Comparison the effect of ephedrine and phenylephrine in treatment of hypotension after spinal anesthesia during cesarean section

doi:10.4236/ojog.2012.23038

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Open Journal of Obstetrics and Gynecology, 2012, 2, 192-196 OJOG

http://dx.doi.org/10.4236/ojog.2012.23038 Published Online September 2012 (http://www.SciRP.org/journal/ojog/)

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: *[email protected]

Received 24 June 2012; revised 27 July 2012; accepted 15 August 2012

ABSTRACT

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

Outcome

1. INTRODUCTION

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.

2. METHODS AND MATERIALS

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.

OPEN ACCESS

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

surgery.

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.

3. RESULTS

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)

A. Simin et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 192-196

194

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).

4. DISCUSSION

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

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).

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