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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 2  |  Issue : 2  |  Page : 92-97

Comparison between phenylephrine and ephedrine in preventing hypotension during spinal anesthesia for cesarean section


Department of Anaesthesiology and Critical Care, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, J and K, India

Date of Web Publication17-Dec-2012

Correspondence Address:
Mubasher A Bhat
65, Alfarooq Colony, Sanatnagar Bypass, Srinagar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4472.104734

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  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 μg IV at the time of intrathecal block with rescue boluses of 50 μg. 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.

Keywords: Ephedrine, fetal acidosis, hypotension, phenylephrine, spinal anesthesia


How to cite this article:
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

How to cite this URL:
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 [serial online] 2012 [cited 2019 May 21];2:92-7. Available from: http://www.joacc.com/text.asp?2012/2/2/92/104734


  Introduction Top


Spinal 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, pulmonary aspiration, respiratory depression, and cardiac 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, 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 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 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 Top


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 μg i/v of phenylephrine at the time of intrathecal block, plus rescue boluses of 50 μg phenylephrine, whenever maternal systolic blood pressure was less than 90 mmHg.

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 O 2 saturation (SaO 2 ) 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 μg 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 μg 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 Top


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].
Table 1: Comparison of age and weight between group 1 and group 2

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Figure 1: Comparison between surgical times in groups 1 and 2

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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) [Table 3] and [Table 4].
Table 2: Comparison of baseline heart rate, systolic, diastolic and mean blood pressure in groups1 and 2

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Table 3: Comparison of heart rate, systolic and diastolic blood pressure between groups 1 and 2 before delivery

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Table 4: Comparison of mean pulse rate, systolic blood pressure and diastolic blood pressure between groups 1 and 2 after delivery

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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 [Table 3], [Table 4], [Table 5], [Table 6] (P value < 0.05: significant).
Table 5: Comparison of mean blood pressure (mmHg) till delivery between groups 1 and 2

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Table 6: Comparison of mean blood pressure (mmHg) after delivery in groups 1 and 2

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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].
Table 7: Comparison of birth weight and umbilical cord pH between groups 1 and 2

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  Discussion Top


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 and neonate. These effects include decrease in uteroplacental 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.

We confirmed in this study that there was no difference between ephedrine and phenylephrine in their efficacy for managing 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 Magalhγes 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 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 Top


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.

 
  References Top

1.Cyna AM, Andrew M, Emmett RS, Middleton P, Simmons SW. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2006;4:CD002251.  Back to cited text no. 1
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2.Prakash S, Pramanik V, Chellani H, Salhan S, Gogia AR. Maternal and neonatal effects of bolus administration of ephedrine and phenylephrine during spinal anaesthesia for caesarean delivery: A randomized study. Int J Obstet Anesth 2010;19:24-30.  Back to cited text no. 2
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3.Balki M, Carvalho JC. Intraoperative nausea and vomiting during cesarean section under regional anesthesia. Int J Obstet Anesth 2005;14:230-41.  Back to cited text no. 3
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4.Lee A, Warwick D, Kee N, Gin T. Trails of ephedrine versus phenylephrine for the management of hypotension during spinal anaesthesia for caesarean section. Anaesth Analg 2002;94:920-6.  Back to cited text no. 4
    
5.Kinsella SM. Lateral tilt for pregnant women. Why 15 degrees? Anaesthesia 2003;58:835-6.  Back to cited text no. 5
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6.Rout CC, Rocke DA, Gouws E. Leg elevation and wrapping in the prevention of hypotension following spinal anaesthesia for elective caesarean section. Anaesthesia 1993;48:304-8.  Back to cited text no. 6
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7.Kinsella SM, Pirlet M, Mills MS, Tuckey JP, Thomas TA. Randomised study of intravenous fluid preload before epidural analgesia during labour. Br J Anaesth 2000;85:311-3.  Back to cited text no. 7
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8.Kubli M, Shennan AH, Seed PT, O'Sullivan. A randomized controlled trial of fluid preloading before low dose epidural analgesia for labour. Int J Obstet Anesth 2003;12:256-60.  Back to cited text no. 8
    
9.Ralston DH, Shnider SM, deLorimier AA. Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology 1974;40:354-70.  Back to cited text no. 9
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10.Ngan Kee WD, Khaw KS, Lee BB, Ng FF, Wong MM. A randomized controlled study of colloid preload before spinal anaesthesia for Caesarean section. Br J Anaesth 2001;87:772-4.  Back to cited text no. 10
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11.Weiner CP, Martinez E, Chestnut DH, Ghodsi A. Effect of pregnancy on uterine and carotid artery response to norepinephrine, epinephrine, and phenylephrine in vessels with documented functional endothelium. Am J Obstet Gynecol 1989;161:1605-10.  Back to cited text no. 11
    
12.Ngan Kee WD, Khaw KS, Ng FF. Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for caesarean section. Br J Anaesth 2004;92:469-74.  Back to cited text no. 12
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13.Erler I, Gogarten W. Prevention and treatment of hypotension during caesarean delivery. Anasthesiol Intensivemed Notfallmed Schmerzther 2007;42:208-13.  Back to cited text no. 13
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14.Adigun TA, Amanor-Boadu SD, Soyannwo SD. Comparison of intravenous ephedrine with phenylephrine for the maintenance of arterial blood pressure during elective caesarean section under spinal anaesthesia. Afr J Med Med Sci 2010;39:13-20.  Back to cited text no. 14
    
15.Gunda CP, Malinowski J, Tegginmath A, Suryanarayana VG, Chandra SB. Vasopressor choice for hypotension in elective Cesarean section: ephedrine or phenylephrine?. Arch Med Sci 2010;6:257-63.  Back to cited text no. 15
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16.Magalhães E, Govêia CS, Ladeira LC, Nascimento BG. Ephedrine versus phenylephrine: Prevention of hypotension during spinal block for cesarean section and effects on the fetus. Rev Bras Anestesiol 2009;59:11-20.  Back to cited text no. 16
    
17.Cooper DW, Sharma S, Orakkan P. Retrospective study of association between choice of vasopressor given during spinal anaesthesia for high-risk caesarean delivery and fetal pH. Int J Obstet Anesth 2010;19:44-9.  Back to cited text no. 17
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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