Management of Postspinal Anesthesia Hypotension During Elective Cesarean Section: Baby Norepinephrine Versus Ephedrine
Phase: NA
Conditions: Anesthesia Complication, Vasopressor, Cesarean Section Complications, Hypotension During Surgery
Sponsor: Hopital Charles Nicolle

 
 
 
 
Study Protocol 
 
Background : Spinal anesthesia emerges as the preferred anesthesia technique for elective 
cesarean section . It offers a preferable alternative to general anesthesia because it provides 
better maternal safety and néonatal outcomes. However, spinal anesthesia is not free of 
inherent risks.  Among the feared complications, hypotension remains the most common 
complication which threates  both mother and child .  In this perspective, several preventive 
and curative means have been studied to optimize maternal and fetal homeostasis. The 
common methods include fluid loading and the use of vasopressors such as ephedrine and 
phenylephrine. One promising approach is the administration of diluted norepinephrine.  Due 
to its low agonist activity of the ß receptor and its powerful α adrenergic agonist activity, it 
presents a good alternative to preserve maternal blood pressure while minimizing adverse 
effects on the mother and fetus. Thus, our study proposes to evaluate the efficacy and 
safety of diluted norepinephrine boluses compared with ephedrine on the management of 
post- spinal anesthesia hypotension during scheduled cesarean sections. 
Patients and methods : After approval from the Local  Ethical Commitee of the Hospital 
(N° FWA 00032748) ,  and after obtaining informed written consent this prospective  
randomized double –blind study will be undertaken from Jun to October 2024 in the 
Department of Anesthesiology and Intensive care and Gynecology and Obstetrics department 
of Charles Nicolle Hospital of Tunis. 
Inclusion criteria:  Singleton full-term consenting pregnant females of ASA grade II, aged 
18-38 years, scheduled for elective cesarean section under spinal anesthesia are included in 
the study. 
Non inclusion criteria : Any parturient falling in the category ASA grade III and IV, 
contrindications to spinal anesthesia, preeclampsia, chronic hypertension, comorbidity with 
diabetes mellitus, cardiovascular disorders and psychiatric illness are non-included. 
FWA 00032748                                                                                           July 4, 2024 
     IORG0011243 
 
Management of Postspinal Anesthesia Hypotension Duing Elective 
Cesarean Section: Baby Norepinephrine Versus Ephedrine 

Exclusion criteria: They are excluded the case of failure of spinal anesthesia, conversion to 
general anesthesia, post-partum bleeding, and failure to follow protocol. 
Patient groupes: 
Sample size: It was calculated by (https://statulator.com/SampleSize/ss2M.html), by 
adjusting a power of 80%, confidence level of 95%, and margin of error of 5%. The primary 
outcome variable of our study is to compare the number of vasopressor boluses to maintain 
mean blood pressure ≥ 80% between the groupes, which was estimated from the study 
conducted by Elnabtity and Selim. The least number of patients required in each groupe with 
a standard deviation of 2 is 63. 
A total of 126 parturienst are randomly divided into two equal groups by an investigator not 
directly linked to the study.  
Groupe N: patients  will received norepinephrine boluses (8 µg) ; prophylactic bolus 
immediately after spinal anesthesia induction and therapeutic boluses when systolic blood 
pressure falls to ≤ 20% of baseline. Groupe E : parturients will received ephedrine boluses 
(6 mg) ; systematic bolus after the induction of spinal anesthesia and therapeutic boluses if 
hypotention. 
 The syringes will be labeled as syringe A and syringe B and the anesthesiologist who will 
give the bolus cannot know if it is ephedrine or norepinephrine. 
The preparation of diluted norepinephrine is done by two dilutions: first dilution: 1ml of 
norepinephrine 2 mg/ml is diluted to 50 ml with 0.9% normal saline to have a concentration 
of 40 µg/ml. The second  dilution: 1ml of norepinephrine 40µg/ml is diluted to 10 ml with 
0.9% normal saline in 10 ml syringe prepared  as final concentration of 4 µg/ml. 
Ephedrine is preparated in 10 ml syringe at a concentration of 3 mg/ml. 
Preoperative period: A preanesthesia consultation is performed for patients included in 
the protocol. The modalities of the young preoperative, the anesthetic technique, the 
protocol of the study are explained to the parturients. Written and signed informed consent 
by the patients included in the study is obtained. 
Intraoperative setting: On arrival to the operating room after a Check list, The parturient 
is positioned on the operating table in the supine position with left uterine displacement. 
Standard monitoring is used including non-invasive blood pressure (NIBP), pulse oxymeter 

(SpO2) and electrocardiogram (ECG). We record three values of systolic, diastolic, and mean 
blood pressure and heart rate before any patient stimulation. An intravenous canula 18 G is 
inserted and antibiotic prophylaxis is administered 30 minutes before  surgical incision  using  
2 g of cefazoline or  900 mg of clindamycin in case of allergy to penicillins. 
Induction of spinal anesthesia: Co fluid loading 10 ml /kg of crystalloids is commenced. In 
the sitting position, under all aseptic precautions, introduction of spinal needle 25 gauge at 
L3-L4 or L4-L5 vertebral interespace. After obtaining free flow of cerebrospinal fluid, a 
standard mixture of anesthetic product : 10 mg of  hyperbaric bupivacaine 0.5% (08 mg if 
parturient’s size ≤ 160 cm) with 2.5 µg of sufentanil and  morphine 0.1 mg is injected. After 
intrathecal injection, parturients take quickly their initial position and the first prophylactic 
bolus of the vasopressor  (2 ml) from syringe A or syringe B is administrated. Oxygen is 
administred by ventimask at rate of 3 l/min till the delivery of the baby. The level of  sensory 
block is evaluated by pin prick test. Successful sensory block is defined as block reaching T4 
dermatomal level. If after 20 minutes the sensory block  level remains < T10, a conversion 
to general anesthesia is performed and the patient is excluded from the study. 
Heart rate, systolic, diastolic and mean blood pressure are recorded every minute for the 
first 15 minutes after spinal anesthesia and every five minutes until the end of the 
intervention. 
Management of hypotension: When systolic blood pressure (SBP) decreases to ≤ 20% of 
baseline, a rescue bolus of vasopressor  (2 ml of syringe A or syringe B) is given. Reinjection 
of the same bolus is repeated after 1 minute if hypotension persists. Administration of 
boluses is stopped when the value of the SBP finds ≥ 80% of the baseline. 
After clamping of the umbilical cord, Oxytocin is given as an initial bolus of 10 UI over 3 
minutes followed by slow infusion of 15 UI in 0.9% normal saline. Neonatal APGAR score at 
1 minute and five minutes is recorded. 
Primary outcome: Number of vasopressor  boluses used in each group to treat 
hypotension (SBP decreases to ≤ 20% of baseline) is recorded. 
Secondary outcomes: Complication during the surgery as incidence of hypertension (SBP 
≥ 20% of baseline), tachycardia (Heart rate ; HR ≥ 120 beats/min), bradycardia (HR ≤ 60 
beats/min), nausea and vomiting are recorded. We’ll also recorded neonatal APGAR score of 
the first and 5th minute. 

Statistical study:  
Data entry and analysis will be performed by SPSS version 25.0 software 
We will use Excel 2019 software to edit the charts. Descriptive study: Continuous 
quantitative variables following a normal distribution will be expressed by their means and 
standard deviation. Continuous quantitative variables not following a normal law will be 
expressed by their median and interquartile [25%-75%]. Qualitative variables will be 
expressed as simple frequencies (n) and relative frequencies as a percentage. Analytical 
study: For the analysis of the association between two qualitative variables, Pearson chi-2 
test for the comparison of two frequencies under verified application conditions and the 
Fischer test otherwise will be used. For the analysis of the association between a qualitative 
variable and a quantitative variable, T test of Student will be used for the comparison of two 
means and the non-parametric test of Mann Whitney otherwise. A significance threshold for 
p 5% will be retained. In the multivariate study, risk was calculated by the Odds Ratio (OR) 
with a retained confidence interval of 95% (95% CI). 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
July 4, 2024