People on hemodialysis need their arteriovenous fistula (a blood vessel access point) punctured with a needle three times a week, which can cause pain and worry. This study compares three ways of managing that pain: (1) usual care, (2) applying an ice pack to a specific point on the hand before the needle is inserted (cryotherapy), and (3) applying a numbing gel (lidocaine/prilocaine) to the skin before the needle is inserted.

Adult hemodialysis patients with a working fistula were randomly assigned to one of these three groups. Over three dialysis sessions, researchers measured each patient's pain, anxiety, and other symptoms right before, right after, during, and after dialysis, as well as their quality of life and a physical stress marker (heart rate variability). The goal is to find out whether the ice pack method works as well as or better than usual care and the numbing gel at reducing pain and anxiety, so that a simple, low-cost, non-drug option could be offered to more patients in the future.

Background: Patients undergoing chronic hemodialysis require repeated arteriovenous fistula (AVF) cannulation, typically three times per week, resulting in over 300 needle punctures per year. Puncture-related pain and anxiety are common and can contribute to treatment avoidance and reduced quality of life. Cryotherapy has been proposed in prior literature as a simple, inexpensive, non-pharmacological method to reduce puncture-related pain by slowing nerve conduction velocity, but its comparative effectiveness against topical anesthetic gel and usual care has not been well established in clinical practice.

Objective: To compare the effectiveness of cryotherapy, topical lidocaine/prilocaine gel, and usual care in reducing AVF puncture-related pain and anxiety among hemodialysis patients, and to evaluate their effects on quality of life and physiological stress response.

Design: This is a randomized controlled trial with three parallel arms. Eligible participants were randomly assigned by dice-roll allocation to one of three groups:

1. Usual care: application of a room-temperature water bag to the puncture site for 5 minutes before cannulation.
2. Cryotherapy: application of a 200g ice pack, wrapped in a single layer of cotton cloth, to the LI4 (Hegu) acupoint on the non-fistula hand for 5 minutes before cannulation.
3. Topical anesthetic: application of lidocaine/prilocaine gel to two puncture areas under an occlusive dressing for up to 1 hour before cannulation.

All participants underwent the same cannulation procedure performed by the same operator using a 16Fr fistula needle, over three consecutive dialysis sessions (three times per week). Outcome assessors collecting data were blinded to group assignment.

Outcome Measures: Pain and symptom distress were assessed using the Edmonton Symptom Assessment Scale-revised (ESAS-r, 10 items) at four time points (pre-puncture, post-puncture, during dialysis, post-dialysis) across all three sessions. Quality of life was assessed using the EQ-5D-5L before dialysis, after dialysis, and before the next dialysis session. Heart rate variability (HRV), as an objective marker of sympathetic nervous system activity, was measured at the same time points as the EQ-5D-5L. Vital signs, dialysis blood flow rate, and pre/post-dialysis body weight were also recorded.

Statistical Analysis: Descriptive statistics (means, standard deviations, frequencies, percentages) were used to summarize demographic and clinical characteristics. Between-group comparisons were conducted using t-tests, chi-square tests, and two-way ANOVA to evaluate the effects of the interventions on pain, anxiety, and quality-of-life outcomes.

Inclusion Criteria:

• Age 18 years or older
• Diagnosed with end-stage renal disease requiring long-term hemodialysis
• Receiving hemodialysis with no hospitalization or arteriovenous fistula-related complications (e.g., infection, steal syndrome, aneurysm, pseudoaneurysm) within the past month
• Has a functioning arteriovenous fistula access (adequate vessel diameter, elastic and intact vessel wall, no significant stenosis or occlusion, superficial location, healthy surrounding tissue)
• Clear consciousness and able to express pain sensation, with no psychiatric symptoms interfering with communication
• Able to communicate in Mandarin or Taiwanese

Exclusion Criteria:

• Not using an arteriovenous fistula for dialysis vascular access
• History of stroke or peripheral neuropathy/sensory abnormality (e.g., numbness, tingling)
• Confused consciousness, unable to clearly express pain sensation
• Dysfunctional fistula, deep vein thrombosis, or cannulation difficulty preventing full use of the arteriovenous fistula

Data collectors assessing pain, anxiety, and other outcomes were blinded to group allocation; blinding of participants and intervention providers was not feasible due to the visible nature of the interventions (ice pack vs. topical gel vs. usual care).