|Year : 2015 | Volume
| Issue : 3 | Page : 155-159
Comparison of intravenous bolus phenylephrine and intravenous ephedrine during crystalloid coloading in ameliorating hypotension under spinal anesthesia for caesarean section
Arun Kumar Natarajan, Nongthombam Ratan Singh, Laithangbam Pradipkumar Singh, Rajkumari Shanti Devi, N Anita Devi, Ashem Jack
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||1-Dec-2015|
N Anita Devi
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Maternal hemodynamic changes are common during spinal anesthesia for caesarean delivery and many agents are used for treating hypotension. In this study, we compared the efficacy of ephedrine and phenylephrine in ameliorating hypotension in spinal anesthesia for caesarean delivery during crystalloid coloading and their effect on fetal outcome. Materials and Methods: A total of 80 American Society of Anesthesiologists (ASA) grade I/II patients undergoing elective cesarean delivery under spinal anesthesia with a normal singleton pregnancy beyond 36 weeks gestation were randomly allocated into two groups of 40 each. Group 1 received bolus dose of intravenous (IV) ephedrine 6 mg and group 2 received bolus doses of IV phenylephrine 100 μg. Hemodynamic variables like blood pressure and heart rate (HR) were recorded every 2 min up to delivery of the baby and thereafter every 5 min. Neonatal outcome was assessed using Apgar score at 1 min and 5 min and neonatal umbilical cord blood pH values. Results: There was no difference found in managing hypotension between the group 1 and group 2. The incidence of bradycardia was higher in phenylephrine group (group 2). The differences in umbilical cord pH, Apgar score, and birth weight between the two groups were found to be statistically insignificant. Conclusion: Phenylephrine and ephedrine are equally efficient in managing hypotension during spinal anesthesia for elective caesarean delivery. There was no difference between the two vasopressors in the incidence of true fetal acidosis and neonatal outcome.
Keywords: Caesarean delivery, Ephedrine, Hypotension, Phenylephrine, Spinal anesthesia
|How to cite this article:|
Natarajan AK, Singh NR, Singh LP, Devi RS, Devi N A, Jack A. Comparison of intravenous bolus phenylephrine and intravenous ephedrine during crystalloid coloading in ameliorating hypotension under spinal anesthesia for caesarean section. J Med Soc 2015;29:155-9
|How to cite this URL:|
Natarajan AK, Singh NR, Singh LP, Devi RS, Devi N A, Jack A. Comparison of intravenous bolus phenylephrine and intravenous ephedrine during crystalloid coloading in ameliorating hypotension under spinal anesthesia for caesarean section. J Med Soc [serial online] 2015 [cited 2021 Dec 8];29:155-9. Available from: https://www.jmedsoc.org/text.asp?2015/29/3/155/170784
| Introduction|| |
Spinal (subarachnoid) anesthesia is considered to be the "gold standard" technique for caesarean delivery.  However, hypotension is the most common side effect of neuroaxial blocks in the obstetric patient. Spinal anesthesia for caesarean delivery is associated with 80% of hypotension cases without prophylactic measures. 
Many interventions such as pelvic tilt,  leg elevation and wrapping,  and the prophylactic administration of fluids  or vasopressors  have been proposed and used to reduce the incidence of maternal hypotension. Despite all these measures, approximately 25% of patients still experience hypotension episodes. 
Crystalloid prehydration has poor efficacy for preventing hypotension, probably because it undergoes rapid distribution.  As an alternative, rapidly administering crystalloid at the time of initiation of anesthesia (called coloading) may be more physiologically appropriate as the maximum effect can be achieved during the time of block and consequent vasodilation evolution.  Ephedrine has been the vasopressor of choice since it has been shown to have a more protective effect on uterine blood flow and perfusion pressure than α-adrenergic agonists.  However, ephedrine is no longer the gold standard for prophylaxis and treatment of hypotension after spinal anesthesia for caesarean delivery. Moreover, higher dose of ephedrine causes significant maternal tachycardia and fetal acidosis.  More recent evidence has supported the use of alpha agonists such as phenylephrine demonstrating better acid base status and similar efficacy in blood pressure control. 
Hence, the present study was designed to compare the vasopressor effects of ephedrine and phenylephrine in ameliorating hypotension in elective caesarean delivery receiving crystalloid coloading during intrathecal bupivacaine injection.
| Materials and Methods|| |
After a proper approval of the institute's ethical committee and a written informed consent, 80 American Society of Anesthesiologists (ASA) grade I/II patients undergoing elective caesarean delivery under spinal anesthesia with a normal singleton pregnancy beyond 36 weeks gestation at a tertiary health care teaching hospital at Imphal, Manipur, India were recruited. Patients with pregnancy-induced hypertension, history of diabetes, cardiovascular and cerebrovascular diseases, fetal abnormalities, and contraindication to spinal anesthesia were excluded from the study. Patients were randomly allocated into two groups of 40 each. Taking α = 0.05, 1-β = 0.8, and sigma value of 20% in mean SBP between the two groups, a sample size of minimum 40 patients per group based on a previous study was calculated. 
Group 1 received bolus of intravenous (IV) ephedrine 6 mg whenever there was a fall in maternal SBP >20% from the baseline.
Group 2 received bolus of phenylephrine 100 μg IV whenever there was a fall in maternal SBP >20% from the baseline.
In order to maintain blinding, the vasopressor solutions were prepared in identical syringes by an anesthetist who was not involved in subsequent patient care. Each subject received oral ranitidine 150 mg on the previous evening and 2 h preoperatively as premedication with a sip of water. On arrival in the operation theater, the heart rate (HR), electrocardiogram (ECG), noninvasive blood pressure (NIBP), respiratory rate, and arterial O 2 saturation (SpO 2 ) were monitored. An infusion of normal saline was started in all the patients to maintain the patency of the IV cannula. Patients were placed in the left lateral position and lumbar puncture was performed with 25-gauge Quincke needle in L 3 -L 4 intervertebral space. Once free flow of the cerebrospinal fluid was obtained, 1.5 mL (7.5 mg) of 0.5% bupivacaine (heavy) with 0.5 mL (25 μg) of fentanyl was administered over 0.2 mL/s. Coloading with rapid administration of 20 mL/kg Ringer's lactate solution was started simultaneously after identification of the cerebrospinal fluid. The time of injection of the drug was noted and the patient was placed in a supine position. Immediately after induction of spinal anesthesia, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and HR were recorded.
Hemodynamic variables such as blood pressure and HR were monitored every 2 min up to delivery and thereafter every 5 min. Whenever SBP fell >20% from the baseline, vasopressor was administered, either 6 mg of ephedrine or 100 μg of phenylephrine.  On each occasion, when maternal HR decreased to <50 beats per minute (bpm), glycopyrollate 0.1 mg IV was administered.
Neonatal outcome was assessed using Apgar score at 1 min and 5 min and neonatal umbilical cord blood pH values. At delivery, the umbilical cord was clamped and 1 mL of blood sample was collected in heparinized syringe for acid base analysis. Continuous data were expressed as mean ± standard deviation (SD) and therefore, the intergroup comparisons were made by Student's t-test and chi-square test for categorical variable. P value <0.05 (P < 0.05) was taken to be statistically significant. The analysis was performed on Statistical Package for Social Sciences (SPSS) version 20.
| Results|| |
The two groups, i.e., group 1 and group 2 matched with regard to their age, body weight and height [Table 1]. The differences observed in baseline HR, SBP, DBP, and mean blood pressure between the two groups were statistically insignificant. Overall, 19/40 (48%) patients in the phenylephrine group and 19/40 (48%) patients in the ephedrine group had one or more episode of hypotension and required one or more bolus of vasopressor. The number of rescue doses required in group 1 and group 2 was statistically insignificant [Table 2].
|Table 2: Table showing incidence of hypotension, bradycardia, nausea, and vomiting|
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There was a higher incidence of bradycardia in patients receiving phenylephrine than those receiving ephedrine [Table 2]. In both the groups, HR was maintained around the baseline value till the induction of block after which the HR increased considerably for around 6 min corresponding to the interval of fall in the MAP [Figure 1]. After this period, the HR settled to the baseline values. The difference in mean HR and MAP till delivery between the two groups was insignificant till 40 min. However, at the 30th min and 60th min observations, the mean HR was in the range of 80-85 bpm in group 1 and 77-81 bpm in group 2 that were statistically significant (P < 0.05) though clinically not significant. However, 5/40 patients in group 2 and none in group 1 had HR <50 bpm, requiring intervention.
|Figure 1: Showing the mean heart rate and mean arterial pressure between the two groups (serial heart rate and mean arterial pressure; values are mean ± SD)|
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As shown in [Figure 2], a rapid fall from the baseline value of the mean SBP, mean DBP, and mean arterial blood pressure of both the groups till 8-10 min (i.e., till delivery) was observed; then, mean SBP was maintained near the baseline values in both the groups. The difference in the incidence of hypotension between the groups was not statistically significant (P > 0.05). However, at the 40th min, the range of SBP in the two groups in our study was 110-114 mmHg (P = 0.03); mean DBP was 59-63 mmHg (P = 0.03), and MAP was 76-80 mmHg (P = 0.02) and at the 50th min, DBP was 60-64 mmHg (P = 0.01) and mean blood pressure was 77-81 mm Hg. (P = 0.01) that were statistically significant but clinically not significant.
|Figure 2: Showing the mean systolic and diastolic blood pressure of the two groups (mean systolic and diastolic blood pressure; values are mean ± SD)|
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The difference in birth weight of neonates between the two groups was statistically insignificant. No neonate had Apgar score <7 at 1 min and 5 min. The mean neonatal umbilical cord pH in group 1 versus group 2 was 7.32 ± 0.05 versus 7.35 ± 0.03, respectively. Parturients who were administered phenylephrine delivered neonates with higher umbilical cord pH than those given ephedrine, and the difference was statistically significant (P < 0.007) [Table 3].
|Table 3: Apgar score and umbilical pH of the two groups at different time intervals|
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| Discussion|| |
In the present study, there was no statistically significant difference in the incidence of hypotension with rapid administration of crystalloid at the time of induction of spinal anesthesia (coload) in both the groups (P > 0.05). Moreover, the overall incidence of hypotension in the study population was 48% that was significantly less compared to the incidence (more than 80%) observed in other studies.  Khan et al.  observed a statistically significant (P < 0.008) difference in the incidence of hypotension in the coload group (44%) compared to the preload group (70%) in a study on 100 parturients.
In this study, there was a 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 that might lead to reactive bradycardia (baroreceptor reflex). However, this was responsive to glycopyrollate without adverse consequences. The result of this study is in accordance with the studies of Nazir et al.  (5/50 vs 17/50 in the phenylephrine group) and Lee et al.  [relative risk (RR) of 4.79; 95% confidence interval (CI), 1.47-15.60] with P < 0.05. On the other hand, the incidence of nausea and vomiting was also more in the phenylephrine group than the ephedrine group 14/40 (35%) versus 9/40 (22.5%) in our study that was not statistically significant (P = 0.16).
In this study, HR changes reflected a trend inverse to that of the MAP. The difference in mean HR and MAP till delivery between the two groups was insignificant till 40 min. However, at the 30th min and 60th min observations, statistically significant (P < 0.05) though clinically not significant differences in the mean HR of both the groups were observed. Similar findings were found by Khan et al.  who observed HR changes with an increased trend for around 10 min. This change was attributed to causes such as anxiety, aortocaval compression, and hypotension.
In our study, the average vasopressor consumption was reduced in the ephedrine group compared to the phenylephrine group, assuming that the equivalent doses of ephedrine and phenylephrine were 6 mg and 100 μg, respectively.  The incidence of fall in blood pressure was maximum during the first 10 min following the subarachnoid block and we observed that vasopressor use was maximum during this period. This corresponds to the immediate sympathetic block after intrathecal injection. We also observed that phenylephrine was used more frequently in 10 min compared to ephedrine. It is distinctly apparent by the wider SDs of mean SBP values in the phenylephrine group but no statistical significant difference was observed (P > 0.05). On the other hand, Ngan Kee et al.  and Dyer et al.  opined that vasopressor requirements was reduced till the time of delivery in their studies. The average median dose was 0 mg versus 10 mg of ephedrine (P < 0.001) in the study by Ngan Kee et al. 
We observed in this study that there was no difference between ephedrine and phenylephrine in their efficacy for managing hypotension following spinal anesthesia in parturients undergoing caesarean delivery in the range of doses that have been studied. The results of this study are in accordance with the study of Nazir et al.  and Adigun et al.  They observed that both vasopressors effectively restored both the systolic and DBP.
Gunda et al.  compared the effectiveness and side effects of vasopressors ephedrine and phenylephrine administered for hypotension during cesarean delivery under spinal anesthesia. However, their study suggested that phenylephrine may be the more appropriate vasopressor when considering maternal well-being. This may have been due to less dose of ephedrine (3 mg) that was used in their study as compared with this study.
In our study, the difference in birth weight of neonates between the two groups was not statistically significant. Parturients who were administered phenylephrine delivered neonates with higher umbilical cord pH than those given ephedrine but the difference was clinically not important as there was no true fetal acidosis (pH<7.2). Our study results regarding umbilical cord pH were in accordance with other investigators. ,, They concluded in their studies that the umbilical artery pH was similar in both the groups irrespective of whether ephedrine or phenylephrine was used to maintain blood pressure during spinal anesthesia in parturients undergoing caesarean delivery.
However, our study results are not consistent with the studies carried out by Ngan Kee et al.  and Lee et al.  where the umbilical artery pH was less in neonates in the ephedrine group than the phenylephrine group. Acidotic changes in the umbilical artery are sensitive indicators of uteroplacental insufficiency. The study findings are indirect evidence that uterine blood flow may in fact be better with phenylephrine compared with ephedrine. One of the reasons ephedrine causes acidosis is that it crosses through the placenta and has a direct effect (β3 action) on the fetus so as to cause acidosis. But there was no difference in Apgar score between the two groups at 1 min and 5 min. The difference in birth weight of neonates between the two groups was also statistically not significant.
| Conclusion|| |
We conclude from the present study that ephedrine 6 mg and phenylephrine 100 μg are equally efficient in managing hypotension during spinal anesthesia for caesarean delivery. Maternal bradycardia was more in the phenylephrine group and there was no difference in the incidence of fetal acidosis in the two groups. Neonatal outcome remains equally good in both the groups.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]