Clinical trial NCT05502146: Comparison of Two Different Norepinephrine Bolus Doses for Management of Spinal Anesthesia-Induced Maternal Hypotension
Official title: Comparison of Two Different Norepinephrine Bolus Doses for Management of Spinal Anesthesia-Induced Hypotension in Cesarean Section: A Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Spinal Anesthetic Toxicity
Hypotension Drug-Induced
Cesarean Section Complications
Lead sponsor: Mersin University
Sponsor class: OTHER
First posted: 2022-08-16
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study the investigators will compare two doses of norepinephrine bolus (6 mcg and 8 mcg) in management of maternal hypotensive episode after spinal block during cesarean delivery.

Detailed description: Maternal hypotension after spinal anesthesia is a common and serious complication during cesarean delivery. Despite all preventive measures, the incidence of hypotension is still around 20%. In these cases, maternal hypotension treatment is usually required using vasopressor boluses. One of the vasopressors commonly used during cesarean delivery is norepinephrine, especially recently.

Although phenylephrine has long been the first choice for the prevention and treatment of maternal hypotension, its use may cause bradycardia and decreased maternal cardiac output.

Norepinephrine is an alpha adrenergic agonist with weak beta adrenergic agonistic activity; therefore, it does not cause significant cardiac depression like phenylephrine. Norepinephrine has been introduced for use during cesarean delivery with promising results. Several previous studies have investigated the efficacy of norepinephrine infusion in preventing maternal hypotension. A dose-response study investigated the best dose of Norepinephrine for the prevention of hypotension. In the dose-response study mentioned above, a dose of 6 mcg was reported as the best dose for prophylaxis against hypotension.

There are very limited studies investigating the best bolus dose of norepinephrine for the treatment of maternal hypotensive episode, and the optimal dose recommendation is uncertain. In this study, researchers will investigate the efficacy and adverse effects of two bolus doses of norepinephrine (6 mcg and 8 mcg) in the management of a maternal hypotensive episode after subarachnoid block during cesarean delivery.

Eligibility criteria: Inclusion Criteria:

* Woman,
* ASA I-II,
* 18-49 age range,
* Actual body weight \>50 kg,\<90 kg
* Actual height \>150cm, \<180cm
* Patients undergoing surgery under elective conditions and emergency cases for non-bleeding reasons
* Fasting period is appropriate,
* Term pregnancy (38-42 weeks),
* Patients without cardiovascular disease
* Spinal block that does not reach the high level (\<T4),
* Patients without diagnosis of stage 2 or higher hypertension hypertension (Stage 2 hypertension is defined as a systolic blood pressure of more than 160 mmHg and a diastolic blood pressure of more than 90 mmHg.),
* Patients without vasoactive drug use,
* Preop Systolic Blood Pressure \>90 mmHg,
* Bleeding less than 750 ml,
* Patients who signed the informed consent form to be included in the study

Exclusion Criteria:

* ASA III-IV,
* Pregnant women outside the age range of 18-49,
* Actual body weight \>90kg, \<50kg
* Actual height \>180cm, \<150cm
* Patients with inappropriate fasting time
* Preterm pregnancy (\<38 weeks) or postterm pregnancy (\>42 weeks)
* Bleeding amount more than 750 ml
* Emergency surgery with bleeding (previa, placental abruption, etc.)- Pregnant with cardiovascular system disease,
* High block level (\>T4)
* Having a diagnosis of stage 2 or higher hypertension hypertension (Stage 2 hypertension is defined as a systolic blood pressure of more than 160 mmHg and a diastolic blood pressure of more than 90 mmHg.),
* Use of vasoactive drugs,
* Preop Systolic Blood Pressure \<90 mmHg
* Patients who did not sign the informed consent form to be included in the study

Primary outcomes:
measure: Rate of successful management of maternal hypotension
timeFrame: After spinal anesthesia until the end of surgery
measure: Number of Noradrenaline doses administered and total dose amount
timeFrame: After spinal anesthesia until the end of surgery
Secondary outcomes:
measure: Incidence of reactive hypertension
timeFrame: After spinal anesthesia until the end of surgery
measure: Incidence of bradycardia
timeFrame: After spinal anesthesia until the end of surgery
measure: Evaluation of "Appearance, Pulse, Grimace, Activity, and Respiration" (APGAR) score
timeFrame: The first 5 minutes after birth
measure: Umbilical cord blood gas analyses of fetus
timeFrame: The first 5 minutes after birth
measure: Umbilical cord blood gas analyses of fetus
timeFrame: The first 5 minutes after birth
measure: Umbilical cord blood gas analyses of fetus
timeFrame: The first 5 minutes after birth
measure: Umbilical cord blood gas analyses of fetus
timeFrame: The first 5 minutes after birth
measure: Umbilical cord blood gas analyses of fetus
timeFrame: The first 5 minutes after birth
measure: The frequency of side effects after norepinephrine
timeFrame: During surgery after spinal block
measure: The frequency of side effects after subarachnoid block
timeFrame: During surgery after spinal block
measure: Effect of noradrenaline on heart rate variability
timeFrame: Measurements just before and 1 minute after noradrenaline administration
Other outcomes:
Locations:
city: Mersin
country: Turkey
facility: Mersin University
state: Yenişehir
Study officials:
affiliation: Mersin University
name: Levent Özdemir, Assist Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.
citation: Chen D, Qi X, Huang X, Xu Y, Qiu F, Yan Y, Li Y. Efficacy and Safety of Different Norepinephrine Regimens for Prevention of Spinal Hypotension in Cesarean Section: A Randomized Trial. Biomed Res Int. 2018 May 23;2018:2708175. doi: 10.1155/2018/2708175. eCollection 2018.
citation: Carvalho B, Dyer RA. Norepinephrine for Spinal Hypotension during Cesarean Delivery: Another Paradigm Shift? Anesthesiology. 2015 Apr;122(4):728-30. doi: 10.1097/ALN.0000000000000602. No abstract available.
citation: Hassabelnaby YS, Hasanin AM, Adly N, Mostafa MMA, Refaat S, Fouad E, Elsonbaty M, Hussein HA, Mahmoud M, Abdelwahab YM, Elsakka A, Amin SM. Comparison of two Norepinephrine rescue bolus for Management of Post-spinal Hypotension during Cesarean Delivery: a randomized controlled trial. BMC Anesthesiol. 2020 Apr 17;20(1):84. doi: 10.1186/s12871-020-01004-y.