Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 2  |  Page : 221-225

Randomized double-blind comparison of intravenous ephedrine and hydroxyethyl starch 6% for spinal-induced hypotension in elective cesarean section


1 Department of Anesthesia, ICU and Pain Management, Qena Faculty of Medicine, South Valley University, Qena, Egypt
2 Department of Obstetrics and Gynaecology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission01-Apr-2013
Date of Acceptance01-Aug-2013
Date of Web Publication31-May-2014

Correspondence Address:
Ossama Hamdy Salman
Department of Anesthesia, ICU and Pain Management, Qena Faculty of Medicine, South Valley University, Qena
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.133445

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  Abstract 

Purpose
The aim of the study was to compare the efficacy of ephedrine versus hydroxyethyl starch (HES) 6% in prevention of hypotension during spinal anesthesia for cesarean delivery.
Materials and Methods
A total of 120 ASA physical status I and II parturients scheduled for cesarean delivery were assigned into four groups following induction of spinal anesthesia: group E - the ephedrine group (n = 30) received ephedrine 15 mg intravenous bolus immediately after spinal anesthesia was given and the patient returned to the supine position; group HES - the HES 6% group (n = 30) received 1000 ml of HES 6% just before spinal anesthesia was administered; group EHES - the ephedrine and HES 6% group (n = 30) received HES 6% 500 ml before administration of spinal anesthesia and ephedrine 15 mg intravenous bolus right after spinal anesthesia was given; and the last group was the control group, the LR group - lactated Ringer (n = 30), preloaded with lactated Ringer solution, 1000 ml infusion just before spinal anesthesia. The incidence of hypotension, reactive hypertension, nausea and vomiting, and Apgar scores at 1 and 5 min were noted.
Results
No significant demographic differences between groups were noted. The incidence of hypotension was significantly lowest in the group EHES and highest in the LR group (the control group). Moreover, the incidence of rescue ephedrine administration was lowest in the EHES group (3.3%) and highest in the LR group (55%). The incidence of nausea and vomiting was significantly lowest in the group EHES (3.3%) and highest in the group LR (53.3%).
Conclusion
HES 6% 500 ml before administration of spinal anesthesia and ephedrine 15 mg intravenous bolus right after spinal anesthesia is effective in preventing spinal-induced maternal hypotension during cesarean section.

Keywords: Spinal-induced hypotension, ephedrine, hydroxyethyl starch, cesarean section


How to cite this article:
Salman OH, Yehia A H. Randomized double-blind comparison of intravenous ephedrine and hydroxyethyl starch 6% for spinal-induced hypotension in elective cesarean section. Ain-Shams J Anaesthesiol 2014;7:221-5

How to cite this URL:
Salman OH, Yehia A H. Randomized double-blind comparison of intravenous ephedrine and hydroxyethyl starch 6% for spinal-induced hypotension in elective cesarean section. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Oct 27];7:221-5. Available from: http://www.asja.eg.net/text.asp?2014/7/2/221/133445


  Introduction Top


Spinal anesthesia has become the standard technique for elective cesarean delivery [1]. It is easy to perform, quick onset with excellent sensory/motor block quality, and cost effective [2]. However, spinal anesthesia-induced hypotension remains one of the most serious side effects during cesarean delivery, as it carries a potential maternal and neonatal risk outcome. The incidence of hypotension during spinal anesthesia is as high as 80% [3]. The cardiovascular effects of spinal anesthesia are proportional to the height of the block and result from denervation of the sympathetic outflow tracts (T1-L2). This produces dilatation of resistance and capacitance vessels and results in hypotension [3].

A number of protocols aiming at preventing hypotension has been used for decades - for example, left uterine displacement, Trendelenburg position, leg wrapping/compression, intravenous fluid preload or coload, and parenteral vasopressors [4],[5].

In modern anesthesia practice, ephedrine is considered the standard medication in obstetric anesthesia that maintains arteriolar tone and has become the drug of choice to combat hypotension under spinal anesthesia [6]. It is predominantly B-agonist that elevates blood pressure by enhancing cardiac output rather than vasoconstriction action. However, many studies showed that ephedrine at different doses 10, 20, and 30 mg given immediately after spinal anesthesia induction was not effective in preventing hypotension [7],[8],[9],[10]. Moreover, higher doses of vasoconstrictors may decrease uteroplacental perfusion, which has deleterious effect on the fetus [11],[12],[13].

Alternatively, fluid preload has proved to decrease the dose or even eliminate the need to administer vasopressor to prevent hypotension [14]. The direct comparison between crystalloids and colloids as fluid management during cesarean section under spinal anesthesia has shown many interesting outcomes. First of all, crystalloid preload is not effective or at least has poor inconsistent outcome that depends on the volume, infusion rate, and most importantly on the onset of the spinal sympathetic block [15]. Second, preload with colloid hydroxyethyl starch (HES) is reliable and effective in preventing maternal hypotension [15]. Being a suspension of particles rather than true solution, it tends to remain confined to the intravascular compartment for more than 24 h and maintains the intravascular hydrostatic pressure [15]. Nevertheless, in special maternal situations, for example, heart disease, multiple gestations, and pre-eclampsia, fluid preload should be avoided. Moreover, in emergency situation with hemodynamic compromise, fluid coload rather than preload is recommended [16]. However, fluid coload is not the focus of this study.

In our study, we aimed to compare the efficacy of ephedrine versus HES 6% in prevention of hypotension during spinal anesthesia for elective cesarean delivery.


  Materials and Methods Top


This randomized double-blind prospective study was conducted at Department of Anesthesia, ICU and Pain Management, Qena University Hospital, South Valley University between January 2010 and April 2012. After approval from the hospital ethical committee, informed consents were obtained from 120 pregnant women ASA grade I and II, scheduled to have elective cesarean section under spinal anesthesia. Those with gestational age less than 37 weeks, known hypertension, pre-existing cardiac or pulmonary disease, with hepatic or renal disease were excluded from the study. Patients were premedicated with ranitidine 150 mg orally on the day of the surgery and 0.3 mol/l sodium citrate 35 ml on arrival to operating room. In the operating room, intravenous access was established; all patients were preloaded with 500 ml of BSS; and standard anesthesia monitors were connected to the patients. The parameters observed were heart rate, noninvasive blood pressure, ECG, and oxygen saturation (SpO 2 ).

Using sealed precoded random number table envelopes, patients were randomly assigned into four groups: group E - the ephedrine group (n = 30) received ephedrine 15 mg intravenous bolus immediately after spinal anesthesia was given and the patient was returned to the supine position; group HES - the HES 6% group (n = 30) received 1000 ml of HES 6% just before spinal anesthesia was administered; group EHES - the ephedrine and HES 6% group (n = 30) received HES 6% 500 ml before administration of spinal anesthesia and ephedrine 15 mg intravenous bolus right after spinal anesthesia was given; and the last group was the control group, the LR group - lactated Ringer (n = 30), preloaded with lactated Ringer solution, 1000 ml infusion just before spinal anesthesia. In the sitting position, spinal anesthesia was administered to all patients at level L3-L4 or L4-L5 intervertebral spaces with 15 mg hyperbaric bupivacaine 0.5% using 25-G spinal needles. Right after spinal anesthesia was given, patients were turned supine with left tilt of the operating table 15° to avoid aortocaval compression. Oxygen 4 l/min was given to all patients by face masks.

For the purpose of our study, hypotension was defined as 20% decrease in baseline blood pressure, and a 20% increase from baseline was considered reactive hypertension.

If hypotension occurs, 10 mg ephedrine and intravenous crystalloid fluid were rescue medication. Hemodynamic alterations were monitored by an independent researcher who was unaware of the study medications. The incidence of hypotension, reactive hypertension, nausea and vomiting, and Apgar scores at 1 and 5 min were noted. The amount of intraoperative bleeding was recorded.

Statistics

A power analysis based on a previous study [17] showed that a sample size of 30 patients per group was required to achieve a power of 90% and an α-value of 0.05 for detection of a difference between the study groups. Dichotomous parameters were compared between groups using the Fisher exact test. The demographic and procedural data were analyzed for normal distribution by the Shapiro-Wilk test. Data are reported as mean±SD or median (interquartile range). Repeated measurements of continuous variables were analyzed with a two-factor analysis of variance using PROC MIXED procedures.

The Mann-Whitney U-test was used for multiple comparisons between groups.

A P-value of less than 0.05 was considered significant.


  Results Top


A total number of 120 patients were included in the study, 30 patients in each of the four groups, and all of them completed the study. The study groups were comparable with respect to age, weight, duration of pregnancy, and spinal anesthesia delivery time [Table 1]. There was no statistically significant difference in sensory block level [Table 2]. In addition, the amount of intraoperative blood loss was between 300 and 400 ml.
Table 1: Patient demographics

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Table 2: Sensory block level

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Primary outcomes

The incidence of hypotension was 40, 43.4, 16.6, and 63.3% in group E, HES, EHES, and LR, respectively. The incidence of hypotension was significantly lowest in group EHES and highest in the LR group (the control group) in comparison with the E and HES groups [Table 3]. There was no incidence of reactive hypertension in all groups, except group EHES (6.7%), which was statistically insignificant [Table 3].
Table 3: Primary outcomes

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Secondary outcomes

The incidence of nausea and vomiting was 26.7, 20, 3.3, and 53.3% in group E, HES, EHES, and LR, respectively. The incidence of nausea and vomiting was significantly lowest in group EHES (3.3%) and highest in group LR (53.3%) [Table 4]. These two groups also showed statistically significant incidence of rescue ephedrine administration being lowest in the EHES group (16.6%) and highest in the LR group (63.3%) [Table 4]. There was no statistically significant difference between the groups in 1- and 5-min Apgar scores [Table 5].
Table 4: Secondary outcomes

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Table 5: Apgar score

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  Discussion Top


Maternal hypotension during cesarean section under spinal anesthesia is associated with potential harmful effects for both mother and fetus. Strategies that target to prevent hypotension during cesarean surgery under spinal anesthesia may lead to better outcomes than protocols designed to manage hypotension after it has already occurred [11]. Still, during spinal anesthesia, prevention and tight management of hypotension remains a challenging problem and there is no consensus on the ideal management [18].

Crystalloid preload (10-20 ml/kg Ringer lactate solution) has been widely infused for hypotension prophylaxis during regional anesthesia [17]. Several studies showed that the occurrence of hypotension decreased significantly from 71% in unpreloaded patients to 55% in fluid preloaded ones [19,20]. Moreover, further reduction in hypotension incidence occurred on increasing the infusion rate from 10 to 30 ml/kg [17]. In contrast to the previous studies, 1000 ml of crystalloids alone did not result in preventing or decreasing the incidence of maternal hypotension compared with 200 ml or no prehydration [14],[21].

In our study, ephedrine alone is as effective as colloid preload in preventing hypotension in cesarean delivery under spinal anesthesia (40% for the former and 43% for the latter) [Table 3]. This is in accordance with other studies that reported no difference in the incidence of hypotension when either drug is used alone for maternal hypotension prophylaxis during spinal anesthesia [7],[21]. However, concurrent administration of ephedrine and HES markedly lowered the incidence of maternal hypotension to 16.6% but at the expense of occurrence of reactive hypertension (6.7%).

Compensatory thoracic sympathetic overactivity including cardiac nerves (T1-T4) in patients under spinal anesthesia might explain the occurrence of reactive hypertension [22]. Such event occurred also in low spinal and epidural blocks in which T4 sympathetic block has not been reached [23]. In our study, the incidence of reactive hypertension was significantly less than those reported by other studies that showed an incidence of reactive hypertension as high as 45% [10]. This could be explained by the difference in the dose administered, as we used 15 mg intravenous ephedrine and they used 30 mg intravenously. Moreover, the sensory level of spinal anesthesia in our study ranged T4-T6 in comparison with T4-T7 in their study.

An elegant review article by Lee et al. [9] that characterizes the dose-response curve of ephedrine as prophylaxis against maternal hypotension during spinal anesthesia for elective cesarean delivery showed significant dose-response relationship for hypotension and hypertension. They concluded that doses of ephedrine more than 14 mg do not eliminate hypotension but might lead to reactive hypertension. Some studies advocate the use of prophylactic ephedrine intramuscularly rather than intravenously to smoothly sustain blood pressure and to avoid reactive hypertension [24]. However, we administered ephedrine intravenously, as intramuscular administration has inconsistent results, unpredictable peak onset and effect, and reactive hypertension could not entirely be eliminated especially in case of failed spinal block. Moreover, intravenous ephedrine administration gives us the ability to with-hold administration of ephedrine up to the onset of spinal anesthesia and sympathetic block.

Our study, although, have its own limitations. To start with, no placebo group was included, as all parturients have to receive fluids. Second, the untreated controlled group should have been included in our study. Third, the infusion of this large volume of fluid is not suitable for patients with cardiovascular dysfunction or pre-eclampsia. Fourth, we investigated single dose of solutions; different doses might have changed the outcome. Fifth, the hydration status of the studied groups was not assessed or taken into consideration. Sixth, the difficulty of investigating subtle clinical factors, for instance, the proficiency of anesthesiologists or surgeons, might mask the nature of a procedure that might lead to hypotension in less skilled hands. May be in the future, anesthetists should tailor hypotension prophylaxis protocols according to forecasted risk for hypotension. The current techniques are too general or too time consuming for routine use.


  Conclusion Top


HES 6% 500 ml before administration of spinal anesthesia and ephedrine 15 mg intravenous bolus right after spinal anesthesia is effective in preventing spinal-induced maternal hypotension during cesarean section without adverse outcomes to either mothers or babies; however, a low incidence of reactive hypertension was observed and should be taken care for.


  Acknowledgements Top


The authors acknowledge Mrs Shereen A.M. El Shamy for her administrative and secretarial assistance.

Conflicts of interest

None declared.

 
  References Top

1.FJ Mercier. Anesth Analg 2011; 113:677-680.  Back to cited text no. 1
    
2. Riley ET, Cohen SE, Macario A, Desai JB, Ratner EF. Spinal versus epidural anesthesia for cesarean section: a comparison of time efficiency, costs, charges, and complications. Anesth Analg 1995; 80:709-712.  Back to cited text no. 2
    
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20.2LaPorta RF, Arthur GR, Datta S. Phenylephrine in treating maternal hypotension due to spinal anaesthesia for caesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaesthesiol Scand 1995; 39:901-905.  Back to cited text no. 20
    
21.2Jackson R, Reid JA, Thorburn J. Volume preloading is not essential to prevent spinal induced hypotension at caesarean section. Br J Anaesth 1995; 7:76-81.  Back to cited text no. 21
    
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    Tables

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



 

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