Clinical trial NCT03706755: Comparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia
Official title: Comparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia for Cesarean Section
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anesthesia
Adverse Effect
Hypotension
Cesarean Section Complications
Vasopressor
Keywords: spinal anesthesia
blood pressure
norepinephrine
Cesarean Section
Lead sponsor: University Tunis El Manar
Sponsor class: OTHER
First posted: 2018-10-16
Enrollment: 124
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to determine the more effective intravenous bolus of norepinephrine for maintaining blood pressure during a spinal anesthesia for a cesarean delivery with the fewer side effects. Low blood pressure has been shown to decrease uterine perfusion and foetal outcomes during cesarean delivery under spinal anesthesia. For elective or semi-urgent cesarean delivery, all participants will receive spinal anesthesia with a local anesthetic and either sufentanil or fentanyl. This study plans to enroll 124 pregnant women. Patients will be randomly assigned according to a computer generated system to be in one of two groups.

Detailed description: This study will be a prospective, randomized, active treatment controlled trial.

After written and informed consent, the study participants will be randomly assigned using a computer generated table to 1 of 2 treatment groups prior to cesarean delivery.

Group A will receive an intravenous bolus of 1mcg/Kg of norepinephrine bitartrate to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal anesthesia.

Group B will receive an intravenous bolus of 0.5mcg/kg of norepinephrine bitartrate to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal anesthesia.

Patients will be admitted to holding area. Baseline arterial blood pressure and heart rate will be measured in supine position, with left uterine displacement. Baseline blood pressure will be calculated as the mean of three consecutive SBP measurements taken 3 minutes apart. 500 mL of Lactated Ringer solution will be administered immediately after induction of spinal anesthesia at the outflow rate of 100ml per hour.

The primary endpoints are: the percentage of decrease of systolic blood pressure and mean blood pressure respectively measured by delta SBP and delta MBP before delivery ( difference between baseline and the lowest systolic and mean blood pressure respectively) and during cesarean delivery

The secondary endpoints are:

the timing of the first maternal hypotension (defined as a decrease of SBP \>20% of baseline and/or PAS\<100mmHg), duration of hypotension, incidence of hypotension, number of rescue boluses, norepinephrine consumption (mean dose of Norepinephrine to maintain blood pressure between 80 and 100 % of baseline values after the primary preventive bolus), maternal adverse effects and fetal outcomes.

Study participants will receive a standard spinal anesthetic consisting of 0.5% hyperbaric bupivacaine (2 mL) with either sufentanil (5 mcg) or fentanyl (50 mcg) at L3-4 or L4-5. Prior to surgical incision, the spinal sensory level will be tested to the bilateral T6-T4 dermatomal level. The patients will be positioned supine with a wedge placed under the right hip to avoid aortocaval compression. Both the patient and the researcher's assistant (who will collect data) will be blinded as to the administered Norepinephrine bolus A or B.

When PAS\<80% of baseline or \< 100 mmHg a bolus of Norepinephrine will be administrated(half dose A or B).

The study will end when cesarean section is completed and the patient transferred to the post-operative care unit.

Measured variables will include systolic, diastolic and mean non-invasive blood pressure, heart rate, number of rescue boluses and Norepinephrine consumption nausea and vomiting will be recorded whenever present during the surgical procedure as well as reactive hypertension (defined as a rise of SBP \>20% of baseline or SBP\>140mmHg) and arrhythmia. Bradycardia (HR less than 50 BPM) will be treated with Atropine 1mg IV.

Apgar score and fetal cord blood analysis (pH) at delivery.

Eligibility criteria: Inclusion Criteria:

* Elective or semi-urgent CD under spinal anesthesia
* Age over 18 years
* Healthy singleton pregnancy beyond 36 weeks' gestation
* American Society of Anesthesiologists (ASA) physical status classification 2
* Weight 50 to 100 kg, and height 150 to 180 cm

Exclusion Criteria:

* Emergency CD red code ( extraction time \<15 min)
* Allergy or hypersensitivity to norepinephrine or sulfite
* Preexisting or pregnancy-induced hypertension, preeclampsia, eclampsia, the use of cardiac medication or medication for blood pressure control
* multiple gestation
* Cardiovascular or cerebrovascular disease
* Fetal abnormalities
* Suspicion of abnormal placentation
* History of diabetes mellitus (excluding gestational diabetes)
* Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants
* documented history of postoperative nausea and vomiting, previous gastric bypass surgery, history of chronic opioid use (chronic pain syndrome)
* Patient refusal

Primary outcomes:
measure: systolic blood pressure variation before delivery
timeFrame: time from immediately after spinal anesthesia until delivery
measure: mean blood pressure variation before delivery
timeFrame: time from immediately after spinal anesthesia until delivery
measure: systolic blood pressure variation during cesarean delivery
timeFrame: time from immediately after spinal anesthesia until the end of surgery
measure: mean blood pressure variation during cesarean delivery
timeFrame: time from immediately after spinal anesthesia until the end of surgery
Secondary outcomes:
measure: Time to administartion of the first rescue bolus
timeFrame: time from immediately after spinal anesthesia until delivery
measure: duration of hypotension
timeFrame: immediately after spinal anesthesia until the end of surgery
measure: number of rescue boluses
timeFrame: immediately after spinal anesthesia until the end of surgery
measure: Incidence of hypotension
timeFrame: tile from right after spinal anesthesia until delivery
measure: Norepinephrine consumption
timeFrame: time fro right after spinal anesthesia until the end of surgery
measure: Nausea
timeFrame: time of surgery (right after spinal anesthesia until end of surgery)
measure: Vomiting
timeFrame: time of surgery (right after spinal anesthesia until end of surgery)
measure: Bradycardia
timeFrame: immediately after spinal anesthesia until the end of surgery
measure: arrhythmia
timeFrame: time of surgery (right after spinal anesthesia until end of surgery)
measure: Hypertension
timeFrame: right after spinal anesthesia until end of surgery)]
measure: Apgar score
timeFrame: at time of birth
measure: mean pH of the fetal cord blood
timeFrame: time of birth
Other outcomes:
Locations:
city: Tunis
country: Tunisia
facility: Tunis maternity and neonatology center, minisetry of public health
Study officials:
affiliation: University Tunis El Manar
name: HAYEN Hayen maghrebi, professor
role: STUDY_CHAIR
References: