The Effect of Cryoneurolysis for the Treatment of Acute Postoperative Pain Following Total Knee Arthroplasty in High Pain Responders - A Randomized, Participant- and Observer-masked, Sham-controlled Trial

Background Total knee arthroplasty (TKA) is a frequently performed procedure and is expected to increase in numbers due to the aging population and growing obesity rates. Fast-track regimes with multimodal opioid-sparing analgesia have improved postoperative outcomes. However, a subset of patients still experiences unsatisfactory levels of postoperative pain in the weeks following surgery, potentially delaying mobilization and recovery as well as increasing the need for opioid analgesics. Current recommendations for pain management following TKA according to the Procedure Specific Postoperative Pain Management (PROSPECT) Working Group include paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, local infiltration analgesia, and single shot adductor canal block (ACB). However, the role of ACBs for pain after TKA has been under extensive debate in recent years. While an ACB may provide some pain relief, the duration of pain control is usually less than 24 h and the effect on length of stay (LOS) and opioid consumption is questionable.

In the past decades, cryoneurolysis has been used to treat acute pain following herniorrhaphy, tonsillectomy, and thoracotomy via the surgical incision. The emergence of percutaneous cryoprobes and the use of ultra-sound guided techniques has allowed for an increase in potential applications. Recently, the use of cryoneurolysis has gained attention as a potential regional anesthetic technique for the treatment of knee pain. Cryoneurolysis works by freezing peripheral nerves with temperatures in the range of -20⁰C to -100⁰C, causing a Wallerian degeneration of nerve axons distal to the treatment site. This process involves loss of the relative continuity of the axon and its covering of myelin but with a preservation of the surrounding endo-, peri-, and epineurium, thus allowing normal axonal regeneration and remyelination. Axons regenerate at a rate of 1-2 mm/day. Thus, resulting in a nerve block that typically will resolve with full recovery within weeks to months depending on the site of treatment.

The effect of cryoneurolysis on knee pain has been documented in a few studies. A randomized, double-blind, sham-controlled trial found that cryoneurolysis reduced symptoms of knee osteoarthritis for up to 150 days. A retrospective chart-review of 100 patients undergoing TKA found that cryoneurolysis significantly lowered LOS, reduced opioid consumption until 12 weeks after surgery, and reduced pain at the 2- and 6-weeks follow-up. Another retrospective analysis in 267 patients undergoing TKA found a comparable reduction in opioid requirements, pain, and LOS in patients treated with cryoneurolysis compared with historic controls. A recent RCT comparing cryoneurolysis to standard of care in 124 patients undergoing TKA found that cryoneurolysis reduced opioid consumption at 72 h, 6 weeks and 12-week follow-ups.

Although these findings are promising, cryoneurolysis is expensive and comprehensive, and might not be relevant in all patients receiving multimodal analgesia with COX-2 inhibitors, paracetamol, local infiltration analgesia, and high-dose steroid in a fully implemented enhanced recovery program. Several risk factors have been associated with a high pain response including age, gender, preoperative pain, psychological profile, and quantitative sensory testing (QST). However, when including postoperative pain in the prediction of acute pain, movement-evoked pain 24 h postoperatively is the best predictor for pain the week following surgery.

Using postoperative pain 24 h after surgery as a predictor of a sustained high pain response, we hypothesized that postoperative cryoanalgesia compared to a local anesthesia (LA) block with sham cryo treatment would reduce pain in patients with moderate to severe pain following TKA 2-7 days after surgery.