Does tranexamic acid administration reduce postoperative nausea and vomiting after orthognathic surgery?

Introduction

Within orthognathic surgery, there is particular concern for postoperative nausea and vomiting (PONV) attributed to operating in the highly vascular maxillofacial apparatus, while also experiencing hypotension, an increase in swallowed blood, and diet limitations in the perioperative period (1,2). PONV remains an area of improvement in the field of surgery as it has been shown to result in postoperative complications, delay patient discharge, increase hospital costs, and decrease patient satisfaction (1-3). Previous studies report 40–72% of patients experience PONV after orthognathic surgery (2-7).

Multiple strategies have been implemented to mitigate PONV in orthognathic surgery. Beginning preoperatively, a scopolamine patch applied to the patient has been shown to decrease PONV (5,8,9). During surgery, decreasing volatile anesthetic and relying more on propofol for induction and maintenance has also shown to be an effective strategy (2,8,10). Administering dexamethasone and dexmedetomidine as well as dedicated antiemetic medications such as ondansetron has demonstrated efficacy in decreasing PONV (2,5,8,11,12). In addition to medication, surgeons may place a throat pack in efforts to decrease the amount of blood traveling to the stomach, but multiple studies have questioned its effectiveness in decreasing PONV (13-17). Following surgery, a vented nasogastric tube can be placed to evacuate gastric contents such as swallowed blood, but this has been found to have inconclusive effectiveness in decreasing PONV (8,18-20).

Tranexamic acid (TXA) administration has been implemented in various fields of surgery, including orthognathic surgery, for its main utility of decreasing blood loss resulting in decreased surgical time, and it could have a potential impact on PONV (2,18,21,22). TXA is a synthetic lysine analog that blocks fibrinolysis by reversibly binding to plasminogen, reducing fibrin binding and fibrinolysis (22-27). This clot stabilization action has made TXA particularly efficacious in decreasing blood loss in orthognathic surgery specifically by approximately 33–45% (21,28). In addition to decreasing intraoperative blood loss, TXA has the potential to limit post-operative bleeding and the associated ingestion of the blood from the nasopharynx.

To the investigator’s knowledge, the use of TXA as the primary variable in investigating the incidence of PONV after orthognathic surgery has yet to be documented. Decreasing the incidence of PONV has been approached in a multi-faceted way as the mechanism of PONV is multifactorial. TXA could potentially impact incidence of PONV through multiple mechanisms, however, the impact of TXA on PONV has not been fully elucidated. Postoperative bleeding from the maxillary sinuses and nasal cavity may be ingested and contribute to PONV. TXA may result in the patients ingesting less blood during and after surgery which may decrease the incidence of PONV. TXA has also been shown to decrease the length of surgery, a risk factor for PONV (2,19,23,24,29). Hypoperfusion has been postulated to potentially increase the incidence of PONV due to hypoxia or potential ischemia of the GI tract (30,31). Since TXA use has resulted in decreased blood loss and improved surgical field visualization, hypotensive anesthesia may not be as necessary as previously thought (28,29).

Given these mechanisms of potential influences TXA may have on PONV, the objective of the study was to investigate if TXA reduces the incidence of PONV following bimaxillary orthognathic surgery. The hypothesis was TXA administration reduces the incidence of PONV after orthognathic surgery. The specific aims were to (I) establish two cohorts of bimaxillary orthognathic surgery subjects with one group that received TXA and one that did not receive TXA; (II) identify the incidence of PONV in these groups; (III) compare the incidence of PONV between groups to determine the impact of TXA on PONV. We present this article in accordance with the STROBE reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-24-12/rc).

Methods

The investigators conducted a retrospective cohort study of two groups that underwent bimaxillary orthognathic surgery by the senior author, before and after the implementation of TXA into the surgical protocol. The surgeries were completed at UAB Highlands Hospital between 2019 and 2022. The exclusion criteria excluded subjects who only underwent single jaw surgery as well as those outside of the 14–75-year age range. Due to the uncertain risk of thromboembolic events following TXA administration in high thromboembolic risk patients, subjects with a history of a myocardial infarction, ischemic stroke, pulmonary embolism, or deep vein thrombosis were excluded from the study as they were ineligible to receive TXA (32-34). In addition, those with known defective color vision or a known allergy to TXA were also excluded (35).

Statistical analysis

The primary predictor variable was TXA administration. The primary outcome variable was the incidence of PONV after bimaxillary orthognathic surgery. This was defined as episodes reported in the electronic medical record or instances when a patient received anti-emetic medication during their postoperative course until discharged from the hospital. This method is consistent with other studies investigating PONV and orthognathic surgery (2-5). This data was recorded as a binary variable. A secondary variable also recorded was the number of instances of anti-emetic medication administration. In addition, the data was analyzed via univariate analysis between subjects who experienced PONV versus those who did not with the following parameters: TXA administration, age, gender, weight, length of surgery, estimated blood loss, hemoglobin and hematocrit measurements, and time spent under hypotensive anesthesia. After the univariate analysis was completed, those parameters with a P<0.15 were utilized in a multivariate analysis as well as the binary variable of TXA administration as it is the primary variable of the study. Changes in hemoglobin and hematocrit were determined by subtracting the postoperative lab levels taken within 24 hours after surgery from the preoperative lab levels that were collected on day of surgery for the majority of patients but also up to 4 weeks before surgery for a small portion of subjects. A subject was experiencing hypotensive anesthesia when their mean arterial pressure (MAP) decreased more than 30% below their baseline MAP taken preoperatively. A non-invasive blood pressure cuff was utilized, and blood pressure was taken every 5 minutes. The percentage of time spent under hypotensive anesthesia was calculated by dividing the number of MAP measurements qualifying as hypotensive anesthesia by the total number of MAP measurements recorded from surgical start to surgical finish (36,37).

All study subjects participated in the enhanced recovery after surgery (ERAS) protocol utilized by our institution in efforts to improve outcomes such as decreasing PONV, opioids, and patient length of stay (Table 1) (5). Propofol, opioid, and a paralytic were administered for induction with subsequent nasotracheal intubation. Volatile anesthetics, typically sevoflurane, was utilized at a minimum alveolar concentration (MAC) of 0.6–1. Before surgical start, 1 g TXA was given intravenously in the study cohort subjects. Ketamine 0.5 mg/kg and dexamethasone 0.1 mg/kg were then given as a bolus. In addition, a dexmedetomidine infusion set at 0.4 mcg/kg/h and a propofol infusion set at 15 mg/kg/h were utilized. Intravenous fluid goal was capped at 1,800 mL. At the end of surgery, ketorolac 30 mg was administered and the surgeon injected applicable surgical sites with 0.5% bupivacaine with 1:200,000 epinephrine. Other medication decisions and dosages were made by the anesthesia provider for each individual case. For this study, the postoperative period extended from patient arrival in the post anesthesia care unit until discharge from the hospital.

Data was collected via the electronic medical record and subsequently de-identified. Descriptive, bivariate, and multivariate analyses were utilized with P<0.05 considered statistically significant.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of the University of Alabama (IRB-30008753) and individual consent for this retrospective analysis was waived.

Results

A total of 63 subjects met inclusion criteria with 28 male and 35 female subjects. Their mean age was 27.37 years (range, 14–74 years) and their mean weight was 76.6 kg (Table 2). No significant variation was present in regards to sex, age, or weight between those who received TXA versus those who did not (Table 3). No subjects received blood transfusions and no TXA related complications were encountered.

The study’s incidence of PONV regardless of cohort was 57.14%, while the number of antiemetic medications administered for a patient with PONV was 2.28 during the duration of their hospitalization. The TXA cohort had 21 (61.76%) of the 34 subjects experiencing PONV versus 15 (51.72%) of the 29 subjects in the non-TXA group (P=0.42) (Table 4). The average number of recorded episodes of PONV during the hospital stay when positive for PONV was 1.91 for the TXA group and 2.64 for the non-TXA group (P=0.25). The recorded study results were not statistically significant. Also, when comparing multiple parameters in subjects that experienced PONV versus those who did not via univariate analysis, the PONV group had experienced increased blood loss (P=0.02), increased surgical time (P=0.14), and were more likely to be female (P=0.13) (Table 4). Then a multivariate analysis was performed with the aforementioned variables as well as the binary variable of TXA administration (Table 5). In this multivariate analysis, the PONV group had experienced more estimated blood loss (305.8±129.8 mL) than those subjects who did not experience PONV (231.7±105.5 mL) (P=0.04). In this analysis, TXA administration (P=0.16), subject sex (P=0.13), and length of surgery (P=0.24) were not statistically significant.

Discussion

PONV is an important surgical parameter to address as it can delay patient discharge, decrease patient satisfaction, and increase hospital costs as well as potentially causing extensive complications such as wound dehiscence, dehydration, electrolyte imbalance, aspiration, or airway obstruction (1,2). TXA has become increasingly commonplace in the surgical field for its reliability in decreasing blood loss and operative time which are risk factors for PONV (2,18,21,22,28-30). Therefore, the objective of the study was to investigate if TXA reduces PONV after bimaxillary orthognathic surgery. The hypothesis was TXA administration does reduce the incidence of PONV. The specific aims were to two groups, one group that received TXA and one that did not receive, and furthermore, compare the incidence of PONV between groups to determine the impact of TXA on PONV.

The study’s overall PONV incidence was 57.14%, while the number of antiemetic medications administered per patient with PONV was 2.28 during their hospitalization. The study demonstrated with statistical significance that those who experienced PONV had 32% more estimated blood loss than those who did not experience PONV. Overall, the results of the study are inconclusive in determining the effect of TXA on PONV following orthognathic surgery.

The use of TXA as the primary variable investigating the incidence of PONV after orthognathic surgery has not been reported. The Stratton et al. study analyzed the ERAS pathway as a whole and compared it with patients who did not experience the ERAS pathway (5). The ERAS pathway included TXA but also included the addition of ketamine, dexmedetomidine, and other medications that may impact PONV incidence. There was a statistically significant difference between groups in average episodes of PONV per patient (1.6 episodes in the ERAS group and 2.4 episodes in the non-ERAS group) (5). This is similar to the number of episodes per patient in our study as our TXA group experienced an average of 1.9 PONV episodes versus 2.6 episodes in the non-TXA group.

The overall incidence of PONV following orthognathic surgery has been reported by multiple studies ranging from about 40–72% (2-7). This study’s incidence of PONV regardless of cohort was 57.14%. The overall incidence of PONV in the aforementioned Stratton et al. study was 50.5% for the 111 subjects (5). Silva et al. reported a PONV incidence of 40% of PONV of 514 subjects following orthognathic surgery (2). Pourtaheri et al. performed a study of 492 subjects undergoing orthognathic surgery, reporting 59.4% of patients received antiemetic medications for nausea and 28.4% experienced postoperative vomiting (4). Those subjects who experienced PONV received an average of 2.8 antiemetic medications during hospitalization while our study averaged 2.3 antiemetic medications overall (4). Ghosh et al. documented a PONV incidence of 59.4% in their study of 101 orthognathic surgery patients (6). In addition, Phillips et al. conducted a study of 204 subjects who underwent orthognathic surgery, and 67% of the subjects had postoperative nausea and 27% had postoperative vomiting (3). In Dobbeleir et al., of 72 patients undergoing bimaxillary orthognathic surgery, 72% experienced postoperative nausea while 43% experienced postoperative vomiting (7).

The increased incidence of PONV following orthognathic surgery specifically can be attributed to periods of hypotension, an increase in swallowed blood, and diet limitations postoperatively (1). Hypoperfusion has been postulated to potentially increase the incidence of PONV due to hypoxia or potential ischemia of the gastrointestinal (GI) tract (30,31). The GI tract has minimal to no regulatory capacity, making it intolerant to even brief episodes of ischemia (30,31,38). Serotonin levels have been shown to increase in periods of GI hypoperfusion which may cause PONV via 5-HT3 receptors on vagal terminals innervating the intestinal mucosa and the vomiting center in the brainstem (30,31,38,39). As TXA has been shown to decrease blood loss and improve surgical field visualization, TXA may potentially decrease reliance on hypotensive anesthesia (28,29). In a recent study of practice patterns of 85 academic oral and maxillofacial surgeons, 48% of surgeons seek a MAP of 60–64 mmHg intraoperatively, which some consider as hypotensive anesthesia (40). Interestingly, only 25% of respondents utilized TXA for orthognathic surgery patients (40). In addition, our study demonstrated with statistical significance that those who experienced PONV also had 32% more estimated blood loss than those who did not experience PONV; thus, finding ways to prevent blood loss through TXA or other means remains a crucial step toward preventing PONV.

In an effort to decrease PONV, ERAS protocols have been established in part to decrease PONV through a multi-faceted approach (5). Identifying common risk factors for PONV such as the female gender, non-smoking history, use of volatile anesthetics, use of postoperative opioids, and history of PONV or motion sickness may assist in identifying susceptible patients (1,2,7). These crucial efforts to decrease the rates of PONV may help prevent complications such as wound dehiscence, dehydration, electrolyte imbalance, aspiration, or airway obstruction (2,6).

Potential limitations to the study are important to identify in efforts to construct adequate context. The study was retrospective in nature and performed by a single surgeon at one site. This decreases the variability in surgical techniques and protocols which may limit the study’s reproducibility. In an attempt to limit this variability, our department at the University of Alabama at Birmingham has established the ERAS protocol for orthognathic cases to create a standard protocol to be followed by the anesthesia staff (5). An additional limitation is the inability for the electronic medical record to discern between post-op nausea and vomiting as most episodes for the study were recorded as instances the patient received anti-emetics. This method is consistent with other studies investigating PONV and orthognathic surgery, but it could be improved upon for great precision (2-5).

Conclusions

The results of this study did not find a significant association between TXA administration and PONV incidence within orthognathic surgery. Even though a significant difference was not found, this analysis and review is a valuable contribution to the literature pertaining to the use of TXA and the prevention of PONV in orthognathic surgery. TXA may still be a useful adjunct in orthognathic surgery to potentially decrease the incidence of PONV by decreasing blood loss and surgical time, both risk factors for PONV. Future research in the form of a prospective study with a large sample size may assist in determining the impact of TXA alone on the incidence of PONV after orthognathic surgery.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://joma.amegroups.com/article/view/10.21037/joma-24-12/rc

Data Sharing Statement: Available at https://joma.amegroups.com/article/view/10.21037/joma-24-12/dss

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-24-12/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-24-12/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of the University of Alabama (IRB-30008753) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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