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

NCT ID: NCT06769737

Last Updated: 2025-01-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-01

Study Completion Date

2025-09-01

Brief Summary

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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

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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.

Conditions

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Spinal Anesthesia Evaluation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This prospective, single-blinded, randomized clinical trial compares the effects of intrathecal (IT) dexmedetomidine combined with isobaric bupivacaine and intravenous (IV) dexmedetomidine combined with intrathecal isobaric bupivacaine on the duration of spinal anesthesia. The study includes one control group and two interventional groups.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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Controlled

Group A: Control group. Receiving plain isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + 0.15 ml of normal saline (placebo), total volume = 2.4 ml.

Through IV, 15 ml of normal saline ( placebo) will be received over 30 mins.

Group Type NO_INTERVENTION

No interventions assigned to this group

Dexmedetomidine HCL IT

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.

Group Type EXPERIMENTAL

Interventional group#1

Intervention Type DRUG

The intrathecal mixture of spinal anesthesia: 12 mg of isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + 20 mcg of "Fentanyl," "Martindale pharma Fentanyl®," 50mcg/ml (0.4ml) + 3 mcg of "Dexmedetomidine HCL," "Demexa®," 4mcg/ml (0.75 ml) total volume = 3.55 ml.

The Bromage score will be assessed by the anesthesiologist every 5 minutes after positioning the patient supine until the first incision. The Bromage score is a clinical scale used to determine motor block during regional anesthesia by evaluating lower limb movement: Grade 0: Full movement of hips, knees, and ankles (no block). Grade 1: Unable to lift the leg but can move knees and ankles (partial block). Grade 2: Unable to bend the knee but can move ankles (near-complete block). Grade 3: No movement in hips, knees, or ankles (complete block). Dermatomal coverage will be assessed simultaneously till it reaches the L1-L2 level. Also, The Ramsay Sedation Scale (RSS) will be used to evaluate the sedation depth, if any.

Dexmedetomidine HCL IV

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.

Group Type EXPERIMENTAL

Interventional group#2

Intervention Type DRUG

The intrathecal mixture of spinal anesthesia: 12 mg of isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + 20 mcg of "Fentanyl," "Martindale pharma Fentanyl®," 50mcg/ml (0.4ml) total volume = 2.8 ml.

The intravascular mixture consists of 0.5 mcg/kg of "Dexmedetomidine HCL," "Demexa®," and a maximum of 30 mcg diluted to 4 mcg/ml. According to body weight, the total volume is 7.5 ml or less and given using a syringe pump over 30 minutes. The anesthesiologist will start the infusion once the patient is positioned supine post-spinal anesthesia and has stable hemodynamics. The Bromage score will be assessed by the anesthesiologist every 5 minutes after positioning the patient supine until the first incision reaches grade 3: No movement in hips, knees, or ankles (complete block). The anesthesiologist will assess dermatomal coverage until it reaches the L1-L2 and calculate the Ramsay Sedation Scale (RSS) of the depth of sedation aiming for level 2: Patient is cooperative, oriented, and calm

Interventions

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Interventional group#1

The intrathecal mixture of spinal anesthesia: 12 mg of isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + 20 mcg of "Fentanyl," "Martindale pharma Fentanyl®," 50mcg/ml (0.4ml) + 3 mcg of "Dexmedetomidine HCL," "Demexa®," 4mcg/ml (0.75 ml) total volume = 3.55 ml.

The Bromage score will be assessed by the anesthesiologist every 5 minutes after positioning the patient supine until the first incision. The Bromage score is a clinical scale used to determine motor block during regional anesthesia by evaluating lower limb movement: Grade 0: Full movement of hips, knees, and ankles (no block). Grade 1: Unable to lift the leg but can move knees and ankles (partial block). Grade 2: Unable to bend the knee but can move ankles (near-complete block). Grade 3: No movement in hips, knees, or ankles (complete block). Dermatomal coverage will be assessed simultaneously till it reaches the L1-L2 level. Also, The Ramsay Sedation Scale (RSS) will be used to evaluate the sedation depth, if any.

Intervention Type DRUG

Interventional group#2

The intrathecal mixture of spinal anesthesia: 12 mg of isobaric "Bupivacaine 0.5%", "Bucaine®," (2.4 ml) + 20 mcg of "Fentanyl," "Martindale pharma Fentanyl®," 50mcg/ml (0.4ml) total volume = 2.8 ml.

The intravascular mixture consists of 0.5 mcg/kg of "Dexmedetomidine HCL," "Demexa®," and a maximum of 30 mcg diluted to 4 mcg/ml. According to body weight, the total volume is 7.5 ml or less and given using a syringe pump over 30 minutes. The anesthesiologist will start the infusion once the patient is positioned supine post-spinal anesthesia and has stable hemodynamics. The Bromage score will be assessed by the anesthesiologist every 5 minutes after positioning the patient supine until the first incision reaches grade 3: No movement in hips, knees, or ankles (complete block). The anesthesiologist will assess dermatomal coverage until it reaches the L1-L2 and calculate the Ramsay Sedation Scale (RSS) of the depth of sedation aiming for level 2: Patient is cooperative, oriented, and calm

Intervention Type DRUG

Other Intervention Names

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Intrathecal "Dexmedetomidine HCL," "Demexa®," Intravascular "Dexmedetomidine HCL," "Demexa®,"

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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King Abdulaziz Medical City

OTHER_GOV

Sponsor Role lead

Responsible Party

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Hebah Musalem

Anesthesia Assistant consultant

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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King Abdulaziz Medical City

Riyadh, , Saudi Arabia

Site Status

Countries

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Saudi Arabia

Central Contacts

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Hebah Musalem, Anesthesia Asistant consultant

Role: CONTACT

00966533112656

Mohammad Al Harbi, Anesthesia Consultant,

Role: CONTACT

00966508818000

Facility Contacts

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Heba Musalem

Role: primary

0533112656

References

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Abdallah FW, Abrishami A, Brull R. The facilitatory effects of intravenous dexmedetomidine on the duration of spinal anesthesia: a systematic review and meta-analysis. Anesth Analg. 2013 Jul;117(1):271-8. doi: 10.1213/ANE.0b013e318290c566. Epub 2013 Apr 30.

Reference Type BACKGROUND
PMID: 23632057 (View on PubMed)

Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, Ozcan B. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth. 2010 Jan;57(1):39-45. doi: 10.1007/s12630-009-9231-6. Epub 2009 Dec 29.

Reference Type BACKGROUND
PMID: 20039221 (View on PubMed)

Al-Mustafa MM, Abu-Halaweh SA, Aloweidi AS, Murshidi MM, Ammari BA, Awwad ZM, Al-Edwan GM, Ramsay MA. Effect of dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi Med J. 2009 Mar;30(3):365-70.

Reference Type BACKGROUND
PMID: 19271064 (View on PubMed)

Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, Bulbul M, Baraka AS. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand. 2006 Feb;50(2):222-7. doi: 10.1111/j.1399-6576.2006.00919.x.

Reference Type BACKGROUND
PMID: 16430546 (View on PubMed)

Lundblad M, Trifa M, Kaabachi O, Ben Khalifa S, Fekih Hassen A, Engelhardt T, Eksborg S, Lonnqvist PA. Alpha-2 adrenoceptor agonists as adjuncts to peripheral nerve blocks in children: a meta-analysis. Paediatr Anaesth. 2016 Mar;26(3):232-8. doi: 10.1111/pan.12825. Epub 2015 Dec 16.

Reference Type BACKGROUND
PMID: 26671834 (View on PubMed)

Visavakul O, Leurcharusmee P, Pipanmekaporn T, Khorana J, Patumanond J, Phinyo P. Effective Dose Range of Intrathecal Isobaric Bupivacaine to Achieve T5-T10 Sensory Block Heights for Elderly and Overweight Patients: An Observational Study. Medicina (Kaunas). 2023 Mar 1;59(3):484. doi: 10.3390/medicina59030484.

Reference Type BACKGROUND
PMID: 36984485 (View on PubMed)

Uppal V, Retter S, Shanthanna H, Prabhakar C, McKeen DM. Hyperbaric Versus Isobaric Bupivacaine for Spinal Anesthesia: Systematic Review and Meta-analysis for Adult Patients Undergoing Noncesarean Delivery Surgery. Anesth Analg. 2017 Nov;125(5):1627-1637. doi: 10.1213/ANE.0000000000002254.

Reference Type BACKGROUND
PMID: 28708665 (View on PubMed)

Taye MG, Molla A, Teshome D, Hunie M, Kibret S, Fentie Y, Temesgen N, Engidaw MT, Fenta E. Predictors of hypoxemia after general anesthesia in the early postoperative period in a hospital in Ethiopia: an observational study. Multidiscip Respir Med. 2021 Dec 1;16(1):782. doi: 10.4081/mrm.2021.782. eCollection 2021 Jan 15.

Reference Type BACKGROUND
PMID: 35003732 (View on PubMed)

Bekker AY, Kaufman B, Samir H, Doyle W. The use of dexmedetomidine infusion for awake craniotomy. Anesth Analg. 2001 May;92(5):1251-3. doi: 10.1097/00000539-200105000-00031. No abstract available.

Reference Type BACKGROUND
PMID: 11323355 (View on PubMed)

Khan ZP, Ferguson CN, Jones RM. alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999 Feb;54(2):146-65. doi: 10.1046/j.1365-2044.1999.00659.x.

Reference Type BACKGROUND
PMID: 10215710 (View on PubMed)

Other Identifiers

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ICTR24/001/11

Identifier Type: -

Identifier Source: org_study_id

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