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IntroductionUltrasound-guided percutaneous cryoneurolysis provides analgesia using cold temperatures to reversibly ablate peripheral nerves. Cryoneurolysis probes pass a gas through a small internal annulus, rapidly lowering the pressure and temperature, forming an ice ball to envelope the target nerve. Analgesia is compromised if a nerve is inadequately frozen, and laboratory studies suggest that pain may be paradoxically induced with a magnitude and duration in proportion with the incomplete ablation. We therefore investigated the relative effects of various factors that may contribute to the size of the ice ball and the effective cryoneurolysis zone.MethodsA cryoprobe was inserted into a piece of meat, a gas was passed through for 2 min, and the resulting ice ball width (cross-section) and length (axis parallel to the probe) were measured using ultrasound, with the temperature evaluated in nine concentric locations concurrently.ResultsThe factor with the greatest influence on ice ball size was probe gauge: in all probe types, a change from 18 to 14 increased ice ball width, length, and volume by up to 70%, 113%, and 512% respectively, with minimum internal temperature decreasing as much as from -5 to -32 °C. In contrast, alternating the type of meat (chicken, beef, pork) and the shape of the probe tip (straight, coudé) affected ice ball dimensions to a negligible degree. The ice ball dimensions and the zone of adequate temperature drop were not always correlated, and, even within a visualized ice ball, the temperature was often inadequate to induce Wallerian degeneration.ConclusionsPercutaneous probe design can significantly influence the effective cryoneurolysis zone; visualizing a nerve fully encompassed in an ice ball does not guarantee adequate treatment to induce the desired Wallerian degeneration because ice forms at temperatures between 0 and -20 °C, whereas only temperatures below -20 °C induce Wallerian degeneration. The correlation between temperatures in isolated pieces of meat and perfused human tissue remains unknown, and further research to evaluate these findings in situ appears highly warranted.

Daniel Krashin,1 Natalia Murinova,2 Andrea M Trescot31Department of Anesthesiology and Pain Medicine, 2Department of Neurology University of Washington, Seattle, WA, USA 3Algone Pain Center, Wasilla, AK, USAAbstract: Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen). Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity) and potential disadvantages (including altered use patterns and high morphine equivalent dosing) of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone.Keywords: hydrocodone, long-acting opioids, opioid abuse, acetaminophen toxicity, tamper-resistant opioids

BackgroundPostamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later.MethodsThe authors enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction.ResultsPretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [-0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of -0.1 (-1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament-instead of the sensory-only saphenous nerve-which resulted in quadriceps weakness, and possibly a fall and clavicle fracture.ConclusionsPercutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors' specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted.Editor’s perspective

IntroductionTotal knee arthroplasty (TKA) is frequently associated with severe, prolonged postsurgical pain, and therefore local anesthetic-based peripheral nerve blocks are commonly used for postoperative analgesia. Cryoneurolysis involves the use of freezing temperatures to provide a reversible sensory (and motor) block with a duration measured in weeks and months, more commensurate with the typical period of post-TKA pain. We therefore conducted a randomized controlled pilot study to evaluate the use of this modality for the treatment of pain following TKA to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first 3 postoperative weeks.MethodsA convenience sample of 16 patients undergoing primary TKA with a single-injection and/or continuous adductor canal nerve block were randomized to receive either active cryoneurolysis or a sham procedure targeting the infrapatellar branch of the saphenous nerve, in a participant-masked fashion. This was a pilot study with a relatively small number of participants, and therefore resulting data were not analyzed statistically.ResultsCompared with participants receiving sham, the active treatment group reported slightly lower average and worst pain scores as well as opioid consumption and sleep disturbances due to pain at a majority of postoperative time points between postoperative days (POD) 4-21.ConclusionsPreoperative ultrasound-guided cryoneurolysis of the infrapatellar branch of the saphenous nerve is feasible and may provide analgesic benefits for multiple weeks following TKA. A definitive randomized controlled trial appears warranted.

BackgroundUltrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment.MethodsPreoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usually postoperative day 2). The primary endpoint was the average pain level measured using a 0 to 10 numeric rating scale the afternoon of postoperative day 2. Participants were followed for 1 yr.ResultsOn postoperative day 2, participants who had received active cryoneurolysis (n = 31) had a median [interquartile range] pain score of 0 [0 to 1.4] versus 3.0 [2.0 to 5.0] in patients given sham (n = 29): difference -2.5 (97.5% CI, -3.5 to -1.5), P < 0.001. There was evidence of superior analgesia through month 12. During the first 3 weeks, cryoneurolysis lowered cumulative opioid use by 98%, with the active group using 1.5 [0 to 14] mg of oxycodone compared with 72 [20 to 120] mg in the sham group (P < 0.001). No oral analgesics were required by any patient between months 1 and 12. After 1 yr chronic pain had developed in 1 (3%) active compared with 5 (17%) sham participants (P < 0.001).ConclusionsPercutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.Editor’s perspective

Abstract Introduction Ultrasound-guided percutaneous cryoneurolysis provides analgesia using cold temperatures to reversibly ablate peripheral nerves. Cryoneurolysis probes pass a gas through a small internal annulus, rapidly lowering the pressure and temperature, forming an ice ball to envelope the target nerve. Analgesia is compromised if a nerve is inadequately frozen, and laboratory studies suggest that pain may be paradoxically induced with a magnitude and duration in proportion with the incomplete ablation. We therefore investigated the relative effects of various factors that may contribute to the size of the ice ball and the effective cryoneurolysis zone. Methods A cryoprobe was inserted into a piece of meat, a gas was passed through for 2 min, and the resulting ice ball width (cross-section) and length (axis parallel to the probe) were measured using ultrasound, with the temperature evaluated in nine concentric locations concurrently. Results The factor with the greatest influence on ice ball size was probe gauge: in all probe types, a change from 18 to 14 increased ice ball width, length, and volume by up to 70%, 113%, and 512% respectively, with minimum internal temperature decreasing as much as from −5 to −32 °C. In contrast, alternating the type of meat (chicken, beef, pork) and the shape of the probe tip (straight, coudé) affected ice ball dimensions to a negligible degree. The ice ball dimensions and the zone of adequate temperature drop were not always correlated, and, even within a visualized ice ball, the temperature was often inadequate to induce Wallerian degeneration. Conclusions Percutaneous probe design can significantly influence the effective cryoneurolysis zone; visualizing a nerve fully encompassed in an ice ball does not guarantee adequate treatment to induce the desired Wallerian degeneration because ice forms at temperatures between 0 and −20 °C, whereas only temperatures below −20 °C induce Wallerian degeneration. The correlation between temperatures in isolated pieces of meat and perfused human tissue remains unknown, and further research to evaluate these findings in situ appears highly warranted.

BACKGROUND: Acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks. CASE: We report three cases in which preoperative ultrasound-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy. Across all postoperative days and all three patients, the mean pain score on the numeric rating scale was 0 for each day. Similarly, no patient required any supplemental opioid analgesics during the entire postoperative period; and, no patient reported insomnia or awakenings due to pain at any time point. This was a significant improvement over historic cohorts. CONCLUSIONS: Ultrasound-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management which has a duration that better-matches mastectomy than other currently-described techniques. Appropriately powered randomized, controlled clinical trials are required to demonstrate and quantify both potential benefits and risks.

Pain after limb amputation is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration. Furthermore, uncontrolled pain in the immediate postoperative period is associated with persistent postsurgical pain, and frequently phantom limb pain. Cryoneurolysis is an alternative regional analgesic method to local anesthesia-based techniques. We report 3 cases in which ultrasound-guided percutaneous cryoneurolysis was performed in the perioperative period of limb amputation. All reported profound analgesia in the postoperative period without persistent postsurgical residual limb or phantom pain in the following months. No adverse events associated with the cryoneurolysis procedure occurred.

Pain after limb amputation is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration. Furthermore, uncontrolled pain in the immediate postoperative period is associated with persistent postsurgical pain, and frequently phantom limb pain. Cryoneurolysis is an alternative regional analgesic method to local anesthesia-based techniques. We report 3 cases in which ultrasound-guided percutaneous cryoneurolysis was performed in the perioperative period of limb amputation. All reported profound analgesia in the postoperative period without persistent postsurgical residual limb or phantom pain in the following months. No adverse events associated with the cryoneurolysis procedure occurred.

Cryoneurolysis entails using low temperatures to reversibly ablate nerves, with a subsequent analgesia duration measured in weeks or months. Previously, clinical applications for acute pain were limited because treatment originally required exposing the target nerve surgically. However, three developments have now made it possible to provide prolonged postoperative analgesia by cryoneurolysis: 1) new portable, hand-held cryoneurolysis devices, 2) ultrasound machine proliferation, and, 3) anesthesiologists trained in ultrasound-guided peripheral nerve block administration. This report is the first to describe the use of a single preoperative administration of ultrasound-guided percutaneous cryoneurolysis to provide multiple weeks of analgesia following shoulder rotator cuff repair and total knee arthroplasty. Considering the significant benefits of cryoanalgesia relative to continuous peripheral nerve blocks (e.g., lack of catheter/pump care, extremely long duration), this analgesic modality may be a practical alternative for the treatment of prolonged post-surgical pain in a select group of surgical patients.

We report 3 different cases in which ultrasound-guided percutaneous cryoneurolysis was performed to treat acute pain: 1 patient with refractory incisional pain after percutaneous nephrolithotomy; 1 patient with burns to the foot; and 1 patient with pain from iliac crest grafting. Acute pain associated with surgery or injury is a challenge to treat with local anesthetic-based regional anesthesia techniques when the anticipated pain duration exceeds a few days. Cryoneurolysis is an alternative analgesic method that utilizes extremely cold temperatures to reversibly ablate peripheral nerves and is potentially a novel method for acute pain management.

IntroductionCryoneurolysis is the direct application of low temperatures to reversibly ablate peripheral nerves to provide pain relief. Recent development of a handheld cryoneurolysis device with small gauge probes and an integrated skin warmer broadens the clinical applications to include treatment of superficial nerves, further enabling treatments for pre-operative pain, post-surgical pain, chronic pain, and muscle movement disorders.Areas coveredCryoneurolysis is the direct application of cold temperatures to a peripheral nerve, resulting in reversible ablation due to Wallerian degeneration and nerve regeneration. Use over the last 50 years attests to a very low incidence of complications and adverse effects. Cryoprobes have traditionally been applied through a surgical incision; but, recent technical advances allow percutaneous administration. A new hand-held device is now approved for use within the United States. Cryoneurolysis has been used to treat postoperative and chronic pain states as well as spasticity. Expert commentary: Changes in the US healthcare system such as a push for the reduction of opioid use and the incorporation of Diagnostic Related Group codes, as well as recent technological advances including a handheld unit that allows for treatment of superficial nerves while protecting the skin from damage, may contribute to the resurgence of cryoneurolysis for the treatment of peripheral nerves.

Background Acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks. Case We report three cases in which preoperative ultrasound-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy. Across all postoperative days and all three patients, the mean pain score on the numeric rating scale was 0 for each day. Similarly, no patient required any supplemental opioid analgesics during the entire postoperative period; and, no patient reported insomnia or awakenings due to pain at any time point. This was a significant improvement over historic cohorts. Conclusions Ultrasound-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management which has a duration that better-matches mastectomy than other currently-described techniques. Appropriately powered randomized, controlled clinical trials are required to demonstrate and quantify both potential benefits and risks.