208 J I M D C   2 0 1 7  208 

Open Access 
F u l l  L e n g t h  A r t i c l e  

 Use of Ondansetron for Prevention of Spinal Induced Hypotension 
 

Rabia Baig 1, Ammar Ali Shah 2, Tassaduq Khurshid 3, Latif Abid 4, Zubair Tariq 5 
1 Post graduate trainee, Holy family hospital Rawalpindi 

2 Senior Registrar Holy Family Hospital. Rawalpindi 
3 Assistant Professor Anaesthesia, Isra Medical College 

4 Assistant Professor Anaesthesia, Rawalpindi Medical College 
5 Consultant Anaesthetist, NHS England 

A B S T R A C T  

Objective: To compare the efficacy of prophylactic administration of Ondansetron before induction of spinal 

anesthesia with placebo, in preventing spinal induced hypotension. 

Patients and Methods: This Randomized Control trial was carried out at Holy Family Hospital, Rawalpindi from 29 April 

2015 till 28 October 2015. A total of 106 patients were enrolled in the study. Patients in group A, received 6 mg 

Ondansetron. Patients in group B received normal saline. Mean arterial pressure (MAP) and heart rate (HR) were 

recorded every 5 minutes after performing spinal anesthesia. The study drug was considered efficacious if absence of 

hypotension for 20 minutes was recorded after inducing spinal anaesthesia. Data was analyzed using SPSS 17. 

Results: Hypotension occurred in 7.5% cases in Ondansetron group compared to 28.3% in normal saline 

group (p=0.005). 

Conclusion: Ondansetron is effective in preventing spinal induced hypotension. 

Key words: Bupivacaine, Hypotension, Ondansetron, Spinal Anaesthesia. 

Author`s Contribution 
1
 Conception, synthesis, planning of research 

and manuscript writing 
2 

Interpretation and discussion 
3 

Data analysis, interpretation 
4,5

 manuscript writing, Active participation in 
data collection  

Address of Correspondence 
Ammar Ali Shah 
Email: ammarali05@gmail.com 

Article info. 
Received:  June 21, 2017 
Accepted:  2017 

Cite this article. Baig R, Shah AA, Khurshid T, Abid L, Tariq Z. Use of Ondansetron for 
Prevention of Spinal Induced Hypotension. JIMDC.2017;6(4): 

 

Funding Source: Nil 
Conflict of Interest: Nil 

I n t r o d u c t i o n  
 

Spinal anesthesia remains a popular method of 

anesthesia for a wide range of surgeries due to its 

efficacy, simplicity, safety, advent of newer drugs with 

reduced side effects and more benefits for certain patient 

populations.1 Its numerous advantages include blockade 

of the surgical stress response, decreased intraoperative 

blood loss and transfusion requirements, lower incidence 

of venous thromboembolism and reduced morbidity and 

mortality in high-risk patients.2 However, it is also 

frequently associated with undesirable effects such as 

hypotension, bradycardia, and shivering.3 Hypotension is 

the most common side effect of spinal anesthesia with a 

reported incidence as high as 33% in non-obstetric and 

60% in obstetric, non-laboring patients.Error! Bookmark 

not defined. Symapthectomy induced decreased 

systemic vascular resistance and reduced preload 

secondary to vasodilatation in the lower body are the 

major mechanisms for this hypotension.3 Relative 

dominance of parasympathetic system, activation of 

Bezold Jarish reflex (BJR) and increased baroreceptor 

activity are also contributory factors.Error! Bookmark not 

defined.  In the setting of decreased blood volume, 

serotonin may be an important factor inducing the Bezold 

Jarisch reflex via 5-HT3 receptors located in intracardiac 

O R I G I N A L  A R T I C L E  



 

                           209 J I M D C   2 0 1 7  209 

vagal nerve endings, leading to bradycardia and 

hypotension.5 Hemodynamic changes after spinal block 

are usually benign, but they may lead to serious 

consequences such as myocardial ischemia and 

increased stroke risk in certain population groups.6 In 

caesarean sections, hypotension results in decreased 

uteroplacental blood flow, detrimental effects on the fetus 

and maternal nausea vomiting.Error! Bookmark not 

defined. Various strategies employed to prevent spinal-

induced hypotension include fluid preloading and co-

loading, prophylactic administration of vasopressors e.g. 

epinephrine, Trendelenburg positioning, use of lower dose 

of bupivacaine for subarachnoid block.Error! Bookmark 

not defined. Administering fluids, vasopressors and 

anticholinergics for the treatment and prevention of 

hypotension and bradycardia can result in fluid overload, 

hypertension and tachycardia, which may be poorly 

tolerated in elderly and coronary artery disease patients.7  

Furthermore, administration of vasoconstrictors may have 

adverse effects on uterine blood flow in pregnant women. 

Ondansetron, a selective 5-hydroxytryptamine3 (5-HT3) 

receptor antagonist, is an effective antiemetic drug used 

for the prevention and treatment of chemotherapy 

induced, intraoperative and postoperative nausea and 

vomiting.8 Prophylactic administration of Ondansetron has 

been reported to have a perioperative anti-shivering effect 

in patients under anesthesia. Recently, it has also been 

demonstrated to be effective in preventing spinal induced 

hypotension in multiple studies, possibly by preventing 

serotonin-induced Bezold-Jarisch reflex (BJR), 

suppressing venodilatation and augmenting venous 

return.9 

In a study conducted in Iran by Marashi et al, 12 (17%) 

patients in the control group had MAP (Mean arterial 

pressure) < 80 mm Hg and required vasopressors 

compared to 0 patients in Ondansetron groups. (P = 

0.04).3 Owczuk R. et al demonstrated that the minimum 

diastolic and mean blood pressure values obtained over a 

20-minute observation period after spinal anesthesia were 

significantly higher in the Ondansetron group compared to 

the control group.9 However, none of these studies has 

been conducted in Pakistan. The basic aim of our study 

was to look for the effect of prophylactic Ondansetron 

administration on spinal induced hypotension in our 

population, so that Ondansetron if found to be effective, 

may be routinely used for the prevention of hypotension 

after spinal anesthesia in elective surgeries. 

P a t i e n t s  a n d  M e t h o d s  

This Randomized Control trial was carried out at Holy 

Family Hospital, Rawalpindi from 29 April 2015 till 28 

October, 2015. A total of 106 admitted elective patients 

were included in the study. American society of 

anesthesiologist’s classification I and II between the ages 

of 20-50 years who presented for elective urologic, 

orthopedic or gynecologic surgeries were included in the 

study. Exclusion criteria included, patient refusal or any 

contraindications to spinal anesthesia, any allergy to 

Ondansetron or local anesthetics and comorbid conditions 

like hypertension, coronary artery disease or other 

cardiovascular diseases, diabetes mellitus, pulmonary, 

hepatic or renal diseases. Patients receiving selective 

serotonin reuptake inhibitors or migraine medications or 

obesity BMI >35 were also excluded from the study. 

After obtaining approval from hospital ethical committee 

and written informed consent, patients were recruited 

according to selection criteria. All patients were assessed 

a day before surgery for anesthesia fitness. Patients were 

prepared by fasting (8 h for solid foods, 4 hours for clear 

fluids). Patients were randomly divided into two equal 

groups (Group A and Group B) by computer-generated 

random numbers. On arrival to the operating room, 

standard monitor was applied to all patients, including 

pulse oximeter, electrocardiogram and noninvasive 

arterial blood pressure. Oxygen was delivered via a 

Venturi facemask at a rate of 4 L/min. An 18-gauge 

intravenous catheter was placed and patients received 5 

ml/kg lactated Ringer solution over 15 minutes before 

spinal Anesthesia. Then patients in Group-A was given 6 

mg Ondansetron diluted in normal saline to 20 ml. The 

patients in the control group (Group-B) received 20 ml 

normal saline. In both groups, solutions were infused over 

5 minutes just before performing spinal anesthesia. All 

solutions were prepared by a resident of anesthesiology 

who was not involved in patient’s management or data 

collection. Baseline parameters (including heart rate, 

MAP) were recorded 5 minutes prior to induction of spinal 

anesthesia. Subarachnoid block was performed in the 

lateral position with a 25-gauge needle inserted by midline 

approach into the L3-4 interspace. After ensuring the 

correct position of the needle, 15 mg of 0.75% hyperbaric 



 

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bupivacaine was injected. Patients were immediately 

placed in the supine position after spinal block. The upper 

level of sensory blockade was evaluated by pinprick test 

from caudal to rostral direction at 5-min intervals up to 20 

minutes. MAP and HR were recorded every 5 minutes up 

to 20 minutes by an anesthesiologist blinded to the study 

groups. If MAP dropped <80 mm Hg or decreased more 

than 20% from baseline, 50 micrograms intravenous 

Phenylephrine was given, and repeated if necessary. 

Significant bradycardia (heart rate < 50 beats/min) 

accompanied by hypotension was treated with 0.5 mg of 

intravenous Atropine. 

Data was collected on a standardized performa and 

analyzed using SPSS version 17. Mean±SD was 

calculated for quantitative variables like age, weight, BMI, 

and MAP. Qualitative variables like gender and 

hypotension were expressed as frequencies and 

percentages. Chi-square test was used to compare the 

incidence of hypotension in the two groups. Effect 

modifiers like age, gender and indication for surgery were 

controlled by stratification. Post stratification Chi -Square 

test was applied. p value <0.05 was considered 

statistically significant.  

R e s u l t s  

Demographic characteristics of both group have been 

given in table 1. Hypotension occurred in 17.92% patients 

in our study. In the Ondansetron group, hypotension was 

observed in 7.5% of cases. In the normal saline group, 

28.3% of patients had hypotension.  

Frequency of hypotension was significantly lower in the 

Ondansetron group as compared to placebo group (Table 

2). There was no significant difference in the MAP of both 

groups at all times (table 3). Regarding gender, among 

females’ frequency of hypotension was lower in the 

Ondansetron group as compared to placebo but the 

difference was not statistically significant among males 

(Table 4).  

 

Table 1: Comparison of demographic characters 
between two groups (n=106) 
Variables Ondansetron 

group (n=53) 
Placebo group 
(n=53) 

p-value 

Age 
(Years); 
mean±SD 

34.45 ± 1.24 34.98 ± 0.96 0.10 

Weight 
(kg); 
mean±SD 

65.15 ± 1.37 72.58 ± 1.20 0.16 

BMI 
(kg/m2); 
mean±SD 

23.99 ± 0.44 25.97 ± 0.48 0.48 

Gender; n 
(%) Male       
Female 

 
27(44) 
26(58) 

 
34(56) 
19(42) 

 
0.16 

Table 2: Frequency of hypotension between 
Ondansetron and placebo groups 

Groups Hypertension 

Yes No p-value 

n n(%) n n(%) 

Ondansetron 4 7.5 49 92.5  

.005 Placebo  15 28.3 38 71.7 

Table 3: Mean Arterial Pressure in Ondansetron and 
Placebo groups 

Variable Ondansetron 
group (n=53) 
mean±SD 

Placebo 
group (n=53) 
mean±SD 

p-value 

MAP at 
Baseline (5 
minutes 
before 
spinal 
anesthesia) 

106.28 ± 0.98 104.54 ± .96 0.94 

MAP 5 
minutes 
after spinal 
Anesthesia 

97.77 ± 0.94 93.17 ± 1.44 0.08 

MAP 10 
minutes 
after spinal 
anesthesia 

93.77 ± 0.94 89.51 ± 1.28 0.20 

MAP 15 
minutes 
after spinal 
anesthesia 

90.26 ± 0.81 85.92 ± 1.15 0.31 

MAP 20 
minutes 
after spinal 
anesthesia 

86.74 ± 0.75 82.17 ± 0.99 0.07 



 

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There was statistically significant difference in the 

frequency of hypotension between Ondansetron and 

placebo groups in urologic surgeries, but the difference 

between the two groups was insignificant in orthopedic 

and gynecologic surgeries (Table 5). Difference in 

frequency of hypotension was also statistically significant 

between Ondansetron and placebo groups in patients 

belonging to 20-40 years of age, but the difference was 

insignificant in age group 41-50 years (Table 6).  
 

Table 5: Comparison of hypotension between 
Ondansetron and placebo groups stratified by 
indication for surgery (n=106) 

Indications 
for Surgery 

Groups Hypotension p-value 

Yes 
n(%) 

No 
n(%) 

Orthopedic Ondansetron 
Group (n=22) 

2(9) 20(91) 0.06 

Placebo 
Group (n=22) 

7(32) 15(68) 

Urologic Ondansetron 
Group (n=20) 

0(0) 20(100) 0.03 

Placebo 
Group (n=20) 

4(20) 16(80) 

Gynaecologic Ondansetron 
Group (n=11) 

2(18) 9(82) 0.34 

Placebo 
Group(n=11) 

4(36) 7(64) 

Table 6: Comparison of hypotension between 
Ondansetron and placebo groups stratified by age 
of patients 

Age 
groups 
(years) 

Groups Hypotension p-value 

Yes 
n(%) 

No    
n(%) 

20 – 30 Ondansetron 
Group (n=19) 

0(0) 19(100) 0.012 

Placebo 
Group (n=14) 

4(29) 10(71) 

31 – 40 Ondansetron 
Group (n=19) 

1(5) 18(95) 0.029 

Placebo 
Group (n=25) 

8(32) 17(68) 

41 – 50 Ondansetron 
Group (n=15) 

3(20) 12(80) 0.924 

Placebo 
Group (n=14) 

3(21) 11(79) 

D i s c u s s i o n  

It is frequently observed that spinal anesthesia produces 

hemodynamic effects. The most frequent of these is 

hypotension and bradycardia. Hypotension occurs as a 

result of vasodilatation secondary to sympathetic 

blockade. Sympathetic blockade spreads two segments 

higher than the sensory blockade, which in turn spreads 

two segments higher than the motor blockade. 

Vasodilatation causes decrease in systemic vascular 

resistance and central venous pressure.9-12 The same 

mechanism can sometimes lead to bradycardia. Main 

causes of bradycardia are shift in cardiac autonomic 

balance toward the parasympathetic system, activation of 

left ventricular mechanoreceptors from a sudden 

decrease in left ventricular volume (Bezold-Jarisch reflex) 

(BJR). It is suggested by pharmacological and animal 

studies that an important factor in initiating the BJR is 5- 

HT (serotonin) and blockade of 5-HT3 receptor can lead 

to attenuation of this reflex.6 

It was shown by previous studies that Ondansetron 4 mg 

of Ondansetron administration has been occasionally 

used to decrease maternal hypotension and nausea.9 

Spinal anesthesia is the preferred anesthetic technique 

Table 4: Comparison of hypotension between 
Ondansetron and placebo groups stratified by 
gender (n=106) 

Gender Groups Hypotension p-value 

Yes 
n(%) 

No      
n(%) 

Male Ondansetron 
Group (n=27) 

2(7) 25(93)  

0.09 Placebo 
Group (n=34) 

8(24) 26(76) 

Female Ondansetron 

Group (n=26) 

2(8) 24(92)  

 

0.02 
Placebo 

Group (n=19) 

7(37) 12(63) 



 

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for caesarean section as it is simple, safe, fast and 

reliable technique could effectively prevent maternal 

hypotension and nausea secondary to spinal anesthesia. 

Fetal morbidity increases by the decrease in cardiac 

output and uteroplacental flow caused by hypotension 

due to spinal anesthesia.2   A very high sensory block 

requirement (till T5) in caesarean section causes 

extensive sympathetic blockade and hypotension in 55 to 

90% of cases. Maneuvers like the partial left lateral 

decubitus (with the objective of limiting the aorto-caval 

compression caused by the gravid uterus) are partially 

effective. Vascular filling with crystalloids or starches and 

use of vasopressors are mainly used to treat hypotension 

but many studies showed these methods ineffective. It 

was shown by a recent review that hypotension is not 

prevented reliably by any one of these methods. To 

decrease fetal and maternal morbidity and mortality 

during spinal anaesthesia, it is crucial to prevent and treat 

it effectively. Ondansetron can be routinely used to 

prevent maternal hypotension and fetal compromise after 

spinal anesthesia in caesarean sections, as well as 

general surgical and other procedures performed in spinal 

anesthesia. It can be a good alternative for previously 

used methods to treat spinal induced hypotension. 

Ondansetron does not affect the heart and blood 

pressure, even when it is rapidly administered 

intravenously. In both children and adults, this drug is 

widely used to prevent postoperative nausea and vomiting 

prevention.  

Based on above mentioned considerations, we conducted 

this randomized, controlled, double-blind study, that use 

of intravenous Ondansetron can be investigated and it 

can be used prophylactically for spinal induced 

hypotension. A total of 106 patients were enrolled in the 

study and were randomly divided into two equal groups. 

Hypotension occurred in 17.92% of patients in our study. 

The frequency of hypotension was significantly lower in 

the Ondansetron group (7.5%) as compared to placebo 

(28.3%). In a study conducted by Owczuk R et al,Error! 

Bookmark not defined.  two equal groups were made 

out of 53 patients who operated under spinal anesthesia. 

It was observed that 48.1% patients in placebo group and 

38.5% patients in onset group developed hypotension. 

They made the conclusion that Ondansetron is effective in 

preventing decrease in MAP and HR when compared to 

normal saline group. Their results were comparable to 

those observed in our study. In our study, we compared 

Ondansetron 6 mg with placebo. Owczuk et al. compared 

Ondansetron 8 mg with placebo. Sahoo et al. compared 

Ondansetron 4 mg with placebo.5 Marashi et al. 

compared Ondansetron 6mg and 12mg with placebo.3 

Ortiz-Gómez et al.’s study 10 included three doses of 

Ondansetron (2, 4, and 8 mg versus placebo). Owczuk et 

al. and Marashi et al. studied a general surgical 

population. Sahoo et al. and Ortiz-Gómez et al used 

obstetric patients in their study. We on the other hand, 

studied patients undergoing urological, orthopedic and 

gynecological surgeries. 

Anesthetic technique and dose is a very important factor 

that can cause the difference between the studies. A 

different dose of hyperbaric bupivacaine was used in all of 

these above-mentioned studies. We and Marashi et al. 

used 15mg of hyperbaric bupivacaine for spinal 

anesthesia. Sahoo et al. used 10 mg bupivacaine, 

Owczuk et al used 20 mg bupivacaine. Ortiz-Gómez et al. 

personalized each dose to each patient (9.7 ± 0.4 mg in 

the placebo group and 9.6 ± 0.3 mg in Ondansetron 

group), and the mean dose was smaller than our dose of 

15mg. This was a good method as it can be used to 

prevent over or under dosing of patients. Another 

difference is that intravenous fentanyl to treat pain and 

tramadol or promethazine to treat adverse effects was 

used by Sahoo et al. Blood pressure readings can be 

modified directly or indirectly by these medications due to 

a central mechanism. Another difference is that we do not 

use intrathecal opioids for improving effect of spinal 

anesthesia. This is different from the study of Ortiz- 

Gómez et al. in which intrathecal fentanyl was used. 

Ondansetron may be centrally acting and its mechanism 

can be affected by intrathecal opioids. Neither we nor 

Ortiz-Gómez et al used other supplemental analgesia, 

and patients who required it were not included in the 

study. Earlier studies have suggested that when 

Ondansetron is administered intravenously, it can 

antagonize sensory block produced by local anesthetics 

given intrathecally. This is perhaps the reason for the 

attenuated hemodynamic responses after spinal 

anesthesia. 

To summarize, in the current study, we investigated the 

effects of 6 mg of Ondansetron on the patients’ MAP. We 



 

                           213 J I M D C   2 0 1 7  213 

observed that 6 mg of Ondansetron intravenous, when 

given alongside rapid crystalloid infusion, could 

significantly reduce the incidence of spinal induced 

hypotension. However, Ondansetron preloading did not 

appear to have any significant effect in reducing 

hypotension in gynecologic and orthopedic surgeries. We 

can assume that 6 mg of Ondansetron may not be 

sufficient to prevent hypotension in these types of 

surgeries. It seems that Ondansetron enhances the 

contractility and efficiency of the heart by acting at cardiac 

level and stabilizes systemic vascular resistance by acting 

at vascular level through vascular and/or medullary 

specific receptors. 

C o n c l u s i o n  

Ondansetron is effective in preventing hypotension in 

patients undergoing spinal anesthesia. 

R e c o m m e n d a t i o n s  

We do feel the need to include other important variables 

like heart rate, systolic and diastolic blood pressures. The 

duration and type of surgery, blood loss and maintenance 

fluid requirements can influence results of such studies. 

Further studies should be carried out, taking into 

consideration these aspects too. Studies should also be 

done that involve more invasive hemodynamic monitoring 

like Swan-Glanz catheter. It can be helpful to properly 

assess decrease in venous return and cardiac filling 

pressures. The effect of different doses of Ondansetron 

on reducing spinal induced hypotension also needs to be 

further investigated. 

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3. Marashi SM, Soltani-Omid S, SoltaniMohammadi S, 

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8. Demirhan A, Tekelioglu YU, Akkaya A, Ozlu T, Yildiz I, 

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Sawicka W, Wujtewicz MA et Al. Ondansetron attenuates 

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