Local Anesthetic ComplicationNCT04821245

Defining Normal Postoperative Magnetic Resonance Imaging After Total Knee Arthroplasty

An observational study of Local Anesthetic Complication and Local Anesthetic Drug Adverse Reaction, run by Benaroya Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Local Anesthetic Complication, Local Anesthetic Drug Adverse Reaction
How many people: 36 participants
Where: 1 siteUnited States
Study dates: 4 Dec 2018to 2 Aug 2019
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Study population: * Volunteer patients of various age and sex * Number of volunteers and diagnostic studies determined by available grant monies * Volunteers were drawn from a population presenting for unilateral primary TKA performed by 1 of 2 orthopedic surgeons in a single institution

Who may be able to join

Scheduled for unilateral primary TKA with CACB
TKA and early recovery was uncomplicated (no evidence of unexpected leg weakness)

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Benaroya Research Institute
Seattle, Washington, 98101

Other trials in United States

About this study

Official title: Defining Normal Postoperative Magnetic Resonance Imaging and Muscle Enzyme Levels After Total Knee Arthroplasty Associated With Continuous Adductor Canal Block

Read the 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.

Conditions: Local Anesthetic Complication, Local Anesthetic Drug Adverse Reaction
Keywords: Myotoxicity, Myositis, Magnetic resonance imaging, Creatine phosphokinase, Aldolase
Medical subject headings: Myotoxicity, Myositis

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Edema
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.
Measured: 1-2 days postoperative

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Dec 20182 Aug 2019

First posted29 Mar 2021
Study start4 Dec 2018
Primary completion2 Aug 2019
Study completion2 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Local Anesthetic ComplicationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04821245
Sponsor's protocol ID: BRI IRB18-008
Status last verified: May 2021
First submitted: 25 Mar 2021
Last updated: 25 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: De-identified raw data in Excel format may be obtained from Joseph M. Neal, MD upon request.

Publications

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. doi: 10.1097/AAP.0000000000000466.
PubMed 27662067
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. No abstract available.
PubMed 28419048
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.
PubMed 30236244
Mahyar L, Neal JM, Blackmore CC, Jackson DW, Hanson NA, MacDonald KM, Warren D, Verdin PJ. MRI and muscle enzymes do not support the diagnosis of local anesthetic myotoxicity: a descriptive case series. Reg Anesth Pain Med. 2021 Aug;46(8):679-682. doi: 10.1136/rapm-2021-102772. Epub 2021 May 31.
PubMed 34059556

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Local Anesthetic Complication trials

Study at a glance

From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Defining Normal Postoperative Magnetic Resonance Imaging and Muscle Enzyme Levels After Total Knee Arthroplasty Associated With Continuous Adductor Canal Block
ClinicalTrials.gov ID: NCT04821245
Acronym / sponsor ID: BRI IRB18-008
Conditions: Local Anesthetic Complication, Local Anesthetic Drug Adverse Reaction
Keywords: Myotoxicity, Myositis, Magnetic resonance imaging, Creatine phosphokinase, Aldolase
Study type: Observational
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Benaroya Research InstituteUniversity, hospital or other
Collaborators: Washington State Society of Anesthesiologists
Study start: 4 Dec 2018 (actual)
Primary completion: 2 Aug 2019 (actual)
Study completion: 2 Aug 2019 (actual)
First posted: 29 Mar 2021 (actual)
Results: Posted 25 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Observational model: Cohort
Time perspective: Prospective

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: * Volunteer patients of various age and sex * Number of volunteers and diagnostic studies determined by available grant monies * Volunteers were drawn from a population presenting for unilateral primary TKA performed by 1 of 2 orthopedic surgeons in a single institution

Key inclusion criteria (2 listed)

Scheduled for unilateral primary TKA with CACB
TKA and early recovery was uncomplicated (no evidence of unexpected leg weakness)

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Number of Participants With Edema
Time frame: 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.

1 secondary outcome

Postoperative Muscle Enzyme Levels
Time frame: Sample was drawn the morning after surgery

Results and safety

Results posted to the registry on 25 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single Cohort	36	27

Primary outcome: Number of Participants With Edema

Time frame: 1-2 days postoperative. Number. Unit: participants

Measure	Participants Undergoing MRI n = 12
Value	12

Population analysed: Participants that underwent postoperative MRI scan of operated leg

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 10 days. Participant was evaluated at the time of the incident and twice during the 10 days thereafter.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MRI Appearance	0 of 13 (0%)	1 of 13 (7.7%)	0 of 13

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27662067Neal 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. doi: 10.1097/AAP.0000000000000466.
Background: PubMed 28419048Neal 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. No abstract available.
Background: PubMed 30236244Hussain 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.
Derived from this study: PubMed 34059556Mahyar L, Neal JM, Blackmore CC, Jackson DW, Hanson NA, MacDonald KM, Warren D, Verdin PJ. MRI and muscle enzymes do not support the diagnosis of local anesthetic myotoxicity: a descriptive case series. Reg Anesth Pain Med. 2021 Aug;46(8):679-682. doi: 10.1136/rapm-2021-102772. Epub 2021 May 31.
Individual participant dataSharing planned: Yes. De-identified raw data in Excel format may be obtained from Joseph M. Neal, MD upon request.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joseph M Neal, MD principal investigator

Benaroya Research Center at Virginia Mason Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Local Anesthetic Complication and Local Anesthetic Drug Adverse Reaction, run by Benaroya Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Edema (time frame: 1-2 days postoperative). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04821245, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.