Search strategy
The keywords "Transcranial Direct Current Stimulation", "Intraoperative Transcranial Electrical Stimulation", "Evoked Potential", "Intraoperative Neurophysiological Monitoring", "Tongue Bite", "Tongue Laceration", "Adverse reactions", "Tooth damage", "Oral mucosa injury", "Tooth displacement", and "Macroglossia" were used as keywords in PubMed and other foreign databases; corresponding Chinese keywords were also used in Chinese databases such as CNKI, Wanfang, and VIP for retrieval.
Literature review findings
After excluding duplicate cases, 37 articles were included (see Table S1 for a comprehensive review of published reports of tongue injuries in the literature), with 1 in Chinese and 36 in English, published between 1985 and 2024. Combined with the 3 cases reported this time, a total of 242 cases were included in the analysis (which included compound injuries, totaling 249 injured sites), 217 of which were associated with MEP monitoring, and an additional 25 patients without neurophysiological monitoring (Fig. 2A).
There were 230 sites (92.37%) with lip, tongue bite or macroglossia, 6 sites (2.41%) with oral mucosal injuries, 5 sites (2.01%) with incisor injuries, 2 sites (0.80%) with mandibular fractures, and 6 sites (2.41%) with maxillofacial edema (Fig. 2B). Oral injuries produced following MEP monitoring were more severe than those caused by the absence of neurophysiological monitoring, which were characterized mainly by tongue edema and minor ulcers. However, more comprehensive data reporting in the future may be necessary to draw further conclusions. Most reported cases of oral injuries with documented surgery durations involved surgeries lasting more than 3 hours, with nearly half exceeding 6 hours, suggesting that a longer duration is a potential risk factor (Fig. 2C).
The cases reported included 69 cases (42.86%) in the supine position, 74 cases (45.96%) in the prone position, 8 cases (4.97%) in the prone + supine position, 9 cases (5.59%) in the lateral position, and 1 case (0.62%) in the sitting position (Fig. 2D). This finding indicates that oral injuries can occur in any surgical position. Furthermore, analysis of the limited body mass index (BMI) data available did not support our initial hypothesis that obese patients are at increased risk of oral injuries (Fig. 2E).
Among the 146 cases in which bite blocks were used (Fig. 2F), dental pads were used in 5 cases (3.42%), soft bite blocks were used in 117 cases (80.17%), gauze packing was used in 6 cases (4.11%), a combination of hard pads and gauze packing was used in 5 cases (3.42%), a combination of soft bite blocks and gauze packing was used in 2 cases (1.37%), nothing was used in 10 cases (6.85%), and mouth gags were used in 1 patient for surgical maneuvers (0.68%). This finding indicates that even the use of soft bite blocks cannot completely prevent the occurrence of oral injuries during such surgeries.
Among all the cases, 217 were accompanied by MEP monitoring. Of these, 25 used the C1 and C2 sites, 147 used the C3 and C4 sites or were more lateral to C3 and C4, and 45 did not specify the monitoring site. From the reported cases, MEP monitoring remains the primary determinant of oral injuries, especially when stimulating at the C3/C4 points. While oral injuries without MEP monitoring may be underreported due to milder severity and other factors, they should still be taken seriously in clinical practice. Additionally, the current reported cases generally lack accurate records of stimulation parameters, so this systematic analysis has not determined how higher stimulation voltages, currents, and stimulation modes may increase the likelihood of oral injuries.
The prognosis of patients with oral injuries related to spinal surgery or neurosurgery is generally good. Among the 203 patients with a reported prognosis, 56 patients (27.59%) required surgery or specialist treatment, such as extensive tongue necrosis or dental damage, whereas the other 147 patients (72.41%) recovered spontaneously. Four of the 203 patients developed varying degrees of dysfunction, with the most serious adverse event outcomes. Two patients died, one from secondary sepsis and the other from severe airway obstruction[4, 5].
Pathogenic mechanisms of oral injuries following neurosurgical surgery
A systematic review of the literature and our case reports revealed that even without MEP monitoring, oral injuries can still occur. Although injuries are typically less severe in the absence of MEP, they mainly manifest as tongue edema with minor surface damage. This finding underscores the presence of factors independent of MEP stimulation that contribute to oral injuries. In light of this, we have summarized the following mechanisms underlying the occurrence of oral injury in neurosurgery and spine surgery.
The first group of factors is the combination of prolonged surgery and special positioning. Venous return from the tongue, oral cavity, and craniofacial region is directed through the deep lingual, submandibular, and facial veins into the internal jugular vein. Excessive flexion or extension of the head and neck can lead to swelling due to restricted venous outflow (Fig. 3A). Positions that have a significant effect on venous return to the head and neck are prone, lateral and prone–lateral, and sitting positions. To fulfill the need for adequate exposure of the surgical field, the head and neck tend to be hyperflexed, extended, or rotated, and the skin on the operative side is excessively taut, which often causes obstruction of venous return, leading to elevated intracranial pressure and potential venous stasis. Appropriate attention to minimize excessive flexion, extension, and rotation of the head and neck during positioning can help reduce these risks and promote safer surgical outcomes. Moreover, the effect of gravity on positioning is an important influencing factor (Fig. 3B). All three patients in this report were in the lateral position, especially Patient 2, in whom the underside of the tongue was bitten while in the lateral decubitus position. Maintaining these positions for prolonged periods further exacerbates the impact on venous return. The tongue is prone to swelling due to gravitational downward displacement, restricted movement, and venous reflux disorders, which increase the likelihood of tongue-biting injuries[6]. Over time, sustained compression of the jugular veins and other venous pathways can lead to chronic venous congestion, which not only increases intracranial pressure but also exacerbates swelling in the operative and surrounding areas. In addition, prolonged compression of the lingual blood vessels and salivary glands by oral fillings, tracheal tubes, and other intraoral manipulations during surgery may also cause impaired blood return, lymphatic obstruction, and occlusion of Wharton's duct, and the associated secondary congestion and ischemia/reperfusion injuries may be the cause of postoperative salivary gland inflammation, swelling of the tongue, and airway obstruction[7]. Intraoperative injury to the lingual vasculature, such as the placement of tongue electrodes, may also present with postoperative swelling[8]. In addition, macroglossia associated with the posterior cranial fossa may be associated with dysfunction of somatic autonomic reflexes and/or impaired central regulation of the lingual vascular bed, and tracheal intubation may induce tongue swelling through the activation of somatic autonomic reflexes of the tongue and mouth, although clinical evidence is lacking[9]. The three cases reported here all had surgery times exceeding five hours, which is a significant contributing factor to complications. Surgeons should master patient positioning and expedite surgery as much as possible. Intraoperative monitoring of venous return is also necessary, utilizing techniques such as palpation for skin tension and ultrasound examinations. It is also extremely important to avoid prolonged pressure on the tongue.
The second factor is the intense muscle contraction induced by MEP. MEP monitoring is a technique used in surgery to monitor the health of motor pathways in the brain and spinal cord. By applying electrical stimuli to specific areas of the motor cortex, MEP measures the muscle responses. This allows real-time feedback on motor function, aiding surgeons in avoiding damage to these pathways. During the process of monitoring, the stimulating electrode is often placed 2–2.5 cm in front of the scalp C1, C2, or C3, C4, corresponding to the central motor area representing the muscles of the upper limbs, lower limbs, and facial region. Generally, on the basis of cranial-specific anatomical landmarks, such as the highest point of the nose root and occipital protuberance, with the outer ear as a reference, the intersection of the two lines is the CZ, and the left and right sides are opened at 10% of the coronal line length to obtain C1 and C2. Similarly, the left and right sides are opened 20% of the coronal line length to obtain C3 and C4[10–12] (Fig. 4A, 4B). The monitored muscle depends on the surgical site involved. For surgeries that target the nerve conduction areas controlling the upper limbs, monitoring typically involves muscles such as the abductor pollicis brevis to assess hand and arm functions. When the focus is on areas controlling lower limb movement, the tibialis anterior muscle is usually monitored for leg and foot movement evaluation. In cases involving the facial nerve (Cranial Nerve VII) and the trigeminal nerve (Cranial Nerve V), monitoring includes muscles innervated by these nerves: for the facial nerve, muscles with facial expression, such as the orbicularis oris and orbicularis oculi, and for the trigeminal nerve, mastication muscles, such as the masseter and temporalis. This approach ensures that critical nerve functions are preserved and minimizes the risk of surgical damage; however, it also increases the risk of oral injury. The muscles controlling oral opening and closing, mastication, and tongue movement primarily include the masseter, temporalis, and medial and lateral pterygoids for chewing; the intrinsic and extrinsic muscles of the tongue for movement; and the orbicularis oris for lip closure. These muscles are innervated by various nerves: the masseter and temporalis via the mandibular branch of the trigeminal nerve, the muscles of the tongue via the hypoglossal nerve, and the orbicularis oris via the facial nerve. When subjected to strong stimulation, these muscles can contract forcefully, leading to a reduction in the oral cavity space, increased intraoral pressure, protrusion of the tongue, and increased biting force, ultimately resulting in oral injuries. Furthermore, transcranial MEP induction is a nonspecific stimulus that cannot be precisely and exclusively targeted to a single nerve's distribution area. When attempting to elicit responses from facial muscles, this broad stimulation may cause intense contractions across the entire craniofacial region, thereby increasing the risk of oral injury. For example, during brainstem area surgeries, to better monitor the functional status of nerves related to the brainstem, MEP electrodes are typically placed at C3’/C4’ (lateral to C3 and C4, see Fig. 4B), which often directly triggers widespread muscle activity in the craniofacial area. This leads to contraction of the masticatory muscles, movement of the mandible, and contact between the upper and lower teeth, significantly increasing the occlusal force and resulting in injuries (Fig. 4C).
Incidence and associated risk factors for oral injuries
Drawing from our reflection on the 3 cases in this study and the collation of information from relevant reported cases, we posit that the risk factors contributing to oral injuries may include the following.
First, anesthesia-related factors such as the absence of a bite block, the use of a bite block that is too hard, excessively large or small, improperly placed or displaced, and inappropriate depth of anesthesia. The use of hard bite blocks, including standard dental pads, can lead to the accumulation of biting force, resulting in lip and tongue injuries and even alveolar bone fractures[13]; as experienced in our reported case 1, hard dental guards should be avoided. Bite blocks that are overly large or small, improperly affixed, and displaced for extended durations can compress the tongue, leading to ulcers, hematomas, and even ischemic necrosi[2]. In the second case reported here, where the patient was intubated nasally, protection was attempted via a soft dental pad made from gauze in the oral cavity. However, the possibility of an improper fit or displacement during surgery still fails to prevent injury to the tongue. This explains why, according to the literature search, some patients who used soft dental guards nevertheless sustained oral injuries. In addition, the choice of anesthetic drugs and the regulation of anesthesia depth also present a risk for oral injuries. Common anesthetics such as propofol and dexmedetomidine, as well as muscle relaxants, can influence neurophysiological monitoring signals to varying degrees. Similarly, when the concentration of inhaled anesthetics reaches 0.5%, it can lead to a significant decline in MEP amplitude, and complete suppression may occur as the concentration increases[14]. This could amplify the required stimulation intensity and increase the likelihood of oral injury. If the use of muscle relaxants and inhaled anesthetics is limited, the depth of anesthesia can hardly be guaranteed, and patients’ movement following electrical stimulation might cause forced contraction of the masseter muscle, thereby increasing the likelihood of oral injury. Yata et al. also confirmed a significant correlation between tongue-biting injuries and intraoperative body movement[3].
Furthermore, patient factors also exert an impact. Tamkus et al.’s data analysis did not corroborate a correlation between age, sex, and the incidence of postoperative biting injuries[2]. However, malocclusion and missing teeth in patients are risk factors for intraoperative displacement of the bite block, which in turn increases the incidence of tongue-biting injuries. In addition, factors such as hypothermia, hypotension, hypoxemia, anemia, intracranial hypertension, electrolyte imbalance, and blood glucose abnormalities can decrease the MEP signal[15]. Moreover, individuals with a smaller oral cavity, enlarged tongue, or naturally stronger bite force are potentially at greater risk for oral injuries, yet systematic evidence confirming these correlations is currently insufficient. Additionally, angioedema is a common cause of macroglossia. A patient's previous history of allergies and the use of ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) are also points of concern for triggering intraoperative angioedema, leading to or exacerbating tongue injury. Angioedema is typically associated with ACE inhibitors, with an incidence ranging from 0.1–0.7%. The associated pathophysiological mechanisms involve vasodilation and increased permeability and plasma extravasation, which are achieved through the inhibition of bradykinin and substance P degradation, both of which are vasodilatory agents that contribute to edema[13]. Although none of the three patients reported here had previously taken ACE inhibitors and had no history of allergies, patients using such medications may pose an additional risk factor for intraoperative oral injury. Therefore, we recommend that future related reports should include specific patient information, such as preoperative oral conditions, BMI, relevant medication usage, use of bite blocks, intraoperative position, and neurophysiological monitoring sites and parameters, to facilitate colleagues to summarize experience from it.
In addition to the above factors concerning surgery and monitoring, Yata et al.’s experimental results indicate that the incidence of oral injuries caused by maximum stimulation intensity is noticeably greater than that caused by nonmaximum stimulation intensity, even if a statistically significant correlation between stimulation intensity and the incidence of tongue-biting injuries is absent[3]. High stimulation intensity may be a risk factor for oral injuries. Compared with monophasic stimulation, biphasic stimulation, which simultaneously activates both corticospinal tracts, is more likely to induce oral injuries[2]; the second case mentioned in the text employed bidirectional stimulation. In addition, the placement of the stimulation electrode is a crucial factor. Relative to C3/C4 stimulation electrodes, C1/C2 stimulation electrodes might limit direct activation of facial and axial muscles, possibly because the former are closer to the facial motor cortex, mandibular muscles, and trigeminal nerve[2]. In reported cases of oral injuries with MEP stimulation sites, stimulation at C3/C4 accounted for approximately 81.82% of the total cases. Hence, placing electrodes at C3/C4 may increase the risk of oral injuries. Stimulating even further to the outer edge of C3/C4 poses a greater risk, necessitating a balance between monitoring muscle position and stimulation intensity.
Prevention of oral injuries
Good preventive measures can significantly lower the rate of oral injuries during neurosurgical operations. On the basis of an analysis of the mechanisms and influencing factors of these injuries, addressing this issue requires the joint efforts of neurosurgeons, anesthesiologists, neurophysiological monitoring physicians, and nursing staff.
From a surgical standpoint, it is crucial to balance optimal exposure of the surgical area with the effects of positioning on the patient's head, neck tension, and venous return. Excessive bending or stretching of the head and neck should be avoided. Monitoring the jugular vein status during surgery is essential. Any increase in tension or compromised venous return requires immediate adjustment of the patient's position. Additionally, intraoperatively, prolonged compression of local tissues or vessels must be avoided. Improving surgical efficiency to shorten the operation duration can help minimize complications. Furthermore, ensuring that patients maintain good oral hygiene before surgery can reduce the risk of infection following oral injuries.
From the perspective of electrophysiological monitoring, the focus should be on meticulous MEP monitoring. The first step is to select the appropriate stimulation sites with precise localization, avoiding the use of C3/C4 stimulation points whenever C1/C2 can meet the requirements. However, it is crucial to recognize that monitoring certain surgical areas, such as those involving the cerebellopontine angle, as reported in our cases, necessitates the use of C3/C4 locations due to the risk of intraoperative damage to cranial nerves associated with facial movements. Furthermore, surgeries targeting regions related to the movements of the upper and lower limbs should ideally opt for C1/C2, which reduces the stimulation of the head and face motor cortex while obtaining satisfactory potential signals. Additionally, avoiding high-intensity and high-frequency electrical stimulation is recommended. It is best to start with low-intensity titration to achieve the minimum stimulation threshold for satisfactory signals. Simultaneously, enhancing the sensitivity of monitoring equipment and improving monitoring techniques also contribute to reducing the need for high-intensity stimulation. Employing a four-pole stimulation strategy (comprising two anodes and two cathodes) can significantly improve signal quality while allowing for lower stimulation intensities, effectively reducing the risk of nonspecific stimulation and ensuring the accuracy and safety of MEP monitoring during neurosurgical procedures[16].
From the perspective of an anesthesiologist, approaches can be initiated from two aspects: the anesthesia plan and the correct use of dental guards. First, anesthesiologists should formulate appropriate anesthesia plans on the basis of patient condition, drug characteristics, and surgical methods. While satisfying anesthesia depth and surgical safety, the need for neurophysiological monitoring should also be considered. The current recommended anesthesia regimen is anesthesia without muscle relaxants or total intravenous anesthesia[13]. The use of no muscle relaxants and the use of only intravenous anesthesia increases the use of propofol to prevent movement. The addition of dexmedetomidine (0.5 mcg/kg/h) reduces the need for propofol, stabilizing anesthesia and hemodynamics[17]. A subanaesthetic dose of ketamine can also be used in MEP monitoring to deepen anesthesia while causing gradual improvement in amplitudes without affecting latency[18]. A crucial aspect to note is the recommendation to monitor the depth of anesthesia in such surgeries, which ensures stable anesthesia levels, minimizing impacts on monitoring activities and preventing bodily movements, thereby mitigating the risk of oral injuries. Another strategy involves the judicious use of low-dose muscle relaxants to mitigate excessive biting force during stimulation. Research by Zhang, X. et al. indicated that a rocuronium infusion rate of 9 µg.kg^--1.min^--1 strikes a balance between the needs of neurophysiological monitoring and achieving adequate anesthesia depth[15]. Nonetheless, muscle relaxants may dampen or entirely obstruct MEP responses, potentially leading to increased stimulation intensity and subsequent injuries, necessitating close collaboration between anesthesiologists and monitoring physicians. Furthermore, the application of muscle relaxants should be guided by strict train-of-four (TOF) monitoring, accommodating the differential muscle sensitivity to relaxants and their dynamic effects over time. In patients with intraoperative somatic movements, the block can be given again if T1 is between 5% and 50% of baseline or if there are two detectable jerks, MEP baseline levels can be reached early with sugammadex[12, 19, 20]. However, whether these methods can reduce the incidence of oral injuries still lacks clinical data. In addition, the correct use of a bite block is crucial for oral protection. Using a soft bite block or gauze block can decrease the incidence of oral injuries[21]. In Tamkus’s report, the incidence of oral injuries associated with bite pads (4.42%) was significantly greater than that associated with the use of soft bite blocks (1.27%)[2]. The absence of bite blocks not only increases the incidence of oral injury but also increases the possibility of tracheal tube rupture and reintubation. Compared with placing a bite block only at the midline, placing bite blocks between the upper and lower molars on both sides is safe[22]. Salik et al. recommended placing a soft bite block in the midline of the tongue and between the molars on both sides[13]. During monitoring, the anesthesiologist needs to select the appropriate size of bite block, place and determine its position, and pull the lips out to prevent lip compression injury; avoiding pressure on the tongue is crucial. Proper fixation should be ensured to prevent damage to the tongue and teeth. During surgery, attention should be given to the displacement or dislodgment of the bite block[23]. In addition, some researchers suggest the use of tooth protection devices to provide better oral protection[24]. It is also recommended that the tracheal tube be secured to the operative side to minimize contralateral compression and that transnasal intubation be used to minimize the base-of-laryngeal contact area and pressure generation[4]. Regardless of the presence of MEP monitoring and whether intubation is nasal or oral, in high-risk patients, the use of a soft bite block could alleviate tongue pressure by increasing the oral space, thus preventing tongue swelling and biting injuries[25]. The future development of an oral protective pad designed to enlarge the oral cavity space suitably, prevent the tongue from interposing between the teeth, and furnish real-time feedback on alterations in bite force amidst stimulation, with the aim of diminishing interdental bite force, is anticipated to confer substantial benefits.
Table 1
Prevention measures for Oral injuries
| | Measures |
| Anesthetic Measures | 1. Monitor the depth of anesthesia, avoiding Intraoperative Body Movement; 2. Choose the right anesthesia plan, with TIVA recommended; 3. Select and correctly place a soft bite block, properly secure it, and check the position of the bite block during surgery; 4. For severe tongue bite injuries or facial edema, extubation requires careful deliberation. 5. Research and design new types of bite blocks. |
| Patient Measures | 1. Conduct thorough preoperative evaluations to identify those at high risk for oral injuries and customize anesthesia and oral care plans according to individual patient needs. 2. Maintain good oral hygiene before surgery. |
| Surgical and Monitoring Measures | 1. Avoid high-intensity, high-frequency, and bipolar stimulation and choose the appropriate electrode placement sites, C1 and C2 sites are recommended, especially in spinal surgery. 2. Pay attention to the impact of surgical positioning on postoperative oral complications, avoid excessive and long-term neck flexion and pressure; 3. Monitor venous return pressure under surgical positioning during the operation. 4. Minimize the duration of time spent in special positions as much as possible. |
Overall, we require collective efforts from the team (see Table 1 for prevention measures for oral injuries). Preoperative patient assessment is essential to identify high-risk individuals for potential oral injuries and to establish effective protocols for intraoperative oral protection. Additionally, it is crucial to establish an effective protocol for managing oral injuries when they occur. Patients with macroglossia and airway obstruction should be adequately evaluated prior to extubation, and airway patency can be ensured by imaging, visual laryngoscopy, and tracheal tube sleeve leakage testing to avoid postextubation airway obstruction. Notably, in patients with edema caused by prolonged pressure on the tongue, removal of the endotracheal tube without interfering with ventilation may be beneficial. Multidisciplinary collaboration is indispensable for ensuring proper management in such cases.