Ketofol As An Anesthetic Agent in Patients With.8

CLINICAL INVESTIGATION
Ketofol as an Anesthetic Agent in Patients With Isolated

Moderate to Severe Traumatic Brain Injury: A Prospective,
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Randomized Double-blind Controlled Trial

Neha Maheswari, MD, DM,* Nidhi B. Panda, MD,* Shalvi Mahajan, MD, DM,†
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 06/07/2023
Ankur Luthra, MD, DM,† Smita Pattnaik, MD,‡ Nidhi Bhatia, MD,†
Madhivanan Karthigeyan, MCH,§ Narender Kaloria, MD, DM,† Rajeev Chauhan, MD, DM,†
Shiv Soni, MD, DM,† Kiran Jangra, MD, DM,* and Hemant Bhagat, MD, DM*
Background: The effects of ketofol (propofol and ketamine ad-

mixture) on systemic hemodynamics and outcomes in patients
T raumatic brain injury (TBI) is a global problem, with
an annual incidence rate of almost 939 per 100,000
population.1 The initial (primary) injury to brain tissue is
undergoing emergency decompressive craniectomy for traumatic irreversible and nonmodifiable. Subsequent (secondary)
brain injury (TBI) are unknown and explored in this study. brain injury can exacerbate the primary injury and worsen
Methods: Fifty patients with moderate/severe TBI were random- clinical outcomes and is potentially modifiable. The peri-
ized to receive ketofol (n = 25) or propofol (n = 25) for induction operative period is a risk time for secondary brain injury,
and maintenance of anesthesia during TBI surgery. Intraoperative particularly if secondary systemic insults are not prevented
hemodynamic stability was assessed by continuous measurement or adequately controlled. Hypotension is a secondary in-
of mean arterial pressure (MAP) and need for rescue interventions sult and a potent cause of secondary brain injury, and is
to maintain MAP within 20% of baseline. Brain relaxation scores, directly associated with mortality after TBI.2 Hemody-
serum biomarker-glial fibrillary acidic protein levels, and extended namic instability, particularly reductions in mean arterial
Glasgow Outcome Scale (GOSE) at 30 and 90 days after discharge pressure (MAP) and subsequent decreases in cerebral
were also explored. perfusion pressure (CPP), may worsen preexisting neuro-
logical insults.3 In addition, a reduction in CPP triggers
Results: MAP was lower and hemodynamic fluctuations more cerebral vasodilatation and a consequent increase in cer-
frequent in patients receiving propofol compared with those re- ebral blood volume which in turn can increase ICP and
ceiving ketofol (P < 0.05). MAP fell > 20% below baseline in 22 precipitate further injury in potentially salvageable at-risk
(88%) patients receiving propofol and in 10 (40%) receiving ke- brain regions, that is, “penumbral” zones.
tofol (P = 0.001), with a greater requirement for vasopressors (80% Propofol is a popular intravenous anesthetic agent in
vs. 24%, respectively; P = 0.02). Intraoperative brain relaxation neurosurgery; it decreases cerebral electrical activity and,
scores and GOSE at 30 and 90 day were similar between groups. because of substantial preservation of flow-metabolism
Glial fibrillary acidic protein was lower in the ketofol group coupling, decreases cerebral blood flow.4 However, sys-
(3.31 ± 0.43 ng/mL) as compared with the propofol (3.41 ± 0.17 temic vasodilatory effects of propofol result in dose-
ng/mL; P = 0.01) group on the third postoperative day. dependent systemic hypotension. In contrast, ketamine, a
Conclusion: Compared with propofol, ketofol for induction and phencyclidine derivative, increases cerebral metabolic rate
maintenance of anesthesia during decompressive surgery in patients and cerebral blood flow, and has strong sympathomimetic
with moderate/severe TBI was associated with improved hemodynamic activity. For these reasons, it has been infrequently used
stability, lower vasopressor requirement, and similar brain relaxation. during neurosurgical cases.5 However, sympathomimetic
actions of ketamine increase MAP and possibly increase
Key Words: ketamine, ketofol, propofol, blood pressure, traumatic CPP in “at-risk” brain regions, with potential to prevent
brain injury, outcome or minimize secondary ischemic brain injury. Preclinical
(J Neurosurg Anesthesiol 2023;35:49–55) data also suggest that ketamine attenuates excitotoxicity
and offers neuroprotection.6
We hypothesized that ketofol (a ketamine and pro-
Received for publication October 15, 2020; accepted March 28, 2021.
From the *Department of Anesthesia and Intensive Care, Division of pofol admixture) for induction and maintenance of anes-
Neuroanesthesia; Departments of †Anesthesia and Intensive Care; thesia in patients with TBI could minimize intraoperative
‡Pharmacology; and §Neurosurgery, Post Graduate Institute of hemodynamic variability without compromising brain
Medical Education and Research (PGIMER), Chandigarh, India. relaxation compared with propofol anesthesia. Therefore,
The authors have no conflicts of interest.
Address correspondence to: Nidhi B. Panda, MD. E-mail: nidhibp@gmail.com. we aimed to compare the use of ketofol and propofol for
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. anesthesia during TBI surgery. The primary outcome of
DOI: 10.1097/ANA.0000000000000774 this study was intraoperative hemodynamic stability
J Neurosurg Anesthesiol Volume 35, Number 1, January 2023 www.jnsa.com | 49
Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

Maheswari et al J Neurosurg Anesthesiol Volume 35, Number 1, January 2023
(MAP variation > 20% of baseline). Secondary outcomes 50 mL syringe for use in those allocated to group P. Thus,
included quality of brain relaxation, serum glial fibrillary 1 mL of the study drug contained 8.3 mg of propofol and
acidic protein (GFAP) levels, duration of mechanical 1.7 mg of ketamine in group KP, and 10 mg of propofol in
ventilation and hospital length of stay, and clinical out- group P.
comes at 30 and 90 days after discharge from hospital.
Anesthesia Protocol
METHODS Following a detailed preanesthesia assessment, the

This prospective, randomized double-blind trial was patients were moved to the operation room where stand-
approved by the Institutional Ethics Committee (INT/ ard American Society of Anesthesiologists monitoring
IEC/2018/000917, 25/06/2018; NK/4290/DM) and regis- with 5-lead electrocardiogram, noninvasive blood pres-
tered with Clinical Trial Registry of India (CTRI/2019/03/ sure, pulse oximetry, capnography, temperature, and urine
018131). The study was conducted at the Advanced output was instituted. A radial arterial catheter was in-
Trauma Centre, Post Graduate Institute of Medical Ed- serted before induction of anesthesia for continuous
ucation and Research, Chandigarh, India between April monitoring of blood pressure and blood gas analysis.
2019 and December 2019. Written informed consent was A standard anesthesia protocol was followed. All
obtained from patients’ next of kin. patients were preloaded with 8 mL/kg 0.9% saline, before
induction of anesthesia with 0.5 to 1 mL/kg of the relevant
Participants and Study Drug study drug (ketofol or propofol) administered over 40 to
The patients were aged from 18 to 65 years with 60 seconds. Following muscle relaxant with vecuronium
isolated moderate or severe TBI planned for primary de- (0.1 mg/kg), an appropriately sized endotracheal tube was
compressive surgery for unilateral intracranial lesions, in- inserted. Intraoperative analgesia was provided with a
cluding subdural hemorrhage, contusions, or a combination 2 µg/kg bolus of fentanyl followed by fentanyl infusion
of subdural hemorrhage and contusion, with a midline (1 µg/kg/h). The infusion rate of ketofol or propofol was
shift. Exclusion criteria were extradural hematoma, poly- titrated (0.6 to 0.9 mL/kg/h) to maintain MAP within 20%
trauma, history of uncontrolled hypertension, coronary of baseline values. Ventilation was provided with a 50%
artery disease, psychiatric disorder, neurodegenerative dis- oxygen/air mixture and titrated to maintain a PaCO2 of
order, renal or hepatic dysfunction, pregnancy, and refusal between 35 and 40 mm Hg. All patients received an in-
of consent. fusion of 20% mannitol (1 g/kg) before craniotomy. The
study drug infusion was stopped at the end of skin suture.
Study Drugs and Randomization If MAP fell below 20% of baseline, a fluid challenge
An initial pilot study was carried out in 15 neuro- (5 mL/kg 0.9% saline) was administrated and the study
surgical patients (not included in the current study) to drug infusion reduced by 20%. If hypotension persisted
determine the optimal ratio of ketamine to propofol in the despite these interventions, bolus doses of intravenous
ketofol used in this study. We assessed heart rate and phenylephrine (50 μg) were administered at 5-minute in-
MAP during anesthesia with 3 different ketamine/propo- tervals. If MAP was not restored to within 20% of baseline
fol mixtures (1:3, 1:4, and 1:5) and found that hemody- after 2 boluses of phenylephrine, an intravenous infusion
namic stability was optimal with a ketamine/propofol of norepinephrine (0.01 to 0.1 μg/kg/min) was started. If
ratio of 1:5. Previous studies have confirmed that a ket- MAP increased above 20% of baseline, an esmolol bolus
amine/propofol admixture is stable without any ill effects (0.5 to 1 mg/kg over 30 s) was administered and repeated
or precipitation of components.7,8 Similarly, in our pilot at 5-minute intervals as necessary. Labetalol (20 mg over
study we did not observe any precipitation, color change, 2 min) was administered if hypertension was not con-
or any detectable layering or oily droplet formation on trolled after 2 bolus doses of esmolol. Packed red blood
ketofol. cells were transfused if hemoglobin fell below 9 g/dL.
Patients were randomized using a computer-gen-
erated random number table into 2 groups; those in group Data Collection
KP received ketofol (ketamine/propofol ratio 1:5) and Intraoperative parameters, including heart rate,
those in group P received propofol alone for induction and MAP, oxygen saturation, end-tidal carbon dioxide, tem-
maintenance of anesthesia. The opaque sealed envelope perature, and urine output were recorded. Heart rate and
method was used for concealment, with consecutive en- MAP were recorded at the following timepoints: baseline
velopes opened just before a patient’s arrival in the oper- (after fluid preloading), at induction of anesthesia, in-
ating room. The neuroanesthesiologist managing the case, tubation, drilling of burr hole, beginning of craniotomy,
the operating neurosurgeon (having at least 2 y experience removal of bone flap, dural opening, and thereafter at
of trauma neurosurgery), and the neuroanesthesiologist 5-minute intervals until the end of anesthesia. The total
collecting the data were blinded to group allocation. The volume of the study drug used during anesthesia, and the
study drug infusion was prepared by an anesthesiologist duration of anesthesia and surgery were recorded.
who did not participate in the study. Forty milliliters of Following craniotomy, the degree of brain relaxa-
propofol with 8 mL of ketamine (10 mg/mL) was loaded tion was assessed by the operating neurosurgeon (who was
into a 50 mL syringe for use in patients allocated to group blinded to the study drug) according to the following
KP, and 48 mL of propofol (10 mg/mL) was loaded into a scale: Grade 1, fully relaxed brain; Grade 2, tense brain
50 | www.jnsa.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

J Neurosurg Anesthesiol Volume 35, Number 1, January 2023 Ketofol as Anesthetic Agent in TBI Surgery
with mild but acceptable swelling; Grade 3, tight brain the extended Glasgow Coma Scale (GOSE). Outcome was
with moderate brain swelling but no specific change in dichotomized into favorable (GOSE 5 to 8) and un-
management required; and Grade 4, bulging brain with favorable (GOSE 1 to 4) outcomes.10
severe swelling requiring some specific change in man-
agement (eg, administration of mannitol, propofol bo-
luses, etc.).9
Statistical Analysis
GFAP, a biomarker of brain injury, was measured In the absence of similar literature at the time of
3 times to assess the immediate and delayed impact of the planning the study, we calculated the sample size using
study drug on brain injury. Intravenous blood samples MAP data collected during the pilot study described
(2 mL) were taken before starting the study drug infusion above. Assuming a mean MAP of 94.6 mm Hg in the
(preoperative), at the end of the study drug infusion (im- ketofol group, a pooled SD of 4.74 and an α error of 0.05,
mediate postoperative), and on the third postoperative we calculated that a sample size of 46 (23 per group)
day. The samples were allowed to clot in plain Vacutainers would be required to identify a 10% difference in MAP in
at room temperature, and then centrifuged at 2000 rpm for the propofol group with 80% power (www.openepi.com/
15 minutes to separate the serum which was pipetted into SampleSize/SSMean.htm). To allow for dropouts we
cryovials. The serum samples were immediately stored at planned to recruit 50 participants (25 per group).
−80°C in the pharmacology laboratory until analysis. All Statistical analysis was carried out using the Sta-
samples were analyzed in duplicate at the end of the study. tistical Package for the Social Sciences (version 21.0;
GFAP levels were measured using a quantitative SPSS Inc. Chicago, IL). Normally distributed continuous
enzyme-linked immunosorbent assay kit with precoated data was presented as mean ± SD, and the 2 groups were
antigen wells and a double-antibody sandwich technique compared using Student t test. Categorical and nominal
(Genxbio Health Sciences Private Ltd). data was described as proportions, and χ2 test or Fisher
Duration of mechanical ventilation and hospital exact test were used to identify any significant associations.
length of stay (d) were recorded, and neurological out- Paired sample t test was also used for baseline comparison.
comes at 30- and 90-day postdischarge were assessed using P < 0.05 were considered statistically significant.
Assessed for eligibility (n= 56)
Excluded (n= 06)

Not meeting inclusion criteria (n= 06)
Declined to participate (n= 0)
Other reasons (n= 0)
Randomized (n= 50)
Allocation
Allocated to Group KP (n= 25) Allocated to Group P (n= 25)

Received allocated intervention (n= 25) Received allocated intervention (n= 25)
Lost to follow-up Lost to follow-up

30 Day Post-discharge(n=4) 30 Day Post-discharge(n=5)
90 Day Post-discharge (n= 0) 90 Day Post-discharge (n= 0)
Analysis
Analysed Analysed
Primary Outcome (n= 25) Primary Outcome (n= 25)
Secondary Outcome(n=21) Secondary Outcome(n=21)
FIGURE 1. Study flow diagram. KP indicates ketamine/propofol; P, propofol.
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. www.jnsa.com | 51

compared with those who received ketofol (group KP)

TABLE 1. Demographic Characteristics and TBI Morphology
(P < 0.05). Twenty-two (88%) patients in group P had a
Ketofol Propofol greater than 20% reduction in MAP compared with 10
(Group KP) (Group P)
patients (40%) in group KP (P = 0.001) despite similar fluid
Parameters (n = 25) (n = 25) P
requirements (2304+124 in group P vs. 2306+127 mL in
group KP; P = 0.95) (Table 2). As a consequence, more
Age (y) 37.52 ± 11.31 36.28 ± 11.29 0.70

Weight (kg) 70.00 ± 6.30 68.57 ± 4.98 0.42
Sex (male/female)† 22/3 19/6 0.46
patients in group P required phenylephrine to treat
GCS 7.00 ± 1.50 6.92 ± 1.61 0.85 hypotension; 20 patients (80%) and 6 (24%) patients in
ASA status (I/II)† 22/3 22/3 1.00 group P and group KP, respectively (P = 0.001). No patient
Duration of surgery (min) 107.14 ± 14.28 113.57 ± 16.59 0.18 required norepinephrine infusion. There was no difference
Duration of anesthesia (min) 135.71 ± 13.99 140.95 ± 17.00 0.28 between groups in the number of patients with > 20%
Acute SDH/contusion/both† 6/12/7 10/11/4 0.39
Total intravenous fluid (mL) 2306.09 ± 127.16 2304.00 ± 124.06 0.95 increases in MAP above baseline; 4 (16%) and 6 (24%) in
Total urine output (mL) 658 ± 93.09 673 ± 89.90 0.54 groups P and KP, respectively (P = 0.47) (Table 2). Similarly,
Total blood loss (mL) 724 ± 140.77 691 ± 150.49 0.432 the number of patients requiring esmolol for hypertension was
Total propofol (mg) 702.6 ( ± 28.3) 949.3 ( ± 34.8) 0.001* similar between groups; 3 (12%) and 5 (20%) in groups P and
Data are shown as mean ± SD unless otherwise indicated. KP, respectively (P = 0.70). No patient required labetalol.
*P < 0.05 (independent sample t test). There was also no difference in heart rate between groups at
†Presented as number.
ASA indicates American Society of Anesthesiologists; GCS, Glasgow Coma
different timepoints (P = 0.65).
Scale score; KP, ketamine/propofol; P, propofol; SDH, subdural hematoma; TBI, Brain relaxation scores were similar in the 2 groups
traumatic brain injury. (P = 1.00) (Fig. 3A). In group KP, 3 patients had Grade I, 9
patients had Grade II, 13 patients had Grade III, and no
patient had Grade IV brain relaxation scores. In group P, 5
patients had Grade I, 8 patients had Grade II, 12 patients
RESULTS had Grade III, and no patient had Grade IV brain
Fifty-six patients were assessed for eligibility. Six were relaxation scores. Mean EtCO2 was 34.7 ± 2.0 and
excluded because they did not meet the predefined inclusion 35.0 ± 1.0 mm Hg in groups KP and P, respectively
criteria, leaving 50 patients (randomized equally into the 2 (P = 0.58). Other intraoperative variables were also similar
groups) eligible for inclusion in the study (Fig. 1). between groups, except for total propofol dose which was
Demographic characteristics and TBI morphology were higher in group P (949.3 ± 34.8 mg) compared with that in
comparable between groups (Table 1). group KP (702.6 ± 28.3 mg; P = 0.001) (Table 1).
Blood pressure changes are shown in Figure 2. Baseline Baseline and immediate postoperative serum GFAP
MAP was similar between groups (P = 0.38), but patients who levels were similar in the 2 groups, whereas GFAP was
received propofol (group P) had lower intraoperative MAP lower in group KP (3.31 ± 0.43 ng/mL) as compared with
FIGURE 2. Intraoperative mean arterial blood pressure. Data are shown as mean+SD. *P < 0.05. KP indicates ketamine/propofol;
P, propofol.

mixture used on this study (based on our pilot study),

TABLE 2. Intraoperative Hemodynamic Parameters and
Rescue Drugs anticipating that this would be sufficient to minimize re-
duction in MAP secondary to propofol-induced vaso-
Ketofol Propofol
dilation while minimizing the risk of increases in heart rate
(Group KP) (Group P)
(N = 25) (N = 25) P and MAP above baseline because of ketamine’s sym-
pathomimetic effects. We found that hemodynamic fluc-
Hypotension: MAP <20% 10 (40) 22 (88) 0.001* tuations were greater in patients receiving propofol
baseline
Vasopressor requirement 6 (24) 20 (80) 0.001* compared with those receiving ketofol; episodes of MAP
Hypertension: MAP > 20% 6 (24) 4 (16) 0.479 reduction greater than 20% below baseline occurred in
baseline 88% of patients receiving propofol compared with only
Esmolol requirement 5 (20) 3 (12) 0.702 40% of patients receiving ketofol, with consequent in-
Data shown as n (%). creased use of vasopressors in those receiving propofol.
*P < 0.05 (independent sample t test). This finding could be explained by the sympathomimetic
KP indicates ketamine/propofol; MAP, mean arterial pressure; P, propofol.
action of ketamine as described above. In addition, the
total propofol dose was lower in the ketofol group than in
that in group P (3.41 ± 0.17 ng/mL; P = 0.01) on the third the propofol group, and this may have contributed to the
postoperative day (Fig. 3B). There was no difference in the lower incidence of intraoperative hypotension in patients
duration of mechanical ventilation (group KP, 3.44 ± 2.16 receiving ketofol. Similar to our findings, 2 recently pub-
d vs. group P, 3.24 ± 1.56 d; P = 0.70) or length of hospital lished studies reported superior hemodynamic stability
stay (group KP, 6 ± 2.71 d vs. group P, 6.45 ± 2.18 d; and decreased vasopressor requirement in good grade
P = 0.53) between groups. Unfavorable outcome (GOSE aneurysmal subarachnoid hemorrhage patients receiving
score < 5) at 30-day postdischarge was reported in 17 and ketofol (ketamine/propofol ratio 1:5) compared with those
16 patients in groups KP and P, respectively (P = 0.93) receiving propofol during craniotomy for aneurysmal
(Fig. 3C). Four patients in group KP and 5 patients in clipping.12,13 In another study, ketofol provided superior
group P were lost to 90-day follow-up; in those for which hemodynamic stability compared with propofol during
data are available, 16 patients in both groups had an induction of anesthesia; propofol was more likely than
unfavorable outcome at 90 days (P = 1.00). ketofol to be associated with a ≥ 20% reduction in systolic
blood pressure from baseline at 5 minutes (48.8% vs. 12%)
and at 10 minutes (67.4% vs. 39%) after induction.14
DISCUSSION A tight brain during craniotomy can further ag-
In this prospective, randomized clinical trial, we gravate brain injury because of the greater force required
observed that ketofol provided better hemodynamic sta- by the surgeon’s retractor to achieve an adequate surgical
bility as compared with propofol for induction and field. Thus, optimal brain relaxation is another essential
maintenance of anesthesia in patients with moderate/ goal of neuroanesthesia during intracranial surgeries. In
severe TBI undergoing cranial decompressive surgery. this study, there was no difference in the quality of brain
Patients receiving ketofol had higher intraoperative MAP relaxation in patients receiving ketofol or propofol, and
than those receiving propofol and required fewer doses of most patients had moderate brain swelling that did not
phenylephrine to maintain MAP despite similar fluid re- require intervention (Grade III brain relaxation). Thus,
quirements. Maintenance of systemic hemodynamics is a the addition of ketamine to propofol in 1:5 ratio did not
key goal of anesthesia during decompressive surgery for worsen brain relaxation compared with propofol alone, a
TBI. A single episode of hypotension doubles mortality finding similar to those reported in previous studies.13,14
following TBI,11 and increases in MAP are also detri- Historically, ketamine was reported to be associated with
mental because of potential to worsen vasogenic brain increases in intracranial pressure,15,16 but more recent data
edema and intracranial hypertension. We chose a low dose do not support these findings. In one study, a bolus dose
of ketamine (ketamine-propofol ratio 1:5) in the ketofol of ketamine (1 mg/kg) during isoflurane anesthesia in
FIGURE 3. Secondary outcomes: (A) brain relaxation score, (B) serum glial fibrillary acidic protein, (C) extended Glasgow Outcome
Score Scale. Data are shown as mean ± SD. *P < 0.05. KP indicates ketamine/propofol; P, propofol.

neurosurgical patients resulted in a decrease in intracranial groups because electroencephalographic-based monitor-

pressure and middle cerebral artery blood flow velocity in ing anesthetic depth is not reliable during ketamine
the absence of changes in MAP.17 In another study, anesthesia. Finally, the volume of intracranial hema-
ketamine administered to mechanically ventilated TBI tomas and extent of midline shift was not measured
patients sedated with propofol did not result in an increase before surgery.
in ICP, rather a significant reduction in ICP was seen after

different doses of ketamine (1.5, 3, and 5 mg/kg).18 CONCLUSIONS
TBI results in excitotoxicity and activation of ex- We found that ketofol (ketamine/propofol admix-
trasynaptic N-methyl-D-aspartate (NMDA) receptors ture) for the induction and maintenance of anesthesia was
following release of large amounts of glutamate.19 This associated with better hemodynamic stability and lower
further activates postsynaptic NMDA receptor protein vasopressor requirement than propofol anesthesia during
kinase C and tyrosine kinase signaling cascades, which emergent decompressive cranial surgery in patients with
leads to phosphorylate of NMDA receptors and upregu- moderate or severe TBI. Hence, ketofol may have ad-
lation of the signaling currents, resulting in more NMDA vantages over propofol anesthesia in patients undergoing
receptor activation.20,21 Ketamine is an NMDA receptor intracranial surgery for moderate to severe isolated TBI.
antagonist and could be expected to mitigate some of the However, larger multicenter trials designed to assess the
excitotoxic sequelae of TBI. GFAP, an intermediate fila- impact of these 2 anesthesia regimens on neurological
ment protein of the astrocytic cytoskeleton, has been used outcome are required before ketofol can be recommended
to assess injury severity and prognosis in the acute TBI for routine clinical use.
setting and is reported to have a greater prognostic value
than other biomarkers.22,23 To assess any immediate or REFERENCES
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CLINICAL INVESTIGATION

Ketofol as an Anesthetic Agent in Patients With Isolated

Randomized Double-blind Controlled Trial

Background: The effects of ketofol (propofol and ketamine ad-

J Neurosurg Anesthesiol  Volume 35, Number 1, January 2023 www.jnsa.com | 49

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

METHODS Following a detailed preanesthesia assessment, the

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

Assessed for eligibility (n= 56)

Excluded (n= 06)

Randomized (n= 50)

Allocated to Group KP (n= 25) Allocated to Group P (n= 25)

Lost to follow-up Lost to follow-up

FIGURE 1. Study flow diagram. KP indicates ketamine/propofol; P, propofol.

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

compared with those who received ketofol (group KP)

Age (y) 37.52 ± 11.31 36.28 ± 11.29 0.70

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

mixture used on this study (based on our pilot study),

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

neurosurgical patients resulted in a decrease in intracranial groups because electroencephalographic-based monitor-

in ICP, rather a signiﬁcant reduction in ICP was seen after

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

16. Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral jamaneurol.2016.0039

Copyright r 2021 Wolters Kluwer Health, Inc. All rights reserved.

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J Neurosurg Anesthesiol Volume 35, Number 1, January 2023 www.jnsa.com | 49