Ketamine in depression and electroconvulsive therapy.

PURPOSE OF REVIEW: The antidepressant effect of subanesthetic doses of ketamine was recognized 20 years ago. This review briefly summarizes the current understanding of the antidepressant mechanisms and the available clinical research on the use of racemic ketamine and enantiomer esketamine for depression. RECENT FINDINGS: The antidepressant effect of subanesthetic doses of ketamine is currently considered to be predominantly mediated by improved neuroplasticity in cortico-limbic areas in the brain. Single dose of 0.5 mg/kg of ketamine infused intravenously over 40 min, or single intranasal dose of esketamine cause rapid antidepressant and antisuicidal effects within hours of administration, and the antidepressant effect may last up to a week. Repeated administration of nasal spray esketamine is considered to prevent relapse of depression. Longitudinal studies are currently insufficient. When used in various doses for anesthetic induction for electroconvulsive therapy, ketamine improves seizure quality and may possibly diminish posttherapy cognitive impairment. SUMMARY: A rapid onset antidepressive effect of ketamine and esketamine has been proven conclusively. The results of extensive basic science research of the mechanism of action of low-dose ketamine doses has led to an alternative hypothesis of the pathophysiology of depression and the development of a novel neurotrophic concept of depression. Further longitudinal studies are warranted to determine the safety and efficacy of repeated administration of ketamine and its analogs to prevent relapse and recurrence of depression.

Neuroanesthesia Practice During the COVID-19 Pandemic: Recommendations From Society for Neuroscience in Anesthesiology and Critical Care (SNACC).

The pandemic of coronavirus disease 2019 (COVID-19) has several implications relevant to neuroanesthesiologists, including neurological manifestations of the disease, impact of anesthesia provision for specific neurosurgical procedures and electroconvulsive therapy, and health care provider wellness. The Society for Neuroscience in Anesthesiology and Critical Care appointed a task force to provide timely, consensus-based expert guidance for neuroanesthesiologists during the COVID-19 pandemic. The aim of this document is to provide a focused overview of COVID-19 disease relevant to neuroanesthesia practice. This consensus statement provides information on the neurological manifestations of COVID-19, advice for neuroanesthesia clinical practice during emergent neurosurgery, interventional radiology (excluding endovascular treatment of acute ischemic stroke), transnasal neurosurgery, awake craniotomy and electroconvulsive therapy, as well as information about health care provider wellness. Institutions and health care providers are encouraged to adapt these recommendations to best suit local needs, considering existing practice standards and resource availability to ensure safety of patients and providers.

Beta-blocker Use is Associated with a Reduction in Opioid Use 30 Days After Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) can lead to chronic pain and prolonged postoperative opioid use. There are few evidence-based interventions to prevent these outcomes. Recently, beta-blockers have emerged as possible novel analgesics. OBJECTIVES: The objective of this study was to determine whether perioperative beta-blocker use is associated with reduced prolonged postoperative opioid use after TKA. STUDY DESIGN: This study used a retrospective cohort design. SETTING: The research took place within Department of Veterans Affairs hospitals in the United States between April 2012 and April 2016. METHODS: Patients: IRB approval was obtained to examine the records of Veterans Affairs (VA) patients undergoing TKA. Patients using opioids 60 days before surgery were excluded. INTERVENTION: The intervention being investigated was perioperative beta-blocker use, overall and by class. MEASUREMENT: Oral morphine equivalent usage through postoperative day 1 and prescription opioid refills through 30, 90, and 365 days after TKA were recorded. Adjusted models were created controlling for relevant demographic and comorbidity covariates. A secondary analysis examined the same outcomes separated by beta-blocker class. RESULTS: The cohort was 93.8% male with a mean age of 66 years. Among the 11,614 TKAs that comprised the cohort, 2,604 (22.4%) were performed on patients using beta-blockers. After adjustment, beta-blocker use was associated with reduced opioid use through 30 days after surgery (odds ratio [OR] 0.89 [95% confidence interval (CI), 0.80-0.99], P = .026). Selective beta-blockers were associated with reduced opioid use at 30 days (OR 0.88 [95% CI, 0.78-0.98], P = .021), and nonselective beta-blockers were associated with reduced oral morphine equivalent usage through postoperative day 1 (beta = -17.9 [95% CI, -29.9 to -5.8], P = .004). LIMITATIONS: Generalizability of these findings is uncertain, because this study was performed on a cohort of predominantly white, male VA patients. This study also measured opioid use, but opioid use is not a perfect surrogate for pain. Nevertheless, opioid use offers value as an objective measure of pain persistence in a national cohort for which patient-reported outcomes are otherwise unavailable. CONCLUSIONS: Perioperative beta-blocker use was associated with reduced prescription opioid use at 30 days after surgery. Both selective and nonselective beta-blockers were associated with reduced opioid use when analyzed individually. KEY WORDS: Analgesics, opioid, arthroplasty, replacement, knee, adrenergic beta-antagonists, pain management.

Ketamine Anesthesia Does Not Improve Depression Scores in Electroconvulsive Therapy: A Randomized Clinical Trial.

BACKGROUND: Although interest in ketamine use during electroconvulsive therapy (ECT) has increased, studies have been equivocal with regard to its efficacy. The aims of this clinical trial were to evaluate ketamine's antidepressive effects in ECT as a primary anesthetic, determine ketamine's tolerability when compared with standard anesthesia, and determine if plasma brain-derived neurotrophic factor (BDNF) is necessary for treatment response. MATERIALS AND METHODS: Adults meeting criteria for treatment-resistant depression undergoing index course ECT received either methohexital (1 to 2 mg/kg) or ketamine (1 to 2 mg/kg) anesthesia in this dual-arm double-blinded randomized clinical trial (NCT02752724). The primary outcome of this study is change in depression questionnaire scores before and after ECT. Seizure data, depression severity using self-reported and clinician-assessed questionnaires, cognitive scoring, and plasma BDNF concentrations were obtained before and after completion of ECT. RESULTS: There were no differences in seizure lengths, hemodynamics, or seizure stimuli between the ketamine (n=23;138 ECTs) and methohexital (n=27;159 ECTs) groups. Depression scores improved similarly after ECT in both groups. In the methohexital group, 15% of patients failed to achieve adequate seizures and were switched to ketamine and 26% were converted to bilateral ECT stimulus, whereas all ketamine patients achieved adequate seizures and only 4% required bilateral stimulus. Plasma BDNF increased after ECT only in the ketamine group. CONCLUSIONS: Our data show that ketamine does not significantly improve depression when compared with methohexital as a single induction agent for ECT, increases serum BDNF and does not increase rates of post-ECT agitation. Ketamine use in ECT may have some benefits for some patients that are not captured through standard depression assessment questionnaires alone.

A Risk Calculator Using Preoperative Opioids for Prediction of Total Knee Revision Arthroplasty.

OBJECTIVES: Total knee arthroplasty (TKA) is a procedure to improve quality of life. However, some patients require early total knee revision (TKR). Chronic opioid use before TKA is associated with TKR. No risk calculator including opioid use or other risk factors is currently available for predicting TKR. MATERIALS AND METHODS: We retrospectively analyzed medical records of Veterans Affairs patients who underwent TKA from January 1, 2006 to January 1, 2012. Patients were followed until January 1, 2013. Chronic opioid use was defined as opioid use for ≥3 months preoperatively. A cross-validated Cox proportional hazards model was created to predict TKR before initial TKA. Model performance was evaluated by the mean absolute error at 1 and 5 years. RESULTS: Totally, 32,297 patients were included. A risk calculator was generated with a mean absolute error of 0.1% at 1 year and 3.6% at 5 years. Chronic opioid use was a significant predictor of TKR (hazard ratio [HR], 1.27; 95% confidence interval, 1.13-1.43; P<0.001). Other model variables were age (HR, 0.95; P<0.001), female sex (HR, 0.77; P=0.020), body mass index (HR, 0.99; P=0.022), diabetes (HR, 1.20; P=0.001), chronic kidney disease (HR, 1.48; P<0.001), and nonchronic opioid use (HR, 1.07; P=0.313). DISCUSSION: Preoperative chronic opioid use is a predictor of TKR. Using this association and others, a TKA revision risk calculator was generated at http://www.bit.do/tka.

Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery for Traumatic Intracranial Hemorrhage in Elderly Patients.

BACKGROUND: Antiplatelet medications are usually discontinued before elective neurosurgery, but this is not an option for emergent neurosurgery. We performed a retrospective cohort study to examine whether preoperative aspirin use was associated with worse outcomes after emergency neurosurgery in elderly patients. METHODS: We analyzed all cases of emergency neurosurgical procedures for traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center. Demographics, comorbidities, and outcomes were compared for patients ≥65 years by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2) concomitant use of other preoperative anticoagulants or antiplatelet agents, (3) surgical indication other than subdural, extradural, or intraparenchymal hemorrhage, and (4) repeat neurosurgical procedures within a single admission. Estimated intraoperative blood loss, postprocedural intracranial bleeding requiring reoperation, death in hospital, intensive care unit, and hospital lengths of stay and perioperative blood product transfusion from 48 hours before 48 hours after surgery were the study outcomes. We also examined whether platelet transfusion had an impact on outcomes for patients on aspirin. RESULTS: The cohort included 171 patients. Patients receiving preoperative aspirin (n = 87, 95% taking 81 mg/day) were the same age as patients not receiving aspirin (n = 84; 78.3 ± 7.8 vs 75.9 ± 7.9 years, P > .05), had slightly higher admission Glasgow Coma Scale scores (12.8 ± 3.4 vs 11.4 ± 4, P = .02) and tended to have more coronary artery disease (P< .05). Adjusted for Glasgow Coma Scale and coronary artery disease, patients receiving preoperative aspirin had a higher odds of perioperative platelet transfusion (adjusted odds ratio 9.89, 95% confidence interval, 4.24-26.25). There were no other differences in outcomes between the 2 groups. Preoperative or intraoperative platelet transfusion was not associated with better outcomes among aspirin patients. CONCLUSIONS: In patients age ≥65 years undergoing emergency neurosurgery for traumatic intracranial hemorrhage, preoperative low-dose aspirin treatment was not associated with increased perioperative bleeding, hospital lengths of stay, or in-hospital mortality.

Preoperative Opioid Use Is Associated with Early Revision After Total Knee Arthroplasty: A Study of Male Patients Treated in the Veterans Affairs System.

BACKGROUND: Opioid use is endemic in the U.S. and is associated with morbidity and mortality. The impact of long-term opioid use on joint-replacement outcomes remains unknown. We tested the hypothesis that use of opioids is associated with adverse outcomes after total knee arthroplasty (TKA). METHODS: We performed a retrospective analysis of patients who had had TKA within the U.S. Veterans Affairs (VA) system over a 6-year period and had been followed for 1 year postoperatively. The length of time for which an opioid had been prescribed and the morphine equivalent dose were calculated for each patient. Patients for whom opioids had been prescribed for >3 months in the year prior to the TKA were assigned to the long-term opioid group. A natural language processing-based machine-learning classifier was developed to classify revisions due to infectious and non-infectious causes on the basis of the postoperative note. Survival curves for the time to knee revision or manipulation were used to compare the long-term opioid group with the patients who did not take opioids long-term. Hazard and odds ratios for knee revision and manipulation were obtained as well. RESULTS: Of 32,636 patients (94.4% male; mean age [and standard deviation], 64.45 ± 9.41 years) who underwent TKA, 12,772 (39.1%) were in the long-term opioid group and 734 (2.2%) had a revision within a year after the TKA. Chronic kidney disease, diabetes, and long-term opioid use were associated with revision within 1 year-with odds ratios (95% confidence intervals [CIs]) of 1.76 (1.37 to 2.22), 1.11 (0.93 to 1.31), and 1.40 (1.19 to 1.64), respectively-and were also the leading factors associated with a revision at any time after the index TKA-with odds ratios (95% CIs) of 1.61 (1.34 to 1.92), 1.21 (1.08 to 1.36), and 1.28 (1.15 to 1.43), respectively. Long-term opioid use had a hazard ratio of 1.19 (95% CI = 1.10 to 0.24) in the analysis of its relationship with knee revision, but the hazard was not significant in the analysis of its association with knee manipulation. The accuracy of the text classifier was 0.94, with the area under the receiver operating characteristic curve being 0.99. There was no association between long-term use of opioids and the specific cause for knee revision. CONCLUSIONS: Long-term opioid use prior to TKA was associated with an increased risk of knee revision during the first year after TKA among predominantly male patients treated in the VA system. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dexmedetomidine Does Not Affect Evoked Potentials During Spine Surgery.

BACKGROUND: The effect of dexmedetomidine on evoked potentials (EPs) has not been elucidated. We aimed to investigate the effect of dexmedetomidine on somatosensory, motor, and visual EPs. METHODS: After IRB approval, 40 adult patients scheduled for elective spine surgery using total IV anesthesia with propofol and remifentanil were randomly assigned to receive either dexmedetomidine (n = 20) or placebo (n = 20) in a double-blind, placebo-controlled trial. After obtaining informed consent, positioning, and baseline EPs recording, patients were randomly assigned to either IV dexmedetomidine 0.6 µg/kg infused over 10 minutes, followed by 0.6 µg/kg/h, or a corresponding volume of IV normal saline (placebo). EP measures at 60 ± 30 minutes after initiation of study drug were defined as T1 and at 150 ± 30 minutes were defined as T2. Changes from baseline to T1 (primary end point) and from baseline to T2 (secondary end point) in EP latencies (milliseconds) and amplitudes (microvolts) were compared between groups. Data presented as mean ± SD (95% confidence interval). RESULTS: Data from 40 patients (dexmedetomidine: n = 20; age, 54 ± 3 years; 10 males; placebo: n = 20; age, 52 ± 2 years; 5 males) were analyzed. There was no difference between dexmedetomidine versus placebo groups in primary end points: change of somatosensory EPs at T1, latency: 0.01 ± 1.3 (-0.64, 0.65) vs 0.01 ± 1.3 (-0.64, 0.65), P = 0.43 (-1.24, 0.45); amplitude: 0.03 ± 0.14 (-0.06, 0.02) vs -0.01 ± 0.13 (-0.07, 0.05), P = 0.76 (-0.074, 0.1); motor EPs amplitude at T1: 65.1 ± 194.8 (-35, 165; n = 18) vs 109.2 ± 241.4 (-24, 243; n = 16), P = 0.57 (-113.5, 241.57); visual EPs at T1 (right eye), amplitude: 2.3 ± 3.6 (-0.4, 5.1; n = 11) vs 0.3 ± 6.0 (-3.3, 3.9; n = 16), P = 0.38 (-6.7, 2.6); latency N1: 2.3 ± 3.6 (-0.4, 5.1) vs 0.3 ± 6.0 (-3.3, 3.9), P = 0.38 (-6.7, 2.6); latency P1: -1.6 ± 13.4 (-11.9, 8.7) vs -1.4 ± 8.1 (-6.3, 3.5), P = 0.97 (-9.3, 9.7) or secondary end points. There were no differences between right and left visual EPs either at T1 or at T2. CONCLUSIONS: In clinically relevant doses, dexmedetomidine as an adjunct to total IV anesthesia does not seem to alter EPs and therefore can be safely used during surgeries requiring monitoring of EPs.

Prolonged opioid use after knee arthroscopy in military veterans.

BACKGROUND: Chronic postoperative pain occurs with an appreciable incidence after elective surgery. Known risk factors include perioperative pain and posttraumatic stress disorder (PTSD). Military veterans are a population at particular risk for PTSD and hence may be at increased risk for chronic pain after surgery. Our goal was to identify risk factors for chronic postoperative pain in young veterans after minor elective surgery, including the contribution of PTSD. METHODS: We reviewed the medical and pharmacy records of veterans (18-50 years old), undergoing elective knee arthroscopy from 2007 to 2010 at the Veteran's Administration Puget Sound Health Care System. The data included demographics, ASA physical status class, comorbidities, anesthesia medications, and opioid prescriptions starting 3.5 months before surgery and ending 3.5 months after surgery. We documented the presence of PTSD based on either the patient's problem list or the clinical notes. We used prolonged postoperative opioid prescription longer than 3 months after surgery as a surrogate for chronic postoperative pain. RESULTS: We identified 145 patients who met inclusion criteria. The median age was 39 ± 8 years old. Eighty-seven percent of the patients were men. The prevalence of PTSD was 32% (95% confidence interval, 25%-41%). PTSD was associated with increased incidence of smoking (P = 0.009) and preoperative opioid use (P = 0.0006). Preoperative opioids were prescribed in 44% (63 of 145) of the patients: in 64% (30 of 47) of patients with PTSD, compared with 34% (33 of 98) in patients without PTSD (P = .0006). Chronic postoperative pain was identified in 30% (43 of 145) of patients. The strongest independent predictor of chronic postoperative pain was an opioid prescription before surgery (odds ratio = 65.3; 95% confidence interval, 014.5-293.0). In patients older than 27.5 years who did not receive opioids before surgery, PTSD may also have been a risk factor for chronic postoperative pain. CONCLUSIONS: This single-center retrospective study suggests that the most important predictor of chronic postoperative pain is preoperative opioid use. For patients not taking opioids preoperatively, PTSD may increase the risk of prolonged postoperative opioid prescriptions and chronic postoperative pain, potentially related to patient age.

Perioperative management of carotid endarterectomy: a survey of clinicians' backgrounds and practices.

OBJECTIVE: To examine current trends in anesthetic practice for management of carotid endarterectomy (CEA) and how practice may differ by groups of practitioners. DESIGN: An online survey was sent to the Society of Cardiovascular Anesthesiologists and Society of Neuroscience, Anesthesiology, and Critical Care e-mail list servers. Responses were voluntary. SETTING: Academic medical centers and community-based hospitals providing perioperative care for a CEA in the United States and abroad. PARTICIPANTS: Anesthesiologists who provide perioperative care for patients undergoing a CEA. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Of 664 responders (13% response rate), most (66%) had subspecialty training in cardiovascular anesthesiology, had been in practice more than 10 years (68%), and practiced in the United States (US, 81%). About 75% of responders considered general anesthesia as a preferable technique for CA, and about 89% of responders provided it in real life, independent of subspecialty training. The most preferable intraoperative neuromonitoring was cerebral oximetry (28%), followed by EEG (24%), and having an awake patient (23%). Neuroprotection was not considered by 33% of responders, and upon conclusion of a case, 59% preferred an awake patient for extubation, while 15% preferred a deep extubation. Neuroanesthesiologists and non-US responders more often risk stratify patients for perioperative cerebral hyperperfusion syndrome, compared with cardiac anesthesiologists and US responders (p=0.004 and p<0.005, respectively). Additionally, reported management strategies vary substantially from anesthetic practice 20 years ago. CONCLUSIONS: Although there are areas of perioperative management in which there seems to be agreement for the CEA, there are also areas of divergent practice that could represent potential for improvement in overall outcomes. There are many potential reasons to explain divergence in practice by location or subspecialty training, but it remains unclear what the "best practice" may be. Future studies examining outcomes after carotid endarterectomy should include perioperative anesthetic management strategies to help delineate "best practice."

A novel computerized fading memory algorithm for glycemic control in postoperative surgical patients.

BACKGROUND: Hyperglycemia is commonly encountered in critically ill patients and is associated with increased mortality and morbidity. To better control blood glucose levels, we previously developed a new computerized fading memory (FM) algorithm. In this study we evaluated the safety and efficacy of this algorithm in surgical intensive care unit (SICU) patients and compared its performance against the existing insulin-infusion algorithm (named VA algorithm) used in our institution. METHODS: A computer program was developed to run the FM and VA algorithms. Forty eight patients, who were scheduled to have elective surgery, were randomly assigned to receive insulin infusion on the basis of either the FM or VA algorithm. On SICU admission, an insulin infusion was either continued from the operating room or initiated when the glucose level exceeded the target level of 140 mg/dL. Hourly blood glucose measurements were performed and entered into the computer program, which then prescribed the next insulin dose. The randomly assigned algorithm was applied for the first 8 hours of SICU stay, after which the VA algorithm was used. The number of episodes of hypoglycemia (glucose <60 mg/dL) and excessive hyperglycemia (>300 mg/dL) were noted. Additionally, the time required to bring the glucose level within target range (140 ± 20 mg/dL), the number of glucose measurements within the target range, glycemic variability, and insulin usage were analyzed and compared between the 2 algorithms. RESULTS: Patient demographics and starting glucose levels were similar between the groups. With the existing VA algorithm, 1 episode of severe hypoglycemia was observed. Three patients did not reach the target range within 8 hours. With the FM algorithm no hypoglycemia occurred, and all patients achieved the target range within 8 hours. Glycemic variability measured by the SD of mean glucose levels was 28% (95% confidence interval, 14% to 39%) lower for the FM algorithm (P < 0.001). The FM algorithm used 1.1 U/h less insulin than did the VA algorithm (P = 0.043). CONCLUSION: The novel computerized FM algorithm for glycemic control, which emulates physiologic biphasic insulin secretion, managed glucose better than the existing algorithm without any episodes of hypoglycemia. The FM algorithm had less glycemic variability and used less insulin when compared to the conventional clinical algorithm.

Risk of aspiration during anesthesia in patients with congenital insensitivity to pain with anhidrosis: case reports and review of the literature.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease, characterized by episodes of unexplained fever, anhidrosis, pain insensitivity despite intact tactile perception, self-mutilating behavior, mental retardation, and autonomic nervous system (ANS) abnormalities. We present a case series of three patients with CIPA who underwent semielective orthopedic surgery under general anesthesia complicated by intraoperative regurgitation, and subsequent aspiration in two of the three cases. All three patients were nil per os (NPO) for at least 8 h prior to surgery. Two patients had their airways maintained with a laryngeal mask airway (LMA), and one patient had an endotracheal tube (ETT). The patients with an LMA suffered aspiration of gastric contents and subsequently developed hypoxic cardiac arrest. Although the patient with an ETT in situ regurgitated intraoperatively, the presence of the ETT prevented aspiration and any further potential complications. We review the perioperative complications typically observed in patients with CIPA and discuss the risks of using an LMA in these patients. We recommend that patients with CIPA always should be considered as having a "full stomach", regardless of the duration of their NPO status, due to their coexisting ANS abnormalities. Therefore, rapid-sequence induction with an ETT should be utilized for the anesthetic management in every patient with CIPA.

Prolonged propofol anesthesia is not associated with an increase in blood lactate.

BACKGROUND: Lactic acidosis is considered an early sign of propofol infusion syndrome. In this study, we investigated the changes in lactate and pH with propofol versus volatile anesthesia (VA) of long duration. METHODS: Demographic and intraoperative data were recorded retrospectively from the anesthesia records of patients who underwent elective spine surgery longer than 8 h. Propofol patients were matched 1:2 to VA patients, based on anesthesia time (AT) (+/-30 min) and blood loss (BL) (+/-500 mL). RESULTS: Of 246 patients identified, 50 received propofol (AT = 10 +/- 2 h, BL = 1955 +/- 1409 mL) and were matched to 100 VA cases (AT = 10 +/- 1 h, BL = 1801 +/- 1543 mL), and of those, 40 and 72 patients, respectively, had complete lactate data at baseline and at 8 h after anesthesia and were included in the main analysis. The propofol group received 8.8 +/- 2 mg x kg(-1) x h(-1) of propofol. The VA group age was older than the propofol group (58 +/- 12 vs 51 +/- 15 yr, respectively, P = 0.002), but there was no difference between the groups in gender, ASA grade, intraoperative hemodynamic variables, and use of vasopressors. After 8 h, the VA group had a larger increase in arterial lactate from baseline compared with the propofol group (change from baseline: propofol, 0.48 +/- 0.72 mmol/L; VA, 1.2 +/- 1.2 mmol/L, P = 0.001). CONCLUSIONS: During prolonged spine surgery >8 h, VA was associated with higher serum lactate, when compared with propofol infusion. Prospective studies are needed to elucidate the exact mechanisms and clinical implications of this finding.

The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate.

INTRODUCTION: Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate. MATERIALS AND METHODS: A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes. RESULTS: NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS. DISCUSSION: The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.

Anesthesia for functional neurosurgery: the role of dexmedetomidine.

PURPOSE OF REVIEW: The purpose of this review is to summarize current approaches to the anesthetic management of functional neurosurgery and to describe the application of an alpha-2-adrenergic agonist dexmedetomidine in the anesthetic management of functional neurosurgical procedures. RECENT FINDINGS: Dexmedetomidine, an alpha-2-adrenergic agonist, causes a unique kind of sedation, acting on the subcortical areas, which resembles natural sleep without respiratory depression. Experimental data demonstrate both cerebral vasoconstriction and vasodilatation, depending on the model and dose studied. At the clinically relevant doses, dexmedetomidine decreases cerebral blood flow and cerebral metabolic rate of oxygen in healthy volunteers. Clinical experience of dexmedetomidine use in functional neurosurgery is limited to small case-series. Nevertheless, these reports indicate that use of dexmedetomidine does not interfere with electrophysiologic monitoring, thus allowing brain mapping during awake craniotomy and microelectrode recording during implantation of deep-brain stimulators. SUMMARY: Dexmedetomidine has been demonstrated to provide a successful sedation without impairment of electrophysiologic monitoring in functional neurosurgery. Prospective randomized studies are warranted to delineate an optimal regimen of dexmedetomidine sedation and any dose-related influence on neurophysiologic function.