Midodrine for Prophylaxis Against Post Spinal Hypotension in Elderly Population

• ClinicalTrials.gov Identifier: NCT05548985
• Recruitment Status: Completed
• First Posted: September 22, 2022
• Last Update Posted: September 15, 2023
• Sponsor: Cairo University
• Information provided by (Responsible Party): Ahmed Hasanin, Cairo University

Study Description

Brief Summary:

Hip fracture is a common and serious healthcare problem which commonly affects elderly populations. The common route of anesthesia for hip arthroplasty is spinal anesthesia. Elderly populations are characterized by high incidence of post spinal anesthesia hypotension; furthermore, elderly patients commonly have systemic medical disorder; therefore, this population is highly vulnerable to perioperative hypotension. Moreover , intraoperative hypotension during hip surgery has been recently recognized as a major risk factor for postoperative morbidity and mortality.

Through the effect of spinal anesthesia on sympathetic system Veno-dilatation, decreased venous return, and consequently decreased cardiac output and hypotension will be induced. Vasopressors are commonly used for prophylaxis against post spinal hypotension in different patient subgroups. The commonly used drugs are alpha-adrenoreceptor agonists such as ephedrine, phenylephrine, and recently norepinephrine. All these agents are effective in maintenance of blood pressure; however, they have some disadvantages; ephedrine is commonly associated with tachycardia, phenylephrine and norepinephrine are associated with bradycardia. All the former mentioned drugs are used intravenously.

Midodrine hydrochloride is another alpha-adrenoreceptor agonist drug which is used for management of various hypotensive disorders. Midodrine is the prodrug which is metabolized to desglymidodrine which is a direct arteriolar and venous vasopressor. Midodrine is characterized by being an oral drug, with minimal central nervous system side effects, and good oral bioavailability. No studies had evaluated the efficacy of midodrine for prophylaxis against post-spinal anesthesia hypotension in elderly population.

Aim of the work:

This thesis aims to evaluate the efficacy and safety of oral 5 mg of midodrine compared to placebo in prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty

Condition or disease	Intervention/treatment	Phase
Hypotension; Spinal Anesthesia; Elderly	Drug: Midodrine Oral Tablet; Drug: Metoclopramide	Not Applicable

Detailed Description:

Participants will be instructed to fast for 6 hours for solid light meals and 2 hours for clear fluids. The baseline blood pressure will be measured in the preparation room 90 min before spinal anaesthesia as the mean of three measurements with difference of less than 10%. The patients will receive the study drug after measurement of the baseline blood pressure reading. The patient will be monitored for blood pressure and heart rate at 15 min intervals after administration of the study drug. In the operating room, routine monitors (Electrocardiogram, pulse oximetry, and non-invasive blood pressure monitor) will be applied; intravenous line will be secured, and routine pre-medications will be administrated.

Preoperative evaluation of volume status:

All patients will be assessed for volume status before spinal block through evaluation of the inferior vena cava (IVC) collapsibility, and patients who will show IVC collapsibility > 36% will be considered fluid responders and will receive Ringer's lactate solution, 6 mL/kg ideal body weight over 15 minutes.

IVC collapsibility will be calculated as: (maximum IVC diameter - minimum IVC diameter) / maximum IVC diameter.

Anaesthetic management:

Spinal anaesthesia will be performed in the sitting position at level of L3-4 or L4-5 interspaces with a 25-gauge spinal needle. After confirming cerebrospinal fluid flow, 10 mg of 0.5% hyperbaric bupivacaine plus 25 mcg fentanyl will be injected. The degree of sensory block (cold test by alcohol gauze) will be assessed in the study with a goal of T6-8 dermatomal level block. If spinal anaesthesia failed, the patient will be excluded from the study and will be managed according to the attending anaesthetist discretion, local expertise and clinical practice. After induction of spinal anaesthesia maintenance fluid as 2ml/kg/hour of ringer acetate will be commenced.

Post spinal hypotension will be defined as mean arterial pressure < 80% of the baseline reading 30 minutes after spinal block. Hypotension will be managed by 10 mg ephedrine. Severe hypotension will be defined as mean arterial pressure < 70% of the baseline reading and will be managed by 15 mg ephedrine. The dose of ephedrine will be repeated if the hypotensive episode persisted 2 min after the initial bolus. Bradycardia will be defined as heart rate < 50 bpm and will be managed with 0.5 mg of atropine IV.

Blood loss will be replaced using Ringer's lactate solution at a ratio of 3:1 until transfusion threshold is reached. Further blood loss will be replaced using packed RBCs

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: : Oral Midodrine for Prophylaxis Against Post Spinal Anaesthesia Hypotension During Hip Arthroplasty in Elderly Population: A Randomized Controlled Trial
• Actual Study Start Date: October 17, 2022
• Actual Primary Completion Date: July 15, 2023
• Actual Study Completion Date: July 15, 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: control group; oral metoclopramide 10 mg, Metoclopramide tablet was chosen as a placebo because it has the same appearance of midodrine tablet with no cardiovascular effects	Drug: Metoclopramide; oral placebo (metoclopramide 10 mg tablet). 90 min before performing spinal block
Active Comparator: Midodrine group; oral midodrine tablet (5 mg)	Drug: Midodrine Oral Tablet; oral midodrine tablet (5 mg) 90 min before performing spinal block

Outcome Measures

Primary Outcome Measures :

1. Intraoperative ephedrine consumption [ Time Frame: 1 minutes after spinal injection until 45 minutes after induction of spinal anesthesia ]
   mg

Secondary Outcome Measures :

1. Incidence of post-spinal hypotension [ Time Frame: 1 minutes after spinal injection until 45 minutes after induction of spinal anesthesia ]
   defined as mean arterial pressure < 80% of the baseline reading 45 minutes after induction of spinal anesthesia and not related to blood loss
2. Incidence of severe spinal induced hypotension [ Time Frame: 1 minutes after spinal injection until 45 minutes after induction of spinal anesthesia ]
   defined as mean arterial pressure < 60% of the baseline reading 45 minutes after induction of spinal anesthesia and not related to blood loss
3. Incidence of bradycardia [ Time Frame: 1 minutes after spinal injection until 45 minutes after induction of spinal anesthesia ]
   as heart rate less than 50 beats per minutes
4. heart rate [ Time Frame: 1 minute after intervention, every 15 minutes after intervention for 90 minutes, every 2 minutes after spinal anesthesia for 20 min, then every 5 minutes until the end of the procedure ]
   beats per minutes
5. mean arterial pressure [ Time Frame: 1 minute after intervention, every 15 minutes after intervention for 90 minutes, every 2 minutes after spinal anesthesia for 20 min, then every 5 minutes until the end of the procedure ]
   mmHg

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Elderly patients (>65).
• ASA I-II-III.
• Scheduled for hip joint surgery under spinal anaesthesia

Exclusion Criteria:

• • Uncontrolled hypertension

  • Liver cell failure (child B or C).
  • Chronic renal failure on regular dialysis
  • Contraindications of spinal anaesthesia
  • History of allergy to midodrine
  • Cardiac morbidities (impaired contractility with ejection fraction < 50%, heart block, arrhythmias, tight valvular lesions).
  • Acute renal disease, urinary retention
  • Patients on negative chronotropic drugs (such as beta blocker) or vasoconstrictor
  • Patients with glaucoma

Contacts and Locations

Locations

Egypt

Cairo University

Cairo, Egypt

Sponsors and Collaborators

Cairo University

More Information

• Responsible Party: Ahmed Hasanin, Principal Investigator, Cairo University
• ClinicalTrials.gov Identifier: NCT05548985
• Other Study ID Numbers: MD-25-2021
• First Posted: September 22, 2022
• Last Update Posted: September 15, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: data supporting this research will be available from the PI upon reasonable request

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypotension; Vascular Diseases; Cardiovascular Diseases; Midodrine; Metoclopramide; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents