Intercostal Nerve Cryoablation and Pain Outcomes in Robotic Lung Surgery

Abstract

Background

Pain after robot-assisted thoracoscopic lung surgery is a contributing factor to postoperative complications and patient satisfaction. Cryoablation of the intercostal nerves temporarily disrupts nerve function and decreases pain. We evaluated the effect of cryoablation of the intercostal nerves on postoperative pain and opioid use.

Methods

We performed a retrospective single-institution analysis of patients who underwent robot-assisted thoracoscopic lung surgery, with or without cryoablation between 2019 and 2022. We analyzed demographics, postoperative pain scores using a Likert scale, opioid use, postoperative complications, length of stay, and readmission.

Results

Robot-assisted thoracoscopic lung surgery was performed in 230 patients, and 39 (17%) patients underwent cryoablation. Pain scores for the cryoablation group were lower at 12 hours (0 vs 2, P = .04) and higher at 5 weeks (4 vs 1, P = .01). The cryoablation group was more likely to receive an opioid prescription (46.2% vs 29.3%, P = .04) and a higher reported use of narcotics at 5 weeks (61.5% vs 37.7%, P < .01). There were no statistical differences in postoperative morphine milliequivalents per day, minor and major complication rates, total length of hospital stay, and readmission rates.

Conclusions

Cryoablation of multilevel intercostal nerves has higher pain levels at 5 weeks without significant differences in the outcomes. This may be due to an increase in neuroma formation at multiple levels from the cryoablation.

In Short.

• ▪Cryoablation decreased pain in the immediate postoperative robotic thoracic surgery patients.
• ▪Cryoablation of multiple intercostal nerves in robot-assisted thoracoscopic procedure did not assist with long-term pain control.

Robotic-assisted lobectomy is associated with a shorter length of stay and less conversion than video-assisted thoracoscopic surgery and better perioperative outcomes than open lobectomy.¹ The use of a robotic platform is slowly becoming a preferred method for patients undergoing pulmonary lobectomy. Although robotic platforms cause less pain than open lobectomy, pain remains the most common patient complaint after surgery. Chest operations, such as thoracoscopic lung resection, rank highly for postoperative pain. Higher levels of pain lead to increased use of opioids, which can contribute to major patient complications and mortality.² Ports placed between the ribs can cause intercostal neuralgia from irritation and inflammation of the intercostal nerves, resulting in considerable pain that is experienced as pain along the rib space of the affected nerve. One of the newer ways to treat pain in patients undergoing thoracic surgery is cryoablation of the intercostal nerves. Graves and associates³ performed a randomized clinical trial in which they used cryotherapy for patients undergoing the Nuss procedure and demonstrated that cryoanalgesia patients had decreased opioid use and a shorter length of hospital stay than those who received an epidural.

At our institution, we have developed a robust enhanced recovery after surgery program,⁴ along with the use of a robot in pulmonary lobectomy,⁵ which has improved our surgical outcomes. Our protocol includes intraoperative local anesthetic block of the intercostal nerves and multimodal pain medications. At times, cryoablation of the intercostal nerves (Atricure) was used to improve pain control. Following the instructions of the company, we performed cryoablation of five levels from fifth to ninth intercostal space that included all port sites. We aimed to determine the efficacy of cryoablation of the intercostal nerves compared with our standard pain control measures in patients undergoing robot-assisted thoracoscopic lung operations.

Material and Methods

The Houston Methodist Hospital institutional review board approved this retrospective study and waived the need for informed consent. A single-institution retrospective analysis was performed using a database of patients who underwent robot-assisted thoracoscopic operations for lung resections by the Division of Thoracic Surgery between 2019 and 2022. The demographic data included comorbid medical conditions, pulmonary function testing, hemoglobin, creatinine, chronic anticoagulation use, and home oxygen use. Patient characteristic data collected included the type of lung resection performed (wedge, lobectomy, bilobectomy) and preoperative opioid use. The primary endpoint data collected included the pain level and opioid use. Postoperative pain level data were collected using a Likert 10-point scale at various time points: 12 hours after surgery, 24 hours after surgery, after chest tube removal, at discharge, and at 5 weeks (Supplemental Figure 1). The opioid use data collected included preoperative, intraoperative, and postoperative opioid use measured in morphine milligram equivalents (MME) using standard conversion rates. Opioid use data were reported as total MME per day and postoperative MME per day as the median and interquartile range. Postoperative complications were collected for analysis.

Cryoablation of the intercostal nerves was performed by applying a cryoprobe ∼4 cm away from the spine on intercostal nerves 5-9 identified based on rib counting on the respective side of the lung resection. The cryoprobe was applied for 2 minutes at –60°C to each intercostal nerve. The comparison groups included patients who underwent lung resection without intercostal nerve cryoablation. Patients in both groups received tramadol and gabapentin in the preoperative holding area, as well as intravenous acetaminophen and liposomal bupivacaine injection for intercostal spaces 2-10 in the operating room. Postoperatively, patients received scheduled acetaminophen, gabapentin, and methocarbamol as well as opioids as needed. Further analyses were performed in the opioid-naive patient population undergoing cryoablation (n = 27) and standard pain control (n = 169). Similarly, opioid-tolerant patient populations, cryoablation (n = 12), and the standard pain control group (n = 22) were analyzed.

Statistical analysis was performed using χ² or Fisher’s exact test for categorical variables and median and interquartile range for continuous variables using Stata version 17.0 (Stata Corp LLC), with significance set at P < .05. Postoperative complication outcomes were determined using multivariate logistic regression models.

Results

A total of 230 robot-assisted thoracoscopic lung resection procedures were identified. Cryoablation was performed in 39 patients and standard treatment for pain control in 191 patients. There were no statistical differences in patient age, sex, Eastern Cooperative Oncology Group score, preexisting comorbidities, and procedure type between the standard and cryoablation patient groups (Table; Supplemental Table 1). The differences between the cryoablation and standard treatment groups were coexisting cancer (35.9% vs 19.9%), fewer patients on chronic anticoagulation (18% vs 36.1%), fewer patients on home oxygen (0 vs 10%), and higher preoperative opioid use (30.8% vs 36.1%, Table). Postoperative complications, major and minor complications, total hospital length of stay, and readmission rates did not differ statistically between the cryoablation and standard treatment pain control groups (Supplemental Table 2).

Table.

Patient Characteristics

Characteristic	Total	Cryotherapy	No Cryotherapy	P Value
	(N = 230)	(n = 39)	(n = 191)
Age, y	70.0 (64.0-75.0)	70.0 (59.0-77.0)	70.0 (64.0-74.0)	.88
Male	88 (38.3)	16 (41.0)	72 (37.7)	.70
White	192 (83.5)	30 (76.9)	162 (84.8)	.17
Coexisting cancer	52 (22.6)	14 (35.9)	38 (19.9)	.03∗
Home oxygen	19 (8.3)	0 (0.0)	19 (10.0)	.04∗
Chronic anticoagulation	76 (33.0)	7 (18.0)	69 (36.1)	.03∗
Preoperation opioid	34 (14.8)	12 (30.8)	22 (11.5)	<.01∗
Procedure				.75
Lobectomy	126 (54.8)	28 (71.8)	140 (73.3)
Wedge	26 (11.3)	10 (25.6)	49 (25.7)
Bilobectomy	78 (33.9)	1 (2.6)	2 (1.1)

Values are presented as median (interquartile range) or n (%).

^∗P < .05.

Pain score comparisons yielded lower scores in the cryoablation group at the 12-hour postoperative period (0 vs 2, P = .04) (Figure 1A). There were no statistical differences in the pain scores at 24 hours, after chest tube removal, and at discharge. At 5 weeks, pain scores were higher in the cryoablation group (4 vs 1, P < .01) (Figure 1A). Opioid use analysis demonstrated significantly higher opioid prescriptions in the cryoablation group (46.2% vs 29.3%, P = .04) and higher opioid use at 5 weeks (61.5% vs 37.7%, P < .01) (Figure 1B). There were no statistical differences in postoperative MME per day (15.7 vs 16, P = .90) (Supplemental Table 3).

Figure 1.

Pain score and opioid use. There was significantly less pain at 12 hours after surgery in patients who underwent cryotherapy (P < .01); however, at 5 weeks, patients who underwent cryotherapy had significantly higher levels of pain (P = .04; A). Significantly more patients who had cryotherapy were discharged home on opioid medication (P = .04) and used opioid medication at home (P < .01; B).

Subgroup analysis was performed on opioid-naive patients (Supplemental Tables 4-6). The opioid-naive cryoablation group had lower 12-hour pain scores (0 vs 2, P < .01) and higher pain scores at 5 weeks (3 vs 1, P = .04, Figure 2A). In this subgroup analysis, no statistical differences in opioid use were reported at 5 weeks (Figure 2B). We then performed subgroup analysis on those who were opioid-tolerant (Supplemental Tables 7-9). The opioid-tolerant cryoablation group reported significantly higher pain scores at 5 weeks than the standard control pain group (5 vs 2, P = .02) (Figure 2A). Opioid use did not differ between opioid-tolerant groups at 5 weeks (Figure 2B).

Figure 2.

Pain level 5 weeks after surgery and opioid use. (A) Both opioid-tolerant patients (P = .02) and opioid-naive patients (P = .04) who underwent cryotherapy had significantly more pain than patients who did not receive cryotherapy. (B) There was no significant difference in opioid use at home between the opioid-tolerant and opioid-naive patients.

Comment

Our study found that patients who underwent cryoablation for 5 different levels had notable improvement in pain in the first 12 hours after surgery but this improvement disappeared by the time the patient was discharged home and these patients developed considerably higher pain levels and needed opioids for pain control 5 weeks after surgery. This is similar to the findings of a randomized controlled trial of cryoablation in patients undergoing minimally invasive thoracic surgery.⁶ Like our study, patients in the randomized controlled trial had cryoanalgesia to 5-6 intercostal nerves and found that there was no meaningful difference in postoperative pain or narcotic requirements initially with an increase in neuropathic pain in the cryoanalgesia group at 2 weeks. Both studies failed to find a significant benefit of cryoablation of the intercostal nerve in minimally invasive lung resections. This is in contrast to the study by Ba and colleagues⁷ with 178 patients showing that cryoanalgesia at 4 levels provided pronounced benefit after surgery and 4 weeks after surgery for patients undergoing pulmonary lobectomy through open thoracotomy. Other studies have shown that cryoablation is beneficial in patients undergoing thoracotomy.⁸ The main difference was in the approach used in these patients. Cryoablation provides marked benefits for patients undergoing thoracotomy, but it does not seem to provide benefits for patients who are undergoing minimally invasive thoracic surgery. This may be due to the amount of pain that the patient is expected to experience in the short and long term after a different approach. Thoracotomy causes neuropathy; thus, cryoablation provides greater benefit since the overall rate of development of neuropathy and pain from cryoablation is lower than that in patients who develop neuropathy from thoracotomy. In contrast, because the rate of neuropathy from minimally invasive thoracoscopy is lower, cryoablation may lead to higher pain from neuropathy. Since the development of neuropathy from cryotherapy is related to freezing of the nerve,⁹ neuropathy may be a consequence of the number of intercostal nerves undergoing ablation. The limited use of cryoablation, especially at the site of the chest tube port, may improve early postoperative pain control without sequelae of neuropathic pain.

One confounding factor in our study, which was not evident in the Weksler and associates⁶ study, was the presence of a statistically significantly higher use of preoperative opioids in the cryoablation group. Previous studies at our single institution have demonstrated that patients receiving preoperative opioid medications tend to fail nonopioid pain control measures at a higher rate than opioid-naive patients.¹⁰ Subgroup analysis was performed to account for this difference in decreasing differences between the groups, and we discovered that the trend was similar in the opioid-tolerant group. A major limitation of our study is that it was a retrospective cohort study that may have introduced selection bias in the use of cryoablation in select patients. In addition, studies that survey pain outcomes rely on subjective measures, which are not always reliable. However, the data were obtained from a questionnaire that was uniformly administered at follow-up, which can increase the reliability of the data.

Cryoablation of multilevel intercostal nerves decreased pain immediately after surgery; however, at 5 weeks, higher pain scores were observed in patients who underwent robotic lung surgery. This may be due to a higher level of neuroma formation with multilevel cryoablation than with traditional pain control. Studies evaluating the limited cryoablation use for port-site intercostal spaces, specifically the chest tube port site, are warranted in the future.

Supplementary Data

Supplementary Figure

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