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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Noradrenaline Bitartrate
* Drug: Bupivacaine Hydrochloride
* Drug: Noradrenaline Bitartrate
* Drug: Bupivacaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bolus 6 micrograms Noradrenaline group<br>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<br>* An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.<br>* Other names: Stenor;Drug: Bupivacaine Hydrochloride<br>* Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL)<br>* Other names: Marcaine Spinal Heavy;|
| Active Comparator: Bolus 8 micrograms Noradrenaline group<br>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<br>* An intravenous bolus of norepinephrine 8 mcg will be administered for management of maternal hypotension.<br>* Other names: Stenor;Drug: Bupivacaine Hydrochloride<br>* Subarachnoid block will be performed using Bupivacaine hydrochloride (2.5 mL)<br>* Other names: Marcaine Spinal Heavy;|

What is the study measuring?
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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 |