Preoperative Ultrasoundguided Percutaneous Cryoneurolysis for the Treatment of Pain after Mastectomy

A Randomized, Participant- and Observer-masked, Sham-controlled Study

Brian M. Ilfeld, M.D., M.S.; John J. Finneran IV, M.D.; Matthew W. Swisher, M.D. M.S.; Engy T. Said, M.D.; Rodney A. Gabriel, M.D., M.A.S.; Jacklynn F. Sztain, M.D.; Bahareh Khatibi, M.D.; Ava Armani, M.D.; Andrea Trescot, M.D.; Michael C. Donohue, Ph.D.; Adam Schaar, M.P.P.; Anne M. Wallace, M.D.

Disclosures

Anesthesiology. 2022;137(5):529-542. 

In This Article

Abstract and Introduction

Abstract

Background: Ultrasound-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.

Methods: Preoperatively, 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.

Results: On 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).

Conclusions: Percutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.

Introduction

Breast cancer is the most common malignancy in women, with more than 1,600,000 new cases and a half-million deaths identified annually worldwide.[1] Between 36 and 40% of patients diagnosed with breast cancer undergo mastectomy—approximately 100,000 annually in the United States alone—with these numbers increasing during the past 2 decades.[2,3] In addition, tens of thousands of women undergo prophylactic mastectomies due to either identified cancer in the contralateral breast or identification of genetic mutations (e.g., BRCA1), both of which indicate an elevated cancer risk.[4,5] Pain in the acute postoperative period is frequently severe and can last for a month or more.[6]

Furthermore, mastectomy is one of the four surgical procedures at highest risk for transitioning from acute to persistent (chronic) pain,[7] with up to 57% of patients experiencing pain 6 to 12 months after surgery.[8] Inadequately controlled acute pain in the period after surgery is one of the greatest risk factors for the development of chronic pain.[8–10] It therefore follows that improving postoperative analgesia could greatly decrease the incidence of persistent postmastectomy pain.[11,12] Indeed, single-injection peripheral nerve blocks lasting less than 1 day have lowered persistent postmastectomy pain at 3 and 12 months.[13,14] Extending the peripheral nerve block 2 days with a continuous paravertebral nerve block further lowered the incidence of chronic pain.[15]

Cryoneurolysis is an analgesic technique consisting of the application of exceptionally low temperatures (approximately –70°C using nitrous oxide) to reversibly ablate peripheral nerves, resulting in prolonged pain relief termed "cryoanalgesia."[16] Originally, cryoneurolysis was administered via a surgical incision in which the target nerve was surgically exposed for direct treatment with a probe, greatly limiting applicability.[17] However, the development of probes that may be inserted percutaneously using ultrasound guidance enabled application without surgically exposing the target nerve(s).[18] The procedure is essentially the same as placing an ultrasound-guided peripheral nerve block; however, instead of injecting local anesthetic, a gas circulates through the probe inducing cold at the distal end and freezing the target nerve.[16] Nothing remains within the patient, and there is no external equipment to prepare, manage, or malfunction—a single administration results in effects measured in weeks to months without any subsequent patient or healthcare provider interventions.

Although multiple case reports of perioperative ultrasound-guided percutaneous cryoneurolysis suggest substantial analgesic and opioid-sparing benefits after painful surgical procedures,[18] only a single randomized, controlled pilot study involving 12 patients having lower extremity procedures has been published.[19] We theorized that a single preoperative cryoneurolysis application would significantly lower postmastectomy acute and chronic pain, as well as associated opioid requirements. We therefore conducted a randomized, controlled study to evaluate the use of this modality for the treatment of pain after mastectomy 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 postoperative year. The primary hypothesis tested was 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.

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