Original Article

Comparison between phenylephrine and

ephedrine in preventing hypotension during
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spinal anesthesia for cesarean section

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Iqra Nazir, Mubasher A. Bhat,

Syed Qazi, Velayat N. Buchh,
Showkat A. Gurcoo
Department of Anaesthesiology and
Critical Care, Sher-i-Kashmir Institute
of Medical Sciences, Soura, Srinagar,
J and K, India
Address for correspondence:
Dr. Mubasher Ahmad Bhat, 65, Alfarooq
Colony, Sanatnagar Bypass, Srinagar,
India.
E-mail: ahmadmubashir84@yahoo.com
ABSTRACT
Background: Maternal hemodynamic changes are common during spinal anesthesia for
cesarean delivery. Many agents are used for treating hypotension. In this study we compared
the efficacy of ephedrine and phenylephrine in preventing and treating hypotension in spinal
anesthesia for cesarean section and their effect on fetal outcome.
Materials and Methods: A total of 100 ASA Grade I patients undergoing elective cesarean
section under spinal anesthesia with a normal singleton pregnancy beyond 36 weeks gestation
were randomly allocated into two groups of 50 each. Group I received prophylactic bolus dose
of ephedrine 10 mg IV at the time of intrathecal block with rescue boluses of 5 mg. Group II
received prophylactic bolus dose of phenylephrine 100 g IV at the time of intrathecal block
with rescue boluses of 50 g. Hemodynamic variables like blood pressure and heart rate was
recorded every 2 minutes up to delivery of baby and then after every 5 minutes. Neonatal
outcome was assessed using Apgar score at 1 and 5 minutes and neonatal umbilical cord
blood pH values.
Results: There was no difference found in managing hypotension between two groups.
Incidence of bradycardia was higher in phenylephrine group. The differences in umbilical cord
pH, Apgar score, and birth weight between two groups were found statistically insignificant.
Conclusion: Phenylephrine and ephedrine are equally efficient in managing hypotension
during spinal anesthesia for elective cesarean delivery. There was no difference between two
vasopressors in the incidence of true fetal acidosis. Neonatal outcome remains equally good
in both the groups.
Key words: Ephedrine, fetal acidosis, hypotension, phenylephrine, spinal anesthesia

INTRODUCTION pulmonary aspiration, respiratory depression, and cardiac

S pinal anesthesia has been widely used for cesarean section
and has been found efficacious and safe. The incidence of
hypotension during cesarean section under spinal anesthesia
has been reported to be 80–90% or greater depending
on the definition used.[1,2] For the mother, hypotension is
especially associated with nausea and vomiting[3] and in more
severe cases there may be risk of decreased consciousness,
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DOI:
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arrest. Hypotension can have detrimental effects on neonate,
which include decrease in uteroplacental flow, impaired
fetal oxygenation with asphyxial stress, and fetal acidosis.[4]
Because hypotension may be associated with both maternal
and neonatal morbidity, many different methods have been
investigated alone and in combination for both its prevention[1]
and treatment. Left uterine displacement is known to decrease
the effects of aortocaval compression.[5] Leg elevation alone
has not been shown to reduce the incidence of hypotension.[6]
Prehydration or preloading is commonly administered but it
has controversial results.[7,8]
Because of the poor efficacy of nonpharmacological techniques
to effectively manage hypotension, a vasopressor is usually
required during spinal anesthesia for cesarean section. In
choosing an appropriate vasopressor in obstetrics, a number
of factors like efficacy for maintaining blood pressure,

92 Journal of Obstetric Anaesthesia and Critical Care / Jul-Dec 2012 / Vol 2 | Issue 2
 Nazir, et al.: Prevention of Hypotension during Spinal Anesthesia
noncardiovascular maternal effects, ease of use, direct and
indirect fetal effects, cost, and availability need to be considered.
Vasopressor used commonly for preventing hypotension
during spinal anesthesia are ephedrine, phenylephrine,
and metaraminol. Use of ephedrine in obstetric patients is
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supported by animal studies, which showed that uteroplacental
blood flow is better maintained when ephedrine was used to
raise maternal blood pressure.[9] Disadvantages of ephedrine
include a slow onset and relatively long duration, which may
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make accurate titration of blood pressure difficult.[10] Recent
clinical studies have shown ephedrine to be associated with a
dose-related propensity to depress fetal pH and base excess.[4]
Phenylephrine is a potent direct-acting alpha agonist. In
pregnancy, because of a generalized reduction in pressor
response to endogenous and exogenous vasoconstrictors,[11]
relatively large doses of phenylephrine may be required.
However, fetal acidosis has not been demonstrated when
phenylephrine is used liberally to maintain maternal blood
pressure and prevent symptoms.[12]
The present study was designed to assess the effectiveness
of ephedrine and phenylephrine in preventing and treating
hypotension in spinal anesthesia for cesarean section and their
effect on fetal outcome.
MATERIALS AND METHODS
This prospective double blind randomized controlled study was
conducted in the Department of Anesthesiology and Critical
Care from 2008 to 2010.
After a proper approval of Institute ethical committee and a
written informed consent, 100 ASA grade I patients undergoing
elective cesarean section under spinal anesthesia with a normal
singleton pregnancy beyond 36 weeks gestation were recruited.
Patients with pregnancy-induced hypertension, history of
diabetes, cardiovascular and cerebrovascular disease, fetal
abnormalities, and contraindication to spinal anesthesia were
excluded from the study. Patients were randomly allocated into
two groups of 50 each.
Group 1 received prophylactic bolus of ephedrine 10 mg IV
at the time of intrathecal block, plus rescue boluses of 5 mg
ephedrine, whenever maternal systolic blood pressure was less
than 90 mmHg.
Group 2 received prophylactic bolus of 100 g i/v of
phenylephrine at the time of intrathecal block, plus rescue
boluses of 50 g phenylephrine, whenever maternal systolic
blood pressure was less than 90 mmHg.
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In order to maintain blinding, the vasopressor solutions were
prepared in identical syringes by an anesthetist or investigator
who was not involved in subsequent patient care. Each subject
received oral ranitidine 150 mg on the evening before and
2 hours preoperatively as premedication with a sip of water.
On arrival in the operation theatre heart rate (ECG), blood
pressure (NIBP), respiratory rate, and arterial O2 saturation
(SaO2) were monitored. An infusion of normal saline was started
in all patients and preloaded with 10 ml/kg of normal saline.
Patients were placed in lateral or sitting position according
to their convenience. Lumbar puncture was performed with
25 gauge Quincke’s needle in L3-L4 intervertebral space. Once
free flow of cerebrospinal fluid was obtained, 2.5 ml of 0.5%
bupivacaine was administered over 10–15 seconds.
Time of injection of drug was noted and patient was placed
in supine position immediately with a left lateral tilt of 15–20
degrees. Inspired air was supplemented with oxygen at 5 l/min
until clamping of umbilical cord. Immediately after induction
of spinal anesthesia, systolic blood pressure, diastolic blood
pressure, and heart rate were recorded. One minute after
intrathecal injection, patients were given either phenylephrine
100 g IV bolus or ephedrine 10 mg IV bolus. Hemodynamic
variables like blood pressure and heart rate was recorded
every 2 minutes up to delivery of baby and then after every
5 minutes. Whenever systolic blood pressure decreased to less
than 90 mmHg, vasopressor was administered, either 5 mg of
ephedrine or 50 g of phenylephrine. On each occasion when
maternal heart rate decreased to below 60 beats per minute
(bpm), atropine 0.3 mg IV was administered.
Neonatal outcome was assessed using Apgar score at 1 and
5 minutes and neonatal umbilical cord blood pH values.
At delivery umbilical cord was clamped and 1 ml of blood
sample collected in heparinized syringe for acid base analysis.
Umbilical artery pH value < 7.2 indicates asphyxia.
Statistical analysis: Parametric data was expressed as mean
± SD, thereby the inter group comparisons were made by
Student’s t-test. The test was two sided and referred for P-value
for its significance. P-value less than 0.05 (P< 0.05) was taken to
be statistically significant. The analysis was performed on SSPS
version 11.3, statistical software for social sciences, Chicago,
USA for Windows.
RESULTS
A total of 100 patients selected for this study were randomly
divided into two groups of 50 patients each. The two groups
were matched with regard to their age, body weight [Table 1],
and duration of surgery [Figure 1].
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 Nazir, et al.: Prevention of Hypotension during Spinal Anesthesia
Table 1: Comparison of age and weight between group 1 and group 2
Characteristics Group 1 (n=50) Mean±SD
Age (years) 30.28±0.52
Weight (kg) 62.53±8.71
NS=Not significant
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16 15 15
14
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12
12 12
10
8 Induction till delivery time
Delivery till end of surgery
6 and neonate. These effects include decrease in uteroplacental
4
2
0
Group 1 Group 2
Figure 1: Comparison between surgical times in groups 1 and 2
The difference observed in baseline heart rate, systolic,
diastolic, and mean blood pressures between two groups was
statistically insignificant [Table 2]. There was higher incidence
of bradycardia in patients receiving phenylephrine than those
receiving ephedrine. The difference in mean heart rate till
delivery compared between two groups immediately after
spinal anesthesia, at 2, 4, 6, 8, 10, and 12 minutes was significant
while it was insignificant at 0 and 14 minutes (P value < 0.05:
significant). The difference in mean heart rate compared
between two groups at delivery, 5, 10, minutes and at the end of
the surgery was insignificant except at delivery and 15 minutes
after delivery (P value < 0.05: significant) [Tables 3 and 4].
The difference in systolic, diastolic, and mean blood pressure
between two groups till delivery and after delivery at all times
was statistically insignificant. Overall, 35/50 (70%) patients in
the phenylephrine group and 33/50 (66%) patients in ephedrine
group had one or more episode of hypotension and required
one or more bolus of vasopressor. The number of rescue doses
required in groups 1 and 2 were statistically insignificant
[Tables 3-6] (P value < 0.05: significant).
The difference in birth weight of neonates between two groups
was statistically nonsignificant [Table 7]. No neonate had Apgar
score <7 at 1 or 5 minute. Mean neonatal umbilical cord pH in
group 1 was 7.33±0.04 and in group 2 it was 7.34±0.04. Patients
given phenylephrine had neonates with higher umbilical
cord pH than those given ephedrine but the difference was
statistically nonsignificant [Table 7].
94
Group 2 (n=50) Mean±SD P-value Significance
31.26±0.47 0.146 NS
69.53±8.11 0.06 NS
DISCUSSION
The most important physiological response to spinal
anesthesia involves cardiovascular system. Overall incidence
of hypotension during spinal anesthesia in cesarean section is
80%. Hypotension can have detrimental effects on both mother
blood flow, impaired fetal oxygenation with asphyxia stress, fetal
acidosis,[4] and maternal symptoms of low cardiac output such
as nausea, vomiting, dizziness,[3] and decreased consciousness.
Left uterine displacement is known to decrease the effects of
aortocaval compression.[5] Leg elevation alone has not been
shown to reduce the incidence of hypotension.[6] Prehydration
or preloading is commonly administered but it has controversial
results.[7,8] Despite all conservative measures, a vasopressor
drug is often required to prevent hypotension during spinal
anesthesia.[13]
In this study, all patients in the two groups were comparable
with respect to age and ASA status. The difference observed
in baseline parameters, that is, pulse, systolic, diastolic,
and mean arterial pressures between two groups was
statistically insignificant, respectively. There was statistically
nonsignificant difference between surgical times (induction
to delivery time and from delivery till end of surgery) in
groups 1 and 2.
In this study, there was higher incidence of bradycardia
in patients receiving phenylephrine than those receiving
ephedrine This is expected to be due to increase in blood
pressure with an α-agonist may lead to reactive bradycardia
(baroreceptor reflex). However, this was responsive to atropine
without adverse consequences. Atropine was required in 17 of
50 patients in group 2 compared with 5 of 50 patients in group
1. There was no difference in maximum recorded heart rate
between two groups.
The results of this study were in accordance with the study
of Lee et al.[4] in which they reported higher incidence of
bradycardia in patients receiving phenylephrine as compared
with patients receiving ephedrine for prevention of hypotension
during spinal anesthesia for cesarean section.
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 Nazir, et al.: Prevention of Hypotension during Spinal Anesthesia

Table 2: Comparison of baseline heart rate, systolic, diastolic and mean blood pressure in groups1 and 2
Characteristics Group 1 Mean±SD Group 2 Mean±SD t-value P-value Significance
Heart rate 90.32±16.65 87.38±13.03 1.01 0.321 NS
Systolic blood pressure 120.24±12.35 120.44±9.84 0.93 0.921 NS
Diastolic blood pressure 78.32±9.90 76.16±9.30 1.03 0.308 NS
Mean blood pressure 90.30±10.07 92.92±8.85 0.62 0.498 NS
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NS=Not significant

Table 3: Comparison of heart rate, systolic and diastolic blood pressure between groups 1 and 2 before delivery
Heart rate (bpm*) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
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Parameter Group 1 Group 2 P Group 1 Group 2 P Group 1 Group 2 P

till deliyery mean±SD mean±SD mean±SD mean±SD mean±SD mean±SD
Immediately 92.4O±21.45 86.02± 12.02 0.070 107.88±14.87 107.30±13.57 0.843 69.66± 11.79 69.80± 10.50 0.948
after S.A
2 min 99.8±22.38 84.52± 17.86 0.001 119.76±17.44 110.12±17.44 0.071 77.52± 11.76 73.04±12.85 0.055
4 min 99.78±21.37 82.88± 16.90 0.001 112.20±18.05 107.60±17.96 0.089 73.56± 11.16 74.16± 10.67 0.770
6 min 91.80±15.07 82.28±16.20 0.004 108.52±20.21 105.96±16.87 0.500 74.84± 13.19 76.12± 12.58 0.634
8 min 93.4O±15.22 85.80±17.33 0.021 110.96±14.31 106.56±14.92 0.079 74.68± 11.66 73.20± 11.60 0.512
10 min 90.86±15.07 4.28±15.20 0.038 109.84± 10.49 105.76±14.58 0.093 77.16± 11.19 75.88± 9.50 0.528
12 min 91.62±15.83 85.44±15.35 0.056 13.96±12.46 109.56± 10.42 0.D75 75.52± 8.22 76.12± 8.32 0.622
14 min 97.00± 3.93 94.20±5.12 0.215 115A7±5.68 115.20± 5.02 0.093 72.67± 11.36 72.00± 14.24 0.929

Table 4: Comparison of mean pulse rate, systolic blood pressure and diastolic blood pressure between groups 1
and 2 after delivery
Heart rate Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
Parameter Group 1 Group 2 P Group 1 Group 2 P Group 1 Group 2 P
till deliyery mean±SD mean±SD mean±SD mean±SD mean±SD mean±SD
At delivery 97.40±13.42 91.76± 14.00 0.03 116.92±14.60 120.68±12.32 0.22 75.96± 11.75 77.72± 9.72 0.45
5 min 93.94±14.82 88.72± 13.23 0.09 113.56±15.35 112.48±14.06 0.70 74.12± 11.41 74.76±10.52 0.75
10 min 88.26±13.18 86.24± 12.23 0.45 116.84±17.43 112.52±17.05 0.26 76.88± 12.45 72.98± 11.29 0.09
15 min 93.62±8.84 91.63±15.17 0.00 116.04±14.55 114.40±14.86 0.54 75.80± 8.02 73.12± 9.57 0.09
20 min 90.69±5.52 91.80±7.56 0.94 116.00±8.26 104.67±19.66 0.08 71.23± 8.12 68.91± 10.40 0.40
End of surgery 91.12±6.90 85.88±12.98 0.22 115.00± 13.54 114.72±12.74 0.90 75.04± 9.28 72.64± 7.78 0.17

Table 5: Comparison of mean blood pressure (mmHg) till delivery between groups 1 and 2
Mean BP (mmHg) Group 1 Mean±SD Group 2 Mean±SD t-value P-value Significance
Immediately after SA 82.39±11.66 82.30±9.94 0.037 0.971 NS
2 min 90.13±10.43 87.88±12.93 1.863 0.078 NS
4 min 87.17±12.18 88.36±12.15 0.341 0.773 NS
6 min 88.94±13.74 90.97±13.18 0.394 0.814 NS
8 min 88.13±12.67 84.80±12.92 0.732 0.412 NS
10 min 90.04±11.45 85.15±10.13 0.842 0.374 NS
12 min 89.13±9.13 90.26±9.28 0.763 0.451 NS
14 min 85.94±11.36 85.13±13.26 0.124 0.843 NS
NS=Not significant

Table 6: Comparison of mean blood pressure (mmHg) after delivery in groups 1 and 2
Mean BP (mmHg) Group 1 Mean±SD Group 2 Mean±SD t-value P-value Significance
At delivery 89.61±12.00 92.04±9.54 0.994 0.325 NS
5 min after delivery 87.24±11.62 86.92±12.71 0.395 0.693 NS
10 min 89.95±12.37 86.27±12.75 1.724 0.085 NS
15 min 88.72±9.15 85.78±9.34 1.683 0.104 NS
20 min 85.14±9.00 82.37±10.73 1.045 0.273 NS
At the end of surgery 88.36±8.92 86.67±7.60 1.070 0.290 NS
NS=Not significant

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 Nazir, et al.: Prevention of Hypotension during Spinal Anesthesia
Table 7: Comparison of birth weight and umbilical
cord pH between groups 1 and 2
Parameter Birth weight (grams) Umbilical cord pH
Group 1 3253±532.9 7.33±0.04
Group 2 3229±424.88 7.34± 0.04
P value 0.824 0.280
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P value < 0.05: Significant
We confirmed in this study that there was no difference between
ephedrine and phenylephrine in their efficacy for managing
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hypotension following spinal anesthesia in parturients
undergoing cesarean delivery in the range of doses that have
been studied.
The results of this study are in accordance with the study of
Adigun et al.[14] They observed that both vasopressors effectively
restored both the systolic and diastolic blood pressure. They
also concluded that phenylephrine is safe and can be used as
effectively as ephedrine.
Gunda et al.[15] compared the effectiveness and the side effects
of vasopressors, ephedrine, and phenylephrine, administered
for hypotension during elective cesarean section under spinal
anesthesia. They found that for the management of hypotension
there was no difference, similar to our findings. However, the
study suggests that phenylephrine may be more appropriate
vasopressor when considering maternal well-being. This may
have been because less dose of ephedrine was used in this study
as compared with this study.
This study is not consistent with the work of Magalhães et al.[16]
study on ephedrine versus phenylephrine for prevention of
hypotension during spinal block for cesarean section and effects
on fetus. They concluded that ephedrine was more effective
than phenylephrine in the prevention of hypotension. This
may have been because less dose of phenylephrine was used
in their study as compared with this study.
However, this study showed that women who received
phenylephrine had neonates with higher umbilical cord pH
than women who received ephedrine, although the risk of
true fetal acidosis (umbilical artery pH<7.20) was similar. No
neonate in both groups had pH < 7.2. Prakash et al.[2] found
that women who were given phenylephrine had neonates
with higher umbilical arterial pH values than those given
ephedrine. There was no difference between two groups
in the incidence of true fetal acidosis similar to this study
finding.
Cooper et al.[17] concluded in their study that the umbilical
artery pH was similar, whether ephedrine or phenylephrine
was used to maintain maternal arterial pressure, which is
96
consistent with this study. Acidotic changes in umbilical artery
are sensitive indicators of uteroplacental insufficiency. The
study finding is indirect evidence that uterine blood flow may
in fact be better with phenylephrine compared with ephedrine.
The exact reason how ephedrine causes acidosis is unknown.
One of the reasons is that it crosses through placenta and has
a direct effect on fetus to cause acidosis.
There was no difference in Apgar score between the two groups.
In this study, no neonate had an Apgar score < 7 at 1 or at
5 minutes. The difference in birth weight of neonates between
two groups was statistically nonsignificant.
Adigun and Amnaor-Boadu[14] in their study compared
intravenous ephedrine with phenylephrine for the maintenance
of arterial blood pressure during elective cesarean section under
spinal anesthesia. The mean Apgar scores were similar for the
two groups; no baby had Apgar score of <8 in either group.
The results are in accordance with this study.
CONCLUSION
We conclude from this study that phenylephrine and ephedrine
are equally efficient in managing hypotension during spinal
anesthesia for elective cesarean delivery. There was no difference
between two vasopressors in the incidence of true fetal acidosis.
Neonatal outcome remains equally good in both the groups.
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Cite this article as: Nazir I, Bhat MA, Qazi S, Buchh VN, Gurcoo SA.
Comparison between phenylephrine and ephedrine in preventing hypotension
during spinal anesthesia for cesarean section. J Obstet Anaesth Crit Care
2012;2:92-7.
Source of Support: Nil, Conflict of Interest: None declared.

Journal of Obstetric Anaesthesia and Critical Care / Jul-Dec 2012 / Vol 2 | Issue 2 97