Journal of Surgery

Introduction

Total Knee Arthroplasty (TKA) is one of the most successful and frequently performed orthopedic procedures worldwide, offering substantial pain relief and functional restoration for patients suffering from end-stage knee osteoarthritis [1]. Despite significant advancements in surgical techniques, implant design, and perioperative care, effective management of acute postoperative pain remains a formidable challenge. The invasive nature of TKA, involving extensive soft tissue dissection, bone resection, and periarticular manipulation, triggers a profound local inflammatory response, tissue edema, hemarthrosis, and muscle spasm. These factors collectively contribute to substantial pain, which can severely impede early mobilization, delay rehabilitation, diminish patient satisfaction, and prolong hospital stays [2,3]. The conventional reliance on opioid analgesics for postoperative pain control has increasingly come under scrutiny due to their well-documented adverse effects, including nausea, vomiting, sedation, constipation, respiratory depression, and the risk of dependency or misuse [4]. In the context of a global opioid crisis, the development of opioid-sparing analgesic strategies has become both a clinical and public health priority. Enhanced Recovery After Surgery (ERAS) protocols emphasize multimodal analgesia, combining pharmacological agents (e.g., NSAIDs, acetaminophen, gabapentinoids, and local anesthetics) with nonpharmacological interventions to target pain through diverse mechanisms, thereby improving efficacy while minimizing opioidrelated complications [5].

Among non-pharmacological adjuncts, cryotherapy has long been utilized for its anti-inflammatory, analgesic, and anti-edema properties. The application of cold induces vasoconstriction, reduces metabolic demand, decreases the release of inflammatory mediators, and slows nerve conduction velocity, thereby elevating pain thresholds and alleviating swelling [6]. Traditional methods, such as ice packs or gel wraps, are limited by their short duration of action, inconsistent temperature maintenance, and reliance on frequent nursing intervention. Computer-Assisted Cryotherapy (CAC) represents a technological evolution in this domain. These systems deliver continuous, regulated cold compression through a closed-loop circuit, maintaining a consistent therapeutic temperature at the surgical site while often incorporating adjustable compression to further mitigate edema [7]. By ensuring prolonged and controlled cryotherapy, CAC devices may optimize physiological benefits, enhance patient compliance, and reduce the burden on healthcare providers. Although several studies have investigated the role of cryotherapy in TKA recovery, the specific impact of CAC on opioid consumption, within the framework of a modern multimodal analgesic protocol, warrants further rigorous evaluation. Thus, the primary objective of this study was to assess the efficacy and safety of Computer-Assisted Cryotherapy in reducing postoperative opioid use and improving pain control following primary TKA. The hypothesis of the study is that the integration of CAC into a standardized ERAS pathway will significantly decrease opioid consumption while enhancing early functional outcomes and patient satisfaction.

Methods

Study Design and Patient Selection

A prospective, randomized controlled trial was conducted between July 2020 and July 2024 at a high-volume orthopedic center (San Paolo Hospital, Civitavecchia, Rome). A total of 210 patients scheduled for primary unilateral total knee arthroplasty due to endstage osteoarthritis were assessed for eligibility. Randomization was performed using a web-based random number generator, assigning participants to one of two groups in a one-to-one ratio, with 105 patients allocated to each group. Allocation concealment was ensured through sequentially numbered, opaque, sealed envelopes opened after written informed consent was obtained. Inclusion criteria were age between 50 and 85 years, primary total knee arthroplasty for painful osteoarthritis, American Society of Anesthesiologists physical status classification I–III, and the ability to comprehend study protocols and return for followup. Exclusion criteria included revision total knee arthroplasty, active knee infection or systemic sepsis, significant preoperative coronal deformity greater than 15 degrees varus or valgus, fixed flexion contracture greater than 15 degrees and/or flexion less than 110 degrees, documented vascular insufficiency or peripheral neuropathy in the affected limb, known hypersensitivity to cold such as cryoglobulinemia or cold urticaria, chronic opioid use defined as greater than 15 milligrams oral morphine equivalents daily for more than 3 months preoperatively, and contraindications to any components of the standardized multimodal analgesia protocol.

Intervention Protocols

All surgeries were performed by two senior arthroplasty surgeons using a standardized medial parapatellar approach under spinalepidural anesthesia. A cemented, posterior-stabilized prosthesis was implanted in all cases. A tranexamic acid protocol consisting of 1 gram intravenous pre-incision and 1 gram topical intra-articular was uniformly administered. For Group I (Control Group), patients received a standardized, multimodal, opioid-sparing analgesia protocol which included preoperative administration of 1000 mg acetaminophen and 400 mg celecoxib (if no contraindications were present), intraoperative periarticular injection with a mixture of 300 mg ropivacaine, 30 mg ketorolac, 0.5 mg epinephrine, and 10 mg morphine in 100 mL normal saline, and postoperative scheduled acetaminophen 1000 mg every 8 hours, celecoxib 200 mg twice daily (or an alternative NSAID), and gabapentin 300 mg at night. Rescue analgesia was provided with oral oxycodone 5-10 mg every 4 hours as needed for severe pain (defined as a visual analogue scale score >4). All opioid consumption was converted to morphine milligram equivalents (MME) for analysis. For Group II (CAC Group), patients received the identical multimodal analgesia protocol as Group I and additionally received computerassisted cryotherapy using a GameReady GRPro 2.1 system with a standardized protocol. The therapy was initiated in the postanesthesia care unit and consisted of two 3-hour applications per day with a minimum 1-hour break between sessions at a prescribed temperature of 10°C. Each session included intermittent compression, cycled at 50 mmHg for 30 seconds on and 30 seconds off. The device was applied over a single layer of dry gauze for the entirety of the inpatient stay. All patients received identical thromboprophylaxis with daily subcutaneous injections of 4000 IU enoxaparin and underwent the same institutional physiotherapy protocol which involved full weight-bearing as tolerated and active-assisted range of motion exercises initiated on the day of surgery.

Outcome Measures

Data collection was performed by blinded researcher who were not involved in the patients’ clinical care or group allocation. Primary outcomes included pain intensity measured using the visual analogue scale from zero to one hundred millimeters at rest and during active flexion, recorded at twenty-four, seventy-two, and one hundred and twenty hours postoperatively, and opioid consumption with total opioid consumption converted to morphine milligram equivalents calculated for the first five postoperative days from zero to one hundred and twenty hours.

Secondary outcomes included functional recovery with active knee range of motion measured with a goniometer at discharge and at the two-week follow-up, swelling assessed through thigh circumference measured ten centimeters proximal to the superior patellar pole at discharge, safety and complications including rates of blood transfusions, surgical site infections, symptomatic venous thromboembolism confirmed by Doppler ultrasound, and length of hospital stay, and computer-assisted cryotherapy specific tolerability with the skin under the device meticulously assessed daily for local adverse reactions including persistent erythema, blistering, superficial frostbite, or wound healing complications in Group Two.

Statistical Analysis

Statistical analysis was performed by an independent biostatistician using SPSS software version twenty-seven point zero from IBM Corporation; continuous variables such as visual analogue scale scores, morphine milligram equivalents, range of motion, and length of stay were tested for normality using the Shapiro-Wilk test and are presented as mean plus or minus standard deviation; between-group comparisons were made using independent samples t-tests for normally distributed data and Mann-Whitney U tests for non-parametric data; categorical variables such as transfusion rates and infection rates are presented as counts and percentages and were compared using Chi-square or Fisher exact tests as appropriate; a two-tailed p-value of less than zero point zero one was considered statistically significant to account for multiple comparisons and reduce the risk of Type I error.

Results

All 210 randomized patients completed the study and were included in the final analysis (105 in each group). The two groups were well-matched at baseline, with no statistically significant differences in demographic characteristics, preoperative pain scores, or preoperative range of motion (Table 1).

Baseline Demographic and Clinical Characteristics

Table 1: Baseline Demographic And Clinical Characteristics of Study Participants Undergoing Total Knee Arthroplasty.

Primary Outcomes

Patients in the CAC group reported significantly lower pain scores at all measured time points, both at rest and during activity, compared to the control group (p < 0.001 for all comparisons) (Table 2).

Postoperative Pain Scores (VAS, 0-100 mm)

Table 2: Postoperative Pain Intensity Measured By Visual Analogue Scale (Vas) At Rest And During Activity.

Total opioid consumption over the first five postoperative days was 46.5% lower in the CAC group compared to the control group (p < 0.001). The control group consumed a mean of 87.3 ± 28.5 MME, while the CAC group consumed 46.7 ± 19.8 MME (Table 3).

Opioid Consumption And Key Secondary Outcomes

Table 3: Primary And Secondary Outcomes: Opioid Consumption, Functional Recovery, and Clinical Metrics.

Secondary Outcomes And Complications

Functional recovery, as measured by active knee flexion, was significantly better in the CAC group at both discharge and the two-week follow-up (p < 0.001). Postoperative swelling, quantified by the increase in thigh circumference, was also significantly reduced in the CAC group (3.9 ± 1.2 cm vs. 5.8 ± 1.6 cm, p < 0.001). The mean length of hospital stay was shorter for the CAC group (3.1 ± 0.7 days vs. 3.8 ± 0.9 days, p < 0.001). The overall complication rate was low and comparable between groups (Table 4). There were no significant differences in the rates of blood transfusion, symptomatic Venous Thromboembolism (VTE), or Surgical Site Infection (SSI). In the CAC group, device tolerability was excellent. Three patients (2.9%) reported transient, mild skin erythema that resolved spontaneously within hours of discontinuing the device, with no cases of blistering, frostbite, or wound healing complications attributable to the cryotherapy. Postoperative Complications

Table 4: Postoperative Complication Rates Among Study Participants.