Perioperative Nerve Blockade Reduces Acute Postoperative Pain after Orthognathic Surgery

Background The role of perioperative pain management is not only to reduce acute postoperative pain (POP) but also to prevent chronic POP. It would be important to know the usefulness of nerve blockade for perioperative management. However, it has not been extensively studied in orofacial surgery. The objective of the study was to investigate whether perioperative nerve blockade reduces acute POP after orthognathic surgery. Methods Patients scheduled for orthognathic surgery were retrospectively reviewed (“preblock group”: the nerve blockade was performed before emergence from general anesthesia, and “no preblock group”: the nerve blockade was not performed before emergence from general anesthesia). The visual analog scale (VAS; 0–100 mm)-POP intensity, the VAS-POP areas under the curves (VASAUCs (mm × day)) in addition to VASAUCs for postoperative hours 6 (VASAUC_6), 12 (VASAUC_12), 18 (VASAUC_18), and 24 (VASAUC_24), the analgesic requirement period (day), and the number of days with pain (day) were analyzed. Data are presented as median (interquartile range) values. Results Fifty-six patients (preblock group, 22; no preblock group, 34) were included (21 males, 35 females; age: 22.0 [21.0–28.0] years). VASAUC_6, VASAUC_12, VASAUC_18, and VASAUC_24 in the preblock group were significantly smaller than those in the no preblock group (3.5 [2.0–7.2] vs. 7.4 [5.1–10.0], p = 0.0007; 9.5 [6.4–13.7] vs. 15.0 [7.2–22.9], p = 0.042; 15.7 [10.3–23.1] vs. 29.3 [18.9–37.2], p = 0.0002; and 17.6 [12.7–27.2] vs. 39.5 [22.9–46.9], p = 0.001, respectively). There were no significant differences between the 2 groups in VASAUC, the analgesic requirement period, and the number of days with pain (p > 0.05). Conclusions Perioperative nerve blockade reduces POP after orthognathic surgery, especially for the acute postoperative period.


Introduction
Te role of perioperative pain management is not only to reduce acute postoperative pain (POP) but also to prevent the development of chronic POP [1,2].Acute pain management/acute pain service (APS) is being increasingly established to provide good POP control and hence reduce analgesic consumption [3][4][5].Acute POP is an important clinical issue as it can have signifcant efects on rehabilitation, length of hospital stay and/or hospital readmission, and adverse events related to excessive analgesic use [6].Poorly controlled acute POP has also been suggested as a risk factor for the development of chronic POP [7,8], and the use of multimodal analgesia for the management of acute POP is considered an important paradigm in the context of the development of chronic POP [9][10][11][12].Tus, acute pain management/APS is of crucial importance in any surgical setting [4,5,13,14], including in orofacial surgery, an area that has not been extensively studied [15].APS using nerve blockade is useful for perioperative management [16], and it would be important to know whether this is also applicable in orthognathic surgery settings.We hypothesized that the perioperative nerve blockade would reduce acute postoperative pain after orthognathic surgery.
Te aim of this study was to investigate the efect of nerve blockade for acute POP relief after orthognathic surgery.

Methods
2.1.Participants.Tis study was conducted at the Division of Dental Anesthesiology, Department of Diagnostic and Terapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan.A retrospective review of patients scheduled for Le Fort type I osteotomy (Le Fort 1) and bilateral sagittal split ramus osteotomy (SSRO) between July 2017 and June 2023 was performed.
Te study was conducted in accordance with the guidelines of the Declaration of Helsinki and the World Medical Association and was approved by the Ethics Committee of Meikai University (approval number: A1803, approval date: June 15, 2018).Te requirement for informed consent was waived due to the retrospective nature of the study.Study information was available on the website (https://www.meikai.ac.jp/dent/kenkyubu.html), and participants could opt out at any point.

Sample Size
Calculation.An a priori power analysis was performed to establish the necessary sample size for this study using G * Power (version 3.1.9.7) [17] with a probability of type I error of 0.05, a power of 0.8, and an efect size of 0.8.Based on these parameters, the power analysis demonstrated that a total sample size of 52 was required for this study.Since some data may be missed due to various reasons, the initial sample size was increased by 10%.Terefore, the fnal sample size for this study was 56.

Anesthesia.
Orthognathic surgeries were performed under balanced general anesthesia with endotracheal intubation using propofol or remimazolam besylate, remifentanil hydrochloride, and rocuronium bromide.Infltration anesthesia using 1% lidocaine hydrochloride monohydrate with epinephrine (1 : 100,000) was performed 5 min before surgery by the surgeon.Acetaminophen (2000 mg if the body weight of the patient was over 50 kg or 1000 mg if the body weight of the patient was under 50 kg) was administered 30 min before the end of the surgery.Te dose of remifentanil and anesthetic agents was modifed by the anesthesiologist based on the surgical stress and hemodynamic changes.A controlled arterial hypotension strategy with nitroglycerin was used.

Postoperative Pain Management and Evaluation of
Postoperative Surgical Pain.For POP management, multimodal analgesia with nerve blockade was performed.Te nerve blockade was performed by the anatomical landmark techniques with computed tomography evaluation using 0.5% levobupivacaine hydrochloride.Te nerve blockade was performed at the anesthesiologist's discretion based on operative invasion, expected POP intensity, which was over 50/100 on the visual analog scale (VAS, 0-100 mm; the left endpoint (0) of the VAS indicated "no pain," whereas the right endpoint (100) indicated the "worst pain imaginable"), or patient complaint.Acetaminophen, furbiprofen axetil, loxoprofen sodium hydrate, or other pain medications including rescue analgesic administration were provided to individual patients for the management of POP.Te prescription was decided at the anesthesiologist's discretion based on POP intensity and patients' general condition such as liver dysfunction or allergy.
Retrospectively, patients were divided into two groups-the "preblock group": the nerve blockade was performed before emergence from general anesthesia, and the "no preblock group": the nerve blockade was not performed before emergence from general anesthesia.In the no preblock group, if POP intensity on the VAS was over 50/100 and the patient requested the nerve blockade, the nerve blockade was performed.
An APS team consisting of anesthesiologists, nurses, and pharmacologists, in addition to surgeons, was established for POP management.Te VAS was used to evaluate POP intensity (VAS-POP).On the operative day, VAS-POP assessments were performed by anesthesiologists at return to the ward (VAS evaluation1 ), 1 h after the patient returned to the ward (VAS evaluation2 ) at 7 pm and 9 pm, and if needed.From postoperative day (POD) 1 until discharge, VAS-POP was assessed at 8 am by anesthesiologists (during morning rounds) and at 6 am, 1 pm, and 7 pm by nurses.VAS-POP was also evaluated before analgesic administration.
Administration of scheduled analgesics was discontinued if VAS-POP was <30/100 or the patient did not request an additional prescription; this decision was made by anesthesiologists during the morning rounds.If VAS-POP did not reach 0/100 at discharge, patients were requested to record it until it reached 0/100.If the patient had POP after discharge, continuous analgesic treatment (acetaminophen or loxoprofen sodium hydrate) was performed in both the groups.
Te period of analgesic administration was also recorded, and the postoperative "analgesic requirement period" was defned as "the fnal analgesic administration time (day)-the end time of anesthesia (day)."Te number of days until VAS-POP reached 0/100 was designated as the "number of days with pain."Te VAS-POP areas under the curves (VASAUCs (mm × day)) were calculated by adding the corresponding VAS-POP areas.In addition, VASAUC for postoperative hours 6, 12, 18, and 24 was calculated and defned as VASAUC_6, VASAUC_12, VASAUC_18, and VASAUC_24 (mm × day), respectively.
Te primary endpoint was VASAUC in addition to VASAUC_6, VASAUC_12, VASAUC_18, and VASAUC_24 ((mm × day)).Secondary outcome measures were VAS evaluation1 (mm), VAS evaluation2 (mm), the analgesic requirement period (days), and the number of days with pain (days).Tese parameters for the preblock group and the no preblock group were used for further analysis.for the demographic data (patient characteristics: age, height, body weight, and BMI and intraoperative variables: duration of surgery, duration of anesthesia, blood loss, 1% lidocaine for infltration anesthesia, and remifentanil consumption) and postoperative pain parameters (VAS evaluation1 , VAS evaluation2 , VASAUC_6, VASAUC_12, VASAUC_18, VASAUC_24, VASAUC, analgesic requirement period (days), and number of days with pain (days)).Data are presented in terms of the median (interquartile range) values.All statistical analyses were performed using EZR (version 1.53; Jichi Medical University, Tochigi, Japan) [18].Statistical signifcance was set at p < 0.05.

Patient Characteristics and Intraoperative Variables.
Patients scheduled for Le Fort 1 and bilateral SSRO between July 2017 and June 2023 was 60.Four patients were excluded after reviewing their medical records because of missing data.Finally, ffty-six patients were included in this study (21 males, 35 females; age: 22.0 [21.0-28.0]years).Te number of patients in the preblock and no preblock groups was 22 and 34, respectively.Genioplasty was performed in addition to Le Fort type I osteotomy and bilateral SSRO for one patient in the preblock group (1/22; 4.5%) and three patients in the no preblock group (3/34; 8.8%).Patient demographic data (patient characteristics, surgery, and intraoperative variables) are summarized in Table 1.
Tere were no signifcant diferences (p > 0.05) in the homogeneity of variance and normality for the demographic data including height, body weight, and BMI, duration of surgery, duration of anesthesia, blood loss, 1% lidocaine for infltration anesthesia, and remifentanil consumption.Tus, t-tests were performed to determine the diference between the two groups (preblock group (n � 22); no preblock group (n � 34)) for height, body weight, BMI, duration of surgery, duration of anesthesia, blood loss, 1% lidocaine for infltration anesthesia, and remifentanil consumption.Tere was a signifcant diference (p < 0.05) in the normality for the age in the no preblock group.Tus, the Mann-Whitney U test was performed to determine the diference between these two groups (preblock group (n � 22); no preblock group (n � 34)) for age.
Tere were no signifcant diferences between the two groups' patient characteristics: age, height, body weight, and BMI (p > 0.05).Statistical tests showed that there were signifcant diferences between the two groups for intraoperative variables: duration of surgery, duration of anesthesia, blood loss, 1% lidocaine for infltration anesthesia, and remifentanil consumption (p < 0.05).

Nerve Blockade and POP Management within 1 Hour
Postoperatively.In the preblock group, the bilateral maxillary nerve block and the bilateral mandibular nerve block were performed in all patients (N � 22) after surgery and before emergence from general anesthesia by the anesthesiologist.Te administered dose of the agent for the nerve blockade was 14.0 [10.3-16.0]mL of 0.5% levobupivacaine hydrochloride.Concerning one patient who underwent genioplasty in addition to Le Fort type I osteotomy and bilateral SSRO, a bilateral inferior alveolar nerve block was performed in addition to the bilateral maxillary nerve block and the bilateral mandibular nerve block.Seven patients (7/ 22; 31.8%)needed additional analgesic administration (50 mg of furbiprofen axetil (N � 7)) back at the ward.
Tere was a signifcant diference (p < 0.05) in the homogeneity of variance for the analgesic requirement period and the number of days with pain.Tus, the Welch t-test was performed to determine the diference between the two groups (preblock group (n � 22); no preblock group (n � 34)) for the analgesic requirement period and the number of days with pain.Te test showed that there were no signifcant diferences in the analgesic requirement period and the number of days with pain between the 2 groups (p � 0.215 and p � 0.422, respectively).

Discussion
Tis is the frst study to show that the nerve blockade before emergence from general anesthesia can reduce acute POP at back to the ward and 1 h after back to the ward, in addition to 6 h, 12 h, 18 h, and 24 h, compared to the no nerve blockade before emergence from general anesthesia, indicating that the nerve blockade before emergence from general anesthesia results in good quality pain management.Tese results demonstrate that the nerve blockade before emergence from general anesthesia with APS reduces postoperative pain, especially for the acute postoperative period, and is efective for providing POP relief in an orthognathic surgery.

POP after Orthognathic Surgery and Perioperative Nerve
Blockade.APSs are being increasingly established to provide good control of POP and hence reduce analgesic consumption [3][4][5].However, the quality of POP therapy can vary greatly between diferent departments [14].Recently, guidelines for acute pain management have been published [14], but initiatives specifc to the orofacial feld are lacking; only one article on diferent options available to dental clinicians has been published concerning nerve blockade [15].
Multimodal analgesic intervention (including acetaminophen and NSAID administration) [16] should include several drugs and techniques to combat peripheral and central neuroplasticity [3].Well-known pharmacologic agents used for pain control include acetaminophen, ibuprofen, anticonvulsants, opioids, gamma-aminobutyric acid agonists, and local anesthetics [15].Combined analgesic regimens are more efective in achieving POP control and avoiding untoward side efects than single-drug regimens [15].In an attempt to minimize the risk of the transition from acute to chronic pain, regional analgesia has been recommended [19].Te importance and efectiveness of the nerve blockade in oral surgery have also been reported [20][21][22], and peripheral nerve blocks are increasingly being used as a component of multimodal analgesia [23].
A recent randomized controlled clinical trial showed that postoperative bupivacaine use did not show superior analgesic efcacy when compared with normal saline in controlling acute POP after bilateral SSRO [24].Te duration of action for 0.5% levobupivacaine hydrochloride is approximately 6 h [25], and the elimination half-life for bupivacaine hydrochloride hydrate is also approximately 6 h [26].Once the analgesic efects subside, pain reoccurs.Tus, efcient pain management by APS is important to prevent the onset of sudden, severe POP after the efect of a block wears of.Te current study demonstrated that APS with a perioperative nerve blockade is useful for the management of POP.For successful pain control using the nerve blockade, it is important that the APS team continuously evaluates patient POP intensity based on medical interviews to determine the appropriate multimodal analgesia procedures, such as blockade, rescue analgesic administration, and scheduled analgesic administration, for individual patients.
Control of acute and subacute POP is useful for reducing the onset of chronic POP [9][10][11][12], and the intensity and duration of acute POP pain have often been found to be major risk factors for developing chronic POP [7,8,10,27].An observational study reported that one of the risk factors for chronic POP is the amount of time spent in severe unrelieved pain on the frst postoperative day [7].Considerable attention has therefore been focused on controlling acute POP as a possible preventive strategy [27].In addition,

6
Pain Research and Management the need for continuous analgesic treatment after discharge is emphasized after total hip and knee arthroplasty to ensure postoperative function and facilitate rehabilitation [28].Appropriate postoperative follow-up after discharge may lead to an appropriate preventive strategy for chronic POP [4].

Clinical Implication.
Te intraoperative variables were signifcantly diferent in the two groups; the preblock group showed longer duration of surgery and more blood loss.Te nerve blockade was performed at the anesthesiologist's discretion based on operative invasion and expected POP intensity.Tis would result in the signifcant diference in  Pain Research and Management the two groups.Despite bigger surgical stress (longer duration of surgery and more blood loss) in the preblock group, the postoperative pain parameters evaluated as VAS-POP and VASAUC in the acute postoperative period (24 h) resulted in less POP compared to the no preblock group.Tese results are important clinical implications as control of acute and subacute POP, especially on the frst postoperative day [7], is useful for reducing the onset of chronic POP [9][10][11][12].

Limitations.
A limitation of this study was that it was retrospective but not randomized.Terefore, the results could be afected by clinical factors such as patients' pain.
Regardless, the current study clearly demonstrated that the nerve blockade before emergence from general anesthesia and management with APS is efective for POP relief after orthognathic surgery.

Conclusion
Te nerve blockade before emergence from general anesthesia and management with APS was found to be efective for POP relief after orthognathic surgery.APS with a perioperative nerve blockade in combination with suitable multimodal analgesia management should be considered for efective control of acute and subacute POP.Moreover, the nerve blockade with APS could result in efective prevention of the onset of chronic POP in the future.
*Preblock group, nerve blockade was performed before emergence from general anesthesia; no preblock group, nerve blockade was not performed before emergence from general anesthesia.F, female; M, male; BMI, body mass index; n, number of patients.Preblock group, N � 22; no preblock group, N � 34.Data are presented as numbers or median (interquartile range) values.T-tests were performed to compare 2 groups in spite of age which was performed with the Mann-Whitney U test.*

Table 2 :
Additional intervention for the patients in the no preblock group.

Table 3 :
Postoperative pain parameters.Preblock group, nerve blockade was performed before emergence from general anesthesia; no preblock group, nerve blockade was not performed before emergence from general anesthesia.VAS, visual analog scale; VASAUC, VAS score area under the curve; VASAUC_6, VASAUC for postoperative hour 6; VASAUC_12, VASAUC for postoperative hour 12; VASAUC_18, VASAUC for postoperative hour 18; VASAUC_24, VASAUC for postoperative hour 24; VAS evaluation1 denotes the operative pain intensity at return to the ward.VAS evaluation2 denotes the operative pain intensity 1 hour after the patient returned to the ward.Te number of days with pain denotes the number of days required for postoperative pain to reach 0/100 on the VAS.N, number of patients.Preblock group, N � 22; no preblock group, N � 34.Data are presented as median (interquartile range) values.Te t-test was performed to determine the diference between two groups in spite of the analgesic requirement period and number of days with pain, which was performed with the Welch t-test.