Study of the Neuroendocrine Stress Response in Patients Undergoing Endoscopic Transsphenoidal Surgery for Removal of Pituitary Adenomas: Total Intravenous Versus Balanced Anesthesia Background: Anesthetic technique affects the neuroendocrine stress response to surgery. In this retrospective study, we compared the neuroendocrine stress response in patients undergoing endoscopic transsphenoidal pituitary adenoma surgery (ETSPAS) with total intravenous anesthesia (TIVA) with propofol-remifentanil or balanced anesthesia (BAL) with sevoflurane-remifentanil. Materials and Methods: Eighty-nine patients undergoing ETSPAS were anesthetized with either propofol-remifentanil (TIVA group, n=62) or sevoflurane-remifentanil (BAL group, n=27). Data were retrospectively collected regarding preoperative and immediate postoperative serum levels of adrenocorticotropic hormone (ACTH) and cortisol (primary outcome measures), as well as other pituitary hormones and their target organ hormones (secondary outcome measures). Results: There were no significant differences in preoperative pituitary hormone levels between the 2 groups. The immediate postoperative ACTH (89.5 [62.1 to 162.6] vs. 256.0 [92.0 to 570.7] pg/mL; P<0.001) level was lower in the TIVA group than in the BAL group, whereas immediate postoperative cortisol levels were similar between the 2 groups. The immediate postoperative thyroid-stimulating hormone (1.85 [1.21 to 2.98] vs. 1.21 [0.44 to 1.71] μIU/mL; P=0.003), triiodothyronine (91.0 [82.0 to 103.0] vs. 69.1 [64.6 to 76.2] ng/dL; P<0.001), luteinizing hormone (2.2 [1.2 to 4.0] vs. 1.0 [0.5 to 2.3] mIU/mL; P=0.005), and prolactin (22.6±15.8 vs. 12.8±10.2 ng/mL; P=0.005) levels were higher in the TIVA group compared with the BAL group. In both groups, none of the patients who had sufficient preoperative ACTH without hydrocortisone supplementation (n=15) showed hypocortisolism in the immediate postoperative measurement. Conclusions: Compared with BAL, TIVA resulted in reduced release of ACTH and increased release of thyroid-stimulating hormone, triiodothyronine, luteinizing hormone, and prolactin in patients undergoing ETSPAS. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Hee-Pyoung Park, MD, PhD. E-mail: hppark@snu.ac.kr. Received April 18, 2019 Accepted July 16, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Intravenous Propofol Versus Volatile Anesthetics For Stroke Endovascular Thrombectomy Background: The choice of anesthetic technique for ischemic stroke patients undergoing endovascular thrombectomy is controversial. Intravenous propofol and volatile inhalational general anesthetic agents have differing effects on cerebral hemodynamics, which may affect ischemic brain tissue and clinical outcome. We compared outcomes in patients undergoing endovascular thrombectomy with general anesthesia who were treated with propofol or volatile agents. Methods: Consecutive endovascular thrombectomy patients treated using general anesthesia were identified from our prospective database. Baseline patient characteristics, anesthetic agent, and clinical outcomes were recorded. Functional independence at 3 months was defined as a modified Rankin Scale of 0 to 2. Results: There were 313 patients (182 [58.1%] men; mean±SD age, 64.7±15.9 y; 257 [82%] anterior circulation), of whom 254 (81%) received volatile inhalational (desflurane or sevoflurane), and 59 (19%) received intravenous propofol general anesthesia. Patients with propofol anesthesia had more ischemic heart disease, higher baseline National Institutes of Health Stroke Scale scores, more basilar artery occlusion, and were less likely to be treated with intravenous thrombolysis. Multivariable logistic regression analysis showed that propofol anesthesia was associated with improved functional independence at 3 months (odds ratio=2.65; 95% confidence interval, 1.14-6.22; P=0.03) and a nonsignificant trend toward reduced 3-month mortality (odds ratio=0.37; 95% CI, 0.12-1.10; P=0.07). Conclusion: In stroke patients undergoing endovascular thrombectomy treated using general anesthesia, there may be a differential effect between intravenous propofol and volatile inhalational agents. These results should be considered hypothesis-generating and be tested in future randomized controlled trials. Supported by the Neurological Foundation of New Zealand. An earlier version of this work was presented at the 5th European Stroke Organisation Conference, Milan, Italy; 2019. The authors have no conflicts of interest to disclose. Address correspondence to: P. Alan Barber, MBChB, PhD, FRACP. E-mail: a.barber@auckland.ac.nz. Received April 16, 2019 Accepted July 23, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Intraoperative-evoked Potential Monitoring: From Homemade to Automated Systems No abstract available

Cortical Oscillations and Connectivity During Postoperative Recovery Background: The objective of this study was to test whether postoperative electroencephalographic (EEG) biomarkers, parietal alpha power and frontal-parietal connectivity, were associated with measures of clinical recovery in adult surgical patients. Methods: This is a secondary analysis of a prospective cohort study that analyzed intraoperative connectivity patterns in adult surgical patients (N=53). Wireless, whole-scalp EEG data were collected in the postanesthesia care unit and assessed for relevance to clinical and neurocognitive recovery. Parietal alpha power and frontal-parietal connectivity (estimated by weighted phase lag index) were tested for associations with postanesthesia care unit discharge readiness and University of Michigan Sedation Scale scores upon postoperative admission. Bivariable correlation and regression models were constructed to test for unadjusted associations, then multivariable regression models were constructed to adjust for confounding. Results: Postoperative EEG patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, −0.25; 95% confidence interval [CI], −1.41 to 0.90; P=0.657) nor alpha frontal-parietal connectivity (weighted phase lag index, −82; 95% CI, −237 to 73; P=0.287) were associated with time until postanesthesia discharge criteria were met. Furthermore, neither alpha power (−0.03; 95% CI, −0.07 to 0.01; P=0.206) nor alpha frontal-parietal connectivity (−4.2; 95% CI, −11 to 2.6; P=0.226) were associated with sedation scores upon initial assessment. Conclusions: In a pragmatic study investigating clinically relevant endpoints of postoperative recovery, we found no correlation with surrogate measures of brain neurodynamics. These data contribute to the overall impetus of developing anesthetic-invariant and generalizable markers of brain recovery. Supported by the National Institutes of Health, Bethesda, MD, Grants R01GM098578 and K23GM126317 (P.E.V.). Previous presentations of the work: the authors previously published a separate, distinct line of analysis from these participants that focused on dynamic cortical connectivity patterns intraoperatively (Vlisides et al. Anesthesiology 2019;130(6):885–897). In addition, data from this investigation were presented in poster format at the 2019 University of Michigan School of Nursing Honors Symposium (September 4, 2019, Ann Arbor, MI). The authors have no conflicts of interest to disclose. Address correspondence to: Phillip E. Vlisides, MD. E-mail: pvliside@med.umich.edu. Received April 24, 2019 Accepted July 19, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Impact of a Perioperative Protocol on Length of ICU and Hospital Stay in Complex Spine Surgery Background: In an attempt to improve patient care, a perioperative complex spine surgery management protocol was developed through collaboration between spine surgeons and neuroanesthesiologists. The aim of this study was to investigate whether implementation of the protocol in 2015 decreased total hospital and intensive care unit (ICU) length of stay (LOS) and complication rates after elective complex spine surgery. Materials and Methods: A retrospective cohort study was conducted by review of the medical charts of patients who underwent elective complex spine surgery at an academic medical center between 2012 and 2017. Patients were divided into 2 groups based on the date of their spine surgery in relation to implementation of the spine surgery protocol; before-protocol (January 2012 to March 2015) and protocol (April 2015 to March 2017) groups. Outcomes in the 2 groups were compared, focusing on hospital and ICU LOS, and complication rates. Results: A total of 201 patients were included in the study; 107 and 94 in the before-protocol and protocol groups, respectively. Mean (SD) hospital LOS was 14.8±10.8 days in the before-protocol group compared with 10±10.7 days in the protocol group (P<0.001). The spine surgery protocol was the primary factor decreasing hospital LOS; incidence rate ratio 0.78 (P<0.001). Similarly, mean ICU LOS was lower in the protocol compared with before-protocol group (4.2±6.3 vs. 6.3±7.3 d, respectively; P=0.011). There were no significant differences in the rate of postoperative complications between the 2 groups (P=0.231). Conclusion: Implementation of a spine protocol reduced ICU and total hospital LOS stay in high-risk spine surgery patients. Study was presented under the name: “Protocolized Perioperative Care for Complex Spine Surgeries and the Resulting Reduction in ICU/Hospital Length of Stay” at: (1) American Society of Anesthesiologists (ASA) Annual Meeting in San Francisco, October 13, 2018 (Session EA-19-1). (2) SNACC Annual Meeting in San Francisco on October 12, 2018. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Eugenia Ayrian, MD. E-mails: eayrian@med.usc.edu; eugenia.ayrian@gmail.com. Received August 28, 2018 Accepted July 11, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved