The efficacy comparison on femoral vein hemodynamics and morphology between two types of graduated elastic compression stockings among patients undergoing knee replacement: a single center, double-blind, randomized trial

Study design and participants

This was a single center, double-blind, parallel design, randomized trial, conducted from August 10th to December 31st in 2023, adult patients who underwent selective, unilateral total/unicompartmental knee replacement for the first time and did not have any predisposition to VTE were prospectively enrolled. Those with a previous history of either varicose veins or peripheral vascular disease, skin ulcers, dermatitis, wounds or VTE, preoperative prolonged immobilization or limited movement of lower limbs were excluded. The study was approved by the institution ethics board of China-Japan Friendship Hospital (2023-KY-130) and written informed consent was obtained from each patient. The study protocol was registered at Chinese Clinical Trial Registry website (http://www.chictr.org.cn/, registration number: ChiCTR2300074136; registration date: July 31st, 2023).

Randomization

Eligible patients were randomly assigned to type A or B GCS group by a 1:1 ratio through a randomization table generated by SAS 9.4 software (Cary, NC, USA). The group number was sealed in a light-tight envelope and was blind for both researchers and patients. Investigators who measured the outcome and statisticians who performed statistical analysis were also blind to the group assignment.

Assessment

The assessments have been described in our previous study (Yang et al., 2023). Briefly, the graduated compressions of type A GCS were as follows: eight mmHg-ankle, 13 mmHg-crus, 10 mmHg-popliteal fossa, eight mmHg-middle thigh and six mmHg-upper thigh. The graduated compressions of type B GCS were as following: eight mmHg-ankle, 14 mmHg-crus, eight mmHg-popliteal fossa, eight mmHg-middle thigh and six mmHg-upper thigh. The dimensions for the GCS type were selected according to the measuring chart recommended by the manufacturer (Zhende Medical Co., Ltd., Shaoxing, China).

Compressed ultrasound of the lower extremity was conducted before the operation (without GCS, as preoperative baseline) and within 24 h post operation (postoperative baseline, with GCS, and with GCS + ankle pump) on the heathy leg, because the leg which underwent knee replacement would be unable to wear GCS. The postoperative baseline was measured at least half an hour later after the patient returned to the ward. Similarly, measurements of the efficacy of GCS or GCS + ankle pump were also required at least half an hour’s intervals after wearing GCS or with ankle pump movement. Before and during the examination, all participants were asked to lie in the supine position, keep their emotions calm and limbs relaxed, and breath as steady as possible, since the blood flow velocity might be influenced by their breath.

Blood flow velocity and diameters of the femoral vein in healthy legs were assessed using a Doppler ultrasound scanner (Mindray Resona 8 Colour Doppler Equipment; Mindray Co, Shenzhen, China) equipped with a 7–10 MHz linear probe (SuperLinear 14-5; Mindray Co, Shenzhen, China). Measurements were conducted by a single experienced sonographer. Peak velocity (PV, cm/s) and trough velocity (TV, cm/s) of the femoral veins were assessed in four different conditions for each participant: lying down, during ankle pump exercises, with GCS alone, and with GCS while performing ankle pump movements. The probe was placed longitudinally regarding the axis of the vein, maintaining about two mm distance from the skin to reduce compression effects on the vein. The Doppler ultrasound was set to pulsed mode, maintaining an incident angle below 60°, with the sampling volume aligned parallel with blood flow to encompass the center of the venous lumen. The pulse repetition frequency was set between 603–1500 Hz. To ensure higher measurement reliability, once the signal was stable, five images were frozen and averaged for each participant.

Outcomes

The primary outcome was the relative change of TV in femoral vein of the healthy leg after knee replacement operation before and after wearing GCS. The secondary outcomes were the relative changes of diameter and PV of femoral vein in differences between two types of GCS.

Statistical analysis

According to the result of our pilot study (Yang et al., 2023), a trough of 126 patients were necessary to meet the statistical power of 80% at a two-sided significance level of 0.05. If only 90% of patients enrolled in the trial were included in the primary analysis, the sample size was expanded to 140. The full analysis set (FAS) including patients who underwent randomization and were capable for GCS and compressed ultrasound after operation were analyzed. In this study, the per protocol set (PPS) and the safety set (SS) were the same set as FAS. No adverse event was found during the study period. The relative changes of femoral vein parameters were calculated as:

Relative change (%) = $\frac{measurementattimepoint\mathit{B}-measurementattimepoint\mathit{A}}{measurementattimepoint\mathit{A}}$.

Timepoint B refers to a latter timepoint, such as GCS or GCS + ankle pump, timepoint A refers to a prior timepoint, such as preoperative or postoperative.

A positive value of relative change referred to the improvement of parameter value and a negative value referred to the decline of parameter value of femoral vein.

In addition to the comparisons between two types of GCS, a further comparison of the efficacy differences between the left and the right healthy legs among the entire participants was conducted, regardless of GCS types. The before-and-after comparisons were also performed to verify the efficacy of interventions (GCS and GCS + ankle pump) in this study. Numerical variables were summarized as median (interquartile range (IQR)) and categorical variables were expressed as numbers and percentages, and differences between groups were compared using Wilcoxon rank-sum test or chi-square test/Fisher’s exact test, where appropriate. For the paired data within each group, like parameters before and after wearing GCS, Wilcoxon signed rank test was performed. All statistical analysis were performed using SAS 9.4 software (Cary, NC, USA) and a P value <0.05 was considered statistically significant.

Characteristics of the participants

As is shown in the flowchart, a total of 148 patients underwent screening for eligibility for the study. Seven patients were unable to wear GCS and took following measurements due to postoperative nausea and vomiting and were excluded from the study. Finally, 141 patients were randomized and of whom, 71 were assigned to type A GCS and 70 to type B GCS, respectively. All patients who received randomization completed the study (Fig. 1).

The median ages were 67.0 (interquartile range (IQR) 63.0, 71.0) years old in type A GCS group and 68.0 (IQR 60.0, 74.0) years old in type B GCS group. The body mass index (BMI), systolic blood pressure and diastolic blood pressure were comparable between two groups. The median PV and median TV of femoral vein were faster in patients with type A GCS than those with type B GCS (max 14.3 cm/s vs 12.3 cm/s, p = 0.0351; min 6.4 cm/s vs 4.8 cm/s, p = 0.0139). The median diameter of femoral vein was also smaller in patients with type A GCS (9.9 mm vs 11.0 mm, p = 0.0163) (Table 1).

Primary and secondary outcomes of type A and B GCS

According to Table 2, no significant difference was observed between two groups on the relative change of TV in femoral vein of the healthy leg after knee replacement operation before and after wearing GCS. All the other parameters were comparable between type A and type B GCSs (Table 2).

As for the before-and-after relative changes on parameters of femoral vein by GCS types in Table S1, knee replacement significantly impacted the blood stream in femoral vein by reducing diameter and improving TV and PV in both GCS types. Compared with postoperative baseline, GCS + ankle pump significantly constricted femoral veins and improved the TV in both GCS types, while GCS alone did not (Table S1).

Differences between legs

As is shown in Table 3, among enrolled patients, 61 patients accepted knee replacement on left leg and wore GCS on right leg, while 80 patients were on the contrary. For both legs, GCS and GCS + ankle pump significantly constricted femoral veins compared with postoperative baseline (all P < 0.0001). However, compared with postoperative baseline, GCS and GCS + ankle pump also significantly improved the TV (median 1.2%, IQR −21.4% to 58.6%, P = 0.0384; median 14.0%, IQR −24.3% to 93.0%, P = 0.0019, respectively) in left leg, while not in right leg (Table 3).