Health Technology Review

Cryoneurolysis for Patients Undergoing Surgical Stabilization of Rib Fractures

What Is the Issue?

• Rib fractures pose a substantial clinical burden in patients with blunt trauma and result in significant pain and morbidity. Pain from rib fractures is often intense and prolonged, frequently lasting for several weeks following the injury. The adoption of surgical stabilization of rib fractures (SSRF) has emerged as a key therapeutic option for patients with severe rib fractures.

• Cryoneurolysis is a technology that delivers prolonged analgesia by applying a cryoablation probe at temperatures ranging from −40°C to −70°C for approximately 2 minutes to the intercostal nerves corresponding to the fractured rib levels. Cryoneurolysis has been used as an adjunct to SSRF to improve pain management and other outcomes after surgery.

• A comprehensive assessment of the comparative clinical effectiveness and cost-effectiveness of cryoneurolysis as an adjunct to SSRF through a rapid review is essential to examine potential benefits and harms compared with the existing pain management strategies.

What Did We Do?

• To inform decisions regarding the use of cryoneurolysis for pain management for people undergoing SSRF, we conducted a rapid review to summarize evidence that compared the clinical effectiveness and cost-effectiveness of cryoneurolysis to alternative pain management interventions not involving cryoneurolysis for people undergoing SSRF.

• We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020.

What Did We Find?

• We identified 6 retrospective cohort studies addressing the clinical effectiveness of cryoneurolysis in people undergoing SSRF:

  • Cryoneurolysis used as an adjunct to SSRF was associated with statistically significantly lower or similar postsurgery patient-reported pain intensity, opioid consumption, resource use, in-hospital complications, and adverse events compared to SSRF without cryoneurolysis or with alternative pain management strategies.

  • The statistically significant differences between cryoneurolysis and noncryoneurolysis groups were more evident in reduced postsurgery opioid consumption, and intensive care unit (ICU) and postoperative length of stay (LOS).

  • The certainty of evidence was limited, as all studies had a nonrandomized retrospective design.

• We did not find any studies on the relative cost-effectiveness of cryoneurolysis in people undergoing SSRF.

What Does This Mean?

• Cryoneurolysis may improve clinical outcomes in people undergoing SSRF by reducing postsurgery opioid consumption and resource use without increasing hospital complications and adverse events.

• Widespread implementation should be balanced against current evidence limitations, resource implications, and equity considerations.

• Because cryoneurolysis is typically available in specialized centres with established SSRF expertise, there is a risk of uneven access across regions and populations. Mechanisms such as referral pathways, training, or regional planning may be needed to support equitable access.

Research Questions

1. What is the clinical effectiveness of cryoneurolysis compared to pain management interventions not involving cryoneurolysis for patients undergoing surgical stabilization of rib fractures?

2. What is the cost-effectiveness of cryoneurolysis compared to pain management interventions not involving cryoneurolysis for patients undergoing surgical stabilization of rib fractures?

Context and Policy Issues

Pain Management After Rib Fractures

Rib fractures are common among patients with blunt trauma¹ and represent a significant subset of thoracic injuries treated in emergency care.² Rib fractures are a significant source of morbidity and mortality, especially among older adults.³ Pain from rib fractures, particularly with movement and breathing, is often intense and prolonged, frequently lasting for several weeks following the injury.^4,5 Inadequate pain management can result in less coughing, retained secretions, and increased bacterial colonization, which consequently elevate the risk of pneumonia.⁶ In addition, chest wall injuries and rib fractures may lead to long-term consequences, including persistent disability and reduced quality of life, commonly driven by chronic pain and respiratory fatigue.⁷

Addressing pain in this population remains a critical challenge and includes both surgical and nonsurgical strategies.^4,8 Standard nonoperative care worldwide typically consists of analgesia, pulmonary hygiene, and early mobilization.^4,6 Although the use of opioids remains a significant pain management strategy, their use has been linked to numerous adverse effects, including nausea, vomiting, respiratory depression, constipation, prolonged hospitalization, opioid tolerance, and substance use disorder.⁶ In addition, high doses of opioids for patients with rib fractures are associated with increased risks contributing to mortality, as opioids reduce respiratory drive and secretion clearance.^8,9 Consequently, there is a need for more effective pain management strategies that reduce dependence on short-term opioid-based therapies while improving pain control and overall patient outcomes.

What Is Surgical Stabilization of Rib Fractures?

Surgical stabilization of rib fractures (SSRF) has emerged as a safe and effective method for treatment of patients with severe rib injuries.^10,11 SSRF has been evaluated as an intervention to stabilize rib fractures and support pulmonary function.^10,11 Evidence from recent studies suggests that SSRF may be associated with improved pain control and reduced analgesic requirements, as well as shorter hospital and intensive care unit (ICU) length of stay (LOS), fewer days of mechanical ventilation, and a lower likelihood of tracheostomy. Some studies have also reported lower rates of pneumonia incidence and mortality among patients undergoing SSRF.^10,11 These observed effects are hypothesized to be related to improved chest wall stability and respiratory mechanics; however, the magnitude and consistency of these associations vary in the year following surgery.¹²

Pain management after SSRF is typically multimodal, combining regional anesthesia (e.g., epidural, paravertebral, erector spinae plane blocks, or cryoneurolysis), systemic nonopioid and opioid medications, and supportive pulmonary care.¹⁰ The primary objectives are to optimize analgesia, support pulmonary function, and minimize opioid-related harms. Management strategies are generally tailored to injury severity, patient comorbidities, and institutional expertise, and often evolve over the postoperative course.

What Is Cryoneurolysis?

Cryoneurolysis — also known as cryoneuroablation, cryoanalgesia, and intercostal nerve cryoablation (INCA) — was first introduced in the 1960s and has since emerged as a strategy for pain management, particularly for pain associated with specific surgeries.¹³ This technique delivers prolonged analgesia by applying a cryoablation probe to the intercostal nerves corresponding to the fractured rib levels at temperatures of approximately −70°C for about 2 minutes.¹³

Cryoneurolysis produces a localized and reversible injury to the targeted nerve while preserving the endoneurial, perineurial, and epineurial structures. Thermal neurolytic techniques are intended to interrupt peripheral pain signal transmission to the central nervous system, thereby reducing pain perception.¹⁴ Available evidence suggests that nerve conduction is temporarily reduced following treatment, with sensory function typically recovering over several months, commonly reported as occurring within 6 to 12 months.¹³

Cryoneurolysis has been associated with pain relief without permanent nerve injury and may avoid adverse effects on lower-extremity sensory or motor function.¹⁴ Some studies have also reported a lower incidence of complications such as urinary retention, infection, and opioid-related adverse effects.¹⁴ The technique has been evaluated in a range of chronic or refractory pain conditions, particularly when a discrete peripheral nerve can be identified as the primary pain source.^13,15

Cryoneurolysis for Management of Rib Fracture Pain

Cryoneurolysis for rib fracture pain may be delivered either during SSRF or as a separate procedure after SSRF.¹⁶ When performed during SSRF, it is typically done intraoperatively under direct visualization of the nerve, often through an open or thoracoscopic approach, allowing targeted ablation at the time of fixation.¹⁶ Cryoneurolysis may be performed after SSRF or independently of surgery for pain management after rib fractures, using a percutaneous, image-guided technique (most commonly ultrasound or CT), enabling treatment of ongoing pain without returning to the operating room.¹⁶ The choice of approach varies by institutional protocols, surgical workflow, and clinical context.¹⁶

Cryoneurolysis in Canada

In Canada, practice patterns for pain management after rib fractures — including after SSRF — are variable across trauma centres, but generally emphasize multimodal analgesia and individualized care.⁸

SSRF has historically been concentrated in higher-level trauma centres in Canada.¹⁷ In the context of Canada, level I and II trauma centres are typically the sites where advanced interventions (e.g., SSRF, cryoneurolysis, complex regional anesthesia), comprehensive access to trauma surgeons, subspecialty services, and trauma research are provided. Lower-level centres (levels III to IV) generally focus on initial assessment, resuscitation, stabilization, and transferring patients requiring SSRF to level I or II centres.¹⁸ Cryoneurolysis in Canada is currently in the early phase of clinical research use and limited to specialized practice for rib fracture pain.¹⁹ It has not yet been widely adopted as a standard treatment, with most activity taking place in select academic trauma centres and research settings, rather than as part of routine provincial health care delivery.¹⁹

Why Is It Important to Do This Review?

Cryoneurolysis offers prolonged analgesia for people undergoing SSRF.^16,20 However, its impact on patient outcomes — such as respiratory complications, LOS, functional limitations, and chronic pain — remains insufficiently established. In addition, this technique requires specialized equipment, training, and operating room resources, raising important questions about value for money within a publicly funded health system.²⁰ There is a need to synthesize evidence from studies evaluating clinical effectiveness and cost-effectiveness of cryoneurolysis, compared with alternative noncryoneurolysis pain management approaches, for people undergoing SSRF. A comprehensive assessment of cryoneurolysis through a rapid review is essential to evaluate potential benefits and harms compared with the existing pain management strategies, while balancing cost-effectiveness, within the health care context in Canada.

In mid-2025, policy decision-makers requested evidence to inform decisions regarding cryoneurolysis. To assess the available literature, Canada’s Drug Agency compiled a preliminary reference list of relevant research, which was used to prioritize 2 rapid reviews: cryoneurolysis for total knee arthroplasty and cryoneurolysis for SSRF.

Objectives

In response to an external request to support decision-making about cryoneurolysis, we prepared this rapid review to summarize and critically appraise available evidence regarding the clinical effectiveness and cost-effectiveness of cryoneurolysis compared to alternative pain management interventions not involving cryoneurolysis for people undergoing SSRF.

Methods

An information specialist conducted a customized literature search, balancing comprehensiveness with relevance, of multiple sources and grey literature on November 10, 2025.

One reviewer screened citations and selected studies based on the inclusion criteria presented in Table 1, and critically appraised the included publications using 1 critical appraisal tool.²¹ Appendix 1 presents a detailed description of methods and selection criteria for included studies.

Table 1: Selection Criteria

HTA = health technology assessment; RCT = randomized controlled trial; SR = systematic review.

Summary of Evidence

Quantity of Research Available

This report includes 6 publications^22-27 that met our inclusion criteria, all of which were nonrandomized studies and addressed question 1 (clinical effectiveness). No studies were identified that addressed question 2 (cost-effectiveness). We reported on the characteristics and results from the subset of relevant studies. Appendix 2 presents the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)²⁸ flow chart of the study selection.

Summary of Study Characteristics

Summaries of study characteristics are organized by research question. Appendix 3 provides details regarding the characteristics of included publications.

Included Studies for Question 1: Clinical Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

We identified 6 clinical studies addressing this question.^22-27 All studies were retrospective cohort studies.^22-27 Of these, 3 reported data from 1 centre,^24,25,27 2 from multiple centres,^23,26 and 1 from a national deidentified database.²² All studies were conducted in the US.^22-27

Across all studies, populations included adult participants older than 18 years of age undergoing SSRF for rib fractures described as blunt trauma (2 studies),^22,23 acute rib fractures (1 study),²⁴ traumatic rib fractures (2 studies),^25,27 and traumatic chest wall injury (1 study).²⁶ Comorbidities of other medical disorders were reported in 3 studies,^22,25,26 smoking in 3 studies,^22,25,27 and substance use disorders in 2 studies.^22,27 Two studies excluded participants with histories of opioid dependence.^24,26

All included clinical studies^22-27 provided information on the age and sex of participants; the authors did not report how sex was defined or measured. One study²⁵ reported on the race of participants. The authors of 2 studies^25,27 also provided information on body mass index. None of the included studies^22-27 provided participant information for other PROGRESS-Plus criteria,²⁹ such as place of residence, ethnicity, culture, language, occupation, religion, education, socioeconomic status, or social capital.

The study setting was described as level II or higher designated trauma centres located in urban settings in 1 study,²³ a level I trauma centre in 2 studies,^24,25 level I and III trauma centres in 1 study,²⁶ and a level II trauma centre in 1 study.²⁷ The setting was not reported in 1 study.²²

Five^23-27 out of 6 studies reported on the professional role of the person who administered cryoneurolysis; 4 studies^23,25-27 reported that the cryoneurolysis was conducted by surgeons, and 1 study reported that a single faculty member with trainee surgeons²⁴ administered the cryoneurolysis. All included studies^22-27 implemented cryoneurolysis during the SSRF.

Interventions and comparators included:

• cryoneurolysis versus no cryoneurolysis (4 studies)^22-25

• cryoneurolysis versus standard multimodal pain regimen (MMPR) (1 study)²⁶

• cryoneurolysis versus elastomeric infusion pump (EIP) (1 study).²⁷

All 6 studies reported more than 1 outcome on the clinical effectiveness of cryoneurolysis, including:

• pain intensity, including patient-reported postsurgery changes as well as pre- and postsurgery changes in numeric pain score (NPS) (4 studies)^24-27

• analgesic use, including postsurgery changes as well as pre- and postsurgery changes in opioid consumption in oral morphine milliequivalents (MME) (5 studies)^23-27

• resource use (6 studies),^22-27 including:

  • total hospital LOS (6 studies)^22-27

  • postoperative LOS (3 studies)^23,24,27

  • ICU admission or ICU LOS (4 studies)^22,24-26

  • operation times (1 study)²⁴

  • duration of mechanical ventilation (3 studies)^22,25,26

• in-hospital complications (4 studies),^22,24-26 including:

  • overall in-hospital complications (2 studies)^22,26

  • incidence of pneumonia (3 studies)^22,24,25

  • tracheostomy rates (3 studies)^24-26

  • return to operating room (2 studies)^22,26

  • pulmonary complications (3 studies)^22,26,27

  • intubation after surgery (4 studies)^24-263

  • other in-hospital complications (2 studies)^22,26

• postdischarge adverse events (2 studies),^26,27 including:

  • 30-day readmission (2 studies)^26,27

  • chest wall neuralgia or paresthesia (2 studies)^25,27

  • functional limitations (1 study)²⁵

  • long-term pain medications (2 studies)^24,25

  • minor medical complications (1 study)²⁵

• other outcomes (6 studies),^22-27 including:

  • discharge disposition (2 studies)^24,25

  • mortality rate (4 studies)^22,24-26

  • hospital charges (2 studies).^23,27

Four studies^24-27 reported on outcomes at follow-up after SSRF, which ranged from 30 days to 490 days.

Three studies conducted subgroup analyses on patients with flail chest,²² participants who were not sedated with opioid infusion,²⁶ and patients who were opioid-naive.²⁷

Included Studies for Question 2: Cost-Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

This rapid review did not identify relevant studies that addressed research question 2; therefore, no summary can be provided.

Summary of Critical Appraisal

Appendix 4 provides additional details about the strengths and limitations of the included publications.

Included Studies for Question 1: Clinical Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

The authors of the 6 included studies^22-27 provided clear descriptions of study aims, interventions, participant eligibility criteria, and main outcomes. Reporting quality was generally good, with clear descriptions of interventions and clinically relevant outcomes. Additional methodological strengths included the use of valid outcome measures and reporting estimates of random variability (e.g., confidence intervals) and exact P values across all studies.^22-27

Several factors affected the internal and external validity of the included studies. All studies^22-27 were observational and retrospective, with no randomized or prospective comparative designs, which increases the risk of confounding and selection bias and limits causal inference. Many important patient-centred and safety outcomes were not consistently reported.³²³ Because of the nature of the intervention (surgeon’s familiarity with the procedure, absence of contraindications), the decision to conduct the cryoneurolysis was left at the discretion of the operating surgeon performing SSRF in 4^23,25-27 out of 6 studies (1 study²² did not report on the person conducting the surgery). This could have resulted in systematic differences between intervention and comparator groups, potentially introducing bias into the estimates of treatment effects.

Although authors reported some relevant baseline participant characteristics (e.g., age, sex, body mass index), many important characteristics that stratify health opportunities and outcomes were not reported in the included studies, such as race, ethnicity, culture, language, place of residence, socioeconomic status, and other PROGRESS-Plus criteria.²⁹ As a result, it remains unclear whether the study population is representative and whether the findings of these studies conducted in the US can be generalized to settings in Canada. In addition, none of the included studies^22-27 included formal power calculations.

Across all studies,^22-27 authors reported their potential conflicts of interest related to their work; the authors of 3 studies^23,26,27 reported that they had paid affiliations with related medical device companies. Importantly, the authors of 2 studies^23,27 were paid to educate faculty by the medical company developing the cryoneurolysis probe used in these studies. This may have influenced the study’s findings. The authors of 4 studies^22,25-27 reported receiving no financial support for their studies, whereas sources of funding were not disclosed in 2 studies.^23,24

Overall, the studies varied in scope and strength. Smaller single-centre studies^24,25,27 contributed valuable information on feasibility, patient-reported pain intensity, opioid consumption, and postsurgery adverse outcomes, but were limited by small sample sizes, limited adjustment for confounders, and restricted generalizability. Larger multicentre and national database studies^22,23,26 improved external validity and assessment of system-level outcomes such as ICU LOS and in-hospital complications, although contextual details of interventions in various settings and patient-centred outcomes were often lacking.

Included Studies for Question 2: Cost-Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

This rapid review did not identify relevant studies that addressed research question 2; therefore, no appraisal can be provided.

Summary of Findings

Appendix 5 presents additional details regarding the main study findings.

Question 1: Clinical Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

Evidence regarding the clinical effectiveness of cryoneurolysis versus alternative pain management interventions for patients undergoing SSRF was available from 6 primary clinical studies.^22-27

Pain Intensity

Four studies^24-27 reported on the patient-reported postsurgery changes^25,26 as well as pre- and postsurgery changes^24,27 in pain intensity. One study²⁷ showed that receiving cryoneurolysis was associated with a statistically significant reduction in postoperative pain in NPS compared to the EIP group. The other 3 studies^24-26 did not show statistically significant differences in NPS for cryoneurolysis versus comparators (noncryoneurolysis^24,25 and MMPR²⁶).

Analgesic Use

Five studies^23-27 reported on analgesic use, including postsurgery changes^23,25,26 as well as pre- and postsurgery changes^24,27 in opioid consumption, in oral MME. Two studies indicated a statistically significant reduction in total^23,25 and daily²⁵ MME in those receiving cryoneurolysis compared to those not receiving cryoneurolysis after SSRF. One study²⁷ showed that receiving cryoneurolysis was associated with statistically significantly lower inpatient opioid use after SSRF compared to receiving EIP. One study²⁶ comparing cryoneurolysis to MMPR after SSRF indicated statistically significantly lower total and daily MME in the cryoneurolysis group, whereas differences in discharge MME were not statistically significant between groups. One study²⁴ comparing changes in opioid requirements in oral MME, between 12 hours before SSRF and the last 24 admission hours before discharge, did not show statistically significant differences between those receiving cryoneurolysis compared to those not receiving cryoneurolysis after SSRF.

Resource Use

All 6 included studies^22-27 reported on total hospital LOS after SSRF. Of these, 2 studies^23,26 showed statistically significantly shorter total hospital LOS with cryoneurolysis versus noncryoneurolysis²³ and MMPR²⁶ after SSRF.

Three studies reported on postoperative LOS after SSRF.^23,24,27 Of these, 2 studies showed statistically significantly shorter postoperative LOS with cryoneurolysis compared to EIP²⁷ and noncryoneurolysis.²³ The difference in postoperative LOS in 1 study²⁴ comparing cryoneurolysis to noncryoneurolysis was not statistically significant.

Four studies reported on ICU admission²⁴ or ICU LOS.^22,25,26 Three studies indicated that receiving cryoneurolysis after SSRF was associated with statistically significantly shorter ICU LOS compared to noncryoneurolysis^24,25 and MMPR.²⁶ The 1 study reporting on rate of ICU admission²⁴ showed no statistically significant differences for cryoneurolysis versus noncryoneurolysis.

One study²⁴ on operation time showed no statistically significant differences between those who received cryoneurolysis and those who did not receive cryoneurolysis for patients undergoing SSRF.

Three studies^22,25,26 reported on duration of mechanical ventilation: 1 study²⁶ indicated statistically significantly lower duration of mechanical ventilation in the group that received cryoneurolysis compared to those who received MMPR, whereas the differences in 2 studies comparing cryoneurolysis versus noncryoneurolysis were not statistically significant.

Other than these outcomes, none of the included studies reported on factors or outcomes related to human health resources, such as staff time, workflow impacts, or training and credentialing requirements for cryoneurolysis use.

In-Hospital Complications

Four studies^22,24-26 reported on outcomes related to in-hospital complications. Of the 2 studies^22,26 that reported on overall in-hospital complications, 1 study²² showed statistically significantly fewer complications in the cryoneurolysis group than in the noncryoneurolysis group, whereas the other study²⁶ did not report statistically significant differences between the cryoneurolysis and MMPR groups.

Out of the 3 studies^22,24,25 reporting on the incidence of pneumonia in those receiving cryoneurolysis versus those not receiving cryoneurolysis after SSRF, 1 study²² showed statistically significantly lower rates of ventilator-associated pneumonia in the cryoneurolysis group compared to the noncryoneurolysis group. The group differences in the other 2 studies^24,25 were not statistically significant.

Three studies reported on tracheostomy rates in groups receiving cryoneurolysis versus noncryoneurolysis^24,25 and MMPR.²⁶ Of these, 1 study²⁵ showed statistically significantly lower rates of tracheostomy in the cryoneurolysis group than in the noncryoneurolysis group.

Of the 2 studies^22,26 reporting on return to the operating room after SSRF, neither showed a statistically significant difference with cryoneurolysis versus comparators (i.e., noncryoneurolysis²² or MMPR²⁶).

Three studies^22,26,27 reported on pulmonary complications after SSRF. One study²² indicated statistically significantly fewer pulmonary complications with cryoneurolysis versus noncryoneurolysis; however, the differences between cryoneurolysis and MMPR²⁶ or EIP²⁷ were not statistically significant in 2 studies.

Four studies^22,24-26 reported on intubation after surgery. Two studies showed that a statistically significantly lower percentage of patients who received cryoneurolysis were intubated compared with those in the noncryoneurolysis²⁵ or MMPR groups.²⁶ The differences in 2 studies^22,24 comparing cryoneurolysis to noncryoneurolysis were not statistically significant.

Two studies^22,26 reported on other in-hospital complications after SSRF. In 1 study²⁶ reporting on unplanned reintubation, hardware removal, chest tube reinsertion, COVID+ [as reported by the study authors], and postoperative nerve block, authors did not find any statistically significant differences between those who received cryoneurolysis versus MMPR after surgery. The other study²² reported on cerebrovascular accidents, extremity compartment syndrome, delirium, acute respiratory distress syndrome, myocardial infarction, cardiac arrest, acute kidney injury, deep vein thrombosis, sepsis, and various infections (superficial, deep, and organ space surgical site infection, central line-associated bloodstream infection, and catheter-associated urinary tract infection). Participants who received cryoneurolysis showed a statistically significant reduction in extremity compartment syndrome and cerebrovascular accident events compared to those in the noncryoneurolysis group.²² Other group differences were not statistically significant in this study.²²

Postdischarge Adverse Events

Four studies^24-27 reported on short-term and long-term adverse events after SSRF, which ranged from 30 days to 490 days.

No statistically significant group differences were shown in 2 studies^26,27 reporting on post-discharge adverse events, including 30-day readmission and incidence of chest wall neuralgia at a 1-year follow-up.

One study²⁴ that reviewed long-term adverse events, to assess long-term safety, reported that patients who underwent SSRF with cryoneurolysis did not experience any functional limitations or other complications of cryoneurolysis, except for 1 patient (6%) who reported mild lateral chest wall paresthesia at a 6-month follow-up. Of those who did not receive cryoneurolysis, 1 patient reported difficulty sleeping due to chest wall pain at a 1-month follow-up. No statistical comparison was reported between groups for these adverse events. Authors did not find statistically significant differences in the proportion of patients requiring opioids or other pain medications at a follow-up of 2 weeks after discharge.²⁴

One study²⁵ reported on short-term (0 to 3 months) and long-term (3 to 6 months) follow-up of patients who received cryoneurolysis versus noncryoneurolysis after SSRF. The authors reported that short-term adverse events occurred in 86.3% of the patients receiving cryoneurolysis and 87.5% of patients in the noncryoneurolysis group. No statistical comparison was reported between groups for these adverse events.²⁵

Other Outcomes

All 6 included studies^22-27 reported on other outcomes. Of the 2 studies^24,25 that reported on discharge disposition, 1 study²⁵ found that those who received cryoneurolysis versus noncryoneurolysis after SSRF had a statistically significantly higher likelihood of being discharged to their home. The group differences in the other study²⁴ reporting on the percentage of people being discharged to home, long-term care hospitals, or skilled nursing and other facilities were not statistically significant.

Four studies^22,24-26 reported on mortality rate between those received cryoneurolysis versus noncryoneurolysis^22,24,25 or cryoneurolysis versus MMPR.²⁶ None of the group differences related to these outcomes were statistically significant.

Two studies^23,27 reported on hospital charges. One study²³ indicated statistically significantly lower postoperative hospital charges, and charges related to the day of surgery among those receiving cryoneurolysis versus the noncryoneurolysis group, despite similar total hospital charges. The other study²⁷ observed lower mean hospital costs in the cryoneurolysis group compared to the EIP group; however, this difference did not reach statistical significance.

Subgroup Analyses

Three studies^22,26,27 conducted subgroup analyses related to data from their research participants.

One study²² performed a subgroup analysis of patients with flail chest. The decreased ICU LOS in the cryoneurolysis versus noncryoneurolysis groups remained a statistically significant outcome in the flail chest subset.

One study²⁶ conducted analyses excluding participants who were sedated with opioid infusion. Total MME, hospital LOS, and ICU LOS remained statistically significant in both univariate and multivariable analyses.²⁶

The third study evaluated opioid dependence at 1 year following surgery for patients who were opioid-naive.²⁷ At discharge, patients who were opioid-naive and received cryoneurolysis were prescribed a statistically significantly lower median opioid dose than those who received EIP.

Question 2: Cost-Effectiveness of Cryoneurolysis for Patients Undergoing SSRF

We found no relevant evidence regarding the cost-effectiveness of cryoneurolysis for patients undergoing SSRF; therefore, no summary can be provided.

Limitations

Evidence Gaps

Despite a growing number of studies evaluating cryoneurolysis during SSRF, important gaps remain in the evidence base. No randomized controlled trials or well-designed prospective comparative studies were identified, limiting the ability to draw firm conclusions about comparative clinical effectiveness. Evidence is particularly limited for head-to-head comparisons with established analgesic modalities, such as thoracic epidural analgesia or paravertebral blocks.⁸

Several clinically relevant outcomes were either inconsistently reported or not reported, including long-term pain intensity, functional recovery, quality of life, return to work, and patient satisfaction.^22,23 Evidence is also lacking for many populations of interest, such as older adults with frailty, individuals with multiple comorbidities, and those with chronic pain or opioid use disorder, for whom analgesic strategies may have different risk and benefit profiles. An additional evidence gap is the lack of evidence on the effectiveness and other considerations for postoperative cryoneurolysis, as all included studies^22-27 applied cryoneurolysis intraoperatively during SSRF, leaving its impact when delivered after surgery unknown. Another limitation of the literature is the absence of data on human health resource implications of cryoneurolysis, as included studies did not assess staff time, workflow impacts, or training and credentialing requirements, limiting understanding of its feasibility and scalability in routine clinical practice.

Evidence on long-term outcomes remains sparse. Although cryoneurolysis is intended to provide analgesia for several months, few studies reported on long-term outcomes, such as postdischarge opioid use or pneumonia beyond the index hospitalization.^22-27 In addition, the available follow-up data were limited in duration, incomplete, and not systematic. Two single-centre studies^24,27 that included limited postdischarge follow-up data did not identify persistent neuropathic pain or long-term complications. However, these findings were based on small samples and were not powered to detect uncommon or delayed adverse events.

Large database studies²² and multicentre cohorts^23,26 did not capture outcomes related to long-term pain, opioid use, pulmonary complications, functional recovery, or quality of life. As a result, substantial uncertainty remains regarding the durability of analgesic benefit and long-term safety, highlighting an important gap in the evidence base.

The overall quantity of evidence is limited to a small number of observational studies conducted in a narrow range of settings. While findings are directionally consistent, the limited number of studies and their overlapping designs reduce confidence in the robustness of conclusions. The conclusions from findings rely heavily on outcomes such as opioid consumption and LOS rather than patient-reported outcomes. As a result, there is limited certainty regarding the strength of conclusions that can be drawn about the magnitude of benefit associated with cryoneurolysis for SSRF.

This rapid review did not identify any relevant evidence regarding the cost-effectiveness of cryoneurolysis in people undergoing SSRF. This limits the ability to evaluate their economic value. Without evidence on costs relative to health and/or social outcomes, policy-makers may face challenges in how to allocate scarce resources and how to prioritize cryoneurolysis implementation over other alternative pain management after SSRF.

Generalizability

Generalizability of findings is constrained by the clinical and institutional contexts in which the studies were conducted. Most studies were performed in high-volume trauma centres with established SSRF programs and access to specialized surgical and anesthetic expertise.^23-25,27 Patients included in these studies often had injury patterns and clinical trajectories that may not reflect those seen in smaller or rural hospitals.^22,23 The lack of standardization across centres regarding both the number of nerves cryoablated and the ablation technique limits comparability across studies.^22,23,26 It remains unclear whether similar outcomes would be achieved in settings without comparable resources, experience, or multidisciplinary pain management infrastructure.

Applicability to Clinical Practice in Health Care Context in Canada

The applicability of the findings to clinical practice in Canada is uncertain, as none of the included studies were conducted in Canada. Differences in trauma system organization, access to SSRF, availability of cryoneurolysis technology, and postoperative pain management pathways may influence both feasibility and effectiveness in the context of Canada. System-level considerations in publicly funded care — such as operating room time, staffing, and costs — are particularly relevant, and without evidence from hospitals in Canada, findings should be interpreted cautiously.

Equity Considerations

Equity considerations are largely absent from the current literature. None of the studies reported outcomes stratified by sex, gender, race, ethnicity, socioeconomic status, or rurality, nor did they address barriers to accessing SSRF or cryoneurolysis. This limits understanding of whether the benefits of cryoneurolysis are equitably distributed or whether certain groups may face disproportionate barriers to access. Additionally, because cryoneurolysis is typically available in specialized centres,^23-25,27 there are concerns that its adoption could exacerbate existing disparities in trauma care, particularly for patients living in rural or remote communities and those with limited access to tertiary trauma services. The absence of patient engagement data further limits insight into patient-valued outcomes and equity-related impacts.

Conclusions and Implications for Decision- or Policy-Making

This rapid review evaluated the literature regarding the clinical effectiveness and cost-effectiveness of cryoneurolysis compared with alternative noncryoneurolysis pain management interventions for people undergoing SSRF. We identified 6 retrospective cohort studies^22-27 addressing clinical effectiveness and no studies evaluating the cost-effectiveness of cryoneurolysis.

Summary of Evidence

Results from the 6 included studies^22-27 suggest that cryoneurolysis used during SSRF is generally associated with improved postoperative pain-related outcomes compared with SSRF without cryoneurolysis or with alternative pain management strategies (i.e., MMPR²⁶ or EIP²⁷). Benefits were most consistently observed for reduced opioid consumption, lower pain scores, and shorter postoperative and ICU LOS, with no evidence of increased complications. Subgroup analyses across 3 studies showed that cryoneurolysis was associated with shorter ICU or hospital LOS and reduced opioid use.^22,26,27 Among patients who were opioid-naive, cryoneurolysis was linked to lower opioid prescribing at discharge and no reported long-term opioid use at 1 year.²⁷

Earlier research²⁴ established the technical feasibility and short-term safety of cryoneurolysis used during SSRF, whereas subsequent single-centre and multicentre cohort studies demonstrated consistent reductions in opioid consumption, as well as shorter postoperative or ICU LOS compared with SSRF without cryoneurolysis^23,25 or with other analgesic strategies.^26,27 Importantly, the national database analysis²² extended these findings to a system level, suggesting that improved analgesia may result in fewer serious in-hospital complications and reduced ICU utilization.

Although causality cannot be established, the convergence of findings across diverse settings and outcomes strengthens confidence that cryoneurolysis may provide incremental clinical benefit within SSRF pathways. However, limitations in the evidence base highlight the need for randomized and longitudinal research.

Despite the review’s intention to assess economic evidence, no studies evaluating cost-effectiveness were identified. However, all included studies provided direct^23,27 and indirect^22-27 information on cost and resource use about the economic implications of cryoneurolysis used during SSRF. Across studies that reported financial outcomes, cryoneurolysis was not associated with higher overall hospital costs²⁷ and, in some cases, was linked to lower postoperative charges²³ and resource use.^22,23,27 Importantly, no study reported increased LOS or complication-related costs attributable to cryoneurolysis.

Overall, while the available evidence suggests cryoneurolysis is unlikely to increase costs and may be cost-neutral or cost-saving in some settings, economic conclusions remain uncertain. There is a need for robust cost-effectiveness analyses incorporating procedural costs, human health resource implications, downstream resource use, and longer-term outcomes.

Considerations for Future Research

Future research should focus on generating comparative evidence to clarify the independent effectiveness of cryoneurolysis during SSRF. Prospective and, where feasible, randomized controlled trials comparing cryoneurolysis with established analgesic strategies are needed to reduce uncertainty and better define its role within multimodal pain management pathways.

Research should also prioritize patient-reported and longer-term outcomes, including functional recovery, chronic pain, and sustained opioid use, while improving representation across care settings and equity-deserving populations. Finally, integrating robust economic evaluations into future studies is essential to determine the value of cryoneurolysis within publicly funded health care systems.

Considerations for Clinical Practice or Considerations for Decision- or Policy-Making

Cryoneurolysis may offer meaningful benefits in postoperative pain management, particularly through opioid-sparing effects and potential reductions in postoperative and ICU LOS. These benefits appear to be achieved without an observed increase in complications, which supports the consideration of cryoneurolysis as an adjunct within specialized SSRF programs. However, decisions about adoption should be made in the context of limited certainty, as the evidence is derived entirely from observational studies conducted in a limited number of high-volume trauma centres. Cryoneurolysis should therefore be viewed as a potentially beneficial option for pain management; however, its use may be most appropriate in centres with established SSRF expertise, multidisciplinary pain management teams, and the technical capacity to perform the procedure safely.

In addition, the generalizability of findings to the context of Canada and its health care systems is limited, as none of the included studies were conducted in Canada. The absence of robust cost-effectiveness evidence warrants a cautious and context-sensitive approach. While available data suggest that cryoneurolysis is unlikely to increase overall hospital costs and may reduce downstream resource use, these findings are indirect and dependent on the setting and country. Phased or selective implementation approaches, along with the systematic collection of data on clinical outcomes, resource use, and patient-reported experiences, could help inform future decision-making.

Because cryoneurolysis is typically available in specialized or high-level trauma centres with established SSRF programs, experienced surgical teams, and advanced pain management infrastructure, findings may not be directly generalizable to lower-level trauma centres where SSRF is less common and access to cryoneurolysis expertise and resources may be limited. As a result, there is a risk of uneven access across regions and populations.¹³ Targeted strategies, such as referral pathways, training, or regional planning, may be required to support equitable access.

Overall, cryoneurolysis may be considered a beneficial adjunct for pain management for individuals undergoing SSRF within appropriate clinical contexts; however, broader implementation should be balanced against current evidence limitations, resource implications, and equity considerations, with ongoing evaluations to reduce uncertainty over time.

References

1.Mayberry JC, Trunkey DD. The fractured rib in chest wall trauma. Chest Surg Clin N Am. 1997;7(2):239-61. PubMed

2.Racine S, Émond M, Audette-Côté JS, et al. Delayed complications and functional outcome of isolated sternal fracture after emergency department discharge: a prospective, multicentre cohort study. CJEM. 2016;18(5):349-57. doi:10.1017/cem.2016.326 PubMed

3.Bergeron E, Lavoie A, Clas D, et al. Elderly trauma patients with rib fractures are at greater risk of death and pneumonia. J Trauma. 2003;54(3):478-85. doi:10.1097/01.Ta.0000037095.83469.4c PubMed

4.Stopenski S, Binkley J, Schubl SD, Bauman ZM. Rib fracture management: A review of surgical stabilization, regional analgesia, and intercostal nerve cryoablation. Surg Pract Sci. 2022;10:100089. doi:10.1016/j.sipas.2022.100089 PubMed

5.Fabricant L, Ham B, Mullins R, Mayberry J. Prolonged pain and disability are common after rib fractures. Am J Surg. 2013;205(5):511-5. doi:10.1016/j.amjsurg.2012.12.007 PubMed

6.Hammal F, Chiu C, Kung JY, Bradley N, Dillane D. Pain management for hospitalized patients with rib fractures: A systematic review of randomized clinical trials. J Clin Anesth. Feb 2024;92:111276. doi:10.1016/j.jclinane.2023.111276 PubMed

7.Marasco S, Lee G, Summerhayes R, Fitzgerald M, Bailey M. Quality of life after major trauma with multiple rib fractures. Injury. 2015;46(1):61-5. doi:10.1016/j.injury.2014.06.014 PubMed

8.Yu S, Patton P, Vogt K, et al. Examining Canadian trauma centres' analgesic protocols for rib fractures. West J Emerg Med. 2025;26(5):1367-73. doi:10.5811/westjem.24945 PubMed

9.Karmakar MK, Ho AM. Acute pain management of patients with multiple fractured ribs. J Trauma. Mar 2003;54(3):615-25. doi:10.1097/01.Ta.0000053197.40145.62 PubMed

10.Fokin AA, Hus N, Wycech J, Rodriguez E, Puente I. Surgical stabilization of rib fractures: indications, techniques, and pitfalls. JBJS Essent Surg Tech. 2020;10(2):e0032. doi:10.2106/jbjs.St.19.00032 PubMed

11.Shaban Y, Frank M, Schubl S, et al. The History of surgical stabilization of rib fractures (SSRF). Surg Pract Sci. 2022;10:100084. doi:10.1016/j.sipas.2022.100084 PubMed

12.Caragounis EC, Fagevik Olsén M, Pazooki D, Granhed H. Surgical treatment of multiple rib fractures and flail chest in trauma: a one-year follow-up study. World J Emerg Surg. 2016;11:27. doi:10.1186/s13017-016-0085-2 PubMed

13.Law L, Rayi A, Hendrix JM, Derian A. Cryoanalgesia. StatPearls Publishing LLC. Accessed December 22, 2025, https://www.ncbi.nlm.nih.gov/books/NBK482123/

14.Biel E, Aroke EN, Maye J, Zhang SJ. The applications of cryoneurolysis for acute and chronic pain management. Pain Pract. 2023;23(2):204-215. doi:10.1111/papr.13182 PubMed

15.Huang J, Delijani K, El Khudari H, Gunn AJ. Intercostal cryoneurolysis. Semin Intervent Radiol. 2022;39(2):167-171. doi:10.1055/s-0042-1745763 PubMed

16.Muldiiarov V, Bauman ZM. Role of intercostal nerve block and cryoneurolysis in the management of rib fractures: a narrative review. Current Challenges in Thoracic Surgery. 2025;7

17.Kane ED, Jeremitsky E, Pieracci FM, Majercik S, Doben AR. Quantifying and exploring the recent national increase in surgical stabilization of rib fractures. J Trauma Acute Care Surg. 2017;83(6):1047-1052. doi:10.1097/ta.0000000000001648 PubMed

18.Caminsky NG, Wong EG. Trauma systems in Canada: striving for quality across an expansive landmass. Emergency and Critical Care Medicine. 2023;3(3):89-93. doi:10.1097/ec9.0000000000000102

19.Jew MK, Evtushevski B, Liang J, Wang KH. Ultrasound-guided, percutaneous cryoneurolysis of intercostal nerves in high-risk, traumatic rib fracture patients. Reg Anesth Pain Med. 2025;05:05. doi:10.1136/rapm-2025-106973

20.Cha PI, Min JG, Patil A, Choi J, Kothary NN, Forrester JD. Efficacy of intercostal cryoneurolysis as an analgesic adjunct for chest wall pain after surgery or trauma: Systematic review. Review. Trauma Surgery and Acute Care Open. 2021;6(1)e000690. doi:10.1136/tsaco-2021-000690 PubMed

21.Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377-384. doi:10.1136/jech.52.6.377 PubMed

22.Aryan N, Nahmias J, Grigorian A, et al. Inpatient outcomes of intercostal nerve cryoablation with surgical rib fixation. Journal of Surgical Research. 2024;303:105-110. doi:10.1016/j.jss.2024.08.022 PubMed

23.Bauman ZM, Loftus J, Raposo-Hadley A, et al. Surgical stabilization of rib fractures combined with intercostal nerve cryoablation proves to be more cost effective by reducing hospital length of stay and narcotics. Injury. 2021;52(5):1128-1132. doi:10.1016/j.injury.2021.02.009 PubMed

24.Choi J, Min JG, Jopling JK, Meshkin S, Bessoff KE, Forrester JD. Intercostal nerve cryoablation during surgical stabilization of rib fractures. Conference Paper. Journal of Trauma and Acute Care Surgery. 2021;91(6):976-980. doi:10.1097/ta.0000000000003391 PubMed

25.Fernandez CA, Narveson JR, Niu F, et al. In-hospital outcomes of intercostal nerve cryoablation and surgical stabilization of rib fractures. Journal of Trauma and Acute Care Surgery. 2022;93(5):695-701. doi:10.1097/ta.0000000000003623 PubMed

26.Marturano MN, Thakkar V, Wang H, et al. Intercostal nerve cryoablation during surgical stabilization of rib fractures decreases post-operative opioid use, ventilation days, and intensive care days. Injury. 2023;54(9)110803. doi:10.1016/j.injury.2023.05.034 PubMed

27.O'Connor LA, Houseman B, Cook T, Quinn CC. Intercostal cryonerve block versus elastomeric infusion pump for postoperative analgesia following surgical stabilization of traumatic rib fractures. Injury. 2023;54(11) 111053. doi:10.1016/j.injury.2023.111053 PubMed

28.Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. doi:10.1136/bmj.n160 PubMed

29.O'Neill J, Tabish H, Welch V, et al. Applying an equity lens to interventions: using PROGRESS ensures consideration of socially stratifying factors to illuminate inequities in health. J Clin Epidemiol. 2014;67(1):56-64. doi:10.1016/j.jclinepi.2013.08.005 PubMed

30.Canada’s Drug Agency. Canada's Drug Agency Style: A Guide for Authors and Editors. 2025. Accessed December 22, 2025. https://www.cda-amc.ca/sites/default/files/pdf/style_guide_2025_digital.pdf

Appendix 1: Detailed Methods and Selection of Included Studies

Please note that this appendix has not been copy-edited.

What Is a Rapid Review?

Rapid reviews are based on accelerated and abbreviated systematic review methods, balancing timeliness with rigour, to allow for timely decision-making. Due to these abbreviated methods, rapid reviews have some limitations. For example, following full-text review, the research questions and eligibility criteria were refined to align with project timelines and to focus the rapid review on SSRF, the priority area identified by the customer. This decision was informed by the review’s initial aim to examine chest wall surgery more broadly, with SSRF identified as the highest-priority topic for the customer. In addition, unlike in systematic reviews, for which at least 2 independent reviewers are needed to screen studies to reduce selection bias, a single reviewer was required to include, extract the data, and appraise a study. Similarly, we included studies published from 2020, excluding older studies. Albeit, focusing on more recently published articles may be more reflective of current practices. Our rapid review intends to summarize the available evidence, rather than provide recommendations. These findings should not be interpreted as prescriptive guidance.

Literature Search Methods

An information specialist conducted a literature search on key resources including MEDLINE, the Cochrane Database of Systematic Reviews, the International HTA Database, the websites of health technology assessment (HTA) agencies in Canada and major international HTA agencies, as well as a focused internet search. The search approach was customized to retrieve a limited set of results, balancing comprehensiveness with relevance. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. Search concepts were developed based on the elements of the research questions and selection criteria. The main search concepts were cryoneurolysis and chest surgery. Search filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, or indirect treatment comparisons, randomized controlled trials, controlled clinical trials, or any other type of clinical trial, observational studies, economic studies, and citations related to health utilities or quality of life. Conference reviews, conference abstracts, and clinicaltrials.gov records were excluded. Retrieval was limited to the human population. The search was completed on November 10, 2025, and limited to English-language documents published since January 1, 2020. The search strategy is available on request.

Selection Criteria and Methods

One reviewer screened citations and selected studies examining the clinical effectiveness and cost-effectiveness of cryoneurolysis for patients undergoing chest wall surgery. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. Following full-text review, the scope of the review was further refined to focus on SSRF, reflecting a modification of the original research questions and inclusion criteria to align with project timelines and the priority area. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Exclusion Criteria

Articles were excluded if they:

• did not meet the selection criteria outlined in Table 1

• were focused on using cryoneurolysis for chest surgeries other than SSRF

• were duplicate publications or were published before 2020

• were of any design published only as abstracts, conference proceedings, presentations, thesis documents, or preprints

• were single-arm before-and-after studies, case studies, and case reports

• were published in languages other than English (for feasibility reasons).

Critical Appraisal of Individual Studies

The included publications were critically appraised by 1 reviewer using the Downs and Black checklist²¹ for randomized and nonrandomized studies as a guide. Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.

Data Extraction

One reviewer extracted data directly into standardized tables created in Microsoft Word, which were modified as necessary. The extracted information included study characteristics, methodology (e.g., study design), population, intervention, comparator, and results regarding the outcomes of interest.

One reviewer extracted information from the included studies using the PROGRESS-Plus²⁹ tool to describe different population groups. Each included study was checked to determine if PROGRESS-Plus²⁹ criteria were reported by study authors to describe the participants; detailed characteristics, if available, were then extracted and reported in tables in Appendix 2. The main PROGRESS-Plus²⁹ criteria include place of residence; race, ethnicity, culture, and/or language; occupation; gender and/or sex; religion; education; socioeconomic status; and social capital. As part of report writing, we discuss these characteristics across the evidence, where available, when presenting results within the text.

When reporting on sex, gender, race, or ethnicity in this rapid review, we planned to retain the language used by the original study authors, and, whenever possible, we referred to these groups based on guidance from Canada’s Drug Agency Style: A Guide for Authors and Editors³⁰ at the time this rapid review was conducted, with an understanding that language is constantly evolving.

Appendix 2: Selection of Included Studies

Please note that this appendix has not been copy-edited.

Figure 1: Selection of Included Studies — PRISMA²⁸ Flow Chart of Selected Reports

PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analyses.

Appendix 3: Characteristics of Included Publications

Please note that this appendix has not been copy-edited.

Table 2: Characteristics of Included Primary Clinical Studies

AIS = abbreviated injury scale; BMI = body mass index; bpm = beats per minute; CAUTI = catheter-associated urinary tract infection; CLABSI = central line-associated bloodstream infection; COPD = chronic obstructive pulmonary disease; EIP = elastomeric infusion pump; GCS = Glasgow coma score; HLOS = hospital length of stay; ICU = intensive care unit; IQR = interquartile range; ISS = injury severity score; LOS = length of stay; MME = morphine milliequivalents; MMPR = multimodal pain regimen; NA = not applicable; NOS = not otherwise specified; NPS = numeric pain score; NR = not reported; SD = standard deviation; SSI = surgical site infection; SSRF = surgical stabilization of rib fractures; vs. = versus.

^aIntervention group vs. comparator group, respectively.

^bSignificant differences between groups (defined as P < 0.05).

^cThe main PROGRESS-Plus criteria include place of residence, race, ethnicity, culture, language, occupation, gender, sex, religion, education, socioeconomic status, and social capital, personal characteristics associated with discrimination (e.g., age, disability), features of relationships, and time-dependent relationships.²⁹

^dMore than 22 breaths per minute.

^eSystolic blood pressure less than 90 mm Hg.

^fOpioid tolerance was defined as daily use within 2 weeks before presentation and duration of use more than 4 weeks, illicit drug use with positive urine or serum toxicology results.

^gChange was recorded at baseline (24 hours before surgery) and on postoperative days 1 to 3.

^hChange measured by generalized estimating equation comparing 12 hours before SSRF and the last 24 admission hours.

Appendix 4: Critical Appraisal of Included Publications

Please note that this appendix has not been copy-edited.

Table 3: Strengths and Limitations of Primary Clinical Studies Using the Downs and Black Checklist²¹

AIS = abbreviated injury scale; CI = confidence interval; IQR = interquartile range; LOS = length of stay; MME = morphine milliequivalents; SSRF = surgical stabilization of rib fractures.

Appendix 5: Main Study Findings

Please note that this appendix has not been copy-edited.

Table 4: Summary of Findings by Outcome — Pain Intensity

Cryo = cryoneurolysis; IQR = interquartile range; MMPR = multimodal pain regimen; NPS = numeric pain score; SE = standard error; SSRF = surgical stabilization of rib fractures.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

^aChange measured by generalized estimating equation comparing 12 hours before SSRF and last 24 admission hours.

Table 5: Summary of Findings by Outcome — Association of Cryo vs. EIP and Patient-Reported NPS

CI = confidence interval; Cryo = cryoneurolysis; df = degrees of freedom; EIP = elastomeric infusion pump; SE = standard error.

^aA linear mixed-effects model was used to estimate the association of Cryo and EIP on patients’ outcomes while controlling for other covariates, including opioid tolerance, sex, age, number of ribs fractured, number of ribs fixed, rib injury severity score (ISS), trauma ISS, presence of flail segment, smoking status, and postoperative length of stay.

Table 6: Summary of Findings by Outcome — Analgesic Use

Cryo = cryoneurolysis; EIP = elastomeric infusion pump; IQR = interquartile range; MME = morphine milliequivalents; MMPR = multimodal pain regimen; rSE = robust standard error; SSRF = surgical stabilization of rib fractures.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

^aChange measured by generalized estimating equation comparing 12 hours before SSRF and the last 24 admission hours.

Table 7: Summary of Findings by Outcome — Association of Cryo vs. EIP and Opioid Consumption in Oral MME (mg)

CI = confidence interval; Cryo = cryoneurolysis; df = degrees of freedom; EIP = elastomeric infusion pump; MME = morphine milliequivalents; SE = standard error; vs. = versus.

^aA linear mixed-effects model was used to estimate the association of Cryo and EIP on patients’ outcomes while controlling for other covariates, including opioid tolerance, sex, age, number of ribs fractured, number of ribs fixed, rib injury severity score (ISS), trauma ISS, presence of flail segment, smoking status, and postoperative length of stay.

Table 8: Summary of Findings by Outcome — Resource Use

CI = confidence interval; Cryo = cryoneurolysis; EIP = elastomeric infusion pump; ICU = intensive care unit; IQR = interquartile range; LOS = length of stay; MMPR = multimodal pain regimen; noncryo = no cryoneurolysis.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

Table 9: Summary of Findings by Outcome — In-Hospital Complications

CAUTI = catheter-associated urinary tract infection; CLABSI = central line-associated bloodstream infection; Cryo = cryoneurolysis; IQR = interquartile range; MMPR = multimodal pain regimen; noncryo = no cryoneurolysis; NR = not reported; SSI = surgical site infection; vs. = versus.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

Table 10: Summary of Findings by Outcome — Association of Cryo vs. EIP With In-Hospital Complications Related to Pulmonary Function^a

CI = confidence interval; Cryo = cryoneurolysis; df = degrees of freedom; EIP = elastomeric infusion pump; SE = standard error; vs. = versus.

^aPulmonary function is reflected by incentive spirometry (IS) effort in mL.

^bA linear mixed-effects model was used to estimate the association of Cryo and EIP on patients’ outcomes while controlling for other covariates, including opioid tolerance, sex, age, number of ribs fractured, number of ribs fixed, rib injury severity score (ISS), trauma ISS, presence of flail segment, smoking status, and postoperative length of stay.

Table 11: Summary of Findings by Outcome — Postdischarge Adverse Events

Cryo = cryoneurolysis; EIP = elastomeric infusion pump; MMPR = multimodal pain regimen; NA = not applicable; noncryo = no cryoneurolysis; NR = not reported; vs. = versus.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

^aMinor medical complications included incisional infection, delayed wound healing, small pleural effusion, residual pneumothorax, and seroma formation.

^bShort-term (0 to 3 months) functional limitations included vocal cord paralysis, scapular winging, and scapular or clavicular pain.

^cLong-term (3 to 6 months) functional limitations included hardware infection (n = 1), neuropathic pain (n = 3), and functional limitations associated with winging scapula.

Table 12: Summary of Findings by Outcome — Other

Cryo = cryoneurolysis; EIP = elastomeric infusion pump; IQR = interquartile range; MMPR = multimodal pain regimen; noncryo = no cryoneurolysis; NR = not reported; SD = standard deviation; vs. = versus.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

Table 13: Summary of Findings — Subgroup Analysis

Cryo = cryoneurolysis; EIP = elastomeric infusion pump; ICU = intensive care unit; IQR = interquartile range; LOS = length of stay; MME = morphine milliequivalents; MMPR = multimodal pain regimen; noncryo = no cryoneurolysis; NPS = numeric pain score; NR = not reported; SD = standard deviation; vs. = versus.

Note: Bold numbers are representing significant P values, defined as P < 0.05.

^aOnly this outcome was reported from the subgroup analysis on patients with flail chest.

^bAnalyses were adjusted for age, underlying lung disease, number ribs broken, injury severity score, and preoperative peripheral nerve block.

^cAnalysis was adjusted for age.