Hydrodissection is a minimally-invasive procedure that involves injecting fluid into anatomic spaces to
facilitate dissection and adhesiolysis during surgery as proposed by Graesser et al. in 2022. In the past decade,
it has been applied to the management of nerve entrapments by injecting fluid around the nerve to create space
and separate them from surrounding structures. Injectates used are either saline, corticosteroids, anesthetic,
dextrose water, platelet-rich plasma, or combinations of these injectates. This study undertakes a scoping
review of the available evidence on nerve hydrodissection to determine the extent of research done and report
on information particular to this procedure. PubMed, EBSCOhost, Google Scholar, and ScienceDirect were
searched, and a total of 70 articles were included in this study. Due to the lack of standardization of the factors
such as injectate choice and volume, firm recommendations for the effectiveness of nerve hydrodissection are
difficult to develop. Further research, especially those that aim to standardize aspects of nerve hydrodissection,
is needed.

hydrodissection, nerve hydrodissection, pain, scoping review

Hydrodissection is a minimally invasive procedure that involves injecting fluid into anatomic spaces to facilitate dissection and adhesiolysis during surgery [1]. In the past decade, it has been applied to the management of nerve entrapments by injecting fluid around the nerve to create space and separate them from surrounding structures. Injectates used are either saline, corticosteroids, anesthetic, dextrose water, platelet-rich plasma (PRP), or combinations of these injectates [2,3]. The most studied indication for nerve hydrodissection is median nerve entrapment at the wrist and it has, in fact, been included as one of the management options for carpal tunnel syndrome in Harrison’s Principles of Internal Medicine [2]. Nerve hydrodissection has also been applied to other neuropathies; however, most are case reports and narrative reviews.

The present study undertakes a scoping review with the following objectives: (1) identify the available evidence on nerve hydrodissection, (2) clarify key concepts such as definition and mechanism of action, (3) report on available information on the injection techniques, injectate choices, outcomes and outcome measures used, possible adverse effects and potential application of the procedure to knee osteoarthritis pain management, and (4) identify the gap in the literature.

The protocol for this review was registered in the Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/RQS42). The Joanna Briggs Institute (JBI) framework for the conduction and preparation of scoping reviews [4] was used as a guide in the conduct of this review, and reporting is in accordance with the PRISMA extension for scoping reviews [5].

Following the JBI recommended “PCC” pneumonic which corresponds to Population, Concept, and Context [4], inclusion in the review was guided by the following criteria: Population—studies that included patients with pain secondary to nerve entrapment or neuropathic pain; Concept—studies that evaluated the effect of nerve hydrodissection; Context—observational studies, randomized and nonrandomized clinical trials, reviews, qualitative studies, and case reports in English or with available English translations, published in the last 10 years (2011–2022). Unpublished work limited to conference proceedings and preprints were also considered. Encyclopedia entries and book chapters were excluded. The year 2011 was chosen because although hydrodissection has been around since the 1990s, the surge of studies on ultrasound-guided hydrodissection specifically applied to nerve entrapment occurred in the past decade [1,6].

Medline/PubMed and EBSCOHost were initially searched for available articles within the field of study. Terms and words found in the abstracts and titles of articles were used for a more refined search strategy for MEDLINE, EBSCOhost, Google Scholar, and ScienceDirect. The search terms used are summarized in Table 1.

Table 1. Search Terms and Parameters Used for the Search Strategy

All identified potential citations were collated and uploaded into the data management software Covidence©. Two reviewers independently assessed titles and abstracts based on the inclusion criteria set. Full-text articles were retrieved and re-tested against the parameters for inclusion. Reference lists were examined for additional studies that were also reviewed for inclusion.

The method of data charting was guided by JBI recommendations [7] and adapted from the study of Rüeger et al. [8]. A data charting form was developed using Microsoft Excel and underwent pilot testing. A reviewer (MB) charted the data as follows: title, first author, year of publication, country of the first author or where the study was conducted (whichever is available), type of study, objective, intervention/term used, definition of intervention/hydrodissection, proposed mechanism of action, nerve hydrodissected/location of hydrodissection, indication, study population and sample size, comparator, injectate and frequency of injection, injection technique, outcome and outcome measure/s, follow-up, side-effects, or other key information. The completed charting form was reexamined by a second author (EG) to ensure the correctness of the extracted data. Disagreements were resolved through discussion.

Descriptive statistics were calculated to summarize the data. Frequencies and percentages were utilized to describe nominal data.

A total of 1,787 potentially relevant articles were obtained from databases and registries, and an additional 5 studies were discovered from searching the reference lists. After duplicates were removed, the titles and abstracts of 1,488 studies were screened against the inclusion criteria. Among the 1,347 articles that were excluded, 1,242 were not within the concept of the study and discussed topics beyond the scope of nerve hydrodissection. Eighty-three articles were not within the context and were a combination of table of contents, indexes, and book chapters. Nine articles were about hydrodissection but investigated surgical patients which are beyond the intended population of the study. Thirteen articles had erroneous links and were not retrievable.

A total of 121 articles were assessed for eligibility, and a final count of 70 studies were included in the scoping review. A summary of the article selection process is depicted in Figure 1.

The descriptive-analytical method [9] was used in analyzing the data gathered from the included studies. To fulfill the objectives of the study, the data gathered were categorized into the following themes: (1) general characteristics of the studies—which will include the year of publication, country of origin, types of studies/methodology, (2) nerve targets and indications, (3) terminology used, definition and mechanism of action, (4) injection technique, (5) injectate and needles used, (6) outcome and outcome measures, and (7) adverse effects.

Figure 1. PRISMA Flow Diagram—Study Selection Process

Figure 2. General Characteristics of Included Studies
This figure presents the general characteristics of the included studies. (A) Distribution of studies by year of publication, (B) distribution of stud-
ies based on country of origin, (C) distribution of studies based on types of study or methodology.

Figure 3. Nerve Targets and Indications
This figure presents the distribution of included studies based on (A) nerve targets cited, and (B) indications mentioned.

In this study, 51% (36/70) of the included articles were published from 2011–2020 while 49% (34/70) were published in the last three years (Figure 2A).

The country with the highest number of included studies was Taiwan at 25/70 (36%), followed by the USA (27%), India (9%), HK China (4%), Indonesia (4%), and Turkey (3%). The remaining countries, namely, Australia, Belgium, China, Egypt, Ireland, Japan, Malaysia, Philippines, Poland, Slovenia, and Thailand, contributed one study each to the pool. However, one article, a poster presentation, did not provide information on its country or origin (Figure 2B).

The types of studies included were: 20 case reports (29%), 12 literature reviews (17%), 9 randomized controlled trials (13%), 9 retrospective studies (13%), 5 letters to the editor (7%), 4 posters (6%), 2 case series (3%), 2 technical image studies (3%), 2 video gallery papers (3%), 1 abstract (1%), 1 commentary (1%), 1 pilot study (1%), 1 prospective cohort (1%), and 1 systematic review (1%) (Figure 2C).

The most common nerve that underwent hydrodissection cited by the included studies was the median nerve at the wrist at 30%, followed by the peroneal nerve (10%), ulnar nerve (9%), radial nerve (9%), lateral femoral cutaneous nerve (7%), saphenous nerve (7%), sciatic nerve (4%), dorsal scapular nerve (3%), superior cluneal nerve (2%), and sural nerve (2%). The rest of the nerve targets were each cited once: anterior interosseous nerve, Baxter’s nerve, cervical plexus, femoral nerve, greater occipital nerve, ilioinguinal nerve, iliohypogastric nerve, lateral antebrachial cutaneous nerve, posterior tibial nerve, posterior interosseous nerve, pudendal nerve, spinal accessory nerve, and suprascapular nerve (Figure 3A).

The most frequently cited indication was carpal tunnel syndrome (28%) followed by cubital tunnel syndrome (8%), peroneal nerve entrapment (7%), saphenous nerve entrapment (7%), meralgia paresthetica (7%), superficial radial nerve entrapment (4%), radial nerve palsy (4%), dorsal scapular nerve entrapment (3%), sciatica (2%), sural nerve entrapment (2%), and superior cluneal nerve entrapment (2%). Other indications mentioned were: median nerve entrapment at the pronator tunnel, Baxter’s neuropathy secondary to plantar fasciitis, thoracic outlet syndrome, superficial cervical plexus entrapment after neck lymphoma, femoral nerve entrapment, cervicogenic headache, ilioinguinal nerve entrapment, iliohypogastric nerve entrapment, lateral antebrachial cutaneous nerve entrapment, posterior interosseous nerve entrapment, urologic chronic pelvic pain syndrome (UCPPS), spinal accessory nerve entrapment, suprascapular nerve impingement, symptomatic sural nerve neuroma, piriformis syndrome, sciatic nerve tethering s/p mid-hamstring tendon repair, ulnar nerve entrapment at Arcade of Struthers, complex regional pain syndrome, peroneal nerve entrapment in knee osteoarthritis, deep peroneal neuroma, median nerve entrapment secondary to electric shock and pronator teres syndrome (Figure 3B).

The intervention under study was most commonly termed as “hydrodissection” (46%). Other terms used to pertain to the intervention were “nerve hydrodissection” (19%), “perineural hydrodissection” or “perineural neurolysis” (10%), “perineural injection therapy” (3%), “percutaneous hydrodissection” or “percutaneous neurolysis” (2%), “perineural dextrose injection” (2%). Other terms encountered were: “perineural deep injection”, “neural prolotherapy”, and “percutaneous hydrotherapy”.

Among the studies that included a definition of hydrodissection, the common theme is that it is an ultrasound-guided technique that involves high-pressure injection of fluid, either an anesthetic, saline, dextrose water, PRP, or combinations of these fluids, to dissect anatomic planes and tissue spaces. This technique is used to manage nerve entrapments as it separates nerves from the surrounding tissue, fascia, or adjacent structures.

Two common mechanisms of action emerged from the studies reviewed: the mechanical release and decompression of the entrapped nerve, and the pharmacologic effect or the effect of the injectate used. Relief of pressure on the neurovascular structures decreases nerve hypersensitivity and creates space to limit adhesions, increase blood flow, and remobilize the nerve which secondarily decreases the neurogenic inflammation, improves nerve conduction, and prevents the onset and/or progression of ischemic damage to the nerve. The pharmacologic effect, on the other hand, depends on the injectate used. Anesthetics work to decrease pain and steroids are used to decrease inflammation but the effect of 5% dextrose water (D5W) is less understood. Studies that did discuss the proposed effect of D5W presented that chronic neuropathic pain may signify glycopenia around the nerve and injecting D5W may correct this and consequently reduce neuropathic pain. Another proposed mechanism of D5W is the decrease of neurogenic inflammation by inhibiting transient receptor potential vanilloid receptor-1 (TRPV-1) that can be found on peripheral nerves.

There was great variation with regard to the injection technique utilized by the studies included due to the different areas and nerve targets presented; however, the following techniques were common to them:

．The choice of ultrasound machine and probe was based on the type most appropriate for the structure and depth of the nerve to be injected and the availability of the probe.

．The procedure starts with basic scanning of the involved structures to identify the site of entrapment, plan the injection course and visualize structural abnormalities and anatomical variations that may affect the procedure.

．Aseptic preparation is done prior to injection.

．The total injectate is divided into different locations around the area of entrapment (e.g., upper part of the nerve, then the lower part of the nerve) to ensure complete hydrodissection and release of the entrapment.

．Hydrodissection is done in the short- and long-axis views.

．The injection is done gradually and the operator maintains continuous visualization of the needle or the needle tip as it dissects the structure/s to be separated.

．Participants were monitored for 30 minutes after injection for possible side effects.

．After injection, the operator scans the injected areas to confirm delivery of injectate throughout the entrapment site.

There was not a common practice on the use of local anesthetic prior to hydrodissection. Of the 9 studies that mentioned local anesthetic, 7 [10-16] mentioned injecting 1%–2% lidocaine 1% lidocaine to the area, while two [17,18] did not use local anesthesia.

The commonly used injectates were D5W, saline, anesthetic, steroid, and combinations of these fluids. Although PRP was mentioned in 4 studies [15,19- 21], only two investigated its effectiveness [15,19]. Hyaluronidase (Hyalase) was mentioned twice but was only investigated by one study [22] and progesterone was only mentioned once [21]. The summary of the combinations of injectates used is presented in Appendix 1. There was great variation seen with regard to the injectate volumes and the needles used. A summary of the injectate volumes is presented in Table 2.

Table 2. Summary of Injectate Volumes Used by the Included Studies

There were 55 studies that reported on outcome and outcome measures, 17 (44%) of those reported on carpal tunnel syndrome, and 38 (69%) reported on other indications. Of the studies that investigated nerves other than the median nerve at the wrist, pain was the most common outcome (87%), with 36% using the Visual Analog Scale and 33% using Numerical Rating Scale, followed by subjective reports of “paresthesia”, “numbness” or “tingling” (29%), reports on “resolution of symptoms” (11%), strength or manual muscle test (11%), electrodiagnostic findings or nerve conduction velocity studies (11%), and range of motion (ROM) (8%) and ultrasonographic findings (2%). Additional outcome measures were the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, which was used by studies that investigated the proximal median nerve and median nerve, shear wave elastography (shear wave velocity) was used for radial nerve palsy, and the Functional Pelvic Pain Score was for the study on UCPPS.

Of the 17 studies that had information on outcome and outcome measures, the most common outcome measure reported was the Boston Carpal Tunnel Questionnaire (76%), next was pain (53%) and cross-sectional area of the median nerve (53%), electrodiagnostic findings/nerve conduction studies (47%), ultrasonographic findings (12%), “resolution of symptoms” (12%), subjective findings of “paresthesia”, “numbness” or “tingling” (6%), hand grip strength (6%), shear wave elastography (6%), DASH questionnaire (6%), Short-Form 12 (6%), patient satisfaction (6%), and a survey on injection experience (6%). A summary of the outcomes and outcome measures is presented in Table 3.

Table 3. Outcome Measures Used

Out of the 70 included studies, only 15 articles reported on the presence or absence of side effects.Twelve studies reported that there were no side effects observed. One study cautioned on the risk of intraneural injection, and another study mentioned the risk of increased numbness and tightness felt during the injection caused by the volume effect of hydrodissection-related dragging effect on the nerve. Though one study reported that no serious adverse events were noted, two patients in the intervention group were noted to have minor post-injection pain on the first day after the intervention, which resolved spontaneously, without the need for additional treatments.

The first aim of this scoping review is to identify the available evidence on nerve hydrodissection. Interestingly, almost half of the 70 studies included were written in the last three years. Aside from this, there are 17 countries that have produced some form of study in the field. An expansion of the application of nerve hydrodissection can also be seen in the number of indications (34) and different nerve targets (25) presented by the included studies. This highlights the growing interest in hydrodissection as an emerging management option for nerve entrapment. It is also noteworthy that Taiwan emerged as the country leading the production of papers on nerve hydrodissection, followed by the USA.

Most of the studies available are case reports and literature reviews, with randomized controlled trials comprising only 13% of the included studies. This underscores the need for more studies with higher-level methodologies to truly examine the effectiveness of nerve hydrodissection on different neuropathies.

The second objective of this review is to clarify the key concepts such as the definition and mechanism of action of hydrodissection. Although there were eight other variations to the terminology “hydrodissection” and “nerve hydrodissection”, the included studies have shown a general uniformity in the definition and mechanism of action of hydrodissection. The pharmacologic effect, specifically the effect of D5W on neuropathic pain is a less well-understood mechanism of benefit of hydrodissection and is a topic worthy of further examination.

The third objective of the study is to report on the available information on the injection techniques, injectate choices, outcomes and outcome measures used, possible adverse effects, and potential application of the procedure to knee osteoarthritis pain management. The included articles varied widely in terms of injection techniques, but this study was able to summarize the techniques and steps common to these studies. This may be helpful in the conduct of future research especially those that aim to develop standardized protocols for ultrasound-guided procedures.

There was also great variation in terms of the injectate, volume, and types of needles used. The general trend seen was the use of D5W or different combinations of D5W, steroid, anesthetic, and saline. However, this trend is too broad to facilitate the development of recommendations for clinical practice. To promote generalizability, more studies are needed to investigate the effectiveness of different injectates and injectate combinations as well as comparisons of different injectate volumes.

This study presented the different outcomes and outcome measures used by the included studies. It is interesting to note that apart from the usual outcomes of pain, strength, ROM, and questionnaires specific to certain indications, newer outcome measures, like shear wave elastography, are being mentioned.

Based on the results of this review, hydrodissection can be considered a relatively safe procedure with only one study mentioning the occurrence of mild post-procedural pain that was spontaneously relieved without additional management. Among the studies included, there was one case report on the possible application of hydrodissection for knee osteoarthritis targeting the peroneal nerve.

The final objective of this study is to identify the gap in the literature. The lack of standardization in the different aspects of hydrodissection presented in this study underscores the need for further research. More studies are needed on nerves that were mentioned in this scoping review as well as other nerves that are potential targets for the relief of nerve entrapment and neuropathic pain. As mentioned, studies on injection technique and choice of injectate are needed to establish the effectiveness of nerve hydrodissection.

Despite attempts to be as comprehensive as possible, this review may not have identified all scoping reviews in the published literature. Authors of the papers that were excluded due to the unavailability of full texts and those without available English translations were not contacted. Furthermore, the authors did not contact any researchers or experts for additional scoping reviews we may have missed.