









































Anesthesia eJournal
Volume 4 - Issue 1 2016

AEJ

Educated Hand Publishing LLC 
“The Science Behind the Art”  

 Anesthesia eJournal - Online
ISSN 2333-2611

Page 50

Efficacy of Ondansetron as a Prophylactic Anti-Hypotensive Pharmacologic Intervention 
Among Obese Parturients Undergoing Spinal Anesthesia for Cesarean Delivery

Melissa Dawn Hudson1,MSNA, DNP, CRNA, APRN
Neva L Crogan1, Ph.D., ARNP, GNP-BC, FNGNA, FAAN
Edward J. Bilsky2, Ph.D

Affiliation:
1 Gonzaga University
2 University of New England

Funding/Conflict of Interest Disclosure: 
None

KEYWORDS: Ondansetron; obesity; pregnancy; spinal anesthesia; hypotension; cesarean delivery

INTRODUCTION
Background

Recognized as a pandemic nutritional disorder by the World Health Organization,1 obesity has become one of the most 
critical global health issues. Obesity in the United States has been on the rise for more than 30 years despite the objectives 
of Healthy People 2000 through Healthy People 2020. In fact, prevalence estimates by the Centers for Disease Control and 
Prevention (CDC) indicate that more than one-third of the population of the United States is overweight (body mass index 
[BMI] of 25–29.9), while more than one-fourth of the population is obese (BMI of 30–99.8).2 In 2012, Washington State 
reported that 35.4% of its residents were overweight and 26.8% of its residents were obese.3 Among those surveyed in the 
2011-2012 National Health and Nutrition Examination Survey, 34.9% of women were considered obese.4 In alignment with 
this trend in population health is the statement by the CDC that “in the United States, obesity during pregnancy is common 
and it increases obstetrical risks.”5

As obesity has increased in both incidence and prevalence in the general population, the rate of obesity in the obstetric 
population has correspondingly grown. Among the greatest contributing factors to anesthetic risk in pregnancy are the 
sequelae resultant from obesity.5,6 Increased anesthetic risk is a result of the multisystemic physiologic changes associated with 
pregnancy. The most significant contributors to maternal mortality are the elevated physiologic demands on the respiratory and 
cardiovascular systems. Associated with serious morbidity, obesity in the parturient further increases anesthetic risk as well as 
the incidence of instrumental and cesarean deliveries.5

Abstract
Background and Purpose: Obesity is a risk factor for hypotension after spinal anesthesia among parturients 

undergoing cesarean delivery. Although researchers have demonstrated that prophylactic administration of ondansetron 
is efficacious in attenuating maternal hypotension following spinal anesthesia, no studies have examined the efficacy of 
prophylactic ondansetron in the high-risk population of obese parturients. The primary objective of this study was to 
assess the efficacy of the novel application of ondansetron as a prophylactic anti-hypotensive pharmacologic intervention 
among obese parturients to facilitate practice recommendations for reducing maternal-fetal risk associated with the 
administration of spinal anesthesia for cesarean delivery.

Methods: Retrospective chart analyses of 46 patients with a body mass index > 30 were conducted between August 1, 
2014, and May 10, 2015, to determine whether the intravenous administration of 4 mg ondansetron before the induction 
of spinal anesthesia reduced the frequency of vasopressor administration during cesarean delivery.

Results: The incidence of vasopressor administration among patients who received prophylactic ondansetron was 
35.7%, whereas 46.9% of patients who did not receive prophylactic ondansetron required vasopressor administration (X2 
= 0.144, df = 1, P = 0.704).

Conclusions: Obese parturients undergoing spinal anesthesia for cesarean delivery demonstrated improvements in 
hemodynamic stability when prophylactically treated with ondansetron.



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Volume 4 - Issue 1 2016 Page 51

For the obese parturient, the subsequent necessitation of the 
administration of anesthesia additionally burdens the cardiovascular 
and respiratory systems. Tan and Sia stated, “The engagement of the 
obstetrical anesthetist in the management of this group of high-risk 
patients should be performed antenatally so that an appropriate 
management strategy can be planned in advance to prevent an 
adverse outcome.”7 Among the most common adverse outcomes 
observed in obese parturients undergoing spinal anesthesia for 
cesarean delivery is hypotension.8 The sequelae resultant from 
hypotension among parturients are particularly worrisome as they 
include both maternal and fetal effects and occur at an incidence 
of 20% to 100%.8 Serious maternal-fetal consequences secondary 
to hypotension include fetal hypoxia resultant from utero-placental 
insufficiency and an increased incidence of maternal nausea and 
vomiting secondary to hypoperfusion of the chemoreceptor trigger 
zone and vomiting centers within the medulla.9 Therefore, Nani and 
Torres concluded in their study correlating the BMI of pregnant 
women with the development of hypotension after spinal anesthesia 
for cesarean delivery that anesthetic techniques should be improved 
to reduce the consequences of spinal-induced hypotension in both 
pregnant women and their fetuses.8

Prophylactic utilization of intravenous ondansetron has been 
identified as a mechanism by which to decrease anesthetic risk 
among parturients undergoing spinal anesthesia for cesarean 
delivery via the abatement of the Bezold-Jarisch reflex (BJR), 
with resultant improvements in hemodynamic stability including 
a decrease in the incidence of hypotension.10,11 Through increased 
vagal tone, the BJR has been identified as a contributing factor to 
maternal hypotension following induction of spinal anesthesia. 
Characterized by bradycardia and worsening hypotension, the 
reflex is initiated by chemoreceptors in the left ventricle, identified 
as 5-hydroxytryptamine-3 (5HT3) receptors, in response to spinal 
anesthetic-induced systemic vasodilation and resultant relative 
hypovolemia.12 Attenuation of the BJR may therefore decrease 
the incidence of severe refractory hypotension in obese parturients 
undergoing spinal anesthesia for cesarean delivery. As a result, 
reduction of anesthetic risk in this specific vulnerable population of 
obese parturients may be feasible.10

Significance
Many are affected by and invested in the health and well-being 

of pregnant patients with BMI > 30. As obesity is passed down 
from mother to child, the obesity epidemic continues to become 
more prevalent and more profound despite national efforts to 
address the issue. Stakeholders therefore include community 
health care systems, agencies, and providers who confront 
unique challenges associated with caring for obese parturients. 
Anesthetists are directly affected by the obesity pandemic given 
that elevated BMI is associated with increased perioperative risk.

The CDC5 drew on the work of Chu et al6 in finding that 
“obesity during pregnancy is associated with increased use of 
health care and physician services, and longer hospital stays for 
delivery.” Cesarean delivery rates are also higher at 45.2% for 
extremely obese women versus 21.3% for nonobese women.1 
Delivery via cesarean incurs greater anesthetic risk and is 
associated with higher medical costs. In fact, the estimated annual 
medical cost of obesity in the United States was calculated to be 
$147 billion in 2008.3 Compared with the nonobese population, 
medical costs for obese patients were $1429 higher per person.13

Literature Review
Ondansetron, when administered 5 minutes before a 

subarachnoid block, has been identified as an efficacious 
intervention to reduce the incidence of spinal anesthesia-
associated hypotension for cesarean delivery. Sahoo et al10 
conducted a randomized controlled trial (RCT) that was later 
expanded upon by Wang et al.14 The researchers demonstrated 
that 4 mg of ondansetron given intravenously 5 minutes before 
a subarachnoid block was effective in reducing the incidence 
of spinal anesthesia-associated hypotension during cesarean 
delivery. The researchers’ purpose was to clearly define the effect 
of ondansetron on the hemodynamic response following spinal 
anesthesia for cesarean delivery, based on the physiologic effects 
of 5HT3 antagonists on the BJR. The BJR results in profound 
hypotension and bradycardia as a result of increased vagal tone 
due to stimulation of chemoreceptors in the left ventricle. A 
sample size of 52 parturients was randomized to 2 groups. One 
group received intravenous ondansetron; the other received 
normal saline before spinal anesthetic for cesarean delivery. 
Vital signs and vasopressor administration were recorded and 
quantified as outcome measures. The results revealed fewer 
hypotensive episodes and a resultant decrease in vasopressor 
administration in the ondansetron group (P < 0.001). Of the 
26 parturients in the ondansetron group, 2 required vasopressor 
administration (7.69%). Of the 26 parturients in the saline group, 
11 required vasopressor administration (42.31%). The absolute 
difference was a 34.62% decrease in vasopressor administration 
when ondansetron was administered prophylactically.10 Compared 
with the results of the current study, a similar decrease in the 
frequency of vasopressor administration was observed in both 
the obese and the nonobese patient populations following initial 
doses of 4 mg ondansetron administered before spinal anesthesia.

Wang et al conducted a double-blind RCT that included 66 
parturients scheduled for elective cesarean delivery. Five minutes 
before receiving spinal anesthesia, patients received ondansetron 
or saline. In addition to maternal hemodynamics, Wang et 
al analyzed umbilical cord blood samples after delivery to 
determine the incidence of fetal acidosis. Study findings included 
increased fetal pH as well as decreased incidence of maternal 
hypotension and nausea among those prophylactically treated 
with ondansetron.14

Chu and colleagues reported in the New England Journal 
of Medicine that higher BMI was related to increased rates of 
cesarean delivery and obesity-related high-risk conditions.6 It 
is consequently more likely that an obese parturient will require 
the intervention of an anesthetist during labor and delivery as 
a result of the increased incidence of cesarean or instrumental 
delivery among such patients. Furthermore, owing to the 
increased incidence of obesity-related high-risk conditions during 
pregnancy, anesthetic risk is compounded. According to Cooper 
and McClure, complications directly related to anesthesia were 
deemed responsible for the deaths of 6 women in the United 
Kingdom, thereby demonstrating anesthesia as one of the leading 
causes of death among parturients.15

Numerous research studies over recent years have confirmed 
that obese parturients present even greater anesthetic risk than 
their nonobese counterparts.8,16-22 Nani and Torres specifically 
addressed the incidence of hypotension after the administration 
of spinal anesthesia as it relates to BMI. The sample size for 



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 52

normal-weight patients, as defined by a BMI less than 25, was 
49. The sample size for the overweight group, as defined by a 
BMI greater than or equal to 25, was 51. The results reflected 
fewer episodes of hypotension in the non-overweight group. 
Confidence intervals of 5.89 ± 0.53 episodes versus 7.80 ± 0.66 
episodes, with a P value of 0.027, were reported, compared with 
5.36 to 6.42 episodes of hypotension following spinal anesthesia 
for cesarean in patients with BMI < 25. The P value was 
determined to be 0.027.8

Risk Versus Benefit
Researchers have demonstrated that anesthetic risk 

associated with spinal anesthesia-related hypotension among 
parturients undergoing cesarean delivery may be attenuated 
with the prophylactic administration of ondansetron.10,14 Obese 
parturients undergoing spinal anesthesia for cesarean delivery 
have a higher incidence of severe refractory hypotension than 
do their nonobese counterparts.8-22 Hence, the population that 
may benefit most from the application of prophylactic anti-
hypotensive ondansetron administration is obese parturients. 
However, incorporation of such evidence into clinical practice 
by anesthesia providers has been slow and inconsistent. This may 
be due, in part, to the fact that the findings of current literature 
support the need for further evaluation of evidence-based 
practice recommendations for the specific population of high-
risk obese parturients undergoing spinal anesthesia for cesarean 
delivery.

Ondansetron, a widely used anti-emetic and serotonin 
antagonist, has been safely used to blunt the BJR, resulting in 
less bradycardia and hypotension first in animals and later in 
humans undergoing a subarachnoid block.10,14 Ondansetron is 
a selective serotonin antagonist specific to the 5HT3 receptor. 
Although initially designed to target 5HT3 receptors in the 
chemoreceptor trigger zone responsible for nausea and vomiting, 
the novel administration of ondansetron for the prevention of 
hypotension secondary to blockade of 5HT3 receptors in the left 
ventricle has shown potential for clinical utility in the prevention 
of hypotension and bradycardia associated with the BJR.10

Ondansetron is a drug commonly administered in hospital 
operating rooms throughout the United States for the prevention 
of postoperative nausea and vomiting. As such, it has a well-
established safety record provided it is given within the 
recommended dose of 4 mg intravenous for adult patients and 
0.1-0.15 mg/kg for pediatric patients. The primary side effects 
associated with ondansetron include asthenia, constipation, 
diarrhea, headache, and somnolence.11 As with all pharmacologic 
interventions, judicious administration is recommended.
METHODS
Ethical Concerns

Institutional Review Board (IRB) exemption was obtained 
through Gonzaga University. Because the scholarly project was 
a retrospective, observational chart review, no patient informed 
consent was deemed necessary. Site support for the project was 
obtained by the Department of Anesthesia at our community 
hospital, the Hospital Administrator, and the Director of Health 
Information.

Setting
As of the last census data, the county studied was tied for 

the county with the second highest prevalence of obesity in 
Washington State. The city that was the focus of the study is 
rural, with a population of less than 8000, within this county. 
The Hispanic population of the city represents 61.4% of the 
total population, compared with 11.9% in Washington State. In 
addition, persons living below the poverty level in the city account 
for 22.9% of the population, compared with 13.4% statewide.3 
Of those undergoing a cesarean delivery at our community 
hospital in 2014 (n = 117), the majority, approximately 97%, 
were Hispanic. Hispanic ethnicity and higher rates of poverty are 
associated with higher rates of peripartum obesity.23 Therefore, a 
retrospective chart review of obese parturients who necessitated 
spinal anesthesia for cesarean delivery was productive and 
efficacious in the assessment of ondansetron administration for 
the prevention of intraoperative hypotension at our community 
hospital. As a result, this study provided useful clinical 
information regarding the reduction of anesthetic risk in this 
specific vulnerable population6 and will facilitate evidence-based 
practice recommendations.

Intervention
By use of a retrospective design, we analyzed medical records 

from parturients with a BMI greater than or equal to 30 who 
were admitted to the community hospital between August 1, 
2014, and May 10, 2015, to determine whether the intravenous 
administration of 4 mg ondansetron prior to the induction of 
spinal anesthesia reduced the frequency of administration of 
vasopressors during cesarean delivery. Utilization of prophylactic 
ondansetron was based on current literature and had only been 
implemented into clinical practice at this institution as of August 
2014. Therefore, August 1, 2014, was established as the start date 
for all data collection. Numerous data points were included in 
the chart review. Patient information included BMI, maternal 
age, gestational age, and ethnicity. Interventional information 
collected included time of initiation of spinal anesthetic, time of 
prophylactic ondansetron administration (if applicable), dose of 
0.75% spinal bupivacaine with dextrose (milliliters) administered, 
dose of spinal morphine sulfate (milligrams) administered, 
time of initial vasopressor administration (if applicable), 
total ephedrine dose administered (if applicable), and total 
phenylephrine dose administered (if applicable). The same data 
were also collected and analyzed on the nonobese population for 
purposes of comparison. Data were analyzed from the charts of 3 
different anesthesia providers.
Data Analysis

Descriptive analyses were conducted by using Excel software 
for Windows (Microsoft Corp) to synthesize and describe patient 
characteristics (age, BMI, ethnicity, and gestation) as well as 
frequency, mean, median, and mode of all data. A chi-square 
test was used to analyze whether the observed difference in the 
vasopressor requirements of the group of patients who received 
ondansetron and the group of patients who did not receive 
ondansetron was significant. An independent samples t-test was 
utilized to determine the statistical significance of the observed 
decrease in ephedrine dosing among patients who received 
prophylactic ondansetron versus those who did not.



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Volume 4 - Issue 1 2016 Page 53

Hypotension was considered significant and counted among 
the incidents included in the statistical analysis if it necessitated 
treatment as evidenced by administration of phenylephrine or 
ephedrine as documented on the anesthetic record. The total dose 
of vasopressor administration was recorded for each patient and 
subsequently compared between obese patients who did and did 
not receive ondansetron before the induction of spinal anesthesia.
RESULTS

Retrospective chart analysis of 46 patients with BMI > 30 at 
our community hospital between August 1, 2014, and May 10, 
2015, revealed an 11.175% decrease in vasopressor administration 
among the 14 patients who received 4 mg IV ondansetron 5 
minutes before spinal anesthesia for cesarean delivery compared 
with the 32 patients who were not treated with prophylactic 
ondansetron (Figure 1). Although not included in the study of 
obese parturients, data were collected from nonobese patients for 
the purposes of comparison. Among the 24 patients excluded 
from the chart review because of having a BMI < 30, 7 patients 
received prophylactic ondansetron. Of the nonobese patients who 
received prophylactic ondansetron, none required vasopressor 
administration intraoperatively, representing a substantial 
improvement in maternal hemodynamics. Of the 17 nonobese 
patients who did not receive prophylactic ondansetron, 47% 
required intraoperative vasopressor administration. However, 
this difference was not significant (X2 = 0.144, df = 1, p = 0.704) 
(Table 1).

 Figure 1. Ondansetron administration versus vasopressor 
administration.
Of 46 patients, 32 were not treated and 14 were treated with 
prophylactic ondansetron. The chart visually demonstrates the 
11.175% decrease in the rate of vasopressor administration with 
the prophylactic administration of ondansetron.

	

	

Case Processing Summary 

Cases 

Valid Missing Total 

 N Percent N Percent N Percent 

Ondansetron 1=yes; 0=no * 

Vasopressor 1= yes; 0=no 
46 100.0% 0 0.0% 46 100.0% 

Ondansetron 1=yes; 0=no * Vasopressor 1= yes; 0=no cross tabulation 

Vasopressor 1= yes; 0=no 

 No Vasopressor Yes Vasopressor Total 

Count 17 15 32 No 

Ondansetron Expected Count 18.1 13.9 32.0 

Count 9 5 14 

Ondansetron  

1=yes; 0=no 

Yes 

Ondansetron Expected Count 7.9 6.1 14.0 

Count 26 20 46 Total 

Expected Count 26.0 20.0 46.0 

Chi-Square Tests 

 Value df 

Asymp. Sig.  

(2-sided) 

Exact Sig.  

(2-sided) 

Exact Sig.  

(1-sided) 

Pearson Chi-Square .494a 1 .482   

Continuity Correctionb .144 1 .704   

Likelihood Ratio .499 1 .480   

Fisher's Exact Test    .535 .355 

Linear-by-Linear Association .483 1 .487   

N of Valid Cases 46     

a. 0 cells (.0%) have expected count less than 5. The minimum expected count is 6.09. 

b. Computed only for a 2x2 table 



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 54

Only 3 obese parturients who received ondansetron 
required ephedrine administration, with a mean dose of 10 mg 
administered. Of the obese parturients not prophylactically 
treated with ondansetron, 14 required ephedrine administration, 
with a mean dose of 18.57 mg administered.

Similarly, only 2 obese parturients who received prophylactic 
ondansetron required phenylephrine, with a mean dose of 0.1 
mg administered. Of the obese parturients not prophylactically 
treated with ondansetron, 1 required phenylephrine 
administration, with a dose of 0.05 mg administered.

An independent samples t-test revealed that there was not a 
significant mean difference in vasopressor administration dosage 
between those who received ondansetron (M = 10, SD = 5) and 
those who did not receive ondansetron (M = 18.57, SD = 7.45; 
t(15) = 1.35, p > 0.05) (Table 2).

Overall results showed a reduced pattern of vasopressor 
administration among obese women who received 4 mg IV 
ondansetron 5 minutes before receiving spinal anesthesia. 
However, when compared with women who did not receive 
ondansetron administration, the frequency of vasopressor 
administration did not significantly differ between the groups.

The average BMI for the obese patients included in the study 
was 36.97, compared with 27.55 for patients excluded from the 
study for being nonobese. The average maternal age was 30.06 
years for the obese group and 29.833 for the nonobese group. 
The average gestational age was 38 weeks for the obese group, 
compared with 38.67 weeks for the nonobese group. Among the 
obese group, 39 (84.7%) were Hispanic, whereas 5 (10.8%) were 
white, and 2 (4.3%) were of other ethnicity (Figure 2).

	

	

Case Processing Summary 

Cases 

Valid Missing Total 

 N Percent N Percent N Percent 

Ondansetron 1=yes; 0=no * 

Vasopressor 1= yes; 0=no 
46 100.0% 0 0.0% 46 100.0% 

Ondansetron 1=yes; 0=no * Vasopressor 1= yes; 0=no cross tabulation 

Vasopressor 1= yes; 0=no 

 No Vasopressor Yes Vasopressor Total 

Count 17 15 32 No 

Ondansetron Expected Count 18.1 13.9 32.0 

Count 9 5 14 

Ondansetron  

1=yes; 0=no 

Yes 

Ondansetron Expected Count 7.9 6.1 14.0 

Count 26 20 46 Total 

Expected Count 26.0 20.0 46.0 

Chi-Square Tests 

 Value df 

Asymp. Sig.  

(2-sided) 

Exact Sig.  

(2-sided) 

Exact Sig.  

(1-sided) 

Pearson Chi-Square .494a 1 .482   

Continuity Correctionb .144 1 .704   

Likelihood Ratio .499 1 .480   

Fisher's Exact Test    .535 .355 

Linear-by-Linear Association .483 1 .487   

N of Valid Cases 46     

a. 0 cells (.0%) have expected count less than 5. The minimum expected count is 6.09. 

b. Computed only for a 2x2 table 

Figure 2. Demographic data on ethnicity.
Pictorial summary of the ethnicity of the 46 patients included in 
the study.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 55

It is vital to examine the association between ondansetron 
administration and vasopressor administration in a larger sample 
of obese women in the future. It is challenging to detect a 
significant association between ondansetron administration and 
vasopressor administration in a limited sample size such as that 
used in the present study.24-26

DISCUSSION

Limitations
Although the results of the retrospective chart review 

demonstrated improvements in hemodynamic stability among 
obese parturients undergoing spinal anesthesia for cesarean 
delivery, the project was limited by a small sample size and a 
retrospective design. Future research should be conducted via 
prospective RCT with a larger sample size to provide definitive 
recommendations for practice change.

Additional limitations of this retrospective chart review 
included an inability to control for variances in fluid management, 
including volume of crystalloid or colloid pre-loading. Provider 
preference and threshold for vasopressor administration also 
impacted the results of the chart review and will be difficult to 
control in an RCT as well.

Implications for Practice
The findings from this retrospective analysis, although based 

on a small sample size, support the recommendation for routine 

prophylactic administration of 4 mg IV ondansetron 5 min before 
the administration of spinal anesthesia for cesarean delivery.

Considerations regarding differences in the apparent efficacy 
of ondansetron as a prophylactic anti-hypotensive pharmacologic 
intervention in obese versus nonobese groups are many. Obesity-
related physiologic changes include increased aorto-caval 
compression secondary to increased weight, greater volume 
of distribution, and elevated preoperative fluid requirements. 
Pharmacologic considerations include weight-based dosing 
of ondansetron and the addition of colloids to crystalloids to 
maximize intravascular volume before the administration of 
spinal anesthesia among obese parturients.

Summary
As a result of this retrospective chart analysis, it has been 

demonstrated that the novel application of ondansetron as a 
prophylactic anti-hypotensive agent administered 5 minutes 
before the induction of spinal anesthesia may improve 
hemodynamic stability among patients with a BMI > 30 
necessitating cesarean delivery. These findings are consistent with 
current recommendations for the nonobese population based 
on the extant medical literature. It may be possible to attenuate 
the maternal-fetal risk associated with the administration 
of spinal anesthesia in the vulnerable and ever-increasing 
population of obese parturients if this evidence-based practice is 
further established in a larger sample size in an RCT and with 
subsequent widespread adoption into anesthetic protocols.



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Volume 4 - Issue 1 2016 Page 56

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