Femoral Peri-arterial Local Anesthetic Injection Decreases Tourniquet Associated Ischemic Hypertension

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03390426
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.8
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

The purpose of this prospective randomized double-blind study is to determine if the novel technique of ultrasound guided peri-arterial injection of local anesthetic around the femoral artery decreases ischemic hypertension associated with prolonged lower extremity tourniquet time during total ankle arthroplasty (TAA) and foot fusion surgeries. Patients will be randomized 1:1 to receive either local anesthetic or saline, which will be injected superomedially to the femoral artery in an attempt to block sympathetic afferents and decrease tourniquet associated hypertension intraoperatively.

Condition or Disease	Intervention/Treatment	Phase
Tourniquet Hypertension; Intraoperative Hypertension; Total Ankle Arthroplasty; Ankle Fusion	Drug: Mepivacaine; Procedure: Perifemoral Injection of Local Anesthetic; Drug: Saline	Phase 4

Detailed Description

The purpose of this prospective randomized double-blind study is to determine if the novel technique of ultrasound guided peri-arterial injection of local anesthetic around the femoral artery decreases ischemic hypertension associated with prolonged lower extremity tourniquet time during total ankle arthroplasty (TAA) and foot fusion surgeries. Efficacy will be determined by analyzing incidence of intraoperative ischemic hypertension, defined as >30% increase in systolic blood pressure, associated with tourniquet inflation times greater than 90 minutes. The study will involve a total of 30 patients (15 in each group) and with a power of 80% to detect a 50% difference. The patients involved in the study will be ASA 1-3 patients who are undergoing either TAA or foot fusion surgeries. Patients will receive standard of care for their anesthesia, which at Duke Hospital includes placement of popliteal and saphenous perineural catheters and a general anesthetic with a laryngeal mask airway. Patients will be randomized to receive femoral peri-arterial injection with either 1.5% mepivacaine with 1:400,000 epinephrine or 0.9% saline which will be performed preoperatively at time of perineural catheter placement. Patients will assume standard risk associated with nerve blocks, including theoretical risk of nerve damage and local anesthetic systemic toxicity. Possible benefits include improved intraoperative hemodynamic stability, decreased intraoperative opioid and antihypertensive medications, and decreased tourniquet associated pain post-operatively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Femoral Peri-arterial Local Anesthetic Injection Decreases Tourniquet Associated Ischemic Hypertension
• Actual Study Start Date: May 3, 2018
• Actual Primary Completion Date: Oct 27, 2018
• Actual Study Completion Date: Oct 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepivacaine Block Group Injection of local anesthetic (mepivacaine) above and beside the femoral artery.	Drug: Mepivacaine; An ultrasound guided injection of mepivacaine superomedially to the femoral artery.; Other Names: Carbocaine ; Procedure: Perifemoral Injection of Local Anesthetic; An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.; Other Names: Femoral periarterial injection
Placebo Comparator: Saline Sham Group Injection of salt water (saline) above and beside the femoral artery.	Procedure: Perifemoral Injection of Local Anesthetic; An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.; Other Names: Femoral periarterial injection ; Drug: Saline; An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.; Other Names: Salt Water placebo

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Experiencing Tourniquet Hypertension [Intraoperatively (~3 hours)]

   Measuring systolic blood pressure using a cuff, aim to keep <30mmHg change from baseline

Secondary Outcome Measures

1. Pain Scores as Measured by the Numeric Rating Scale (NRS-11) [While in PACU (~1 hour)]

   The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. 0 = No Pain, 1-3 = Mild Pain, 4-6 = Moderate Pain, 7-10 = Severe Pain.

2. Amount of Opioid Pain Medications Used by Patient [Perioperative period (~4 hours)]

   Amount of opioid pain medication used by patient over a 4 hour period immediately after surgery. Opioids taken are converted to morphine equivalents.

3. Amount of Esmolol Used Intraoperatively [Intraoperatively (~3 hours)]

   Amount of esmolol (in mg) used intraoperatively to decrease blood pressure after subject achieved tourniquet hypertension.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Patients that will be included in the study are English speaking 18-75 year old ASA 1-3 patients undergoing total ankle arthroplasty.

Exclusion Criteria:

1. ASA 4 or 5

2. Diagnosis of chronic pain

3. Daily chronic opioid use (over 3 months of continuous opioid use).

4. Inability to communicate pain scores or need for analgesia.

5. Infection at the site of block placement

6. Age under 18 years old or greater than 75 years old

7. Pregnant women (as determined by standard of care day-of surgery urine bHCG)

8. Intolerance/allergy to local anesthetics

9. Weight <50 kg

10. Suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.

11. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, may interfere with study assessments or compliance.

12. Current or historical evidence of any clinically significant disease or condition that, in the opinion of the investigator, may increase the risk of surgery or complicate the subject's postoperative course

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Hospital	Durham	North Carolina	United States	27713

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: William M Bullock, Assistant Professor

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 8, 2018

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03390426
• Other Study ID Numbers: Pro00089161
• First Posted: Jan 4, 2018
• Last Update Posted: May 5, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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 Duke University: Perifemoral; Tourniquet; Mepivacaine; Tourniquet Hypertension
• Additional relevant MeSH terms: Hypertension; Anesthetics; Mepivacaine; Anesthetics, Local

Study Results

Participant Flow

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
Period Title: Overall Study
STARTED	15	16
COMPLETED	15	15
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group	Total
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 33.3%	7 46.7%	12 40%
>=65 years	10 66.7%	8 53.3%	18 60%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.47 (11.84)	65.67 (4.61)	63.81 (9.95)
Sex: Female, Male (Count of Participants)
Female	2 13.3%	5 33.3%	7 23.3%
Male	13 86.7%	10 66.7%	23 76.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.7%	0 0%	1 3.3%
White	14 93.3%	15 100%	29 96.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	15 100%	30 100%
ASA Status (Count of Participants)
ASA 1	2 13.3%	0 0%	2 6.7%
ASA 2	6 40%	7 46.7%	13 43.3%
ASA 3	7 46.7%	8 53.3%	15 50%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.11 (4.63)	32.64 (5.41)	31.63 (5.11)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Experiencing Tourniquet Hypertension
Description	Measuring systolic blood pressure using a cuff, aim to keep <30mmHg change from baseline
Time Frame	Intraoperatively (~3 hours)

Outcome Measure Data

Analysis Population Description

Subjects who completed the study.

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
Measure Participants	15	15
Count of Participants [Participants]	5 33.3%	14 93.3%

2. Secondary Outcome

Title	Pain Scores as Measured by the Numeric Rating Scale (NRS-11)
Description	The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. 0 = No Pain, 1-3 = Mild Pain, 4-6 = Moderate Pain, 7-10 = Severe Pain.
Time Frame	While in PACU (~1 hour)

Outcome Measure Data

Analysis Population Description

Subjects who completed the study.

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	1.80 (2.86)	1.07 (1.71)

3. Secondary Outcome

Title	Amount of Opioid Pain Medications Used by Patient
Description	Amount of opioid pain medication used by patient over a 4 hour period immediately after surgery. Opioids taken are converted to morphine equivalents.
Time Frame	Perioperative period (~4 hours)

Outcome Measure Data

Analysis Population Description

Subjects who completed the study.

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
Measure Participants	15	15
Mean (Standard Deviation) [morphine equivalents]	10.48 (5.77)	8.19 (4.65)

4. Secondary Outcome

Title	Amount of Esmolol Used Intraoperatively
Description	Amount of esmolol (in mg) used intraoperatively to decrease blood pressure after subject achieved tourniquet hypertension.
Time Frame	Intraoperatively (~3 hours)

Outcome Measure Data

Analysis Population Description

Subjects who completed the study.

Arm/Group Title	Mepivacaine Block Group	Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.	Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
Measure Participants	15	15
Mean (Standard Deviation) [mg]	8.00 (14.24)	95.33 (107.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepivacaine Block Group, Saline Sham Group
	Comments	We determined 30 subjects were needed to detect a 50% difference in THN incidence between the two groups using a one-sided Fisher's exact test with alpha = 0.05 and 80% power while allowing up to 20% drop-out. For primary and secondary outcomes, comparisons were made between the two groups using a two-sample t-test or Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. p-value of <0.05 was considered to be statistically significant.
	Type of Statistical Test	Superiority
	Comments	this is a superiority study and the "non-inferiority or equivalence analysis" is not required
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Comparisons were made between the two groups using a two-sample t-test or Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. p-value of <0.05 was considered to be statistically significant.
	Method	t-test, 2 sided
	Comments	Comparisons were made using a two-sample t-test or Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables.

Adverse Events

Time Frame	24 hours
Arm/Group Title	Mepivacaine Block Group		Saline Sham Group
Arm/Group Description	Injection of local anesthetic (mepivacaine) above and beside the femoral artery. Mepivacaine: An ultrasound guided injection of mepivacaine superomedially to the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively.		Injection of salt water (saline) above and beside the femoral artery. Perifemoral Injection of Local Anesthetic: An ultrasound guided injection of mepivacaine superomedially to the formal artery in an effort to numb the nerves that contribute to tourniquet hypertension intraoperatively. Saline: An ultrasound guided injection using a medication that does NOT numb any nerves called saline, or salt water.
All Cause Mortality
	Mepivacaine Block Group		Saline Sham Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Mepivacaine Block Group		Saline Sham Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Mepivacaine Block Group		Saline Sham Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.