The Prolonging Effect of Dexmedetomidine on Spinal Anesthesia Through Different Routes if Administrations

Phase 4

Not yet recruiting

• Conditions: Spinal Anesthesia Evaluation
• Interventions: Drug: Interventional group#1; Drug: Interventional group#2

• Registration Number: NCT06769737
• Lead Sponsor: King Abdulaziz Medical City

Brief Summary

This prospective, double-blinded, randomized clinical trial aims to examine the effects of combining isobaric bupivacaine with dexmedetomidine administered intrathecally (IT), compared to the combination of isobaric bupivacaine administered intrathecally and dexmedetomidine administered intravenously (IV), on spinal anesthesia prolongation time in minutes, time of regression from Bromage score 3 to 0.

Detailed Description

Dexmedetomidine, an α2-adrenergic agonist, is commonly used in anesthetic practice for various applications, including premedication, as an adjunct to general anesthesia, sole anesthetic agent, and sedation in intensive care settings. Its effects include enhancing the efficacy of other anesthetic drugs, inducing perioperative sympatholysis, and lowering blood pressure by stimulating central α2 and imidazoline receptors.

Spinal anesthesia is a type of regional anesthesia that involves administering a local anesthetic directly into the cerebrospinal fluid surrounding the spinal cord and nerve roots. It is primarily used for procedures below the umbilicus, such as orthopedic surgeries involving joints and bones.

The 0.5% isobaric formulation of bupivacaine is characterized by a slower onset compared to hyperbaric formulations but provides a longer duration of both sensory and motor blockade. Achieving successful spinal anesthesia (SA) depends on selecting the appropriate dose of isobaric bupivacaine. Administering an excessive dose can lead to high spinal anesthesia, while an insufficient dose may result in inadequate cephalad spread.

A retrospective observational study involving 1,079 adult patients who received spinal anesthesia with 0.5% isobaric bupivacaine between 2018 and 2021 investigated the relationship between the bupivacaine dose and block height. The study concluded that for patients younger than 60 years, doses of 15-17 mg (3.0-3.4 mL) were optimal, while doses of 10.5-16 mg (2.1-3.2 mL) were suitable for patients aged 60 years or older. These doses achieved a T5-T10

Over the years, various agents have been combined with local anesthetics (LA) to extend the duration of action in both spinal anesthesia via intrathecal (IT) administration and peripheral nerve blocks (PNB), achieving varying levels of success. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, offers several advantages as an adjuvant. These include its sedative and analgesic effects (acting at both spinal and supraspinal levels), anti-anxiety properties, inhibition of sympathetic activity, mild respiratory depression, and hemodynamic stability.

Intrathecal α2-adrenergic receptor agonists, including dexmedetomidine, have been shown to exhibit antinociceptive properties for both somatic and visceral pain. Studies using small doses of intrathecal dexmedetomidine (e.g., 3 µg) in combination with bupivacaine for spinal anesthesia demonstrated faster motor block onset, prolonged motor as well as sensory block durations, and preserved hemodynamic stability without causing significant sedation.

The dose-dependent effects of dexmedetomidine have been extensively studied. Randomized clinical trials (RCTs) comparing doses (e.g., 3 µg vs. 5 µg with isobaric Ropivacaine and 5 µg vs. 10 µg with isobaric bupivacaine) consistently concluded that higher doses of dexmedetomidine enhanced the onset and prolonged the duration of sensory and motor block when used as an adjuvant in spinal anesthesia.

Intravenous dexmedetomidine has also been shown to prolong the sensory and motor block of bupivacaine through its supraspinal anesthetic and analgesic actions. However, its intravenous administration is associated with a dose-dependent risk of bradycardia. A systematic review and meta-analysis conducted in 2013, which included 364 patients from seven randomized controlled trials of intermediate to high quality, examined the effects of intravenous dexmedetomidine on spinal anesthesia duration. The analysis found that motor block duration increased by approximately 21% (P \< 0.00001). Importantly, no significant differences in the incidence of hypotension or postoperative sedation were observed between the dexmedetomidine and placebo groups, and none of the patients experienced respiratory depression.

Study Timeline

• Study First Submitted: 2024-12-02
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-10
• Last Update Posted: 2025-01-10
• Study Start: 2025-03-01
• Primary Completion: 2025-08-15
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Male and female patients in adult age group more than 18 years old
• ASA classification I, II, and III.
• Orthopedic surgery, including total hip replacement (THR) and total knee replacement (TKR).
• No history of Obstructive sleep apnea

Exclusion Criteria

• Patient below 18 years old of both genders.
• ASA classification of IV and more.
• Patients with a height of less than 150 cm.
• Patients on alpha-two antagonist ACE inhibitors and CCB.
• Patient received intrathecal morphine, intravascular dexamethasone, or Midazolam
• Patient who can't tolerate fluid challenge. Example: ESRD, HF...etc.
• Any contraindication for neuraxial procedure. Examples: coagulopathy, severe AS, sepsis...etc.
• Psychiatric patients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine HCL IT	Interventional group#1	Group B: RECEIVING IT "Dexmedetomidine HCL," "Demexa®," Through IT, receiving plain isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) +3mcg of "Dexmedetomidine HCL, (0.15 ml), total volume = 2.4 ml. Through IV, 15 ml of normal saline ( placebo) will be received over 30 mins.
Dexmedetomidine HCL IV	Interventional group#2	Group C: RECEIVING IV "Dexmedetomidine HCL," "Demexa®," Through IT, receiving plain isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + Placebo of normal saline (0.15 ml), total volume = 2.4 ml. Through IV, 0.5 mcg/kg of "Dexmedetomidine HCL" is prepared in a concentration of 2 mcg/ml ( maximum of 15 ml, 30 mcg) over 30 mins.

Primary Outcome Measures

Name	Time	Method
Regression time of Bromage score from 3 to 0	Patients' recruitment and participation in the study will be over 3-4 month, as the load of lower limb surgery at KAMC is high. Subjects' participation will be throughout the surgery time and 45 mins later in PACU if there was not a reason for delay.	This double-blind study will include 75 participants divided equally into three groups: A, B, and C. The IT medication injection / IV infusion start time is considered time zero. The Bromage score will be assessed at the motor block's onset, representing a Bromage score of 3, recorded in minutes. The record of the time to reach Bromage 3 represents the spinal anesthesia's onset time.; The Bromage scale is a clinical scale used to determine motor block during regional anesthesia. It evaluates lower limb movement, grade 0, no motor block, to grade 3, complete motor block.; Bromage 0; the patient can move hip, knee, and ankle. No motor block Bromage 1: the patient cannot move the hip but can move the knee and ankle. Partial block Bromage 2: the patient cannot move the hip and knee but can move the ankle. partial block Bromage 3: the patient cannot move the hip, knee, and ankle. Complete motor block A Bronage score regression to 0 during a PACU stay will represent a spinal anesthesia offset

Secondary Outcome Measures

Name	Time	Method
Hypotension, bradycardia and desaturation with dermatome coverage <T4 or >T4, checked by Ice test.	Patients' recruitment and participation in the study will be over 3-4 month, as the load of lower limb surgery at KAMC is high. Subjects' participation will be throughout the surgery time and 45 mins later in PACU if there was not a reason for delay.	Investigators will monitor the side effects associated with each route of administration through close hemodynamic monitoring for heart rate (HR) in Beat per minute (BPM), Oxygen saturation (SpO2) presented in percentage (%), and blood pressure (BP) presented in millimeter mercury (mmHg), aiming for HR above 50 bpm, oxygen saturation \>94%, and BP 15% around the patient's baseline blood pressure. All data will be recorded on the data collection sheet.; To differentiate high spinal-related hemodynamic instability ( dermatome \>4) versus dexmedetomidine (dermatome less than T4), the sensory block level will be checked with an ICE test, where the dermatomal coverage will be checked along the midaxillary line with an ice bag, as nipple line is representing dermatome T4.; HR limits: 60 to 100 bpm. Lower bradycardia, higher tachycardia. BP limits, systolic 100 - 120 mmHg. Lower hypotension, higher hypertension. SpO2 limit: 100-94%, 100% standard, \<94% desaturation.
Sedation score using Ramsay sedation score, aiming for score 2; calm and oriented.	Patients' recruitment and participation in the study will be over 3-4 month, as the load of lower limb surgery at KAMC is high. Subjects' participation will be throughout the surgery time and 45 mins later in PACU if there was not a reason for delay.	The Investigators will check the Ramsay Sedation Scale (RSS) throughout the procedure. It is used to evaluate the depth of sedation in patients and divided into six scales (from scale no.1, anxious to scale no.6, no response), aiming for scale no.2: cooperative, oriented, and calm. All data will be recorded on the data collection sheet every 10 minutes for the first hour of "Dexmedetomidine" administration and 45 minutes in PACU.; The scale is getting worse while the moving up in the scale Score 1: anxious, agitated, and restless. Score 2: Cooperative-oriented and tranquil. Score 3: The patient responds to commands only. Score 4: The patient responds to a brisk response to a light glabellar tap or loud auditory stimulation.; Score 5: Patient sluggishly responds to a light glabellar tap or loud auditory stimulus.; Score 6: The patient exhibits no response.

Trial Locations

Locations (1)

King Abdulaziz Medical City; 🇸🇦 Riyadh, Saudi Arabia