A. Castro

A. Ferreira

J. Gabriel

P. Amorim

S. Pedrosa

English

Repositório Aberto da Universidade do Porto

Abstracts published in the Journal of Neurosurgical Anesthesiology have beenreviewed by the organizations or JNA Affiliate Societies at whose meetings theabstracts have been accepted for presentation. These abstracts have not undergonereview by the Editorial Board of the Journal of Neurosurgical Anesthesiology. Insome instances the print quality of submitted figures and tables is not up to JNAstandards, but has been published in the interest of time.Abstracts From the 43rd Annual Meeting of the Societyfor Neuroscience in Anesthesiology and Critical Care,San Diego, CA, October 23, 2015[SNACC-1] Inhibition of RhoA Activity with TAT-C3 AttenuatesPropofol-mediated NeurotoxicityJian M*, Pearn Mw, Egawa J*, Head B*, Patel P*, Han Rz. *Universityof California, San Diego, San Diego, California, United states. wUniver-sity of California, San Diego, San Diego, California, United states.zBeijing Tiantan Hospital, Beijing, Beijing, China.Background: Propofol (PPF) exposure to developing neurons during syn-aptogenesis results in neurodegeneration; the resulting cognitive dysfunctionin adulthood has bene attributed to apoptosis. However, recent data indicatethat apoptosis per se might not be the primary mechanism that leads tocognitive dysfunction. Anesthetic induced disruption of neuronal cytoske-leton leads to loss of neuritis, dendrites and synapses, thereby disruptingdevelopment of neuronal networks. PPF induced activation of RhoA playsa central role in neurite loss. Inhibition of RhoAmight prevent PPF toxicity.To determine whether RhoA inhibition prevents neurite loss and preventsthe adverse effects of PPF on the development of neuronal networks in thehippocampus, we investigated the effect of TAT-C3, a RhoA inhibitor, onneurite loss in cultured rodent neurons and in mice in vivo. Similar studieswere undertaken in human neurons in vitro to determine whether RhoA isof relevance to PPF toxicity in human tissue.Methods: Primary fetal human neurons (Advanced Bioscience Re-sources, Alameda, CA) and postnatal day 5-7 (PND5-7) mice were ex-posed to PPF (3 mM) or DMSO for 6 hours, with pre-treatment of TATconjugated C3 (TAT-C3) (50 ug/mL, 2 h), a highly specific pharmaco-logic inhibitor of RhoA or TAT control. RhoA activation was evaluatedby staining for RhoA-GTP (active form). Dendritic spine changes wereevaluated with the neuronal spine marker, drebrin. Changes in synapsesin PND5-7 mouse hippocampi were assessed by electron microscopy.Histological sections of the entire hippocampus were stained for syn-aptoporin to quantify the area and volume of suprapyramidal and in-frapyramidal mossy fibers from the dentate granule neurons to the CA3pyramidal neurons (SPM and IPM, respectively) in vivo.Results: Exposure of human neurons in vitro to PPF increased active RhoA,decreased drebrin staining, and decreased dendritic arborization. Theseadverse effects of PPF were mitigated by TAT-C3. These are the first data inhuman neurons to demonstrate PPF neurotoxicity. In PND7 rodent pupsexposed to PPF, a reduction in SPM was apparent. By 1 week after ex-posure, the SPM fibers were restored. By contrast, there was a significantreduction in IPM volume that was apparent even 4 weeks post exposure.Conclusions:Our previous results, which demonstrated that PPF inducedtoxicity was prevented by RhoA inhibition in rodent neurons, were re-capitulated in human neurons. These data indicate that RhoA may alsoplay an important role in anesthetic neurotoxicity in human tissue. Inaddition, our results demonstrate that PPF causes a dramatic alterationin neuronal networks in vivo. A single exposure at PND7 led to per-sistent alteration of the mossy fibers of hippocampus four weeks postexposure (at PND35). This alteration in the architecture of the hippo-campus may contribute to cognitive dysfunction in adulthood.[SNACC-2] Effect of Early Repeated Anesthetic Exposure onLong-term CognitionLee B, Sall J.University of California, San Francisco, San Francisco, CA, US.Background: Early anesthetic exposure in humans and rodents leads tolong-term cognitive effects. In rodents, longer exposures result in worseoutcomes.1 Studies have also demonstrated that multiple anesthetic ex-posures may be more harmful than a single exposure.2,3 Those studies,however, do not account for the increased cumulative duration of gen-eral anesthesia associated with multiple exposures to anesthesia.Therefore, it is unclear whether the worse outcome is due to repeatedexposures or simply a greater total duration of anesthesia.Methods: Postnatal day (P)7 male rats were anesthetized using iso-flurane. In one group, subjects were exposed to isoflurane for 6 hourscontinuously. In the other group, animals were anesthetized for 3 hourson P7 and then again for 3 hours on P8, resulting in a combined total of6 hours. A control group was included that did not undergo anesthesia.Long-term behavioral outcome was assessed weeks later using a series ofassociative memory tests which included various novel object recog-nition (NOR) tasks and an item association task (IA). Both memorytests evaluate context-specific memory and the ability to recognize ob-jects and scents using specific contextual cues.Results: Animals in the repeat exposure group (“Iso 3+3”) demon-strated worse behavioral outcomes than those in the single exposuregroup (“Iso 6”). Iso 3+3 subjects were impaired in all variants of theNOR task while Iso 6 animals were only impaired in the most complextask. In the IA task, both groups were impaired relative to control whenrelying on proximal and distal contextual cues. Iso 3+3 (repeat ex-posure) performed worse than Iso 6 (single exposure) in the proximalcontextual cue task.Conclusion: Isofurane exposure in neonatal rats results in impaired long-term associative memory. Repeated exposure leads to worse outcomethan a single exposure even when the total anesthetic duration isequivalent.References:1. Stratmann G, May LD, Sall JW, et al. Effect of hypercarbia andisoflurane on brain cell death and neurocognitive dysfunction in 7-day-old rats. Anesthesiology. 2009;110:849–861.2. Flick RP, Katusic SK, Colligan RC, et al. Cognitive and behavioraloutcomes after early exposure to anesthesia and surgery. Pediatrics.2011;128:e1053–e1061.3. Murphy KL, Baxter MG. Long-term effects of neonatal single ormultiple isoflurane exposures on spatial memory in rats. Frontiers inneurology. 2013;4:87.[SNACC-3] Caveolin-1 is a Biomarker of Propofol MediatedNeurotoxicity in Developing NeuronsPearn M*, Elvina D*, Patel Hw, Patel P*, P Bw. *University of Californiaat San Diego, San Diego, California, United States. wVeterans AffairsMedical Center, La Jolla, California, United States.Background: A wide body of evidence indicates that anesthetic exposureduring synaptogenesis in the developing brain causes widespread neu-rodegeneration, electrophysiologic abnormalities of neuronal networksand long-term cognitive deficits. Although the mechanism by whichanesthetics injure the neonatal brain is not known, GABA-A mediatedexcitation, NMDAR antagonism mediated excitotoxicity, aberrant cellcycle entry, mitochondrial injury and free radical mediated toxicity playa role. Work from our laboratory has demonstrated that preferentialsignaling of proBDNF via p75NTR leads to downstream activation ofCopyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.ABSTRACTSJ Neurosurg Anesthesiol  Volume 27, Number 4, October 2015 www.jnsa.com | 399Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.[SNACC-57] Anesthesia Induction with Propofol and Re-mifentanil for Neurosurgery: Identification of a BIS Time DelayS C*, Leitão Ferreira Aw, Castro Az, Pedrosa Sy, Gabriel J8, AmorimPz. *Universidade Aberta and Centro De Investigação Clinica Em Anes-tesiologia (Chp), Porto, Portugal. wFaculdade De Engenharia Da Uni-versidade Do Porto, Porto, Portugal. zInstituto De Telecomonicacoes,Porto, Portugal. yCentro Hospitalar Do Baixo Vouga, Aveiro, Portugal.8Inegi, Faculdade De Engenharia Up, Porto, Portugal. zCentro Hospi-talar Do Porto, Porto, Portugal.There is a delay in the bispectral index (BIS) related to the smoothingrate, which is approximately 5-10 seconds, according to the manu-facturer1–3 suggest longer delays, but were criticized for not using aclinical approach. The aim of this study was to evaluate the existence ofAbstracts J Neurosurg Anesthesiol  Volume 27, Number 4, October 2015432 | www.jnsa.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.a delay in the BIS response through an innovative approach using thedifference between the predicted and the actual BIS in the induction ofgeneral anesthesia with propofol/remifentanil. Another aim was to an-alyze the delay according to two different induction protocols.A posteriori (IRB approval) the induction data of patients scheduled forneurosurgery with 2 different anesthesia protocols were analyzed: G1–propofol infusion starts at 200mL/h until loss of consciousness (LOC)followed by remifentanil with an effect-site concentration (Ce) target of2.5 ng/mL; G2– remifentanil infusion starts with a Ce target 2.5 ng/mLand 1 minute after the remifentanil Ce target is achieved, propofol in-fusion starts at 200mL/h until LOC. After LOC drug’s infusion (TCI)are changed according to patient needs to maintain BIS at 40-60. Thefollowing data were recorded every 5 seconds, during the first 20 minutesof induction, with Rugloops: propofol Ce (Pk-Schnider), remifentanilCe (Pk-Minto) and BIS. These data were used to identify the pharma-codynamics (PD)4 of each patient and to predict the BIS response. TheBIS time delay was identified as the difference between the predictedresponse of the PD model and the actual BIS of the patient. Data areMean±SD. T-test was applied (P<0.05).Data from 45 patients for each group were analyzed, demographics didnot differ. Propofol Ce, Remifentanil Ce and predicted BIS versus actualBIS of each patient are shown in Fig. 1, The mean absolute error (MAE)between predicted and actual BIS was of 5.8±2.7 in G1 and 9.9±4.4in G2 (P<0.001). Delays of 0.59±0.43 minutes in G1 and1.15±0.63 minutes in G2 were identified (P<0.001).These results suggest a delay in the BIS response on average 0.59 or 1 mi-nute, a much higher value than the announced by the manufacturer andclinically significant. This delay is similar to that suggested in other studies,but in our study we had the advantage of using real patient data. Thedifferent delay depending on the induction protocol (G1 or G2) may berelated to the fact that the PKmodels Ke0 do not correctly predict the effect/concentration delay, or due to the inter-patient variability which can begreater than expected. The difference between groups suggests that thedrug’s interaction may have different magnitudes according to the protocolof induction. The results are clinically relevant: during induction BIS mustbe interpreted taking into account the time delay and drug infusion protocol.References:1. Covidien BIS Manual.2. Br J Anaesth. 2009;103(3):394–9.3. Anesthesiology. 2006;104(3): 488–94.4. Anesthesiology. 2000;92(6):1603–16.Funding: FCT-UID/SEM/50022/2013;SFRH/BD/98915/2013.[SNACC-58] Evaluation of Facial Nerve Motor Evoked Poten-tials Using Threshold Level Stimulation Method During SkullBase SurgeryHayashi H, Ogawa Y, Takatani T, Kawaguchi M. Nara Medical Uni-versity, Kashihara, Nara, Japan.Background: The preservation of facial nerve function is one of theprimary objectives in skull base surgery. Recently, transcranial facialnerve motor evoked potentials (Tc-FNMEP) has been used to monitorintraoperative facial nerve function. However, there are some difficultiesin interpretation of waveform change due to low reproducibility of Tc-FNMEP waveform. The present study was designed to investigate thereliability of intraoperative Tc-FNMEP using threshold level trans-cranial stimulation during skull base surgery.Methods: Twenty-five patients (57.5±13.1 y, 8 males and 17 females)undergone elected skull base surgery using Tc-FNMEP monitoring werestudied. General anesthesia was maintained by total intravenous anes-thesia using propofol without neuromuscular blockade. Threshold leveltranscranial stimulation of Tc-FNMEP was established with minimumintensity to elicit the waveform from recording muscles. A train of 4pulses with 500Hz was delivered through corkscrew electrodes at C3/C4(international 10/20 method). Subdermal needle electrodes placed in theorbicularis oculi muscle at the lateral angle of the bilateral eyes and inthe orbicularis oris muscle at the bilateral angle of the mouth for re-cording Tc-FNMEP. MEE-1232 (Nihon Kohden, Tokyo, Japan) wasused as an electrophysiological device. Significant change of amplitudewas defined as more than 50% decrease compared with baseline am-plitude. Facial nerve function was evaluated preoperatively and post-operatively using the House and Brackmann grading system. Thereliability of intraoperative Tc-FNMEP was assessed by sensitivity andspecificity to detect postoperative facial nerve dysfunction.Results: Control Tc-FNMEP waveforms were successfully recorded inall patients. Of 25 patients, significant sustained decreases of Tc-FNMEP until the end of surgery were observed in 6 patients. Post-operative new facial nerve dysfunction or worsen facial nerve functionwere observe in 6 patients. Of the 6 patients with postoperative deteri-oration of facial nerve function, 4 patients had intraoperative significantdecline of Tc-FNMEP. The sensitivity and specificity of intraoperativeTc-FNMEP to detect postoperative facial nerve dysfunction were 66.7%and 84.2%, respectively.Conclusions: The results in this study indicated the feasibility of intra-operative Tc-FNMEP using threshold level transcranial stimulationduring skull base surgery.[SNACC-59] Assessment of Neuromonitoring Techniques in In-tracranial Aneurysm SurgeriesRamani R*, Razia D*, Callahan Bw, Fomberstein K*. *Yale UniversitySchool of Medicine, New Haven, CT, United States. wImpulse Monitor-ing, Columbia, MD, USA.Introduction: Intracranial aneurysm clipping is associated with sig-nificant mortality and morbidity primarily due to ischemia in the vas-cular territory of the aneurysm. Surgical clipping of aneurysms ispreferred when the morphology of the aneurysm does not permit en-dovascular coiling. Over the last 10 years intraoperative neuro-monitoring (IONM) of motor evoked potential (MEP), sensory evokedpotential (SSEP) and electroencephalography (EEG)- collectively, neu-romonitoring, has been advocated to identify ischemic insults potentiallyresulting in poor outcomes. The premise being, an ischemic insult willlead to an alert, which, with corrective measures could be resolved,preventing ischemic damage. Our aim in this study is to assess theclinical value of neuromonitoring during aneurysm surgery.Methods: After approval from Yale University IRB electronic records ofall patients who were monitored with MEP, SSEP & EEG during sur-gical clipping of aneurysm between 2010 -14 were reviewed. Intra-operative changes in MEP, SSEP & EEG, (“alerts”) as determined bythe neurophysiologist, and any intervention carried out by the care teamwere identified. The criteria for diagnosing IOM alert was:- EEG - decrease in amplitude and/or frequency or burst suppression.- MEP - decrease in amplitude of the motor action potential.- SSEP - 50% decrease in amplitude and /or 10% increase in latency.We correlated the neuromonitoring alerts with the postoperative out-come (Glasgow Outcome Score - GOS) at 6 weeks.Results: There were 72 patients (14 males & 58 females). In two casesthough clipping was planned endovascular coiling was performed. Pa-tient population included 46 unruptured and 26 ruptured aneurysms.Most of the aneurysms were in the anterior and middle cerebral arteryterritory.Based on GOS, 61/72 patients (84.7%) had a good outcome (minimal or noneurological deficit), while 11/72 (15.3%) had a poor outcome. Of the pa-tients with good outcomes, 19 had one or more alerts that resolved withintervention. Of the 11 patients with deficits, 3 had alerts and 8 did not.In the entire group 22/72 (30.6%) patients had alerts (14 in EEG, 8 inMEP and 6 in SSEP). In 19/22 cases the alerts resolved after interventionand these patients had a good outcome. In the remaining 3, the alerts didnot resolve and patients had significant deficits postoperatively. Amongthe 50 patients with no alerts, 8 had poor outcomes.Conclusions: With the institution of IONM 84.7% patients had a goodoutcome. While the individual monitors by themselves were not sensitiveenough when all the three (EEG, SSEP, MEP) are monitored the sen-sitivity of detection of intraoperative ischemia improves to 73.3% (22/30) considering the 8 cases with no alert and poor outcome. There issome chance that vasospasm or other etiologies may have played a rolein the 6-week postoperative outcomes. We recommend monitoring EEG,SSEP and MEP for all intracranial aneurysm surgical clipping.J Neurosurg Anesthesiol  Volume 27, Number 4, October 2015 AbstractsCopyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. www.jnsa.com | 433Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.

Anesthesia Induction with Propofol and Remifentanil for Neurosurgery: Identification of a BIS Time Delay

Open Repository of the University of Porto

https://repositorio-aberto.up.pt/bitstream/10216/85872/2/152541.pdf

Anesthesia Induction with Propofol and Remifentanil for Neurosurgery: Identification of a BIS Time Delay

Abstract

Similar works

Full text

Available Versions

Repositório Aberto da Universidade do Porto

Open Repository of the University of Porto