Aging Clinical and Experimental Research

https://doi.org/10.1007/s40520-019-01123-8

ORIGINAL ARTICLE

Comparative effects of fentanyl versus sufentanil on cerebral oxygen

saturation and postoperative cognitive function in elderly patients
undergoing open surgery
Jun Zhang1 · Liang Chen1 · Yunyun Sun1 · Wensheng He1

Received: 18 September 2018 / Accepted: 3 January 2019

© Springer Nature Switzerland AG 2019

Abstract
This study was aimed to systematically evaluate the effects of fentanyl and sufentanil on intraoperative cerebral oxygen
saturation changes and postoperative cognitive function in elderly patients undergoing open surgery. Ninety-six elderly
patients who had undergone open surgery under general anesthesia were randomly divided into fentanyl group (F group,
anesthesia by fentanyl, 4 g/kg) and sufentanil group (S group, anesthesia by sufentanil, 0.4 µg/kg). There were no signifi-
cant differences between the F group and S group in the general characteristics of patients. Compared to the F group, the S
group had a better effect on suppressing the stress response, maintaining a stable hemodynamic status and achieving better
anesthesia effects. The anesthesia recovery time of the S group was significantly shorter than that of the F group. There was
no significant difference between the two groups in the intraoperative and postoperative agitation. Patient’s waking time and
extubation time were significantly shorter in the S group than the F group. The VAS scores in the S group were significantly
lower than those in the F group at each time point. The Ramsay scores in the S group were significantly higher than those
in the F group at each time point. The cerebral oxygen saturation (­ SctO2) levels in both groups were significantly increased
following anesthesia induction and intubation compared to that of the awake state (P < 0.05), and ­SctO2 was significantly
decreased during the surgery in both groups. The changes in ­SctO2 levels were not significantly different between the two
groups (P > 0.05). The ­SctO2 level was significantly higher during surgery than that after intubation. Compared with the
F group, the relative value of ­SctO2 decline in the S group was smaller. Compared to the day before surgery, the Montreal
Cognitive Assessment (MoCA) scores of both groups were significantly reduced after surgery. At 1 day post-surgery, the
MoCA scores of the S group were significantly higher and the incidence of postoperative cognitive dysfunction (POCD)
was significantly lower compared to the F group. POCD occurred in three patients (6.2%) in the S group, and the ratio was
significantly lower than that in the F group (11.9%) (P < 0.05). It showed a consistent trend with the ­SctO2 status during the
surgery. The relative value of S­ ctO2 decline in the S group was significantly smaller than that in the F group. The reduction
of cognitive function in the S group was significantly lower than that in the F group. These results indicate that the changes
in ­SctO2 are a good prediction of the incidence of POCD.

Keywords  Anesthesia · Fentanyl · Sufentanil · Cerebral oxygen saturation · Postoperative cognitive dysfunction

Introduction

The life quality of aged individuals has received more and

more attention as a result of the rising aging population [1,
2]. One important aspect of life quality is the postoperative
* Wensheng He rehabilitation of elderly patients as a result of the increased
hewensheng617105@163.com incidence of age related problems [3]. Open surgery is one
1
of the most common surgeries and the procedure requires
Department of Anesthesia, The Second People’s Hospital general anesthesia. The ideal wake-up process after surgery
of Hefei, The Affiliated Hefei Hospital of Anhui Medical
University, No 246 Heping Road, Yaohai District, is that the patient wakes up quickly with rapid and stable
Hefei 230011, Anhui, China breathing accompanied by low postoperative pain without

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any serious side-effects during peri-extubation period. This
process is one of the indicators for evaluating the anes-
thetic effects of the surgery. Another critical indicator is the
incidence of postoperative cognitive dysfunction (POCD).
POCD is a common complication of the central nervous sys-
tem that occurs after anesthesia and surgery [4, 5]. Elderly
patients are among the population with high incidence of
POCD [5]. POCD is characterized by deterioration of a
series of mental functions including long-term and short-
term memory, orientation and attention, as well as cogni-
tion such as personality, social ability and cognitive compe-
tence. These adverse changes can negatively impact patient’s
recovery from the disease and prolong patient’s hospital
stay, resulting in decreased self-care ability and delayed
recovery from the surgery. In summary, it is particularly
important to choose an appropriate anesthetic regimen to
improve the quality of recovery from anesthesia in elderly
patients. Therefore, it is necessary to carry out clinical stud-
ies to observe the postoperative recovery status, investigate
the incidence and severity of POCD in elderly patients with
different types of anesthetics and determine the efficacy and
safety of each anesthetic.
Additionally, changes in cerebral oxygen saturation
­(SctO2) have been shown to be closely related to postopera-
tive cognitive function in elderly patients and are an indi-
cator for monitoring during surgery. For example, reduced
­SctO2 is positively associated with early cognitive dysfunc-
tion in patients undergoing thoracic surgery [6]. Therefore,
real-time dynamic monitoring of regional S ­ ctO2 during sur-
gery is also a predictive measure of POCD that may occur
after surgery. Recently, monitoring of S ­ ctO2 by near-infrared
spectroscopy has been used as a non-invasive monitoring
method for cerebral oxygen supply and demand balance that
provides a more accurate prediction of POCD incidence [7,
8].
Fentanyl and sufentanil are both potent opioids playing
an analgesic role during general anesthesia [9, 10]. Both of
these drugs are widely applied in clinical practice. How-
ever, clear research evidence is still lacking on the anesthesia
recovery time, the quality of recovery and the incidence of
adverse reactions during the peri-recovery period after using
either of the two drugs for general anesthesia. This study
systematically evaluated the analgesic effects and adverse
reactions of fentanyl and sufentanil in elderly patients under-
going open surgery, and focused on the changes of S ­ ctO2
during the surgical procedure and the incidence of POCD.
We aimed to find suitable types and doses between the two
anesthetics, and provide more reliable medical evidence for
subsequent clinical rational application.
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Aging Clinical and Experimental Research
Patients and methods
Subjects
We recruited 96 patients receiving open surgery under gen-
eral anesthesia in the Second People’s Hospital of Hefei,
the Affiliated Hefei Hospital of Anhui Medical University.
These patients aged ≥ 65 and were at ASA levels I–II prior
to the surgery. This study was approved by the Second
People’s Hospital of Hefei, the Affiliated Hefei Hospital
of Anhui Medical University and all patients provided
informed written consent. All patients had normal preop-
erative heart, lung, liver and kidney functions and basi-
cally normal conscious functions. Patients were excluded
if they were allergic to aspirin or parecoxib sodium, had
respiratory depression, bronchial asthma, peptic ulcer,
heart disease, history of severe hypertension, coagulation
and platelet abnormalities, tendency to bleeding or history
of blood system diseases, severe hepatorenal dysfunction,
emergent craniocerebral trauma, preoperative conscious-
ness or cognitive dysfunction. Some studies have shown
that hemoglobin (Hb) is highly involved in the regulation
of ­SctO2. Therefore, we excluded patients with gyneco-
logical disorders and recruited patients with normal Hb.
Additionally, we excluded potential interfering factors that
might affect ­SctO2 such as age, inhaled oxygen concentra-
tion, end-tidal carbon dioxide concentration and patient
position. Since it has been shown that temperature plays a
role on the postoperative recovery and incidence of POCD
[11], we also excluded the effects of temperature changes
on surgical outcomes.
Monitoring of general clinical conditions
Partial pressure of end-tidal carbon dioxide (P ETCO 2),
bispectral index (BIS), central venous pressure (CVP)
and brachial artery pressure were monitored continuously.
Changes in hemodynamic parameters including heart rate
(HR), systolic blood pressure (SBP), diastolic blood pres-
sure (DBP) and mean arterial pressure (MAP) at the time
of preanesthesia, intubation, craniectomy and extubation
were recorded.
Monitoring of the patient’s recovery status
Durations of recovery from anesthesia including recovery
of spontaneous breathing, eye opening, extubation and
recovery of orientation, postoperative agitation and the
presence of nausea and vomiting were recorded. Postop-
erative pain status was determined by the visual analogue
Aging Clinical and Experimental Research
scale (VAS), with scores ranging from 0 to 10 and a higher
score indicating more pronounced pain. The Ramsay seda-
tion scale was used to assess the level of sedation at differ-
ent stages after surgery.
Measurement of ­SctO2 by FORSIGHT absolute
oximeter
SctO2 was measured by the FORSIGHT absolute oximeter
(CASMED, Branford, MT, USA) after anesthesia induction
(T0), at the beginning of surgery (T1), 30 min (T2), 1 h (T3)
and 2 h (T4) after the beginning of surgery, and at the time
of extubation (T5). The FORSIGHT absolute oximeter meas-
ures the oxyhaemoglobin and deoxyhaemoglobin changes by
passing near-infrared light through the skull. It is a non-inva-
sive procedure that can provide continuous monitoring of
brain oxygenation. The procedure was performed according
to a previous study [12]. Briefly, two sensors were placed on
the left and right sides of the lower forehead of each patient
that were covered to prevent the interference of light on the
measurements. The average of left and right ­SctO2 at each
time point was used for the analysis of the average S ­ ctO2,
minimum ­SctO2 and maximum ­SctO2 decline.
Montreal Cognitive Assessment (MoCA)
and incidence of POCD
The cognitive function of the subject was assessed by MoCA
as described previously [13]. MoCA is a tool initially devel-
oped to briefly screen patients for mild cognitive impairment
(MCI) and is highly sensitive and specific in the detection
of MCI [14]. The MoCA scale has a maximum score of
30 points, composed of 11 inspection items in 8 cognitive
areas including attention and concentration, executive func-
tion, memory, language, visual structure function, abstract
thinking, calculation and orientation. Patients in the F group
and the S group were assessed at 1 day prior to surgery, and
1 day and 7 days after surgery. Cognition evaluation criteria:
patient’s cognitive function was assessed at 1 day prior to
surgery according to the MoCA scale. Patients who were
illiterate or had pre-operative cognitive dysfunction were
excluded. At 1 day and 7 days after surgery, patients were
Table 1  Demographic Group n Age (year) Gender (F/M) Body weight (kg) Height (cm) Head cir-
information of the subjects in
the F and S groups
F 48 70 ± 3.1 25/23
S 48 69 ± 2.1 24/24
P / 0.07 / 0.189
Data are expressed as mean ± SD (standard deviation) except gender and ASA level. No significant differ-
ences in any indicators were observed between the two groups
ASA American Society of Anesthesiologists
subjected to the MoCA assessment. The standard deviation
(SD) of each item on the MoCA scale was calculated based
on the scores of all patients prior to the surgery. The scores
of each patient before and after the surgery were compared
to the SD of each item. If the reduction of the scores was
≥ one SD, impaired function was considered to be present
in the test item after surgery. If there were two or more dys-
functional items, the patient was diagnosed with POCD and
the incidence of POCD was recorded [15].
Statistical analysis
The difference between two groups was assessed by Stu-
dent’s t-test or Chi square test. The two-way analysis of
variance (ANOVA) followed by Turkey test was used for
multiple comparisons. Difference was considered statisti-
cally significant if P < 0.05.
Results
Demographic characteristics of the subjects
The basic demographic information of the two groups was
shown in Table 1. Among the subjects in the F group, 23
were male and 25 were female, with an average age of
71 ± 5.1 years, and average weight of 68.2 ± 3.9 kg. The dose
for fentanyl was 4 µg/kg. Among the subjects in the S group,
24 were male and 24 were female, with an average age of
69 ± 2.1 years, and average weight of 69.2 ± 3.4 kg. The dose
for fentanyl was 0.4 µg/kg. We did not observe any signifi-
cant differences in the general demographic characteristics
between the two groups.
Comparison of general clinical conditions
during surgery between the two groups
The general clinical characteristics of the subjects in both
groups were shown in Table 2. We calculated the duration
between anesthesia induction and the beginning of surgery,
the average CVP, BIS, amount of infusion as well as vol-
ume of blood loss. Statistical analysis did not reveal any
ASA level (I/II)
cumference
(cm)
68.2 ± 3.9 162.2 ± 4.1 57.1 ± 1.1 21/27
69.2 ± 3.4 161.1 ± 3.9 56.7 ± 0.9 23/25
0.229 0.058 /
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 Aging Clinical and Experimental Research

Table 2  Comparison of general conditions in both groups during sur- post-operative nausea and vomiting (Table 4). We found that
gery the anesthesia recovery duration including the duration of
Characteristic Group F (n = 48) Group S (n = 48) P respiratory restoration, eye opening, extubation and orienta-
tion recovery was significantly longer in the F group than
T1–T0 (min) 19.1 ± 4.3 18.7 ± 5.3 0.689
that of the S group. We did not observe any significant dif-
CVP 9.1 ± 0.7 8.8 ± 0.9 0.077
ference in the body movement during anesthesia and emer-
BIS 44.2 ± 1.6 44.5 ± 1.4 0.333
gence agitation during recovery between the two groups.
Amount of Infusion 1792.3 ± 398.1 1788 ± 460.5 0.961
Additionally, we assessed the VAS scores and Ramsay
(ml)
sedation scores at different stages after surgery including
Blood loss (ml) 217.9 ± 32.1 219.1 ± 34.0 0.861
5 min, 10 min, 30 min and 60 min after extubation. We
Data are expressed as mean ± SD. No significant differences were found that the VAS scores of the S group at each stage were
observed. T1–T0 means the time duration from anesthesia induction significantly lower than that of the F group, while the Ram-
to operation start
say scores of the S group at each stage were significantly
Amount of Infusion and blood loss of patients’ data were also shown
higher than that of the F group (Table 5). There results sug-
CVP central venous pressure, BIS bispectral index
gest that sufentanil had better analgesic and sedative effects
than that of fentanyl.
significant difference in these indicators between the F and
S groups. Comparison of the ­SctO2 status between the two
Additionally, we also monitored the changes in patient’s groups
hemodynamics including HR, SBP, DBP and MAP at the
time of preanesthesia, intubation, craniectomy and extuba- We monitored S ­ ctO2 at different time points and found that
tion (Table 3; Fig. 1). We did not observe any significant the ­SctO2 levels at the time of intubation were significantly
differences of HR, SBP, DBP and MAP at the time of pre- higher than that at the time of anesthesia induction in both
anesthesia between the two groups. However, the values of groups (Table 6). ­SctO2 levels reduced substantially during
all these indicators were significantly lower in the S group the surgery in both groups. However, the ­SctO2 levels at each
than those of the F group at the time of cannula, craniectomy time points were not significantly different between the two
and extubation (Table 3, P < 0.05). These results suggest that groups (Fig. 2).
sufentanil had a better effect in suppressing stress response We then calculated the average S ­ ctO2 during the whole
than fentanyl. Compared to fentanyl, sufentanil was better monitoring duration, minimum S ­ ctO2 and relative maximum
in ensuring the hemodynamic stability of the patients and decline of S­ ctO2 in the two groups (Table 7; Fig. 3). We
achieved a better anesthetic effect. found that S
­ ctO2 levels during the surgery were significantly
higher than that at the time of intubation after anesthesia
Comparison of the recovery status of the two groups induction. Additionally, the relative maximum decline of
after surgery ­SctO2 of the S group was smaller than that of the F group.

We recorded the duration of respiratory restoration, eye MoCA assessment and incidence of POCD
opening, extubation and orientation recovery of the subjects
as well as the body movement during anesthesia, the pres- We assessed the patient’s cognitive function by the MoCA
ence of pediatric anesthesia emergence delirium (PAED) and scale on the day before surgery, 1 day after surgery and

Table 3  Changes of hemodynamics in patients at different time periods

Time HR (times/min) SBP (mm Hg) DBP (mm Hg) MAP (mm Hg)
F S P F S P F S P F S P

Preanesthesia 83 ± 16 83 ± 17 0.995 134 ± 13 135 ± 16 0.740 78 ± 10 78 ± 12 1.00 97 ± 14 98 ± 18 0.760
Cannula 71 ± 7 59 ± 6 0.000 107 ± 12 106 ± 18 0.752 63 ± 9 56 ± 8 0.000 76 ± 6 74 ± 7 0.141
Craniectomy 80 ± 12 79 ± 7 0.623 120 ± 19 107 ± 13 0.000 69 ± 12 60 ± 7 0.000 80 ± 10 73 ± 13 0.004
Extubation 84 ± 10 80 ± 5 0.017 131 ± 9 114 ± 12 0.000 81 ± 10 73 ± 8 0.000 99 ± 16 88 ± 17 0.002

Data are expressed as mean ± SD

Before anesthesia, no significant differences were observed. After anesthesia, Group S showed lower HR, SBP, DBP and MAP than Group F in
statistical significance
HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure, MAP mean arterial pressure, F Group F, S Group S

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Aging Clinical and Experimental Research

Fig. 1  Changes of hemodynamics in patients at different time peri-
ods. The changes of HR (top left), SBP (top right), DBP (lower left)
and MAP (lower right) values at the time nodes of preanesthesia,
cannula, craniectomy and extubation. Black dashed line represents
Group F, grey solid line represents Group S. Error bar means SD.
HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood
pressure; MAP, mean arterial pressure. F Group F, S Group S. Data
are expressed as mean ± SD. Preanesthesia, no significant differences
were observed. After anesthesia, Group S showed lower HR, SBP,
DBP and MAP than Group F in statistical significance

Table 4  Recovery times, number of patients with movement or emergence agitation

Group n Respiratory restora- Eye opening Extubation Recovery time of Body movement dur- PAED PONV
tion time (min) time(min) time (min) orientation (min) ing anesthesia

F 48 10.1 ± 2.1 11.0 ± 2.4 13.0 ± 2.9 12.9 ± 2.1 5 ± 2.1 8 ± 2.1 10 ± 2.1

S 48 6.9 ± 1.1 7.9 ± 0.8 9.2 ± 1.4 9.8 ± 1.9 2 ± 0.5 3 ± 1.2 3 ± 1.1
P / 0.000 0.000 0.000 0.000 0.000 0.000 0.000

The first four variables are expressed as mean ± SD. The comparison of each variable was observed significant differences
PAED Pediatric Anesthesia Emergence Delirium, PONV Post-operative nausea and vomiting

Table 5  VAS score and Ramsay sedation score were compared between the two groups at different stages after operation
Group n 5 min after extubation 10 min after extubation 30 min after extubation 60 min after extubation

VAS score F 48 4.52 ± 0.12 5.10 ± 0.13 6.09 ± 0.08 6.81 ± 0.16

S 48 2.50 ± 0.12* 2.52 ± 0.13* 3.05 ± 0.14* 3.12 ± 0.10*
P / / 0.000 0.000 0.000 0.000
Ramsay score F 48 2.20 ± 0.33 2.41 ± 0.25 2.39 ± 0.14 2.06 ± 0.36
S 48 3.24 ± 0.17* 3.55 ± 0.24* 3.30 ± 0.25* 3.20 ± 0.21*
P / / 0.000 0.000 0.000 0.000

Data are expressed as mean ± SD

*P < 0.05

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 Aging Clinical and Experimental Research

Table 6  Changes of ­SctO2 in Group T0 T1 T2 T3 T4 T5

patients at different time periods
(%) F 70.5 ± 2.9 73.8 ± 2.6 73.6 ± 2.4 72.5 ± 2.0 70.4 ± 2.5 69.3 ± 2.7
S 70.4 ± 4.8 74.8 ± 3.4 74.1 ± 3.6 72.8 ± 2.9 70.0 ± 2.0 68.8 ± 2.8
P 0.903 0.113 0.431 0.561 0.397 0.381

Cerebral oxygen saturation, ­SctO2. Data are expressed as mean ± SD. No significant differences were
observed between the two groups

while 11 cases in the F group were diagnosed (P < 0.05). The

results were consistent with the intraoperative ­SctO2 status
between the two groups.

Discussion

This study comprehensively evaluated and compared the

anesthetic and analgesic efficacies of fentanyl and sufentanil
in elderly patients undergoing open surgery. Our study of 96
subjects with similar demographic characteristics showed
that the administration of fentanyl and sufentanil resulted in
similar general conditions such as the duration from induc-
tion of anesthesia to the beginning of operation, CVP and
BIS, and did not differ significantly in the volume of infusion
Fig. 2  Changes of ­SctO2 of two different groups at different time
and the amount of blood loss during the surgery. Sufentanil
periods. The changes of ­SctO2 at T0 (after anesthesia induction), T1 administration resulted in better inhibition of stress response
(beginning of the surgery), T2 (30  min after the surgery began), T3 during anesthesia and more stable hemodynamic properties
(1  h after the surgery began), T4 (2  h after the surgery began), T5 than fentanyl, indicating that sufentanil had a better anes-
(extubation). ­SctO2, Cerebral oxygen saturation. Black dashed line
represents Group F, grey solid line represents Group S. Error bar
thetic effect than fentanyl in elderly patients. In terms of
means SD recovery, sufentanil resulted in faster recovery from anes-
thesia as manifested by shortened durations to restoring res-
piration, eye opening and extubation as well as recovery of
Table 7  The changes of ­SctO2 in the two groups during the whole orientation compared to fentanyl. Pain and sedation assess-
monitoring period (%) ments by VAS and Ramsay scales indicated that sufentanil
Group n Average ­SctO2 Minimum ­SctO2 Relative maxi- had a better analgesic and sedative effect than fentanyl. Mon-
mum decline of itoring cerebral oxygenation by oximeter revealed that both
­SctO2 sufentanil and fentanyl resulted similar changed in ­SctO2
F 48 76.1 ± 2.3 62.0 ± 2.4 23.0 ± 4.9 levels at each time point and similar average and minimum
S 48 73.9 ± 1.5 63.8 ± 2.8 14.2 ± 5.0 ­SctO2 levels. However, patients administered with sufentanil
P / 0.000 0.001 0.000 had a smaller maximum decline than fentanyl. Finally, our
study showed that the cognitive functions of patients were
SctO2, Cerebral oxygen saturation. Data are expressed as mean ± SD. significantly impaired in both groups 1 day after surgery
No significant differences were observed
and the decline was more pronounced in patients receiving
fentanyl. To our knowledge, this is the first study comparing
7 days after surgery (Table 8; Fig. 4). We found that com- the anesthetic effects and POCD incidence between fentanyl
pared to the scores of the day before surgery, the scores and sufentanil administration in elderly patients receiving
after surgery were significantly reduced in both groups. The open surgery.
MoCA score of the S group at 1 day after surgery was sig- Pressor response is a phenomenon caused by changes in
nificantly higher than that of the F group and the scores from blood pressure and HR during intubation and operation that
other time points were not significantly different between may lead to severe adverse effects in patients undergoing
the two groups. Additionally, we found that the incidence of surgery if not properly controlled [16]. Both fentanyl and
POCD was significantly lower in the S group than that of the sufentanil have been shown to improve hemodynamic stabil-
F group. In the S group, 3 cases were diagnosed with POCD ity and enhances the duration of analgesia [17]. A previous

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Aging Clinical and Experimental Research

Fig. 3  The changes of ­SctO2 in

the two groups during the whole
monitoring period. From left to
right shown the average S ­ ctO2,
Minimum ­SctO2 and Relative
maximum decline of ­SctO2 of
the two groups, respectively.
­SctO2, Cerebral oxygen satura-
tion. Black bar represents Group
F, gray bar represents Group S,
which were shown in the top-
right corner of the figure. The
statistics results were shown in
the top of each bar pair. n.s.,
P > 0.01; ***P < 0.001

Table 8  Comparison of MoCA scores between two groups at differ- study with patients aging between 18 and 65 years from the
ent time points emergency department showed that there were no differ-
Group n 1 day 1 day after operation 7 day after operation ences in the effects of fentanyl and sufentanil on the hemo-
before dynamic stability [10]. Interestingly, our study revealed that
operation sufentanil had a better effect on the maintenance of hemo-
F 48 27.7 ± 1.3 22.9 ± 1.0(*) 26.3 ± 1.2
dynamic stability and suppression of pressor response. This
S 48 27.9 ± 1.6 26.0 ± 1.6 27.0 ± 1.1
discrepancy may be due to the differences in the subjects.
P / 0.504 0.000 0.004
To better compare the anesthetic effects of these two drugs,
we focused on a relatively homogeneous group of patients
The average MoCA scores of the two groups which were tested on with similar demographic information and excluded factors
the day before operation day, One day after the operation day and that might interfere with the effects. However, since we only
7  days after the operation day, respectively. Data are expressed as
mean ± SD studied elderly patients undergoing open surgery, applica-
MoCA Montreal Cognitive Assessment tion of our findings to other age groups or patients requiring
*P < 0.05 anesthetics due to other causes may need further validation.
Nevertheless, our finding that sufentanil is superior in the
maintenance of hemodynamic stability during anesthesia is
of important clinical significance and warrants further study.
Previous studies have shown that early postoperative
recovery is affected by intraoperative anesthetics [18].
Extended recovery may induce multiple adverse effects such
as neurological dysfunctions and respiratory complications
[19, 20]. Therefore, it is important to ensure early recovery
from anesthetics after surgery. In our study, we compared the
recovery status of patients between fentanyl and sufentanil
administration. Importantly, our results indicate that sufen-
tanil significantly reduced the duration to recovery including
shortened time to restoration of respiration, opening of eyes,
extubation and recovery of orientation. Additionally, sufen-
tanil also had better effects in analgesia and sedation in the
subjects. These results are consistent with a previous study
showing the sufentanil was better in analgesia, sedation and
Fig. 4  Comparison of MoCA scores between two groups at differ- recovery than fentanyl in patients undergoing balloon mitral
ent time points. From left to right, the average MoCA scores of the valvotomy [21]. The consistent findings suggest that sufen-
two groups which were tested on the day before operation day, One
day after the operation day and 7 days after the operation day, respec-
tanil may also exert better recovery and analgesic effects in
tively. Black bar represents Group F, gray bar represents Group S, other clinical settings.
which were shown in the top-right corner of the figure. The signifi- Intraoperative ­SctO2 has been shown to be associated
cant statistics results were shown in the top of each bar pair. MoCA with postoperative neurological function [22, 23]. More
Montreal Cognitive Assessment; **0.01 < P < 0.05; ***P < 0.01

13

than 20% of reduction of ­SctO2 from baseline was associated
with high incidence of POCD and brain dysfunction such as
cerebral ischemia [24]. We thus assessed ­SctO2 in the sub-
jects at different time points including a baseline condition
measured after anesthesia induction and different stages of
surgery. Interestingly, our results showed that at the begin-
ning of surgery, there was an increase in the levels of S­ ctO2
compared to baseline and these levels declined gradually
during the surgery. This initial increase followed by grad-
ual decrease phenomenon is similar to a previous study in
patients undergoing transcatheter aortic valve replacement
[24]. Interestingly, we did not find any significant differ-
ence in the levels of S­ ctO2 at each time points between the
F and S groups. However, a more detailed analysis showed
that relative maximum decline of ­SctO2 in the S group is
significantly smaller than the F group. This result is in line
with our finding that the incidence of POCD in the S group
is significantly lower in the S group than that of the F group.
POCD is associated with anesthesia and surgery and
occurs more frequently in elderly patients [25]. Previously
it has been shown that cognitive function is differentially
affected by different anesthesia methods while some studies
showed no difference between two specific anesthetics [26].
Comparison between sevoflurane and propofol anesthesia
showed that these two anesthetics did not differ signifi-
cantly in POCD incidence or ­SctO2 of patients undergoing
lung surgery [27]. De Cosmo et al. compared the effects
of remifentanil and fentanyl and did not find any advan-
tages of remifentanil in reducing the incidence of POCD
[28]. Similarly, Rasmussen et al. did not find any difference
between remifentanil and sufentanil in the POCD incidence
in patients undergoing cardiac surgery [29]. Other studies
also revealed controversial conclusions on the effects of
remifentanil and sufentanil. A study by Bilotta et al. showed
that propofol-remifentanil resulted earlier cognitive recovery
than propofol sufentanil in patients undergoing supratento-
rial craniotomy [30]. On the other hand, Martorano et al.
found that sufentanil-propofol resulted better postoperative
cognitive function in patents undergone neurosurgery that
remifentanil-propofol [31]. Both fentanyl and sufentanil have
been shown to be neurotoxic in rats [32]. A previous study
by Silbert et al. showed that high dose fentanyl was better
in reducing early postoperative POCD resulting in shorter
hospital stay than that of low dose fentanyl [33]. However,
a comparison between the two drugs in clinically setting has
not been available. In the current study, we for the first time
compared the cognitive function of elderly patients between
fentanyl and sufentanil administration. We used a dose of
fentanyl that was higher that the Silbert study. Our results
showed that the incidence of POCD is higher in patients
receiving fentanyl than sufentanil 1 day after surgery. How-
ever, the effect is transient. We did not observe any signifi-
cant difference in the cognitive function 7 days after surgery.
13
Aging Clinical and Experimental Research
Opioid analgesics have been shown to be negatively asso-
ciated with cognitive function. Patients with chronic pain
taking opioid analgesics perform worse in tests of cogni-
tive functions and cessation of opioid significantly improves
neurocognition including verbal learning and memory [34,
35]. Although both sufentanil and fentanyl are potent opi-
oid agonists that induce neuronal hyperpolarization and sup-
press neuronal excitability and both of them possess similar
pharmacodynamics properties, previous studies have shown
that sufentanil is a more potent opioid than fentanyl [36].
Consistently, our study showed that use of sufentanil as an
anesthetics resulted a faster recovery than fentanyl. Even
though the mechanisms underlying anesthetics induced
cognitive impairment are still elusive, previous studies have
indicated that the effects of anesthesia on cognition is related
to the pharmacokinetics of the anesthetics and shorter action
duration is correlated with shorter duration of POCD and
that longer duration of anesthesia is associated with longer
respiratory depression [37]. This is in fact consistent with
our finding that lower incidence of POCD was identified
in patients taking the faster acting sufentanil than fentanyl.
Although beyond the scope of our current study, our inter-
esting finding warrants future studies on the more detailed
molecular mechanisms underlying the different effects of
sufentanil and fentanyl on cognitive function.
One limitation of this study is that this is one center
study and patients were recruited in the study when they
were admitted to our hospital for surgery. This may cause
sampling bias. Further multi-center randomized studies are
required to confirm our findings.
Conclusion
Sufentanil provided a better hemodynamic stability and
analgesic and sedative effects without causing more adverse
events than fentanyl. Importantly, patients in the group of
sufentanil administration recovered faster, showed a reduced
maximum ­SctO2 decline and reduced incidence of POCD
compared to that of fentanyl. These findings suggest that
sufentanil may be preferred for use in elderly patients under-
going open surgery. Our promising results warrant further
research on the application of sufentanil in other clinical
scenarios.
Funding  No sources of funding were used to assist in the preparation
of this article.
Compliance with ethical standards 
Conflict of interest  Jun Zhang, Liang Chen, Yunyun Sun and Wen-
sheng He have no conflict of interest to declare.
Aging Clinical and Experimental Research
Statement of human and animal rights  All human studies were in
accordance with Declaration of Helsinki, Ethical Principles for Medi-
cal Research Involving Human Subjects.
Informed consent  Informed consents were derived from all partici-
pants.
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