Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial

This randomized control trial was carried out at Shahid Modarres Hospital during 2016. [29] and it was retrospectively registered at www.​irct.​ir (ID: IRCT2017041513442N13).

Women aged between 20 to 60 years referring to the physical medicine and rehabilitation clinics with signs and symptoms of CTS and a confirmed diagnosis of mild and moderate CTS based on history (paresthesia or dysesthesia and painful swelling of the hand with clumsiness due to weakness that is exacerbated by repetitive use or sleep and improved by shaking the hand), physical examination (sensory loss and numbness in the areas of the hand, innervated by the Median Nerve (MN), positive Phalen’s test and/or Tinel’s test) and electrophysiological studies, were included as the sample population. The severity of CTS was determined according to the electrophysiological classification proposed by Stevens et al. [30]. Mild CTS was defined as sensory latency of longer than 3.6 ms with normal motor latency (≤4.2 ms) and moderate CTS was defined as sensory latency of longer than 3.6 ms plus a prolonged motor latency (4.3–6 ms).

On the other hand bilateral CTS, pregnancy, history of underlying metabolic diseases (such as diabetes mellitus, thyroid diseases, rheumatoid arthritis and etc.), history of local corticosteroid injection in the past 3 months, atrophy of thenar muscles, previous carpal tunnel release surgery and evidence of concomitant neuropathy or radiculopathy were considered as the exclusion criteria. Patients with PRP contraindications including history of malignancies, autoimmune or hematologic disorders, NSAID consumption 2 days prior to injection, treatment with antiplatelet and anticoagulant agents, Hb level under 12 g/dl, and platelet count under 150,000 in ml were also excluded.

The study protocol was thoroughly explained to the patients and they were reassured that their data will be only accessible by the main researchers, will be used anonymously and that they can withdraw from the study at their will. The treatment carried low risk of adverse effects and the patients were advised to contact the physician in case of experiencing infection or fibrosis at the site of injection, continued pain and swelling or any related neuromuscular complications.

An informed written consent was obtained from the enrolled subjects. The study protocol was evaluated and approved by the institutional review board of Shahid Beheshti University of Medical Sciences and the trial was conducted according to the Declaration of Helsinki’s principles.

To calculate sample size, change in VAS (ΔVAS) was considered as the main outcome.

Based on previous studies, we considered SD (Standard Deviation) of ΔVAS as 1.5; ΔVAS in control group as 1 and ΔVAS in treat group as 2.3.The type one error (α) was set as 95% and type 2 error (β) as 80%. Using the formula for comparing two means, the sample size was calculated as 21 in each group.

Patients were randomly allocated to one of two groups: (1) PRP plus wrist splint or (2) wrist splint, using an online randomization website [30] (https://​www.​randomizer.​org). To conceal the randomization sequence, we used sequentially numbered, opaque sealed envelope (SNOSE) method. After inclusion of a patient, a physiatrist drew an envelope and opened it [31]. Figure 1 depicts the study flow diagram.

Patients in the wrist splint group received a prefabricated wrist splint at 5-degree wrist extension and they were instructed to put on the splint overnight for 8 weeks.

Subjects in the PRP group also received wrist splints and were instructed to use it similar to the control group. They were also treated with a single local injection of leukocyte-poor PRP, processed using the Rooyagen kit (made by Arya Mabna Tashkis Corporation, RN:312,569). Since few studies are conducted on the treatment of CTS with PRP injection, it is not clear how much PRP should be administered for these patients to yield the best response. Since corticosteroids are routinely injected in CTS patients at a volume of 1 ml and to minimize the possibility of a flare reaction along with the associated pain and discomfort following PRP injection, we decided to administer 1 ml of PRP for our patients.

For preparing 1 mL of PRP, 10 mL of blood was initially drawn from the patient’s upper limb cubital vein using an 18G needle. Then, 1 mL of ACD-A was added to the sample as an anticoagulant and passed two stages of centrifugation; first at 1600 rpm for 12 min to separate the erythrocytes and then at 3500 rpm for 7 min in order to concentrate the platelets. The resulting PRP contained leukocytes with mean concentrations of 5–10%. Eventually, PRP quantification was performed to confirm that the platelet concentration has reached 4–6 times that of the whole blood, since some studies have shown a positive effect of PRP at this concentration in musculoskeletal diseases and others have indicated that concentrations higher than 8 times can negatively affect the repair process and inhibit cellular proliferation [32, 33].

A 0.5 ml injection of lidocaine was administered via a 25G needle, inserted at the distal carpal skin crease ulnar side to the palmaris longus tendon. With the needle kept steady at the mentioned site, the syringe was changed and 0.8–1 ml of the prepared PRP was injected. Right after injection, the patients were asked to score their pain severity on a scale of 0 to 10 based on the Visual Analogue Scale (VAS). Patients were then observed in the ward for 30 min and prior to discharge, were educated about activity restrictions, probable side effects and the method of icing on the injection site. Patients’ wrists were immobilized by splints and they were administered acetaminophen codeine to use as needed for the pain. All the measured variables were assessed for both groups after 10 weeks of treatment .

Collected information included age, duration of symptoms, pain severity, electrophysiological findings, and the symptom severity and functional status of the subjects were gathered by one of the researchers. The pain severity was determined by the patients, on a scale of 0 (no pain) to 10 (agonizing pain) according to the VAS.

Electrophysiological parameters including the peak latency (PL) of sensory nerve action potential (SNAP) and the onset latency (OL) of the compound muscle action potential (CMAP), were measured for all patients using a Caldwell Sierra® Wave electromyography device by the same physician with the same settings.

The Farsi translation of Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), whose validity and reliability had been assessed and confirmed by Rezazadeh et al. [34], was used for evaluating the severity of symptoms and functional status of patients.

SPSS software for Windows v.22 (IBM Corp., Chicago, IL, USA) was used for data analysis [35]. Qualitative variables were presented as frequency and percentage and quantitative variables were calculated as mean and standard deviation. Considering the normal distribution of change variables according to Shapiro-Wilk normality tests, parametric paired t-test was used to compare the changes in each variable within one group in different follow ups. Chi-square test was also used to compare qualitative variables between the two groups. In order to control for the effects of age when comparing the change variables between the two groups, ANCOVA test was run. A p value of less than 0.05 was considered as statistically significant in all analyses.