|Year : 2020 | Volume
| Issue : 2 | Page : 101-105
A new horizon in needle-less anesthesia: Intranasal tetracaine/oxymetazoline spray for maxillary dental anesthesia - An overview
Sauvik Galui, Raju Biswas, Niharika Pandey, Avik Narayan Chatterjee, Subrata Saha, Subir Sarkar
Department of Pedodontics and Preventive Dentistry, Dr. R Ahmed Dental College and Hospital, Kolkata, West Bengal, India
|Date of Submission||11-Sep-2019|
|Date of Decision||02-May-2020|
|Date of Acceptance||19-May-2020|
|Date of Web Publication||22-Jul-2020|
Departemnt of Pedodontics and Preventive Dentistry, Dr. R Ahmed Dental College and Hospital, 114 AJC Bose Road, Kolkata - 700 014, West Bengal
Source of Support: None, Conflict of Interest: None
Local anesthesia is routinely employed for different dental procedures ranging from simple tooth extraction to complex periodontal surgery in day to day dental practice. Although 2% lidocaine with epinephrine in the different ratio is the most commonly used injectable local anesthetic agent, different noninjectable techniques have also been tried. Intranasal 3% tetracaine/0.05% oxymetazoline spray is currently the Food and Drug Administration (USA) approved for performing single restoration in maxillary teeth up to the second premolar, though maximum success rate has been found with maxillary anterior. Different clinical trials were done to evaluate the efficacy and safety of this combination spray for the maxillary teeth anesthesia. Although this technique has some limitations like it cannot be used in patients weighing <88lb, it has some advantages too. This technique is very useful in needle-phobic patients and it also avoids the risk of needle stick injury. This article reviews the efficacy, safety, and clinical utility of this intranasal spray for the use in the dental procedure and also encourage further clinical trials and research for its safety in pediatric patients and efficacy in more invasive procedures.
Keywords: Needle-less anesthesia, recent advancement in local anesthesia, tetracaine/oxymetazoline intranasal spray
|How to cite this article:|
Galui S, Biswas R, Pandey N, Chatterjee AN, Saha S, Sarkar S. A new horizon in needle-less anesthesia: Intranasal tetracaine/oxymetazoline spray for maxillary dental anesthesia - An overview. J Oral Res Rev 2020;12:101-5
|How to cite this URL:|
Galui S, Biswas R, Pandey N, Chatterjee AN, Saha S, Sarkar S. A new horizon in needle-less anesthesia: Intranasal tetracaine/oxymetazoline spray for maxillary dental anesthesia - An overview. J Oral Res Rev [serial online] 2020 [cited 2020 Aug 10];12:101-5. Available from: http://www.jorr.org/text.asp?2020/12/2/101/290505
| Introduction|| |
Local anesthesia is routinely employed for different dental procedure ranging from simple extraction of the tooth to complex implant placement. Minor oral surgical procedure and endodontic treatment requires profound anesthesia of the surgical site or offending tooth for patient's comfort and efficient clinical outcome. Two percent lidocaine with 1:100,000 ephineprine is most commonly used in day-to-day dental procedure although 2% lidocaine with 1:50,000 ephineprine and 2% lidocaine without vasoconstrictor are also available. Another commonly employed local anesthetic agent is 4% articaine with 1:100,000 epinephrine which is 1.5 times more potent than lidocaine. After the injection of a single cartridge containing 1.7–1.8 ml of solution of any of these two commonly used local anesthetic formula, it produces pulpal anesthesia in a success rate of 93%–97% in maxillary arch., Buccal infiltration of 4% articaine with 1:100,000 epinephrine in mandibular arch can be used as an alternative to inferior alveolar nerve block with a high success rate of 91%.,
Although local anesthetic injection is the primary intraoperative pain control measure, it has some disadvantages too. As the injection procedure is painful, it is difficult to perform in a fearful child or anxious patient. Sometimes too rapid injection or accidental intravascular deposition of anesthetic solution complicate the situation. Moreover, needle stick injury carries potential risk of hepatitis C and HIV transmission. A newly developed intranasal anesthetic spray containing 3% tetracaine and 0.05% oxymetazoline effectively overcomes the above said drawbacks and was approved by the Food and Drug Administration (FDA) in 2016 for anesthesia of the maxillary teeth up to the second premolar and seems to be very effective in performing needle-less anesthesia of all maxillary teeth in child patient weighing more than 88lb.
| Materials and Methods|| |
Articles were searched using terms such as “intranasal local anesthetic spray,” “tetracaine/oxymetazoline spray in maxiilary teeth anesthesia” in the Google scholar and PubMed. The search included double blind and randomized trials. A total five articles of clinical trials were found and analyzed for review of literature.
| Evolution of Intranasal Tetracaine/oxymetazoline Spray|| |
Tetracaine is a water-soluble long acting ester local anesthetic agent which is five to eight times more potent than cocaine when applied topically. It is metabolized in plasma by plasma pseudocholinesterase and a concentration of 0.15% and 2% are used as injection and topical application, respectively. It is used as an anesthetic agent for nasal and nasopharyngeal tissue before surgical and explorative procedure., In a prospective randomized controlled trial Drivas et al. recommended 2% tetracaine with adrenaline as the choice of anesthetic agent for nasal septoplasty. Another study was conducted using 0.25% tetracaine solution for nasal pack removal also confirmed its analgesic effect on nasal tissue. A study was done by Bourolias et al. where they compared the anesthetic efficacy of 10% lidocaine spray with 2% tetracaine solution for the transnasal fibreoptic laryngoscopy. They also used 0.1% oxymetazoline nasal spray as vasoconstrictor before application of 80 mg tetracaine or 180 mg lidocaine and concluded that patients with tetracaine group showed lower pain score than lidocaine group. Oxymetazoline is a post synaptic alpha 2 agonist which is widely used as nasal decongestant and provides necessary vasoconstriction when administered with tetracaine. It was Dr. Mark Kollar, who first recognized the pulpal anesthesia of his own maxillary anterior teeth after application of tetracaine gel and oxymetazoline spray for nasal diagnostic procedure. After that different studies were conducted using 0.05% oxymetazoline and different concentration of intranasal tetracaine, and it was concluded that 3% tetracaine in combination with 0.05% oxymetazoline is adequate and safe in providing pulpal anesthesia for the maxillary teeth up to the second premolar.
| Different Studies Done on Tetracaine/oxymetazoline Intranasal Spray as Anesthetic Agent for Maxillary Teeth|| |
- Giannakopoulos et al. conducted an unblinded dose escalation study and the cardiovascular effects and pharmacokinetics of 3% tetracaine/0.05% oxymetazoline intranasal spray was evaluated. The proposed maximum recommended dose (MRD) was administered to twelve healthy volunteers after screening. This MRD (18 mg tetracaine/0.3 mg oxymetazoline) was administered as three 0.1 ml intranasal spray in each nostril and after 1–3 weeks twice of MRD dose was administered to the same volunteers and heart rate, blood pressure, and oxygen saturation were monitored at several points. They found that in first 40–50 min after administration of both MRD and two times MRD doses heart rate was decreased by 6–8 beats per minute. A statistical significance level was achieved where P < 0.05 at 40 min and at 50 min after administration of two times MRD and MRD doses respectively. There was no significant increase in systolic blood pressure after administration of both anesthetic doses, however systolic blood pressure of one participant increased by 23 mm of Hg at 120 min time point after MRD administration and by 26 mm of Hg at 80 min time point after two times MRD administration. This same participant also showed a rise in diastolic blood pressure from baseline values at same time points. The diastolic blood pressure was increased by 30 mm of Hg at 120 min time point after MRD and 29 mm of Hg at 80 min time point after two times MRD administration. Oxygen saturation was also evaluated and mean value remained between 99% and 100% with no significant decrease in any time point. Different pharmacokinetic parameters such as maximum blood concentration, plasma half life of both tetracaine, and oxymetazoline were also evaluated in this study, and they concluded that there was 40%–50% increase in systemic oxymetazoline exposure after two times MRD administration when compared with MRD dose
- A double-masked randomized, placebo-controlled study was done among 150 participants by Hersh et al. to evaluate the efficacy and tolerability of 3% tetracaine/0.05% oxymetazoline (K305) intranasal spray in maxillary teeth anesthesia. Two 0.2 ml of spray were delivered at 4 min interval into ipsilateral nostril and a third spray was also administered if needed. The overall success rate of pulpal anesthesia in performing restorative procedure in maxillary incisors, canine and premolars was reported 88% with 95% confidence interval. This was quite higher than that of placebo spray which was 28%. Although they did not find any serious adverse effect in participating volunteers, but around 57% of K305 group participants presented with rhinorrhea and 26% were presented with nasal stuffiness
- Another study was conducted to compare the efficacy of tetracaine/oxymetazoline intranasal mist with that of tetracaine and placebo intranasal spray among 110 participants. They concluded that a combination of 3% tetracaine/0.05% oxymetazoline intranasal spray achieved pulpal anesthesia for restorative procedure in maxillary non molar tooth with a success rate of 84.1% whereas the success rate was only 27.3% for both tetracaine and placebo spray indicating the necessity of adding oxymetazoline as a vasoconstrictor. They also found the success of anesthesia was greater in the anterior teeth than premolar and this could be due to a genetic variation where the middle superior alveolar nerve is absent and maxillary premolars are supplied by the posterior superior alveolar nerve. The most common adverse reactions they encountered were running nose and nasal stuffiness which subsided within 2–3 h after treatment and these side effects were mostly seen with combination spray than only tetracaine spray
- In an another study, Ciancio et al. evaluated the efficacy of teteracaine/oxymetazoline nasal spray for restorative procedure in the maxillary teeth. A total 45 participants were included in this study. Active nasal spray followed by sham injection was administered to 15 patients while another 15 received sham injection and then active nasal spray. Eight patients received lidocaine injection, followed by buffered saline nasal spray while seven received buffered saline nasal spray and then lidocaine injection. They found a success rate of 83.3% for active nasal spray group and 93.3% for lidocaine injection group and 90% of test individuals experienced successful anesthesia from premolar to premolar in maxillary arch
- Capetillo et al. conducted a single blind crossover study on fifty individuals who received a 3% tetracaine plus 0.05% oxymetazoline (Kovanaze) nasal spray and mock infiltration or a mock nasal spray and 2% lidocaine with 1:100,000 epinephrine infiltration at the maxillary lateral incisor or first premolar in two appointments within a week interval. They found that the anaesthetic success was significantly lower for nasal spray with mock infiltration (22%–37%) than that of mock nasal spray with standard infiltration (89%–91%). Also unwanted effects were reported among participants such as nasal drainage and congestion, burning, pressure, and sinus congestion. Before participating in the study, more participants (56%) preferred the nasal spray route versus a standard infiltration (44%). After experiencing both routes of administration, 100% of participants preferred the standard infiltration
In evaluation of pharmacokinetics of 3% tetracaine/0.05% oxymetazoline nasal spray it was found that 4 of 12 participants in a study presented with quantifiable plasma concentration of tetracaine after administration of 18 mg tetracaine/0.3 mg oxymetazoline, whereas 7 of 12 participant exhibited quantifiable tetracaine plasma concentration after 36 mg tetracaine/0.6 mg oxymetazoline administration and purpose-built backup appliance (PBBA) which is primary metabolite of tetracaine was readily detected in all participants. The maximum plasma concentration and area under plasma concentration curve from time zero to infinity for PBBA were approximately double after two times MRD than MRD. A similar pharmacokinetics was experienced in an another study among 24 participants after intranasal spray of 18 mg tetracaine/0.3 mg oxymetazoline mist where tetracaine was only detectable in plasma of one individual among 24participants.
| Safety and Adverse Reaction|| |
Tetracaine is highly water-soluble ester local anesthetic agent which is mainly used for topical application with a duration of action around 45 min. On other hand, oxymetazoline is a direct acting relatively selective alpha 2 agonist and widely used as over-the-counter drug for topical application as intranasal spray in a concentration of 0.05%–0.1%., This is because of their ability to produce vasoconstriction in nasal mucosa. Persistent vasoconstriction due its regular use might produces atrophic rhinitis, anosmia, and impaired nasal cilliary function. Although systemic adverse effects are less common, it may cause central nervous system depression and rise in blood pressure when taken in large doses.
As tetracaine local anesthetic undergoes rapid degradation in plasma by plasma esterases, it was merely detectable in plasma after administration of 3% tetracaine/0.05% oxymetazoline as intranasal spray at MRD in most of the study participants., Although it was reported to be safely tolerated at MRD and two times MRD as intranasal spray,, the overzealous use of topical tetracaine in naso-oropharyngeal procedure may cause severe respiratory depression, seizures, convulsion, and disorientation. The most frequent adverse effects that were encountered are rhinorrhea and nasal congestion and they were self limiting., Although no severe systemic complications were reported in clinical trials, its safety in patients with cardiovascular disease and with other comorbidities should be further evaluated.
| Discussion|| |
Three percent tetracaine/0.05% oxymetazoline intranasal spray was recently approved by FDA for performing single restorative procedure in the maxillary tooth from premolar to premolar. It was also approved for single restoration in any maxillary deciduous teeth if the child's weight is >88lb. This approval has a narrow spectrum of uses as its anesthetic efficacy in intensive dental procedure, multiple restoration or in simple extraction is not still evaluated. Although it has a high anesthetic success rate in maxillary anterior teeth, the anesthetic success is unpredictable in maxillary premolars and least success for the maxillary second premolars were experienced in clinical trials., This could be due to a genetic variation where middle superior alveolar nerve is absent and premolars are supplied by posterior superior alveolar branch.
Oxymetazoline which is a vasoconstrictor is added with 3% tetracaine in this intranasal formulation to prevent redistribution of tetracaine away from applied site and it is mandatory to have high anesthetic success rate. However, oxymetazoline is relatively contraindicated in hyperthyroid patient explaining the significant pressor response appeared in one participant in the Ciancio et al. study. Similar response was also found in one subject with the history of seasonal allergy in Giannakopoulos et al. study after MRD.
Although this intranasal spray reduces the chances of needlestick injuries and allow simple restorative procedure in the maxillary anterior tooth in needle phobic patients effectively, its safety in small children (weighing <88lb) and in patients with cardiovascular complications are still need to be evaluated.
| Conclusion|| |
Although it has been approved by the FDA, its clinical field of application is still narrow. Research is needed to evaluate its safety and efficacy in small children and in patients with systemic complications. Nevertheless still it has opened a new horizon in needle-less anesthesia for single tooth restorative procedure in maxillary arch particularly in anterior region.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Malamed SF. Handbook of Local Anesthesia. 5th
ed.. India: Mosby Elsevier; 2004.
Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: A review and rationale for use. J Am Dent Assoc 1983;107:623-30.
Moore PA, Boynes SG, Hersh EV, DeRossi SS, Sollecito TP, Goodson JM, et al
. The anesthetic efficacy of 4 percent articaine 1:200,000 epinephrine: Two controlled clinical trials. J Am Dent Assoc 2006;137:1572-81.
Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endod J 2009;42:238-46.
Nydegger B, Nusstein J, Reader A, Drum M, Beck M. Anesthetic comparisons of 4% concentrations of articaine, lidocaine, and prilocaine as primary buccal infiltrations of the mandibular first molar: A prospective randomized, double-blind study. J Endod 2014;40:1912-6.
Ciancio SG, Hutcheson MC, Ayoub F, Pantera EA Jr., Pantera CT, Garlapo DA, et al
. Safety and efficacy of a novel nasal spray for maxillary dental anesthesia. J Dent Res 2013;92:43S-8.
Hersh EV, Saraghi M, Moore PA. Intranasal tetracaine and oxymetazoline: A newly approved drug formulation that provides maxillary dental anesthesia without needles. Curr Med Res Opin 2016;32:1919-25.
Saraghi M, Hersh EV. Three newly approved analgesics: An update. Anesth Prog 2013;60:178-87.
Drivas EI, Hajiioannou JK, Lachanas VA, Bizaki AJ, Kyrmizakis DE, Bizakis JG. Cocaine versus tetracaine in septoplasty: A prospective, randomized, controlled trial. J Laryngol Otol 2007;121:130-3.
Bourolias C, Gkotsis A, Kontaxakis A, Tsoukarelis P. Lidocaine spray vs. tetracaine solution for transnasal fiber-optic laryngoscopy. Am J Otolaryngol 2010;31:114-6.
Lachanas VA, Karatzias GT, Pinakas VG, Hatziioannou JK, Sandris VG. The use of tetracaine 0.25% solution in nasal packing removal. Am J Rhinol 2006;20:483-4.
Hersh EV, Saraghi M, Moore PA. Two Recent Advances in Local Anesthesia: Intranasal Tetracaine/Oxymetazoline and Liposomal Bupivacaine. Curr Oral Health Rep 2017;4:189-96. https://doi.org/10.1007/s40496-017-0144-0
Giannakopoulos H, Levin LM, Chou JC, Cacek AT, Hutcheson M, Secreto SA, et al
. The cardiovascular effects and pharmacokinetics of intranasal tetracaine plus oxymetazoline: Preliminary findings. J Am Dent Assoc 2012;143:872-80.
Hersh EV, Pinto A, Saraghi M, Saleh N, Pulaski L, Gordon SM, et al
. Double-masked, randomized, placebo-controlled study to evaluate the efficacy and tolerability of intranasal K305 (3% tetracaine plus 0.05% oxymetazoline) in anesthetizing maxillary teeth. J Am Dent Assoc 2016;147:278-87.
Ciancio SG, Marberger AD, Ayoub F, Garlapo DA, Pantera EA Jr., Pantera CT, et al
. Comparison of 3 intranasal mists for anesthetizing maxillary teeth in adults: A randomized, double-masked, multicenter phase 3 clinical trial. J Am Dent Assoc 2016;147:339-470.
Capetillo J, Drum M, Reader Al, Fowler S, Nusstein J, Beck M, et al
. Anesthetic efficacy of intranasal 3% tetracaine plus 0.05% oxymetazoline (kovanaze) in maxillary teeth. J Endod 2019;45:257-62.
Cacek AT, Gobbur u JV, Gopalakrishnan M. Population pharmacokinetics of an intranasally administered combination of oxymetazoline and tetracaine in healthy volunteers. J Clin Pharmacol 2016; [doi: 10.1002/jcph. 799].
Tripathi KD. Essentials of Medical Pharmacology. 6th
ed.. India: Jaypee Brothers Medical Publishers (P) Ltd; 2006.
Katzung BG. Basic and Clinical Pharmacology. 10th
ed.. New York : Lange Medical Books: Mc Graw Hill; 2007.
Adriani J, Campbell D. Fatalities following topical application of local anesthetics to Mucous membranes. JAMA 1956;162:1527-30.