Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity (1). It is caused by compression of the median nerve at the wrist, where it passes beneath the transverse carpal ligament. The most commonly used non-surgical treatments include activity modification, oral medication, wrist splinting, and local corticosteroid injection(s) (2).

The exact pathophysiology of CTS remains elusive (3). Previous studies (4–7) have reported that thickening and fibrosis of the subsynovial connective tissue plays an essential role in the development of CTS and restricts median nerve mobility within the carpal tunnel. A previous systematic review included 10 case-control studies and demonstrated reduced excursion of the median nerve at the proximal wrist among the CTS population compared with normal subjects (8).

Ultrasound-guided hydrodissection is an emerging therapy for entrapment neuropathy described by Malone et al. in 2010 (9). The procedure creates a perineural fluid plane and releases perineural adhesion(s) mechanically. Normal saline, 5% dextrose, and platelet-rich plasma can be used as injectates for hydrodissection (10, 11). By dissecting the subsynovial connective tissue, hydrodissection releases perineural adhesions, which may improve the symptoms of CTS. A cadaver study demonstrated a decrease in gliding resistance of the median nerve in the carpal tunnel after hydrodissection (12).

Local corticosteroid injection has been widely used for the treatment of CTS, with well-established short-term efficacy (13, 14). However, the optimal volume in corticosteroid-containing regimens remain unclear, although it ranges from 1 to 3 mL in most literature reports (14–17). To date, there is no strong evidence supporting whether corticosteroid hydrodissection using a larger volume of injectate(s) provides additional clinical improvement. The purpose of this study, therefore, was to examine whether hydrodissection using corticosteroids could improve pain and function in patients with CTS better than corticosteroid perineural injection alone.

The present clinical trial yielded several important observations. First, corticosteroid injection with or without additional hydrodissection led to a significant decrease in pain, symptoms, functional impairment, and electrophysiological abnormalities in patients with CTS. Second, there was no difference in clinical effectiveness between corticosteroid injection with and without hydrodissection, based on evidence from our RCT.

Various injectates have been used for nerve hydrodissection, including normal saline, corticosteroid, 5% dextrose in water (D5W), and platelet-rich plasma (10). One published RCT assessed the effect of different volumes of D5W on the treatment of CTS (28). Lin et al. compared 1, 2, and 4 mL of D5W injection in patients with CTS and found that 4 mL of D5W was more effective than 1 and 2 mL in symptom and functional improvement at 1, 4, and 12 weeks' post-injection (28). However, the superiority of the clinical effectiveness of 4 mL of injectate declined at 24 weeks post-injection.

Corticosteroids are the most commonly used injectates for CTS. Its mechanism of action is mainly through anti-inflammatory reactions, with a decrease in the number of lymphocytes, as well as inhibition of cytokine expression and phospholipase activation (29). Furthermore, corticosteroids also reduce vasogenic edema by affecting the permeability of the vascular wall (30). Previous studies evaluating the efficacy of corticosteroid hydrodissection have been limited to case series without a control group or a comparative therapeutic arm (9, 31). Malone et al. treated 44 wrists in 34 patients with CTS using ultrasound-guided hydrodissection of the median nerve [9 mL normal saline, 1 mL 1% lidocaine, and 1 mL triamcinolone acetonide (40 mg/mL)] and fenestration of the flexor retinaculum, yielding complete symptom resolution in 30 wrists at an average of 8 months post-intervention (9). DeLea et al. managed 14 patients with CTS related to rheumatoid arthritis and 12 with painful scleroderma of the hand using ultrasound-guided hydrodissection (3 mL 1% lidocaine and 80 mg triamcinolone acetonide). At the second post-injection week, they found a 47 and 67% reduction in pain scores in the former and latter groups, respectively (31).

Through our literature search from PubMed and EMBASE, we could only find one other paper with similar methodology. The small RCT was designed to investigate the influence of corticosteroid hydrodissection on CTS (27). Schrier et al. enrolled 20 patients randomly assigned to either ultrasound-guided hydrodissection using 1 mL of betamethasone (6 mg), 1 ml of 1% lidocaine, and 3 mL saline or injection only with 1 mL of betamethasone (6 mg) and 1 mL of 1% lidocaine (27). The results revealed no significant differences in the visual analog scale of pain or BCTQ scores between the groups at 24 weeks after the intervention. Therefore, our RCT was complementary to the aforementioned study, whose clinical evidence was limited by the small number of cases. The comparisons of the demographic and intervention characteristics between ours and the aforementioned study are summarized in Tables 3, 4, respectively.

Based on evidence from our RCT, we did not observe any significant difference in clinical effectiveness between the two groups after the intervention. We believe that a total of 10 mL was sufficient for the hydrodissection of perineural adhesions. Complete separation of the median nerve from the surrounding tissues was confirmed along the entire nerve length in the carpal tunnel in our study. Furthermore, an increase in intra-carpal tunnel pressure is a pathogenic factor of CTS (3). The volume (10 mL) used in our study is known to be the highest among the existing literature (10). It is possible that such a high volume within the carpal tunnel may elevate intra-carpal tunnel pressure and counteract the benefit(s) of hydrodissection.

Regarding the dose of corticosteroid, most reports in the literature describe injections of 20–40 mg triamcinolone acetonide or an equivalent potency dosage of methylprednisolone for treating CTS (32–35). The dose of triamcinolone acetonide (10 mg) used in the present study was small, which facilitated the comparison of the add-on benefit of hydrodissection. A study by Peters-Veluthamaningal et al. reported that one or two intra-carpal tunnel injections with 10 mg triamcinolone was more effective than placebo injections for CTS (36) in a short blinded follow-up period. A recent RCT confirmed that a single 10 mg triamcinolone acetonide injection was as effective as 40 mg for CTS management (21). In addition, both groups in the present study received the same dosage of corticosteroid, which theoretically had minimal impact on the between-group comparison of clinical effectiveness. Furthermore, because our chosen corticosteroid type was triamcinolone, potential toxicity of peripheral nerves (37) should be considered in case of accidental intra-neural injection. The aforementioned reasons made us choose 10 mg triamcinolone at the first place. However, an antecent RCT (38) pointed out that 80 mg methylprednisolone was better than 40 mg methylprednisolone in improving symptoms of CTS and decreasing the rate of needing for surgeries. Therefore, a higher dose of triamcinolone, like 40 mg, should be prioritized as the treatment regimen for hydrodissection, although extra caution should be taken during injections for prevention of neurotoxicity.

Our study had some limitations, the first of which was the short follow-up period of only 12 weeks. Based on the results of most literature, corticosteroid injections for CTS only provide short-term benefits. In a retrospective analysis of 233 patients treated with intracarpal corticosteroid injections, Green et al. (39) reported that the majority of the patients displayed recurrent symptoms at 2–4 months after the initial treatment. In a prospective study, Gelberman et al. (40) reported that the maximal improvement of CTS symptoms occurred at 1–2 months after corticosteroid injections. Armstrong et al. (41) reported that after a median interval of 103 days following the initial corticosteroid injection, more than 50% of patients requested a second injection for recurrent symptoms. In a systemic review, Marshall et al. (14) concluded that the effect of corticosteroid injection beyond 1 month remained uncertain. Moreover, our previous study (42) revealed the effects of intracarpal corticosteroid (10 mg triamcinolone) declined at the post-injection 6 weeks. Therefore, we chose 12 weeks to evaluate if hydrodissection had an add-on benefit to corticosteroid injections for managing CTS. However, further prospective studies with longer follow-up periods to obtain the rates of relapsing and needing for surgeries are still needed.

Second, the study did not include a placebo group; thus, the effect of hydodissection or corticosteroid perineural injection using a small volume compared with the natural course could not be determined through our analysis. Third, the cross-sectional area, flattening ratio and stiffness of the median nerve have been identified to be different between patients with CTS and those without by ultrasound imaging. A previous meta-analysis (43) has demonstrated that the diagnostic odd ratio of the nerve cross-sectional area could reach 31.11 [95% confidence interval (CI), 20.42–47.40] over the carpal tunnel inlet, whereas another meta-analysis (44) has shown that the sensitivity and specificity for diagnosing CTS could be up to 0.94 (95% CI, 0.90–0.97) and 0.80 (95% CI, 0.71–0.88), respectively, by evaluating nerve stiffness using shear wave sonoelastography. Regarding the adhesion of subsynovial connective tissue, Park et al. (45) revealed a reduction of median nerve gliding employing dynamic ultrasound imaging in the CTS group. Through reviewing the aforementioned meta-analyses (43, 44) and original study (45), the use of ultrasound image has gradually become an alternative modality for the diagnosis and follow-up of CTS. Furthermore, clinical assessments, such as the grip and pinch strength (46), performance of fine motor control (47), and two-point discrimination (48) would be helpful in providing objective data. Nevertheless, we did not incorporate the aforementioned ultrasound and clinical assessments at the beginning of the study, which should be encompassed in future relevant research. Fourth, the Likert scale (49), a psychometric measurement, is widely used for assessing the participant's agreement with various statements. However, we did not include this scale to evaluate their acceptability/satisfaction for both interventional modalities in the beginning of this RCT, which should be added in our subsequent pertinent study. Fifth, the addition of the local anesthetics in the injectates could possibly interfere the estimation of the treatment effect and also elicited temporary numbness of the region innervated by the median nerve distal to the carpal tunnel. Therefore, there is no need to add local anesthetics in future clinical practice. Sixth, the grading system for CTS severity (18) used in this research might be out-of-date and a modern severity grading tool (50, 51) should be adopted in our next trial.

Ultrasound-guided hydrodissection using triamcinolone acetonide and corticosteroid perineural injection alone both resulted in clinical and electrophysiological improvement in patients with CTS at 12 weeks' post-treatment. However, additional hydrodissection did not provide additional benefit compared with corticosteroid injection perineural alone. More prospective studies are needed to investigate the long-term effectiveness of corticosteroid hydrodissection, as well as its influence on median nerve mobility.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Institutional Review Board of Taipei Veteran General Hospital. The patients/participants provided their written informed consent to participate in this study.

J-CW and K-VC: conceptualization, methodology, resources, funding acquisition, and formal analysis. P-CH: software. K-VC: investigation, supervision, and writing—review and editing. P-CH and KW: data curation and visualization. J-CW and KW: writing—original draft preparation. J-CW and P-CH: project administration. All authors contributed to the article and approved the submitted version.

This study was made possible by the research funding of the Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan; Ministry of Science and Technology (MOST 106-2314-B-002-180-MY3, 109-2314-B-002-114-MY3, and 109-2314-B-002-127), and Taiwan Society of Ultrasound in Medicine.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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