Appropriate dosage for BTX use in the abdominal wall has been described anywhere between 100 IU (10) and 500 IU (3, 4, 19). The doses most frequently encountered in the literature being 200 IU (23), 300 IU (8, 24), and 500 IU (19). Some small studies have also given different doses to each patient throughout the study (25). The total dose is then divided equally between 3 and 5 injection sites each side of the midline. Some groups have altered their practise over the last decade; such as Jacombs et al. (17) who describe their reduction from 300 IU between 2012 and 2016 to 200 IU between 2016 and 2019. This reduction was related to a reduction from infiltrating 3 layers of the lateral muscle complex to just 2 layers.

Some discrepancy in dosage between groups may be due to different BTX preparations, such as Botox® or Dysport®. In their largest, most recent paper Bueno Lledó et al. (19) describe using Dysport® (Ipsen, Boulogne-Billancourt, France) whereas both Yurtkap et al. (18) and Deerenberg et al. (14) describe using Botox (Botulinum toxin Allergan, Inc., Irvine, California). Jacombs et al. (17) describe using an equivalent dose of either of the two formulations. Recent literature has described a possible 3:1 concentration ratio between the two formulations; (26) a factor clinicians should be aware of when choosing a treatment regime.

The technique originally described by Ibarra-Hurtado et al. involved 500 IU injected over 5 sites on each side: “two over the midaxillary line, between the costal border and the superior iliac crest, and three over the external oblique muscle” (7). Years later, when Smoot et al. published their experience using BTX for post-op analgesia they described a 3-site, 300 IU technique (8) without specifying the injection sites. This method was then better described in two publications by the same group, describing six injection sites in total: “right/left subcostal; right/left anterior axillary; right/left lower quadrants” (9, 27).

Some have suggested that nearly all published BTX injection protocols adhere to one of these two camps (Ibarra-Hurtado OR Zielinski/Smoot) (18). Groups like the Spanish Bueno-Lledó group have followed the description by Ibarra-Hurtado et al. giving BTX in 5 very similar locations to the Mexican group (3). Others such as Yurtkap et al. and Catalan-Garcia et al. have adopted the Zielinski/ Smoot protocol (15, 18). Some studies have used mixed protocols, using the higher 500 IU dose but between 3 injection sites (21).

When BTX use was first described, convention was that all three (External Oblique, Internal Oblique and Transversus Abdominus) lateral abdominal wall muscles were infiltrated. This idea has however been challenged in recent years. In their 2020 paper, Elstner et al. conducted a prospective study of 46 patients to assess whether selective 200 IU BTX infiltration of only the 2 most superficial lateral muscle layers could achieve a sufficient medialisation of the rectus muscles (23). Their conclusion that this technique was effective, altered their practise for some patients. This new 200 IU regime was used in patients with certain back complaints, due to Tranversus Abdominis' key role in thoracic spine stabilisation. This practise has been adopted by other groups (14) who noted no difference in numbers of patients requiring fascial release between 2 and 3 layer infiltration.

Other groups have made use of certain adjuncts to aid the BTX infiltration process. The Bueno-Lledó group routinely use electromyography (EMG) to ensure that the BTX is injected where it is most effective (19). They argue that this establishes whether the targeted muscle is denervated or fibrotic (28).

Due to its long-acting effects, the ideal timing of pre-operative BTX likely involves a window of several days and has been described differently between authors. Early papers affirmed that the maximum effect of BTX is achieved at 2 weeks after injection (9, 27), however a recent systematic review and meta-analysis found BTX being given anywhere between 6 and 45 days before surgery (12). When originally described, CT images were reviewed 4 weeks post BTX—upon which most patients has experienced a reduction in fascial defect size (7). The Bueno-Lledó group aim to give BTX 4 weeks before surgery and have a mean pre-op injection of around 32–38 days (3, 19). This is similar to Deerenberg et al. who gave BTX an average of 32.5 days pre-operatively (14). Jacombs et al. give BTX 7–30 days pre-operatively, unless the hernia is particularly large in which case BTX is given between 21 and 30 days (17). In their 2021 paper Yurtkap et al. gave BTX a median of 45 days before surgery but with a large range of anywhere between 28 and 119 days (18). Please see Table 1 for a summary of recent studies and their BTX treatment regimes.

The precise quantifiable benefits of BTX treatment are yet to be established. One issue complicating the evidence is the number of different criteria used to quantify BTX's effects, creating heterogeneity. Commonly recorded outcomes such as rate of fascial closure can be confounded by various factors, making other measures such as reduction in fascial defect or increase in lateral muscle length more objective and repeatable outcomes.

When first described, the efficacy of BTX was assessed by its capacity to reduce hernia defect size (7). Ibarra-Hurtado described 10 patients in which the mean hernia defect had been reduced by a mean of 5.25 cm from an original mean defect size of 13.85 cm (7). Chavez-Tostado et al. also analysed reduction in hernia defect width after only 100 IU of BTX but found no significant improvement (10).

Five years after their initial publication, Ibarra-Hurtado et al. published the results for 17 of their BTX patients – this time describing the effects of BTX upon lateral muscle elongation. They concluded that the BTX treatment facilitated a reduction in lateral muscle thickness by around a 1 cm, and an increase in lateral muscle length by 2.44 and 2.59 cm on the left and right, respectively (11). Hernia Institute Australia have published their outcomes in terms of lateral muscle elongation on several occasions. They have previously published mean increases of 4.2 (16) and 4 cm (29), and their largest cohort to date achieved a mean increase in lateral length of 4.7 cm per side (17).

There have now been several systematic reviews that have looked at the quantifiable benefits of BTX. Early reviews only assessed fascial closure rates and hernia defect reduction (30) whereas others chose to focus on fascial closure rates as a primary variable (12). Wegdam et al. (31) focused specifically on the quantifiable benefits of preoperative BTX. Their intended primary outcome was the elongation of the lateral muscle complex and secondarily reviewed the reduction in fascial defect width. They analysed 14 studies which summarised the findings for 344 patients. They identified four papers that had measured lateral muscle complex elongation — giving a median elongation of around 4 cm. This result was similar to a previous systematic review (3.33 cm) by Weissler et al. (32). When the review looked at their secondary effects such as reduction of hernia defect width, they identify three studies that reveal a defect reduction of 4.8 cm, and two other studies that reveal a statistically significant reduction of 5.1 cm (31). In the meta-analysis from Weissler et al. a mean hernia width reduction was identified at 5.79 cm (32).

Some studies have focused on measuring the potential improvements to LOD measurements. Bueno-Lledó et al. observed a 15% reduction in the Hernia/Abdomen volume ratio (VIH/VAC) when using both BTX and PPP (19). In an earlier study focusing on 70 patients with LOD hernias (28) there was a similar mean reduction in the VIH/VAC ratio of 16.6%.

BTX was originally investigated for managing post-operative abdominal wall pain in 2011 when Smoot et al. gave BTX injections to treat muscular spasms after a laparoscopic hernia repair. They achieved a reduction in pain scores which lasted through 3 months of follow-up (8). Zendejas et al. conducted a larger study where they compared the post-op pain scores and opioid use in 22 BTX cases and 66 controls. They were able to conclude that in at least 2 of the 6 post-operative days assessed, that BTX patients were taking a significantly smaller dose of opiate analgesia, and also reported less pain on post op days 2 and 4 (27). There is not complete consensus however—one study of 97 BTX patients noticed they experienced more pain at 30 days post-op than the non BTX group (n = 291) (22).

Whilst the literature lacks robust evidence, some have asserted that BTX treatment may help reduce hernia recurrence. Theoretically the paralysis of the lateral abdominal wall muscles would reduce tension across the wound, creating a more tension-free healing process. van Rooijen et al. (12) and Deerenberg et al. (14) have both commented on the particularly low hernia recurrence rates after BTX treatment, the latter adding that insufficient long term studies exist to confirm how BTX may effect recurrence rates. Rodiriguez-Acevedo et al. assert in their work that that BTX helps to protect midline wounds over the initial 3 months of healing (16). The same group have also described giving BTX post-operatively as a prophylactic adjunct to aid the initial healing of the rectus sheath (33).

After a decade of use, BTX seemingly offers a low side-effect profile, and has been described as so by analysis from the Abdominal Core Health Quality Collaborative (22). Its use has been described as either safe, low morbidity or lacking complications in several publications (13–15, 22). Given its inherent non-invasiveness, it is likely to be significantly safer than techniques such as PPP. Yurtkap et al. found that nearly one third of their 17 PPP patients had suffered complications, without any of their BTX patients suffering similarly (18). This is not to say that BTX is without side-effects, and those commonly described in the literature include weak cough, back pain, and superficial bruising at the site of injection (12). Some efforts have been made to mitigate these side-effects, such as Jacombs et al. providing their BTX patients with abdominal binders after treatment (17). The same group from Hernia Institute Australia have also begun omitting injections into the Transversus Abdominis for patients with back issues (23).