Effectiveness of cooling therapy (cryotherapy) on leg pain and self-efficacy in patients with chronic venous disease: A randomized controlled trial.

BACKGROUND: Individuals with chronic venous disease (CVeD) frequently experience associated leg pain that may influence disease management self-efficacy. OBJECTIVE: To evaluate the influence of a cooling intervention on leg pain associated with more severe stages of CVeD and self-efficacy. This was a secondary aim of the trial. DESIGN: Randomized, blinded, comparator-controlled, multisite trial. SETTING: Three wound clinics and an academic medical research center in the United States of America. PARTICIPANTS: 276 participants (54.3% female, 46.7% male) with stage 4 and 5 CVeD were randomly assigned by computer generated tables to the cooling intervention group (n = 138) or control group (n = 138). INTERVENTIONS: Participants received either a cooling (intervention) leg cuff or placebo cuff (control) to apply topically over the affected skin area. Both groups performed standard of care including wearing compression wraps and elevating legs for 30 min during the intervention. Study visits occurred at baseline, and months 1, 3, 6, and 9. METHODS: Visit measures included: Numeric Rating Scale (NRS) for short term pain; VEINES-QOL/Sym questionnaire for long-term pain; and, the Self Efficacy for Managing Chronic Disease Scale (SEMCD-6) for self-efficacy. Data were collected from September 2010 to December 2015 and analyzed using pooled t-tests, Chi-square tests, and mixed effects models. Observed 9-month patient retention rates were 94/138 (68.1%) in the intervention group and 91/138 (65.9%) in the control group. The primary analysis was based on the intention-to-treat principle. RESULTS: Both the cooling intervention and control group experienced statistically significant decreases in unadjusted and adjusted mean NRS pain scores of 1.2 (95% CI: (-1.82, -0.64); p < 0.0001) and 1.8 (95% CI: (-2.31, -1.24); p < 0.0001) respectively from baseline, however, no statistically significant differences in change scores were observed between groups. The unadjusted mean VEINES-QOL/Sym pain scores had statistically significant decreases of 0.9 ((95% CI: (-1.07, -0.62) p < 0.0001 cooling)) and 0.8 (95% CI: (-1.09, -0.55) p < 0.0001 - control) points. When adjusting the scores for demographic and clinical features, both cooling and control groups maintained statistically significant decreases (p < 0.001 for both). No statistically significant differences in change scores were observed between groups. The unadjusted and adjusted mean self-efficacy scores had no statistically significant improvements from baseline to month 9 within and between the cooling and control groups. CONCLUSIONS: Pain was reduced in both groups while self-efficacy did not change. Findings suggest that strictly implemented standard of CVeD care in each study group, with or without cooling, improved pain while there were no effects on self-efficacy.

Symptoms Associated With Chronic Venous Disease in Response to a Cooling Treatment Compared to Placebo: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to examine the efficacy of a self-administered cooling treatment on clinically meaningful differences (CMDs) in symptom changes in patients with chronic venous disease. DESIGN: Blinded, prospective, randomized controlled trial. SUBJECTS AND SETTING: Two hundred seventy-six community-dwelling adults 21 years and older with skin changes and/or a healed venous leg ulcer (Clinical-Etiologic-Anatomic-Pathologic [CEAP] 4 and 5 classification) completed the 6-month active treatment period. METHODS: Participants were recruited from wound and medicine clinics and from the general population through referrals or advertisements. Participants were randomly allocated to a sham control cuff or interventional cooling cuff group. Demographic and symptom-specific data were collected at baseline and at months 1, 3, and 6 with the 11-item symptom Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES QOL/Sym) questionnaire subscale for heavy legs, aching legs, swelling, night cramps, heating or burning sensation, restless legs, throbbing, itching, tingling sensation (pins and needles), pain, and irritability. Participants in the intervention group received a cooling gel cuff and those in the control group received a cotton-filled cuff to be place around the most affected lower leg during leg elevation. Both groups received standard of care for their chronic venous disease with compression wraps and skin hygiene. Dosing consisted of daily 30-minute treatment for 1 month, twice weekly for 2 months, and then thrice weekly for 3 months. To analyze and compare data, a mixed percentage clinically meaningful percentage change was used to assess CMDs in symptoms between groups for treatment modality, sex, and age group. RESULTS: All symptoms showed improvement, with throbbing, aching, itching, and pain demonstrating the greatest CMD in response to the cooling treatment. For throbbing and aching, similar improvements were noted in response to cooling; 50% in the cooling group showed improvement, whereas 60% in both groups responded favorably to pain. More than 50% of females and males reported improvements in throbbing; both males and females reported 60% improvements in pain in response to cooling. In contrast, far fewer females reported worsening of aching in the treatment group as compared to male participants (8% vs 20%). Age differences were noted for throbbing in the younger group (<65 years of age); older individuals 65 years or older saw CMDs in aching in response to cooling. CONCLUSIONS: Of the 11 symptoms, aching, throbbing, itching, and pain had greater clinically meaningful improvements in response to a cooling cuff applied to lower leg skin affected by chronic venous disease. These CMDs inform evidence-based practice by enhancing clinician understanding of which symptoms, physical, physiological, and behavioral outcomes, respond to treatment change in a meaningful way for the patient.

Does cryotherapy improve skin circulation compared with compression and elevation in preventing venous leg ulcers?

This trial compared skin blood flow, temperature and incidence of venous leg ulcers in patients with chronic venous disease using compression wraps and elevation pillows. Patients with CEAP C4 skin damage and C5 history of ulcers were randomly assigned to a cryotherapy intervention (n = 138) or placebo cuff control (n = 138) applied to the lower legs over 9 months. The time the ulcers healed prior to enrollment in the study for the cryotherapy group ranged from 1 to 2218 days (n = 8, median = 32 days); for the control group, the range was 24 to 489 days (n = 6, median = 390 days). There were no statistically significant blood flow changes measured in perfusion units with a laser Doppler flowmetre within or between the groups; mean difference between the groups was 0·62, P = 0·619. No differences were noted in skin temperature measured with an infrared thermometer within and between the groups; mean difference between the groups was -0·17°C, P = 0·540. Cryotherapy did not improve skin blood flow or temperature and did not show efficacy in preventing ulcers. However, at least 30% of intervention and 50% of control participants were anticipated to develop an ulcer during the study; only ∼7% occurred. These findings suggest that strict adherence to standard of care decreases the incidence of leg ulcers and remains a best practice for leg ulcer prevention.