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Elhage et al. Plast Aesthet Res 2020;7:16 I http://dx.doi.org/10.20517/2347-9264.2020.03 Page 7 of 9
[22]
of the EO and IO can be performed, sparing the TA and its truncal stabilizing function. Elstner et al.
found comparable results of two and three layer BTA injection in laparoscopic hernia repair. A total of
at least 200 BTA units at a concentration of 2 U/mL or more was used in all studies. Since there is great
heterogeneity in timing, sites and total BTA units injected in the studies, no conclusion on the optimal
dose, concentration, sites, or target muscle layer(s) can be formulated. Furthermore, one study which
assessed abdominal wall effects of BTA with both functional CT and EMG at 1-4 weeks after injection
[31]
showed non-uniform distribution and duration of the induced paralysis .
BTA has also been shown to prevent release of the pain-modulating molecules calcitonin gene-related
peptide and substance P from the presynaptic motor nerve terminal and could have a positive effect on
[15]
postoperative pain control . One study reported on post-operative pain and found promising results
with decreased morphine use and pain reported in the short-term postoperative period. Nevertheless, the
[17]
analgesic effects of BTA would benefit from further research .
With the introduction of new medications for clinical use, patient safety is of utmost importance. The
majority of studies did not report complications with the use of BTA and of those that did, they were minor
in nature. Complaints after BTA injection included a mild cough or sneeze, bloating, and back pain, and
nearly all resolved after application of an abdominal binder. However, serious adverse effects of BTA injection
can occur and have been described after administration at other sites of the body. These adverse effects are
[32]
often related to the specific injection site, non-sterile injection technique, or injection into infected tissue .
Four cases of life-threatening botulism have occurred after injection of highly concentrated, unlicensed
[33]
preparation of BTA for cosmetic purposes . Although the precise human lethal dose of crystalline BTA
is not known, extrapolation from primate studies suggest an approximate intravenous or intramuscular
lethal dose of 40 U/kg of BTA in humans [34,35] . Therefore, for an average 70 kg human, the lethal dose
would be 2800 units in total; in AWR, the maximum reported total dose used is 300 units of BTA, which
is drastically lower than the described lethal dose. Proper storage of the product, selection of the correct
dose, and proper administration techniques are necessary to prevent these adverse events when injecting
BTA into the abdominal wall. Patients with neuromuscular junction disorders such as myasthenia gravis,
Lambert-Eaton syndrome, and anterior horn disorders are particularly susceptible to the adverse events of
[32]
botulinum toxin and should not be injected with BTA .

CONCLUSION
The initial results of BTA use in AWR are promising and safe, with beneficial alterations to the abdominal
wall and high rates of fascial closure, and only minor side effects reported. There remains much variance
in BTA treatment regimens and at this time, a consensus on the dosage, technique, and timing of injection
has yet to be reached. There remains a lack of high-level evidence and the existing literature is limited by
studies with small sample sizes, unclear patient selection criteria, and treatment regimen heterogeneity.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Elhage SA, Deerenberg EB, Shao JM, Augenstein VA, Heniford BT
Performed data acquisition, as well as provided administrative, technical, and material support: Elhage SA,
Deerenberg EB, Shao JM
Drafting of manuscript and critically important revisions: Elhage SA, Deerenberg EB, Shao JM, Augenstein
VA, Heniford BT

Availability of data and materials
Not applicable.