Keywords desflurane - sevoflurane - anesthesia - supratentorial craniotomy - elderly
Introduction
The growing population of elderly and the extension of life expectancy have resulted
in increase in demand for surgical services and associated workload without compromising
the quality of care.[1 ] Due to the aging-related changes, diminished physiological reserve and high prevalence
of co-occurring age-related disorders, elderly patients are more susceptible to perioperative
morbidity and mortality.[2 ]
[3 ] Stress of trauma, surgery, and anesthesia pose greater risk for geriatric patients
to develop postoperative complications.[4 ] The use of anesthetic agents in elderly is highly challenging due to reduced cardiorespiratory
reserve, underlying organ system diseases and age-related variation in pharmacokinetic
and pharmacodynamic factors.[5 ]
[6 ] Postoperative delirium and postoperative cognitive dysfunction are the most common
anesthesia-related surgery risks found in elderly.[7 ] The use of volatile anesthetics that are quickly removed with little metabolic breakdown
may lessen postoperative delirium and cognitive dysfunction in elderly patients by
promoting quicker recovery.[8 ] In neurosurgical patients, an early recovery helps in identifying patients with
new neurological deficits and triaging patients requiring immediate evaluation or
reintervention.
It has been well established that lower blood:gas partition coefficient of volatile
inhalation agent improves the recovery time following surgery. Hence, desflurane with
low blood:gas partition coefficient (0.42) is preferred for ambulatory anesthesia
and it has the shortest recovery time of approximately 5 minutes.[9 ] On the other hand, the blood:gas partition coefficient of sevoflurane is 0.65 and
the recovery time is around 14 minutes.[9 ]
[10 ] Several clinical trials have reported the efficiency of desflurane and sevoflurane
anesthesia in elderly patients.[5 ]
[8 ]
[11 ]
[12 ]
[13 ] Although the use of desflurane in neurosurgical patients is debatable due to its
cerebral vasodilating properties, it does not cause any variation in intracranial
pressure in normocapnic adult patients undergoing removal of supratentorial tumors.[14 ] Although the pharmacokinetic properties of both sevoflurane and desflurane favor
rapid emergence from anesthesia, several studies have reported that recovery from
anesthesia has been proven to be faster for desflurane than sevoflurane.[13 ]
[14 ]
[15 ]
[16 ]
Despite the wider use of sevoflurane and desflurane as inhaled anesthetics for outpatient
surgeries, there are very few studies comparing the effect of these two agents in
elderly patients undergoing supratentorial craniotomy. The primary objective of the
study was to compare the two agents in elderly patients undergoing elective supratentorial
craniotomy in terms of emergence time, extubation time and recovery time. As a secondary
objective, the study has compared intraoperative hemodynamic changes, intraoperative
brain conditions, and postoperative cognitive function between the two groups. This
study has hypothesized that desflurane could offer better recovery profile in elderly
neurosurgical patients than sevoflurane.
Materials and Methods
The prospective, randomized, open-label study considered elderly neurosurgical patients
who visited a Bangalore based super specialty hospital between January 2020 and June
2021. The inclusion criteria considered for patient enrolment were American Society
of Anesthesiologists (ASA) physical status 1 to 3, patients more than 65 years of
age, and those scheduled to undergo elective supratentorial craniotomies for extra-axial
lesions/pathologies (prolonged for >2 hours). Written informed consent and approval
by the institutional review board and ethics committee (MSRMC/EC/AP-59/10–2019) were
obtained prior to the study. The trial has been registered under the Clinical Trial
Registry of India (CTRI/2020/03/024294). Patients with Glasgow coma scale score less
than 15 prior to the surgery, body mass index (BMI) more than 30, computed tomography
evidence of increased intracranial pressure, intracranial aneurysm or arteriovenous
malformations, history of psychiatric illness, and/or receiving neuropsychiatric drugs,
history of alcohol or substance abuse, and patients who required postoperative mechanical
ventilation due to any intraoperative complications were excluded from the study.
The sample size calculation was based on a previous study[5 ] that compared elderly patients undergoing craniotomy for extubation time between
the groups with a minimum difference of 0.70 minutes and common standard deviation
of 1.4 minute. To attain significance, with type I error of 5%, 85% statistical power,
and 95% confidence interval, 78 was the total sample size estimated for the present
study (after adjusting for lost to follow-up, drop-out rate, and nonresponse rate).
The selected patients were randomly allocated to either desflurane (group D) or sevoflurane
(group S) arm and their demographic characteristics were recorded. Preanesthesia checkup
for baseline cognitive function was done using short orientation memory concentration
test (SOMCT, total score of 28).[17 ] All the selected participants were induced with propofol (dose titrated to response),
fentanyl 2 µg/kg, and vecuronium 0.1 mg/kg. Following intubation, radial artery cannulation
was performed for invasive blood pressure monitoring. Central venous cannulation was
performed at the discretion of attending anesthetists. A nasopharyngeal probe was
used to measure temperature, and warm blankets and fluids were used to maintain normothermia.
All subjects received scalp block 0.2% ropivacaine, and prior to the pin insertion,
the skull pin sites had been injected with 2% lignocaine. The anesthesia workstation
used was the GE ET (end-tidal) control machine (Datex-Ohmeda, Inc General Electric
Company Madison, United States). Air oxygen mixture and sevoflurane/desflurane were
used to attain a minimum alveolar concentration (MAC) of 1.0 with flows 0.5 to 1.0
L/min. End-tidal carbon dioxide (EtCO2) was maintained between 28 and 32 mm Hg using
controlled ventilation. Depth of anesthesia was monitored with patient state index
using MASIMO (United States) SedLine technology and was maintained between 25 and
50. Following exposure of the skull, all patients received 100 mL of 20% mannitol
intravenously. Intraoperative heart rate (HR), systolic blood pressure, diastolic
blood pressure, and mean arterial pressure (MAP) were recorded at baseline (before
induction), immediately following induction and intubation, once either agent had
achieved MAC of 1.0, at the time of head pin application, and every 15 minutes until
the inhalation agents were tapered at the end of the surgery.
After dural opening, the operating neurosurgeon, who was blinded to the study, assessed
the brain condition and graded on a 4-point scale as follows: (1) perfectly relaxed,
(2) satisfactory relaxation, (3) firm brain, and (4) tight brain. Interventions like
corrections in head position, further reduction of EtCO2, and additional doses of
mannitol were undertaken to achieve better brain condition to the satisfaction of
the neurosurgeon. Levetiracetam (1 gm) was administered intravenously, whenever indicated.
At the beginning of skin closure, all the patients received 1 gm of paracetamol intravenously.
Subsequently, neuromuscular blockade was reversed, and trachea was extubated in accordance
with conventional standards (after confirming adequate oxygenation, ventilation, hemodynamic
stability, sustained 5-second head lift/hand grip, and consciousness with intact cough/gag
reflex).
All the outcome variables were recorded by the lead investigator. GE Aisys workstation
monitor was used to measure HR, MAP, MAC, EtCO2, SPO2, and temperature. Anesthesia
recovery was evaluated by timing the emergence, extubation time, and recovery time.
Emergence time was defined as the time interval between the end of the anesthetic
and the eye-opening either naturally or in response to verbal cues. The interval between
cessation of volatile agent and tracheal extubation was considered as tracheal extubation
time. The recovery time was defined as the period between the termination of an anesthetic
drug and regaining consciousness to recollect their names. Scores of brain relaxation
were recorded and the postoperative recovery was assessed using the modified Aldrete
score. One hour after shifting the patients to intensive care unit (ICU), cognitive
function was measured by SOMCT, and differences between the two groups were assessed.
A language that the patient could understand was used to translate SOMCT.
Based on the anesthesiologist's discretion, patients with MAP and HR more than 20%
from baseline were treated with boluses of intravenous fentanyl, esmolol, or labetalol.
MAP less than or equal to 20% from the baseline were treated with ephedrine 6 mg intravenous
boluses, crystalloids, colloids, blood, or noradrenaline infusion.
Statistical Analysis
Statistical analyses were performed using SPSS 22.0, and R environment ver.3.2.2.
Descriptive variables were analyzed using a Student's t -test or chi-squared test. Continuous variables were compared by Student's t -test and categorical variables by chi-squared test. Line graphs were plotted using
MS Excel (2019). A p -value less than 0.05 was considered as statistically significant.
Results
Hundred eligible elderly patients diagnosed with supratentorial extra-axial lesions
were enrolled based on inclusion and exclusion criteria. These 100 subjects were randomized
into sevoflurane and desflurane groups in the ratio of 1:1 (50 each) of which 78 (39
in each group) patients were analyzed as some on them were eliminated due to various
reasons. The 2010 CONSORT flow diagram depicting the patient enrolment and allocation
is provided as [Fig. 1 ].
Fig. 1 The 2010 CONSORT flow diagram depicting the patient enrolment and allocation. PRBC,
packed red blood cell; SOMCT, short orientation memory concentration test.
The demographic characteristics such as age, gender, BMI, ASA scores, and preoperative
SOMCT were similar in both the groups. The diagnoses noted in the selected patients
were meningioma (parasagittal, frontal/temporal convexity), chronic subdural hematoma,
chordoma, depressed fracture without underlying brain parenchymal involvement, and
subdural empyema. There was no statistical difference with regard to patients' diagnosis
between the groups ([Table 1 ]).
Table 1
Demographic, preoperative characteristics, and diagnoses noted in the two groups
Variables
Sevoflurane (n = 39)
Desflurane(n = 39)
p -Value
Age (years)
69.21 ± 4.48
68.08 ± 3.56
0.11[a ]
Gender (M/F)
27 (12)
23 (16)
0.48[b ]
BMI (kg/m2 )
25.66 ± 3.15
25.08 ± 3.28
0.21[a ]
ASA score
1
2 (5.13%)
2 (5.13%)
0.61[b ]
2
24 (61.54%)
28 (71.80%)
0.47[a ]
3
13 (33.33%)
9 (23.08%)
0.45[a ]
Preoperative SOMCT
21.51 ± 3.01
21.69 ± 2.36
0.38[a ]
Diagnosis
Frontal M
8 (20.51%)
7 (17.94%)
1.00[b ]
Temporal M
7 (17.94%)
4 (10.25%)
0.26[c ]
Parasagittal M
9 (23.07%)
10 (25.64%)
1.00[b ]
Chronic SDH
8 (20.51%)
10 (25.64%)
0.8[b ]
Chordoma
2 (5.13%)
3 (7.69%)
0.50[c ]
Depressed fracture
4 (10.25%)
4 (10.25%)
1.00[c ]
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; M,
meningioma; SDH, subdural hematoma; SOMCT, short orientation memory concentration
test.
a
t -Test.
b Chi-squared test.
c Fisher's exact test.
p ≤ 0.05 has been considered as significant.
The mean emergence time was found to be significantly longer in sevoflurane group
as opposed to desflurane (p = 0.02). Similarly, the mean recovery time was significantly longer for sevoflurane
group than desflurane (p = 0.03). The mean extubation time was comparable between the groups (p = 0.09 non-significant). Early postoperative SOMCT difference between the groups
was noted to be trending toward significance (p = 0.05) with desflurane having better scores. Average duration of surgery, the number
of patients who attained satisfactory and perfect brain relaxation, and mean modified
Aldrete score were also comparable ([Table 2 ]). A statistically significant difference between pre- and postoperative SOMCT was
observed between the two groups (p = 0.04). No statistically significant difference in the intraoperative HR and MAP
was noted between the groups ([Figs. 2 ] and [3 ]).
Fig. 2 Comparison of heart rate (HR) between sevoflurane and desflurane groups.
Fig. 3 Comparison of mean arterial pressure (MAP) between sevoflurane and desflurane groups.
Table 2
Comparison of intraoperative, postoperative, and recovery variables between the groups
Variables
(n = 78)
Sevoflurane
(n = 39)
Desflurane
(n = 39)
p -Value
Brain relaxation
Satisfactory (%)
27 (69.23%)
28 (71.80%)
1.0[
a
]
Perfect (%)
12 (30.77%)
11 (28.21%)
Emergence time (minutes)
9.44 ± 2.07
8.28 ± 2.53
0.02[
b
]
Extubation time (minutes)
13.23 ± 2.88
12.23 ± 3.65
0.09[
b
]
Recovery time (minutes)
17.33 ± 3.36
15.64 ± 4.63
0.03[
b
]
Average duration of surgery (minutes)
292.31 ± 58.39
285.77 ± 80.92
0.34[
b
]
Postoperative SOMCT
16.21 ± 3.58
17.36 ± 2.55
0.05[b ]
Difference in SOMCT
5.31 ± 2.89
4.33 ± 1.74
0.04[
b
]
Modified Aldrete score
9.08 ± 0.66
9 ± 0.56
0.29[
b
]
Abbreviation: SOMCT, short orientation memory concentration test.
a Chi-squared test.
b
t -Test.
p ≤0.05 has been considered as significant.
Discussion
Emergence from anesthesia in elderly patients should be smooth and rapid to avoid
further complications and to permit early recognition of neurological deficits or
postsurgical complications. Due to the low solubility of sevoflurane and desflurane,
these agents confer the advantages of better control of anesthetic depth and more
rapid recovery from anesthesia.[18 ] Since desflurane has considerably lower blood:gas partition coefficient than sevoflurane,
desflurane is anticipated to give an early and quick awakening from anesthesia.[19 ]
[20 ]
This study has noted significant difference in mean emergence time between the two
groups (p = 0.02), shorter for desflurane than sevoflurane (8.28 ± 2.53 vs. 9.44 ± 2.07 minutes).
This is in line with previous literature findings suggesting shorter emergence time
for desflurane.[21 ]
[22 ] Nathanson et al reported significantly lesser emergence time for desflurane as opposed
to sevoflurane (4.8 ± 2.4 vs. 7.8 ± 3.8 minutes) in outpatient surgeries.[21 ] In contrast, the study conducted by Dube et al in adult patients undergoing supratentorial
craniotomy has reported that intraoperative brain condition, hemodynamics, and postoperative
recovery profile were comparable for sevoflurane and desflurane (emergence time: group
D 7.4 ± 2.7 minutes vs. group S 7.8 ± 3.7 minutes; p = 0.65).[14 ]
The study has also noted that the mean recovery time was significantly longer for
sevoflurane group than desflurane (17.33 ± 3.36 vs. 15.64 ± 4.63, p = 0.03). This finding concurs with the studies by Magni et al and Dogru et al.[23 ]
[24 ] Magni et al have found that the mean emergence time was comparable between groups,
whereas the mean extubation time and recovery time were longer for sevoflurane (15.2 ± 3.0 minutes
for S vs. 11.3 ± 3.9 minutes for D and 18.2 ± 2.3 minutes for S vs. 12.4 ± 7.7 minutes
for D, respectively; p < 0.001).[23 ] Dogru et al concluded that in patients undergoing hip replacement surgery, desflurane
conferred significantly more rapid early recovery than sevoflurane, but there were
no beneficial effects for desflurane on intermediate recovery.[24 ] Several other studies have also corroborated the rapid recovery time noted for sevoflurane.[16 ]
[25 ]
[26 ] Heavner et al have reported faster recovery time upon using desflurane in elderly
patients undergoing surgical procedures requiring two or more hours of anesthesia
(p ≤0.05).[15 ]
The mean extubation time was found to be comparable between the two present study
groups. A similar finding was reported by Dube et al, whereas other studies have noted
that the extubation time was faster for desflurane than sevoflurane.[21 ]
[22 ]
[23 ]
[24 ] In clinical settings, 1 to 2 minutes difference in individual outcome parameters
may not be very relevant. But the consolidated difference of 5 to 10 minutes noted
with desflurane aids in early neurological assessment of elderly patients and effective
usage of operation theaters in settings where case turnover is high.
The factors that may influence patient's postoperative cognition include patient's
age, preoperative cognition, comorbid conditions, preoperative drugs, type of anesthetic
agents used, and intraoperative events.[27 ] In this study, the pre and postoperative cognition function was assessed by SOMCT,
which has been used extensively to study orientation levels of patients (either for
comparison between pre and postoperative cognition or for screening or establishing
baseline cognitive status in patients with neurological conditions).[28 ] This test, which is derived from the longer Blessed scale, correlates significantly
(r = 0.92) with the latter and has comparable sensitivity. As per the scoring, score
more than 20 is considered as normal.[17 ]
All the patients in this study had normal scores on preoperative assessment of SOMCT
(>20). The postoperative cognition was evaluated only at early time point (1 hour
after shifting to ICU) and it was better in desflurane group (17.36 ± 2.55 vs. 16.21 ± 3.58).
Cognitive function studied at later time points would have given a clear picture,
and this has been found to be comparable in both the groups in previous studies on
non-neurological patients.[1 ]
[5 ] In clinical practice, improved early cognitive profile would help in the earlier
recognition of neurological deficits.
Similar results were noted in studies by Dube et al and Magni et al in adult patients
undergoing supratentorial craniotomy.[14 ]
[23 ] A study by Bilotta et al involving 18- to 75-year-old overweight and obese patients
undergoing craniotomy reported desflurane had an earlier postoperative cognitive recovery
than the sevoflurane group.[29 ] Similar cognitive recovery assessed by SOMCT by desflurane compared with sevoflurane
was reported by Saha et al.[25 ] In this study, a statistically significant difference in SOMCT was observed between
the two groups (5.31 ± 2.89 vs. 4.33 ± 1.74, p = 0.04). Although the preoperative SOMCT was comparable between the groups, the difference
in SOMCT score noted could be due to comparatively lower postoperative SOMCT score
observed in sevoflurane group. Brain relaxation, average duration of a surgery, and
modified Aldrete score were also comparable between this study arms.
This study holds relevance in the field of neurosurgery, as there is very limited
literature evidence comparing the recovery profile of these two volatile anesthetics
in elderly neurosurgical population. Moreover, the power of the study (85%) is good
to draw valuable conclusions. This study has certain limitations. The study findings
are less generalizable due to the single-center study design. Though the study design
was open label randomized, there was no influence of physician's assessment or opinion
on parameters, as they were objective. The time of discontinuation of the inhalational
agent was left to the discretion of the attending anesthesiologist and was not standardized.
The effect of postoperative hemodynamic variations on the postoperative SOMCT within
the same group or between the groups was not assessed.
Conclusion
In conclusion, patients who received desflurane had a shorter emergence, recovery
time, and better early cognitive function compared with sevoflurane, but intraoperative
traits were similar in both the groups. The rapid emergence and recovery from anesthesia
may enable conducting earlier neurological examination in elderly neurosurgical population
and more effective usage of the operating room.
