The complementary effects of galvanic current electrical stimulation associated with conservative treatment to increase vasodilation in patients with Raynaud’s phenomenon: a randomized trial

Abstract

Objective:

To analyze the effectiveness of an electrotherapy intervention with galvanic current on symptoms associated with Raynaud’s phenomenon.

Design:

Single-blind randomized controlled trial, parallel design (1:1 ratio) and intention-to-treat analysis.

Setting:

Virgen de las Nieves Hospital, Granada, Spain.

Subjects:

Thirty-four participants with Raynaud’s phenomenon, with a mean (SD) age of 43.43 (17.62) years.

Interventions:

The patients were randomly assigned to a control group with conservative treatment (anti-inflammatory, vasodilatory and analgesic drugs) or an intervention group that received conservative treatment and vasodilatory electrical stimulation during seven weeks, three times/week for a total of 20 sessions.

Main measures:

The primary outcome was the number of attacks. Secondary outcomes were pain, peripheral blow flow, oxygen saturation, upper limb disability, central sensitization, pain catastrophizing and temperature recovery. All outcomes were assessed at baseline, posttreatment and at two months of follow-up.

Results:

The galvanic current electrotherapy group showed significantly greater improvements in the number of attacks (mean difference = 26.3, 95% confidence interval (CI) = 14.4 to 38.3), pre-cold stress pain (95% CI = 0.6 to 2.4), radial artery blood flow (95% CI = −7.8 ⩾ x ⩽ 1.3), ulnar artery blood flow (95% CI = −8.63 to 0.60), oxygen saturation (95% CI = −1.7 ⩾ x ⩽ −0.29), upper limb disability (95% CI = 1.1 to 22.3), central sensitization (95% CI = 6.7 to 18.2) and temperature recovery (95% CI = −5.7 ⩾ x ⩽ −0.32) than the conservative treatment group.

Conclusion:

This study suggests that a complementary treatment with galvanic current in combination to conservative approach is superior to conservative applied as isolate, in reducing the clinical manifestations and disability in Raynaud’s phenomenon.

Keywords

Raynaud disease electric stimulation therapy randomized controlled trial

Introduction

Raynaud’s phenomenon is a peripheral vascular disorder characterized by recurrent episodes of vasospasm and ischemia in response to cold or emotional stimuli, which usually affect the cutaneous microvasculature of the fingers and toes.^1,2 Vasospasm’s attacks are accompanied by a change in skin color, varying levels of pain and functional impotence.^1,2 The estimated prevalence of Raynaud’s phenomenon varies across studies between 3% and 21% and it is classified into two main types: primary and secondary.^1,2 Primary form is the most common type, its etiology is still unknown and it is considered a “benign” condition because clinical manifestations tend to be milder.^3,4 Secondary Raynaud is associated with an underlying disease; it usually shows worse clinical course over time and may progress to irreversible tissue damage.^4,5 In addition, Raynaud-related symptoms cause upper limb disability and reduce quality of life, involving patients in a chronic condition that generates a significant healthcare costs.^5,6

Treatments for Raynaud depend of its severity and etiology.^2,5 The main option for primary Raynaud is generally conservative, including life style recommendations. In patients who have not responded adequately to conservative treatment, the pharmacological therapy based on vasodilators should be considered.^2–5 Secondary Raynaud requires pharmacological therapy for the treatment of the underlying pathology, in addition to conservative approach.^2,3 When patients do not respond to pharmacological treatment and develop severe symptoms such as ulcers or gangrene, surgery is recommended.^2,3 There is also a wide variety of alternative treatment options such as spinal cord stimulation, laser therapy or acupuncture.^2,4,5 However, none of these therapies has shown definitive efficacy, and many of them have significant side effects.⁵

Currently, electrical stimulation techniques are being used in the treatment of vascular disorders, for example, the application of a galvanic electrical current on the skin, which produces a vasodilatory effect on dermal blood flow.^7,8 High-voltage pulsed galvanic stimulation seems to be superior to other electrical applications for healing ulcers, due to this vasomotor effect.⁹ However, scientific evidence regarding the use of galvanic stimulation in the treatment of Raynaud is as yet very limited. In our concern, only four studies^7,8,10,11 have used galvanic current by iontophoresis and vasoactive drugs, showing positive effects on clinical symptoms, tissue flexibility and skin color. However, no studies were found on the application of locally galvanic current without vasodilator drugs.

In light of this background, the purpose of this study was to analyze the complementary effectiveness of galvanic electrical stimulation associated with the conservative treatment in improving attacks, pain, blow flow, oxygen saturation, upper limb functionality, central sensitization, pain catastrophizing and temperature in patients with primary and secondary Raynaud’s phenomenon in comparison to a control group. We hypothesized that treatment with a galvanic electrical current might have a vasodilatory effect which in turn could improve local symptoms and functionality. This new approach may benefit clinical practice since it is less invasive, easier to implement and usually produce minimal side effects, in comparison to galvanic current applied with drugs or other surgical procedures.

Methods

A randomized controlled trial with a parallel design (allocation ratio 1:1) was performed to test the main objective of the study. The study was approved by the University Bioethics Committee of the University of Granada (Spain) on 12 May 2015 (no. 27/CEIH/2015), was conducted in accordance with the amended version of the Declaration of Helsinki, 2013, and was registered on ClinicalTrials.gov as record number NCT03699436. In addition, authors have addressed the main recommendations included in CONSORT (Consolidated Standards of Reporting Trials) guidelines and Intervention Description and Replication checklist (TIDieR).

The study was conducted between October 2018 and February 2019 in order to perform trials during the coldest months of autumn and winter in the Northern Hemisphere and thereby minimize seasonal variability. The University of Granada was responsible for the study.

Participants were recruited from the Rheuma-tology Service of Virgen de las Nieves Hospital in Granada (Spain). The rheumatologist referred patients who were consecutively admitted to this service and met the following selection criteria. Inclusion criteria were age over 18 years; diagnosis of primary or secondary Raynaud from rheumatologist according to LeRoy and Medsger criteria:¹² (1) vasospastic attacks precipitated by cold or emotional stress at the hands (primary: symmetrical pattern, secondary: asymmetrical); (2) issue necrosis or gangrene (primary: absence, secondary: presence); history of physical findings suggestive of a secondary cause (primary: absence, secondary: presence); capillaroscopy (primary: normal, secondary: abnormal); erythrocyte sedimentation rate (primary: normal, secondary: abnormal); test for antinuclear antibodies (primary: low or negative, secondary: high or positive); and a history of at least one year of regular Raynaud’s phenomenon attacks. Exclusion criteria were (1) skin alterations (scars, gangrene or ulcers in the area to be treated); (2) upper limb entrapment syndrome; (3) in women, pregnancy or breastfeeding; and (4) any tumoral process. Written informed consent was obtained from all participants.

To randomize participant assignments to the intervention or control group, the investigator who screened eligibility criteria did not participate in the rest of the study and created identical letter-sized cards sequentially numbered, with the random assignment generated by a computerized random software. Each randomization card was placed into opaque envelopes which were opened by a research assessor who allocated each patient to their corresponding treatment groups. Group allocation was concealed from the physical therapists who recorded all outcome measures at baseline, after treatment and at two months of follow-up. A physical therapist with extensive clinical experience (more than 10 years of clinical experience in the rheumatology service and who received a special training in electrotherapy) performed all interventions and was blinded to the outcome measures and baseline examination findings, but not to the group assignments (due to the manual nature of the intervention to apply the galvanic current).

First, patients were screened for inclusion/exclusion criteria taking into account comorbidities by exploring their medical report. In addition, sociodemographic data and clinical characteristics were registered for each participant at the beginning of the study. Data were recorded on the number of attacks as the primary outcome and pain intensity, blood flow, oxygen saturation, upper limb disability, central sensitization, catastrophizing, skin temperature at baseline and after a cold stress test, and temperature recovery as secondary outcome measures. All variables were evaluated at three time points: baseline, posttreatment (at seven weeks, 24 hours after the last treatment session) and at two months’ follow-up (at 15 weeks). The time between the randomization and the initiation of the evaluation was two days. Each participant was evaluated on the same day, over a total time of 90 minutes, under the same stable conditions:¹³ patients were acclimatized for 20 minutes in a climate-controlled room without direct ventilation at 24°C with humidity of 50%–60% and seated in a comfortable position with both hands placed on a table and forearms uncovered. They were previously informed that they should avoid physical activities and refrain from consuming any vasoactive substance (alcohol, caffeine, nicotine) in the 2 hours prior to the evaluation.

Participants recorded the number of attacks per day in a diary register, during seven days and the average number of attacks per week was calculated for primary outcome.

A visual analog scale, consisting of line from 0 (no pain) to 10 cm (the worst pain imaginable) was used to evaluate pain intensity; this instrument has demonstrated good reliability and internal consistency.¹⁴ The minimal clinically important difference for the visual analog scale in chronic pain clinical trials has been determined as follows: 1 point change indicates minimal effects and 2 points represent meaningful decrease in chronic pain.¹⁵

We evaluated blood flow with a Hadeco Bi-Directional Vascular Doppler®. Measurements were taken according to the protocol described in a previous study¹⁶ where blood flows in radial and ulnar arteries were evaluated in the same way on the volar surface of the wrists of both hands. Result was expressed in cm/s⁻², and the mean of the three measurements was calculated. To determine oxygen saturation, a finger pulse oximeter (MEGOS Oxi-Pulse®, SONMEDICA S.A) was used. The oximeter was placed on the middle finger and the percentage of oxygen saturation values on both hands was used for statistical analysis. This is a well-established method to quantify oxygen saturation.¹⁷ To assess disability, we used the Spanish version of the Shortened Disabilities of the Arm, Shoulder and Hand Questionnaire (Quick-DASH).^18,19 This instrument has demonstrated good reliability, validity and responsiveness.¹⁸ The minimal clinically important difference values for Quick-DASH have been determined in patients with arthritis where changes of 14 points (with 95% confidential intervals of 9–20) represent minimal clinically important changes.²⁰

To obtain information about central sensitization we used the Central Sensitization Inventory, which has been shown to have high reliability and validity.²¹ For catastrophizing we used the Pain Catastrophizing Scale, which has good internal reliability and high internal consistency.²² To record temperature, we used a hand-held infrared thermographic scanner (Derma Temp® DT-1001) applied to the fingertip of the third finger on both hands. Three parameters were obtained: pre-cold stimulation test, post-cold stimulation test and temperature recovery. Participants performed the cold stimulation test by immersing both hands in cool water (10°C) for two minutes.^23,24 Finally, temperature recovery was determined for a 35-minute period with recordings every five minutes.²³

Both the experimental and control groups received a conservative approach (life style recommendations: maintaining high core body temperature, avoidance of cold exposure, use of gloves and cessation of smoking) and pharmacological treatment based mainly on nonsteroidal anti-inflammatory, vasodilatory, analgesic, antidepressants and insulin drugs. Conservative treatment was maintained throughout the study. Medication intake was controlled in both groups through a diary, where the patients included the dosage. Patients were encouraged not to change the dosage established by the rheumatologist until the end of the experimental phase. Weekly telephonic reminders were also carried out during all the study to follow up and encourage patients in registering their diary medical treatment.

The experimental group also received a physical therapy intervention, applied one on one, based on galvanic current electrotherapy. An Enraf Nonius-Mod Myomed 932 galvanic generator was used, with an input current of 220–240 V and 50/60 + 10% Hz. We applied parameters for the electrical stimulation according to the protocol described in a previous study.²⁵ The output current was a continuous polarized galvanic current with a maximum amplitude of 30 mA. For treatment, two flexible rubber electrodes measuring 12 cm × 8 cm were used. First two polyvinyl trays with a surface area of 315 cm² and a volume of 1260 cm³ were filled with water. After the electrodes with their corresponding pads (13.5 cm × 0.5 cm) were placed at the bottom of the tray, the patient’s hands were immersed. Prior to treatment, petroleum jelly was applied as a skin protector over possible cuts or other wounds. The patients were seated with their hands inside the two containers filled with water up to the base of their fingernails and with their fingers separated. A galvanic current was administrated for 20 minutes; the polarity was changed after 10 minutes. The current intensity was increased up to the maximum tolerated by the patient using a verbal rating scale from 0 to 10, or up to a maximum of 30 mA. The physical therapist applied the intervention following always the same order. This protocol was used three times/week for seven weeks, in a total of 20 sessions.

Adherence and adverse effects in the experimental group were controlled by the physical therapist who administered the treatment, registering the number of sessions completed and incidences of events. Patients in the control group were also instructed in communicating to the principal investigator, any change in their medication or adverse effect.

The sample size was calculated with Ene 3.0 software (Autonomous University of Barcelona, Spain). The calculations were based on detecting a posttreatment difference of 3.4 points in the primary outcomes measure, that is, weekly number of attacks, in accordance with a previous study by Denton et al.²⁶ Assuming a standard deviation (SD) of 1.30 points, for a two-tailed test, an alpha level (α) of 0.05, and a desired power (β) of 95%, the estimated minimum sample size was calculated as 12 participants per group. Previously we had calculated a total sample size of 60 participants, as noted in the Clinical Trials record, in order to allow for a 62.5% dropout rate. However, as the trial progressed, the adherence rate approached 100% so we opted to reduce recruitment to a total of 48 participants, allowing for a 50% dropout rate. This ensured adequate power while reducing the cost of the trial.

For data analysis, we used the SPSS© version 20.0 for Windows. Normality of the variables was verified with the Kolmogorov–Smirnov test. Demographic variables were compared between groups with Student’s t-test for continuous data and chi-square tests for categorical data. We performed a separate 2 × 3 repeated-measures analysis of variance (ANOVA) to evaluate the effect of the intervention on the number of attacks per week as the primary outcome, and on pain intensity, oxygen saturation, blood flow, temperature recovery, upper limb disability, catastrophizing and central sensitization as secondary outcomes. The within-subject variable was time, that is, baseline, after treatment (seven weeks after baseline) and two months of follow-up (15 weeks from baseline), and the between-subjects variable was group (experimental or control). All analyses followed the intention-to-treat principle and groups were analyzed as randomized. Baseline scores were introduced in the overall analysis when missing values were reported. We recorded the changes in variables within and between groups as means (with 95% confidential intervals) of t-tests for paired or independent samples as appropriate. We calculated the effect size according to Cohen’s d statistic. An effect size of <0.2 indicated a negligible difference, between ⩾0.2 and <0.5 a small difference, between ⩾0.5 and <0.8 a moderate difference and ⩾0.8 a large difference. A P value <0.05 was considered significant in all tests.

Results

Of the 48 patients recruited for the study, 34 patients with an average age of 43.41 years (SD = 17.62) met the inclusion criteria. A CONSORT flow diagram of the participants throughout the study is shown in Figure 1.

Figure 1.

Flow diagram of the recruitment and follow-up of participants through the study following CONSORT 2010 guidelines.

The baseline characteristics of participants in each group are presented in Table 1. There were no significant differences between the groups (P ⩾ 0.48) (Table 1). The effect of treatment and final values in each group are shown in Table 2 and Supplemental Table 3.

Table 1.

Sociodemographic characteristics, comorbidities and pharmacologic treatments in participants.

Outcomes	Treatment group	Control group
Age (years)	43.2 ± 18.1	43.5 ± 17.7
Sex
Male	5 (29.4)	6 (35.3)
Female	12 (70.6)	11 (64.7)
Hand dominance
Right	14 (82.4)	15 (88.2)
Left	2 (11.8)	1 (5.9)
Ambidextrous	1 (5.9)	1 (5.9)
Time since onset (years)	12.8 ± 10.5	12.8 ± 9.8
Type of RP
PRP	6 (35.3)	7 (41.2)
SRP	11 (64.7)	10 (58.8)
Smoking history (%)
Active smoker	1 (5.9)	2 (11.8)
Non-smoker	13 (76.5)	11 (64.7)
Ex-smoker	3 (17.6)	4 (23.5)
Comorbidity (%)
Hypertension	8 (47.1)	6 (35.3)
Hypercholesterolemia	6 (35.3)	7 (41.2)
Diabetes mellitus	1 (5.9)	2 (11.8)
Fibromyalgia	6 (35.3)	5 (29.4)
Rheumatoid arthritis	5 (29.4)	4 (23.5)
Scleroderma	3 (17.6)	4 (23.5)
Depression	6 (35.3)	7 (41.2)
Hyperhidrosis	3 (17.6)	2 (11.8)
Pharmacologic treatment
NSAIDs	8 (47.1)	8 (47.1)
Analgesics	10 (58.8)	11 (64.7)
Vasodilators	3 (17.6)	5 (29.4)
Antidepressants	5 (29.4)	7 (41.2)
Insulin	1 (5.9)	2 (11.8)

RP: Raynaud’s phenomenon; PRP: primary Raynaud’s phenomenon; SRP: secondary Raynaud’s phenomenon; NSAIDs: nonsteroidal anti-inflammatory drugs.

Data are expressed as the mean ± SD for quantitative variables, or the frequency and % for qualitative outcomes.

Table 2.

Baseline, posttreatment and follow-up values, and score changes in each group (95% confidence interval) for average number of weekly RP attacks, pain intensity, blood flow, oxygen saturation, upper limb disability, central sensitization and catastrophizing.

	Baseline	Posttreatment at seven weeks	Follow-up at 15 weeks	Within-group Cohen’s d (baseline/follow-up)	Score change		Between-group Cohen’s d (follow-up)
	Baseline	Posttreatment at seven weeks	Follow-up at 15 weeks	Within-group Cohen’s d (baseline/follow-up)	Within-group	Between-group	Between-group Cohen’s d (follow-up)
Average number of RP attacks
Experimental	31.29 ± 21.02	11.53 ± 8.55	8.23 ± 9.97	1.40	23.06 (11.21, 34.91)	26.35 (14.37, 38.33)*	2.20
Control	25.11 ± 9.91	27.17 ± 8.16	28.00 ± 7.83	0.32	−2.88 (−7.30, 1.54)
Pain intensity pre-CST
Experimental	2.64 ± 2.22	1.66 ± 1.92	2.59 ± 2.64	0.02	0.05 (−0.97, 1.07)	1.22 (0.57, 2.39)*	0.88
Control	3.60 ± 2.58	4.4 ± 2.66	4.79 ± 2.33	0.48	−1.17 (−1.83, −0.51)
Pain intensity post-CST
Experimental	7.34 ± 2.65	8.41 ± 0.97	8.25 ± 1.16	0.44	−0.91 (−2.89, 0.14)	−1.01 (−2.44, 0.42)	0.26
Control	8.72 ± 1.38	8.46 ± 1.56	8.62 ± 1.56	0.06	0.11 (−0.62, 0.84)
Blood flow radial artery
Experimental
D	9.12 ± 5.11	9.82 ± 2.69	9.30 ± 2.90	0.04	−0.17 (−2.63, 2.30)	−3,32 (−6.24, 0.39)*	1.18
ND	8.73 ± 3.72	11.40 ± 3.04	10.13 ± 3.25	0.39	−1.40 (−3.51, 0,73)	−5.10 (1.34, −7.82)*	1.27
Control
D	9.29 ± 2.80	7.26 ± 1.59	6.14 ± 2.40	1.20	3.15 (1.36, 4.94)
ND	10.11 ± 3.22	7.76 ± 1.53	6.40 ± 2.56	1.27	3.71 (1.84, 5,59)
Blood flow ulnar artery
Experimental
D	10.39 ± 6.32	10.08 ± 3.97	10.70 ± 4.06	0.04	−0.31 (−3.75, 3.27)	−4.62 (−8.63, −0.60)*	1.37
ND	9.53 ± 3.24	9.21 ± 3.13	8.79 ± 2.07	0.27	0.74 (−0.89, 2.37)	−1.57 (−3.50, 0.35)	1.16
Control
D	10.63 ± 4.02	8.60 ± 2.98	6.25 ± 2.10	1.36	4.38 (2.10, 6.66)
ND	8.79 ± 2.08	7.93 ± 1.73	6.40 ± 2.03	1.16	2.39 (1.15, 3,47)
Oxygen saturation
Experimental
D	97.00 ± 1.27	97.82 ± 0.73	97.41 ± 0.79	0.38	−0.41 (−1.12, 0.29)	−0.94 (−1.76, −0.12)*	0.61
ND	97.29 ± 0.85	97.65 ± 0.93	98.47 ± 0.80	0.22	−1.18 (−0.59, 1.24)	−0.82 (−1.35, −0.29)*	1.96
Control
D	97.51 ± 0.80	96.88 ± 0.78	96.88 ± 0.93	0.72	0.63 (0.04, 1.01)
ND	97.47 ± 0.72	97.06 ± 0.83	96.82 ± 0.88	0.80	0.65 (0.29, 1.01
Quick-DASH (%)
Upper limb disability
Experimental	45.20 ± 22.25	37.75 ± 18.70	37.03 ± 23.50	0.36	8.17 (1.17, 15.16)	11.69 (1.10, 22.29)*	0.19
Control	38.10 ± 24.10	39.13 ± 21.07	41.64 ± 23.59	0.15	−3.54 (−12.06, 4.99)
Work module
Experimental	57.35 ± 31.96	45.96 ± 35.28	46.53 ± 32.59	0.33	10.82 (−2.88, 23.64)	17.82 (1.75, 33.89)	0.23
Control	56.97 ± 34.50	49.26 ± 32.69	54.41 ± 35.34	0.07	2.56 (−17.63, 2.74)
Sports/performing arts
Experimental	61.39 ± 30.32	47.06 ± 33.59	48.16 ± 36.23	0.39	13.23 (−1.04, 27.51)	20.95 (4.56, 37.34)*	0.22
Control	48.15 ± 35.21	44.85 ± 26.90	55.83 ± 31.36	0.23	−7.68 (−17.06, 1.62)
Central sensitization inventory
Experimental	53.94 ± 21.41	50.59 ± 20.84	50.90 ± 20.90	0.14	3.04 (0.79, 7.44)	12.47 (6.68, 18.25)*	0.34
Control	49.82 ± 20.35	51.88 ± 21.90	58.18 ± 21.56	0.39	−8.36 (−13.37, −3.34)
Pain Catastrophizing Scale
Experimental	21.23 ± 12.41	18.94 ± 10.94	18.40 ± 14.90	0.20	2.83 (0.19, 8,86)	6.94 (−0.72, 14.60)	0.04
Control	16.70 ± 13.81	21.23 ± 12.36	19.11 ± 13.79	0.17	−2.41 (−9.10, 4.28)

RP: Raynaud’s phenomenon; CST: cold stress test; D: dominant side; ND: non-dominant side.

Values are expressed as mean ± SD for baseline, posttreatment (after 20 sessions) and two-month follow-up, and as means (95% confidence interval) for within-group (baseline to follow-up) and between-group score changes (at follow-up).

Significant group × time interaction (analysis of variance, P < 0.05).

At the end of the follow-up period (15 weeks), the results showed significant differences between groups in the average number of attacks per week (F = 17.99, P < 0.001), visual analog scale pre-cold stimulation test (F = 7.43, P = 0.005), radial artery blood flow (dominant side: F = 3.96, P = 0.035; non-dominant side: F = 14.56, P = 0.001), ulnar artery blood flow (dominant side: F = 5.47, P = 0.026), oxygen saturation (dominant side: F = 7.91, P = 0.002; non-dominant side: F = 10.05, P = 0.003), total Quick-DASH score (F = 3.37, P = 0.046), Sports/Performing Arts Module score (F = 3.19, P = 0.048) and Central Sensitization Inventory score (F = 9.72, P < 0.001). The intervention group showed better results than controls in all the variables mentioned above. Therefore, patients reported less number of attacks, an increase in blood flow and oxygen saturation and lower upper limb disability and central sensitization at the end study (Table 2). However, within-groups score changes in the experimental group for pain was 0.44 cm and only 8 point for disability. Therefore, those variables did not reach the minimal clinically importance difference.

The results at final follow-up also showed better recovery in the temperature curve in the intervention group than in the control group at 25 minutes (dominant side: F = 4.53, P = 0.014), 30 minutes (dominant side: F = 4.70, P = 0.016; non-dominant side: F = 4.84; P = 0.014) and 35 minutes (dominant side: F = 3.74, P = 0.030; non-dominant side: F = 3.89, P = 0.029) (Supplemental Table 3).

Cohen’s effect size for between group’s differences was large in all significant outcome measures with the exception of central sensitization, temperature and upper limb disability which was small or negligible (d ⩽ 0.39).

Discussion

The results of this study suggest that at two months’ follow-up after electrotherapy treatment with galvanic current associated with a conservative treatment, the patients with Raynaud’s phenomenon showed improvements in the average number of weekly attacks, pre-cold stress pain intensity test score, blood flow, oxygen saturation, upper limb disability, central sensitization and temperature recovery in comparison to the control group. Therefore, our hypothesis that the proposed treatment protocol would improve the main symptoms of Raynaud’s phenomenon was supported by our results.

The use of galvanic current in the treatment of pathologies with microvascular dysfunction such as hyperhidrosis²⁷ or nail psoriasis²⁸ has been widely reported; however, studies of its effectiveness in Raynaud’s phenomenon are still scarce. Previous studies^11,29 that used galvanic current in combination with drugs in patients with Raynaud’s phenomenon secondary to systemic sclerosis showed that digital skin perfusion increased after a single session. Murray et al.,⁷ in their pilot study, designed a device for local chemical iontophoresis in the index finger and demonstrated that vasoactive drugs could be administered without systemic side effects in healthy controls. A later study¹⁰ in patients with systemic sclerosis demonstrated that iontophoresis was effective in increasing blood flow and reducing digital ischemia.

The exact mechanisms of action of galvanic current are still unclear.²⁹ Some authors have proposed that the benefits of the electrical current are based on the vasodilator effect produced in the hands, where the density of vessels and arteriovenous anastomoses is high.²⁹ Other authors reported that galvanic current decreased sweat gland activity, acting on the process of thermogenesis. Diminishing transpiration in the hands increased blood flow and temperature in the digital skin.³⁰

Our results showed a large reduction of 23.06 points in the number of weekly attacks in the intervention group. A systematic review³¹ on the use of calcium channel blockers in Raynaud’s phenomenon found that this therapy reduced the average number of attacks per week by 6 points. Denton et al.,²⁶ who tested an oral prostacyclin analog, reported that it did not reduce the number of attacks in patients with Raynaud’s phenomenon secondary to systemic sclerosis compared to a placebo group. A recent review³² highlighted that intravenous therapies with prostanoids also reduce the frequency and severity of attacks and digital ulcers in patients with severe secondary Raynaud’s phenomenon; however, the therapy had important disadvantages including systemic vasodilator side effects.

In this study, electrotherapy with galvanic current also produced an increase in peripheral temperature and a significant improvement in arterial blood flow. In this connection, an earlier study³³ showed that topical nitrate therapy to the fingers caused vasodilation, increased local blood flow, reduced the number of attacks and shortened recovery time after a cold challenge, but currently this therapy has not been approved for the treatment of Raynaud’s phenomenon. In contrast, another study with botulinum toxin injections in patients with severe Raynaud’s phenomenon³⁴ found no improvement in blood flow to the hands. The discrepancies between studies may be related to the lack of a local vasodilatory effect, given that botulinum toxin acts only by blocking sweat glands in the hands, thus modifying thermogenesis.

Regarding upper limb disability, our results showed a significant minimal reduction in the Quick-DASH questionnaire score which did not reach the minimal clinically importance difference. A previous study³⁵ of treatment based on the administration of phosphodiesterase type 5 inhibitors also reported a minimal significant improvement in the scleroderma-specific Health Assessment Questionnaire score in comparison to a placebo. To the best of our knowledge, there is no further previous evidence from studies designed to evaluate functionality and disability after treatment for Raynaud’s phenomenon.

Our results showed a significant difference of 12.47 points between groups in the Central Sensitization Inventory score after the follow-up period, but this improvement seems to be related more to the worse total scores (i.e. an 8-point increase) in the control group than to the reduction in symptoms in our intervention group. It should be noted that there was no change in pain catastrophizing. This finding is consistent with a recent study that highlighted the importance of new approaches such as pain education or cognitive behavioral therapy to improve cognitive and affective aspects related to pain, such as catastrophizing or central sensitization.³⁶

This study has some limitations. First, the short duration of electrotherapy makes it necessary for future research to evaluate the effects of multiple applications over a longer period and to extend the follow-up period. Second, although our sample size calculations ensured that the study was sufficiently powered for the primary outcome; further studies with larger sample sizes are needed to corroborate the findings and verify our conclusions regarding the secondary outcomes. Third, due to the nature of the intervention we tested, blinding the physical therapist who performed the interventions was not possible, although the therapist was blinded to the outcome measures and baseline examination findings. Fourth, patients were not blinded to their group allocation due to the nature of the interventions, and this may have influenced the expected responses. Finally, due to the reduced sample size, we were not able to stratify sample uniformly by sex in the data analysis. Accordingly, caution is needed in extrapolating the results of our study to the treatment of all patients with Raynaud’s phenomenon.

Nevertheless, the strengths of this study were that it was a well-designed randomized controlled trial that used blinded assessment and sample size calculation prior to recruitment. To the best of our knowledge, this study represents the first attempt to analyze the effectiveness of an electrotherapy intervention with galvanic current in patients who have symptoms of Raynaud’s phenomenon.

This study shows that the electrotherapy intervention as complementary treatment of conservative approach appears to be an effective modality to improve the symptoms of both forms of Raynaud’s phenomenon. The present findings have important implications for clinical practice. First, galvanic current can potentiate the effect of conservative approach when it fails as first therapeutic option. Second, the intervention proposed acts locally, avoiding systemic effects; therefore, it may be safer than other therapeutics options described in clinical guidelines for Raynaud, such as galvanic current applied with vasodilatory drugs or surgery. Finally, vasodilatory effect administrated by galvanic current might be beneficial for those patients with Raynaud-related finger ulcers, which can be difficult to heal.

Main findings serve to stimulate future research on the development of novel electrotherapy devices self-administrated for home treatment of Raynaud’s phenomenon. Additional researches are also needed to study aspects related to the central processing of pain, and upper limb functionality and disability, in order to optimize existing therapeutic options for this pathology.

Clinical messages

An electrotherapy intervention with galvanic current associated with conservative treatment, during seven weeks, provided significant improvements in the main vascular symptoms and signs of disability in patients with Raynaud’s phenomenon, and these improvements were maintained in the short term.

Supplemental Material

Supplemental_table – Supplemental material for The complementary effects of galvanic current electrical stimulation associated with conservative treatment to increase vasodilation in patients with Raynaud’s phenomenon: a randomized trial

Supplemental material, Supplemental_table for The complementary effects of galvanic current electrical stimulation associated with conservative treatment to increase vasodilation in patients with Raynaud’s phenomenon: a randomized trial by Rosa María Tapia-Haro, Mª Carmen García-Ríos, Sonia Toledano-Moreno, Antonio Casas-Barragán, Adelaida Mª Castro-Sánchez and María Encarnación Aguilar-Ferrándiz in Clinical Rehabilitation

Footnotes

Acknowledgements

The authors would like to thank all participants in the present study. The results reported in this study are based on research done for the doctoral thesis of the main author, who is affiliated with the Biomedicine Program (B 11.56.1) of the University of Granada, Spain. We thank K. Shashok for improving the use of English in the manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and/or publication of this article.

ORCID iD

Rosa María Tapia-Haro

Supplemental material

Supplemental material for this article is available online.

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