Comparative Dose-Response of Intrathecal Dexmedetomidine for Post-Spinal Shivering

Comparative Efficacy and Dose-Response of Intrathecal Dexmedetomidine in Attenuating Post-Spinal Shivering: Double-Blinded Randomized Controlled Trial

Dexmedetomidine, a highly selective α2-adrenergic agonist, when used intrathecally as an adjuvant to local anesthetics, prolongs sensory/motor block and may blunt thermoregulatory shivering mechanisms. Several randomized controlled trials and meta-analyses have demonstrated decreased shivering incidence with intrathecal dexmedetomidine, but reported doses vary (commonly 2.5, 5, and 10 µg, and in some trials up to 15-20 µg), and the balance between efficacy and adverse effects (sedation, bradycardia, and hypotension) is not fully established. Hence, a head-to-head randomized comparison of several low-to-moderate intrathecal doses is warranted.

Objective: to compare the safety and efficacy of three intrathecal dexmedetomidine doses (2.5 µg, 5 µg, 10 µg) versus placebo for the prevention of post-spinal shivering.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-Spinal Shivering
• Intervention / Treatment: Drug: Group P (Placebo Control Group); Drug: Group D2.5 (Low-Dose Dexmedetomidine Group); Drug: Group D5 (Moderate-Dose Dexmedetomidine Group); Drug: Group D10 (Higher-Dose Dexmedetomidine Group)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Neveen A Kohaf, Ph.D; Phone Number: +201060383012; Email: nevenabdo@azhar.edu.eg

Study Locations

• Egypt
  • Egypt
    • Cairo, Egypt, Egypt, 11865
      • Al-Azhar University
      • Contact: Neveen A. Kohaf, PhD; Phone Number: 01060383012; Email: nevenabdo@azhar.edu.eg
      • Principal Investigator: Hany Baumy, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (age 18-75 years)
• Scheduled for ureteric stone removal surgery
• ASA(American Society of Anesthesiologists) physical status I, II, or III
• Able to provide informed consent

Exclusion Criteria:

• Known allergy to dexmedetomidine, bupivacaine, or other study medications
• Preexisting bradycardia (heart rate <50 beats per minute)
• Second- or third-degree atrioventricular (AV) block without a pacemaker
• Severe hepatic dysfunction
• Uncontrolled hypotension
• Pregnancy
• Chronic use of α₂-agonists or antagonists (e.g., clonidine, tizanidine)
• Infection at the planned spinal puncture site
• Coagulopathy or bleeding disorder
• Inability to rate or communicate shivering (e.g., language barrier, cognitive impairment)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group P; Patients in this group will receive the standard spinal anesthetic consisting of hyperbaric bupivacaine 0.5% (15 mg) combined with an equivalent volume of normal saline (0.9% NaCl), containing no active dexmedetomidine. The total intrathecal injection volume will be standardized to 3.5 mL across all groups by adjusting the volume of saline added.	Drug: Group P (Placebo Control Group); Patients in this group will receive the standard spinal anesthetic consisting of hyperbaric bupivacaine 0.5% (15 mg) combined with an equivalent volume of normal saline (0.9% NaCl), containing no active dexmedetomidine. The total intrathecal injection volume will be standardized to 3.5 mL across all groups by adjusting the volume of saline added. This group serves as the control to establish the baseline incidence and characteristics of post-spinal shivering and block dynamics without the intervention of the α2-adrenergic agonist.
Experimental: Group D2.5; Patients in this group will receive the standard spinal anesthetic (15 mg hyperbaric bupivacaine 0.5%) supplemented with a low dose of 2.5 µg of dexmedetomidine. Normal saline will be added to achieve the standardized total intrathecal volume of 3.5 mL.	Drug: Group D2.5 (Low-Dose Dexmedetomidine Group); Patients in this group will receive the standard spinal anesthetic (15 mg hyperbaric bupivacaine 0.5%) supplemented with a low dose of 2.5 µg of dexmedetomidine. Normal saline will be added to achieve the standardized total intrathecal volume of 3.5 mL.
Experimental: Group D5; Patients in this group will receive the standard spinal anesthetic combined with a moderate dose of 5 µg of dexmedetomidine. The total volume will be adjusted to 3.5 mL with normal saline.	Drug: Group D5 (Moderate-Dose Dexmedetomidine Group); Patients in this group will receive the standard spinal anesthetic combined with a moderate dose of 5 µg of dexmedetomidine. The total volume will be adjusted to 3.5 mL with normal saline.
Experimental: Group D10; Patients in this group will receive the standard spinal anesthetic supplemented with a higher dose of 10 µg of dexmedetomidine, with normal saline used to standardize the total volume to 3.5 mL.	Drug: Group D10 (Higher-Dose Dexmedetomidine Group); Patients in this group will receive the standard spinal anesthetic supplemented with a higher dose of 10 µg of dexmedetomidine, with normal saline used to standardize the total volume to 3.5 mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically significant shivering	Incidence of clinically significant shivering within 60 minutes after spinal injection, defined as Crossley and Mahajan shivering scale grade ≥2 (scale 0-4)The highest intensity of shivering experienced by the patient, scored on the 0-4 scale. The Crossley and Mahajan shivering scale is a clinically validated, four-grade ordinal scale (0-4) used to objectively quantify the severity of post-anesthetic shivering. It is defined as follows: Grade 0 signifies no shivering; Grade 1 indicates mild, intermittent fasciculations of the face, neck, or chest; Grade 2 represents visible, intermittent shivering involving more than one muscle group; Grade 3 denotes generalized, continuous shivering of the whole body; and Grade 4 describes gross, bed-shaking tremors that interfere with monitoring or procedure. Grade ≥2 is typically considered clinically significant and often triggers therapeutic intervention. The scale is assessed through direct visual observation of the patient by trained personnel.	Throughout the intraoperative period until 60 minutes post-spinal.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first shivering episode	The duration from the completion of the spinal injection to the onset of the first observable shivering (any grade).	Intraoperative period, up to 60 minutes post-spinal.
Requirement of rescue anti-shivering drug	the number of patients required pharmacologic intervention (meperidine or tramadol) to treat severe shivering.	Intraoperative period, as needed.
Dose of rescue anti-shivering drug	The total amount of pharmacologic intervention (meperidine or tramadol) to treat severe shivering.	Intraoperative period, as needed.
Sedation level	The Ramsey Sedation Scale (RSS) is a simple, widely used six-level clinical tool (scores 1-6) for assessing a patient's level of sedation and responsiveness. It is scored as follows: 1 - Patient is anxious, agitated, or restless; 2 - Patient is cooperative, oriented, and tranquil; 3 - Patient responds only to commands; 4 - Patient exhibits a brisk response to a light glabellar tap or loud auditory stimulus; 5 - Patient exhibits a sluggish response to such a stimulus; and 6 - Patient exhibits no response to stimulus.	Postoperative 24 hour
Patient satisfaction	The patient's overall satisfaction with the anesthesia experience.Using a Likert scale (e.g., 1-5 or 1-10) or a standardized satisfaction questionnaire.	Postoperatively (e.g., prior to discharge from PACU).
Time to first analgesic request	The duration from the end of surgery until the patient first requires supplemental pain medication.	24 hours Postoperatively.

Collaborators and Investigators

• Sponsor: Al-Azhar University
• Collaborators: Benha University

Study record dates

Study Major Dates

• Study Start (Estimated): January 28, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 26, 2025
• First Submitted That Met QC Criteria: December 26, 2025
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Intrathecal Dexmedetomidine
• Other Study ID Numbers: RC. 2.12.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data can be shared upon a reasonable request from the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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