Midodrine for Improving Hemodynamics After Spinal Anesthesia

Preoperative Midodrine for Improving Hemodynamics in Orthopedic Patients Undergoing Spinal Anesthesia

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 leg bindings and compression stockings. Midodrine is a direct acting α1-adrenoceptor agonist which causes venous and arterial vasoconstriction through stimulation of α1- receptors located in the vasculature. The aim of this study is to evaluate the efficacy and safety of prophylactic midodrine use with preoperative fluid hydration before spinal anesthesia in the prevention of hypotension in patients undergoing elective orthopedic surgery. We hypothesize that intraoperative hypotension would be less in patients given midodrine and intravenous fluid prehydration preoperatively before spinal anesthesia.

Study Overview

• Status: Completed
• Conditions: Hypotension After Spinal Anesthesia
• Intervention / Treatment: Drug: Midodrine Oral Product; Drug: Inert tablet containing sugar (placebo)

Detailed Description

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. Several techniques and methodologies have been adopted for the prevention of this neuraxial hypotension with varying degree of success. Techniques currently in use for preventing hypotension include intravenous fluid prehydration, sympathomimetic drugs, and physical methods such as leg bindings and compression stockings. Midodrine is a direct acting α1-adrenoceptor agonist which causes venous and arterial vasoconstriction through stimulation of α1- receptors located in the vasculature. The net result is an increase in vascular tone and systolic blood pressure. Cardiac β-receptors are unaffected and there is no significant blood brain barrier penetration. We hypothesize that intraoperative hypotension would be less in patients given midodrine and intravenous fluid prehydration preoperatively before spinal anesthesia. The study will include 80 patients who will be scheduled for elective orthopedic surgery on the lower extremities undergoing spinal anesthesia. It will be conducted in Mansoura University Hospital after getting approval from Institutional Review Board (IRB), Faculty of medicine, Mansoura University. Informed written consents will be obtained from all subjects in the study after ensuring confidentiality. Patients will be randomly allocated using computer generated random numbers to either treatment with midodrine (group M) or control (group C) using the sealed opaque envelope technique. Patients in group M will receive oral 10 mg tablet of midodrine with small sips of water one hour before arrival in the operation room while patients in group C will receive inert tablet containing sugar (placebo) at the same time. All patients will be monitored in with noninvasive blood pressure as well ascontinuous electrocardiogram (ECG) and pulse oximetry (SpO2). Before placement of spinal anesthesia, all patients will receive an IV bolus of 10mL/kg of Lactated Ringer's. Spinal anesthesia (midline puncture) will be performed in sitting position by a staff anesthetist at L3-L4 or L4-L5 with a 25-gauge Withacre needle injecting 12.5 mg of hyperbaric 0.5% bupivacaine (2.5 mL) with 10μg fentanyl. After injection,the patients will be turned supine. The baseline arterial blood pressure (mean) will be calculated as the average of 3 consecutive measurements before placement of the SA every 15 min after taking midodrine and every 5 min for 30 min after spinal anesthesia. Any vasovagal syncopes will be recorded. After placement of the SA, the patient's heart rate will be obtained every five minutes for 30 minutes and thereafter, in accordance with standard clinical practice, every 5 minutes until the end of surgery. The dermatome level of the sensory block using loss of pinprick will be checked every 5 minutes for 20minutes. The modified Bromage scale (0 = no motor block, 1 = straight leg hip flexion blocked, 2 = knee flexion blocked, 3 = complete motor block) will be used to quantify the degree of motor block at 20 minutes. Reqirements of ephedrine and atropine and fluide intake will be recorded. time to onset of the first hypotension, the proportion of patients without hypotension, and the number of bradycardic episodes per patient will also be recorded. Perioperative copmlications such as reactive hypertension, nausea, vomiting, hypothermia, shivering and postdural puncture headache will be recorded. An investigator who is blind to type of intervention wil be responsible for collection of data.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Mansoura, Egypt
    • Mansoura University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • American Society of Anesthesiologists (ASA) status: 1 or 2 .

  • Orthopedic surgery on the lower extremities

Exclusion Criteria:

• • Pheochromocytoma. .Throtoxicosis. .Structural heart disease.

  • Baseline blood pressure more than 140/90 .Acute kidney failure.
  • Any contraindications to spinal anesthesia such as local infection and coagulopathy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (midodrine group); Midodrine will be given orally with small sips of water one hour before arrival in the operation room before spinal anesthesia	Drug: Midodrine Oral Product; Patients will receive oral 10 mg tablet of midodrine with small sips of water one hour before arrival in the operation room. All patients will be monitored in with noninvasive blood pressure as well as continuous electrocardiogram (ECG) and pulse oximetry (SpO2). Before placement of spinal anesthesia, all patients will receive an IV bolus of 10mL/kg of Lactated Ringer's . Spinal anesthesia (midline puncture) will be performed in sitting position by a staff anesthetist at L3-L4 or L4-L5 with a 25-gauge Withacre needle injecting 12.5 mg of hyperbaric 0.5% bupivacaine (2.5 mL) with 10μg fentanyl. After injection,the patients will be turned supine.; Other Names: spinal anesthesia
Placebo Comparator: Group B (placebo group): Inert tablet containing sugar (placebo) will be given orally with small sips of water one hour before arrival in the operation room before spinal anesthesia	Drug: Inert tablet containing sugar (placebo); : Patients will receive Inert tablet containing sugar (placebo) with small sips of water one hour before arrival in the operation room. All patients will be monitored in with noninvasive blood pressure as well as continuous electrocardiogram (ECG) and pulse oximetry (SpO2). Before placement of spinal anesthesia, all patients will receive an IV bolus of 10mL/kg of Lactated Ringer's . Spinal anesthesia (midline puncture) will be performed in sitting position by a staff anesthetist at L3-L4 or L4-L5 with a 25-gauge Withacre needle injecting 12.5 mg of hyperbaric 0.5% bupivacaine (2.5 mL) with 10μg fentanyl. After injection,the patients will be turned supine; Other Names: spinal anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. incidence perioperative hypotension	the number of hypotensive patients will be recorded	Up to 4 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in mean arterial blood pressure	Mean arterial blood pressure will be recorded basal and every 15 min after taking midodrine and every 5 min after spinal anesthesia till end of surgery and every	Up to 4 hours after surgery
change in heart rate	heart rate will be recorded basal and every 15 min after taking midodrine and every 5 min after spinal anesthesia till end of surgery and every 15 minutes after surgery	Up to 4 hours after surgery
requirements of ephedrine and atropine	amount of ephedrine and atropine to treat hypotension and bradycardia	Up to 4 hours after the procedure
incidence of adverse effects	nausea, vomiting, shivering and postdural puncture headache will be recorded	Up to 24 hours surgery

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Mahmoud M Alseoudy, MD, Faculty of Medicine, Mansoura University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): December 29, 2020
• Study Completion (Actual): December 29, 2020

Study Registration Dates

• First Submitted: May 16, 2020
• First Submitted That Met QC Criteria: May 16, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 18, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: midodrine before spinal anesthesia
• 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; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Anesthetics; Midodrine
• Other Study ID Numbers: Midodrine and SA

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