Is cryoanalgesia superior to thoracic epidural analgesia for postoperative recovery after the Nuss procedure? An updated meta-analysis

Abstract

Background

The Nuss procedure is commonly used to correct pectus excavatum, with cryoanalgesia (CA) and thoracic epidural analgesia (TEA) as pain management options. While a prior meta-analysis showed shorter hospital stays with CA, publication of recent studies warrants a more comprehensive evaluation of outcomes not previously reported.

Methods

A literature search identified studies comparing CA and TEA in Nuss procedures. Pooled odds ratios, mean differences (MDs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using RevMan 8.13.0, with a subgroup analysis of randomized and propensity matched studies.

Results

Fifteen studies were included, comprising 1,391 patients, of whom 823 (62.4%) received CA. CA was associated with a longer operative duration (MD 29.1 minutes, 95% CI 17.3 to 40.8; P < 0.001) and increased hospitalisation costs (MD 1,655.3 US dollars, 95% CI 1,154.1 to 2,156.5; P < 0.001), but conferred benefits such as a reduced hospital stay (MD –2.7 days, 95% CI –3.1 to –2.4; P < 0.001), lower postoperative pain on postoperative day 3 (SMD –0.6, 95% CI –0.9 to –0.3; P < 0.001), and decreased opioid consumption (MD –253.7 morphine milligram equivalent, 95% CI –336.6 to –170.8; P < 0.001). The subgroup analysis corroborated these findings, demonstrating shorter hospital stay with no differences in complication rates.

Conclusions

Consistent with the prior meta-analysis, the authors’ updated meta-analysis indicates that CA is associated with reduced hospital stay. Additionally, their analysis revealed that CA lowers postoperative pain and opioid consumption, however, the increased costs necessitate a cost-benefit evaluation.

INTRODUCTION

Pectus excavatum is congenital deformity of the chest wall which can be corrected surgically with the Nuss procedure [1]. This intervention is effective, but the process of recovery is challenging due to significant postoperative pain [2]. To help patients control this pain, two main approaches are used which include cryoanalgesia (CA) and thoracic epidural analgesia (TEA) [3].

A prior meta-analysis, which included 4 observational studies and 1 randomized controlled trial (RCT) with a total of 196 patients, concluded that CA is associated with shorter hospital length of stay (LOS) as compared to TEA [4]. However, the analysis was by its small sample size and narrow outcome scope, lacking several clinically important endpoints such as postoperative pain, opioid consumption, complication rates, and the cost of hospitalization.

Since the prior meta-analysis, a substantial number of additional studies have become available including 10 additional observational studies, contributing a further 1,195 patients [3,5–18]. This represents a more than sevenfold increase in the total sample size, bringing the overall number of patients included in the analysis to 1,391. These new publications make it necessary to re-examine the comparative efficacy and safety of CA vs. TEA, including important endpoints such as complication rates, postoperative pain, total opioid consumption, and hospitalization costs that were not addressed in the previous analysis.

Therefore, the authors’ aim is to conduct an updated meta-analysis building on prior work by not only including a significantly larger number of patients but also evaluating a broader range of outcomes and including subgroup analysis focusing on higher quality evidence from RCTs and propensity matched studies as well as meta-regression and sensitivity analyses. To their knowledge, this is the most comprehensive and methodologically robust comparison of CA and TEA in patients undergoing the Nuss procedure.

MATERIALS AND METHODS

This systematic review and meta-analysis were conducted according to the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [19]. Since this study analyzed previously published data and did not involve the direct participation of human or animal subjects, institutional review board approval of this analysis was not required. This review was registered in the National Institute for Health Research International Registry of Systematic Reviews (PROSPERO CRD42025633724).

1. Search strategy

A thorough literature search was carried out in MEDLINE, Scopus, Embase, and the Cochrane Library including only papers published in English and published prior to December 2024. The search strategy included words such as “cryoanalgesia,” “thoracic epidural,” “pectus excavatum,” and “Nuss procedure” as well as their related terms. In addition, the references of all included studies were manually reviewed to capture any other relevant articles.

The titles, abstracts, and full-text articles were screened by two independent reviewers using predetermined search criteria to identify eligible studies with any discrepancies resolved by consensus. The full search strategy can be found in the Supplementary Material 1.

2. Inclusion criteria

Only studies that met all the following eligibility criteria were included in this meta-analysis: (1) non-randomised observational studies (prospective or retrospective) or randomised controlled trials; (2) studies with patients who had undergone the Nuss procedure for the treatment of pectus excavatum; (3) studies directly comparing CA and TEA for postoperative pain management; and (4) studies reporting quantitative data for at least one of the clinical outcomes of interest. Studies were excluded if they (1) involved animals instead of human subjects; (2) were single-arm studies lacking direct comparison between CA and TEA; and (3) were case reports, reviews, editorials, or (4) were studies that lacked enough data for comparative analysis.

3. Outcomes

Our meta-analysis looked at perioperative outcomes which included operative duration, LOS, patient reported pain scores, total opioid consumption during hospitalization, incidence of complications, and hospitalization costs.

Postoperative pain was defined as patient-reported pain intensity using a standard pain scale such as the numerical rating scale (NRS) or the visual analogue scale (VAS), focusing on pain levels recorded for postoperative day (POD) zero, one, two and three. Total opioid consumption was defined as the total amount of opioids given during the hospital stay measured in morphine milligram equivalents (MMEs). The costs of hospitalization were stated in US dollars (USDs), including all costs from admission to discharge. Lastly, complication rates were defined as the cumulative incidence of intraoperative or postoperative complications, including adverse events like infections, bleeding, sensory disturbances, pneumothorax or other conditions that may require intervention or lead to prolonged hospitalization.

Our primary outcome was LOS. This was chosen because it is clinically meaningful and it reflects overall recovery, pain control efficacy, and resource utilization.

4. Data extraction and preparation

The data extraction was done by two reviewers using a standardized data extraction form. Any discrepancies between them were resolved through discussion and consensus.

In studies with incomplete summary statistics or missing data, standard statistical methods were used to generate the required measures. Conversion of medians and interquartile range to means and standard deviation (SD) was done as suggested by Abbas et al. [20]. When conversions were not feasible, studies were excluded from the analysis.

5. Statistical analysis

The odds ratios (ORs), mean differences (MDs) and standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were calculated for dichotomous and continuous variables, respectively. The Mantel–Haenszel random-effects model was used in this meta-analysis to account for the study variance and the heterogeneity that was expected across the studies [21]. The I² statistic was used to measure heterogeneity and was considered substantial if I² > 50% [22]. RevMan version 8.13.0 (Cochrane Collaboration) was used for all analyses.

For postoperative pain outcomes, the SMD was used instead of the MD, as studies employed different pain measurement tools, primarily the VAS and the NRS. Given the variation in scale type and scoring systems, the use of SMD allowed for appropriate pooling of results across studies by standardizing the effect sizes.

6. Quality assessment

The Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool (Cochrane Collaboration) was used to assess the risk of bias in the included non-randomized studies [23] and RoB 2 tool (Cochrane Collaboration) for randomized studies [24] by two independent reviewers. Any disagreements between the reviewers were resolved by discussing the reasons for the discrepancy, with a third reviewer consulted when necessary. Additionally, publication bias was investigated via funnel-plot analysis.

7. Sensitivity analyses

To assess the robustness of the results and to ensure that they were not unduly influenced by any single study, sensitivity analyses were performed. This included a leave-one-out analysis to evaluate the stability of the effect estimates and to confirm that no individual study disproportionately affected the overall findings. In addition, a meta-regression analysis was carried out to investigate whether the mean preoperative Haller index acted as a moderator of the primary outcome, LOS. This analysis was conducted using Comprehensive Meta-Analysis (CMA) version 4 software [25], applying a random-effects model. The strength and significance of the association were assessed using the regression coefficient and the corresponding P value.

RESULTS

1. Study selection

The PRISMA diagram depicted in Fig. 1 shows the study selection process. The initial search yielded a total of 101 results from four databases. After removing 57 duplicate records, 44 studies were screened by title and abstract, which resulted in the exclusion of 21 studies. Ultimately, 14 observational studies and 1 RCT were included in the meta-analysis [3,5–18]. A list of the excluded studies has been included in the Supplementary Material 2.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart illustrating the process of study screening and selection.

2. Baseline characteristics

Table 1 presents the demographic and baseline data of the patient populations in the included studies. A total of 1,391 patients were analyzed and 823 (62.4%) of them received CA while 568 (37.6%) of them received TEA. The mean age of patients ranged from 15.0 to 32.8 in the CA group and 14.0 to 32.0 years in the TEA group. All the studies had a high male participation which ranged from 74.0% to 100.0%. The preoperative Haller index, which represents the severity of pectus excavatum, was only marginally different between the two groups, ranging from 3.9 to 5.11 in the CA cohort and 3.2 to 5.7 in the TEA cohort. The number of Nuss bars implanted also differed across studies with some reporting single bar implantations while others documented either one or two bars. Body mass index was not well documented but when available it ranged from 18.0 to 20.3 kg/m2. Finally, most studies described the use of bilateral cryoablation across multiple intercostal levels, typically ranging from T3 to T7, in alignment with the bilateral nature of the Nuss procedure.

Table 1.

Baseline and demographic characteristics of included studies

Study	Study design	Intervention	No. of Patients	Age (yr)	Male	BMI (kg/m2)	Preoperative Haller index	No. Nuss bars implanted (1 bar/2 bars)
Keller et al. [3], 2016	OBS	CA	26	15.6 ± 1.5	20 (77)	NR	4.2 ± 1.4	24/2
		TEA	26	15.3 ± 1.6	23 (88)	NR	3.8 ± 1.0	26/0
Graves et al. [6], 2017	OBS	CA	10	16.8 [9–31]	8 (80)	NR	4.4 [3.2, 8]	NR
		TEA	15	NR	NR	NR	NR	NR
Harbaugh et al. [8], 2018	OBS	CA	19	15.0 [15–17]	19 (100)	NR	4.3 [3.6, 4.9]	19/0
		TEA	13	17.0 [16–18]	11 (85)	NR	3.2 [2.8, 4]	10/3
Graves et al. [7], 2019	RCT	CA	10	20.9 [14–31]	9 (90)	20.3	4.2 [3.6, 5.7]	NR
		TEA	10	16.1 [13–21]	8 (80)	19.8	3.7 [2.9, 5.1]	NR
Dekonenko et al. [5], 2020	OBS	CA	35	16.0 [14–17]	29 (82.4)	18.2 [17–20]	4.6 [3.6, 5.4]	35
	RCTa	TEA	32	15.0 [14–16]	29 (90.6)	18.8 [18–20]	3.4 [3.3, 4.2]	32
Rettig et al. [13], 2021b	OBS	CA	40	15.7 [13–28]	33 (82.5)	NR	NR	14/26
		TEA	39	15.0 [12–18]	30 (76.9)	NR	NR	22/17
Sun et al. [12], 2021	OBS	CA	65	16 [15–17]	59 (91)	19.3 [17–21]	4.0 [3.6–4.5]	60/5
		TEA	26	16 [15–17]	21 (81)	19.9 [18–21]	4.6 [4–5.2]	21/5
Song et al. [15], 2022	OBS	CA	38	17[4–33]	8 (21)	19 [13–23]	3.9 [2.8,9.7]	0/38
		TEA	26	14 [11–25]	5 (19)	18 [14–23]	4.4 [2.9,13.2]	0/26
Mehl et al. [16], 2023	OBS	CA	98	16 [15–17]	90 (91.8)	NR	4.0 [3.5–4.6]	78/20
		TEA	36	16 [15–17]	29 (80.6)	NR	4.5 [4.0–4.9]	31/5
Perez Holguin et al. [9], 2023	OBS	CA	31	15.8 [14.4–19.2]	28 (90.3)	18.6 [17.7–19.8]	4.5 [3.7–6.0]	NR
		TEA	127	15.9 [14.4–17.2]	100 (78.7)	19.0 [17.7–20.6]	4.3[3.6–5.4]	NR
Toselli et al. [17], 2024	OBS	CA	176	16.8 ± 4.6	163.7(93)	NR	5.11 ± 1.7	NR
		TEA	62	18.2 ± 5.2	NR	NR	5.70 ± 2.5	NR
van Braak et al. [18], 2024	OBS	CA	33	16 [16–17]	29 (87.9)	NR	NR	32/1
		TEA	33	16 [14–16]	27 (81.8)	NR	NR	24/9
Rook et al. [14], 2025	OBS	CA	18	16.4 ± 2.3	16(88.9)	NR	4.2 ± 1.0	12/6
		TEA	15	19.5 ± 4.0	14(93.3)	NR	4.2 ± 0.7	12/3
Jaroszewski et al. [10], 2024b	OBS	CA	50	32.8 ± 10.4	37(74)	NR	NR	NR/26
		TEA	50	32 ± 9.1	37(74)	NR	NR	NR/27
Mariconti et al. [11], 2026	OBS	CA	13	15 [14–16]	12 (92.3)	NR	4 [3.6–5.0]	NR
		TEA	18	15 [14–17]	15 (83.3)	NR	4 [3.5–4.6]	NR

Values are presented as number only, median [interquartile range], number (%), or mean ± standard deviation.

BMI: body mass index, OBS: observational study, CA: cryoanalgesia; NR: not reported, RCT: randomized controlled trial, TEA: thoracic epidural analgesia.

aData from previous RCT. bData from matched cohorts.

3. Pooled analysis of all studies

In patients undergoing the Nuss procedure, CA was associated with a reduced hospital LOS (MD –2.7 days, 95% CI –3.1 to –2.4; P < 0.001, I² = 84) (Fig. 2), lower total opioid consumption during hospitalization (MD –253.7 MME, 95% CI –336.6 to –170.8; P < 0.001, I² = 94) (Supplementary Fig. 1A), and postoperative pain scores on POD 3 (SMD –0.6, 95% CI –0.9 to –0.3; P < 0.001, I² = 0) (Supplementary Fig. 1B) compared to TEA. However, CA was also associated with a longer operative time (MD 29.1 minutes, 95% CI 17.3 to 40.8; P < 0.001, I² = 79) (Supplementary Fig. 1C) and hospitalization costs (MD 1,655.3 USD, 95% CI 1,154.1 to 2,156.5; P < 0.001, I² = 68) (Supplementary Fig. 1D).

Fig. 2.

Forest plot displaying the pooled mean difference in hospital length of stay between cryoanalgesia and thoracic epidural analgesia. aCl calculated by Hartung-Knapp-Sidik-Jonkman method. bTau2 calculated by Restricted Maximum-Likelihood method.

The two techniques were comparable with regards to pain scores on POD 0 (SMD –0.3, 95% CI –0.9 to 0.4; P = 0.420, I² = 85) (Supplementary Fig. 1E), POD 1 (SMD –0.2, 95% CI –0.6 to 0.2; P = 0.320, I² = 63) (Supplementary Fig. 1F), and POD 2 (SMD –0.4, 95% CI –1.0 to 0.3; P = 0.250, I² = 79) (Supplementary Fig. 1G). Additionally, there was no significant difference between the two pain management approaches in terms of intraoperative opioid use (MD 14.7 MME, 95% CI –30.6 to 60.0; P = 0.530, I² = 96) (Supplementary Fig. 1H) and complication rates (OR 0.8, 95% CI 0.4 to 1.6; P = 0.490, I² = 54) (Supplementary Fig. 1I). Table 2 shows a summary of outcomes for the total cohort.

Table 2.

Summary of outcomes for the total cohort

Outcome	No. of studies	No. of patients	Effect estimate (95% CI; P value, I2)
Surgical time	10	1,031	MD 29.05 minutes (95% CI 17.33 to 40.78; P < 0.001, I2 = 79%)
Hospital LOS	13	1,296	MD –2.73 days (95% CI –3.09 to –2.37; P < 0.001, I2 = 82%)
Post-op complication	10	1,005	OR 0.77 (95% CI 0.36 to 1.62; P = 0.490, I2 = 54%)
Post-op pain on POD 0	5	260	SMD –0.27 (95% CI –0.94 to 0.40; P = 0.420, I2 = 85%)
Post-op pain on POD 1	6	293	SMD –0.20 (95% CI –0.59 to 0.19; P = 0.320, I2 = 63%)
Post-op pain on POD 2	4	228	SMD –0.35 (95% CI –0.95 to 0.25; P = 0.250, I2 = 79%)
Post-op pain on POD 3	3	162	SMD –0.58 (95% CI –0.90 to –0.26; P < 0.001, I2 = 0%)
Intraoperative opioid use	2	65	MD 14.69 MME (95% CI –30.64 to 60.01; P = 0.530, I2 = 96%)
Post-op total opioid	9	615	MD –253.71 MME (95% CI –336.59 to –170.83; P < 0.001, I2 = 94%)
Discharged on narcotics	2	224	OR 0.01 (95% CI 0.00 to 0.05; P < 0.001, I2 = 0%)
Hospitalisation cost	3	371	MD 1,655.31 USD (95% CI 1,154.09 to 2,156.53; P < 0.001, I2 = 68%)

CI: confidence interval, LOS: length of stay, Post-op: postoperative, POD: postoperative day, MD: mean difference, OR: odds ratio, SMD: standardised mean difference, MME: morphine milligram equivalent, USD: US dollar.

4. Subgroup analysis

Three studies comprising 199 patients were included in the subgroup analysis of exclusively RCT and matched data. This analysis revealed that CA was associated with a significantly shorter hospital stay compared to TEA (MD –2.1 days, 95% CI –2.7 to –1.4; P < 0.001; I² = 65) (Supplementary Fig. 2A) while surgical time (MD 32.4 minutes, 95% CI –24.2 to 89.0; P = 0.260; I² = 89) (Supplementary Fig. 2B) and postoperative complication rates (OR 0.8, 95% CI 0.1 to 4.8; P = 0.820; I² = 64) (Supplementary Fig. 2C) were comparable between the groups. Table 3 shows a summary of outcomes from the subgroup analysis of propensity-matched studies.

Table 3.

Summary of outcomes for the subgroup analysis of propensity matched data

Outcome	No. of studies	No. of patients	Effect estimate (95% CI; P value, I2)
Surgical time	2	120	MD 32.42 minutes (95% CI –24.18 to 89.02; P = 0.260, I2 = 89%)
Length of hospital stay	3	199	MD –2.05 days (95% CI –2.68 to –1.43; P < 0.001, I2 = 65%)
Complications	3	199	OR 0.81 (95% CI 0.14 to 4.82; P = 0.820, I2 = 64%)

CI: confidence interval, MD: mean difference, OR: odds ratio.

5. Meta-regression

The meta-regression analysis, presented in Fig. 3, evaluated the relationship between the preoperative Haller index and the difference in LOS between CA and TEA. The analysis showed no significant correlation between the two variables (r = 0.33; P = 0.370), suggesting that variation in deformity severity did not substantially influence the observed differences in hospital stay.

Fig. 3.

Meta-regression analysis evaluating the association between the mean preoperative Haller index and the difference in hospital length of stay.

6. Quality assessment

The risk of bias assessment for non-randomized studies was performed using ROBINS-I tool and is presented in Fig. 4A. Moderate risk of bias was frequent in confounding (D1), deviations from intended interventions (D4), and outcome measurement (D6), while serious risk due to confounding was found in seven studies. Low risk was consistently noted for intervention classification (D3), participant selection (D2), missing data (D5), and reported results (D7). Among the studies, seven were found to have serious risk of bias, while the rest were moderate.

Fig. 4.

(A) Risk of bias assessment of non-randomised studies using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool (Cochrane Collaboration). (B) Risk of bias assessment of randomised controlled trials using the RoB 2 tool (Cochrane Collaboration).

The single RCT was assessed using RoB 2 as shown in Fig. 4B and received an overall judgement of “some concerns” due to issues in intervention deviations and outcome measurement, despite low risk in randomization, missing data, and reported results. These findings suggest that the results should be interpreted with caution, especially the serious risks of bias due to confounding and participant selection.

7. Publication bias

The funnel plot for hospital LOS illustrated in Supplementary Fig. 3 shows that the studies are symmetrically distributed around the pooled effect size, indicating no publication bias or small study effect. The points are mostly in the triangular area but three of them are outside the triangle and may contribute to the heterogeneity. The missing small studies in the lower triangular region may be due to true absence of such studies or publication bias. Though overall symmetry suggests consistency, the presence of outliers and missing small studies requires cautious interpretation.

8. Sensitivity analysis

The leave-one-out sensitivity analysis was conducted due to the high heterogeneity seen in length of stay (I² = 82%) and total opioid consumption during hospitalization (I² = 94%). The results of the pooled estimates for both outcomes did not change direction or magnitude when the analysis was conducted, indicating that the results were robust and not overly influenced by any single study.

DISCUSSION

In this systematic review and meta-analysis, 15 studies were analyzed involving 1,391 patients to compare the outcomes of CA and TEA in patients undergoing the Nuss procedure. The main findings indicate that CA is associated with (1) reduced hospital stay, (2) decreased postoperative pain scores on day 3, (3) decreased total opioid consumption, and (4) higher hospital costs compared with TEA. Other outcomes, including complication rates, postoperative pain on days 0, 1, and 2, as well as intraoperative opioid use, were comparable between CA and TEA.

CA and TEA represent two distinct approaches to pain management following the Nuss procedure. CA is the process of applying extreme cold to the intercostal nerves which results in Wallerian degeneration and a nerve conduction block that usually lasts for several weeks or even months before the nerve regenerates [26]. This long-lasting effect leads to pain relief for a period of time without the patient requiring additional analgesia. On the other hand, TEA depends on the use of a continuous infusion of local anesthetics and opioids to achieve effective though transient pain relief [27]. Though TEA provides good intraoperative and early postoperative pain management, its effectiveness wears off once the infusion is stopped, thus requiring systemic analgesics [27].

The authors’ findings indicate that CA may provide better postoperative pain management, particularly on POD 3. Pain scores on this day demonstrated a statistically significant difference, with a SMD of –0.6. However, assessing the clinical significance of this result is challenging, as the SMD expresses the effect size in units of SD rather than in absolute terms, thereby limiting its direct clinical interpretability. The use of SMD was necessary to facilitate the pooling of results from studies that utilized different pain assessment tools, including the NRS and the VAS. Myles et al. [28] have suggested that a difference of less than 1 point on the VAS may not be clinically meaningful, although there is currently no universally accepted minimal clinically important difference (MCID) for the NRS. Therefore, while the observed effect size indicates a moderate improvement in pain, its clinical relevance should be interpreted with caution.

Our analysis also demonstrated that a key advantage of CA is the significant reduction in opioid consumption during hospitalization. The reported mean reduction of –253.7 MMEs is not only statistically significant but is also likely to be clinically meaningful. Although there is no universally accepted MCID for opioid reduction in this specific surgical context, existing literature offers some insight. For example, studies have shown that postoperative opioid prescriptions exceeding 400 MME are associated with a 1.17-fold increased risk of developing long-term opioid use [29]. Therefore, a reduction of approximately 250 MME may meaningfully reduce the likelihood of prolonged opioid dependence, supporting the clinical value of CA as an opioid-sparing analgesic strategy. Furthermore, the substantial decrease in opioid requirements observed with CA aligns with enhanced recovery protocols aimed at minimizing opioid exposure and improving postoperative outcomes. This magnitude of reduction is likely to translate into tangible clinical benefits, including shorter hospital stays and improved patient satisfaction [14]. In addition, this may help prevent opioid related side effects such as respiratory depression, nausea, constipation, and long-term dependency [30]. Given the increasing concern over opioid misuse, the opioid-sparing properties of CA present a major clinical benefit.

In addition, CA was associated with a significantly shorter length of hospital stay compared to TEA. This is likely a downstream effect of improved postoperative pain control and reduced opioid consumption, which together contribute to fewer analgesia-related side effects and facilitate a more rapid return to baseline function. Although a shorter hospital stay enhances healthcare resource utilization and overall efficiency, CA was also associated with higher hospitalization costs. These increased costs are likely attributable to the specialized equipment required for CA and the additional procedural time involved. However, such expenses may be offset by the benefits of faster recovery, reduced incidence of opioid-related complications, and potentially greater patient satisfaction, all of which support the broader clinical value of CA.

Importantly, postoperative complication rates were comparable between CA and TEA, indicating that CA does not introduce additional procedural risks. This further reinforces the safety and efficacy of CA as a viable, and potentially superior, alternative to TEA, particularly in patients for whom TEA is contraindicated. Given the observed advantages in pain control, reduced opioid use, and earlier discharge, CA may be considered a strategic and patient-centered approach to perioperative pain management in individuals undergoing the Nuss procedure.

The present findings align with and expand upon those of Daemen et al. [4], who also found that CA is associated with shorter hospital stay and longer operation time than TEA in their meta-analysis of five studies. However, their analysis was weak due to the small number of studies and mostly observational design. The meta-analysis of the present study includes a larger dataset of 15 studies involving 1,391 patients. This larger sample size increases the statistical power of the analysis. In addition, the authors included a subgroup analysis of propensity matched data and RCT which provided a more robust evaluation. The current meta-analysis presents the first quantitative evidence of CA’s substantial opioid-saving impact which the earlier review by Daemen et al. [4] had merely qualified based on limited studies. The authors’ pooled analysis presents more robust evidence for the opioid-saving effect that is critical in the context of rising opioid-related complications and dependence. This study also demonstrated that CA results in significantly lower pain scores on POD 3 whereas the previous meta-analysis found no significant difference which may potentially be due to the small sample size and the heterogeneity in pain assessment. Additionally, unlike Daemen et al. [4], the analysis in the present study also examined hospitalization costs, revealing that CA, despite reducing hospital stay, is associated with higher costs, likely due to equipment and procedural expenses. Whether these costs are offset by the benefits of reduced opioid use and faster recovery is yet to be determined and further economic analysis is clearly needed.

Given the increasing adoption of CA and the publication of numerous new studies since the last meta-analysis, an updated synthesis of the evidence was both timely and necessary. A major strength of the authors’ meta-analysis is its methodological rigor. In addition to conventional pooled analyses, subgroup analyses were conducted focusing on RCTs and propensity-matched studies. Sensitivity analyses and meta-regression analysis were also performed to explore sources of heterogeneity and assess the robustness of the authors’ findings. Furthermore, by including more studies, increasing the sample size by more than seven times and evaluating broader outcome measures, the present review reflects current clinical practice more accurately than previous work. Together, these features enhance the reliability, applicability, and clinical relevance of these findings, thereby supporting more informed decision-making in perioperative pain management for patients undergoing the Nuss procedure.

Despite its strengths, this study has several limitations that must be acknowledged. Firstly, the pain scores were reported using different assessment tools across the included studies, most commonly the VAS and the NRS. This variability necessitated the use of SMD in the pooled analysis, which, although methodologically appropriate, reduces the interpretability of pain outcomes in clinical terms. Furthermore, these differences in pain scales may have introduced measurement bias and contributed to the observed heterogeneity in pain-related outcomes.

Secondly, data on hospitalization costs were inconsistently reported. Only a minority of studies provided sufficient detail to enable robust comparisons of the economic impact of CA vs. TEA. Important cost components such as resource utilization, equipment costs, length of operating time, and postoperative opioid requirements were not uniformly captured. As a result, the analysis of cost outcomes remains limited and should be interpreted with caution.

Thirdly, most included studies were retrospective observational studies, which are inherently susceptible to selection bias, information bias, and confounding. While the authors attempted to mitigate these limitations through a subgroup analysis of RCTs and propensity-matched studies, this subset still comprised a relatively small proportion of the total sample, and residual confounding may have persisted from outcomes that could not be fully adjusted for, such as baseline pain tolerance, surgeon experience, perioperative analgesic protocols, and institutional discharge criteria, all of which may have influenced pain scores, opioid use, and LOS.

Additionally, there was considerable variability in surgical and analgesic protocols across institutions including differences in the laterality and number of intercostal nerves targeted during CA, variations in the timing and administration of multimodal analgesia, and differing discharge criteria. This likely contributed to the observed heterogeneity, particularly in length of stay and opioid use. Additionally, individual complications were inconsistently reported, limiting separate analysis. Complications were therefore pooled as a composite outcome, reducing clinical specificity. While overall complication rates did not differ between CA and TE, CA-specific side effects—such as hypoesthesia, neuropathic pain, or delayed nerve recovery—were rarely reported and could not be reliably assessed. This under-reporting limits the authors’ ability to fully assess the safety profile of CA and highlights the need for future studies to systematically document sensory outcomes.

The meta-regression analysis did not identify a significant association between the preoperative Haller index and LOS. This may be due to the limited number of studies reporting Haller index values and possible inconsistencies in measurement or reporting practices. Furthermore, the Haller index may not fully capture the functional severity or complexity of the surgical procedure, which could limit its utility as a predictor of recovery-related outcomes.

Moreover, publication bias could not be fully excluded, particularly given the small number of RCTs and the tendency for studies with favorable outcomes to be more likely to be published. Although sensitivity analyses were conducted to evaluate the robustness of the authors’ findings, the inherent limitations of the available evidence base highlight the need for further high-quality research.

Lastly, although the Nuss procedure is currently the most widely used surgical approach for the correction of pectus excavatum, it is not the only operative technique available. Alternative methods, such as the modified Ravitch procedure or minimally invasive variants, are also used in selected patient populations [31]. The authors’ analysis focused exclusively on patients undergoing the Nuss procedure and did not include studies involving other surgical approaches. As a result, the findings may not be generalizable to patients undergoing different forms of pectus excavatum repair, and future research should consider comparative analyses across various surgical techniques.

Future studies should focus on prospectively collected data from well-powered RCTs using standardized pain assessment tools. Furthermore, economic evaluations that include both short-term and long-term costs will be essential to establish the cost-effectiveness of CA in comparison to TEA. Standardization of surgical and analgesic protocols across centers would also help reduce heterogeneity and improve comparability between studies.

In conclusion, the authors’ meta-analysis of 15 studies demonstrated that CA is associated with significantly reduced length of hospital stay, postoperative pain scores on POD 3, and reduced total opioid consumption during hospitalization compared with TEA in patients undergoing the Nuss procedure. Despite longer operative times and higher hospitalization costs, CA did not increase complication rates, reinforcing its safety and efficacy.

SUPPLEMENTARY MATERIALS

Supplementary materials can be found via https://doi.org/10.3344/kjp.25189.