THE EFFECT OF GRANISETRON AND ONDANSETRON ON

HEMODYNAMIC DURING CESAREAN SECTION UNDER SPINAL

ANESTHESIA

Ahmad Nur Islam 1*, Alamsyah A.A.2, Muh. Ramli Ahmad2, Syafruddin Gaus2, Hisbullah2
1
Resident at Departement of Anesthesiology, Intensive Care and Pain Management Hasanuddin
University, Faculty of Medicine, Makassar, Indonesia
2
Staff at Departement of Anesthesiology, Intensive Care and Pain Man agement, Hasanuddin
University, Faculty of Medicine, Makassar, Indonesia
*Telp: +62-813-5566-6826, email: behoss2014@gmail.com

Abstract

Spinal anesthesia is the most popular technique of anaesthesia for Caesarean section (Cs) which is
frequently associated with hypotension and bradycardia. Hypotension is harmful for maternal and
fetal outcome. The Bezold–Jarisch reflex (BJR) is one of the mechanisms which explain the
occurrence of hypo tension after spinal anesthesia through serotonin-mediated vasodilatation. These
receptors located peripherally as cardiac chemoreceptors on the cardiac vagal afferent and centrally
in the chemoreceptor trigger zone. The aim of our study was to evaluate the effect 5-
hydroxytryptamine 3 (5-HT3) receptor antagonists between Granisetron and Ondansetron on
hemodynamic in parturients undergoing Cs with spinal anesthesia. Fourty patients underwent Cs
under spinal anesthesia randomly divided into two groups (20 parturients in each group). Group G
received intravenous 0.03 mg/kg Granisetron 30 min before spinal anesthesia, group O recieved
intravenous 0.1 mg/kg Ondansetron. Mean Arterial Blood Pressure (MABP), Heart Rate (HR), and
vasopressor used were assessed. MABP changes was higher in group O compared to group G
(p<0.05), although this result was not statistically significant (p>0.05). However, incidence of
nausea and vomiting was significantly decreased in group G (p<0.05). Granisetron and Ondasetron
have similar effect in prevent hemodynamic changes during Cs under spinal anesthesia .

Keywords: Granisetron, Ondansetron, hemodynamic, Caesarean section, spinal anesthesia.

Introduction
Spinal anesthesia is the most popular technique of anaesthesia for Cs, which is frequently
associated with hypotension and bradycardia. Hypotension is harmful for maternal and fetal
outcome. Hypotension resulted from the decrease in systemic vascular resistance and central
venous pressure due to sympathetic block. Sudden bradycardia may occur from shift in cardiac
autonomic balance toward the parasympathetic system. 1,2
Ondansetron and Granisetron are selective 5-HT3 receptor antagonists. These receptors
located peripherally as cardiac chemoreceptors on the cardiac vagal afferent and centrally in the
chemoreceptor trigger zone. On the other hand, the BJR is one of the mechanisms which explain the
development of hypotension after spinal anesthesia through serotonin-mediated vasodilatation.
Stimulation of cardiac chemoreceptors in the heart due to decreased in venous return increases
parasympathetic activity, while decreases the sympathetic activity resulting in hypotension and
bradycardia.2,3 From systematic review and meta-analysis, Heesen et al. in 2016 suggested 5-HT3
receptor antagonist were effective in reducing the incidence of hypotension and bradycardia. 1 The
effect are only significant in patients undergoing Cs, therefore in this study, we evaluated the effect
of Granisetron and Ondansetron on the hemodynamic and side effects following spinal anaesthesia
in women undergoing elective Cs.

Methods
This study was conducted at Mother and Child Hospital in Makassar, Indonesia between
February and March 2018. Institutional ethical committee approval and informed written consent
were obtained from all patients. Participants were evaluated one day before surgery by an
anaesthesiologist. Obstetric patients with ASA Physical Status (PS) II, between 20 and 45 years old,
and undergoing an elective CS were included. Patients who refused to participate, had any
contraindications to spinal anesthesia, history of hypersensitivity to local anesthetic agent, bleeding
disorder, hypertensive and cardiovascular disorders in pregnancy were excluded. For eligible
patients, demographic information was collected and a physical examination was performed. Age,
BMI, and ASA PS class were recorded and analyzed.
In the pre-anaesthesia room, baseline value recorded, non-Invasive blood pressure (NIBP)
and HR were recorded and a peripheral 18-Gauge i.v. cannula was inserted. Patients were randomly
assigned to receive 0.1 mg/kg Ondansetron (group O) or 0.03 mg/kg Granisetron (group G) 30 min
before spinal anesthesia, where each group consists of 20 parturients. All patients received i.v 50
mg Ranitidine and preloading with 10 mL/kg Ringer’s lactated solution given over 15 min. The
spinal technique was performed at L3-4 or L4-5 with the patient in the left lateral decubitus
position. The 10 mg 0.5% hyperbaric bupivacaine with adjuvant 25 mcg fentanyl was administered
after confirmation of cerebrospinal fluid through a 25- or 26-Gauge Quincke spinal needle. Patients
were immediately placed in the supine position with 15 o left tilt. The second anaesthesiologis was
blinded to the study solution, measured haemodynamic parameters and recorded the presence of
nausea and vomiting.
HR and MABP were recorded before spinal anesthesia and at 2-min intervals up to 15 min,
followed by 30-min intervals until the end of surgery. Rescue i.v. bolus doses of 10 mg ephedrine
were given if the parturient had hypotension (hypotension was defined as a decrease in SBP <90
mmHg or in MABP more than 20% from the baseline). Decrease in HR to less than 50 beat/min
was treated with 0.5 mg atropine sulphate intravenous.
The Statistical Program SPSS (SPSS Inc., Chicago, Illinois, USA) for Windows, version 25,
was used for data entry and analysis. Data were expressed as number and mean±SD for quantitative
variables. Categorical variables were analyzed using Chi-squared test or Fisher’s exact test.
Numerical variables normally distributed were compared between groups by Student’s independent
samples t-test with p<0.05 was statistically significant.

Results
Fourty patients were recruited: 20 parturients in each group. No significant differences were
observed in patients demographic (age, BMI, and ASA PS) between the two groups (p>0.05). The
incidence of nausea and vomiting significantly reduced in group G (see Table 1).
MABP and HR were observed in the two groups. The difference in time of measurement in
each group was observed. MABP changes was higher in group O compared to group G (p<0.05),
although this result was not statistically significant (p>0.05) (see Figure 1). There was no difference
of HR changes between the two groups (p>0.05) (see Figure 2).
Table 1. Demographic details and side effect by each group
Group G Group O p value
(n=20) (n=20)
Age (years) † 28.95±4.45 28.55±6.32 0.818
BMI (kg/m2) † 25.38±2.24 25.88±2.74 0.532
ASA PS‡ 20 (100) 20 (100) 1.000
Nausea/Vomiting § 0(20) 5(20) 0.047*
Vasopressor Use § 0 0 -
Data presented in number of patient (n) or mean±SD. .*:p<0.05, analyzed with Fisher’s exact test. †:
analyzed with Student’s independent samples t-test, ‡: analyzed with Chi-square test. § : analyzed
with Fisher’s exact test.

Figure 1. Comparison MABP (mmHg) changes in group G and group O

Figure 2. Comparison HR (bpm) changes in group G and group O

Discussion
Sympathetic blockade from spinal anaesthesia decreases systemic vascular resistance and
induces peripheral pooling of blood leading to hypotension. In response to hypovolaemia,
stimulation of cardiac sensory receptors in the left ventricle induces the BJR and results in reflex
bradycardia, vasodilation and hypotension. Chemoreceptors are activated in response to decreased
blood volume by serotonin. Activation of 5-HT3 receptors, which are G protein coupled, ligand-
gated fast-ion channels, results in increased efferent vagal nerve activity which frequently
producing bradycardia. However, bradycardia occurs less frequently than hypotension following
spinal anaesthesia.6,7,8
Ondansetron and Granisetron, although both of them from the same category and have
same mechanism of action, may be due to the action of Ondansetron on mixed receptors and the
high selectivity of Granisetron on 5-HT3 receptors, but it has minimal affinity for other 5-HT
receptors, adrenergic, histaminic, dopaminergic, or opioid receptors. 10,11
In the present study, two 5-HT3 antagonists, Ondasnetron and Granisetron, as they block
the BJR and may successfully treat postspinal hypotension, were used prophylactically and given 30
min before spinal anesthesia. The important finding in this study is that, despite the reduction in
MABP changes in Ondasetron group higher than Granisetron group, there were no statistically
difference in MABP changes in the two groups.
Our findings is consistent with study by Mahmoud and Shaaban in 2017 showed that
prophylactic intravenous 4 mg Ondansetron or 1 mg Granisetron compared to saline as placebo
were significantly reduced the severity of hypotension induced by spinal anesthesia. 6 In our study,
we gave prophylactic 0.03 mg/kg Granisetron and 0.1 mg/kg Ondansetron 30 min before spinal
anesthesia. It showed there were no difference in hemodynamic changes and there was no
incidence vasopressor use in each group.
This study showed that Granisetron and Ondansetron have protective effect on
hemodynamic response during Cs. Our results indicated that Ondansetron and Granisetron
prevented the serotonin-induced BJR, suppressed venodilatation, augmented venous return to the
heart and resu lted in lesser reductions in MABP. 10
Limitations of this study were small sample size, used one dose of each drugs only, and
amount of blood loss was not recorded in this study, which may influence the hemodynamic profile
of parturients. We recommend further studies with larger sample size and large doses of Granisetron
and Ondansetron to evaluate the effect on hemodynamic.

Conclusion
Granisetron and Ondansetron has similar effect on preventing hemodynamic changes
during Cs under spinal anesthesia.

Acknowledgement
Author thanks to staff and resident Departement of Anesthesiology, Intensive Care, and
Pain Management, Faculty of Medicine, Hasanuddin University for the ideas, supporting, and
advising this study. Thanked to Mother and Child Hospital staffs and all of participants of this study.

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