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 Table of Contents  
Year : 2019  |  Volume : 9  |  Issue : 2  |  Page : 75-80

Prophylactic ephedrine to prevent postspinal hypotension following spinal anesthesia in elective cesarean section: A prospective cohort study in ethiopia

1 Department of Anesthesia, Arba Minch Health Science College, Arba Minch, Ethiopia
2 Department of Anesthesia, College of Medicine and Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
3 Department of Anesthesia, College of Medicine and Health Sciences, Dilla University, Dilla, Ethiopia

Date of Submission04-Aug-2018
Date of Decision05-Mar-2019
Date of Acceptance05-May-2019
Date of Web Publication06-Sep-2019

Correspondence Address:
Mr. Tewoderos Shitemaw
Department of Anesthesia, Arba Minch Health Science College, Arba Minch
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joacc.JOACC_49_18

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Introduction: Spinal anesthesia is commonly used for cesarean section (CS); however, hypotension is a common clinical problem after spinal anesthesia. Prophylaxis ephedrine can safely be administered by bolus intravenous (IV) route which is simple and cheap, because of its longer duration of action than other vasopressors. Methods: A sample size of 88 consecutive parturients scheduled for elective CS under spinal anesthesia was recruited for this study. Based on the responsible anesthetist's management plan, prophylactic group (Group 1) received IV prophylaxis ephedrine (10 mg) with fluid co-loading, while the nonprophylactic group (Group 2) received fluid co-loading only. The drug norepinephrine was used intraoperatively for the treatment of hypotension in both groups. The primary outcome was the incidence of hypotension. Secondary outcomes were blood pressure (BP), first hypotension incidence time, vasopressor for hypotension treatment, and pulse rate (PR). Results: Hypotension occurred in 22 [50.0% (95% confidence interval, CI, 35%–65%)] of patients in nonprophylactic group (Group 2) and 10 [22.7% (95% CI, 10%–36%)] of the patients in prophylactic group (Group 1) [X2 (1, N = 88) = 7.07,P= 0.008]. Mean values of systolic and diastolic BP were significantly different between groups from 5th min until the 20th min [P < 0.05]. The first hypotension incidence time was significantly different between groups with log rank test [P = 0.003]. Number of patient that required rescue vasopressor and total dose of rescue vasopressor were significantly different between the groups [19 (43.2%) vs. 6 (13.6%) and 7.5(5) vs. 15(15)], respectively. Differences in heart rate and Apgar score between groups were not statistically different. Conclusion: Prophylaxis IV bolus 10 mg ephedrine reduced the incidence of hypotension and greater arterial pressure stability was achieved following spinal anesthesia in parturient undergoing elective CS.

Keywords: Cesarean section, Ethiopia, ephedrine, spinal anesthesia, spinal hypotension

How to cite this article:
Shitemaw T, Aregawi A, Fentie F, Jemal B. Prophylactic ephedrine to prevent postspinal hypotension following spinal anesthesia in elective cesarean section: A prospective cohort study in ethiopia. J Obstet Anaesth Crit Care 2019;9:75-80

How to cite this URL:
Shitemaw T, Aregawi A, Fentie F, Jemal B. Prophylactic ephedrine to prevent postspinal hypotension following spinal anesthesia in elective cesarean section: A prospective cohort study in ethiopia. J Obstet Anaesth Crit Care [serial online] 2019 [cited 2019 Sep 17];9:75-80. Available from: http://www.joacc.com/text.asp?2019/9/2/75/266149

  Introduction Top

Spinal anesthesia is commonly used for cesarean section (CS) due to the advantages for the mother include remaining awake for the birth, avoiding risks of general anesthesia, and facilitating effective postoperative pain relief.[1],[2] Spinal blocks also have the advantage of being more cost-effective when compared with epidural anesthesia.[3] To successfully administer spinal anesthesia for cesarean delivery, however, requires vigilance and consistent attention to details to decrease the side effects, such us nausea, vomiting, failed or total block, and the predominant and most common one being maternal hypotension.[1],[2] Spinal hypotension can occur precipitously and, if severe, can result in maternal and perinatal unwanted and adverse outcomes, such as maternal nausea and vomiting, fetal acidosis and can be an important contributory factor for maternal death related to regional anesthesia.[4]

The high incidence of postspinal hypotension (PSH) with different pharmacological and nonpharmacological methods necessitates for combination of different methods for prevention and management of this problem. Spinal hypotension in CS is a common daily situation facing all anesthetists. Focusing on simple and rapid protocols that can be easily applied by anesthetists with moderate and low experience and minimal need to complex devices is necessary. Ephedrine is a sympathomimetic that has both a direct (α-and β-receptor agonist) and an indirect mechanism of action (release of norepinephrine) to maintain arterial pressure mainly by increasing cardiac output (CO) and heart rate.[5],[6],[7] The prophylactic administration of ephedrine by the intramuscular route is controversial as its systemic absorption and peak effect are difficult to predict.[8] Prophylaxis ephedrine can safely be administered by bolus intravenous (IV) route which is simple and cheap, because of its longer duration of action than other vasopressors.[9] Bolus IV injection of ephedrine is more effective than infusion to prevent arterial hypotension during CS.[10] This property is advantageous for those facilities expensive controlled infusion devices are unavailable.

Hence, the primary outcome of this study is to determine the effect of 10 mg prophylaxis ephedrine IV bolus on the incidence of hypotension during elective CS under spinal anesthesia. The secondary outcomes are comparing blood pressure (BP), first hypotension incidence time, vasopressor treatment, PR, and Apgar scores between the two groups.

  Methods Top

The study was conducted after approval by Addis Ababa University, Ethical review board to conduct the study. An institutional based prospective observational cohort study design was conducted from January 01, 2018 to April 27, 2018 at Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, the capital city of Ethiopia. Before commencing the study informed consent was obtained from all parturient after full explanations of the goals and procedures of the study. Sample size was determined by using Epi info version 7 stat calc program.[11] By considering a power of 80%, confidence interval 95% and ratio of unexposed to exposed 1:1. The primary outcome variable was incidence of hypotension which was estimated from previous study done in Nigeria,[12] with 30% difference in the incidence of hypotension. A sample size of 44 patients per group was determined.

Anesthetic management including intraoperative treatment of hypotension, selection of fluid protocols, and vasopressor prophylaxis given before spinal anesthesia was done with the discretion of the personnel anesthetist assigned to each case and hospital protocol. We the investigators did not involve in the perioperative management of patients. Since randomized control trial (RCT) was not yet allowed in our university, the patients were not randomized for anesthetic management. Since there is no protocol on the use of prophylaxis vasopressor for spinal hypotension in the study site, patients were classified into prophylaxis group (Group 1) and nonprophylactic group (Group 2) based on the responsible anesthetists' independent decision. Those patients who received 10 mg of prophylaxis ephedrine during induction of spinal anesthesia were considered as prophylactic group (Group 1). The nonprophylactic group was defined, in this study, as those patients who did not receive any prophylactic vasopressor during the induction of spinal anesthesia (Group 2). By random start, every selected participant after then was placed to either group based on the responsible anesthetist's management plan (whether they received prophylaxis ephedrine or not) by the data collectors. This continues until the desired sample in each groups was achieved. We hypothesized that using prophylaxis ephedrine to maintain maternal BP during spinal anesthesia for elective CS provides better arterial pressure stability with better maternal outcomes compared to nonprophylactic group.

Patients with Preoperative hypotension, Pregnancy-induced hypertension, eclampsia, essential hypertension (diagnosed on history, BP records, and lab findings on antenatal visits), Any known cardiovascular disease (valvular heart disease, cardiomyopathies), Failed spinal block or total spinal converted to general anesthesia, and CS indication secondary to placenta previa were excluded.

The protocol and routine procedures before CS at the study site were as follows:

Preanesthetic evaluation was done in the morning of the surgery. Vital sign, organ-function test together with history and physical examinations are among the parameters used to decide for anesthesia plan, whether to cancel or precede the surgery. On arrival to the operating room, patients were premedicated with metoclopramide 10 mg IV bolus before induction of anesthesia. Two 18 gauge IV cannula needle is secured on bilateral arms. While preparing the monitoring equipment, during preparation of the skin and during spinal anesthesia induction lactated Ringer's or normal saline solution was administered for co-loading as fast as possible by both IV line secured. Sub arachnoid block was done in the sitting position after strict aseptic technique. Isobaric bupivacaine with 0.5% of 2.5 mL using 23 gauge needle was administered at L3-L4 level for all parturient. After intrathecal administration patients were positioned to supine position with slight head elevation using pillow and 100% oxygen was delivered by a Venturi face mask at 3 L/min.

The monitors used during intraoperative period is mindray patient monitor, model: MEC-2000. The baseline value for this study is calculated as an average of three systolic blood pressure (SBP) values taken over 5–10 minutes prior to induction of spinal anesthesia in the left lateral position using noninvasive BP monitor, heart rate using an ECG and pulse rate, and O2 saturation using pulse oximeter. Hemodynamic data were recorded every 5 min after initiation of spinal anesthesia until 40th min. The level of sensory block was evaluated with cold sensation 5 min after spinal anesthesia. Data were collected by three BSc. Anesthesia professional after 1 day training given on the objective of the study, data collection tool, and exclusion and inclusion criteria.

For the purpose of this study, the following definitions were used:

Baseline value: Measurement taken before induction or spinal anesthesia given

Prophylactic group: Patients that received prophylactic IV bolus ephedrine (10 mg) along with fluid co-loading.

Nonprophylactic group: Patients that received fluid co-loading only.

Hypotension: Defined as a decrease in SBP ≥20% of baseline or systolic arterial BP less than 80 mm Hg.

Hypertension: Defined as an increase of SBP >20% of baseline.[12],[13]

Bradycardia: A decrease in heart rate ≥30% from baseline value or heart rate less than 60.[12],[14]

PSH: Hypotension that occurs after administration of intrahechal local anesthetics.

Onset of analgesia: This was defined as the inability to sense pinprick sensation at T-10 (umbilicus).

Motor block: This was defined as the inability to move hip, knees, or toes.

Time to achieve highest sensory block: Minute to loss of cold sensation and will be recorded bilaterally in the anterior axillary line or midclavicular line.

Time to first recording of hypotension: The first time a decrease in SBP ≥20% of baseline or systolic arterial BP less than 80 mm Hg is recorded.

Number of episodes of hypotension: The number of episode recorded showing a decrease in SBP ≥20% of baseline or systolic arterial BP less than 80 mm Hg is recorded.

Total dose of rescue vasopressors: Total dose of the vasoconstrictor drug given intraoperatively for the treatment of hypotension.

Data processing and analysis

Data were coded, edited, and then entered and cleaned using Epi Info version 7 and exported and analyzed using Statistical package for Social Sciences (SPSS) software version 20.0. Shapiro–Wilk test was used to test for distributions of data, while homogeneity of variance was assessed using Levene's test for equality of variance. Numeric data were described in terms of mean ± SD for symmetric and median (interquartile range) for asymmetric data, respectively. Comparisons of numerical variables between study groups were done using unpaired Student's t-test (independent t- test) for symmetric data [age, height, weight, body mass index (BMI), maternal hemoglobin level, SBP, diastolic BP (BP), and heart rate]. Manny–Whitney U test was used for asymmetric data (para, gravida rescue dose of norepinephrine, Apgar, weight of the baby, duration of surgery, blood loss, intraoperative IV fluid, incision to delivery time). Frequency and percentage were used to describe categorical variable (level of sensory block, indications for CS, incidence of nausea between groups, intraoperative bradycardia between groups, incidence of hypotension, and number of patients rescue vasopressor received) and statistical difference between groups were tested using Chi square or Fisher's exact test, as appropriate. The incidence and timing of hypotension occurrence was further analyzed by using Kaplan–Meier survival analysis, with comparison between groups using the log-rank test. Significance was determined at P value <0.05.

  Result Top

A total of 88 patients were recruited to this study, with 44 patients receiving either ephedrine prophylaxis or not for postspinal hypotension. Demographic data and further relevant anesthesia data, including baseline BP and heart rate are presented in [Table 1]. There were no differences between groups with respect to age, BMI, gestational age, baseline arterial pressure measurement, or relevant time intervals. Block height was comparable between groups with a range from T4 to T10, and no patient required supplemental analgesia predelivery. All Apgar scores at 1 and 5 min were greater than 7.
Table 1: Patient characteristics and intraoperative data of patients who underwent elective cesarean section at TASH, Ethiopia, 2018

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BP was recorded every 5 min starting from induction of anesthesia. There was statistically significant decreased incidence of hypotension in ephedrine prophylaxis group (Group 1) with 10 [22.7% (95% CI, 10%–36%)] compared with nonprophylactic group (Group 2) 22 (50.0% [95% CI, 35%–65%)] incidence at the end of the study period, X 2 (1, N = 88) = 7.07, P= 0.008. Mean of the BP trends between groups is presented on [Figure 1]. After 5 min of spinal anesthesia induction, patients in the ephedrine prophylaxis group (Group 1) maintained significantly higher BPs than those in the nonprophylactic group until 20 min in both SBP and DBP (P < 0.05).
Figure 1: Change in systolic and diastolic arterial pressures of the prophylactic and nonprophylactic group under spinal anesthesia for elective cesarean section at TASH, 2018. [P < 0.05]

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The drug norepinephrine was used intraoperatively for the treatment of hypotension in both groups. In the nonprophylactic group (Group 2) for 19 [43.2% (95% CI, 27.9%–58.4%)] patients, rescue vasopressor (norepinephrine) was administered compared to 6 [13.6% (95% CI, 3.0%–24.1%) in ephedrine prophylaxis group (Group 1) [X 2 (1, N = 88) = 9.44, P= 0.002]. The total dose of rescue norepinephrine in microgram given for treatment of hypotension intraoperatively was compared using Mann–Whitney U test and showed statistically significant difference between groups with median and interquartile range of [7.5(5) vs 15(15)] (P = 0.043) [Figure 2].
Figure 2: Median, range, interquartile Range of the total rescue dose of norepinephrine between nonprophylactic and prophylactic group under spinal anesthesia for elective cesarean section

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Results of the Kaplan–Meier survival analysis are shown in [Figure 3]. The Kaplan–Meier survival curves shows proportion of patients with the incidence of hypotension (event) time from the initiation of spinal anesthesia to the end of the study. There was a significant difference between the groups with log rank test (P = 0.003). In the nonprophylactic group (Group 2) mean time to the first episode of hypotension after induction of anesthesia was 25.5 (95% CI, 21.05-30.08) min. The prophylactic group (Group 1) records a mean time to the first episode of hypotension incidence after induction of anesthesia being 36.2 (95% CI, 33.51–38.99) min.
Figure 3: Kaplan–Meier survival curves showing systolic blood pressure from the initiation of spinal anesthesia to end of surgery

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[Figure 4] shows trends of heart rate across time. There was no statistical significant difference in heart rate between Group 1 and Group 2 from the start of induction of spinal anesthesia until the end of the study time. Intraoperative nausea between the groups was significantly different as shown in [Table 2]. [X 2 (1, N = 88) = 3.87, P= 0.049]. An incidence of vomiting was not recorded in both groups.
Figure 4: Changes in mean heart rate in prophylactic and nonprophylactic group under spinal anesthesia for elective cesarean section at TASH, 2018

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Table 2: Incidence of nausea and bradycardia data of patients who underwent elective cesarean section at TASH, Ethiopia, 2018

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  Discussion Top

Considering the results of the present study, the incidence of hypotension was high in those parturient who did not take prophylactic ephedrine than those who took prophylactic ephedrine. Patients who received prophylactic ephedrine had greater BP stability compared to nonprophylactic group, as evidenced by greater values for serial measurements of SBP and DBP. It decrease rescue vasopressor dose administered and also increase the time to first episode of hypotension. The neonatal outcome was comparable between groups as it was evidenced by Apgar score of 1st and 5th min. Moreover, low incidences of maternal nausea were recorded in the prophylactic group.

The incidence of hypotension in our study is comparable with results observed by Hasanin et al. done in Egypt [48% vs. 24%].[15] Our finding was in accordance with a study conducted by Shafaq Hanif and Afridi with incidence of hypotension significantly higher (56%) in nonprophylactic group as compared to group with prophylactic group (16%).[2] Similar results to our study were reported in other studies.[16],[17],[18] The intraoperative BP (systolic and diastolic) stayed lower in the nonprophylactic group significantly starting from 5 min after induction of spinal anesthesia until the 20th min. The same result was showed in another study with statistical difference in SBP between the groups from 6 to 20th min.[2],[17]

Even though the sensory and motor onset of SA starts around after 5 min, its autonomic effect is expected to start immediately after SA which is evidenced by significant hypotension in those without ephedrine prophylaxis at earlier times after spinal anesthetic injection.[19] The present study showed that in nonprophylaxis group around 90% of the hypotension occurred within 20 minutes after spinal anesthesia induced. The same result was also observed by another study that patients in nonprophylaxis group who experienced hypotension did so earlier than those in the ephedrine prophylactic group.[12] In the present study, 60% of the hypotension incidences in the prophylaxis group were recorded after 20 minutes of anesthesia induction. Ephedrine is not metabolized by catechol-O-methyltranserease enzymes because it lacks hydroxyl groups, and monoamine oxidase enzyme deamination does not occur because of its a-methyl group. Thus, this explains the relatively long duration of action of ephedrine compared to other vasopressors.[9],[19]

Moreover, patients that were hypotensive intraoperatively were managed with additional vasopressor. Literature's show despite different maneuvers used to treat spinal induced hypootension (SIH), anesthetists will have to treat with vasopressor medications 40%–60% of women undergoing cesarean delivery.[19] In our study more of the nonprophylactic group patients required rescue vasopressor (norepinephrine) compared to the prophylaxis ephedrine group. Similar results were found in different studies.[2],[16],[20]

In our study, the intraoperative heart rate was not significantly different between the two groups. This could be explained as baroreceptor-mediated reflex increases heart rate in patients who became hypotensive and additional atropine was applied for incidence of bradycardia in the nonprophylactic group. Evidence has shown that ephedrine has effects on cardiac beta receptors indirectly, which lead to sinus node stimulation and consequently preventing decrease in heart rate following spinal anesthesia. In some cases, this led to increase in heart rate though not significantly.[18],[21] Other studies reported where heart rate significantly increased in the prophylactic group.[2],[12],[22] In our study, intraoperative incidence of nausea was significantly higher in the nonprophylactic groups. Nausea is thought to be secondary to brainstem ischemia or reflex response to decreased venous return. This was in agreement with the results of some previous studies,[16],[17] unlike another study which found that the incidence of nausea was not significantly different between the two groups.[12] In addition, no incidence of vomiting in both groups recorded. This might be due to the administration of prophylaxis metoclopramide before induction of anesthesia.[23] It is important to acknowledge some limitations to our study. Limitation of this study includes that it is not a RCT study as our university ethical board prohibits RCT. BP measurements were not beat to beat and could not appreciate the duration of hypotension in between episode of hypotension. In addition; the study only included elective CS. Thus, the results of the present study cannot be explanatory for emergency CS group of patients.

  Conclusion Top

In conclusion, employing combination of co-loading of fluid with prophylactic IV bolus of 10 mg ephedrine reduced the occurrence of hypotension following spinal anesthesia in parturient undergoing elective CS. It is associated with fewer interventions for treatment, decreased episode of nausea, as well as greater arterial pressure stability.

Research registration number

Not required.


We would like to thank Addis Ababa University College of Medicine and Health Science for funding this research. Our gratitude goes to supervisors, data collectors, and study respondents. Finally, we would like to thank all those, who in one way or another have contributed in this work.

Financial support and sponsorship

This work was funded by Addis Ababa University.

Conflicts of interest

There are no conflicts of interest.

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Shahzadi I, Hanif S, Afridi Y. Role of Ephidrin infusion in spinal anaesthesia induced hypotension. Pak J Physiol 2016;12:12-5.  Back to cited text no. 2
Yeoh SB, Leong SB, Heng AST. Anaesthesia for lower-segment caesarean section: Changing perspectives. Indian J Anaesth 2010;54:409-14.  Back to cited text no. 3
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Hegde BK, Bhat MT. Prophylactic crystalloids or prophylactic crystalloids with ephedrine: Comparison of hemodynamic effects during caesarean section under spinal anaesthesia using 0.5% bupivacaine. J Obstet Anaesth Crit Care 2017;7:26-32.  Back to cited text no. 16
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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