Defining Normal Postoperative Magnetic Resonance Imaging After Total Knee Arthroplasty

• Sponsor: Benaroya Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT04821245
• Collaborator: Washington State Society of Anesthesiologists (Other)
• Enrollment: 36
• Location: 1
• Actual Duration (Months): 7.9
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

The aim of this study was to describe the postoperative "baseline" magnetic resonance imaging (MRI) appearance of the ipsilateral thigh musculature after total knee arthroplasty (TKA). The secondary aim was to describe baseline muscle enzyme levels under the same clinical scenario. Neither of these measures have been reported previously.

Condition or Disease	Intervention/Treatment	Phase
Local Anesthetic Complication; Local Anesthetic Drug Adverse Reaction

Detailed Description

• In 2016, 3 sentinel cases of presumed local anesthetic-induced myotoxicity were reported after TKA with associated continuous adductor canal block (CACB) analgesia. The diagnosis was made based on its consistency with animal and human descriptions of local anesthetic myotoxicity, including: a) exposure to local anesthetic, b) delayed symptom onset after a period of normal recovery, c) rapid development of profound muscle flaccidity, and d) complete to partial recovery of motor function after weeks to months. MRIs obtained in these patients showed diffuse intra- and inter-muscular edema (inflammation) of the ipsilateral thigh, which was believed to support the presumptive diagnosis. However, because baseline MRI appearance of upper leg muscles has never been described for this clinical scenario, it is possible that the MRI scans represented "normal, baseline" appearance.

• This case series intended to prospectively describe postoperative MRI appearance in a cohort of asymptomatic volunteer patients that underwent uncomplicated TKA/CACB. In addition, because obtaining biomarkers of muscle injury might also be a reasonable diagnostic step, we sought to measure preoperative and postoperative creatine phosphokinase (CPK) and aldolase levels.

• MRI scans were read by 5 board-certified musculoskeletal radiologists masked to the study's purpose. Grading was done using a standard grid that facilitated systematic evaluation of various regions within the upper leg. At least 3 of 5 radiologists were required to declare edema as present within a given region of the leg.

• Only those volunteer patients that presented a normal postoperative course, i.e., had no unexpected leg muscle weakness, were entered into the study. As such, the MRI and muscle enzyme analysis results had no impact on the volunteer patients' clinical outcome or management. This was a prospective, observational/descriptive case series. There was no control group and we did not intend to investigate issues of cause-and-effect.

Study Design

• Study Type: Observational
• Actual Enrollment: 36 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Defining Normal Postoperative Magnetic Resonance Imaging and Muscle Enzyme Levels After Total Knee Arthroplasty Associated With Continuous Adductor Canal Block
• Actual Study Start Date: Dec 4, 2018
• Actual Primary Completion Date: Aug 2, 2019
• Actual Study Completion Date: Aug 2, 2019

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Edema [1-2 days postoperative]

   Regions of the ipsilateral thigh were defined by muscle group, neuromuscular bundle, subcutaneous tissue, or inter-muscular fascial layers. Five board-certified musculoskeletal radiologists analyzed the scans for presence of edema. Edema was considered present if judged to be so by at least 3 of the 5 radiologists.

Secondary Outcome Measures

1. Postoperative Muscle Enzyme Levels [Sample was drawn the morning after surgery]

   Participants with Postoperative Creatine Phosphokinase (CPK) or Aldolase levels above the upper limit of normal

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Scheduled for unilateral primary TKA with CACB

• TKA and early recovery was uncomplicated (no evidence of unexpected leg weakness)

Exclusion Criteria:

• Contraindication to spinal anesthesia or adductor canal-based analgesia

• History of muscle wasting or related disease

• History of autoimmune disorders that may affect muscles

• History of neurologic condition affecting the lower extremities

• Contraindications to MRI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Benaroya Research Institute	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Benaroya Research Institute
• Washington State Society of Anesthesiologists

Investigators

• Principal Investigator: Joseph M Neal, MD, Benaroya Research Center at Virginia Mason Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan: w/o statistical comment - Apr 13, 2018
• Statistical Analysis Plan: Statistical Analysis Plan (specific comment) - Apr 9, 2018
• Informed Consent Form - Apr 25, 2019

More Information

Publications

• Hussain N, McCartney CJL, Neal JM, Chippor J, Banfield L, Abdallah FW. Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis. Br J Anaesth. 2018 Oct;121(4):822-841. doi: 10.1016/j.bja.2018.05.076. Epub 2018 Aug 8.
• Neal JM, Salinas FV, Choi DS. Local Anesthetic-Induced Myotoxicity After Continuous Adductor Canal Block. Reg Anesth Pain Med. 2016 Nov/Dec;41(6):723-727.
• Neal JM, Salinas FV, Choi DS. Reply to Dr Kelly et al. Reg Anesth Pain Med. 2017 May/Jun;42(3):414. doi: 10.1097/AAP.0000000000000574.

• Responsible Party: Joseph M. Neal, Affiliate Investigator, Benaroya Research Institute
• ClinicalTrials.gov Identifier: NCT04821245
• Other Study ID Numbers: BRI IRB18-008
• First Posted: Mar 29, 2021
• Last Update Posted: May 25, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Joseph M. Neal, Affiliate Investigator, Benaroya Research Institute: Myotoxicity; Myositis; Magnetic resonance imaging; Creatine phosphokinase; Aldolase
• Additional relevant MeSH terms: Drug-Related Side Effects and Adverse Reactions

Study Results

Participant Flow

Recruitment Details	Tertiary care medical center December 2018 through August 2019 Potential volunteers were contacted by the principal investigator at least 24 hours prior to their surgery. Informed consent was obtained at this point. Volunteers could decline to proceed at any point from initial informed consent through MRI scan or final blood draw
Pre-assignment Detail	-Volunteer patients only entered the study if they showed no signs of unexpected ipsilateral upper leg weakness prior to drawing blood samples or obtaining MRI scans

Arm/Group Title	Single Cohort
Arm/Group Description	All volunteer patients
Period Title: Overall Study
STARTED	36
COMPLETED	27
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All enrolled subjects
Overall Participants	27
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	18 66.7%
Male	9 33.3%
Race and Ethnicity Not Collected (Count of Participants)
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	89

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Edema
Description	Regions of the ipsilateral thigh were defined by muscle group, neuromuscular bundle, subcutaneous tissue, or inter-muscular fascial layers. Five board-certified musculoskeletal radiologists analyzed the scans for presence of edema. Edema was considered present if judged to be so by at least 3 of the 5 radiologists.
Time Frame	1-2 days postoperative

Outcome Measure Data

Analysis Population Description

Participants that underwent postoperative MRI scan of operated leg

Arm/Group Title	Participants Undergoing MRI
Arm/Group Description	Number of Participants with Edema
Measure Participants	12
Number [participants]	12 44.4%

2. Secondary Outcome

Title	Postoperative Muscle Enzyme Levels
Description	Participants with Postoperative Creatine Phosphokinase (CPK) or Aldolase levels above the upper limit of normal
Time Frame	Sample was drawn the morning after surgery

Outcome Measure Data

Analysis Population Description

Participants with CPK levels 12% to 111%, and aldolase levels, in excess of high normal values

Arm/Group Title	CPK Analysis	Aldolase Analysis
Arm/Group Description	CPK Levels Above High Normal	Aldolase Levels Above High Normal
Measure Participants	19	19
Count of Participants [Participants]	5 18.5%	0 NaN

Adverse Events

Time Frame	10 days. Participant was evaluated at the time of the incident and twice during the 10 days thereafter.
Arm/Group Title	MRI Appearance
Arm/Group Description	Volunteers undergoing MRI examination
All Cause Mortality
	MRI Appearance
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	MRI Appearance
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	MRI Appearance
	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Warmth around adductor canal catheter during MRI	1/13 (7.7%)	1

Limitations/Caveats

This case series aimed to describe MRI appearance and muscle enzyme levels presented under the same clinical conditions as the 3 sentinel cases of presumed local anesthetic myotoxicity after TKA/CACB. This descriptive design was not intended to sort cause-and-effect (that is, the relative role of surgery, pneumatic tourniquet, local anesthetic, etc.) in causing muscular edema or raising enzyme levels.

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.