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

Primary Purpose

Spinal Anesthetic Toxicity, Hypotension Drug-Induced, Cesarean Section Complications

Status
Completed
Phase
Phase 4
Locations
Turkey
Study Type
Interventional
Intervention
Noradrenaline Bitartrate
Bupivacaine Hydrochloride
Noradrenaline Bitartrate
Bupivacaine Hydrochloride
Sponsored by
Mersin University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Anesthetic Toxicity

Eligibility Criteria

18 Years - 49 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Mersin University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bolus 6 micrograms Noradrenaline group

Bolus 8 micrograms Noradrenaline group

Arm Description

Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.

Mothers in this group will receive a bolus of Norepinephrine 8 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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).
Incidence of bradycardia
Patients with a heart rate less than 40 bpm
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.
Umbilical cord blood gas analyses of fetus
Potential of hydrogen (pH): Normal range is between 7.35-7.45
Umbilical cord blood gas analyses of fetus
Partial arterial oxygen pressure (PaO2, mmHg): Normal range is between 50-100 mmHg
Umbilical cord blood gas analyses of fetus
Partial carbon dioxide pressure (PaCO2, mmHg): Normal range is between 35-45 mmHg
Umbilical cord blood gas analyses of fetus
Bicarbonate (HCO3, mEq/liter): Normal range is between 22-26 mEq/liter
Umbilical cord blood gas analyses of fetus
Base deficit (BE, mEq/liter): Normal range is between +2 to -2 mEq/liter
The frequency of side effects after norepinephrine
the number of patients with side effects (Nausea, vomiting, headache, tinnitus, arrhythmia, chest pain, etc.)
The frequency of side effects after subarachnoid block
Side effects seen after spinal block and in patients who have not yet received noradrenaline
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.

Full Information

First Posted
August 10, 2022
Last Updated
January 16, 2023
Sponsor
Mersin University
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1. Study Identification

Unique Protocol Identification Number
NCT05502146
Brief Title
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
August 17, 2022 (Actual)
Primary Completion Date
October 1, 2022 (Actual)
Study Completion Date
October 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mersin University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Anesthetic Toxicity, Hypotension Drug-Induced, Cesarean Section Complications

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bolus 6 micrograms Noradrenaline group
Arm Type
Experimental
Arm Description
Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.
Arm Title
Bolus 8 micrograms Noradrenaline group
Arm Type
Active Comparator
Arm Description
Mothers in this group will receive a bolus of Norepinephrine 8 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride.
Intervention Type
Drug
Intervention Name(s)
Noradrenaline Bitartrate
Other Intervention Name(s)
Stenor
Intervention Description
An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.
Intervention Type
Drug
Intervention Name(s)
Bupivacaine Hydrochloride
Other Intervention Name(s)
Marcaine Spinal Heavy
Intervention Description
Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL)
Intervention Type
Drug
Intervention Name(s)
Noradrenaline Bitartrate
Other Intervention Name(s)
Stenor
Intervention Description
An intravenous bolus of norepinephrine 8 mcg will be administered for management of maternal hypotension.
Intervention Type
Drug
Intervention Name(s)
Bupivacaine Hydrochloride
Other Intervention Name(s)
Marcaine Spinal Heavy
Intervention Description
Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL)
Primary Outcome Measure Information:
Title
Rate of successful management of maternal hypotension
Description
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.
Time Frame
After spinal anesthesia until the end of surgery
Title
Number of Noradrenaline doses administered and total dose amount
Description
Evaluation of the number of bolus noradrenaline doses and the total dose required for the treatment of maternal hypotension after spinal block.
Time Frame
After spinal anesthesia until the end of surgery
Secondary Outcome Measure Information:
Title
Incidence of reactive hypertension
Description
Number of patients with reactive hypertension (defined as systolic blood pressure ≥120% from the baseline reading after administration of norepinephrine bolus).
Time Frame
After spinal anesthesia until the end of surgery
Title
Incidence of bradycardia
Description
Patients with a heart rate less than 40 bpm
Time Frame
After spinal anesthesia until the end of surgery
Title
Evaluation of "Appearance, Pulse, Grimace, Activity, and Respiration" (APGAR) score
Description
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.
Time Frame
The first 5 minutes after birth
Title
Umbilical cord blood gas analyses of fetus
Description
Potential of hydrogen (pH): Normal range is between 7.35-7.45
Time Frame
The first 5 minutes after birth
Title
Umbilical cord blood gas analyses of fetus
Description
Partial arterial oxygen pressure (PaO2, mmHg): Normal range is between 50-100 mmHg
Time Frame
The first 5 minutes after birth
Title
Umbilical cord blood gas analyses of fetus
Description
Partial carbon dioxide pressure (PaCO2, mmHg): Normal range is between 35-45 mmHg
Time Frame
The first 5 minutes after birth
Title
Umbilical cord blood gas analyses of fetus
Description
Bicarbonate (HCO3, mEq/liter): Normal range is between 22-26 mEq/liter
Time Frame
The first 5 minutes after birth
Title
Umbilical cord blood gas analyses of fetus
Description
Base deficit (BE, mEq/liter): Normal range is between +2 to -2 mEq/liter
Time Frame
The first 5 minutes after birth
Title
The frequency of side effects after norepinephrine
Description
the number of patients with side effects (Nausea, vomiting, headache, tinnitus, arrhythmia, chest pain, etc.)
Time Frame
During surgery after spinal block
Title
The frequency of side effects after subarachnoid block
Description
Side effects seen after spinal block and in patients who have not yet received noradrenaline
Time Frame
During surgery after spinal block
Title
Effect of noradrenaline on heart rate variability
Description
Comparison of the rates of change in heart rate in measurements before and after two different bolus doses of noradrenaline.
Time Frame
Measurements just before and 1 minute after noradrenaline administration

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female patients with cesarean delivery
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Levent Özdemir, Assist Prof
Organizational Affiliation
Mersin University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mersin University
City
Mersin
State/Province
Yenişehir
ZIP/Postal Code
33343
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28248702
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.
Results Reference
background
PubMed Identifier
29951531
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.
Results Reference
background
PubMed Identifier
25654435
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.
Results Reference
background
PubMed Identifier
32303180
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.
Results Reference
result

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

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