Botulinum Toxin A for Complex Hernia Repair: Advancing Evidence to Support Clinical Practice

Abstract

Dear Editor,

A hernia is defined as the abnormal protrusion of an organ or tissue through a defect in the abdominal wall¹ and is a common postoperative complication, particularly in areas of anatomical weakness in the abdominal musculature. After 10 years, the recurrence rate of incisional hernias can reach up to 64%², posing a significant challenge in the management of these patients.

Complex hernias negatively impact patients' quality of life and are closely associated with complications such as intestinal obstruction or strangulation.  Only in the United States, more than 500,000 hernia repairs are performed annually^3,4, generating an annual cost of $3.4 billion⁵. A 5% reduction in the incidence of incisional hernias could lead to an annual cost decrease of around €4 million⁶. Thus, preventing the recurrence of incisional hernias is a significant challenge in the medical field.

Due to the high recurrence rate, morbidity, and economic impact associated with incisional hernia recurrences—especially considering that the recommended treatment for these hernias typically involves additional surgical intervention—it is crucial to explore and test various methods for hernia repair.

The primary objective of incisional hernia repair is to achieve a tension-free midline fascial closure reinforced by mesh⁷. Mesh reinforcement directly supports the reconstruction and reduces lateral forces, or shear stress, on the repair site⁷. However, in patients with large hernia defects, chronically retracted lateral abdominal wall muscles, or irreducible visceral contents within the hernia, midline closure may be challenging or even unfeasible. Bridged hernia repair should generally be avoided due to its association with unacceptably high recurrence rates^8,9.

To overcome these challenges, in 1990, Ramirez et al. introduced the original component separation (CST) techniques^10,11, and it was designed to reduce midline tension and enable mesh placement through sequential fascial layer release along the abdominal wall¹². Although CST improves outcomes by reducing tension on the midline, it also carries a heightened risk of surgical site morbidity, including infection, wound dehiscence, and seroma formation, with risk profiles varying across techniques^9,12. Since Ramirez’s original approach, several alternative techniques have emerged. The posterior component separation with transversus abdominis release (TAR) enables significant fascial advancement with less dissection, achieving primary closure rates of up to 97.2%¹³.

Minimally invasive approaches, including laparoscopic and robotic techniques, have also been developed to increase intraoperative strategies, especially in complex hernias or incisional hernias¹⁴. Despite these benefits, each approach has unique risks; for instance, laparoscopic repairs have shown an increased incidence of intestinal injury¹⁵. For large or complex hernia defects, preoperative interventions such as progressive preoperative pneumoperitoneum (PPP) and tissue expanders have been investigated to enhance abdominal cavity volume and reduce closure tension¹⁶. However, outcomes for these preoperative strategies remain variable and somewhat limited in effectiveness¹⁷.

Given the limitations of existing techniques for managing large incisional hernias and complex abdominal wall defects—such as high recurrence rates and complications tied to elevated intra-abdominal pressure¹⁸ and suture line tension—botulinum toxin A (BTX) has emerged as a potential preoperative adjunct. As a neuromodulator, BTX has shown promise in abdominal wall surgeries by reducing lateral tension, facilitating hernia closure¹⁹, and providing postoperative pain relief ²⁰.

By inducing flaccid paralysis²¹ in the abdominal muscles, botulinum toxin A (BTA) reduces muscle tension, facilitating the approximation of defect edges without the need for extensive fascial dissection. First described in 2009²², this preoperative chemical paralysis of the lateral abdominal wall provides a less invasive alternative to traditional component separation techniques (CST), which also aim to increase abdominal wall flexibility and reduce lateral tension for easier midline closure^23,24. Unlike CST, however, BTA affects all injected muscle layers simultaneously, rather than targeting a single muscle layer for transection, broadening its effect across the entire lateral abdominal wall and enhancing pliability. Furthermore, most studies report minimal direct complications following BTA injections, reinforcing its profile as a safe and effective adjunct in complex hernia repair^25-32.

The role of botulinum toxin A (BTA) as a preoperative adjunct in abdominal wall reconstruction (AWR) has gained significant attention in the management of complex hernias. Recent meta-analyses and observational studies have highlighted its potential benefits in facilitating tension-free midline fascial closure, particularly in patients with large hernia defects and severe loss of domain.

In 2020, Deerenberg et al. presented a comprehensive clinical perspective based on data from ten studies (n = 398 patients) ³³, advocating for the use of botulinum toxin A (BTA) as a safe, straightforward, and promising technique in ventral hernia repair. However, the authors noted a lack of consensus regarding patient selection criteria, emphasizing the need for further research to guide its application. Building on this, Wegdam et al. conducted a systematic review of 14 studies examining the use of botulinum toxin A (BTA) in patients with ventral hernia³⁴. The primary outcome analyzed was abdominal wall compliance, measured as the elongation of the lateral abdominal wall. Based on data from four studies, they reported a median elongation of the lateral abdominal muscles of 4.0 cm. However, as medians may overestimate the true effect, this value should be interpreted cautiously. To address these gaps, Timmer et al. performed a meta-analysis in 2021 involving 23 studies and 995 patients³⁵. This analysis demonstrated significant elongation of the lateral abdominal wall by a mean of 3.2 cm per side (95% CI 2.0 – 4.3, I² = 0%, p < 0.001), resulting in a total elongation of 6.3 cm. Additionally, they reported a significant but heterogeneous decrease in transverse hernia width (95% CI 0.2–6.8, I² = 94%, p = 0.04) and increased fascial closure rates in BTA-pretreated patients [RR 1.08, 95% CI 1.02–1.16, I² = 0%, p = 0.02]. However, as with previous studies, the quality of evidence was limited, and outcomes were influenced by factors such as hernia size, loss of domain, tissue quality, and surgical techniques. A systematic review by Dias et al. (2023) analyzed seven studies with a total of 261 patients, demonstrating a mean lateral abdominal wall elongation of 4.11 cm per side (95% CI 3.76–4.46, I² = 27%). This confirmed BTA's efficacy in improving abdominal wall compliance as measured through pre- and post-treatment imaging. Secondary outcomes included recurrence (0.03; 95% CI: 0.01; 0.06), surgical site infections (0.06; 95% CI: 0.04; 0.10), and surgical site occurrences (0.12;  95% CI: 0.09; 0.16), though these outcomes exhibited substantial heterogeneity, reflecting variations in surgical techniques, follow-up durations, and patient populations³⁸.

Since the initial meta-analyses on this topic, new studies with larger sample sizes have been conducted to address questions that remained unresolved. Among these, key areas of investigation include the impact of botulinum toxin A (BTA) on facilitating primary fascial closure in large ventral hernias and the associated need for adjunctive techniques such as component separation (CST). Bueno-Lledó et al. conducted a prospective study at a tertiary center involving 80 patients with large ventral hernias (12–18 cm), reporting that 40 patients pretreated with BTA achieved primary fascial closure without requiring CST ³⁶. Similarly, Deerenberg et al. examined 220 patients with large hernias (75 treated with BTA and 145 without), matched by BMI and defect size (mean hernia width of 14.1 cm). Their findings demonstrated a higher rate of fascial closure in the BTA group (92% vs. 81%, p = 0.036), although these patients more frequently required CST (61% vs. 47%, p = 0.042) ³⁷.

In this context, the meta-analysis conducted by Dias aimed to address these open questions with greater depth. Specifically, it sought to evaluate whether BTA reliably enhances fascial closure, quantify the extent of its benefit, and determine whether these outcomes are attributable solely to the toxin or to a combination of the toxin and adjunctive surgical techniques³⁸. By synthesizing the available evidence, Dias’ study aimed to fill the gaps left by previous research, particularly regarding the relationship between BTA administration and the reliance on more invasive approaches such as CST.

Botulinum toxin A (BTA) shows significant promise as a preoperative adjunct in the management of complex hernias, particularly for facilitating fascial closure in challenging cases. However, its clinical application is currently constrained by gaps in evidence and the variability of existing protocols. Many studies are observational or descriptive rather than analytical and often lack control groups, as highlighted in prior reviews ^37,39,40. Additionally, there is little consensus on key preoperative factors, such as the optimal timing for BTA administration, effective dosing strategies, injection techniques, and patient selection criteria. While the widely accepted four-week interval between BTA administration and surgery is based on its pharmacodynamic properties, this has yet to be validated in translational or clinical research. Such limitations underscore the need for systematic investigation to standardize preoperative BTA use and maximize its efficacy once ensuring that BTA is administered at the right time to fit the optimal surgery window can be complex in a busy clinical workflow, especially if imaging or other assessments are required to monitor its effect before proceeding with the surgery.

A translational research approach is essential to address these gaps, starting with studies in animal models to optimize preoperative protocols. These models can provide critical insights into the effects of BTA on the abdominal wall, the ideal dose and injection sites, and the timeline for peak efficacy before surgery. These findings can then inform early-phase human studies to refine indications for BTA use, including patient stratification based on hernia complexity and other factors. Translational research should also explore whether BTA offers additional preoperative benefits, such as reducing tension during repair. By focusing on these preoperative applications, a stepwise, evidence-based strategy can establish BTA as a safe and effective tool, bridging the gap between promising experimental data and practical clinical guidelines.

In summary, while botulinum toxin A presents a promising adjunctive strategy for managing complex abdominal wall defects and large hernias by reducing tension and potentially alleviating postoperative pain, its clinical application is still hampered by significant gaps in research. The lack of rigorous, controlled studies limits our understanding of BTX’s full benefits and optimal protocols in this context. We urge the scientific community to prioritize high-quality experimental research to validate and refine BTX’s role in hernia surgery. By doing so, we may advance toward more effective, standardized treatment options for this challenging and costly condition.