Botulinum Toxin Type A Injected Into the Temporalis and Masseter Before Orthognathic Surgery to Improve Postoperative Pain

Background and Rationale: Dentofacial deformities in the maxillofacial skeleton often require surgical intervention to correct aesthetic and functional deficiencies (Naran, Steinbacher, and Taylor, 2018). Often, patients suffer a number of postoperative complications, including postoperative pain and muscle spasms (Phillips, Blakey, and Jaskolka, 2008). While post-operative analgesics are used, regimens are often unsatisfactory in their ability to alleviate patient discomfort (Raschke et al. 2018). Botulinum toxin type A variants (BoNT-A; including Botox®) are becoming an increasingly used intervention to treat muscle-related disorders in the head and neck region, including migraines, myofascial pain, and temporomandibular joint disorders (Walker & Dayan, 2014; Dodick et al, 2010; Mimeh, Fenech, Myers, & Ghanem, 2019; Khalifeh et al., 2016, Machado et al., 2020). This occurs by inducing a flaccid muscle paralysis, which alleviates tension-related discomfort (Kwon et al., 2019). Thus by injecting Botox® into the muscles surrounding the surgical area preoperatively, patients may experience a relief in tension-related muscle pain and better jaw function during recovery from surgery. In addition to its great safety profile, where side effects are either very minimal or exceedingly rare, Botox® may serve as a great supplemental option to current postoperative analgesic regimens (Dressler et al., 2015, Yeh et al., 2018).

Objective: The primary objective of this study is to investigate whether preoperative injection of Botox® into the temporalis and masseter in patients undergoing bilateral sagittal split osteotomies (BSSO) will improve pain scores and spasms in the immediate 2 week, as well as 6 week, postoperative periods. Additionally, patients will be followed 5 years from the time of surgery to look for indicators of relapse, including infection and hardware failure.

Research question: Can injecting Botox® into facial muscles 2 weeks prior to orthognathic surgery result in decreased pain and muscle spasms postoperatively?

Methods: The investigators plan to do a pilot study involving patients undergoing BSSO to evaluate postoperative pain scores and muscle spasms. There is a lack of evidence investigating post-operative pain management in orthognathic surgery using Botox®, thus the studies outlined in this proposal will serve as a pilot project. However, to guide sample size determination, another study investigating incobotulinumtoxinA, one of the variants of botulinum toxin with a similar potency profile to Botox® (Scaglione, 2016), was used. This product has been used as a therapeutic treatment for temporomandibular disorders to manage myofascial pain (Patel, Lerner, and Blitzer, 2017). For these studies, based on previous experiences, a pain difference of 15% was determined to be clinically significant. Assuming a normal distribution, a continuous pain outcome, with an ⍺-level of 0.05, and a power of 80%, the investigators estimate 32 patients/group will need to be enrolled to capture this difference.

This will be a double-blinded study. The patients, principal investigators and trained observers analyzing the data will be blinded to the two groups. Half of the patients will receive BoNT-A injections (Botox® Therapeutic by Allergan, Inc), with the other half receiving 0.9% normal saline injections as a control cohort. Injections for both cohorts will be done two weeks preoperatively. Patients will be randomly designated to one of the two groups by a research assistant at Kingsway Oral and Maxillofacial surgery not named to the investigative team. Patients will be randomized into two groups using a 2:2 randomized block design. A computer-generated algorithm developed the randomization sequence which allowed for allotment of each patient into either group 1 (indicating Botox® injection) or 2 (indicating saline injection). Patients will not be informed of the group they belong to, only that they will be injected with either Botox® or saline; the surgical assistants will prepare either the Botox® injection or the 0.9% normal saline injection. The injection will be given to the surgeons performing the procedures with no knowledge of which patients will be getting which injection.