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Ding et al. BMC Anesthesiology (2023) 23:135
https://doi.org/10.1186/s12871-023-02078-0 BMC Anesthesiology
†Xiahao Ding and Dapeng Chen contributed equally to this study.
*Correspondence:
Bo Gui
guibosy@163.com
1Department of Anesthesiology and Perioperative Medicine, 1st Affiliated
Hospital with Nanjing Medical University, Nanjing 210029, China
2Department of Anesthesiology, The Huai’an Maternity and Child
Healthcare Hospital, Huai’an 223002, China
3Department of Anesthesiology, Jiangsu Province Official Hospital,
Nanjing 210009, China
4Department of General Surgery, 1st Affiliated Hospital with Nanjing
Medical University, Nanjing 210029, China
Abstract
Background Postoperative nausea and vomiting (PONV) is a common and distressing complication of laparoscopic
bariatric surgery (LBS). Penehyclidine hydrochloride has been reported to be effective in preventing PONV.
Considering the potential preventive effects of penehyclidine against PONV, we hypothesized that intravenous
infusion of penehyclidine may alleviate PONV within the first 48 h in patients scheduled for LBS.
Methods Patients who underwent LBS were randomly assigned (1:2) to receive saline (Control group, n = 113) or a
single intravenous dose of penehyclidine 0.5 mg (PHC group, n = 221). The primary outcome was incidence of PONV
within the first 48 h postoperatively. Secondary endpoints included severity of PONV, need for rescue antiemetic
therapy, volume of water intake, and time to first flatus.
Results PONV occurred in 159 (48%) patients within the first 48 h postoperatively, including 51% in the Control
group and 46% in the PHC group. There was no significant difference in the incidence or severity of PONV between
the two groups (P > 0.05). Within the first 24 h and 24–48 h, no significant difference was found in incidence or
severity of PONV, postoperative nausea, postoperative vomiting, need for rescue antiemetic therapy, or volume of
water intake (P > 0.05). Kaplan–Meier curves showed that penehyclidine was significantly associated with a prolonged
time to first flatus (median onset time: 22 h vs. 21 h, P = 0.036).
Conclusions Penehyclidine did not decrease incidence and severity of PONV in patients undergoing LBS. However, a
single intravenous dose of penehyclidine (0.5 mg) was associated with a slightly prolonged time to first flatus.
Trial registration Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.
aspx?proj=134893, date of registration: 25/10/2021).
Keywords Laparoscopic bariatric surgery, Penehyclidine hydrochloride, Postoperative nausea and vomiting, Time to
first flatus
Penehyclidine hydrochloride for treating
postoperative nausea and vomiting after
laparoscopic bariatric surgery: a double-
blinded randomized controlled trial
Xiahao Ding1†, Dapeng Chen1†, Jinxing Che1,2, Siyang Xu1,3, Hui Liang4 and Bo Gui1*
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Page 2 of 9
Ding et al. BMC Anesthesiology (2023) 23:135
Background
Laparoscopic bariatric surgery (LBS) has been gener-
ally recognized as a safe and effective procedure for
obese adults, given the global prevalence of overweight
and obesity [1, 2]. Postoperative nausea and vomiting
(PONV) is a common and distressing complication after
a surgery involving general anesthesia. PONV occurs
frequently after LBS, at an incidence of 35–89% [3, 4].
Moreover, PONV has been shown to be strongly corre-
lated with several adverse clinical consequences, such as
patient dissatisfaction, incision disruption, water-elec-
trolyte imbalance, prolonged length of hospital stay, and
increased medical expenses [3, 5]. As such, increasing
attention has been paid to this common and burdensome
complaint. Multiple intervention strategies are required
to prevent and manage PONV after LBS.
e etiology of PONV is multifactorial involving
patient, surgical, and anesthesia-related factors. Several
types of neurotransmitters, including serotonin, dopa-
mine, muscarine, neurokinin-1, opioids, and histamine
are closely associated with PONV [6]. Stimulation of ves-
tibular-cochlear, glossopharyngeal, and vagus nerves may
also be responsible for occurrence of PONV. Preclinical
and clinical evidence revealed that multi-modal approach
to target these pharmacological sites is important for
controlling PONV [7]. Penehyclidine hydrochloride is
an anticholinergic drug widely used for the treatment of
organic phosphorus poisoning, as preanesthetic medica-
tion, and for the protection of certain visceral organs [8].
Prophylactic medication with penehyclidine may prevent
PONV in patients undergoing gynecological laparoscopic
surgery, bimaxillary orthognathic surgery, and strabismus
surgery [9–11]. e underlying mechanism of penehycli-
dine may be related to the inactivation of the M3 mus-
carinic acetylcholine receptor [12, 13]. A combination of
prophylactic antiemetic drugs with different mechanisms
of action should be administered to patients with moder-
ate to high risk of developing PONV.
Considering the potential preventive effects of pene-
hyclidine against PONV, we hypothesized that intrave-
nous infusion of penehyclidine may alleviate PONV and
improve postoperative recovery within the first 48h in
patients scheduled for LBS.
Methods
Study design and ethical approval
is prospective, double-blinded, randomized con-
trolled trial was conducted in an accredited bariatric
center of a tertiary hospital in China between 01/11/2021
and 13/05/2022. e study protocol was approved by
the Ethics Committee (No. 2020-SR-059, 11/03/2020)
and registered in the Chinese Clinical Trial Registry
(ChiCTR2100052418, 25/10/2021). All participants
signed an informed consent form before enrollment in
the study. is study is reported in line with the Con-
solidated Standards of Reporting Trials (CONSORT)
guidelines.
Study participants
e same surgeon performed all procedures, includ-
ing laparoscopic sleeve gastrectomy (LSG), laparoscopic
sleeve gastrectomy plus duodenojejunal bypass (LSG-
DJB), laparoscopic sleeve gastrectomy plus jejunojejunal
bypass (LSG-JJB), and one anastomosis gastric bypass
(OAGB). e inclusion criteria were the American Soci-
ety of Anesthesiologists (ASA) physical status I–III, aged
18–60 years, and scheduled for elective LBS under gen-
eral anesthesia. e exclusion criteria were listed as fol-
lowed: contraindication to penehyclidine administration
(glaucoma, basal ganglia disease, Parkinson’s disease,
pheochromocytoma, myasthenia gravis, severe central
nervous depression, and ECG showing prolonged Q-T
interval) and already using antiemetic drugs within 48h
before surgery.
Randomization and blinding
e participants were randomly assigned (1:2) using a
computer-generated randomization system to receive
saline (Control group) or a single intravenous dose of
penehyclidine 0.5 mg (PHC group) (Chengdu Lisite
Pharmaceutical Co., Ltd., Chengdu, China) after enroll-
ment into the trial. e random allocation sequence was
sealed in opaque envelopes. Participants, care providers,
and investigators were all blinded to treatment allocation.
For safety reasons, the anesthesiologists responsible for
administering the anesthetic were aware of the grouping.
However, they were not responsible for the postoperative
assessment and data collection.
Anesthesia protocol
After the patients arrived in the operating room, elec-
trocardiogram (ECG), blood pressure (BP), oxygen
saturation (SpO2), heart rate (HR), end-tidal carbon
dioxide (EtCO2), and body temperature (T) were moni-
tored. All patients received a loading infusion of lactated
Ringer’s solution (10 ml/kg). Anesthesia induction was
accomplished using dexamethasone 10 mg, midazolam
0.05mg/kg, propofol 1.5‒2.5mg/kg, fentanyl 4–6µg/kg,
plus rocuronium 0.9mg/kg or cis-atracurium 0.15mg/
kg to facilitate tracheal intubation. Meanwhile, patients
in the PHC group received a single intravenous dose of
penehyclidine 0.5mg, while patients in the Control group
received same volume of saline. All patients were endo-
tracheally intubated and mechanically ventilated with
a tidal volume of 6–8 ml/kg (ideal body weight) and a
respiratory rate of 12–16 breaths per minute to main-
tain EtCO2 at the level of 35–45 mmHg. Anesthesia
was maintained with a continuous infusion of propofol
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Ding et al. BMC Anesthesiology (2023) 23:135
100–200 µg/kg/min, remifentanil 0.05–0.15 µg/kg/min,
rocuronium 5–10µg/kg/min or cis-atracurium 1–3µg/
kg/min. e depth of anesthesia was monitored using
the bispectral index, which was maintained between 40
and 60. Neuromuscular blocking drugs (NMBDs) were
selected according to the choice of reversal agent. Only
patients with a BMI ≥ 35kg/m2 undergoing elective LBS
are recommended to receive sugammadex for neuromus-
cular blockade (NMB) reversal in our center. If NMB was
reversed by sugammadex, rocuronium would be used
for both induction and maintenance. If neostigmine, cis-
atracurium would be used instead. e sevoflurane con-
centration was adjusted as necessary. BP was maintained
at a fluctuation of ± 20% of the baseline value by adjusting
the depth of anesthesia or using vasoactive agents during
surgery. All patients received a single intravenous dose of
palonosetron (0.25mg) 30min before the completion of
surgery. Continuous infusion of rocuronium or cis-atra-
curium was stopped after deflation of the pneumoperi-
toneum, and the infusion of propofol and remifentanil
was discontinued at completion of surgery. Patients were
admitted to the post-anesthesia care unit (PACU) with
an endotracheal tube for recovery from anesthesia. We
used clinically physical signs for assessing the recovery of
neuromuscular function and guiding the use of antago-
nists of NMBDs. NMB was allowed to recover sponta-
neously to the moderate block state, and the residual
effects of rocuronium were antagonized via administra-
tion of either sugammadex 200mg or neostigmine 2mg
plus atropine 1mg. Ventilatory support was maintained
until a unified extubation standard was achieved. Tra-
cheal extubation was performed according to a standard-
ized protocol: fully conscious, stable circulation (BP and
HR remain within 20% of the baseline values without any
inotropes), a respiratory rate < 30 breaths/min, maximal
inspiratory pressure < − 20 cmH2O, tidal volume > 6 ml/
kg, SpO2 > 93% as well as ability to lift head for 5s. e
criterion used for patient discharge from PACU was the
achievement of a modified Aldrete score ≥ 9 [14]. After
patients returned to the ward, an intramuscular injection
of metoclopramide 10 mg was administered as an ini-
tial rescue antiemetic therapy at the request of a patient
or when a patient experienced > 5 episodes of vomiting
within 24 h. If the symptoms persisted one hour after
metoclopramide administration, another 10mg of meto-
clopramide was administered as a second rescue drug.
No more than 20mg of metoclopramide was allowed in
any 24-h period. A total of 10mg of dezocine was admin-
istered intravenously as rescue analgesia in the ward
when the visual analog scale score was ≥ 4.
Data collection
Data on clinical characteristics, including age, sex, body
mass index, coexisting disorders, and potential risk
factors for PONV, were collected to assess comparabil-
ity. We also recorded the simplified Apfel score for each
patient [15]. e primary outcome was incidence of
PONV within the first 48 h postoperatively. Secondary
endpoints included severity of PONV, need for rescue
antiemetic therapy, volume of water intake, and time to
first flatus. PONV was defined as at least one episode of
nausea, vomiting, retching, or any combination of these
symptoms. PONV was evaluated as follows: I = no nau-
sea or vomiting, II = nausea but no vomiting, III = mild to
moderate vomiting, and IV = severe and frequent vom-
iting more than five times within 24h. e severity of
postoperative nausea (PON) was assessed with a numeric
rating scale (I = mild, II = moderate, III = severe). e
severity of postoperative vomiting (POV) was recorded
according to the number of vomiting episodes (I = no
vomiting, II = vomiting episodes occurring 1–2 times
within 24h, III = vomiting episodes occurring 3–5 times
within 24 h, IV = vomiting episodes occurring > 5 times
within 24h). e simplified Apfel score contains four risk
factors, including female gender, history of motion sick-
ness or PONV, nonsmoking status, and postoperative
opioid use. Intraoperative opioid consumption means
the total amount of opioids used in the operating room
and PACU. All opioid doses were converted to morphine
intravenous equivalent. According to clinical guidelines,
patients were instructed to drink clear liquids for the first
24–48h after LBS, with the volume gradually increasing
to 2L to promote the recovery of gastrointestinal func-
tion [16]. Accordingly, the volume of postoperative water
intake was measured during the two periods (0–24 h
and 24–48h). e time to first flatus was defined as the
time to the first passage of flatus, as reported by patients,
minus the end time of the surgery.
Sample size
e sample size calculation was based on our preliminary
data, which indicated that 55% of the patients experi-
enced PONV within the first 48h postoperatively. us,
we considered a 35% reduction in the incidence of PONV
as clinically significant. e required sample size was
estimated using Power Analysis and Sample Size software
(PASS, version 15.0. NCSS, LLC. Kaysville, Utah, USA).
e result suggested that 104 patients in the Control
group and 207 in the PHC group would be necessary to
achieve a power of 90% (β = 0.1) with a two-sided confi-
dence interval of 95% (α = 0.05). Considering an attrition
rate of approximately 10%, we increased the sample size
to 346 patients (116 in the Control group and 230 in the
PHC group).
Statistical analysis
Descriptive statistics are presented as mean ± standard
deviation for continuous variables and as frequencies or
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Page 4 of 9
Ding et al. BMC Anesthesiology (2023) 23:135
proportions for categorical variables. Normal distribu-
tion of the data was confirmed using the Shapiro–Wilk
test. For normally distributed data, an independent Stu-
dent’s t-test was used to assess significant differences
between the two groups. For data with a skewed distri-
bution, the Mann–Whitney U test was used. Categorical
variables were analyzed using either the chi-square test
or Fisher’s exact test, as appropriate. ere were no miss-
ing values in our findings. Statistical significance was set
at P < 0.05. All statistical analyses were performed using
IBM SPSS Statistics for Windows (version 21.0. SPSS Inc.
Chicago, Illinois, USA).
Results
A flow diagram of the study is shown in Fig.1. A total
of 362 patients undergoing elective LBS were assessed for
eligibility, of whom 346 were available for primary analy-
sis between 01/11/2021 and 13/05/2022. Sixteen patients
were excluded before randomization because they did
not meet the inclusion criteria (n = 13), declined to par-
ticipate (n = 1), or case cancellation on the day of surgery
(n = 2). ree patients in the Control group were excluded
because of changes in the surgical procedure during the
operation (n = 2) and unscheduled ICU admission (n = 1).
Nine patients in the PHC group were excluded owing to
temporary alteration of the surgical procedure (n = 5),
severe intraoperative arrhythmia (n = 1), and unsched-
uled ICU admission (n = 3). Ultimately, 113 patients in the
Control group and 221 in the PHC group were examined.
e baseline demographics and intraoperative variables
of patients are shown in Table1. Participant characteris-
tics were similar between the two groups (P > 0.05).
PONV occurred in 159 (48%) patients within the first
48h postoperatively, including 58 (51%) patients in the
Control group and 101 (46%) in the PHC group (Table2).
ere was no significant difference in the incidence or
severity of PONV between the two groups (P > 0.05).
Within the first 24h postoperatively, 48% of the patients
experienced PONV. e incidence of PONV decreased
to 14% in the Control group and 11% in the PHC group
within 24–48 h after surgery (Table 3). As shown in
Table 3; Fig. 2, the incidence of PONV was almost
the same in both groups during the two time periods
(P > 0.05). Specifically, no significant difference was found
in the incidence or severity of PONV, PON, or POV
within the first 48h after LBS (P > 0.05).
As shown in Tables2 and 3, no significant difference
was observed in the proportion of patients receiving
postoperative rescue antiemetic therapy or the amount
Fig. 1 Flow diagram of patients enrolled in the study. ICU intensive care units, PHC penehyclidine hydrochloride
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Page 5 of 9
Ding et al. BMC Anesthesiology (2023) 23:135
of water intake between the two groups during the two
postoperative periods (P > 0.05).
As shown in Fig.3, the time to first flatus was signifi-
cantly higher in patients in the PHC group (median onset
time, 22h) than in those in the Control group (median
onset time, 21h), as shown by the Kaplan–Meier curves
(P = 0.036).
Discussion
In this prospective, double-blinded, randomized con-
trolled trial, our findings show that 48% of the patients
experienced PONV within the first 48h postoperatively,
with 51% in the Control group and 46% in the PHC
group. Moreover, the expected results were not obtained.
During the early postoperative period, penehyclidine
failed to induce a significant difference with respect to
the incidence and severity of PONV, PON, and POV;
need for rescue antiemetic therapy; or volume of water
intake. However, a single intravenous dose of penehycli-
dine (0.5 mg) was associated with a slightly prolonged
time to first flatus.
e consensus guidelines for the management of
PONV include bariatric surgery as having an increased
risk of PONV [17]. However, the complex etiology and
pathophysiology of PONV remain elusive. e gut vagal
afferent fibers innervate the gastrointestinal tract and
constitute a specific neural pathway to the nucleus of the
solitary tract in the hindbrain that triggers vomiting [18,
19]. Considering that surgical manipulation involves the
gastric vagal nerve, the stimulation of these fibers may
be responsible for the high incidence of PONV after
LBS, especially in LSG. is would explain why patients
undergoing LSG are more prone to develop PONV than
those undergoing other bariatric procedures [3, 4]. More-
over, current evidence strongly suggests a role for the use
of CO2 pneumoperitoneum in the pathogenesis of PONV
[20, 21]. e CO2 pneumoperitoneum is attributed to
increased intra-abdominal pressure, which decreases
intestinal blood flow, especially in obese patients. In
addition to residual intra-abdominal CO2, a recently pub-
lished retrospective study by Lu et al. [22] suggested that
aseptic inflammation caused by ischemia and hypoxia
also plays a role in the occurrence of PONV by inducing
the release of a variety of transmitters. e reason is that
the intestine is probably the most sensitive internal organ
for ischemia. Even short periods of ischemia can induce
the release of neurotransmitters, such as serotonin, that
could stimulate the emetic chemoreceptor trigger zone
Table 1 Baseline demographics and intraoperative variables
Variable Control
group
(n = 113)
PHC group
(n = 221)
P-value
Age (years) 34 ± 9 33 ± 8 0.347
Sex (Male) 25 (22) 68 (31) 0.091
Height (cm) 168 ± 8 168 ± 8 0.909
Weight (kg) 108 ± 25 107 ± 23 0.503
BMI (kg/m2)38 ± 7 38 ± 7 0.391
ASA physical status
II 49 (43) 103 (47) 0.573
III 64 (57) 118 (53)
Apfel risk score
0 2 (2) 12 (5) 0.126
1 13 (11) 39 (18)
2 48 (42) 97 (44)
3 46 (41) 67 (30)
4 4 (4) 6 (3)
Comorbidities
Diabetes mellitus 42 (37) 84 (38) 0.881
Hypertension 22 (20) 43 (20) 0.998
Smoking 17 (15) 46 (21) 0.196
History of motion sickness 3 (3) 6 (3) 0.974
Types of surgery
LSG 70 (62) 134 (61) 0.904
LSG-JJB 28 (25) 55 (25)
LSG-DJB 10 (9) 18 (8)
OAGB 5 (4) 14 (6)
Duration of the anesthesia (min) 93 ± 22 92 ± 23 0.619
Duration of the operation (min) 77 ± 22 76 ± 22 0.867
IOC (mg) 56.8 ± 6.9 58.2 ± 7.5 0.103
Sugammadex 34 (30) 61 (28) 0.635
Neostigmine 79 (70) 160 (72) 0.635
Fluid infusion (ml) 1369 ± 341 1402 ± 370 0.433
Fluid output (ml) 203 ± 67 191 ± 83 0.183
Duration of mechanical ventila-
tion (min)
120 ± 28 120 ± 27 0.768
Duration of PACU stay (min) 66 ± 27 66 ± 23 0.968
Rescue opioids 75 (66) 124 (56) 0.071
Categorical data are presented as n (%), and continuous data are presented as
mean ± standard deviation
Abbreviations: ASA American Society of Anesthesiologists, BMI body mass
index, IOC intraoperative opioids consumption (as intravenous morphine
equivalent), LSG laparoscopic sleeve gastrectomy, LSG-DJB laparoscopic
sleeve gastrectomy plus duodenojejunal bypass, LSG-JJB laparoscopic sleeve
gastrectomy plus jejunojejunal bypass, OAGB one anastomosis gastric bypass,
PACU postanes thesia care unit, PHC penehyclidine hydrochloride
Table 2 Comparison of primary and secondary outcomes within
48 h postoperatively between the two groups
Variable Control
group
(n = 113)
PHC group
(n = 221)
P-
val-
ue
PONV 58 (51) 101 (46) 0.330
PON 12 (11) 22 (10) 0.850
POV 46 (41) 79 (36) 0.377
Rescue antiemetic therapy 30 (27) 49 (22) 0.376
Water intake (ml) 1645 ± 506 1571 ± 515 0.212
Categorical data are presented as n (%), and continuous data are presented as
mean ± standard deviation
Abbreviations: PHC penehyclidine hydrochloride, PONV postoperative nausea
and vomiting, PON postoperative nausea, POV postoperative vomiting
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Page 6 of 9
Ding et al. BMC Anesthesiology (2023) 23:135
and result in PONV [7, 23]. Given the high levels of
serotonin in the gut, exposing the gut to surgical proce-
dures and anesthetics may increase the excitability of the
gut–vagus–brain reflex that contributes to PONV [24].
Furthermore, PONV is associated with a higher gastric
intraluminal pressure and less distensibility after bariatric
surgery [25, 26].
To date, penehyclidine, as a preanesthetic medica-
tion, is used mainly to reduce respiratory secretions
and inhibit the vagus nerve reflex without increasing
the heart rate. Nevertheless, there is insufficient high-
quality evidence to confirm the protective effect of
penehyclidine against PONV. In a recent prospective
study of 228 pediatric patients undergoing strabismus
surgery, patients receiving penehyclidine (0.01 mg/kg,
maximal dose 0.5 mg, intravenously) after anesthesia
induction had a significantly lower incidence and severity
of PONV within 48h postoperatively [11]. e result of
the marked reduction of PONV by penehyclidine admin-
istration was revealed in the pediatric and non-obese
population, with an intervention performed not on gas-
trointestinal tract but for strabismus. However, Zhang
et al. [9] found that the incidence of POV and need for
antiemetic rescue were both lower in patients receiving
Table 3 Comparison of primary and secondary outcomes within the first 24 h and 24–48 h postoperatively between the two groups
Variable 0–24h after surgery P-value 24–48h after surgery P-value
Control
group
(n = 113)
PHC
group
(n = 221)
Control
group
(n = 113)
PHC
group
(n = 221)
PONV 58 (51) 101 (46) 0.330 16 (14) 24 (11) 0.385
Severity of PONV
I 55 (49) 120 (54) 0.481 97 (86) 197 (89) 0.147
II 12 (11) 22 (10) 11 (10) 14 (6)
III 21 (19) 45 (20) 2 (2) 9 (4)
IV 25 (22) 34 (15) 3 (3) 1 (1)
PON 12 (11) 22 (10) 0.850 11 (10) 14 (6) 0.273
Severity of PON
I 5 (4) 6 (3) 0.051 4 (4) 6 (3) 0.236
II 7 (6) 10 (5) 7 (6) 6 (3)
III 0 (0) 6 (3) 0 (0) 2 (1)
POV 46 (41) 79 (36) 0.377 5 (4) 10 (5) 0.967
Severity of POV
I 67 (59) 142 (64) 0.489 108 (96) 211 (96) 0.133
II 6 (5) 15 (7) 2 (2) 6 (3)
III 15 (13) 30 (14) 0 (0) 3 (1)
IV 25 (22) 34 (15) 3 (3) 1 (1)
Rescue antiemetic therapy 30 (27) 49 (22) 0.376 3 (3) 5 (2) 0.826
Water intake (ml) 450 ± 160 459 ± 158 0.628 1195 ± 380 1112 ± 390 0.065
Categoric al data are presented as n (%), and cont inuous data are presente d as mean ± s tandard deviation
Abbreviations: PHC penehyclidine hydrochloride, PONV postoperative nausea and vomiting, PON postoperative nausea, POV postoperative vomiting
Fig. 2 Stacked bar charts showing the severity of PONV (A), PON (B), and POV (C) within 48 h postoperatively between the two groups. The severity of
PONV was evaluated as follows: I = no nausea or vomiting, II = nausea but no vomiting, III = mild to moderate vomiting, and IV = severe and frequent vom-
iting more than five times within 24 h. The severity of PON was evaluated as follows: I = mild, II = moderate, III = severe. The severity of POV was evaluated
as follows: I = no vomiting, II = vomiting episodes occurring 1–2 times within 24 h, III = vomiting episodes occurring 3–5 times within 24 h, IV = vomiting
episodes occurring > 5 times within 24 h. PONV postoperative nausea and vomiting, PON postoperative nausea, POV postoperative vomiting
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Ding et al. BMC Anesthesiology (2023) 23:135
tropisetron, a long-acting 5-hydroxytryptamine-3 antag-
onist, than in patients receiving penehyclidine (0.01mg/
kg, maximal dose 1.0mg, intramuscularly) after gyneco-
logical laparoscopic surgery. In contrast, a combination
of tropisetron and penehyclidine was more effective in
preventing PONV than monotherapy with either tropi-
setron or penehyclidine. Considering the mean elimina-
tion half-life of penehyclidine from a pharmacokinetic
perspective, a low-dose bolus (0.5 mg, intravenously)
plus continuous infusion (a dose of 0.25mg added to 100
ml at a rate of 2 ml/h for 48h, intravenously) of pene-
hyclidine was confirmed to be more effective in reducing
PONV after bimaxillary orthognathic surgery [27]. We
speculated that the following reasons may be responsible.
First, penehyclidine may reduce the vagus nerve reflex,
which may inhibit vagal afferent activation to mitigate
PONV. Second, penehyclidine has been confirmed to
relieve gastrointestinal smooth muscle spasms by acting
on the cholinergic receptors in the glands and smooth
muscles of the digestive tract, which is effective in low-
ering gastric intraluminal pressure after surgery. ird,
a previous study suggested that penehyclidine post-con-
ditioning could improve small intestinal mucosal injury
and reduce damage to the barrier function of the small
intestinal mucosa caused by limb ischemia-reperfusion
[28]. Accordingly, we presume that improving intesti-
nal microcirculation might be beneficial in decreasing
PONV. However, penehyclidine was not found to be sig-
nificantly associated with a lower incidence of PONV
in our study. A meta-analysis confirmed that LSG is
associated with an increase in the vagal tone [29]. e
dosage of penehyclidine used in the study may have been
inadequate for the effective inhibition of the gut vagal
afferent activation. Considering that the volume of dis-
tribution of the drug in obese patients may change, the
dosage needs to be adjusted to achieve the desired effect.
erefore, we also need to bring in the assessment of the
pharmacokinetics of penehyclidine when we explored its
effects on PONV. Moreover, gastric denervation remains
difficult to avoid during LBS and may weaken penehycli-
dine’s action in relieving gastrointestinal smooth muscle
spasms. In addition, whether penehyclidine has an effect
on intra-abdominal pressure and the release of neu-
rotransmitters warrants further investigation.
Postoperative water intake volume and time to first
flatus are two important indices for evaluating recov-
ery of gastrointestinal function after surgery. Early oral
hydration after laparoscopic cholecystectomy has been
associated with a lower incidence of PONV in the ward
[30]. is may be owing to two possible reasons. First,
patients exhibiting a low incidence of PONV are more
likely to drink more water. Early oral hydration and
increased water intake reduce postoperative gastroin-
testinal tract dysfunction and accelerate gastric emp-
tying, which is beneficial for lowering PONV. Second,
theoretically, penehyclidine use may be associated with
delayed recovery of intestinal functions postoperatively
owing to its anticholinergic effects on the gastrointesti-
nal tract. Indeed, we found that penehyclidine was sig-
nificantly associated with a prolonged time to the first
flatus. But this difference is just one hour, which may be
not clinically significant. In the present study, patients
on penehyclidine treatment also showed a trend of lower
postoperative water intake volume within 24–48h after
surgery, but the difference was not significant. Although
the use of anticholinergic agents has been verified to be
the main independent risk factor for moderate-to-severe
postoperative thirst [31], this effect appeared to be mod-
est after LBS, especially in the ward.
A few issues concerning our study need to be clarified.
Sugammadex and neostigmine are both commonly used
to antagonize NMBDs-induced neuromuscular paralysis
in the clinical setting. Considering its beneficial effects
on providing fast recovery of neuromuscular function, we
tend to recommend sugammadex for the patients with
BMI ≥ 35 kg/m2 as a NMB reversal agent in our center
upon their informed consent. erefore, the differences
in the selection of NMBDs and their reversal agents may
call into the question whether the use of these medica-
tion is associated with PONV. However, we detected
no difference in the use of NMB reversal agent between
the two groups. Furthermore, rocuronium and cis-atra-
curium are both intermediate-acting nondepolarizing
NMBDs, which means the effect of the two drugs are
Fig. 3 Kaplan-Meier curves of the time to first flatus postoperatively be-
tween the two groups. CON control; PHC penehyclidine hydrochloride
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 8 of 9
Ding et al. BMC Anesthesiology (2023) 23:135
comparable. Although the train of four is not routinely
used for monitoring of curarization during surgery in our
center, both groups strictly followed the same indications
for extubation and discharge from PACU. Considering
that our primary outcome is the incidence and severity
of PONV during postoperative stay in the ward, it seems
unlikely that the choice of NMBDs and the degree of
intraoperative curarization would influence PONV long
after administration in the present study.
is study has some limitations. First, we just enrolled
patients undergoing elective LBS, who are aged 18–60
years and ASA physical status I–III. Futhermore, this
was a single-center study with relatively small sample
size, which limits the generalizability of the results. e
results of this trial should be considered with caution.
In the future, large multi-center randomized controlled
prospective studies should be conducted to comprehen-
sively observe the safety and efficacy of penehyclidine in
patients undergoing LBS. Second, further in-depth stud-
ies are needed to determine the appropriate dosage of
penehyclidine to prevent PONV in obese patients, which
needs to bring in the assessment of the volume of distri-
bution. An improved understanding of the pathophysi-
ology of PONV in patients undergoing LBS is needed to
guide future studies.
Conclusions
Penehyclidine did not decrease PONV in patients who
underwent LBS. As “metabolic surgery” is increasingly
recognized by the public, further well-designed random-
ized controlled trials are warranted to validate the results
and provide high-quality evidence for improving anti-
emetic treatment for the prevention and management of
PONV.
Abbreviations
ASA American Society of Anesthesiologists
BMI body mass index
BP blood pressure
CONSORT Consolidated Standards of Reporting Trials
ECG electrocardiogram
EtCO2 end-tidal carbon dioxide
HR heart rate
IOC intraoperative opioids consumption
LBS laparoscopic bariatric surgery
LSG-DJB laparoscopic sleeve gastrectomy plus duodenojejunal bypass
LSG-JJB laparoscopic sleeve gastrectomy plus jejunojejunal bypass
NMB neuromuscular blockade
NMBDs neuromuscular blocking drugs
OAGB one anastomosis gastric bypass
PACU post-anesthesia care unit
PHC penehyclidine hydrochloride
PONV postoperative nausea and vomiting
PON postoperative nausea
POV postoperative vomiting
SpO2 oxygen saturation
Acknowledgements
We thank Dr. Yuting Wang for the assistance of data collection. We thank Prof.
Honggang Yi for his statistical analysis assistance. We also would like to thank
Editage (www.editage.cn) for English language editing.
Author Contribution
Xiahao Ding: Data collection, methodology, formal analysis, writing – original
draft; Dapeng Chen: Methodology, formal analysis, writing – original
draft; Jinxing Che: Methodology, formal analysis; Siyang Xu: Methodology,
validation; Hui Liang: Conceptualization; Bo Gui: Conceptualization, formal
analysis, supervision, validation, writing – review and editing. All authors read
and approved the final manuscript.
Funding
This research did not receive any specific grant from funding agencies in the
public, commercial, or not-for-profit sectors.
Data Availability
The datasets generated and/or analyzed during the current study are not
publicly available due to potential patient privacy compromise but are
available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the Institutional Review Board of the 1st
Affiliated Hospital with Nanjing Medical University (IRB #2020-SR-059) on
March 11, 2020 and written informed consent was obtained from all subjects
participating in the trial. All methods were performed following the relevant
guidelines and regulations.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Received: 1 February 2023 / Accepted: 4 April 2023
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