Open Journal of Obstetrics and Gynecology, 2012, 2, 192-196 OJOG Published Online September 2012 (
Comparison the effect of ephedrine and phenylephrine
in treatment of hypotension after spinal anesthesia
during cesarean section
Atashkhoyi Simin1*, Fardiazar Zahra2, Hatami Marandi Pouya3, Torab Reza3
1Department of Anesthesiology, Women’s Reproductive Research Center, Alzahra Hospital, Tabriz University of Medical Sciences,
Tabriz, Iran
2Department of Obstetrics & Gynecology, Alzahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
3Tabriz University of Medical Sciences, Tabriz, Iran
Email: *
Received 24 June 2012; revised 27 July 2012; accepted 15 August 2012
Background and Objective: The effectiveness of ephe-
drine and/or phenylephrine, in treatment of hypoten-
sion secondary to spinal anesthesia for cesarean sec-
tion and their effects on fetal/neonatal outcome were
studied. Methods and Materials: Sixty healthy partu-
rients were randomly assigned to two groups; group
E (n = 33) received boluses 5 mg/ml increments
ephedrine and group P (n = 27) received a boluses of
phenylephrine 100 µg/ml increments for treatment of
hypotension after spinal block during cesarean sec-
tion. Changes in maternal blood pressure and heart
rate, and incidence of nausea-vomiting, neonatal Ap-
gar score at 1 and 5 minutes of delivery, and umbili-
cal arterial blood gas values were recorded. Results:
There were no differences in treatment of hypoten-
sion following sympathectomy after spinal block with
two drugs. Neonatal outcome was similar in two
groups. There were not significant differences in um-
bilical arterial values in two groups. Conclusion:
Ephedrine and phenylephrine are both effective vaso-
pressores for treatment of hypotension associated to
spinal block during cesarean section without adverse
effects on inf ants/neonates.
Keywords: Cesarean Section; Spinal Anesthesia;
Hypotension; Ephedrine; Phenylephrine; Fetal/Neonatal
Hypotension is perhaps the most common complication
of neuraxial anesthesia in obstetric patients [1]. It has
been estimated to occur in approximately 30% - 90% of
cases [2].
Maternal hypotension produces unpleasant symptoms
such as nausea, vomiting, and lightheadedness. More
importantly, when severe and sustained, hypotension can
impair uterine and intervillous blood flow and ultimately
result in fetal acidosis and neonatal depression [1-4].
Prevention measures include fluid preload, left lateral tilt,
and use of vasopressors [1-6].
Traditionally, ephedrine “which has a strong β-adren-
ergic and a weaker α-adrenergic effects” has been re-
commended in this situation, but its position has been
challenged because of potential complication that supra-
ventricular tachycardia, tachyphylaxis, and most impor-
tantly fetal acidosis [1-7]. Phenylephrine, an α-adrener-
gic agonist, can be used for prevention and treatment of
maternal hypotension. Moreover, phenylephrine reduces
the incidence of nausea and vomiting as well as fetal
acidosis, but it may cause maternal bradycardia [1,3-6].
Cooper and colleagues [7-9] in their studies and Lee et
al. [10] in a quantitative and systematic review have re-
ported that managing of maternal hypotension with
phenylephrine has fewer propensities to depress fetal pH
than ephedrine.
Although recent studies have confirmed the beneficial
fetal effects of phenylephrine [5-11], but there are a num-
ber controversies in this concept.
Present study compared ephedrine with phenylephrine
in treatment (not prevention) of maternal hypotension
induced spinal anesthesia regarding the maternal cardiac
response to hypotension in terms maternal hemodynamic
and fetal/neonatal status.
This was a prospective, double-blind, and case-control-
led study. After the approval of the hospitals ethics Com-
mittee and obtaining written informed consent, 60 partu-
rients of ASA physical status I, age > 18 years, undergo-
*Corresponding author.
A. Simin et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 192-196 193
ing elective cesarean section under spinal anesthesia
during 6 months.
A priori excluded were patients with classic contrain-
dications to spinal block, allergy to local anesthetics,
pre-existing systemic disease, known fetal abnormalities,
and history of tacking any medications that could influ-
ence hemodynamic responses.
Patients were fasted for 6 hours. In the operating room
routine standard monitoring with non-invasive arterial
pressure (NIBP), electrocardiography (ECG), and pulse-
oximetry was established. Baseline measurements were
performed 5 minutes before spinal anesthesia. A canola
was introduced into a peripheral vein. Each patient was
preloaded 15 ml/kg of ringer lactate solution. With the
patient in the sitting position, lumbar puncture was per-
formed at the L3-4 or L4-5 interspaces with 1ml of 5%
hyperbaric lidocaine (lidocaine spinal 5% Heavy; Orion
corporation, Espoo, Finland) and 15 µg fentanyl in 1.5
ml via a 25-guage Quincke spinal needle. Total volume
of subarachnoid solution was 2.5 ml. Immediately after
completing the intrathecal injection, patients were posi-
tioned supine on the operating table. From this moment
on, the level of the sensory block was evaluated by loss
of Pinprick discrimination at the time to incision and
every 5 minutes. Sensory block to T5 dermatome was
considered adequate surgery.
Parturients were assigned to receive one of two vaso-
pressor solutions whenever maternal systolic arterial
pressure (SAP) decreased to 80% of baseline or less.
Group E received boluses 5 mg/ml increments ephedrine
if there was maternal decreased heart rate (HR 20%
lower than baseline values) with a SAP 20% less than
baseline; group P received a bolus of phenylephrine 100
µg/ml increments whenever there was increased heart
rate( heart rate 20% higher than baseline levels).
The collection of the data and analysis were performed
by a physician who was not involved in the syringe with
the study solutions.
All hemodynamic evaluations were performed at 2-
minutes interval until delivery. After that, these parame-
ters were determined at 5-minutes interval until end of
Changes in maternal BP (SAP, DAP) and HR through-
out anesthesia, incidence of nausea and vomiting, total
dose and the number of boluses of vasopressors, sensory
block level (dermatome), and total volume of fluids,
were recorded.
Apgar scores at 1 and 5 minutes of delivery for all
newborns were noted and a score < 8 was considered low.
Umbilical arterial blood sampling was obtained for de-
termination of acid-base status.
Data are presented as means (SD), medians (range),
and counts. Means were analyzed using Student’s t-test,
medians using Mann-Whitney U-test and counts using
Fisher’s exact and x2 tests. All analyses were performed
using the SPSS statistical software, version 13.00 (SPSS
Inc., Chicago, IL, USA). P < 0.05 was considered sig-
nificant. Sample size estimations were based on data
from a previous study which showed that a minimum of
60 subjects with 80% power.
Total 60 patients were enrolled in this study, 33 patients
for ephedrine group and 27 patients for phenylephrine
group. The groups were comparable with respect to age,
weight, height, gravidity, iv fluid volume, and median
level of sensory block (Table 1).
Figures 1 and 2 present changes of SAP, and HR in
two groups. There were no significant differences in SAP
Table 1. Patient’s characteristics and intraoperative variables in two groups.
Group E (n = 33) Group P (n = 27) P
Age (yr) 28.10 ± 4.86 29.56 ± 4.89 0.72
Weight (kg) 73.42 ± 9.48 75.03 ± 10.17 0.89
Height (cm) 159.53 ± 5.50 161.77 ± 4.05 0.62
Gestational age (wk) 39 (37 - 39) 39 (37 - 39) 1.00
Upper sensory level (median, range) T5 (T3 - T6) T5 (T3 - T6) 1.00
Duration of anesthesia (min) 75.52 ± 8.65 73.24 ± 8.42 0.65
Duration of surgery (min) 54.46 ± 6.61 51.71 ± 6.85 0.82
Total fluid during anesthesia (ml) 1850 ± 120 2050 ± 150 0.75
Total dose of vasopressor 8.36 ± 0.85 (mg) 123.33 ± 40.96 (μg) -
Number of vasopressor administration 2 (1 - 3) 2 (1 - 2) 0.25
Incidence of nausea-vomiting (%) 5 (15.1) 2 (7.1) 0.34
Values are number (%), mean (SD) or median (range)
Copyright © 2012 SciRes. OPEN ACCESS
A. Simin et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 192-196
Figure 1. Systolic arterial pressure (SAP) changes before and
after spinal anesthesia, and after administration of vasopressors.
Figure 2. Heart rate (HR) changes before and after spinal an-
esthesia, and after administration of vasopressors (*P < 0.05).
value at the same time points between two groups, but
HR values were significant in the two groups at the 2 and
4-minutes time point of spinal block. There was no sig-
nificant difference in number of vasopressor administra-
tion between two groups (P = 0.25). Total dose of ephed-
rine was 8.36 ± 0.85 mg, and for phenylephrine was
123.33 ± 40.96 μg (Table 1).
The overall incidence of nausea was low, with no sig-
nificant differences being observed in incidence (five in
the E group and 2 in the P group) or severity (Table 1).
Neonatal data are presented in Table 2. Apgar score at
1 and 5 were comparable in two groups. No neonatal had
an Apgar score < 8 at any time point. No umbilical artery
pH values were 7.20. Umbilical artery pH was lower in
group E than the group P, but it was not significant (P =
0.12). Other umbilical artery parameters were not differ-
ing between two groups of neonates (Table 2).
In this study, we showed that there was no difference
between ephedrine and phenylephrine in their efficacy
for managing hypotension in healthy parturients under-
going cesarean section. In addition, results of our study
have shown that the neonatal outcome was similar be-
tween groups. There were no differences in Apgar scores
at 1 and 5 minutes of birth. So that, there were differ-
ences between groups in umbilical artery pH and base
excess values. The severity of these differences was
small and true acidosis (pH 7.20) was not seen in any
of neonates.
The prevention and treatment of maternal hypoten-
sion-induced spinal anesthesia remains the most impor-
tant problem, with no consensus to the optimal mode of
management [1,4,12]. Clinical data have suggested that
α-adrenergic agonists such as ephedrine or phenylephrine
may be given safely for prevention or treatment of hy-
potension during administration of regional anesthesia
for cesarean section [1,4,10]. Earlier studies have been
confirmed the beneficial phenylephrine effects on um-
bilical pH [5-12], as phenylephrine has been recently the
first line drug for this purpose [13,14]. However, more
recent studies results show that some caution with the
use of phenylephrine may be warranted.
Although phenylephrine is efficient for managing blood
pressure, it causes reflexes bradycardia and it may reduce
cardiac output [10-12]. The clinical significance of this,
is more reduction of utero-placental blood flow [12,
15-17]. Ephedrine also is associated with tachycardia.
For decreasing of the cardiac effects of vasopressors,
Ngan Kee et al. [18] investigated the combination of
phenylephrine and ephedrine in different ratios adminis-
tered by infusion. They found combination of vasopres-
sors appeared to have no advantage compared with
phenylephrine alone. Loughey et al. [3] have been noted
that the combination of two vasopressors is not superior
to ephedrine alone.
Unlike of the previous studies, a recent study reported
that phenylephrine was associated with higher values of
fetal lactate [19]. There is evidence that fetal lactate may
be a better predictor of severe neonatal morbidity than
PH. In the later study by Ngan Kee [20] et al., they
compared the phenylephrine with ephedrine in non-elec-
tive cesarean section. They concluded that despite small
differences between groups in umbilical cord blood lac-
tate concentration and PO2, there were no differences in
fetal acid-base status or clinical neonatal outcome be-
tween the two vasopressors. Our study results relatively
conform to the Ngan Kee [20] study.
In this study, we didn’t administer vasopressors as pro-
phylaxis, for two reasons. First, it is not ethically right;
for example we couldn’t administer ephedrine to a pa-
tient had tachycardia. Second, clinical studies have not
supported the prophylactic use of vasopressors for pre-
vention of spinal hypotension [1,4,21].
The trigger for rescue vasopressor use in most studies
Copyright © 2012 SciRes. OPEN ACCESS
A. Simin et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 192-196 195
Table 2. Neonatal outcome in two groups.
Group E (n = 33) Group P (n = 27) P
Apgar score at:
1 min 8.46 ± 0.32 8.58 ± 0.30 0.22
5 min 9.70 ± 0.59 9.86 ± 0.40 0.15
Apgar score < 8 at 1 and 5 min 0 0 -
Umbilical artery blood gas analysis
pH 7.26 (7.24 - 7.32) 7.28 (7.25 - 7.33) 0.12
PCO2 (mmHg) 51 (48 - 57) 53 (49 - 66) 0.26
PO2 (mmHg) 14 (12 - 18) 12 (11 - 16) 0.27
HCO (mmol) 23 (18 - 22) 21 (16 - 23) 0.61
Base deficit (mmol) 1.6 (0.1 - 2.3) 1.9 (0.3 - 3.2) 0.20
Values are mean (SD), or median (range)
was hypotension. The trigger for rescue iv vasopresor
use in our study was not only 20% - 30% reduction in
SAP, but also the presence heart rate changes secondary
to sympathetic blockade of spinal anesthesia. This is rou-
tine practice for treatment of hypotension in our ward.
Five patients of the ephedrine group vs. 2 of pheny-
lephrine group had nausea. Nausea and vomiting may be
due to the magnitude of hypotension that was similar in
two groups, and may be related to the faster response
time to vasopressors [20]. In this study there was no sig-
nificant difference in this term between two groups.
The bolus doses of phenylephrine (100 µg) and ephed-
rine (5 mg) used in our study was determined empirically.
Bases on our clinical experience and Prakash et al. [16]
study, we chose these doses. Although Saravanon et al.
[17] demonstrated a potency ratio of 80:1 (100 µg phe-
nylephrine ~10 mg ephedrine) for equivalence between
phenylephrine and ephedrine as infusion in prevention of
hypotension induced spinal anesthesia. Prakash et al. [16]
compared the efficacy of phenylephrine 100 µg and
ephedrine 6mg in the treatment maternal hypotension.
Total dose for requirement vasopressors in present
study were lower than the previous studies. The rela-
tively small doses of vasopressors used in this study may
explain the finding that umbilical blood gases values
were not significant different in two groups. Ephedrine-
induced fetal acidosis appears to be associated both with
the total dose of ephedrine given before delivery and
with the duration of fetal exposure to ephedrine, but not
with hypotension. In our study duration of fetal exposure
to vasopressors is less because we used those drugs for
treatment (not prophylaxis) of hypotension. These results
are agreement with other observations previously re-
ported in the literatures.
In summary, the results of this study, shows that
phenylephrine and ephedrine (with respect to maternal
hemodynamic changes) are both efficient and suitable
vasopressors for treatment (not prophylaxis) hypotension
following spinal block in patients undergoing cesarean
section. Both drugs have similar effects on neonates.
Further our work is to determine the optimal managing
of spinal induced hypotension in high-risk pregnancies
(fetal asphyxia).
[1] Chestnut, D.H. (2009) Chestnut’s obstetric anesthesia
principles and practice. 4th Editon, Mosby, Philadelphia.
[2] Rasanen, J., Alahuhtat, S., Kangas-Saarelat, T., Jouppilat,
R. and Jouppila, P. (1991) The effects of ephedrine and
etilefrine on uterine and fetal blood flow and on fetal
myocardial function during spinal anaesthesia for caesar-
ean section. International Journal of Obstetric Anesthesia,
1, 3-8. doi:10.1016/0959-289X(91)90022-I
[3] Loughrey, J.P.R., Yao, N., Datta, S., Segal, S., Pian-Smith,
M. and Tsen, L.C. (2005) Hemodynamic effects of spinal
anesthesia and simultaneous intravenous bolus of com-
bined phenylephrine and ephedrine versus ephedrine for
cesarean delivery. International Journal of Obstetric An-
esthesia, 14, 43-47. doi:10.1016/j.ijoa.2004.07.011
[4] Miller, R.D. (2010) Miller,s anesthesia. 7th Edition, Chur-
chill Livingstone, Philadelphia.
[5] Adigun, T.A., Amanor-Boadu, S.D. and Soyannwo, O.A.
(2010) Comparison of intravenous ephedrine with pheny-
lephrine for the maintenance of arterial blood pressure
during elective caesarean section under spinal anaesthesia.
African Journal of Medicine & Medical Sciences, 39,
[6] Ngan Kee, W.D., Khaw, K.S., Ng, F.F. and Lee, B.B.
(2004) Prophylactic phenylephrine infusion for prevent-
Copyright © 2012 SciRes. OPEN ACCESS
A. Simin et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 192-196
ing hypotension during spinal anesthesia for cesarean de-
livery. Anesthesia & Analgesia, 98, 815-821.
[7] Cooper, D.W., Carpenter, M., Mowbray, P., Desira, W.R.,
Ryall, D.M. and Kokri, M.S. (2002) Fetal and maternal
effects of phenylephrine and ephedrine during spinal an-
esthesia for cesarean delivery. Anesthesiology, 97, 1582-
1590. doi:10.1097/00000542-200212000-00034
[8] Cooper, D.W. and Mowbray, P. (2004) Advantages of
using a prophylactic phenylephrine infusion during spinal
anaesthesia for caesarean section. International Journal
of Obstetric Anesthesia, 13, 124-125.
[9] Cooper, D.W., Gibb, S.C., Meek, T., Owen, S., Kokri,
M.S., Malik, A.T. and Koneti, K.K. (2007) Efects of in-
travenous vasopressor on spread of spinal anesthesia and
fetal acid-base equilibrium. British Journal of Anaesthe-
sia, 98, 649-656. doi:10.1093/bja/aem056
[10] Lee, A., Ngan Kee, W.D. and Gin, T. (2002) A Quantita-
tive, systematic review of randomized controlled trials of
ephedrine versus phenylephrine for the management of
hypotension during spinal anesthesia for cesarean deli-
very. Anesthesia & Analgesia, 94, 920-926.
[11] Magalhaes, E., Goveia, C.S., de Araujo Ladeira, L.C.,
Nascimento, B.G. and Kluthcouski, S.M. (2009) Ephed-
rine versus phenylephrine: Prevention of hypotension
during spinal block for cesarean section and effects on the
fetus. Rev Bras Anestesiol, 59, 11-20.
[12] Ayorinde, B.T., Buczkowski, P., Brown, J., Shah, J. and
Buggy, D.J. (2001) Evaluation of pre-emptive intra-
muscular phenylephrine and ephedrine for reduction of
spinal anaesthesia-induced hypotension during caesarean
section. British Journal of Anaesthesia, 86, 372-376.
[13] Tanaka, M., Balki, M., Parkes, R.K. and Carvalho, J.C.A.
(2009) ED95 of phenylephrine to prevent spinal-induced
hypotension and/or nausea at elective cesarean delivery.
International Journal of Obstetric Anesthesia, 18, 125-
130. doi:10.1016/j.ijoa.2008.09.008
[14] Allen, T.K., Muir, H.A., George, R.B. and Habib, A.S.
(2009) A survey of the management of spinal-induced
hypotension for scheduled cesarean delivery. Interna-
tional Journal of Obstetric Anesthesia, 18, 356-361.
[15] Ngan Kee, W.D. (2010) Prevention of maternal hypo-
tension after regional anaesthesia for caesarean section.
Current Opinion in Anaesthesiology, 23, 304-309.
[16] Prakash, S., Pramanik, V., Chellani, H., Salhan, S. and
Gogia, A.R. (2010) Maternal and neonatal effects of
bolus administration of ephedrine and phenylephrine
during spinal anaesthesia for caesarean delivery: A ran-
domised study. International Journal of Obstetric Anes-
thesia, 19, 24-30. doi:10.1016/j.ijoa.2009.02.007
[17] Saravanan, S., Kocarev, M., Wilson, R.C., Watkins, E.,
Columb, M.O. and Lyons, G. (2006) Equivalent dose of
ephedrine and phenylephrine in the prevention of post-
spinal hypotension in caesarean section. British Journal
of Anaesthesia, 96, 95-99. doi:10.1093/bja/aei265
[18] Ngan Kee, W.D., Khaw, K.S. and Ng, F.F. (2005) Pre-
vention of hypotension during spinal anesthesia for ce-
sarean delivery: An effective technique using combina-
tion phenylephrine infusion and crystalloid cohydration.
Anesthesiology, 103, 744-750.
[19] Erkinaro, T., Kavasmaa, T., Pakkila, M., Acharya, G.,
Makikallio, K., Alahuhta, S. and Rasanen, J. (2006)
Ephedrine and phenylephrine for the treatment of ma-
ternal hypotension in a chronic sheep model of increased
placental vascular resistance. British Journal of An-
aesthesia, 96, 231-237. doi:10.1093/bja/aei305
[20] Ngan Kee, W.D., Khaw, K.S., Lau, T.K., Ng, F.F., Chui,
K. and Ng, K.L. (2008) Randomised double-blinded
comparison of phenylephrine vs ephedrine for main-
taining blood pressure anaesthesia for non-elective cae-
sarean section. Anaesthesia, 63, 1319-1326.
[21] Thomas, D.G., Robson, S.C., Redfern, N., Hughes, D. and
Boys, R.J. (1996) Randomized trial of bolus pheny-
lephrine or ephedrine for maintenance of arterial pressure
during spinal anaesthesia for caesarean section. British
Journal of Anaesthesia, 76, 61-65.
Copyright © 2012 SciRes. OPEN ACCESS