Keywords desflurane - emergence - propofol - sevoflurane - trans-sphenoidal pituitary surgery
Introduction
Smooth and early emergence is a major concern in neurosurgical patients. Early emergence
from anesthesia facilitates early neurological examination and immediate postoperative
intervention, if necessary. It is especially important in patients undergoing transnasal
trans-sphenoidal surgery (TSS) because straining or coughing during emergence from
anesthesia can precipitate hemorrhage, cerebrospinal fluid (CSF) leakage, and dislodgement
of nasal pack.[1 ] These patients are extubated only when they are fully awake so as to prevent airway
obstruction and restlessness in post extubation period. Anesthetic technique that
facilitates early awakening with clear higher mental functions is highly desirable
in these patients to avoid complications.
Anesthetic agents are the major determinants of the time of emergence and extubation,
thus making short-acting anesthetic agents preferable as maintenance agents in these
cases.[2 ] Propofol, an intravenous (IV) anesthetic agent with short duration of clinical effects
due to rapid distribution into peripheral tissues and minimal cumulative effect, has
been used commonly to achieve the same. Sevoflurane and desflurane are third-generation
volatile anesthetic agents, having property of rapid emergence from anesthesia due
to low blood–gas partition coefficient of 0.65 and 0.42, respectively.[3 ]
[4 ]
[5 ]
Ali et al[6 ] compared propofol, sevoflurane, and isoflurane in patients undergoing TSS and observed
that propofol and sevoflurane were better than isoflurane for emergence from anesthesia
under bispectral index (BIS) guidance. There is little literature on comparing desflurane
with other short-acting anesthetic agents on emergence from anesthesia in cases of
TSS. We hypothesized that emergence from anesthesia will be faster with desflurane
compared with propofol and sevoflurane in TSS. Therefore, we planned to evaluate the
effect of three short-acting anesthetic agents, namely propofol, sevoflurane, and
desflurane, used for the maintenance of anesthesia at the time of emergence and recovery
from anesthesia as the primary outcome and quality of recovery as the secondary outcome
in cases of TSS in this study.
Methodology
This prospective randomized trial was conducted in 75 patients undergoing elective
TSS surgery for pituitary tumors after getting approval from the institute ethics
committee and informed consent from the patients. Patients aged 18 to 65 years, the
American Society of Anesthesiologists (ASA) classes I and II were included while patients
with pituitary apoplexy and redo surgery were excluded from the study.
Patients were randomly allocated by a computer-generated random number table and serially
numbered opaque envelope technique into three groups—P, S, and D—according to the
anesthetic agent they received (propofol, sevoflurane, or desflurane) for the maintenance
of anesthesia, respectively.
A standardized anesthesia protocol was followed in all cases. Pre-induction monitoring
included electrocardiogram (ECG), noninvasive blood pressure (NIBP), pulse oximetry
(SpO2), neuromuscular transmission (NMT), and BIS using Aspect 2000 monitor with sensor
Xp. Anesthesia was induced with fentanyl (2 μg/kg) followed by propofol (1–2 mg/kg)
until loss of verbal response in all the three groups. Muscle relaxation was achieved
with vecuronium (0.1 mg/kg), and trachea was intubated when train-of-four (TOF) count
was zero in NMT. Anesthesia was maintained as per the group allocation and was titrated
to maintain BIS in the range of 45 to 55. Intraoperative analgesia was maintained
with fentanyl infusion (1 μg/kg/h), while muscle relaxation was maintained with intermittent
doses of vecuronium (1 mg/dose) maintaining the TOF count less than 2 throughout the
surgery. All patients received a mixture of oxygen and nitrous oxide (50:50) with
gas flows at 2 L/min to keep end-tidal carbon dioxide (EtCO2 ) between 35 and 40 mm Hg during mechanical ventilation. Radial artery of nondominant
hand was cannulated for continuous monitoring of invasive blood pressure. Posterior
hypopharynx was packed with moist rolled gauze.
Patients in Group P received propofol infusion (3–8 mg/kg/h), while those in Groups
S and D received sevoflurane and desflurane, respectively, for the maintenance of
anesthesia titrated to keep BIS between 45 and 55 in all the three groups. Intranasal
mucosa was prepared by instilling 20 mL of lignocaine containing adrenaline (1:400,000)
into cotton pellets and packing the nose prior to surgery. Hemodynamic parameters
were noted at regular interval. Blood pressure beyond 20% of the baseline value was
treated with either esmolol (0.5 mg/kg) or mephenteramine (3 mg/dose).
At the end of the surgery, fentanyl infusion was stopped 30 minutes prior to emergence,
and anesthetic agents used for maintenance were decreased to keep BIS around 60 and
were finally discontinued immediately after nasal packing. Nitrous oxide was also
stopped, and residual neuromuscular block was reversed. Trachea was extubated when
the patient had adequate muscle power and regular respiration generating adequate
tidal volume and was able to respond to verbal commands.
Emergence time was defined as the time interval between discontinuation of the anesthetic
agent and the time to open eye on verbal commands. Extubation time was defined as
the time interval between discontinuation of anesthetic agent and tracheal extubation.
Immediate postoperative cognitive function to assess clear higher mental function
was evaluated at 5, 10, and 15 minutes after extubation using a modified Short Orientation
Memory Concentration (SOMC) test. The questionnaire includes—where are you at present,
which year is it now, which month is it now, count numbers from 1 to 10, and count
reverse numbers from 10 to 1. If the patient was able to recall and count with minimal
mistakes (1–3), it was regarded as good, with more than three errors as fair, and
if he/she was not able to recall at all, it was regarded as poor. It was done to ensure
complete awakening and orientation of the patient before proceeding for the neurological
and visual field assessment. Recovery characteristics were assessed with a modified
Aldrete's score at 10 and 15 minutes after extubation. Postoperative pain (by 11 points
numeric rating scale [NRS]) and incidence of postoperative nausea and vomiting (PONV)
(by number of patients having PONV) at 5, 10, and 60 minutes after extubation were
also measured.
Duration of emergence and extubation was noted and analyzed as the primary outcome
of the study. Hemodynamic parameters, rescue drugs to maintain hemodynamic stability,
modified SOMC score, modified Aldrete's score, pain score, and PONV score were recorded
to assess quality of recovery as the secondary outcome of the study.
Sample Size Calculation
The sample size was estimated based on the study by Ali et al.[6 ] Twenty-four patients were needed in each group to demonstrate a 40% improvement
in emergence time with the new agent (desflurane) with respect to propofol with an
α-error of 0.05 and power of 80%. Considering 5% attrition of cases during the study,
we included 25 patients in each group to ensure adequate power of the study for assessing
emergence from anesthesia.
Statistical Analysis
Demographic variables were presented as mean ± standard deviation (SD) and were compared
among the groups using one-way analysis of variance (ANOVA). Skewed data and ordinal
distributed data were presented as median ± quartiles (interquartile range) and were
analyzed using repeated ANOVA or by using Kruskal–Wallis test or Mann–Whitney test
as appropriate. Categorical variables were presented as frequency or percentage and
were compared among the groups using chi-square test. Hemodynamic parameters were
compared by two-way repeated measures ANOVA with Bonferroni correction. Emergence
and extubation were compared among the groups using one-way ANOVA followed by Bonferroni
correction. A p -value < 0.05 was considered as significant.
Results
All the patients included in the study completed it. Seventy-five patients included
in the study were randomized into three groups of 25 each. The three groups were comparable
with respect to the demographic parameters, pituitary pathology, duration of surgery,
intraoperative fentanyl requirement, intraoperative IV fluids administered, and urine
output ([Table 1 ]).
Table 1
Demographic and intraoperative parameters
Group P (n = 25)
Group S (n = 25)
Group D (n = 25)
p -Value
Abbreviations: IV, intravenous; M/F, male/female; NFPT, nonfunctioning pituitary tumors;
SD, standard deviation.
Values expressed as mean ± SD or n.
Age (in years)
39.64 ± 12.24
39.92 ± 11.66
40.9 ± 13.5
0.935
BMI (kg/m2 )
27.69 ± 3.30
25.74 ± 3.07
26.9 ± 3.0
0.095
Sex (M/F) (n )
15/10
7/18
15/10
0.074
ASA status (I/II) (n )
7/18
11/14
12/13
0.311
Pituitary pathology (acromegaly/Cushing's disease/NFPT) (n )
5/3/17
4/3/18
4/2/19
0.952
Duration of surgery (minutes)
101.28 ± 31.30
98.72 ± 31.47
95.8 ± 21.2
0.793
Intra-operative fentanyl (μg)
176.40 ± 18.68
168.40 ± 17.95
168.8 ± 20.5
0.254
Total intra-operative IV fluid (mL)
1226.00 ± 218.9
1204.00 ± 190.4
1168.0 ± 197.3
0.077
Total urine output (mL)
182.8 ± 27.7
166.4 ± 37.3
163.4 ± 27.3
0.067
There was a statistically significant shorter emergence time in Group D (3.16 ± 0.62
min) as compared with group P (4.32 ± 0.90 min) and group S (5.24 ± 1.01 min) (p < 0.001). Similarly, the extubation times were also significantly shorter statistically
in the group D (6.28 ± 1.40 minutes) as compared with groups P (7.56 ± 1.87 min) and
S (8.72 ± 1.64 min) ([Table 2 ], [Fig. 1 ]). Modified SOMC test scores were comparable among all the three groups ([Table 2 ]).
Table 2
Parameters at emergence from anesthesia and postoperative period
Group P (n = 25)
Group S (n = 25)
Group D (n = 25)
p -Value
Abbreviations: NRS, numeric rating scale; SOMC, Short Orientation Memory Concentration.
a Between group P and group S, p = 0.001 for emergence and p = 0.04 for extubation.
b Between group S and group D, p = 0.000 for emergence and extubation.
c Between group P and group D, p = 0.000 for emergence and p = 0.023 for extubation.
d
p -Value < 0.05 on comparing among the three groups. Data were presented as number.
Emergence time (minutes)
4.32 ± 0.90a
5.24 ± 1.01b
3.16 ± 0.62c
0.00d
Extubation time (minutes)
7.56 ± 1.87a
8.72 ± 1.64b
6.28 ± 1.40c
0.00d
Emergence agitation (calm/agitated)
23/2
22/3
23/2
0.13
Postoperative Cognitive function (modified SOMC test)
At 5 minutes (good/fair/poor)
20/5/0
20/5/0
21/4/0
0.47
At 10 minutes (good/fair/poor)
23/2/0
20/5/0
24/1/0
0.16
At 15 minutes (good/fair/poor)
25/0/0
24/1/0
25/0/0
0.36
Modified Aldrete's score
At 10 minutes
9.92 ± 0.40
9.76 ± 0.66
9.52 ± 0.87
0.12
At 15 minutes
10.00 ± 0.00
9.92 ± 0.40
9.92 ± 0.40
0.60
Postoperative pain score (NRS)
At 5 minutes
2.40 ± 0.57
2.36 ± 0.57
2.36 ± 0.63
0.92
At 10 minutes
3.24 ± 0.52
3.56 ± 0.58
3.48 ± 0.71
0.06
At 60 minutes
4.40 ± 0.57
4.60 ± 0.50
4.20 ± 0.57
0.67
Postoperative nausea and vomiting (number of patients)
At 5 minutes
0
2
3
0.22
At 10 minutes
0
3
1
0.16
At 60 minutes
0
0
0
1
Fig. 1 Recovery profile in minutes. *Indicates p -value < 0.05 on comparing among the groups.
The heart rate (HR) and mean arterial pressure was compared in all the three groups
at the baseline, discontinuation of the anesthetic agents at the end of the surgery,
discontinuation of nitrous oxide, at emergence (eye opening on command), and at the
time of extubation. The mean baseline HR was comparable in all the three groups. There
was an increase in HR at emergence and extubation in all the three groups compared
with baseline value, but the difference in between the groups was not statistically
significant ([Table 3 ]). Mean arterial pressure was comparable at baseline and at all other stages except
for during the extubation when there was a rise in mean airway pressure (MAP) in the
desflurane group as compared with propofol and sevoflurane group (p = 0.02) ([Table 4 ]).
Table 3
Mean heart rate at various stages (in beats/minute)
Events
GROUP P (n = 25)
GROUP S (n = 25)
GROUP D (n = 25)
p -Value
Abbreviations: N2 O, nitrous oxide; SD, standard deviation.
Values expressed as mean ± SD.
Baseline
75.36 ± 9.08
78.67 ± 5.68
79.05 ± 6.50
0.16
Discontinuation of test agent
81.08 ± 6.970
82.96 ± 3.900
82.96 ± 6.41
0.44
Discontinuation of N2 O
82.52 ± 6.98
84.60 ± 3.72
84.68 ± 6.15
0.33
At emergence (eye opening)
86.40 ± 6.62
86.68 ± 3.90
87.68 ± 5.46
0.68
At extubation
94.280 ± 3.921
92.48 ± 4.788
94.52 ± 5.501
0.365
Table 4
Mean map at various stages (in mm Hg)
Events
Group P (n = 25)
Group S (n = 25)
Group D (n = 25)
p- Value
Abbreviations: N2 O, nitrous oxide; SD, standard deviation.
a
p -Value < 0.05 on comparing among the groups. Values expressed as mean ± SD.
Baseline
89.22 ± 7.437
86.16 ± 5.853
86.49 ± 4.846
0.199
Discontinuation of test agent
87.08 ± 5.69
87.60 ± 4.65
87.72 ± 3.76
0.88
Discontinuation of N2 O
89.92 ± 5.80
89.16 ± 4.70
89.68 ± 3.64
0.85
At emergence (eye opening)
92.44 ± 5.60
91.04 ± 5.47
92.08 ± 4.46
0.62
At extubation
99.48 ± 5.07
97.16 ± 5.41
100.32 ± 4.65
0.02a
All the patients had hypertension during the emergence and extubation. The esmolol
requirement in intraoperative period in all the three groups P, S, and D was found
to be comparable (p = 0.131).
Modified Aldrete's score measured in the post anesthesia care unit (PACU) at 10 and
15 minutes was also comparable in all the three groups. Pain and PONV scores were
also similar among the groups ([Table 2 ]).
Discussion
Emergence from anesthesia should be smooth and predictable with minimum hemodynamic
and metabolic perturbations. Following TSS surgeries, the nose is packed, which makes
these patients obligate mouth breathers in the early postoperative period.[6 ] It may cause restlessness and agitation in postoperative period if patient is not
fully awake and able to understand the situation. The goal of anesthesia in neurosurgical
patients in the immediate postoperative period is a fully awake and comfortable patient
with adequate respiratory efforts and stable hemodynamics.
Desflurane due to lower blood–gas partition coefficient has the property of rapid
recovery. No study till date has compared the effect of desflurane with other anesthetic
agents in cases of TSS. In this study, we compared the three short-acting anesthetic
agents (propofol, sevoflurane, and desflurane) used for maintenance of anesthesia
and evaluated their effects on emergence from anesthesia. We observed a significant
difference in the time of emergence and the time to extubation among the three anesthetic
agents. The time to emergence and extubation was shortest in desflurane as compared
with propofol and sevoflurane with sevoflurane having the longest time to emergence.
Though the difference was statistically significant, its clinical significance is
questionable.
Various studies have compared these three anesthetic agents in neurosurgical patients
with contradictory results. Magni et al and Bilotta et al have reported shorter recovery
with desflurane as compared with sevoflurane in supratentorial surgeries, similar
to our observation.[7 ]
[8 ] On the other hand, Bastola et al[9 ] did not find a statistical difference in the time to emergence among propofol, sevoflurane,
and desflurane, though they reported prolonged time to response to verbal commands
with sevoflurane in patients undergoing surgery for supratentorial tumors similar
to our results. Dube et al have reported a comparable recovery time between sevoflurane
and desflurane in patients undergoing supratentorial craniotomy.[10 ] Our study was done in patients undergoing TSS in cases of pituitary adenoma in which
early recovery from anesthesia is crucial. Our results were comparable to that of
Magni et al and Billotta et al, with desflurane having the shortest recovery time
as compared with sevoflurane.[7 ]
[8 ] The low blood–gas partition coefficient of desflurane (0.42) could account for the
rapid emergence compared with sevoflurane (0.65).[3 ]
[4 ]
Ali et al observed shorter emergence time in propofol and sevoflurane groups (5 min)
compared with isoflurane (9 min), while the duration was comparable for propofol and
sevoflurane in patients undergoing TSS.[6 ] Cafiero et al reported faster recovery with sevoflurane–remifentanil combination
as compared to propofol with remifentanil (7.4 vs. 12.8 min, p < 0.01) in endonasal TSS while Citerio et al found no difference in time to eye opening
with propofol and sevoflurane.[11 ]
[12 ] Several other authors have also reported no difference in time to recovery with
inhalational anesthesia and total intravenous anesthesia (TIVA) in neurosurgical patients.[13 ]
[14 ]
[15 ]
[16 ] We observed a small, but statistically significant difference in time of emergence
and extubation between desflurane and sevoflurane groups (emergence time: Group D:
3.16 ± 0.62 vs. Group S: 5.24 ± 1.01 min, p = 0.000; extubation time: Group D: 6.28 ± 1.40 vs. Group S: 8.72 ± 1.64 min, p = 0.000). Emergence in desflurane group was even faster than in the propofol group
(emergence time: Group D: 3.16 ± 0.62 vs. Group P: 4.32 ± 0.90 min, p = 0.000; extubation time: Group D: 6.28 ± 1.40 vs. Group P: 7.56 ± 1.87 min, p = 0.023). The small difference in duration observed between the groups may be of
doubtful clinical significance.
Smooth emergence aims at preventing emergence hypertension and agitation. Hypertension
is frequent during emergence with a reported incidence of 70 to 90%.[17 ]
[18 ]
[19 ] while 40 to 90% of patients require antihypertensive therapy during emergence.[18 ]
[19 ]
[20 ] The most common feared complication after neurosurgery is the development of intracranial
hematoma (0.8–2.2%),[21 ] which has been associated with postoperative systemic hypertension, though a direct
causal relationship could not be made.[22 ] Basali et al have described a link between perioperative hypertension and intracranial
hemorrhage after craniotomy in a retrospective case control study and reported that
patients with postoperative intracranial hemorrhage were 3.6 times more likely to
be hypertensive. They observed a very strong association between intracranial hemorrhage
and patients being normotensive intraoperatively, but hypertensive postoperatively.[22 ] In our study, we observed a statistically significant difference in the MAP only
at the time of extubation with a rise observed in the desflurane group followed by
propofol and sevoflurane. The difference among the groups is small, so again clinical
significance of the difference in MAP is doubtful.
In contrast to our finding, Bastola et al had observed a comparable incidence of emergence
hypertension among the three agents used for elective craniotomy.[9 ] Sevoflurane and desflurane have a dose-dependent systemic vasodilator effect, while
propofol has both vasodilator and negative inotropic effects.[23 ]
[24 ]
[25 ] Hemodynamic parameters were comparable between the groups.
Modified SOMC test was done to assess cognition in the form of the clear higher mental
function. It is used after the emergence from anesthesia to ensure complete awakening
and orientation of the patient before proceeding for the neurological and visual field
assessment. The modified SOMC scores achieved at 5, 10, and 15 minutes were comparable
among the three groups with scores slightly better in desflurane and propofol groups
as compared with the sevoflurane group, though the difference was statistically insignificant.
Ali et al had also reported better cognitive scores in propofol group than in the
sevoflurane group, while Billotta et al observed earlier postoperative cognitive recovery
with desflurane-based anesthesia as compared with sevoflurane in overweight and obese
patients.[6 ]
[8 ] In our observation, all the three agents are comparable in terms of immediate postoperative
cognitive recovery with more number of patients having good scores in patients receiving
desflurane. Modified Aldrete score was comparable in all the three groups at 10 and
15 minutes.
Limitations of the Study
We have not measured serum catecholamine concentrations at emergence and extubation,
which could have provided further valuable information related to anesthetic agent
of choice in such situations.
Conclusion
Desflurane had shorter emergence and extubation time in comparison to propofol and
sevoflurane when used for maintenance of anesthesia under BIS guidance during TSS
for pituitary adenoma without any significant side effects. Immediate postoperative
cognitive functions were comparable in all three groups. As the difference in emergence
criteria between the groups were small, the clinical significance of the difference
is questionable.
We conclude that desflurane can be used as an alternative to propofol and sevoflurane
for maintenance of anesthesia in patients undergoing transnasal trans-sphenoidal pituitary
surgery for its excellent recovery profile after anesthesia.
