Intercostal nerve cryoablation for postoperative analgesia following minimally invasive lung resection: a retrospective cohort study

Introduction

Comprehensive pain management after thoracic surgery is of the utmost importance; dire complications like atelectasis and pneumonia can arise from splinting and ineffective coughing by patients experiencing postoperative pain (1). Given that the thoracic cavity is often accessed through incisions in/near the intercostal spaces during lung resections, multiple intercostal nerves transmit incisional pain and are vulnerable to damage by instrumentation (by trocar manipulation or retraction) (2). Additional nociceptive input by the phrenic and vagus nerves to traumatized contents of the thorax contributes to the multifactorial nature of post-thoracic surgery pain, further increasing the complexity of pain management (3). The development of minimally invasive procedures, such as robotic-assisted thoracoscopic surgeries (RATS), has led to decreased postoperative pain compared to open techniques; however, pain remains a significant aspect of the patient’s postoperative experience (2,4).

According to the Society of Thoracic Surgeons, over 13,000 anatomic lung resections were performed as RATS in 2022, a substantial increase from 9,300 in 2020 (5). Optimizing postoperative pain control in the acute period is a priority as acute pain is strongly associated with the development of chronic pain following these procedures (6,7).

Cryoablation is a procedure in which a cold temperature probe is used to disrupt nerve function. When applied to a nerve, the −50 to −70 ℃ probe induces axonal degeneration distal to the area of application while leaving the perineurium, epineurium, and endoneurium intact. In this manner, the transmission of pain signals in the distribution of the nerve is temporarily disrupted, returning later as the axon regenerates by approximately 1−2 mm per day (8-11). Intercostal nerve cryoablation (INC) has shown promise as an adjunct postoperative pain management modality for thoracic procedures. Current standards of postoperative pain management can vary, but generally involve multimodal strategies that utilize opioids, acetaminophen, nonsteroidal anti-inflammatory agents, gabapentin, and muscle relaxants.

Epidurals as well as regional anesthesia techniques, including paravertebral blocks and fascial plane blocks, are also frequently employed (12). While INC may result in uncomfortable dermatomal numbness, it does not confer the adverse effects associated with opioid and epidural analgesia (3).

Previous studies have demonstrated superior effectiveness of cryoablation when compared to standard methods of pain management. INC during Nuss procedures results in reduced hospital length of stay (LOS) and opioid requirements for pain control (13,14). For thoracic and thoracoabdominal aortic repair, the use of cryoablation can significantly reduce patients’ pain scores and opioid usage following their thoracotomy (15). Likewise, pediatric patients who underwent open pulmonary metastasectomy with INC had a shortened hospital stay with fewer administered opioids, albeit similar pain scores, compared to controls (16). For minimally invasive surgeries, the mitigating effect of INC on postoperative pain and opioid administration has been less definitively established. Maxwell et al. (2023), Miller et al. (2025), and O’Connor et al. (2022) found that INC reduced the need for opioid analgesia in the short-term following video-assisted thoracoscopic procedures (VATS) (17), as well as in the long term in a pooled cohorts of patients who underwent open resection, VATS, or RATS (18,19). Conversely, Koliakos et al. (2025) reported that INC did not decrease postoperative pain scores or postoperative opioid consumption following VATS (20), while Weksler et al. (2025) reported the same for a cohort of patients who underwent VATS or RATS (21). Although acute and chronic pain has been shown to be similar following VATS or RATS (22), RATS procedures are associated with longer procedure durations and decreased LOS compared to VATS (23,24), warranting the study of RATS in isolation with regard to INC.

To date, there exist no published data that compare outcomes with and without intraoperative INC following only RATS. In this study, we hope to contribute to the ongoing discourse regarding cryoanalgesia in minimally invasive thoracic surgery by investigating analgesic and clinical outcomes of patients undergoing anatomic lung resection by RATS with intraoperative INC. We present this article in accordance with the STROBE reporting checklist (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-39/rc).

Methods

Study design

A retrospective cohort study was conducted on thoracic surgery patients who underwent RATS for anatomic lung resection, such as segmentectomy, lobectomy, wedge resection, and bilobectomy, between December 2022 and April 2024 at Stony Brook University Hospital. Reasons for lung resection included removal of known malignant disease, diagnostic removal to identify malignancy, and non-healing benign disease (i.e., chronic infection). IRB approval was obtained for the study. Included were patients of at least 18 years of age who underwent a robotic-assisted lung resection without opioid use at baseline or opioid dependence. No a priori sample size analysis was conducted. Individuals were assessed for eligibility prior to being asked to participate in the study. At the time of consent for the study, patients elected to either receive or not receive INC based on shared decision making between the patient and surgeon. After discharge from the hospital, the use of intraoperative cryoablation was determined from operative notes, and patients were stratified into INC and no-INC groups for the purpose of analysis. Regardless of INC status, patients received a multimodal pain regimen consisting of opioids, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin, and/or methocarbamol for muscle relaxation as needed in addition to treatment for their underlying condition.

Data collection

Following discharge from the hospital, several variables were abstracted from patient charts, including demographic variables [age, gender, body mass index (BMI), hypertension, chronic obstructive pulmonary disease (COPD), diabetes, alcohol overuse, atrial fibrillation, aortic stenosis, and smoking status], administered opioids in morphine milligram equivalents (MMEs), estimated time-to-perform INC, inpatient postoperative complications as defined by the National Surgical Quality Improvement Program [air leak, pneumothorax, acute kidney injury (AKI), urinary retention, and atelectasis] (25), and LOS. Furthermore, postoperative emergency department visits (EDVs) without readmission and readmissions for causes related to the procedure (i.e., surgical site infection, surgical site pain, pleural effusion) in the short term (up to 30 days after discharge) and long term (31 days to 1 year after discharge) were collected for each patient based on chart review. Opioids administered during a patient’s stay were categorized based on where they were given [intraoperatively, in the post-anesthesia care unit (PACU), or on the wards] and were standardized into MMEs (Table 1). Using this information, MMEs were calculated for the entire LOS, the postoperative period (in the PACU and wards), and in the wards alone for each patient. Both time-to-perform INC and postoperative complications were recorded based on operative notes and progress notes, respectively. LOS was calculated from the official patient registration preoperatively until discharge. The primary outcome was opioids administered on the wards in MME/day, and secondary outcomes were total postoperative opioids in MME/day, total inpatient opioids in MME/day, postoperative inpatient complications, LOS, EDVs, and readmissions.

Surgical technique

All patients routinely received local intercostal nerve blocks at the beginning of every procedure immediately after robotic trocar placement. The nerve blocks were performed under direct visualization using 30 cc of 0.25% bupivacaine distributed across five intercostal spaces, including those in which trocars were placed.

After nerve block placement, cryoanalgesia was applied to all intercostal nerves beginning one intercostal space above the most cephalad trocar extending to the intercostal space containing the most caudal trocar. Cryoablation was not performed below the 8^th intercostal space to avoid abdominal bulging as an unwanted side effect. These nerves were identified after leaving the spine with blunt dissection of the pleura and intercostal fat as needed to aid in direct visualization. Cryoablation was performed using a cryoSPHERE probe (Atricure Inc, Mason, OH, USA) by cooling the probe to −50 to −70 ℃ and gently applying it to the nerve for 120 seconds. Special care was taken to apply the probe at least 4 cm away from the spine to avoid activation of the sympathetic ganglia. Two different primary attending surgeons (Surgeon 1 and Surgeon 2) performed the lung resections in this study; the same assisting attending surgeon (A.D.) was present for all the procedures (INC and no-INC) to help perform cryoablation and ensure consistency in application for the INC group.

Statistical analysis

Baseline characteristics were summarized by treatment group and reported as median [interquartile range (IQR)] for continuous variables and count (percentage) for categorical variables; between-group differences for non-normal continuous variables (including LOS) were compared with two-sided Wilcoxon rank-sum tests, and categorical variables with chi-square or Fisher’s exact tests as appropriate.

The primary endpoint was inpatient opioid consumption on the wards, expressed as MME per hospital day on the wards. Secondary continuous outcomes included postoperative opioid use per day, total opioid use per day, intraoperative opioids, and hospital LOS. Continuous outcomes were analyzed using generalized linear models with a Gamma distribution and Log link to accommodate positive, right-skewed outcome distributions. The primary Gamma-log analysis was fit among patients with nonzero ward opioid use and adjusted for covariates selected a priori based on clinical relevance and potential confounding: age, body mass index, sex, American Society of Anesthesiologists (ASA) class, smoking status, race, and comorbidities (hypertension, COPD, diabetes, atrial fibrillation, and aortic stenosis). Treatment effects are reported as ratios of adjusted means with 95% confidence intervals (CIs) using robust standard errors, and adjusted group means and differences were obtained from model predictions (g-computation). To incorporate patients with zero wards opioid use and to validate distributional assumptions, a log-normal specification was fit using linear regression of log (1 + outcome) with robust standard errors, and coefficients exponentiated on the ratio scale for comparability.

Because intraoperative methadone administration was imbalanced between groups, it was evaluated as a sensitivity analysis; additional models were fit that included an indicator for any intraoperative methadone administration and, separately, models restricted to patients who did not receive intraoperative methadone. Propensity score-based analyses were performed as confirmatory analyses for the primary endpoint to assess the robustness of confounding adjustments, using inverse probability treatment weighting for the average treatment effect.

Binary outcomes, including EDVs without readmission, hospital readmissions, and postoperative complications were analyzed using modified Poisson regression to estimate risk ratios and differences, with Fisher’s exact tests applied where appropriate for low event counts.

All tests were two-sided with an alpha level of 0.05, and 95% CIs where applicable. Analyses were conducted in Python (version 3.9).

Ethical consideration

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics board of Stony Brook University (No. 00000125) and individual consent for this retrospective analysis was waived.

Results

Out of 87 eligible patients, 36 underwent INC and 51 patients did not undergo INC. Additional patients were excluded at the time of data analysis due to the presence of intra- and postoperative circumstances that likely interfered with accurate data collection, which were instances when patients underwent an additional procedure after their index resection procedure, received anesthesia via an epidural, or had their procedure converted to an open thoracotomy (Figure 1). The final cohort for analysis consisted of 34 patients who underwent INC and 48 patients who did not undergo INC.

Figure 1 Flowchart of patient inclusion/exclusion. INC, intercostal nerve cryoablation.

The no-INC group featured 31 lobectomies, 12 segmentectomies, 1 wedge resection, and 5 multi-resections (2 resections in one procedure) while the INC group featured 14 lobectomies, 7 segmentectomies, 9 wedge resections, and 4 multi-resections. For the INC group, the median time spent performing a cryoablation was 25 minutes according to surgeon reporting in operative notes. An average of 3.79 intercostal nerves were ablated during procedures involving INC. No data point values were found to be missing during data collection.

Baseline characteristics

The median age of both groups was 70 years and both groups were predominantly female (58.3% female for no-INC and 61.8% female for INC). The groups did not differ significantly in terms of other demographic variables, comorbidities, or smoking status (Table 2).

Primary outcome

In terms of opioids administered on the wards alone, INC patients received significantly fewer opioids than no-INC patients [median 14.43 (IQR: 8.45, 20.54) vs. 29.16 (IQR: 9.06, 38.37) MME/day, P=0.04]. When adjusted using a gamma generalized linear model with baseline characteristics as covariates, this difference persisted [ratio of means, 0.704 (95% CI: 0.526, 0.943), P=0.02] (Table 3). Five patients in the INC group and 6 patients in the no-INC group did not receive opioids on the wards and were excluded from this adjusted analysis. In a sensitivity analysis that included these patients using a linear model of log(1 + MME/day), results were directionally consistent [median 0.801 (IQR: 0.472, 1.36)]. After propensity score weighting by baseline characteristics, INC patients continued to demonstrate lower opioid requirements (ratio of means 0.686, 95% CI: 0.508, 0.926) (Table 4, Figure S1).

Notably, 14 patients in the INC group were given methadone intraoperatively in contrast to 0 patients in the no-INC group. Given the differential administration of methadone between groups, additional sensitivity analyses were carried out to assess the impact of methadone as a confounding variable. These analyses yielded qualitatively similar conclusions, with point estimates consistently favoring lower opioid requirements with INC (Table S1).

Secondary outcomes

Postoperative and total opioid administration

Intraoperative opioid administration was statistically similar between the groups but showed a trend toward decreased administration in the INC group [median, 60.00 (IQR: 45.00, 75.00) MME] compared to the no-INC group [median, 67.50 (IQR: 58.50, 84.60) MME] (P=0.07). With the exception of methadone, there were no statistical differences between groups in administration of individual types of opioids (Table 5). In terms of the intra- and postoperative period, patients in the no-INC group received, on average, a greater, albeit not statistically significant, amount of MMEs per day compared to treatment arm patients [median 61.48 (IQR: 34.91, 82.29) vs. 54.76 (IQR: 32.52, 73.61) MMEs/day, P=0.44] (Table 6). However, when removing intraoperative opioid administration and only analyzing opioid use in the PACU and wards, INC patients received statistically significantly fewer MMEs per day overall than no-INC patients. Combined opioid administration in the PACU and wards was 31.90 (IQR: 15.82, 54.18) MMEs/day for no-INC patients and 18.31 (IQR: 12.14, 27.86) MMEs/day for INC patients (P=0.03) (Table 6). The covariate-adjusted values for total opioid administration and total postoperative opioid administration produced results congruent in significance and trend to the unadjusted data (Table 6).

LOS

Median LOS was nearly the same for both groups: 3.15 days for the INC group and 3.16 days for the no-INC group (P=0.30). After covariate adjustment, there remained a lack of statistically significant difference in mean LOS for the groups [3.39 days for INC and 2.88 days for no-INC (95% CI: 0.877, 1.578); P=0.28] (Table 6).

Complications

No intraoperative complications were reported for any of the 72 included patients. The most common complications postoperatively were air leak, persistent pneumothorax, urinary retention, AKI, and atelectasis. INC and no-INC patients did not significantly differ in risk of postoperative complications (Table 7).

EDVs and readmissions

In the 30 days following RATS, there were no significant differences in procedure-related EDVs or readmissions between the two groups. EDV rates were 2.1% (1/48) for no-INC patients and 5.9% (2/34) for INC patients (P=0.57). Reasons for EDVs were persistent cough and surgical site pain for the no-INC patient and neck swelling with right upper extremity edema (requiring evaluation by thoracic surgery) and procedure-related chest pain for the 2 INC patients. Only 6.3% (3/48) of control arm patients and 2.9% (1/34) of treatment arm patients were readmitted in this period (P=0.64) (Table 7). The no-INC patients were readmitted for serosanguinous drainage from a prior chest tube site, recurrent right pleural effusion, and completion lobectomy (due to positive margins on primary resection). The INC patient was readmitted for surgical site drainage and pain. There were no procedure-related readmissions from 31 days to 1 year postoperatively for either group. One patient in each group passed away prior to the 1-year postoperative mark.

Discussion

Comparative analysis of opioid usage stratified by time of administration indicated that while total opioid usage did not differ significantly, patient-driven opioid usage in the inpatient recovery period after surgery was significantly reduced for those who underwent INC compared to those who did not. Intraoperative opioid administration can represent a substantial portion of the total MMEs administered to a patient, especially in those with a short LOS. Total opioid administration may be an inappropriate metric to evaluate the difference between the no-INC and INC groups as it may be confounded by a variation of intraoperative opioid administration by anesthesia providers. In 2025, Koliakos et al. and Weksler et al. both reported that INC and no-INC patients received similar amounts of intraoperative opioids (20,21). Studies that stratified inpatient narcotic use based on the number of days since the operation demonstrated mixed results. Maxwell et al. observed a reduction in opioid usage for INC patients as early as postoperative day 1 that was maintained throughout the hospital stay, while Koliakos et al. reported similar usage on postoperative day 1 and throughout the hospital stay (17,20). Though INC typically takes 24–48 hours to have effect, the pain relief from cryoablation can be immediate (28). This study, in which opioid administration is stratified by patient location, broadly reflects these findings, as statistically significant reductions in opioid use between INC and non-INC patients appear as early as the PACU and persist during the rest of the patient’s stay on the wards.

In the process of calculating intraoperative opioid administration, it was noted that 14 INC patients received methadone in contrast with 0 patients from the no-INC group. Anesthesia regimens were not standardized across procedures in the study; methadone was administered at the discretion of the anesthesia providers and differential administration of between groups may reflect hospital-wide changes in anesthesia operating procedures. Since the initiation of this study, intraoperative methadone administration has become associated with improved pain following thoracic procedures (29,30), indicating it as a potential confounding variable for the observed relationship between INC and decreased postoperative opioid requirements. Additional sensitivity analyses taking methadone administration into account demonstrated a persistent (albeit not statistically significant) decrease in ward opioid administration for the INC group compared to the no-INC group (Table S1).

As reported in prior studies, there were no significant differences in postoperative complication rates between INC and no-INC patients (15,17,18).

Hospital LOS was not significantly different between INC and non-INC patients in this study. The impact of INC on postoperative LOS varies across procedures in the available literature (13,14,31). In line with our findings, other studies that evaluated INC during minimally invasive thoracic procedures did not appreciate any significant differences in LOS despite the lack of difference in complication rates and reductions in postoperative opioid use (17,18). Similarly, EDVs and hospital readmissions in the first 30 days following RATS were statistically similar for the INC and non-INC cohorts as was the case for other studies that analyzed readmissions in the early postoperative period (18,19). Differences in outpatient opioid use between INC and non-INC patients following open resection, VATS, and RATS only became apparent 90 days after surgery according to Miller et al. (18). To assess the long-term benefits of INC as a pain control adjunct following RATS, we extended the procedure-related EDV and readmission period to 1 year postoperatively. Per chart review, there were no EDVs or readmissions from 31 days to 1 year postoperatively for either group, indicating that pain following minimally invasive thoracic procedures may not be clinically significant enough to warrant presentation to the hospital. Future prospective studies should quantify the degree of opioid use and presentation to outpatient clinics for uncontrolled postoperative pain with follow-up over a long (1 year) period.

As an accessory intraoperative intervention requiring specialized equipment, INC will inevitably prolong procedure duration. Procedure duration is a particularly important metric due to its relationship with cost and outcomes across all surgical disciplines (32). In our study, surgeons reported a median time of 25 minutes to perform INC, these times would likely decrease with the development of more efficient probes and mastery of the learning curve. As an additional operative intervention requiring specialized equipment, one might also expect INC to carry an economic burden. Interestingly, Miller et al. found that operating room costs were significantly decreased for lobectomy patients undergoing INC (although supply costs did ultimately increase) with a trend toward decreased total healthcare costs at 6 months post-procedure for INC patients (18). In 2026, Stasiak et al. reported a non-significant increase in total hospital stay cost for INC patients compared to no-INC patients (33). Future studies of INC specifically during RATS should ideally include a comparison of operative duration, patient outcomes, a comparative pain scoring system as well as detailed cost analysis to establish the feasibility of INC.

Limitations

This study is a retrospective chart review of patients who either did or did not undergo INC during RATS based on clinical decision-making by surgeons and patients at a single medical center; patients were not randomized into the INC and no-INC groups of the study. This introduces an opportunity for bias in patient assignment that may confound the results reported above. Factors like age, sex, ethnicity, and comorbidities could impact the postoperative recovery course (34-36). In an effort to minimize the impact of selection bias, propensity-matching and covariate analyses were carried out, which robustly support the observed decrease in postoperative opioid requirements for INC patients. Furthermore, a higher-powered study would be better equipped to elucidate any differences between INC and no-INC patients in terms of complications, LOS, EDV, and readmissions.

The non-blinded nature of this study meant that both patients and nurses were aware when a patient had received INC. Nurses may have thus been biased to provide fewer opioid analgesics to INC patients regardless of patients’ pain levels knowing that they had received an additional intervention for their pain. There also exists the possibility that INC patients’ self-perceived pain and subsequent desire for pain control were diminished by a placebo effect.

The procedural and postoperative care which served as the basis of this study’s data were carried out at a single medical center. Thus, the generalizability of the results may be limited based on the operative protocols, pain management protocols, and patient population that are specific to this hospital. Due to the limited sample size, this study may lack the statistical power to detect subtle between-group differences in secondary outcomes (e.g., complications, LOS). Inpatient complication rates were determined based on what physicians, many of whom were third-party to the study, reported in their progress notes. Thus, the validity of this analysis is limited by the accuracy of their notes; it is possible that some complications were undocumented. Likewise, given that EDVs and readmissions in the early and late postoperative periods were determined based on chart documentation, any patients who presented to institutions in other hospital networks for procedure-related issues would have been missed by this method of data collection.

Conclusions

Patients who underwent INC were administered significantly less opioids postoperatively compared to patients who did not undergo the procedure with comparable LOS, complication rates, and readmission rates. Overall, INC has shown promise as an adjunct pain management modality compared to a standard postoperative regimen for patients undergoing minimally invasive thoracic surgery, although additional large randomized controlled trials are needed.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-39/rc

Data Sharing Statement: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-39/dss

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-39/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-39/coif). A.D. has participated in educational events for Atricure, Noah Medical, and Biodesix as well as proctoring for Intuitive. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics board of Stony Brook University (No. 00000125) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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