Intraoperative intercostal nerve cryoablation vs. patient-controlled analgesia after thoracotomy: a single-center retrospective cohort study demonstrating comparable early pain and opioid use

Abstract

Background and Aims

Thoracotomy is among the most painful surgical procedures and is associated with a high risk of chronic postoperative pain. Optimizing perioperative analgesia is essential for enhancing recovery and reducing opioid-related side effects. This study evaluated whether adding intraoperative intercostal nerve cryoablation to standard postoperative analgesia improves pain control and reduces opioid use following thoracotomy.

Materials and methods

This retrospective cohort study included patients who underwent thoracotomy at a tertiary cancer center in 2024. Patients receiving intraoperative intercostal nerve cryoablation in addition to standard postoperative analgesia (n = 32) were compared with patients receiving standard postoperative analgesia alone (n = 33). Primary outcomes were pain scores at multiple postoperative intervals and opioid usage, converted into morphine milligram equivalents (MME).

Results

Baseline demographics were comparable between groups. Mean pain scores did not differ significantly at 30 min (2.3 vs. 2.3; p = 0.97), Day 1 (2.9 vs. 2.9; p = 0.40), or Day 2 (2.9 vs. 2.9; p = 0.99). Opioid requirements were also similar on Day 1 (14.8 vs. 13.9 mg MME, p = 0.56) and Day 2 (17.7 vs. 20.6 mg MME, p = 0.22). On Day 3, statistical comparison was not applicable due to PCA discontinuation, though mean opioid use was comparable. Female patients reported higher Day 1 pain scores (3.0 vs. 2.8; p = 0.03), without differences in opioid consumption.

Conclusions

The addition of intercostal nerve cryoablation was not associated with improved postoperative pain control or reduced opioid use. These findings support cryoablation as a feasible component of multimodal analgesia after thoracotomy. Larger prospective trials with long-term follow-up are warranted to clarify its role in thoracic enhanced recovery pathways.

Introduction

Severe postoperative pain is common after thoracotomy due to rib spreading and intercostal nerve trauma [1]. Inadequate pain control impairs ventilation, delays mobilization, and predisposes patients to pulmonary complications such as atelectasis and pneumonia [2].

Current analgesic strategies include intravenous patient-controlled analgesia (PCA), thoracic epidural analgesia, and paravertebral or fascial plane blocks [3, 4]. While effective, these modalities have limitations: PCA is opioid-dependent and associated with nausea, sedation, and respiratory depression [5]; epidural and paravertebral blocks may be technically challenging or contraindicated in patients with coagulopathy [6]. Consequently, there is a need for alternative strategies that provide reliable analgesia while minimizing opioid use and procedure-related risks.

Intercostal nerve cryoablation, more accurately termed cryoneurolysis when used for postoperative pain control, is an intraoperative technique in which extreme cold is applied to intercostal nerves using a cryoprobe, typically at − 60 °C for 60–120 s, thereby interrupting nociceptive transmission but allowing regeneration over several weeks [7]. This results in prolonged postoperative analgesia that may extend beyond the immediate perioperative period [7]. Although generally considered safe, cryoablation is associated with potential adverse effects including transient chest wall numbness, sensory disturbances, intercostal neuralgia, neuropathic pain, and, rarely, traumatic neuroma formation, Isolated reports of procedural complications such as chest wall hematoma and pneumothorax have also been described [7, 8]. Nevertheless, cryoablation primarily targets somatic intercostal nerve pain and may not adequately address visceral or chest wall reconstruction–related pain, which are common components of oncologic thoracotomy. Despite this promise, its role in adult thoracotomy remains inadequately established, with variable results reported in clinical studies.

Despite growing interest internationally, there are no published data from the Middle East on cryoablation in thoracic surgery. This study therefore aimed to evaluate whether the addition of intraoperative intercostal nerve cryoablation to standard postoperative analgesia, including intravenous patient-controlled analgesia (PCA), improves postoperative pain control and reduces opioid consumption following thoracotomy at a tertiary cancer center in Jordan.

Materials and methods

Study design and setting

We conducted a single-center, retrospective cohort study of consecutive adult patients who underwent open thoracotomy at King Hussein Cancer Center (Amman, Jordan) between June 2024 - December 2024.

Surgical technique and analgesia regimens

All thoracotomies were performed using standardized open approaches.

Intraoperative anesthetic management was performed according to routine clinical practice. Opioid administration, primarily intravenous morphine, and anesthetic adjuncts were similar in both groups and were administered at the discretion of the attending anesthesiologist.

Cryoablation group

Following completion of the primary thoracic procedure, a cryoprobe was applied directly to the intercostal nerves adjacent to the thoracotomy incision. Each nerve was frozen at − 60 °C for 60 s per cycle. Typically, three intercostal levels above and three below the incision were treated, depending on incision length. Following surgery, patients also received standard intravenous morphine patient-controlled analgesia (PCA) and multimodal analgesia identical to that used in the control group.

Control Group

Patients received standard opioid analgesia via programmable intravenous morphine PCA pumps (2 mg demand dose, 10-minute lockout).

Adjunct multimodal analgesia (both groups)

All patients received paracetamol (1 g every 8 h) and non-steroidal anti-inflammatory drugs (NSAIDs) unless contraindicated.

By postoperative Day 3, PCA was routinely discontinued as patients were typically clinically improving, mobilizing, and being prepared for chest tube removal and discharge. From Day 3 onward, analgesia was transitioned to oral-based regimens including paracetamol and ibuprofen (unless contraindicated), with oral morphine provided as needed.

Inclusion/exclusion Criteria

• Inclusion: Adults ≥ 18 years undergoing elective thoracotomy during the study period, who underwent intraoperative intercostal nerve cryoablation in addition to standard postoperative analgesia or received standard postoperative analgesia alone.

• Exclusion: Patients with pre-existing chronic pain, incomplete medical records, or use of alternative analgesic modalities, patient refusal and emergent thoracotomies.

Selection criteria

Selection of analgesic modality was based on routine clinical practice and was influenced by surgeon preference, anesthesiology team availability, and patient consent following preoperative discussion. Patients undergoing emergent thoracotomy were excluded, as analgesic modality could not be prospectively discussed in these cases.

Data collection

Collected variables included demographics (age, sex, BMI), postoperative pain scores (numeric rating scale from 0 to 10 at 30 min, Day 1, Day 2, Day 3), and cumulative opioid use converted to oral morphine milligram equivalents (MME). Because many patients had been discharged or were in the process of discharge by postoperative Day 3, complete and standardized opioid data were not consistently available, and therefore statistical comparison of Day 3 opioid use between groups was not performed.

Statistical analysis

Continuous variables were analyzed with t-tests or Mann-Whitney U tests. Categorical data were analyzed with chi-square or Fisher’s exact tests. A p-value < 0.05 was considered statistically significant.

Pain score distributions were visually assessed and were considered suitable for parametric reporting as means ± standard deviations.

Ethical consideration

The study protocol was approved by the institutional review board (IRB approval no. 24 KHCC 244). The requirement for informed consent was waived due to the retrospective design. All patient data were de-identified and handled in accordance with institutional and international policies.

This study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational cohort studies.

Results

Patient demographics

A total of 65 patients were included: 32 in the cryoablation group and 33 in the standard opioid group. The median age of the cohort was 59 years (range, 21–79), and 60.9% were male. Baseline demographic characteristics, including age, sex, and BMI, were comparable between groups (Table 1).

Table 1.

Patient Demographics

Variable	Cryoablation (n = 32)	Standard PCA group (n = 33)
Age (median, years)	59 (21–79)	58 (22–78)
BMI (mean, kg/m²)	28.7 ± 6.6	29.5 ± 6.2
Male, n (%)	20 (62.5%)	19 (57.6%)

Postoperative pain scores

Pain scores were similar between the two groups at all recorded time points. At 30 min postoperatively, mean scores were 2.3 in both groups. On postoperative Days 1 and 2, mean scores remained 2.9 in each group, with no statistically significant differences (Table 2).

Table 2.

Postoperative Pain Scores (Numeric Rating Scale 0–10)

Time Point	Cryoablation (mean ± SD)	Standard PCA group (mean ± SD)	P-value
30 min	2.3 ± 1.1	2.3 ± 0.8	0.9685
Day 1	2.9 ± 0.4	2.9 ± 0.5	0.4028
Day 2	2.9 ± 0.7	2.9 ± 0.5	0.9870

Postoperative opioid consumption

Postoperative opioid requirements, expressed in oral morphine milligram equivalents (MME), are summarized in Table 3. No significant differences were observed between the cryoablation and control groups on postoperative Days 1 and 2. On Day 1, mean opioid use was 14.8 mg in the cryoablation group and 13.9 mg in the control group. By Day 2, consumption increased to 17.7 mg and 20.6 mg, respectively, without statistically significant differences.

Table 3.

Postoperative Opioid Use (mg MME)

Day	Cryoablation (mean ± SD)	Standard PCA group (mean ± SD)	P-value
Day 1	14.8 ± 17.4	13.9 ± 10.3	0.5579
Day 2	17.7 ± 15.5	20.6 ± 13.9	0.2233
Day 3	19.9 ± 18.2	23.1 ± 14.6	N/A*

*PCA typically removed by Day 3; statistical comparison not applicable

On postoperative Day 3, mean opioid use was 19.9 mg in the cryoablation group and 23.1 mg in the control group. However, statistical comparison was not applicable, as PCA devices were typically discontinued by Day 3, as patients were transitioned to oral analgesia in preparation for chest tube removal and discharge, limiting direct group comparison.

Gender differences

Female patients reported higher mean pain scores on Day 1 compared with males (3.0 vs. 2.8, p = 0.03). No significant sex-based differences were observed in opioid consumption on postoperative Days 1 or 2 (Table 4).

Table 4.

Gender Differences in Pain and Opioid Use

Outcome	Female (n = 25)	Male (n = 40)	p-value
Pain at Day 1 (mean ± SD)	3.0 ± 0.2	2.8 ± 0.5	0.03
Pain at Day 2 (mean ± SD)	3.0 ± 0.8	2.9 ± 0.5	0.45
Opioid use Day 1 (mg MME)	15.2 ± 19.2	13.8 ± 10.0	0.46
Opioid use Day 2 (mg MME)	18.1 ± 13.0	19.7 ± 15.7	0.89

Discussion

In this single-center cohort, intraoperative intercostal nerve cryoablation provided postoperative analgesia and opioid consumption comparable to control group after thoracotomy. No clear superiority was demonstrated, suggesting that while cryoablation is safe and feasible, it may not consistently improve short-term pain outcomes compared with established methods. The low absolute pain scores observed in both groups (mean NRS scores ranging from 2.3 to 2.9) suggest a possible floor effect. Because postoperative pain levels were already relatively low, there was limited opportunity for further reductions in pain scores, which may have reduced our ability to detect an additional analgesic benefit from cryoablation.

Our findings are consistent with recent randomized controlled trials in adults, which reported no significant opioid-sparing effect with cryoanalgesia and, in some cases, increased rates of early neuropathic pain [7]. In contrast, earlier observational studies suggested potential benefits, particularly reduced opioid requirements [9]. Stronger evidence exists in pediatric chest wall surgery, especially in pectus excavatum repair, where cryoablation has been associated with reduced opioid use, shorter length of stay, and improved functional recovery [10, 11]. The discrepancy between pediatric and adult outcomes underscores differences in patient selection, pain sources, and surgical complexity.

One plausible explanation for these mixed results lies in the nature of oncological thoracotomy. Such procedures frequently involve rib resection, chest wall reconstruction, and other complex pain generators. While intercostal cryoneurolysis targets pain transmitted through the intercostal nerves, pain arising from extensive musculoskeletal manipulation associated with chest wall reconstruction may not be completely addressed by this technique alone [7, 12]. In addition, technical variability—such as the number of intercostal levels treated, freeze duration, and probe temperature—likely contributes to heterogeneity in outcomes across published studies [11]. Standardization of cryoablation protocols is therefore essential to generate reproducible data.

We also observed higher Day 1 pain scores among female patients, consistent with prior reports demonstrating sex-based differences in pain perception and reporting [13, 14]. However, opioid consumption did not differ significantly, highlighting the complexity of pain assessment and the need to consider both biological and psychosocial determinants when evaluating analgesic strategies.

The strengths of this study include evaluation of cryoablation in a real-world thoracotomy cohort, use of standardized multimodal analgesia across groups, and transparent reporting of effect sizes.

Nonetheless, several limitations must be acknowledged. The principal limitation of this study is its relatively small sample size and the low statistical power demonstrated by the post-hoc power analysis for most outcomes. Consequently, the study may be underpowered to detect small but clinically meaningful differences between groups, increasing the possibility of a type II error. Furthermore, given the retrospective design and non-randomized allocation influenced by clinician judgment and patient consent, selection bias cannot be excluded. In addition, exclusion of emergent thoracotomy cases limits the generalizability of our findings to elective surgical populations. Short-term follow-up precluded assessment of chronic neuropathic pain, an outcome of particular importance in thoracotomy patients. Potential variability in surgical technique and cryoablation application may also have influenced results. Additionally, detailed operative characteristics, including thoracotomy indication, ASA classification, operative duration, and postoperative complications, were not systematically collected and therefore could not be analyzed, limiting further assessment of potential confounding factors. Finally, although non-opioid adjuncts were standardized, their use could still have attenuated differences between groups.

Future research should therefore focus on prospective, adequately powered randomized trials with standardized cryoablation protocols and long-term follow-up specifically addressing neuropathic pain. Additional priorities include incorporation of enhanced recovery metrics such as pulmonary function, length of stay, and quality of recovery, as well as subgroup analyses to identify patients most likely to benefit from cryoablation. In summary, the addition of intraoperative intercostal nerve cryoablation to standard postoperative analgesia did not significantly improve pain scores or reduce opioid consumption compared with standard postoperative analgesia alone. These findings add to the growing body of evidence evaluating intercostal nerve cryoablation for postoperative pain control after thoracotomy.

Author contributions

AE and RAJ conceived the study and contributed to its design. MAY, KS, and AA collected the clinical data. AS, MK, and IA contributed to data curation and patient record review. RAQ and MS assisted with literature review and manuscript drafting. MBG and RAJ conducted the statistical analysis and verified the data. AE, AA, and MK prepared the initial manuscript draft. All authors (AE, RAJ, MAY, KS, AA, AS, MK, IA, RAQ, MS, MBG) critically revised the manuscript for important intellectual content, approved the final version, and agree to be accountable for all aspects of the work.

Funding

This study did not receive any specific funding for its design, conduct, or analysis.

Data availability

The data used in this study are confidential in nature and cannot be shared due to privacy and confidentiality agreements but are available from the corresponding author upon reasonable request.

Declarations

Ethics approval

This study was approved by the Institutional Review Board (IRB) of King Hussein Cancer Center (Approval number: 24 KHCC 244).

Patient consent statement

The requirement for written informed consent was waived by the IRB, as the study involved retrospective analysis of de-identified patient data and posed no more than minimal risk to participants, in accordance with institutional and international ethical standards.

Competing interests

The authors declare no competing interests.