Comparison of Intra-articular Dexmedetomidine and Magnesium in Postoperative Pain

• Sponsor: Derince Training and Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03479216
• Collaborator: (none)
• Enrollment: 62
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.2
• Patients Per Site Per Month: 14.7

Study Details

Study Description

Brief Summary

Arthroscopic meniscus surgeries are the most frequent orthopedic procedures. The objective of the study is to compare the effects of intraarticular local anesthetic and adjuvant (dexmedetomidine vs magnesium) combinations in postoperative pain and analgesic requirement. The investigators' hypothesis is adjuvants added to the local anesthetics decreases the total local anesthetic dose, provides more effective pain relief according to local anesthetic only, and decreases the postoperative systemic non-steroidal analgesic and opioid doses.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain; Intra-articular Injection; Dexmedetomidine; Magnesium Sulfate	Drug: Precedex; Drug: Magnesium Sulfate	Phase 4

Detailed Description

Arthroscopic meniscus surgeries are the most frequent orthopedic procedures. However, irritation of free nerve endings in the synovial tissue and anterior fat pads and stretching and resection in the joint capsule lead to pain at various levels. Proper pain management enhances recovery, provides early mobilization and shortens length of hospital stay.

"Opioid-free" analgesia methods are frequently emphasized in published postoperative pain management guidelines and multimodal treatment approaches such as local anesthetic infiltration is recommended. In the treatment of knee pain, intra-articular drug injections are the most commonly used method because of minimal systemic side effects.

The drugs most commonly administered intraarticularly included local anesthetics (bupivacaine, levobupivacaine, lidocaine), opioids (morphine, fentanyl), magnesium sulfate, steroids, and α2 agonists (clonidine, dexmedetomidine).

Dexmedetomidine is a selective, specific, lipophilic and potent α2 adrenergic receptor agonist with sedative, anxiolytic, analgesic, antihypertensive and sympatholytic effects. It provides analgesic activity through both the central and peripheral nervous system. The analgesic effects of intra-articular administration of dexmedetomidine in arthroscopic surgeries have been demonstrated. Most side effects of this drug included hypotension and bradycardia. However, these side effects have never been encountered with intra-articular injection of the drug.

Magnesium is also an adjuvant drug which has a key role in nociceptive transmission, and acts as a NMDA (N-Methyl-D-Aspartate) antagonist in spinal neurons.

While opioid free anesthesia and analgesia methods gain importance nowadays, there has been increased interest in non-opioid analgesic drugs and multimodal analgesia applications. In order to increase the effects of local anesthetics and prolong their analgesic times, the addition of various adjuvants to local anesthetics is frequently used.

In the randomized controlled trials, intraarticular local anesthetic drugs combined with adjuvant drugs for postoperative analgesia were found to be superior to local anesthetic drugs alone. It is also known that local anesthetics have negative effects on chondrocytes. One of the goals of the investigators' in this study is to reduce the amount of local anesthetic used by adding adjuvant to local anesthetics.

In this study, the investigators plan to compare the efficacy of 2 adjuvants (magnesium sulfate and dexmedetomidine) combined with local anesthetics to be given intraarticularly for postoperative pain management after elective arthroscopic surgery.

Intraarticular high-volume drug injections may cause pain due to tension in the joint capsule. Additionally, the investigators aim to decrease the total drug volume with adjuvant drugs used in combination with local anesthetic, and thus to prevent joint capsule tension pain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Comparison of Intra-articular Dexmedetomidine and Magnesium in Postoperative Pain
• Actual Study Start Date: Mar 26, 2018
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Precedex 5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml)	Drug: Precedex; 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.; Other Names: bupivacaine
Experimental: Magnesium Sulfate 5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml)	Drug: Magnesium Sulfate; 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.; Other Names: bupivacaine

Outcome Measures

Primary Outcome Measures

1. Postoperative Pain [24 hours]

   postoperative pain scores (rest and movement) (ward) Pain scores were assessed with a 10-cm Visual Analogue Scale (VAS) (with 0 = no pain and 10 = the worst imaginable pain)

Secondary Outcome Measures

1. Postoperative Opioid/NSAID Consumption [24 hours]

   nonsteroid antiinflammatory drugs (NSAID) or opioid drugs that are applied to patients will be noted.

2. Rescue Analgesic Time [24 hours]

   Time to first analgesic demand at the orthopedics ward (from intraarticular injection to first analgesic requirement)

3. Surgery Time [24 hours]

   time from skin incision to closure

4. Time to the End of Spinal Anesthesia [24 hours]

   time from the start of spinal anesthesia (total block = Bromage 3) to the end of spinal anesthesia (Bromage 0)

5. Mobilization [24 hours]

   First mobilization time after surgery

6. Number of Participants With Complications Due to Intraarticular Injection [24 hours]

   post-injection complications due to intraarticular injection will be noted.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age >18, <65

• scheduled for elective knee arthroscopy under spinal anesthesia

• ASA I and ASA II

Exclusion Criteria:

• age <18 and >65

• patients who received general anesthesia

• diabetes

• refusal of the patient

• known allergy to the specified drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Derince Training and Research Hospital	Kocaeli	Derince	Turkey	41900

Sponsors and Collaborators

• Derince Training and Research Hospital

Investigators

• Study Chair: Tolga K Saracoglu, Ass Prof, Derince Training and Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 12, 2018

More Information

Publications

None provided.

• Responsible Party: Hande G. Aytuluk, Principal Investigator, Derince Training and Research Hospital
• ClinicalTrials.gov Identifier: NCT03479216
• Other Study ID Numbers: U1111-1211-1791
• First Posted: Mar 27, 2018
• Last Update Posted: Nov 13, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Hande G. Aytuluk, Principal Investigator, Derince Training and Research Hospital: Analgesia; Anesthesia; Arthroscopy; Bupivacaine; Dexmedetomidine; Injections, Intra-Articular; Magnesium; Pain, Postoperative
• Additional relevant MeSH terms: Pain, Postoperative; Magnesium Sulfate; Dexmedetomidine; Bupivacaine

Study Results

Participant Flow

Recruitment Details	History of cardiac, hepatic or renal disorders, diabetes mellitus, chronic pain treatment, contraindication to/refusal of spinal anesthesia, a known allergy to the study drugs, or who refused to participate in the study were excluded. (10 patients excluded: 5 declined regional anesthesia, 4 had diabetes mellitus,1 failure of regional anesthesia)
Pre-assignment Detail	52 patients aged between 18 and 65 years with ASA I or II who were scheduled for elective arthroscopic meniscectomy under spinal anesthesia were included in this prospective, randomized, double-blind study.

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Period Title: Overall Study
STARTED	31	31
COMPLETED	26	26
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Precedex	Magnesium Sulfate	Total
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.	Total of all reporting groups
Overall Participants	26	26	52
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	41.62	42.73	42.18
Sex: Female, Male (Count of Participants)
Female	6 23.1%	4 15.4%	10 19.2%
Male	20 76.9%	22 84.6%	42 80.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Turkey	26 100%	26 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Postoperative Pain
Description	postoperative pain scores (rest and movement) (ward) Pain scores were assessed with a 10-cm Visual Analogue Scale (VAS) (with 0 = no pain and 10 = the worst imaginable pain)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

visual analogue scale (VAS) scores at rest at 2nd hour (VAS2 R), 4th hour (VAS4 R), 6th hour (VAS6 R), 8th hour (VAS8 R), 12th hour (VAS12 R), 18th hour (VAS18 R) VAS scores at movement at 2nd hour (VAS2 M), 4th hour (VAS4 M), 6th hour (VAS6 M), 8th hour (VAS8 M), 12th hour (VAS12 M), 18th hour (VAS18 M)

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
VAS 2 R	0	0.04
VAS2 M	0.19	0.23
VAS4 R	0.81	0.12
VAS4 M	2.04	1.19
VAS6 R	1.50	1.31
VAS6 M	3.46	3.31
VAS8 R	1.23	1.77
VAS8 M	3.08	4.08
VAS12 R	0.73	1.15
VAS12 M	2.62	3.19
VAS18 R	0.23	0.27
VAS18 M	1.62	1.69

2. Secondary Outcome

Title	Postoperative Opioid/NSAID Consumption
Description	nonsteroid antiinflammatory drugs (NSAID) or opioid drugs that are applied to patients will be noted.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
NSAID	17	14
opioid	0	1

3. Secondary Outcome

Title	Rescue Analgesic Time
Description	Time to first analgesic demand at the orthopedics ward (from intraarticular injection to first analgesic requirement)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Time to first analgesic demand at the orthopedics ward (from intra-articular injection to first analgesic requirement) was calculated in minutes among patients who required analgesics

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	15	13
Mean (Full Range) [minutes]	477.33	498.46

4. Secondary Outcome

Title	Surgery Time
Description	time from skin incision to closure
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
Mean (Full Range) [minutes]	24.23	25.58

5. Secondary Outcome

Title	Time to the End of Spinal Anesthesia
Description	time from the start of spinal anesthesia (total block = Bromage 3) to the end of spinal anesthesia (Bromage 0)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
Mean (Full Range) [minutes]	148.1	147.5

6. Secondary Outcome

Title	Mobilization
Description	First mobilization time after surgery
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
Mean (Full Range) [minutes]	143.27	139.42

7. Secondary Outcome

Title	Number of Participants With Complications Due to Intraarticular Injection
Description	post-injection complications due to intraarticular injection will be noted.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Precedex	Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.	5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
Measure Participants	26	26
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	an average of 1 month (from hospitalization to re-admissions due to complications (if any))
Arm/Group Title	Precedex		Magnesium Sulfate
Arm/Group Description	5ml 0.25% Bupivacaine ve 50mcg Dexmetedomidin (diluted to 5ml with normal saline) intraarticularly at the end of surgery (total volume: 10 ml) Precedex: 10 ml of Bupivacaine ve 50mcg Dexmetedomidin mixture will be injected intraarticularly at the end of the surgery.		5ml 0.25% Bupivacaine ve 5ml Magnesium Sulfate intraarticularly at the end of surgery (total volume: 10 ml) Magnesium Sulfate: 10 ml of Bupivacaine ve magnesium sulfate mixture will be injected intraarticularly at the end of the surgery.
All Cause Mortality
	Precedex		Magnesium Sulfate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)
Serious Adverse Events
	Precedex		Magnesium Sulfate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Precedex		Magnesium Sulfate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.