Allergic Reactions to Tetracaine-Phenylephrine in Neonatal Lingual Frenotomy: Clinical Insights

Introduction

Until the mid-1980s, it was believed that newborns had an immature central nervous system and, therefore, were protected from the sensation of pain [1]. Currently, neonatal pain is recognized as an increasing concern among healthcare professionals, with various studies showing that fetuses and preterm newborns have physiological and behavioral responses to pain, which reinforces the need for appropriate treatment, even without verbal communication from the patient [2–4].

In dentistry, pain is associated with tissue damage, making it essential to minimize pain in any procedure [1]. For newborns with ankyloglossia and breastfeeding difficulties, lingual frenulum release is frequently indicated, but the choice of anesthetic is not consensual in the literature [5,6]. Some studies suggest the absence of anesthesia, although there is no evidence proving that patients do not feel pain during the procedure [7]. The lingual frenulum is a tissue that attaches the tongue to the floor of the mouth. When it is shorter or thicker, it restricts tongue movement, which can lead to feeding difficulties in infants [8]. This condition can be classified as anterior or posterior, based on the frenulum’s location [9]. The posterior form is more controversial, but it is believed to contribute to breastfeeding difficulties, along with other factors such as nipple anatomy and maternal experience [8]. Ankyloglossia in infants primarily causes breastfeeding difficulties, including poor latch, irritability, and developmental failure, while mothers can experience pain, low milk supply, nipple ulceration, infection, or bleeding [8]; older children and adults can face limitations in tongue movement, affecting speech and oral functions [10]. Treatment options for infants with ankyloglossia include conservative approaches, such as observation, lactation support, and speech pathology consultation, while frenotomy is generally recommended when conservative treatments fail [9,11]. The treatment of ankyloglossia involves various healthcare specialties, and while observation is often the first step, frenotomy is commonly recommended when feeding difficulties persist [12,13].

Topical anesthetics such as 5% lidocaine and ophthalmic solutions containing tetracaine and phenylephrine are considered for such interventions [14–16]. These act on the affected area, providing relief to the superficial layers of tissue, and their effectiveness depends on the application time, toxicity, and reversibility of the anesthesia, without causing damage to deeper nerves or tissues [17].

The most commonly used anesthetics in dentistry include amides, such as lidocaine, and esters, such as tetracaine [17]. Amides are safer and have a lower risk of allergic reactions, while esters, such as tetracaine, are more toxic and carry a higher risk of adverse reactions, especially in neonates, making them contraindicated [18]. Lidocaine is frequently used as a topical anesthetic in concentrations ranging from 2% to 10%, with rapid onset and moderate duration [19,20].

Local anesthetics can cause allergic reactions, such as immediate hypersensitivity and contact dermatitis, as well as complications, such as methemoglobinemia, commonly associated with substances like benzocaine and prilocaine. The improper use of these anesthetics can put the patient’s health at risk, which is why it is crucial for healthcare professionals to understand the effects and mechanisms of these substances before prescribing them [21].

Although topical anesthetics are widely used in dental procedures, there is a lack of evidence regarding the effectiveness of solutions developed to completely eliminate pain and needle discomfort, particularly in neonates [22–25].

The ophthalmic solution containing tetracaine hydrochloride and phenylephrine hydrochloride is a sterile topical formulation with a rapid onset of local anesthesia and a duration of action lasting approximately 15 min. The vasoconstrictive properties of phenylephrine help limit systemic absorption and prolong anesthetic effects [14]. According to the product’s package insert, this formulation is specifically indicated for ocular anesthesia in surgeries, the removal of corneal and conjunctival foreign bodies, and diagnostic procedures.

However, some studies report its use in pediatric frenotomies with ophthalmic solution, describing the procedure as minimally invasive with a favorable prognosis and no documented adverse reactions [15]. The enhanced absorption of the solution in moist mucosa promotes greater depth of action and prolonged anesthetic effects [16]. Nevertheless, after a thorough review of the Practical Guide for Prescribing and Dispensing Medications in Dentistry, we noted the prohibition of prescribing medications outside the scope of dentistry or when they are not directly related to dental treatment and follow-up care [26]. Therefore, despite its use in specific situations, this ophthalmic solution is not recommended for oral application or for use in other structures of the oral region.

This report describes the case of a 48-day-old female infant who experienced an allergic reaction to ophthalmic tetracaine solution and phenylephrine during a frenotomy procedure, which was required due to breastfeeding difficulties caused by ankyloglossia (tongue-tie). This case report was prepared following the CARE Checklist to enhance transparency and adhere to rigorous reporting guidelines.

Case Report

DIAGNOSIS OF ANKYLOGLOSSIA:

After the initial clinical evaluation, the baby underwent the Bristol Tongue Assessment Tool, scoring 3, which suggested significant limitations in tongue mobility (Figure 1). According to the guidelines, when the score is less than or equal to 3 and there is breastfeeding interference attributed to the lingual frenulum, a re-evaluation of breastfeeding and the frenulum is recommended. If the score is confirmed, with no other factors justifying the breastfeeding difficulties, and considering that the frenulum alteration is the main cause, the indication for surgical intervention is recommended, although the evidence on improvements in breastfeeding and nipple pain relief after frenotomy remains limited.

Thus, the diagnosis of ankyloglossia was confirmed after joint clinical analysis by the pediatrician, speech therapist, and pediatric dentist. Other potential causes for breastfeeding difficulties, such as anatomical or neurological issues, were evaluated and ruled out based on clinical history and examinations.

With the diagnosis of ankyloglossia confirmed, the team recommended surgery for lingual frenulum release. The mother was thoroughly informed about the risks and benefits of the intervention, and an informed consent form was signed. Before the procedure, a new clinical evaluation and analysis of breastfeeding were carried out, with no contraindications for surgery identified.

SURGICAL PROCEDURE DESCRIPTION:

The dental procedure was performed in a fully equipped private practice setting, with the appropriate infrastructure and the presence of a qualified dental team, ensuring technical accuracy and patient safety. All clinical steps were conducted in strict adherence to current biosafety protocols, in line with best practices in dental care. The study was approved by the Research Ethics Committee (approval number: 78132724.4.0000.5509), thereby fulfilling all ethical and sanitary requirements for research involving human subjects. Topical anesthesia was applied using an ophthalmic solution of tetracaine + phenylephrine, left in contact with the affected area for 1 min with the aid of a cotton swab. During the application of the anesthesia, the onset of edema and the appearance of vesicles on the infant’s lower lip were observed (Figure 2). As the pediatrician was present, and the condition did not present immediate signs of severity, it was decided to proceed with the procedure. Additional local anesthesia was administered via an injection of 2% lidocaine with epinephrine (1: 100 000), with the dosage calculated according to the child’s weight. The operators used vinyl gloves during the procedure. The tongue was lifted with the aid of a cannula, and the lingual frenulum release was performed using a high-power diode laser operating at 1.2 W in continuous mode. The choice of the diode laser was based on its characteristics, such as its ability to reduce bleeding and promote faster recovery. During the pre-procedure consultation, the laser option was discussed with the family, who were informed about the advantages of this technique, including the lower likelihood of complications and reduced recovery time. Although cold scalpel was also considered as an alternative, the final decision was guided by the clinical advantages of the laser, which were transparently presented to the family, leading to the selection of the most appropriate method for the case.

POSTOPERATIVE FOLLOW-UP:

After the frenotomy, the baby was monitored in observation to track the evolution of the condition. The mother was instructed to begin breastfeeding immediately after the procedure. During the observation period, the team closely monitored the development of the edema and vesicles, observing the baby’s clinical response. Fortunately, no additional interventions were necessary, and the clinical condition showed gradual improvement (Figure 3), with symptom resolution and no complications.

CONFIRMATION OF ANGIOEDEMA DIAGNOSIS:

The diagnosis of ophthalmic anesthetic-induced angioedema was made clinically, based on the observation of clinical signs by the pediatrician in charge, who was present during the procedure. During the application of the anesthetic, the pediatrician noticed the onset of edema and the appearance of vesicles on the baby’s lower lip, which was interpreted as an adverse reaction to the anesthetic agent. No specific diagnostic tests were performed, as the clinical evaluation was considered sufficient for the diagnosis, particularly given the context of the procedure and the absence of other plausible causes for the presented condition.

Discussion

The importance of this study goes beyond reporting a case of allergic reaction to an ophthalmic anesthetic solution. It opens a broader discussion about professional responsibility in using medications not specifically indicated for the oral cavity and the potential complications that can arise. It also highlights the need for continuous professional education on neonatal pain management, emphasizing the importance of using appropriate anesthetics and avoiding substances that could pose additional risks. This case highlights a gap in the literature regarding the safety and selection of anesthetics for newborns undergoing oral procedures.

The release of the lingual frenulum is widely recommended for infants with breastfeeding difficulties, but its benefits beyond this context remain debated due to limited high-quality evidence and a lack of consensus on the ideal age for intervention [27]. Some authors suggest that surgical intervention should be performed before the development of speech, to prevent future issues with diction and difficulties in the physiological process during breastfeeding [28,29]. However, there is still no conclusive evidence supporting the effectiveness of this approach, particularly in terms of long-term benefits [28].

Surgical treatment with high-power diode laser offers advantages such as reduced scarring and bleeding, as well as better precision and field visibility. Various surgical techniques are available, with the choice of instruments and anesthetics depending on the surgeon’s expertise [28,30].

In addition, the literature presents a range of options regarding the use of anesthetic solutions [5–16,28]. The present clinical case report suggests an important reflection on the applicability of the ophthalmic solution containing tetracaine and phenylephrine in the oral cavity. This solution contains an ester that is recognized as being more toxic than lidocaine, which is an amide that could be an option for topical anesthesia [18]. It is also essential to point out that the ophthalmic solution can induce an allergic reaction, as demonstrated in the present clinical case. Moreover, this solution is designed for ocular use and not recommended by the manufacturers for application in the oral cavity [17,26].

However, some studies suggest the use of topical anesthetics in infants undergoing lingual frenulum surgery [6,14–16]. A clinical case report using ophthalmic anesthetic (tetracaine hydrochloride 1% and phenylephrine 0.1%) with 2 drops applied sublingually (right and left of the frenulum) for 5 min, without injectable anesthetics, reported a favorable prognosis and minimally invasive procedure [15]. Another clinical case using the same ophthalmic anesthetic reported better absorption in moist mucosa, greater depth, and longer duration of action, following the principles of minimally invasive dentistry [16]. In a series of cases, different anesthetics were used with no reported differences, and the authors concluded that the earlier the diagnosis of ankyloglossia and the intervention, the more effective and easier breastfeeding would be [6].

A randomized study comparing topical anesthetics, such as benzocaine 20% gel, ophthalmic anesthetic (tetracaine hydrochloride 1% and phenylephrine 0.1%), and a control group with no topical anesthetic, concluded that noninvasive topical applications were better than invasive ones. Additionally, the analysis of crying showed that the topical application of ophthalmic eye drops with tetracaine and phenylephrine in frenotomy surgeries in infants proved to be an effective anesthetic [14]. None of these articles reported adverse reactions. However, in a retrospective observational study with 64 cases (11% neonates, 30% infants, 36% children, and 23% adolescents) using lidocaine, lidocaine + prilocaine, ropivacaine, mepivacaine, lidocaine + bupivacaine, and bupivacaine, it was concluded that the systemic toxicity of local anesthetics could lead to severe systemic reactions, even death. The recommended doses did not prevent the occurrence of systemic toxicity.

Given the complexity and unique considerations, particularly for neonates, further research is needed to establish safer and more effective anesthetic practices.

It is also essential to highlight the importance of the administration of local anesthesia in the area to be submitted to surgery in order to ensure comfort and avoid pain during the surgical procedure [17,31]. The occurrence of pain and stress in newborns implies the activation of neural and endocrine pathways, resulting in similar responses. While pain generally emerges due to damage to tissues and harmful stimuli, stress results from situations that disrupt the homeostatic balance. In newborns, pain and stress trigger short-term and long-term neurobiological and behavioral changes [1].

Newborns are patients with special conditions that merit being treated with a differentiated approach and additional observations with regards to care in order to ensure that they do not feel pain during procedures. Moreover, any complication during the surgical procedure, such as the rupture of a blood vessel and need for local suturing, can result in intense pain if the patient is not adequately anesthetized.

According to our literature review, no correlation was found between this specific case and other previously documented reports. To the best of our knowledge, this is the first clinical case report addressing an adverse effect associated with the use of ophthalmic anesthetic solution in neonates undergoing a lingual frenotomy procedure. This case, therefore, represents a novel contribution, highlighting potential complications related to the use of medications not indicated for the oral cavity in neonates. Future studies should focus on evaluating alternative anesthetic solutions and exploring their safety and efficacy in neonatal procedures.

Conclusions

This report presented a rare complication of topical anesthesia with tetracaine and phenylephrine in a frenotomy procedure in a 48-day-old infant. The findings of this case highlight the importance of a cautious approach, especially when considering non-conventional anesthetics for this purpose, such as ophthalmic solution. Furthermore, it underscores that ankyloglossia can be a cause of breastfeeding difficulties in newborns.