Comparison of Two Different Norepinephrine Bolus Doses for Management of Spinal Anesthesia-Induced Maternal Hypotension

Comparison of Two Different Norepinephrine Bolus Doses for Management of Spinal Anesthesia-Induced Hypotension in Cesarean Section: A Randomized Controlled Study

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.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications; Hypotension Drug-Induced; Spinal Anesthetic Toxicity
• Intervention / Treatment: Drug: Noradrenaline Bitartrate; Drug: Bupivacaine Hydrochloride; Drug: Noradrenaline Bitartrate

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Yenişehir
    • Mersin, Yenişehir, Turkey, 33343
      • Mersin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bolus 6 micrograms Noradrenaline group; Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.	Drug: Noradrenaline Bitartrate; An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.; Other Names: Stenor; Drug: Bupivacaine Hydrochloride; Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL); Other Names: Marcaine Spinal Heavy; Drug: Noradrenaline Bitartrate; An intravenous bolus of norepinephrine 8 mcg will be administered for management of maternal hypotension.; Other Names: Stenor
Active Comparator: Bolus 8 micrograms Noradrenaline group; Mothers in this group will receive a bolus of Norepinephrine 8 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.	Drug: Noradrenaline Bitartrate; An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.; Other Names: Stenor; Drug: Bupivacaine Hydrochloride; Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL); Other Names: Marcaine Spinal Heavy; Drug: Noradrenaline Bitartrate; An intravenous bolus of norepinephrine 8 mcg will be administered for management of maternal hypotension.; Other Names: Stenor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful management of maternal hypotension	Number of patients with successful management of a maternal hypotensive episode (defined as systolic blood pressure greater than 80% of baseline measurement and systolic blood pressure greater than 90 mmHg) Successful management is considered to be successful management if blood pressure does not fall below 90 mmHg and 80% of baseline measurement within 6 minutes after norepinephrine administration after hypotension develops.	After spinal anesthesia until the end of surgery
Number of Noradrenaline doses administered and total dose amount	Evaluation of the number of bolus noradrenaline doses and the total dose required for the treatment of maternal hypotension after spinal block.	After spinal anesthesia until the end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of reactive hypertension	Number of patients with reactive hypertension (defined as systolic blood pressure ≥120% from the baseline reading after administration of norepinephrine bolus).	After spinal anesthesia until the end of surgery
Incidence of bradycardia	Patients with a heart rate less than 40 bpm	After spinal anesthesia until the end of surgery
Evaluation of "Appearance, Pulse, Grimace, Activity, and Respiration" (APGAR) score	The minimum score that can be obtained from this scale is 0 and the maximum is 10 points. Scoring will be calculated at 1 and 5 minutes immediately after birth. A score of 9 to 10 is consistent with a better clinical outcome, while a score of 8 or less will be considered a poor clinical outcome.	The first 5 minutes after birth
Umbilical cord blood gas analyses of fetus	Potential of hydrogen (pH): Normal range is between 7.35-7.45	The first 5 minutes after birth
Umbilical cord blood gas analyses of fetus	Partial arterial oxygen pressure (PaO2, mmHg): Normal range is between 50-100 mmHg	The first 5 minutes after birth
Umbilical cord blood gas analyses of fetus	Partial carbon dioxide pressure (PaCO2, mmHg): Normal range is between 35-45 mmHg	The first 5 minutes after birth
Umbilical cord blood gas analyses of fetus	Bicarbonate (HCO3, mEq/liter): Normal range is between 22-26 mEq/liter	The first 5 minutes after birth
Umbilical cord blood gas analyses of fetus	Base deficit (BE, mEq/liter): Normal range is between +2 to -2 mEq/liter	The first 5 minutes after birth
The frequency of side effects after norepinephrine	the number of patients with side effects (Nausea, vomiting, headache, tinnitus, arrhythmia, chest pain, etc.)	During surgery after spinal block
The frequency of side effects after subarachnoid block	Side effects seen after spinal block and in patients who have not yet received noradrenaline	During surgery after spinal block
Effect of noradrenaline on heart rate variability	Comparison of the rates of change in heart rate in measurements before and after two different bolus doses of noradrenaline.	Measurements just before and 1 minute after noradrenaline administration

Collaborators and Investigators

• Sponsor: Mersin University
• Investigators: Principal Investigator: Levent Özdemir, Assist Prof, Mersin University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Sympathomimetics; Vasoconstrictor Agents; Bupivacaine; Norepinephrine
• Other Study ID Numbers: 2022/05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No