Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: Systematic review protocol.

The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future systematic reviews evaluating adverse events in Emergency Medicine.

Introduction

Rationale and objectives

The use of ultrasound-guided regional anesthesia (USGRA), or ultrasound-guided peripheral nerve blocks, for pain control and painful procedures, has become increasingly prevalent in Emergency Medicine (EM), with a recent survey noting 84% of respondents employing USGRA in their EM training programs 1]. The variety of nerve targets successfully performed by Emergency Physicians (EPs) has expanded over time, and includes both single nerves (e.g. femoral nerve) and fascial planes (e.g. fascia iliaca, serratus anterior plane) [1]. Nearly universally, USGRA has been noted to provide effective pain control and reduce opioid-equivalents administered [2-4]. However, in a 2016 survey, no EM training program employing USGRA reported having a quality assessment program in place [1]. USGRA is not without complications, which can include procedural pain, infection, nerve injury, blood vessel injury, compartment syndrome, allergic reactions, and the potentially fatal local anesthetic systemic toxicity, among other adverse events. The primary objective of this study is to systematically review the reported incidence of adverse events related to USGRA performed by EPs.

Protocol design

This study is a systematic review to summarize randomized controlled trials and observational studies evaluating USGRA performed by EPs and related adverse events. The study protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and recommendations for conducting systematic reviews of adverse events as per Loke, et al. [5, 6]. This review has been registered with PROSPERO (CRD42021241168).

Study characteristics

This review will include randomized controlled trials and case-control studies investigating USGRA as performed by EPs, evaluating incidence of adverse events related to USGRA as our primary outcome. This review will also consider case series and case studies for inclusion with the purpose of highlighting additional adverse events not reported in more robust trials and describing the scope of USGRA as performed by EPs in the literature. Review articles will be excluded from inclusion. Published studies, studies pending publication, abstracts, conference presentations, and unpublished studies will be considered for inclusion [7, 8].

Methods

Eligibility criteria

This review will include studies evaluating participants of all age groups, with subgroup analysis of children (age < 18) and adults (age > 18).

Interventions

All ultrasound-guided peripheral nerve and fascial plane blocks by EPs the ED will be considered for inclusion. A secondary aim of this study will be to document the wide variety of USGRA applications performed by EPs published in the literature thus far.

Outcome measures

The primary outcome will be adverse events resulting directly from USGRA procedures performed by EPs. Consideration for adverse events will include descriptions of “adverse event,” “adverse effect,” “adverse drug reaction,” “side effect,” “toxic effect,” and “complication”, as recommended by Loke, et al. [6]. Specific expectant adverse events may include, but will not be limited to, nerve injury, blood vessel injury, local infection, sepsis, allergic reactions, and local anesthetic systemic toxicity (e.g. perioral paresthesias, tachycardia, dizziness, arrhythmia, seizures, hypotension) and/or use of intralipid emulsion infusion. Information provided regarding adverse events in control/comparator groups will also be assessed.

Types of studies

Randomized controlled trials, observational studies, and case series and reports will be included in analysis of the primary outcome of adverse events related to USGRA performed by EPs (attending physicians, fellows, and residents). For the secondary aim of documenting the variety of ultrasound-guided nerve and plane blocks performed by EPs, randomized controlled trials, cohort studies, case reports, case series, and case-control studies will be considered.

Information sources

Our search strategy will be performed with the aid of a trained medical librarian (MD) with experience in conducting searches for systematic reviews [9]. Relevant search concepts will include regional anesthesia, nerve block, ultrasound, ultrasound-guided, Emergency Medicine, and Emergency Department. Databases utilized will include Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and clinicaltrials.gov. Search will not be limited by language, but non-English manuscripts will be translated into English using Google Translate, which has been demonstrated to be a valid translation program for manuscript review [10]. Each database will be searched from inception to March 2022, and updated as appropriate when preparing submission for publication.

Study records

Data management

Database search results will be exported to and stored in EndNote (Philadelphia, PA) with duplicate entries removed.

Selection process

After the initial search result list is compiled, each title and abstract will be reviewed by two reviewers (SPS, DSK) for relevance. Entries potentially meeting inclusion criteria will be reviewed in full-text for final determination of appropriateness for inclusion. Disagreements between the two reviewers regarding inclusion of a study will be settled by a third team member reviewer (EAA). A flowchart will be published to highlight the step-wise results of the selection process.

Data collection process

Reviewers will independently extract study characteristics and data using a standardized data collection form. Reviewers will also reach out to study authors as necessary for clarification and to obtain further data when appropriate [11].

Data items

Extracted data will include lead author, year of publication, study population, number of participants, nerve block performed, control or comparator intervention, anesthetic used, training of person performing the procedure (i.e. attending, fellow, or resident), study primary outcome and result, number (raw and percentage of study group) of adverse events in nerve block group, and types of adverse events in nerve block group, number of adverse events in control group, types of adverse events in control group, how adverse events were captured and managed (if described), and funding source of the study (if described). All collected data will be included in the final manuscript.

Risk of bias assessment

Risk of bias will be assessed using the Cochrane Risk of Bias version 2 tool for randomized clinical trials, the Newcastle-Ottawa Scale for non-randomized trials, and the Joanna Briggs Institute critical appraisal checklists for case series and case studies [12-15]. Two independent reviewers (CKK, RJS) will apply the Risk of Bias tool to included studies, with discrepancies handled by discussion or a third independent reviewer (DT) if consensus cannot be reached.

Data synthesis

Due to the expected heterogeneity of results inherent in including all USGRA applications documented in the literature, a meta-analysis is not planned. Instead, data for similar procedures will be compiled and reported together in whole. Strength of available evidence will be evaluated using the Evidence-based Practice Center guidelines [16].

Subgroup analysis

Subgroup data by procedure type (e.g. femoral nerve block, ulnar nerve block, serratus plane block, etc.) age group (i.e. adults [over 18 years of age], elderly [over 65 years of age] and pediatrics [under 18 years of age]), analgesic used, and experience levels of sonographers will be reported, although no meta-analysis for these groups is planned.

Discussion

Providing adequate analgesia for painful procedures is a core skill in EM [17]. While USGRA was initially described in anesthesia literature, the last 15 years has seen a shift in the approach to analgesia in the ED with USGRA becoming more commonplace, particularly amongst academic centers [1, 18]. However, there remain numerous barriers to further implementation of USGRA into the practice of EPs in academic centers as well as community EDs, paramount to them being procedural knowledge, and by extension, safety [1, 19, 20].

This systematic review will quantify the safety of USGRA performed in EDs as evidenced by available published literature. A previous systematic review evaluating regional anesthesia for hip and femur fractures only included one study utilizing ultrasound [2]. To our knowledge, no systematic review exists that has aimed to detail the safety of USGRA by EPs across all target nerves and tissue planes. The value in this is to determine if certain applications may require more training and expertise than others to optimize patient safety and comfort, as well as provider time and liability. It has been suggested that USGRA may become an integral part of EM resident and fellow training, but determining whether all USGRA applications are “created equal” in terms of safety will be necessary to improve clinician knowledge and advance the practice further [21, 22]. This process of considering applicability and safety prior to widespread utilization has been previously experienced with point-of-care ultrasound as a whole, and serves as an ideal example of a medical advancement adopted from another specialty and applied to EM to patient benefit [23].

USGRA presents a means of optimizing care for numerous patient populations in the ED, particularly those with allergies or intolerances to opioid and sedative medications, and elderly patients who may be more prone to adverse reactions to said medications. However, although there are benefits to USGRA, evaluation of its safety profile when performed by EP is pivotal to patient safety and quality. Our systematic review will serve as a valuable asset to inform clinical decision-making, enhance trainee education, and advance clinical research surrounding USGRA by EPs.

PRISMA checklist.

(DOC)

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Sample search strategy.

(DOCX)

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Extracted data collection form.

(XLSX)

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11 Mar 2022

30 Mar 2022

Dear Dr. Bahl and PLoS One Reviewers,

Thank you for your insightful comments on our submission and for your recommendations on improving our work. Overall, we felt your suggestions were helpful and improve the quality of our work. We also appreciate you highlighting some of the formatting particulars that were initially overlooked.

Below, have included our responses in brackets beside the original comments, indicating how we have addressed the concerns in our revised manuscript.

Additionally, we noticed that one of the authors names (Dr. Lee) had a misspelling in his name on the title page. This has been corrected.

Sean Stickles, MD (corresponding author)

----

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https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf -- [This has been corrected.]

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--[Thank you for pointing this out, this has been added to the manuscript file itself.]

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--[As a protocol paper, we do not have any current data sets to present. However, we have provided clarification that our intent is to publish all available collected data extracted from our review.]

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--[All references listed are correct at this time to the best of our knowledge.]

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

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(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present a protocol for a systematic review of existing literatures published on the safety and variety of ultrasound guided nerve blocks performed by emergency physicians. While there are several systematic reviews looking at regional nerve blocks as well as ultrasound guided regional nerve blocks, I would agree with the authors that none have been published looking at the specific topic which they propose here. Their protocol is precise, well written, and feasible. I commend the authors for their efforts and am excited to see this systematic review published.

There are several items that should be addressed prior to publication of this protocol:

1. In the methods section clarity is needed regarding if studies performed outside of the ED will be considered. The interventions section currently states that all ultrasound guided studies will be considered. However, the remainder of your protocol seems to suggest that only ED based studies will be included. – [This was clarified.]

2. According to PRISMA guidelines for systematic review protocol, your section discussing search strategy should include a complete draft search strategy for at least one database including planned limits such that it could be repeated. – This is now included.

3. Should consider adding funding source as a collected data item from the studies. –[This is now included.]

4. If intended by the authors to allow for open access to their data, there is currently no description of how data will be made available after publication. –[We anticipate all data collected will be included in a table or tables in the final manuscript. We have added a sentence to the manuscript indicating such.]

5. Consider including your standardized data collection form as a supplementary figure.—[This is now included.]

Reviewer #2: I believe that this systematic review will provide useful information at a time when emergency provider performed USGRA is rapidly increasing. There is a lot of information regarding safety and efficacy of these procedures in orthopedic and anesthesiology literature, but this same body of research does not exist in emergency medicine.

Eligibility criteria - it may be relevant to include a subgroup analysis of geriatric patients (>65yo), as this is a patient population that oftentimes benefits greatly from USGRA. There is an especially large body of orthopedic literature stating that fascia iliaca compartment blocks/PENG blocks, femoral nerve blocks, etc.) decrease need for breakthrough pain/opioid medications, decrease hospital length of stay and morbidity/mortality, decrease time to post-surgical ambulation, decreased PNA/UTIs/nosocomial infections after surgery. The population that sustains these hip fractures are often >65yo, which may warrant further analysis.—[This is now included.]

Lines 29-32 state that "USGRA is not without complications, which can include procedural pain, infection, nerve injury, blood vessel injury, allergic reactions, and the potentially fatal local anesthetic systemic toxicity, among other adverse events." There is a lack of substantial evidence regarding USGRA effects on detecting compartment syndrome. This may specifically be an adverse event/sequelae of extremity injuries that is worth investigating as this is oftentimes a concern that orthopedics has regarding administration of these nerve blocks.—[This is now included.]

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Reviewer #1: No

Reviewer #2: No

Submitted filename: Response to reviewers - 3.30.22.docx

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9 May 2022

16 May 2022

Data extraction form uploaded and labeled. Sorry for the confusion.

Submitted filename: Response to reviewers - 3.30.22.docx

Click here for additional data file.

26 May 2022

Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: systematic review protocol

PONE-D-21-35950R2

Dear Dr. Stickles,

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Reviewers' comments:

14 Jun 2022

PONE-D-21-35950R2

Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: systematic review protocol

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