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Cardiovascular effects of hyoscine butylbromide in patients under general

anaesthesia

Article  in  Journal of Perioperative Practice · March 2022

DOI: 10.1177/17504589211072698

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research-article2022
PPJ0010.1177/17504589211072698Journal of Perioperative PracticeQuintero et al.

Original Article The Association for Perioperative Practice

Journal of Perioperative Practice

Cardiovascular effects of hyoscine 1­–6

© The Author(s) 2022
Article reuse guidelines:
butylbromide in patients under sagepub.com/journals-permissions
DOI: 10.1177/17504589211072698
https://doi.org/10.1177/17504589211072698

general anaesthesia
journals.sagepub.com/home/ppj

Carlos Quintero1, Maria F Molano2, Sebastian Amaya3 , Jose J

Maya3 and María J Andrade3

Abstract
Background: Cardiovascular effects for drugs such as hyoscine butylbromide are poorly documented in the
literature, unlike atropine, which is considered the antimuscarinic of choice in the presence of intraoperative
bradycardia.
Aim: The aim of the study was to describe the dose-related cardiovascular effect of hyoscine butylbromide in
patients between 18 and 65 years of age, with low perioperative risk undergoing elective surgery under general
anaesthesia on an outpatient basis or hospitalised at our institution between 1 January and 31 May 2019.
Methods: Descriptive, cross-sectional, retrospective study; 28 patients with low perioperative risk who underwent
general anaesthesia were selected. Changes in heart rate and blood pressure were analysed during the first 6 minutes
after the administration of hyoscine butylbromide. The data obtained was recorded in a Microsoft Excel database and
analysed using the Excel analysis tool and IBM SPSS.
Results: The average dose of 0.15mg/kg of hyoscine butylbromide achieved an increase in heart rate and mean
arterial pressure in 96% and 92.8%, respectively, in the first 6 minutes after the administration. Significant changes in
heart rate and blood pressure were obtained during the first 6 minutes at doses between 0.05mg/kg and 0.15mg/kg.
Conclusion: Hyoscine butylbromide generates positive effects on the heart rate and blood pressure of patients
under general anaesthesia, representing a possible alternative in the management of intraoperative bradycardia.

Provenance and Peer review: Unsolicited contribution; Peer reviewed; Accepted for publication 18 December 2021.

Keywords
General anaesthesia / Cardiovascular drugs / Hyoscine butylbromide / Bradycardia / Blood pressure / Descriptive study

Introduction conducted a retrospective descriptive study of the

Hyoscine butylbromide (HB) and atropine have
similarities in their molecular structure and
pharmacodynamic properties (Evers et al 2011, Tytgat
2007). HB is mainly used for its antispasmodic effects
in treatment of abdominal cramps induced by
gastrointestinal spasms (Tytgat 2007). However, there
are few studies that evaluate the use of HB in the
treatment of intraoperative bradycardia. One study
carried out in the equine surgical setting found that the
use of this drug induced tachycardia and arterial
hypertension (Perotta et al 2014). Likewise, a study by
Grainger and Smith (1983) found that the use of HB
induced a positive chronotropic effect in healthy human
patients; however, the sample size for this study was
very small. The impact that HB can have on heart rate
(HR) and blood pressure (BP) during general
anaesthesia (GA) is not well documented; therefore, we
cardiovascular effects obtained after administration of
HB in patients under GA. This study was designed to
describe the positive chronotropic and vascular
properties of HB, the dose/response relationship for
this effect, and the time to onset of cardiovascular
changes after HB administration in patients during the
intraoperative period.
1
Department of Anesthesiology, Hospital Simón Bolivar, Bogotá,
Colombia
2
Department of Anesthesiology, Clinica Colsubsidio, Bogotá, Colombia
3
Anesthesiology and Critical Care Interest Group UEB, Colombian
School of Medicine, Universidad El Bosque, Bogotá, Colombia
Corresponding author:
Sebastian Amaya, Anesthesiology and Critical Care Interest Group UEB,
Colombian School of Medicine, Universidad El Bosque, Ak. 9 #131a-20,
110141 Bogotá, Colombia.
Email: samayac@unbosque.edu.co
2 Journal of Perioperative Practice 00(0)

Methods Table 1  Population demographics

A descriptive, cross-sectional, retrospective study
was carried out in which the haemodynamic variables
of patients registered in the database of our hospital
were examined and analysed between January 2019
and May 2019. For research purposes, our patient
database is regularly updated using strict
parameters; therefore, the data obtained
retrospectively were from patients who were directly
cared for by the authors; the study was approved by
the hospital’s research ethics committee. Patients
between 18 and 65 years of age, with no
cardiovascular history, classified as low perioperative
risk (ASA I and ASA II patients), who underwent
elective surgery under GA and received HB within
their intraoperative pharmacological analgesic
regimen were the selected study population. The
following patient populations were excluded:
1. Patients with intraoperative awakening
2. Patients who were administered vasopressor
medications or medications with positive
chronotropic effects
3. Patients who received antihypertensive medications
or beta-blockers
4. Pregnant women
5. Patients who presented with any contraindications
to the administration of HB
Since the patients were classified as ASA I and ASA II,
basic monitoring was performed including a three-lead
electrocardiogram, non-invasive blood pressure
measurement, pulse oximetry, capnography and
temperature. HR data (measured by visoscope with a
three or five-lead electrocardiographic recording) and
BP (obtained by automatic inflation tensiometer) were
obtained every minute, during the first 6 minutes after
the administration of HB (dose per kg of weight). The
changes in the haemodynamic variables after
administration, the average time of onset of the
cardiovascular effects and the relationship between the
dose and the observed effect were analysed.
Statistical analysis
Descriptive statistical tools were estimated, and a
univariate analysis was performed. The qualitative
variables were determined with absolute and relative
frequencies and the quantitative variables by measures
of central tendency and dispersion, mean and standard
deviation for those of normal distribution and median
and interquartile range for data without normal
distribution. The data obtained were recorded in a
Microsoft Excel database and analysed using the
Microsoft Excel data analysis tool and the IBM SPSS
statistical software. The 95% confidence intervals were
calculated, with p values less than 0.05 being
considered significant.
Variable Result
Sexa
 Female 19 (67.9)
 Male 9 (32.1)
Ageb 36 ± 29 [18–65]
ASAa
 I 13 (46.4)
 II 15 (53.6)
Antecedentsa
 Diabetes 1 (3.6)
 Hypertension 2 (7.1)
  Chronic kidney disease 0 (0.0)
 None 13 (46.4)
 Others 10 (35.7)
Table demonstrating the demographics of the patient population of this
study.
a
Absolute frequency (relative frequency).
b
Median interquartile ± Range [Minimum–Maximum].
Results
For this study, a search for patients who were
administered HB intraoperatively was done using our
hospital’s patient database, yielding a total of 52
patients for the selected time period. Of the 52, 24
patients were excluded because they did not meet the
inclusion criteria and/or had exclusion criteria. Of the
24 excluded, 11 received monitored anaesthetic care,
10 received regional anaesthesia (neuraxial regional
anaesthesia and/or peripheral regional anaesthesia),
and 3 had ASA III classification, leaving the accepted
patient population as 28 patients.
Within the demographic findings, a male:female ratio of
1: 2.1 was found, with a median age of 36 years. In
addition, 53.6% of the sample had ASA II classification,
an average weight of 62.6 kilograms, and a variety in
the presentation of associated comorbidities without
predominance of any of the medical history questioned
(arterial hypertension, diabetes mellitus type 1 and 2,
chronic kidney disease and others, such as
osteoarthritis, hypothyroidism, obesity, cerebral palsy,
convulsive syndrome, dystonia, and constitutional
syndrome) (Table 1).
Heart rate
The 28 patients in this study received an average dose
of HB (0.15mg/kg), after which increases in HR in
minutes 1, 2, 3, 4, 5 and 6 by 42%, 58%, 58%, 59%,
57% and 58%, respectively, were found. An increase in
HR was observed in 24 of the 28 patients (85%) in the
first minute and in 27 of the 28 patients (96%) from the
second minute that was maintained until the sixth
minute after the administration of HB.
Within the HR variability, the median baseline resting
HR of the patients was 64.5 beats per minute (BPM),
Quintero et al. 3

Table 2  Heart rate variability
Variable a
Result
Resting heart rate 64.50 ± 12.75 [38–84]
Dose in mg/kg  0.12 ± 0.10 [0.06–0.4]
HR minute 0 44.00 ± 13.25 [28–75]
HR minute 1 66.00 ± 22.75 [28–91]
HR minute 2 70.50 ± 18.25 [49–100]
HR minute 3 68.50 ± 19.25 [50–103]
HR minute 4 69.00 ± 16.75 [48–101]
HR minute 5 68.00 ± 19.00 [47–99]
HR minute 6 68.50 ± 20.00 [50–95]
HR: heart rate. Table demonstrating the heart rate variability before and
after medication administration.
a
Median ± interquartile range [Minimum–Maximum].
the minimum value was 38BPM, and the maximum was
84 BPM. In the first minute, a significant increase was
observed with a variation of 22 BPM. Later it was
maintained with values of 70.5 BPM, 68.5 BPM, 69
BPM, 68 BPM and 68.5 BPM at minutes 2, 3, 4, 5 and
6, respectively. There were no significant changes in the
minimum and maximum values measured at each
interval as observed in Table 2.
Likewise, a detailed analysis of the HR was performed
according to the administered dose, dividing the
patients into four groups. The first group represented
those patients who received a dose of 0.05–0.09mg/
kg of HB, the second group a dose of 0.1–0.14mg/kg,
the third group a dose of 0.15–0.19mg/kg, and the
fourth group with a dose greater than 0.2mg/kg. In the
first group, a maximum increase in the average HR of
22 BPM was obtained, which represented a 54%
increase with respect to the heart rate prior to the
administration of HB. In the second group, there was an
increase of 28.9 BPM (61%), in the third group of 42.3
BPM (102%) and in the fourth group of 18.7 BPM
(53%). Detailed heart rate results over time at minute
1, 2, 3, 4, 5 and 6 with respect to the dose are shown
in Table 3.
Once all the results of changes in HR and BP were
obtained after the administration of HB, a statistical
analysis of the variables was carried out to determine
the existence of statistical significance in the
haemodynamic changes. This test was performed with
the changes in HR according to the four different doses
of HB into which the sample was divided. The results of
the statistical analysis are detailed in Table 4.
Blood pressure
When analysing the changes in BP with the average
study dose of 0.15mg/kg, an increase in systolic BP
was found of 18% at minutes 3 and 6, an increase in
diastolic BP 35% and 33% at minutes 3 and 6
respectively, and increase in mean arterial pressure
(MAP) of 26% and 25% at minutes 3 and 6 respectively.
On the other hand, it was observed that the MAP
increased in 15 of the 28 patients (53.6%) at minute 3
after the administration of HB, and when the patients
continued to be observed until minute 6, it was
evidenced that the increase occurred in 26 of the 28
patients (92.8%) (data not shown in table).
Performing a detailed analysis of the mean BP (systolic,
diastolic and mean) according to the administered
dose, the patients were divided into four groups and
initial BP values prior to the administration of the drug
were taken into account. It was observed that in group
1 (0.05–0.09mg/kg) a maximum increase in the mean
systolic BP of up to 103.2mmHg was obtained, which
represents 18.2%. Similarly, the mean diastolic BP was
found to be up 61.9mmHg, (32.45%) and mean MAP up
75.8mmHg (25.5%). In group 2 (0.1–0.14mg/kg), there
was an increase in systolic BP of 98.0mmHg (20.1%),
mean diastolic BP of 64.5mmHg (36.5%) and mean
MAP of 75.6mmHg (28.7%). In group 3 (0.15–0.19mg/
kg), the increase in mean systolic BP was up
125.3mmHg (31.6%), mean diastolic BP up 77.6mmHg
(60.6%) and the MAP up 93.6mmHg (46%). Finally, in
group 4 (>0.2mg/kg), an increase in mean systolic BP
up 103.6mmHg (13.6%), mean diastolic BP up
64.8mmHg (39.1%) and mean MAP up 77.6mmHg
(26.3%) (Table 5).
After obtaining the results of the changes in BP at
minute 3 and minute 6 after the administration of HB in
the four groups, statistically significant changes were
obtained only in the dose groups between 0.05mg/kg
and 0.14mg/kg (Groups 1 and 2) (Table 6).

Table 3  Increase in heart rate according to dose from minute 1 to minute 6

Dose Min 1 Min 2 Min 3 Min 4 Min 5 Min 6 Patients

0.05–0.09mg/kg 17.3 (40%) 22.0 (54%) 21.5 (54%) 21.3 (54%) 19.6 (50%) 19.3 (49%) 11
0.1–0.14mg/kg 16.5 (35%) 26.9 (56%) 26.0 (55%) 27.3 (57%) 27.9 (59%) 28.9 (61%)  8
0.15–0.19mg/kg 29.0 (70%) 40.0 (96%) 39.0 (94%) 42.0 (102%) 42.0 (102%) 42.3 (102%)  3
>0.2mg/kg 12.2 (39%) 15.3 (48%) 18.7 (53%) 17.2 (49%) 16.2 (46%) 17.2 (49%)  6

Table demonstrating the changes in heart rate using a specific dose and time after administration.
4 Journal of Perioperative Practice 00(0)

Table 4  Statistical analysis of heart rate variables according to dose

Related samples test
Related differences
 
Mean Standard deviation Significance
(bilateral) p value

Dose 0.05–0.09mg/kg HR min 0–HR min 1 –17.273 13.290 .002

HR min 0–HR min 2 –22.000 11.593 .000
HR min 0–HR min 3 –21.524 11.894 .000
HR min 0–HR min 4 –21.273 12.026 .000
HR min 0–HR min 5 –19.636 10.911 .000
HR min 0–HR min 6 –19.273 10.762 .000
Dose 0.1–0.14mg/kg HR min 0–HR min 1 –16.500 15.919 .022
HR min 0–HR min 2 –26.875 12.766 .001
HR min 0–HR min 3 –26.00 14.726 .002
HR min 0–HR min 4 –27.250 13.079 .001
HR min 0–HR min 5 –27.875 12.733 .000
HR min 0–HR min 6 –28.875 10.829 .000
Dose 0.15–0.19mg/kg HR min 0–HR min 1 –29.000 19.079 .119
HR min 0–HR min 2 –40.000 10.000 .020
HR min 0–HR min 3 –39.000 17.059 .058
HR min 0–HR min 4 –42.000 19.053 .062
HR min 0–HR min 5 –42.000 17.349 .052
HR min 0–HR min 6 –42.333 19.300 .063
Dose > 0.2mg/kg HR min 0–HR min 1 –12.167 18.126 .161
HR min 0–HR min 2 –15.333 21.030 .134
HR min 0–HR min 3 –18.667 17.963 .052
HR min 0–HR min 4 –17.167 18.368 .071
HR min 0–HR min 5 –16.167 16.630 .063
HR min 0–HR min 6 –19.167 8.424 .003

HR: heart rate. Table demonstrating the changes in heart rate according to the different doses administered.

Table 5  Increase in blood pressure according to dose at minutes 3 and 6

Dose, mg/kg SBP (mmHg) DBP (mmHg) MAP (mmHg)

Min 3 Min 6 Min 3 Min 6 Min 3 Min 6

0.05–0.09 103.2 (18.2%) 102.8 (18.9%) 61.9 (32.45%) 58.4 (24.9%) 75.8 (25.5%) 73.1 (21.9%)
0.1–0.14   98.0 (20.1%)   94.1 (14.6%) 64.5 (36.5%) 61.3 (29.5%) 75.6 (28.7%) 72.3 (22.3%)
0.15–0.19 115.6 (22.3%) 125.3 (31.6%) 73.6 (53.3%) 77.6 (60.6%) 87.6 (38.0%) 93.6 (46.0%)
>0.2 103.1 (12.6%) 103.6 (13.6%) 59.3 (26.3%) 64.8 (39.1%) 73.8 (19.5%) 77.6 (26.3%)

SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure. Table demonstrating the changes in blood pressure ac-
cording to time and dose.

Discussion an increase in myocardial oxygen consumption and

In our study, the average administered dose of 0.15mg/
kg of HB achieved an increase in HR in 27 of the 28
patients (96%) in the first 6 minutes after intravenous
administration of the drug. This is mainly explained by
the structural similarity of HB to other anticholinergic
drugs such as atropine, which allows it to antagonise
the response of muscarinic M2 receptors at the cardiac
level. When evaluating the rate of increase in HR in
respect to the average dose (0.15mg/kg), there was a
maximum increase in 61%, which in theory can lead to
thus predispose to an increase in associated coronary
events; however, this increase is less abrupt than what
is seen with atropine use (Modignani et al 1977,
Nuutinen et al 1985, Pennefather et al 1968).
Since the increase in HR began to be observed from
0.05mg/kg, the results of this study suggest that a
titrated administration of the drug be made until the
desired cardiovascular effect is achieved; this way, an
exaggerated and unwanted increase in cardiac
frequency is avoided. Likewise, HB administration
Quintero et al. 5

Table 6  Statistical analysis of mean arterial pressure variables with doses of 0.05–0.09mg/kg, 0.1–0.14mg/kg, 0.15–0.19mg/kg and
greater than 0.2mg/kg

Related samples test

  Related differences

Mean Standard Significance

deviation (bilateral) p value

MAP (0.05–0.09) min 0–MAP (0.05–0.09) min 3 –17.2727 11.0643 .000

MAP (0.05–0.09) min 0–MAP (0.05–0.09) min 6 –14.6364 12.3391 .003
MAP (0.1–0.14) min 0–MAP (0.1–0.14) min 3 –16.2500 9.0040 .001
MAP (0.1–0.14) min 0–MAP (0.1–0.14) min 6 –12.8750 9.8769 .008
MAP (0.15–0.2) min 0–MAP (0.15–0.2) min 3 –24.6667 10.1160 .052
MAP (0.15–0.2) min 0–MAP (0.15–0.2) min 6 –30.6667 17.0392 .089
MAP (greater than 0.2) min 0–MAP (greater than 0.2) min 3 –11.8333 20.6535 .219
MAP (greater than 0.2) min 0–MAP (greater than 0.2) min 6 –15.6667 13.2313 .034

MAP: mean arterial pressure. Table with the statistical analysis of mean arterial pressure according to time and dose.

should be done with caution in those patients with
pre-existing cardiovascular disease or who present risk
factors for coronary artery disease. According to our
results, doses 0.15–0.19mg/kg are not recommended
due to the risk of an excessive increase in heart rate of
up to 102% compared with baseline values. The
adverse effect of tachycardia seen in HB use has
sometimes been used in the intraoperative
environment by the anaesthetist for the management of
bradycardia, due to the advantage that the doses can
be titrated to avoid abrupt and excessive increases in
HR and in oxygen demand as occurs with atropine,
which requires a minimum dose of 0.5mg to avoid
paradoxical effects (Brownlee et al 1965, Herxheimer &
Haefeli 1966, Morton & Thomas 1958). Therefore, HB
could be a safer alternative in those patients with
coronary risk (Evers et al 2011). Another advantage of
HB is that it does not cross the blood–brain barrier
(Evers et al 2011), unlike atropine, which has a higher
rate of delirium in geriatric patients after its
administration (Gropper & Miller 2020).
An increase in MAP was observed in 92.8% of the
patients within the first 6 minutes after the
administration of HB, and an increase of 28.68%, 33%
and 56.95% was observed with doses of 0.1mg/kg,
0.15mg/kg and 0.2mg/kg, respectively. However, when
the diastolic BP data were analysed again with doses
higher than 0.2mg/kg, a greater increase (32.73%) was
not obtained with respect to lower doses. This suggests
that HB could have a maximum effect at a capped dose
of 0.2mg/kg for haemodynamic changes not only in HR,
but also in BP.
In our study, statistically significant changes (p < .05)
were achieved in HR and BP in the groups that were
administered doses of 0.05–0.09mg/kg and 0.1–
0.14mg/kg of HB during all minutes measured, but not
in patients with doses greater than 0.15mg/kg.
However, it is valid to clarify that the sample was small
and this limitation could explain the lack of statistical
significance for these groups. The changes evidenced in
the increase in mean and diastolic arterial pressure
may reflect the increase in HR, taking into account that
arterial pressure is equal to the relationship between
systemic vascular resistance and cardiac output;
considering that cardiac output is given by the
relationship of the stroke volume and the heart
(Nuutinen et al 1985).
Therefore, one can hypothesise that the increase in BP
is a reflection of cardiovascular physiology, which leads
us to infer that increases in HR will generate changes in
cardiac output. We believe that this study shows
promising results for the use of HB in the intraoperative
settings; however, we would like to encourage the
scientific community to take on similar studies to
further our collective knowledge in this area.
Acknowledgements
We acknowledge Dr Anacaona Martínez del Valle for her
excellent guidance, epidemiological expertise and assistance
with statistical analysis.
Declaration of conflicting interests
None.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Protection of humans and animals
The authors declare that the procedures followed were in
accordance with the ethical standards of the responsible
human experimentation committee and in accordance with
the World Medical Association and the Declaration of Helsinki.
In addition, the ethical committee of Hospital Simon Bolivar
was attained in order to access the relevant information for
the study.
6 Journal of Perioperative Practice 00(0)
Confidentiality
Although the identity and personal data of the patients were
kept anonymous, the authors declare that they have followed
the protocols of their workplace on the publication of patient
data. This study was approved by the appropriate Institutional
Review Board of the Simon Bolivar Hospital in Bogotá, Colombia.
ORCID iD
Sebastian Amaya https://orcid.org/0000-0003-1256-2476
References
Brownlee G, Wilson AB, Birmingham AT 1965 Comparison
of hyoscine-N-butyl bromide and atropine sulfate in man
Clinical Pharmacology & Therapeutics 6 177–182
Evers AS, Maze M, Kharasch ED (Eds) 2011 Anesthetic
Pharmacology: Basic Principles and Clinical Practice
2nd ed Cambridge, Cambridge University Press
Grainger SL, Smith SE 1983 Dose-response relationships of
intravenous hyoscine butylbromide and atropine sulphate
on heart rate in healthy volunteers British Journal of
Clinical Pharmacology 16 623–626
Gropper MA, Miller RD 2020 Miller’s Anesthesia New York,
Elsevier/Churchill Livingstone Available at https://www
View publication stats
.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C201
61020047
Herxheimer A, Haefeli L 1966 Human pharmacology of
hyoscine butylbromide The Lancet 2 418–421
Modignani RL, Mazzolari M, Barantani E, Bertoli D, Vibelli C
1977 Relative potency of the atropine-like effects of a
new parasympatholytic drug scopolamine-N-(Cyclopropy1
Methyl) bromide and those of hyoscine-N-butyl bromide
Current Medical Research and Opinion 5 333–340
Morton HJ, Thomas ET 1958 Effect of atropine on the heart-
rate The Lancet 2 1313–1315
Nuutinen EM, Wilson DF, Erecińska M 1985 The effect of
cholinergic agonists on coronary flow rate and oxygen
consumption in isolated perfused rat heart Journal of
Molecular and Cellular Cardiology 17 31–42
Pennefather JN, McCulloch MW, Rand MJ 1968 Observations
on the efficacy of oral hyoscine N-butyl bromide Journal of
Pharmacy and Pharmacology 20 867–872
Perotta JH, Canola PA, Lopes MC, vora PM, Martinez PE,
Escobar A, Valado CA 2014 Hyoscine-N-butylbromide
premedication on cardiovascular variables of horses
sedated with medetomidine Vet Anesthesia Analgesia 41
357–364
Tytgat GN 2007 Hyoscine butylbromide Drugs 67 1343–1357