Preoperative Oral Midodrine Versus Intraoperative Intravenous Norepinephrine in Preventing Post-spinal Anesthesia Hypotension in Cesarean Section: A Prospective Double-blind Randomized Clinical Trial

Neuraxial blockade such as spinal anaesthesia can cause severe hypotension due to pharmacological sympathectomy resulting in potential deleterious consequences for the patient, Prevention of this spinal anaesthesia induced hypotension is of utmost importance, Techniques currently in use for preventing hypotension include intravenous fluid prehydration, sympathomimetic drugs, and physical methods such as positioning and leg compression.

Midodrine is an orally active α-adrenergic agonist ,Used in clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies. Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine , causes venous and arterial vasoconstriction through stimulation of α1- receptors located in the vasculature, However ,Midodrine may cause several side effects as chills ,numbness , tingling ,paresthesia ,polyuria ,dysuria and headache.

On the other hand, Norepinephrine is a vasoconstrictor that predominantly stimulates α1 receptors to cause peripheral vasoconstriction and increase blood pressure. It also has some β1 receptor agonist activity that results in a positive inotropic effect on the heart at higher doses. Norepinephrine also may cause side effects as headache, blurred vision, chest pain ,nervousness, bradycardia or tachycardia.

Study Overview

• Status: Not yet recruiting
• Conditions: Post Spinal Anesthesia Hypotension
• Intervention / Treatment: Drug: Norepinephrine; Drug: Midodrine

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew R Khalafallah, Resident; Phone Number: 01284160711; Email: andrewramsis@med.sohag.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. The study will include 90 adult female patients, 45 in each group (between 18-35 years old).
2. patients of ASA physical status class I and class II.
3. patients scheduled for elective cesarean section under spinal anesthesia.

Exclusion Criteria:

1. Patient refusal.
2. Contraindication to spinal anesthesia .
3. Patients known allergic to Midodrine or Norepinephrine.
4. Patients with preexisting cardiovascular or cerebrovascular disease.
5. Patients with diabetes mellitus.
6. Patients with psychiatric disease or on psychiatric treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A; will receive a norepinephrine bolus at 0.05 μg/kg, followed by norepinephrine infusion at a rate of 0.05 μg/kg.min	Drug: Norepinephrine; after spinal anesthesia, norepinephrine will be injected intravenous as bolus at 0.05 μg/kg, followed by norepinephrine infusion at a rate of 0.05 μg/kg.min to prevent post spinal hypotension
Active Comparator: Group B; will receive 10 mg tablets of midodrine 1 hour before spinal anesthesia.	Drug: Midodrine; 10 mg tablets of midodrine 1 hour before spinal anesthesia to prevent post spinal anesthesia hypotension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post spinal anesthesia hypotension	decrease in Mean Arterial Blood Pressure more than 20% of the baseline reading	within 60 minutes of induction of spinal anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative ephedrine consumption	ephedrine dose injected intravenous to control post spinal hypotension	within 60 minutes of induction of spinal anesthesia
Incidence of post spinal anesthesia bradycardia	decrease in Heart Rate less than 50 Beats per minutes	within 60 minutes of induction of spinal anesthesia

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• McCrae AF, Wildsmith JA. Prevention and treatment of hypotension during central neural block. Br J Anaesth. 1993 Jun;70(6):672-80. doi: 10.1093/bja/70.6.672.
• Alseoudy MM, Nasr MO, Abdelsalam TA. Efficacy of Preoperative Oral Midodrine in Preventing Hypotension After Spinal Anesthesia in Young Adults: A Randomized Controlled Trial. Anesth Analg. 2022 Nov 1;135(5):1089-1096. doi: 10.1213/ANE.0000000000006173. Epub 2022 Aug 10.
• Quaglia MG, Farina A, Palmery M, Desideri N, Donati E, Bossu E, Strano S. Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent. Chirality. 2004 Jul;16(6):356-62. doi: 10.1002/chir.20041.
• Gutman LB, Wilson BJ. The Role of Midodrine for Hypotension Outside of the Intensive Care Unit. J Popul Ther Clin Pharmacol. 2017 Aug 23;24(3):e45-e50. doi: 10.22374/1710-6222.24.3.4.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

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; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Midodrine
• Other Study ID Numbers: Soh-Med-23-12-01MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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