The dosage of thiopental as pharmacological cerebral protection during non-shunt carotid endarterectomy: A retrospective study

Background Thiopental has been used as a pharmacological cerebral protection strategy during carotid endarterectomy surgeries. However, the optimal dosage required to induce burst suppression on the electroencephalogram (EEG) remains unknown. This retrospective study aimed to determine the optimal dosage of thiopental required to induce burst suppression during non-shunt carotid endarterectomy. Methods The Neurological Institute of Thailand Review Board approved the study. Data were collected from 2009 to 2019 for all non-shunt carotid endarterectomy patients who received thiopental for pharmacological cerebral protection and had intraoperative EEG monitoring. Demographic information, carotid stenosis severity, intraoperative EEG parameters, thiopental dosage, carotid clamp time, intraoperative events, and patient outcomes were abstracted. Results The study included 57 patients. Among them, 24 patients (42%) achieved EEG burst suppression pattern with a thiopental dosage of 26.3±10.1 mg/kg/hr. There were no significant differences in perioperative events between patients who achieved burst suppression and those who did not. After surgery, 33.3% of patients who achieved burst suppression were extubated and awakened. One patient in the non-burst suppression group experienced mild neurological deficits. No deaths occurred within one month postoperative. Conclusions The optimal dosage of thiopental required to achieve burst suppression on intraoperative EEG during non-shunt carotid endarterectomy was 26.3±10.1 mg/kg/hr.


Introduction
Stroke is one of the leading causes of death and disability in Thailand, 1 and carotid stenosis is one of the leading causes of stroke. 2 The surgical treatment to prevent stroke is carotid endarterectomy (CEA).It is associated with periprocedural risks, including stroke (embolic or hemodynamic), myocardial infarction, and death.Therefore, strict selection criteria are applied for patients undergoing CEA.Current selection criteria support CEA for symptomatic low-risk surgical patients with 50% to 99% stenosis and asymptomatic patients with stenosis of 70% to 99%. 3 However, the ability of the patient to tolerate the cross-clamp depends on the sufficiency of collateral flow through the circle of Willis.Inadequate collateral cerebral perfusion during the cross-clamp period increases the risk of perioperative stroke. 4Despite routine intraluminal shunt during the temporary occlusion of the ipsilateral internal carotid artery being controversial, intraoperative electrophysiological monitoring, such as electroencephalogram (EEG), is a valuable tool to detect cerebral hypoperfusion and determine selective shunting. 5,6When the neurosurgeon performed the non-shunt technique, adequate cerebral perfusion during carotid cross-clamping could be achieved using several methods to protect the brain. 7Spetzler et al. 8 reported excellent non-shunt surgical outcomes using intra-operative barbiturate and microsurgical techniques.The clinical use of barbiturates is known for cerebral protection against the prevention of focal cerebral ischemia, 9 especially when barbiturate was administered before the ischemic insult with doses large enough to produce burst-suppression activity on the EEG. 10 Despite the lack of clarity, the rationale for inducing burst suppression is based on its theorized potential neuroprotective effects.Burst suppression reduces metabolic demand by decreasing intracellular adenosine triphosphate (ATP) concentration, leading to decreased neuronal activity and electrical signaling, 11 reduction in cerebral blood flow (CBF), 12 and preserving limited energy resources during critical situations.Although, experimental animal studies conducted by Warner DS 13 and Robert Schmid-Elsaesser, 14 indicate that EEG burst suppression may not be necessary for maximum cerebral protection.Additionally, Westermaier T 15 found no additional neuroprotection following mild hypothermic treatment of rats subjected to reversible focal ischemia by barbiturate-induced burst suppression.Despite this, animal studies may not be conclusive in humans due to inter-species differences in burst suppression effects 16 and differences in physiology and the human clinical context.
Human research is crucial for understanding burst suppression benefits in clinical settings.Doyle PW 17 suggests that if the flow-metabolism coupling is intact, complete EEG burst suppression (100% burst suppression) may provide more cerebral protection than 50% burst suppression.However, the study did not evaluate the cerebral protection effects.Thus, further human studies are still needed to fully understand the relationship between burst suppression and cerebral protection, also the definite predetermined amount of barbiturate-induced burst-suppression activity on EEG including the optimal dosage, timing, and administration mode varies among studies to reach the burst-suppression pattern.
The Neurological Institute of Thailand is one of the few medical centers with EEG for intraoperative surveillance.Thus, to fill the knowledge gap, the authors aimed to study the optimal dose of barbiturates as thiopental for inducing EEG burst-suppression patterns in anesthetized patients undergoing carotid endarterectomy with a non-shunt technique.

Study design and participants
The study was approved by The Research Ethics Committee of the Neurological Institute of Thailand (approval number IRB53068).Written informed consent was waived, as this study was a retrospective observational without patient interventions.Data were collected from all consecutive patients with carotid artery stenosis who underwent CEA at the Neurological Institute of Thailand, Bangkok, from January 2009 to December 2019.Patients scheduled for CEA with intraoperative EEG were included, while Patients undergoing CEA without thiopental as pharmacological cerebral protection were excluded.

Pre-operative investigation
Patients with prior minor stroke, reversible ischemic neurological deficit (RIND), or transient ischemic attack (TIA) underwent Computed tomography (CT) brain scans.Carotid duplex ultrasound and magnetic resonance angiography

REVISED Amendments from Version 2
The revised manuscript describes more explicit guidelines for thiopental administration, neuromuscular blockade reversal details, and improved table information.Furthermore, the limitations section also includes the complexity of achieving EEG burst suppression and its implications for thiopental dosage.
Any further responses from the reviewers can be found at the end of the article (MRA) assessed carotid disease, degree of stenosis, and collateral circulation.Some cases had additional angiography to evaluate the carotid disease and the collateral circulation status.Carotid endarterectomy was based on duplex and MRA results.Patients with poor collateral flow had specific intraoperative assessment using the "Backflow technique."Insufficient blood flow led to intraluminal shunt use during carotid clamping.

Management of anesthesia and perioperative care
According to the institution, our neurosurgeons prefer non-shunt carotid endarterectomy under general anesthesia with pharmacological cerebral protection strategies and an increased blood pressure of 10% to promote collateral circulation and prevent ischemic complications during carotid clamping. 18nitoring of burst-suppression patterns by EEG In addition to standard anesthetic monitoring with an arterial line, all patients were monitored with the two-channel cortical EEG using the EEG pod of Infinity Delta Series (Drager Medical AG & Co. Lubeck, Germany).The EEG signal was obtained using silver-silver chloride electrodes located according to the international 10-20 systems.The differential montage was recorded: left and right frontal (FP1-C3, FP2-C4; channels 1 and 2), with a neutral electrode placed at the ear lobe.The impedance was recommended at < 5,000 ohms.Power Spectra analysis (Fast Fourier transform: FFT) was used to simplify the complex EEG to computer-processed EEG (CEEG) for an 8-second epoch.Trained anesthesiologists visually assessed the raw EEG and compressed spectral EEG parameters [Spectral Edge Frequency 95% (SEF95%), Median (MED), and Burst Suppression Ratio (BSR)].Burst Suppression Ratio (BSR) was defined as the percentage of time the EEG waveform is flatlined over the last 60 seconds (when flatline EEG alternates with "bursts" of activity).
Before the temporary occlusion of the carotid artery, a single dose of heparin 5,000 units and Thiopental (5 mg/kg) was given intravenously (IV), followed by continuous infusion of 10 mg/kg/hr.An additional 50 mg was titrated intravenously by the anesthesiologist's decision, with the timing varying to achieve burst suppression on EEG throughout the ischemic period.There are no specific guidelines regarding how often the additional dose of thiopental should be administered.During the carotid clamp time, the blood pressure was raised 10% above the pre-operative level to induce collateral circulation.The inhalation agent was suspended during the thiopental infusion.At the end of the operation, the neuromuscular blockade was reversed with neostigmine 0.02 to 0.07 mg/kg combined with glycopyrrolate 0.2 mg or atropine 0.02 mg/kg.The patient was extubated if the patient had adequate ventilation, eye-opening, and purposeful responses.All patients were transferred to the neurosurgical intensive care unit for postoperative care.

Data collection
Electronic database searches and manual data were abstracted, including demographic data, clinical courses, and outcomes.Patient characteristics were age, gender, American Society of Anesthesiologists Physical Status classification (ASA), Glasgow Coma Scale (GCS), and history of any comorbidities: cerebrovascular accident or transient ischemic attack (TIA), coronary artery disease (CAD), hypertension (HT), diabetes mellitus (DM), and dyslipidemia.Preoperative investigation data such as the site and degree of stenosis measured by carotid duplex ultrasonography and magnetic resonance angiography (MRA) or conventional angiography were abstracted.

Outcome measures
The study's primary outcome was the amount of thiopental required to achieve burst suppression on EEG during cerebral protection.In addition, the study investigated several secondary outcomes related to the patient's recovery, including the percentage of successful extubations after surgery, the time to extubation in the neurosurgical intensive care unit, and the Glasgow Outcome Scale (GOS) at discharge and one month postoperatively.These measures were analyzed to assess the patient's recovery following the procedure.

Statistical analysis
Statistical analysis was performed using SPSS Statistical software, version 22 (IBM SPSS Inc., Chicago, IL).Descriptive statistics were presented as meansAEstandard deviations, percentages, and numbers.The Chi-square test was used to compare categorical variables, while unpaired t-tests were employed for analyzing continuous variables.Paired t-tests were utilized to compare EEG data before and the average of EEG data during the carotid cross-clamp.A significance level of P-value≤0.05was considered statistical significance.

Results
There were 69 carotid endarterectomies performed during the study period, with 12 cases excluded.Of the remaining 57 patients analyzed (Figure 1), only 24 achieved burst suppression on intraoperative EEG despite receiving continuous thiopental infusion with additional titration.These 24 patients were classified as the burst suppression group (BS) for the analysis.The demographic data and related details of both the BS and non-BS group are presented in Table 1.The group had a significantly higher average age of 72.8AE9.1 years than the non-BS group, with an average age of 66.7AE7.2years (p-value=0.007).However, there were no significant differences in gender, body weight, ASA physical status, comorbidities, or pre-operative investigation data between the two groups.Hypertension was a common condition in both groups.The percentage of patients who received thiopental or propofol as induction agents and the  The spectral edge frequency 95% (SEF95%) of both the BS and non-BS groups tended to decrease after carotid clamping, as indicated in Table 3.However, the two groups had no significant difference regarding MED or SEF95% before and after the clamping.Similarly, neither group significantly differed between the left and right MED or SEF95%.After carotid clamping, the BS group had an average BSR of 36.0AE20.4(right) and 36.3AE20.6 (left), but this difference was not statistically significant.In contrast, the non-BS group did not exhibit any burst suppression pattern.
The incidence of hypertension, hypotension, and arrhythmias did not show a statistically significant difference between the two groups.Additionally, there was no notable difference in the incidence of vasopressor intermittent boluses or vasopressor infusions.Following the operation, eight patients (33.3%) in the BS group and sixteen (48.5%) in the non-BS group were awake and extubated.Most patients in both groups were intubated and transferred to the neurosurgical intensive care unit.There was no significant difference in extubation time for patients who were initially unable to extubate between the two groups (BS group 872.4AE593.3min.vs. non-BS group 601.6AE473.9min).One patient experienced a mild neurological deficit.No deaths were reported one month after the operation (Table 4).

Discussion
This study aimed to determine the amount of thiopental required to induce burst suppression patterns on intraoperative EEG monitoring in patients undergoing carotid endarterectomy without a shunt.The main findings indicated that not all patients achieved burst suppression despite the intention to maximize cerebral protection through a continuous thiopental infusion and titrated intravenous administration.Patients who received significantly higher doses of thiopental (26.3AE10.1 mg/kg/hr) were likelier to achieve burst suppression on EEG.However, no significant difference was observed in postoperative outcomes between the burst suppression (BS) and non-burst suppression (non-BS) groups.
Currently, limited data is available on the efficacy and optimal dosage of thiopental for inducing pharmacological burst suppression to prevent perioperative stroke during selective shunting in CEA.
Barbiturates, such as thiopental, are commonly used to prevent cerebral ischemia during cerebrovascular surgery.
Thiopental is a fast-acting, short-duration barbiturate anesthetic that may exert its neuroprotective effects through various mechanisms, including antioxidant activity, GABA-ergic activity, stimulation of protein synthesis, removal of free radicals, and modulation of excitatory synaptic neurotransmission via adenosine. 19[25] The thiopental dose required for EEG burst suppression patterns during cerebrovascular surgery can vary depending on several factors, including variability in monitoring and assessing burst suppression levels among healthcare providers.Sreedhar and Gadhinglajkar 26 have reviewed several dosing regimens of thiopental for cerebrovascular surgery, including a bolus dose (4 mg/kg), a low dose followed by IV infusion (1 to 3 mg/kg IV followed by 0.06 to 0.2 mg/kg/min), and a high dose followed by infusion (loading 25 to 50 mg/kg followed by 2 to 10 mg/kg/hr).The initial bolus doses of thiopental used in our study did not result in EEG burst suppression for most patients, which differs from the findings of Ramesh VJ. 27 According to Ramesh VJ, almost all patients who received a bolus dose of 3 to 5 mg/kg experienced EEG burst suppression with a BSR greater than 25%.The initial bolus doses of thiopental only resulted in temporary suppression durations, consistent with previous studies by Moffat et al. 28 and Gelb et al., 29 which provided limited cerebral protection during the intraoperative period.
Our study used a continuous thiopental infusion to maintain EEG burst suppression during the carotid cross-clamp procedure.We administered a high dose of thiopental, similar to previous studies by McConkey PP et al. 30 and Frawley JE et al. 31 However, not all patients in our study achieved EEG burst suppression, unlike the abovementioned studies where incremental bolus doses of thiopental were titrated.Nonetheless, none of our patients experienced a significant period of ischemia, as defined by a decrease in SEF95% to 50% of the baseline. 32G-confirmed burst suppression is widely recognized as the preferred indicator of cerebral protection during cerebrovascular surgery with barbiturate therapy.
Our institute protocol primarily relied on electroencephalography (EEG) to assess burst suppression.While intraoperative monitoring of burst suppression is commonly performed using EEG or Bispectral Index (BIS), 33,34 it has been observed that BIS-derived Burst Suppression Ratio (BSR) may underestimate the duration of EEG suppression, thereby reducing sensitivity in detecting burst suppression. 35We directly visualized the EEG trace to ensure a more accurate and real-time evaluation of raw EEG changes and BSR values across both brain hemispheres.This approach enabled us to detect potential cerebral ischemia and determine cerebral protection levels.
However, we recognize the significance of monitoring cerebral hemodynamics and function, 36 including sensory-evoked potential (SEP), motor-evoked potential (MEP), and near-infrared spectroscopy (NIRS). 37In 2014, the institute began implementing sensory-evoked potential monitoring (SEP) and motor-evoked potential (MEP) for spinal surgery.However, these methods are not routinely employed for carotid endarterectomy, partly due to the impact of burst suppression on EEG functional assessment. 38,39Additionally, cerebral oximetry was first introduced in 2022.
The study found that older patients were more likely to achieve burst suppression on EEG with thiopental therapy, potentially due to age-related factors. 40Although not all patients achieved burst suppression, the BS and non-BS groups had favorable clinical outcomes without significant perioperative complications.The BS group did have a more extended postoperative intubation period.However, their Glasgow Outcome Scale was not significantly different from the non-BS group at discharge or one month after surgery.These outcomes could be attributed to barbiturate therapy, as research on rats suggests that EEG burst suppression may not be necessary for maximum cerebral protection.
The dosage of thiopental that does not lead to EEG burst suppression may impact cerebral protection during carotid endarterectomy.However, thiopental-induced cerebral protection is only one of several strategies for cerebral protection.
Other factors, such as the degree of stenosis, pre-existing medical conditions, and perioperative risks associated with carotid endarterectomy, influence patient outcomes. 41mitations of this study include the fact that it exclusively focused on the dosage of thiopental and its effects on intraoperative EEG monitoring as a direct tool for evaluating brain electrical activity during carotid endarterectomy.
In the non-BS group, our investigation revealed that both anesthesiologists and nurse anesthetists expressed concern about hypotension and increased thiopental dose, which may lead to delayed extubation in the postoperative period.Consequently, a decision may have been made to avoid increasing the dosage and frequency of thiopental enough to induce EEG burst suppression.As a result, the insufficient thiopental dosage hinders the achievement of EEG suppression, and leaving the exact dosage needed for EEG burst suppression in this patient group undetermined.It is essential to acknowledge that EEG only provides information on brain electrical activity and does not directly measure cerebral blood flow or cerebral oxygen saturation (SjVO 2 ).Therefore, relying solely on EEG may not accurately reflect the actual level of cerebral protection.Multimodal intraoperative monitoring techniques, such as transcranial Doppler (TCD) ultrasound, somatosensory evoked potentials, and cerebral oxygen saturation monitoring, are recommended for a more comprehensive patient status assessment.Additionally, this study did not assess the thiopental serum levels for barbiturate coma treatment.The retrospective cohort design also limited the quality of data collection.The limited number of patients has additional challenges in analyzing patient outcomes.Therefore, a prospective randomized study is recommended to investigate further the role of intraoperative monitoring and barbiturate therapy in optimizing cerebral protection during carotid endarterectomy.
In conclusion, thiopental at a dosage of 26.3AE10.1 mg/kg/hr can induce burst suppression on intraoperative EEG during carotid endarterectomy, potentially providing cerebral protection.However, a cautious approach is recommended when using thiopental to induce EEG burst suppression during carotid clamping.While barbiturate-induced cerebral protection is still considered to have a role, the necessity of EEG burst suppression for cerebral protection requires further investigation.Considering the limitations of our retrospective study, the recommended strategy should be individualized for each patient, considering available resources based on institutional protocols.Further evidence from medical studies, neurophysiology studies, and mathematical modeling is needed to gain a comprehensive understanding of burst suppression and its potential therapeutic applications.Therefore, it is crucial to carefully evaluate the potential benefits and risks of using burst suppression in clinical practice and identify the optimal perioperative settings where it may be beneficial.
of Medicine, University of Chile, Santiago, Chile Dear authors, I have carefully read your manuscript in which the aim was to study the optimal dose of barbiturates, such as thiopental, to induce patterns in the EEG of burst suppression in patients undergoing carotid endarterectomy with a non-shunt technique.The article is interesting and possibly useful for the clinical practice of many centers.I understand that currently, for example, in our center, it is preferred to monitor with sensory or motor potentials in vascular neurosurgeries and in order not to affect the monitoring, we do not induce suppression and, finally, perform an early extubation after the cessation of propofol perfusion.However, knowing the dose needed to reach suppression is a necessary and interesting fact, but I suggest making the following modifications to the manuscript: Feedback: A limitation of the study is its retrospective design.It is not clear why some patients reached burst suppression while in others it was not reached.This fact could affect the recommended dose of thiopental to achieve burst suppression.In the group of patients in which burst suppression was not generated, it is unknown what dose is necessary to achieve suppression.That should be discussed in the limitations. 1.
The factors that could explain why in one case burst suppression was achieved and in others no, it was not explored.At first, one possible explanation was that some clinicians decided to increase the dose of thiopental until they reached suppression while others did not.Therefore, it would be interesting to analyze whether the operators who achieved suppression were the same and those who were others.Another option may have been difficulty maintaining blood pressure above 10% during clamp.Perhaps patients who achieved burst suppression were more likely to reach that goal with fewer doses of vasopressor, while in those who did not reach it was more difficult to reach that goal with higher doses of vasopressors.I suggest incorporating both analyses into the results section and then discussing those analyses.

2.
In the first sentence of the discussion, it is said that one aim was to evaluate the outcomes of patients, but that aim was not the primary one and was not mentioned at the end of the introduction.I suggest removing it in the discussion sentence.Just mention it as a secondary outcome and emphasize that with the number of patients it is difficult to reach a conclusion.

3.
Page 4: this sentence is not well understood: "thiopental (5 mg/kg) was given intravenously (IV) followed by continuous infusion of 10 mg/kg/hr with an additional 50 mg titrated intravenously".The additional 50 mg was always given, at what time? 4.
This sentence is confusing, please review: "glycopyrrolate 0.2 mg for each 1.0 mg of neostigmine or atropine 0.02 mg/kg and neostigmine 0.02 to 0.07 mg/kg".

5.
In Table 2, the values of Sevoflurane/Desflurane (% end tidal), were during the clamp?Or at the end?Please specify.

6.
Please specify the unit when talking about burst suppression or MED.For example, in the sentence "BSR of 36.020.4 (right) and 36.320.6 (left)" and in

Masahiko Kawaguchi
Department of Anesthesiology and Division of Intensive Care, Nara Medical University, Nara, Japan Thank you very much for revising the manuscript, which was originally submitted.The authors seem to respond all comments raised by the reviewer.The contents of this manuscript have become much clearer.Although there are several limitations of this study, the data obtained in this study would be of clinical value.Thank you very much.

Is the work clearly and accurately presented and does it cite the current literature? Partly
Based on the results of this study, the outcome of the patients was similar.In addition, previous animal study indicated that burst suppression is not necessary to achieve neuroprotective effect of thiopental (Schmid-Elsaesser et al. (1999) 1 ).So, this reviewer doubts that burst suppression is really required during the clamping of carotid artery.The authors should mention the rationale to get burst suppression on EEG.Please add the data that burst suppression would be required to have neuroprotective effects.This can be a limitation of this study.
Was any monitoring of cerebral hemodynamics and function performed, including near-infrared spectroscopy (NIRS), motor evoked potential or sensory evoked potential?Strategy to identify the function during carotid clamp is also important to prevent postoperative neurological dysfunction.Under the burst suppression on EEG, assessment of function can be disturbed.
Finally, based on the data of this study, what did the authors recommend as a strategy to use thiopental during carotid clamping?Considering the necessity of burst suppression for neuroprotection, the conclusion should be carefully drawn.

Is the work clearly and accurately presented and does it cite the current literature? No
Is the study design appropriate and is the work technically sound?Partly

If applicable, is the statistical analysis and its interpretation appropriate? Yes
Are all the source data underlying the results available to ensure full reproducibility?Yes

Are the conclusions drawn adequately supported by the results? Partly
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Neuroanaesthesia, neuromonitoring I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
suppression) may provide more cerebral protection than 50% burst suppression.However, the study did not evaluate the cerebral protection effects.Thus, human studies regarding burst suppression and cerebral protection effect are still needed.
3. Was any monitoring of cerebral hemodynamics and function performed, including near-infrared spectroscopy (NIRS), motor evoked potential or sensory evoked potential?Strategy to identify the function during carotid clamp is also important to prevent postoperative neurological dysfunction.Under the burst suppression on EEG, assessment of function can be disturbed.
Response: During the study period from January 2009 to December 2019, our institute primarily relied on electroencephalography (EEG) for assessing burst suppression.However, we recognize the significance of monitoring cerebral hemodynamics and function, including sensory-evoked potential (SEP), motor-evoked potential (MEP), and near-infrared spectroscopy (NIRS).
In 2014, the institute began implementing sensory-evoked potential monitoring (SEP) and motor-evoked potential (MEP) for spinal surgery.However, these methods are not routinely employed for carotid endarterectomy, partly due to the impact of burst suppression on EEG functional assessment.Additionally, cerebral oximetry was first introduced in 2022.Response: Based on our study's data, a cautious approach is recommended when using thiopental to induce EEG burst suppression during carotid clamping.While barbiturateinduced cerebral protection is still considered to have a role, the necessity of EEG burst suppression for cerebral protection requires further investigation.Considering the limitations of our retrospective study, the recommended strategy should be individualized for each patient, considering available resources based on institutional protocols.Further evidence from medical studies, neurophysiology studies, and mathematical modeling is needed to gain a comprehensive understanding of burst suppression and its potential therapeutic applications.Therefore, it is crucial to carefully evaluate the potential benefits and risks of using burst suppression in clinical practice and identify the optimal perioperative settings where it may be beneficial.
The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias • You can publish traditional articles, null/negative results, case reports, data notes and more • The peer review process is transparent and collaborative • Your article is indexed in PubMed after passing peer review • Dedicated customer support at every stage • For pre-submission enquiries, contact research@f1000.com

Figure 1 .
Figure 1.Flow diagram of the study.

4 .
Finally, based on the data of this study, what did the authors recommend as a strategy to use thiopental during carotid clamping?Considering the necessity of burst suppression for neuroprotection, the conclusion should be carefully drawn.

Table 2 )
. Perioperative doses of fentanyl and end-tidal concentrations of sevoflurane or desflurane also showed no significant differences.The amount of thiopental required to achieve burst suppression on intraoperative EEG was significantly higher in the BS group compared to the non-BS group (26.3AE10.1 mg/kg/hr vs. 18.7AE8.8,p-value=0.004).Although the carotid clamp time was slightly shorter in the BS group, it did not reach statistical significance (73.2AE23.7 min vs. 83.3AE34.8,p-value=0.225).
The data are presented as meanAEstandard deviation or n (%), P value<0.05indicates statistical significance.

Table 3 .
The EEG data before and the average of EEG data during the carotid clamp time.
The data are presented as meanAEstandard deviation or n (%), P value<0.05indicates statistical significance.TIA=transient ischemic attack; RIND=reversible ischemic neurological disability; GOS=Glasgow Outcome Scale.

the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests:
No competing interests were disclosed.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Reviewer Report 19 July 2023 https://doi.org/10.5256/f1000research.152260.r183586© 2023 Kawaguchi M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.