Exploring the Effects of Ketofol and Etomidate on Cerebral Blood Flow and Oxygenation during Anesthesia Induction in Supratentorial Tumor Patients: A Randomized Double-Blind Study

Abstract

Objectives During anesthesia induction, fluctuations in systemic hemodynamic may also alter cerebral hemodynamic, especially in patients with intracranial tumors, as these patients might have impaired cerebral autoregulation. This study compared the effects of ketofol (a mixture of ketamine and propofol) and etomidate on cerebral blood flow, oxygenation, and systemic hemodynamics during anesthesia induction for craniotomy in patients with supratentorial tumors.

Materials and Methods This prospective, randomized, double-blind study included 50 patients aged 18 to 65 years, American Society of Anesthesiologists (ASA) classes I to II, undergoing elective craniotomy. Patients were assigned to receive either ketofol or etomidate for induction. Middle cerebral artery (right and left side) mean flow velocity (mFV) and pulsatility index (PI) were measured using transcranial Doppler, and cerebral oxygenation (rSO₂%) of both hemispheres was measured using near-infrared spectroscopy (NIRS) during the first 10 minutes (1, 3, 5, and 10 minutes) following anesthesia induction.

Statistics An independent sample “t” test and one-way analysis of variance was used for continuous data. Chi-squared test was used for categorical data. Linear correlation between two continuous variables was explored using Pearson's correlation (normally distributed data) and Spearman's correlation (non-normally distributed data). A p-value of less than 0.05 was considered statistically significant.

Results Both groups showed a fall in mFV (cm/s) following induction, with a greater fall in the etomidate group (38.32 ± 2.54 vs. 28.88 ± 3.07; p = 0.001). In the etomidate group, mFV returned to baseline within 3 minutes and rose after laryngoscopy, while it remained below baseline in the ketofol group. rSO₂ decreased immediately postinduction but was better preserved in the ketofol group. Mean arterial pressure and heart rate significantly increased during laryngoscopy in the etomidate group (p < 0.001).

Conclusion Ketofol provided more stable cerebral hemodynamics, cerebral oxygenation, and systemic parameters compared with etomidate during anesthesia induction in patients undergoing craniotomy for supratentorial tumors.

Keywords

ketofol - etomidate - cerebral blood flow velocity - regional cerebral oxygenation - craniotomy

Introduction

Maintaining stable systemic and cerebral hemodynamics during anesthesia induction is critical for neurosurgical patients. Anesthesia induction, followed by laryngoscopy and endotracheal intubation, is associated with rapid and sometimes dramatic hemodynamic fluctuations. Systemic blood pressure may drop precipitously due to the vasodilatory effects of anesthetic agents or rise sharply due to the sympathetic response to airway manipulation. In individuals with intact cerebral autoregulation, these systemic changes are counterbalanced to maintain a stable cerebral blood flow (CBF) and ensure adequate cerebral perfusion.

However, in patients with supratentorial tumors, autoregulatory dysfunction may occur due to tumor-induced alterations in neurovascular coupling, compression, or invasion of brain tissue, peritumoral edema, and inflammation. This dysregulation makes the brain highly susceptible to fluctuations in blood pressure, leading to either cerebral ischemia during hypotension or cerebral hyperemia during hypertension. Both extremes are detrimental: ischemia can cause hypoxic injury to neural tissue, while hyperemia can exacerbate intracranial hypertension and worsen cerebral edema.

Given this heightened susceptibility to hemodynamic instability, the choice of anesthetic agents becomes pivotal. Anesthetic agents not only influence the patient's hemodynamic response but may also affect overall outcomes in individuals with intracranial tumors by modulating cerebral perfusion, edema, and intracranial pressure (ICP).[1] [2] [3]

Propofol is one of the most widely used induction agents in neurosurgical patients due to its favorable neuroprotective properties. It reduces the cerebral metabolic rate of oxygen (CMRO₂), CBF, and ICP. However, propofol causes dose-dependent hypotension and bradycardia, which can compromise systemic blood pressure and, consequently, cerebral perfusion pressure making patients with already impaired autoregulation vulnerable to cerebral ischemia.[4] Ketamine, in contrast, has traditionally been avoided in neuroanesthesia due to its ability to increase CBF, CMRO₂, and ICP, effects that are considered undesirable in neurosurgical patients. However, recent evidence suggests ketamine's potential neuroprotective properties, including anti-neuroinflammatory, anti-apoptotic effects, as well as inhibition of excitotoxicity. When combined with propofol, in a formulation known as ketofol, the two agents synergistically balance each other's strengths and mitigate their individual adverse effects. Ketamine's hemodynamic stability counteracts propofol-induced hypotension, while propofol offsets ketamine's excitatory effects on the brain. Together, they provide a balanced anesthetic profile with stable systemic and cerebral hemodynamics, effective hypnosis, and analgesia.[5] Etomidate is another induction agent frequently used in patients with cardiac comorbidities due to its minimal effects on cardiovascular function. Like propofol, it reduces CMRO₂, CBF, and ICP, making it a suitable choice for neurosurgical patients. However, it may cause more fall in CBF than CMRO₂ and may increase the risk of cerebral ischemia. It also carries the risk of adrenal suppression even with a single bolus dose.[6]

Although both ketofol and etomidate are used in neuroanesthesia practice, there is a paucity of studies comparing their effects on cerebral hemodynamics during anesthesia induction. This study aims to fill this gap by evaluating their effects on CBF, measured using transcranial Doppler (TCD), cerebral oxygenation, assessed via near-infrared spectroscopy (NIRS), and systemic hemodynamics (heart rate [HR], mean arterial pressure [MAP]) in patients undergoing elective craniotomies for supratentorial tumors.

Materials and Methods

This prospective, randomized, double-blind exploratory study was conducted at a tertiary level hospital over a period of 1 year. This study was approved by the institutional ethics committee (AIIMS Rishikesh, reg no. ECR/736/Inst/UK/2015/RR-18; AIIMS/IEC/20/506) and registered at clinical trials registry of India (ctri.nic.in; CTRI/2020/10/028732).

All American Society of Anesthesiologists (ASA) class I to II patients, aged 18 to 65 years of either gender, with Glasgow Coma Scale (GCS) score of 15, undergoing elective craniotomy for supratentorial tumors were included in the study. Patients with significant cerebrovascular, cardiac, pulmonary, renal, hepatic, or neuromuscular disease, a known allergy to any of the study drugs, a previous history of radiotherapy, and those who refused consent were excluded. Written informed consent was obtained from all participants.

Upon arrival in the operating room, all patients were connected to standard ASA monitors for continuous monitoring of HR, noninvasive blood pressure, oxygen saturation (SpO₂), and electrocardiogram (ECG). NIRS electrodes (O3 Regional Oximetry by MASIMO) were applied bilaterally to the frontal region to measure baseline regional cerebral oxygenation (rSO₂%). NIRS provided real-time, continuous monitoring of cerebral oxygenation, and data were logged electronically for subsequent analysis.

A handheld TCD probe (Digi-Lite by RIMED, 6th generation) was used to measure the middle cerebral artery (MCA) mean flow velocity (mFV) and its derived indices, including the pulsatility index (PI), which reflects cerebral vascular resistance. Measurements were performed on both the tumor-affected and nonaffected sides. The TCD insonation was conducted through the transtemporal window by a single trained observer who had attained proficiency in the technique after performing over 50 successful insonations prior to the study. This observer remained blinded to the group allocation throughout the study to minimize measurement bias. To ensure accuracy, three consecutive readings were recorded at each time point, and their average was used for analysis.

Patients were randomly assigned to one of two parallel groups (allocation ratio 1:1) using a computer-generated randomization sequence created with an online tool (http://www.randomizer.org). Allocation concealment was ensured using numbered, sealed, opaque envelopes. Blinding was meticulously maintained throughout the study. Both ketofol and etomidate have a similar milky white appearance and lack any distinct smell, making them indistinguishable. The anesthetic agents were prepared in identical 10-mL syringes, labeled only as “study drug,” by an independent investigator who was not involved in patient care or data collection. All personnel responsible for administering the drugs, managing patients, or collecting data, including the primary investigator, were blinded to group assignments to ensure unbiased study execution.

Patients in group A were induced with injection fentanyl (2 µg/kg) and ketofol labeled as study drug. Ketofol was constituted in a 20-mL syringe by combining 2 mL of ketamine (50 mg/mL) with 10 mL of propofol (10 mg/mL) at a ratio of 1:1 (100:100 mg) and this combination was then reloaded in a 10-mL syringe and labeled as study drug. Patients in group B were induced with injection fentanyl (2 µg/kg) and etomidate (2 mg/mL) loaded in a 10-mL syringe labeled as study drug. Once the patient lost verbal response, injection vecuronium (0.1 mg/kg) was administered. Three minutes later, an experienced anesthesiologist (>3 years) performed a smooth laryngoscopy, followed by intubation with an appropriately sized endotracheal tube. Anesthesia was maintained with sevoflurane (1 minimum alveolar concentration [MAC]) in the O₂/air mixture. End-tidal carbon dioxide (EtCO₂) was maintained between 30 and 35 mm Hg throughout the study period.

The primary outcomes measured were rSO₂, mFV, and PI of MCA on both the tumor-affected and nonaffected sides. These measurements were taken at baseline (T0, upon arrival in the operating room) and at 1, 3, 5, and 10 minutes after induction (T1, T2, T3, and T4, respectively). For each time point, the average of three readings was used. Both the TCD and NIRS recorded data in a time-based log, allowing real-time retrieval of measurements. Secondary outcomes measured were MAP and HR, which were recorded at the same time points as the primary outcomes and immediately after laryngoscopy.

Statistical Analysis

Since this was an exploratory study, a sample size of 50 (25 per group) was required to reject the null hypothesis that ketofol would cause less cerebral hemodynamic fluctuations than etomidate with an α error of 0.05 and a power of greater than 80%.

Statistical analysis was performed using statistical package for social sciences (SPSS version 23.0) software. Descriptive data are presented as means and standard deviations. Continuous variables are presented as medians and interquartile ranges. Categorical variables are presented as frequencies and percentages. An independent sample “t” test and one-way analysis of variance was used for continuous data. Chi-squared test was used for categorical data. Linear correlation between two continuous variables was explored using Pearson's correlation (normally distributed data) and Spearman's correlation (non-normally distributed data). A p-value of less than 0.05 was considered statistically significant.

Results

A total of 50 patients, 25 in each group, were included and analyzed at the end of the study ([Fig. 1]). The demographic data and baseline characteristics of the included patients are presented in [Table 1].

Fig. 1 Consolidated Standard of Reporting Trials (CONSORT) flow diagram.

Table 1 Demographic profile and baseline characteristics

Parameters	Group		p-Value
	Ketofol (n = 25)	Etomidate (n = 25)
Age (y)	37.72 ± 13.49	39.52 ± 11.53	0.614
Gender			0.117
Male	16 (64.0%)	23 (92.0%)
Female	9 (36.0%)	2 (8.0%)
ASA status			0.702
I	20 (80.0%)	22 (88.0%)
II	5 (20.0%)	3 (12.0%)
Tumor type			0.932
Glioma	18 (72.0%)	16 (64.0%)
Meningioma	6 (24.0%)	6 (24.0%)
Glioblastoma	1 (4.0%)	1 (4.0%)
Pericytoma	0 (0.0%)	1 (4.0%)
Tuberculoma	0 (0.0%)	1 (4.0%)
Region			0.101
Frontal	7 (28.0%)	6 (24.0%)
Temporal	7 (28.0%)	3 (12.0%)
Parieto-occipital	3 (12.0%)	6 (24.0%)
Falcine	2 (8.0%)	2 (8.0%)
Temporoparietal	4 (16.0%)	0 (0.0%)
Insular cortex	0 (0.0%)	3 (12.0%)
Parasagittal	0 (0.0%)	2 (8.0%)
Parietal	1 (4.0%)	1 (4.0%)
Frontoparietal	0 (0.0%)	1 (4.0%)
Lateral petrous	1 (4.0%)	0 (0.0%)
Lateral ventricular	0 (0.0%)	1 (4.0%)
Affected side of the brain			0.774
Left	10 (40.0%)	11 (44.0%)
Right	15 (60.0%)	14 (56.0%)

Abbreviation: ASA, American Society of Anesthesiologists.

Note: Significant difference at p < 0.05.

The baseline (T₀) mFV (cm/s) of the MCA (mFV-MCA) of the affected side was 48.1 ± 7.59 in the ketofol group and 48.55 ± 7.33 in the etomidate group (p = 0.877). Following induction (T1), mFV-MCA decreased in both groups; however, this decline was significantly more pronounced in the etomidate group compared with the ketofol group (p = 0.001). In the etomidate group, mFV-MCA returned to baseline within 3 minutes of induction (T2, at the time of laryngoscopy) and increased slightly above baseline values at T3 and T4 (after laryngoscopy and intubation). However, in the ketofol group, mFV-MCA remained lower than baseline throughout the study period. On the nonaffected side, mFV-MCA also decreased after induction in both groups, but the decline was significantly lesser than the affected side; also, after laryngoscopy and intubation, velocities increased; however, this rise was higher than the affected side, at the T2–T4 time points ([Table 2]). The PI for the affected side and non affected side in both groups is depicted in [Table 3].

Table 2 Comparison of the mFV (MCA; cm/s) over time between ketofol and etomidate (both affected and nonaffected side), n = 50

mFV (MCA), cm/s	Ketofol		p-Value	Etomidate		p-Value
	Affected	Nonaffected		Affected	Nonaffected
	Mean (SD)	Mean (SD)		Mean (SD)	Mean (SD)
T0	48.10 (7.59)	48.67 (7.74)	0.764	48.55 (7.73)	49.13 (7.86)	0.771
T1	35.09 (3.55)	39.82 (4.05)	<0.001	28.88 (3.07)	32.76 (3.53)	0.001
T2	39.78 (3.95)	45.12 (4.49)	<0.001	47.98 (6.47)	54.48 (7.66)	0.004
T3	38.32 (2.54)	43.44 (2.25)	<0.001	50.69 (6.05)	57.52 (7.06)	0.002
T4	30.41 (2.40)	34.48 (2.51)	<0.001	47.11 (6.48)	53.48 (7.66)	0.005

Abbreviations: mFV (MCA), mean flow velocity of middle cerebral artery; SD, standard deviation.

Note: Significant difference at p < 0.05.

Table 3 Comparison of PI over time between ketofol and etomidate (both affected and nonaffected side), n = 50

PI	Affected side		p-Value	Nonaffected side		p-Value
	Ketofol	Etomidate		Ketofol	Etomidate
	Mean (SD)	Mean (SD)		Mean (SD)	Mean (SD)
T0	0.85 (0.11)	0.85 (0.11)	0.970	0.86 (0.11)	0.86 (0.11)	0.951
T1	0.61 (0.12)	0.67 (0.12)	0.091	0.96 (0.12)	1.05 (0.13)	0.016
T2	0.53 (0.10)	0.42 (0.07)	<0.001	0.83 (0.10)	0.66 (0.06)	<0.001
T3	0.57 (0.09)	0.44 (0.09)	<0.001	0.90 (0.07)	0.69 (0.09)	<0.001
T4	0.72 (0.10)	0.50 (0.10)	<0.001	1.14 (0.07)	0.78 (0.11)	<0.001

Abbreviations: PI, pulsatility index; SD, standard deviation.

Note: Significant difference at p < 0.05.

The changes in regional cerebral oxygenation (rSO₂%) were not significantly different between the groups ([Table 4]). A comparison of hemodynamics during anesthesia induction revealed that the ketofol group exhibited more stable hemodynamic parameters ([Table 5]).

Table 4 Comparison of rSO₂% over time between ketofol and etomidate (both affected and nonaffected side), n = 50

rSO2 (%)	Affected side		p-Value	Nonaffected side		p-Value
	Ketofol	Etomidate		Ketofol	Etomidate
	Mean (SD)	Mean (SD)		Mean (SD)	Mean (SD)
T0	62.24 (4.68)	61.84 (4.42)	0.785	62.96 (4.73)	62.60 (4.55)	0.793
T1	59.00 (3.76)	57.60 (4.32)	0.271	66.80 (2.99)	65.20 (4.40)	0.199
T2	62.32 (4.36)	65.04 (4.33)	0.044	70.72 (4.10)	73.76 (3.69)	0.014
T3	65.56 (4.04)	63.32 (3.90)	0.065	74.28 (3.29)	71.80 (2.99)	0.013
T4	52.88 (3.06)	48.48 (2.96)	<0.001	59.92 (1.29)	54.84 (2.34)	<0.001

Abbreviations: rSO2%, regional cerebral oxygenation; SD, standard deviation.

Note: Significant difference at p < 0.05.

Table 5 Comparisons of hemodynamics during study period

	Ketamine	Etomidate	p-Value
At T0
HR	69.96 (7.27)	70.12 (7.71)	1.000
MAP	72.28 (5.10)	72.16 (4.85)	0.992
At T1
HR	71.80 (2.99)	76.12 (12.87)	0.240
MAP	79.28 (3.29)	78.48 (7.81)	0.719
At T2
HR	70.68 (4.70)	91.16 (12.40)	<0.001
MAP	77.64 (5.33)	98.08 (6.11)	<0.001
At laryngoscopy
HR	88.48 (7.81)	122.88 (11.77)	<0.001
MAP	87.36 (2.06)	100.48 (5.99)	<0.001
At T3
HR	71.28 (3.29)	88.48 (7.81)	<0.001
MAP	78.24 (3.69)	89.16 (5.05)	<0.001
At T4
HR	62.44 (1.00)	68.64 (5.33)	<0.001
MAP	68.44 (1.00)	61.72 (4.10)	<0.001

Abbreviations: HR, heart rate; MAP, mean arterial pressure.

Discussion

Ensuring stability in both systemic and cerebral hemodynamics during anesthesia induction is essential, particularly for neurosurgical patients at risk of cerebral autoregulatory dysfunction. Identifying an optimal induction agent that minimizes hemodynamic variability while preserving cerebral perfusion is crucial for improving patient outcomes. In this study, we aimed to explore the effects of ketofol and etomidate on CBF dynamics, utilizing TCD as a validated and noninvasive proxy for cerebral perfusion. This approach is supported by previous studies that have established MCA flow velocity as a reliable surrogate for CBF, offering real-time insights into cerebrovascular responses during anesthesia induction.[7] Additionally, NIRS was used in this study as a noninvasive and continuous monitor of cerebral perfusion and oxygenation (rSO₂). Regional cerebral oxygenation (rSO₂) levels reflect a balance between cerebral perfusion, oxygen delivery, and cerebral oxygen consumption. It can detect even subtle changes in the CBF.[8] Prior studies have demonstrated that the rSO₂ values correlate well with jugular venous bulb oxygen saturation, a marker of global cerebral oxygenation.[9]

Our findings revealed that after induction, the etomidate group experienced a more pronounced decline in MCA flow velocity on both the affected and nonaffected sides, despite no corresponding drop in MAP. The etomidate group also exhibited a greater rise in MAP during laryngoscopy and intubation, reflected by concurrent increases in MCA flow velocities. Although regional cerebral oxygenation (rSO₂) values were consistently higher in the ketofol group, the difference compared with the etomidate group was not statistically significant.

Yan et al conducted a randomized trial comparing induction with propofol-esketamine (group E) to propofol-sufentanil (group C) in 80 patients undergoing nonintracranial surgery. They found no significant differences in MCA mFV (mFV-MCA) between groups, concluding that esketamine with propofol maintains hemodynamic stability during induction.[10] However, our study included patients with intracranial space-occupying lesions (likely to have impaired autoregulation), and we also observed lesser fluctuation in mFV-MCA and more fluctuations in the etomidate group. Mayberg et al studied the effect of adding ketamine (1 mg/kg) in patients with supratentorial gliomas and cerebral aneurysm anesthetized with isoflurane and nitrous oxide. They concluded that the addition of ketamine led to a fall in the mFV of MCA without much change in MAP.[11]

Thiel et al explored the effects of various intravenous anesthetic agents on mFV-MCA in young patients without intracranial pathology, finding a significant reduction in mFV-MCA after induction with etomidate, propofol, thiopental, and methohexital, while with the fentanyl-midazolam and ketamine-midazolam, there was no significant change.[12] Following endotracheal intubation, mFV-MCA increased for all agents to almost near awake values. Comparable findings were also observed in our etomidate group patients.

Dash et al reported no significant change in mFV-MCA after etomidate induction in patients with intracranial space-occupying lesions but noted an increase in PI 5 minutes postinduction, which persisted on the nonaffected side. In contrast, our study found a significant decrease in mFV-MCA following induction (without a corresponding drop in MAP), followed by a rise during intubation and stabilization thereafter. Similarly, while we observed a postinduction increase in PI, it decreased during intubation and then gradually rose again.[13]

Thiel et al studied PI trends following etomidate induction in non-neurosurgical patients, noting an initial PI increase at 1 minute postinduction, a decrease after intubation, and subsequent stabilization.[12] Our findings were similar on the nonaffected side, with PI initially increasing, then significantly decreasing postintubation, and gradually returning to baseline. However, on the tumor-affected side, PI decreased significantly after induction, reaching only 60% of baseline by the study's end. This disparity in PI behavior likely reflects altered cerebral vasculature and impaired autoregulation on the affected side, influencing cerebral vascular resistance.

Duran et al investigated brain oxygenation with propofol and ketofol using NIRS in elderly patients without intracranial pathology, finding no significant changes in rSO₂ with ketofol. In contrast, our study showed consistently lower rSO₂ on the affected side across both groups, likely due to the brain tumors in our cohort, which may elevate ICP and reduce perfusion, leading to lower cerebral oxygenation.[14]

Similarly, Bhaire et al examined ketofol's effects on cerebral oxygenation in neurosurgical patients using jugular venous oxygen saturation (SjVO₂), reporting higher SjVO₂ and more stable hemodynamics with ketofol compared with propofol alone. Our findings also support ketofol's advantages, showing better hemodynamic stability and higher cerebral oxygenation compared with etomidate.[15] In our study, ketofol resulted in fewer hemodynamic fluctuations. Smischney et al conducted a systemic review and meta-analysis, concluding that ketofol provides superior hemodynamic stability during anesthesia induction and laryngoscopy compared with other agents.[16] Khalili and Soheilipoor found that ketofol offered better regulation of blood pressure and HR than etomidate in elderly patients undergoing induction and intubation.[17] Baradari et al studied the effect of ketofol and etomidate on hemodynamics during anesthesia induction in patients with left ventricular dysfunction undergoing coronary artery bypass graft surgery and noted that etomidate provided better hemodynamic stability.[18] However, their study used a different ketamine-to-propofol ratio (2:3) than ours (1:1), and their patients had preexisting ventricular dysfunction, which may explain the observed differences.

This study has several notable limitations. The sample size was small, which may impact the generalizability of our findings. Additionally, we could not simultaneously measure the mFV in both cerebral hemispheres, restricting our ability to assess bilateral differences comprehensively. rSO₂ was measured, only over the bilateral frontal areas. Use of multichannel NIRS could have provided more precise monitoring of cerebral perfusion and oxygenation in the specific vascular territories most affected by the tumor. We did not evaluate the degree of cerebral autoregulation impairment caused by tumors, which limits our understanding of potential autoregulatory effects. The study focused solely on transient changes during anesthesia induction, without examining hemodynamic and oxygenation changes over the entire course of surgery.

Tumor heterogeneity in terms of histopathology and location may have influenced regional blood flow due to variations in vascularity and depth, introducing variability in the findings. Finally, the study included only neurologically stable patients with full GCS scores, making the results less generalizable to patients with lower GCS scores, elevated ICP, or significant midline shifts.

Future research should explore the tumor-related hemodynamic effects and autoregulatory impairment, analyze perioperative changes, and validate findings in high-risk populations (raised ICP) as multicentric trials.

In conclusion, this study suggests that ketofol induces less fluctuation in cerebral hemodynamics (mFV-MCA and PI), cerebral oxygenation (rSO₂), and systemic hemodynamics (MAP and HR) during anesthesia induction compared with etomidate. Therefore, ketofol may be a more stable and cost-effective induction agent for patients undergoing elective craniotomies for supratentorial tumors. Given the small sample size in our study, we recommend further research with larger sample sizes to validate these findings.

Conflict of Interest

None declared.

Acknowledgments

The authors would like to acknowledge the support of the Department of Anaesthesiology and Neurosurgery, AIIMS, Rishikesh, for the smooth conduct of the study.

Authors' Contributions

S.C. contributed to acquisition, analysis, and interpretation of data and drafting of the manuscript. P.G. contributed to conception of the study design, interpretation of data, drafting of the manuscript, critical analysis, and final approval of the manuscript. S.P. contributed to drafting and editing of the manuscript. A.K. contributed to conception of the study design. S.S. contributed to drafting of the manuscript. A.R.Y. contributed to drafting of the manuscript.

• References

• 1 Bruder NJ, Ravussin P, Schoettker P. Supratentorial masses: anesthetic considerations. In: Cottrell JE, Patel P. eds. Cottrell and Patel's Neuroanesthesia. 6th ed.. Philadelphia, PA: Elsevier; 2017: 189-208
• 2 Sharma D, Bithal PK, Dash HH, Chouhan RS, Sookplung P, Vavilala MS. Cerebral autoregulation and CO₂ reactivity before and after elective supratentorial tumor resection. J Neurosurg Anesthesiol 2010; 22 (02) 132-137
• 3 Dong J, Zeng M, Ji N. et al. Impact of anesthesia on long-term outcomes in patients with supratentorial high-grade glioma undergoing tumor resection: a retrospective cohort study. J Neurosurg Anesthesiol 2020; 32 (03) 227-233
• 4 Gruenbaum SE, Meng L, Bilotta F. Recent trends in the anesthetic management of craniotomy for supratentorial tumor resection. Curr Opin Anaesthesiol 2016; 29 (05) 552-557
• 5 Matsumoto M, Sakabe T. Effects of anesthetic agents and other drugs on cerebral blood flow, metabolism, and intracranial pressure. In: Cottrell JE, Patel P. eds. Cottrell and Patel's Neuroanesthesia. 6th ed.. Philadelphia, PA: Elsevier; 2017: 74-90
• 6 Slupe AM, Kirsch JR. Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection. J Cereb Blood Flow Metab 2018; 38 (12) 2192-2208
• 7 Sorond FA, Hollenberg NK, Panych LP, Fisher ND. Brain blood flow and velocity: correlations between magnetic resonance imaging and transcranial Doppler sonography. J Ultrasound Med 2010; 29 (07) 1017-1022
• 8 Owen-Reece H, Elwell CE, Goldstone J, Smith M, Delpy DT, Wyatt JS. Investigation of the effects of hypocapnia upon cerebral haemodynamics in normal volunteers and anaesthetised subjects by near infrared spectroscopy (NIRS). Adv Exp Med Biol 1994; 361: 475-482
• 9 Kim MB, Ward DS, Cartwright CR, Kolano J, Chlebowski S, Henson LC. Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia. J Clin Monit Comput 2000; 16 (03) 191-199
• 10 Yan S, Li Q, He K. The effect of esketamine combined with propofol-induced general anesthesia on cerebral blood flow velocity: a randomized clinical trial. BMC Anesthesiol 2024; 24 (01) 66
• 11 Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg 1995; 81 (01) 84-89
• 12 Thiel A, Zickmann B, Roth H, Hempelmann G. Effects of intravenous anesthetic agents on middle cerebral artery blood flow velocity during induction of general anesthesia. J Clin Monit 1995; 11 (02) 92-98
• 13 Dash R, Dubey RK, Mishra LD. The effect of propofol versus etomidate induction on middle cerebral artery flow velocities and its derived parameters using transcranial doppler ultrasonography. J Clin Anesth Manage 2017; 2 (01) 1-6
• 14 Duran H, Koksal E, Ustun Y, Bilgin S, Özkan F. The effects of anaesthesia induction with propofol or ketofol on cerebral oxygenation in patients above 60 years of age. Medicine (Baltimore) 2020; 9 (01) 21-25
• 15 Bhaire VS, Panda N, Luthra A, Chauhan R, Rajappa D, Bhagat H. Effect of combination of ketamine and propofol (ketofol) on cerebral oxygenation in neurosurgical patients: a randomized double-blinded controlled trial. Anesth Essays Res 2019; 13 (04) 643-648
• 16 Smischney NJ, Seisa MO, Morrow AS. et al. Effect of ketamine/propofol admixture on peri-induction hemodynamics: a systematic review and meta-analysis. Anesthesiol Res Pract 2020; 2020: 9637412
• 17 Khalili G, Soheilipoor M. Comparison of hemodynamic responses to ketofol versus etomidate during anesthesia induction in elderly patients. Arch Anesth & Crit Care. 2024; 10 (Suppl. 01) 474-481
• 18 Baradari AG, Alipour A, Habibi MR, Rashidaei S, Emami Zeydi A. A randomized clinical trial comparing hemodynamic responses to ketamine-propofol combination (ketofol) versus etomidate during anesthesia induction in patients with left ventricular dysfunction undergoing coronary artery bypass graft surgery. Arch Med Sci 2017; 13 (05) 1102-1110

Publication History

Article published online:
20 February 2025