Successful anesthesia ensures provision of dental treatment in a peaceful environment with least patient discomfort. All dental procedures, from routine restorative treatments to complex surgical procedures, need to be done under profound anesthesia, both for the clinician’s ease and the patient’s comfort.33
If local anesthesia is so effective, why then do we still have major difficulties in dental anesthesiology today? The answer from almost all dentists who will admit it and from the hundreds of thousands of potentially terrified patients is that fear and anxiety are as much a part of the overall problem as is pain and the management of pain itself. General anesthesia effectively manages all the components of the pain package but is beset with other inherent difficulties. Local anesthesia no matter how skillfully administered has no direct effect on reducing fear and anxiety. If anything, because a local has to be administered by needles applied intra orally, the problems are intensified in most patients. Administration of a dental injection also bears a risk of possible transmission of blood borne pathogens via a needle stick injury. In order to reduce this risk, a Needle stick Safety and Prevention Act34 was passed by the US congress that encourages the use of needle-free technology whenever its use is possible. The law also provides incentives for the drug manufacturing companies to develop anesthetics that can be delivered via needle less technologies.
The whole concept of using needle less technologies paved way for the development of a solution containing 3% Tetracaine and 0.05% Oxymetazoline, delivered via an intranasal spray in order to perform restorative procedures on maxillary anterior & premolar teeth. In a study performed by Hersh et al. a comparison was done between the anesthetic efficacy of an intra-nasally administered solution of tetracaine and oxymetazoline (K305) with that of a placebo in adult patients who required restorative treatments on teeth numbers 4 to 13 ( according to Universal tooth numbering system).17 The primary outcome variable was the ability to complete the restorative procedure without the use of a rescue injection for dental anesthesia. The study reported overall success rates of 88% and 28% for K305 and placebo respectively. Participants in the K305 group experienced rhinorrhea (57.0%) and nasal congestion (26.0%). No serious adverse effects were observed in the study. The researchers concluded that K305 was effective and was well tolerated during restorative procedures in adult participants. The combination of Tetracaine/ Oxymetazoline (Kovanaze, St. Renatus USA) received FDA approval on June 29th 2016.
EFFICACY OF INTRANASAL SPRAY ANESTHESIA
In our study twenty one (21) patients had successful anesthesia by two or three intranasal sprays while in nine patients anesthesia could not be achieved by intranasal means. These patients were anesthetized using conventional injectable anesthesia. Success rates of 70% were computed for Lidocaine Xylometazoline combination spray in our study (Table 2).
SG Ciancio et al. compared the anesthetic effects of three different intranasal mists for anesthetizing maxillary anterior & premolar teeth for restorative procedures.35 They compared the anesthetic success rates of tetracaine/oxymetazoline group with tetracaine only group and placebo. They concluded that the combination spray of tetracaine/ oxymetazoline yielded success rates of 84% in contrast to tetracaine and placebo groups, that yielded success rates of 27% each.35 In another study Ciancio et al36 reported success rates of tetracaine oxymetazoline combination at 83.3%.
In another study conducted by Hersh et al.37, they reinstated the anesthetic success rates of tetracaine/ oxymetazoline combination to be in the range of 83-90% with fair tolerability. They concluded that intranasal 3% tetracaine plus 0.05% oxymetazoline provided sufficient dental anesthesia to complete restorative dentistry procedures in maxillary premolar, canine and incisor teeth.
Kumar et al. assessed the knowledge, attitudes and practices regarding the use of nasal spray anesthesia by dental practitioners in Chennai, India.38 He reported that the knowledge and use of intranasal spray anesthesia amongst Indian practitioners was limited and further awareness/ publication of data was required to encourage practitioners to use newer modalities of achieving local anesthesia.
Capetillo J. et al. in their study (2019) studied the anesthetic efficacy of intranasal 3% tetracaine and 0.05% oxymetazoline (K305) in maxillary teeth. They had concluded that the anesthetic success for the Kovanaze nasal spray and mock infiltration (22%–37%) was significantly lower when compared to the anesthetic success of mock nasal spray and lidocaine infiltration (89%–91%).26 More unwanted adverse effects (like nasal drainage and congestion, sensation of burning, pressure sensation, and sinus congestion) were reported by the study participants after the Kovanaze nasal spray and mock infiltration than after a mock nasal spray and maxillary infiltration. More study participants(56%) preferred anesthesia via the nasal spray route as opposed to a standard infiltration (44%) before participating in the study. Once the study participants experienced both the routes of administration, all of the study participants preferred to receive the standard infiltration anesthesia.
Jasdev Bhalla et al. in their study evaluated the effect of time on the clinical efficacy of topical anesthesia. They concluded that topical anesthetic use reduces the pain of needle insertion if left on palatal mucosal surface for 2, 5, or 10 minutes, but has no significant clinical pain relief for anesthetic injection.39
In another study conducted by Masoud Parirokh et al. evaluating the effect of topical anesthesia on pain during needle penetration and infiltration injection, published in Journal of Endodontics40, they concluded that the use of topical dental anesthesia had no significant effect on pain during either needle penetration or injection.
Hence previous two studies enable us to state that topical anesthesia does not alleviate the need for an infiltration injection and thus cannot be considered an alternative to the use of intranasal spray anesthesia, which enabled us to perform restorative procedures on maxillary anterior teeth with ICDAS 4 and 5 lesions without the need for an injection anesthesia. Moreover the mechanism of action of topical anesthesia is numbing of the mucosa and submucosa41 whereas intranasal spray anesthetic is up taken from the nasal mucosa and absorbed by the maxillary sinus leading to anesthesia of the ASA and MSA nerves.
Lidocaine/ Xylometazoline combination is commonly used in nasal cavity for various routine otorhinolaryngology procedures like transnasal fiber optic laryngoscopy and transnasal upper gastrointestinal endoscopy.42 The dental anesthetic effects of this combination have not been assessed to date. Therefore we, in our study aimed to find the dental anesthetic effects of lidocaine/ xylometazoline combination. We could only compare the local anesthetic effects of intranasal lidocaine xylometazoline solution with that of tetracaine/oxymetazoline group (Kovanaze) or with conventional infiltration anesthesia. We can also assess the nasal anesthetic effects of lidocaine xylometazoline combination intranasal spray.
As displayed in Table 2, the results of our study showed that there is a statistically significant difference in the anesthetic effectiveness of lidocaine/xylometazoline combination when compared to conventional dental injection anesthesia. The spray anesthesia yielded success rate of 70% (21 of 30) while injectable anesthesia had a success rate of 100% (30 of 30). The p-value computed is 0.02 which illustrates that there is a statistically significant difference in anesthetic efficacy of intranasal spray anesthesia and injectable local anesthesia. Thus the null hypothesis of our study is rejected.
This is in contrast to the study carried out by Hersh et al. that showed success rate of 88% for tetracaine oxymetazoline spray anesthesia.17 The higher success rates of tetracaine may be attributed to its composition, i.e., tetracaine being an ester as opposed to lidocaine belonging to amide group, which may have an effect on the greater efficacy of tetracaine. Higher success rates of tetracaine/ Oxymetazoline group were also recorded in a study carried out by G.C Sebastian et al. who reported that the combination spray was more effective in producing pulpal anesthesia for maxillary anterior & premolar teeth than tetracaine only spray or placebo.35
Higher success rates for infiltration anesthesia may be attributed to the deposition of anesthetic solution near the teeth apices. Since the thickness of buccal cortex is approximately only 0.7-1.8 millimeters43, in case of an infiltration injection the local anesthetic is administered in proximity to the apices of the teeth. On the contrary, the distance of first premolar apices from the sinus floor is 8 to 9 millimeters43 and the apices of anterior teeth apices are 19 millimeters distant from the nasal floor.44 As is evident by the data, the local anesthetic delivered via an infiltration injection has to travel a much shorter distance in order to reach the apices of these teeth as compared to an intranasal spray, which is administered into the maxillary sinus. This may also be one of the reasons why we have observed a higher anesthetic efficacy of infiltration anesthesia than intranasal spray anesthesia in our study.
Noorily et al assessed topical nasal anesthetic effects of cocaine, lidocaine and tetracaine.45 He concluded that tetracaine had greater decrease in pain perception in the nose than with cocaine or lidocaine.
Somewhat lower success rates of lidocaine xylometazoline combination in our study as compared to Tetracaine oxymetazoline combination (70% vs. 88%) are warded off by the merits offered by lidocaine.
Easy availability, cost effectiveness, fewer side effects and unavailability of tetracaine in Pakistan all make lidocaine a suitable agent to be used for intranasal spray use.46
EFFECT OF AGE ON THE EFFICACY OF INTRANASAL SPRAY ANESTHESIA
The study participants were categorized into two age groups, 18-25 years old and 26 to 40 years old. There was no statistically significant difference of age group on the efficacy of spray anesthesia (p>0.99), as shown in Table 3. This non-significant difference may be due to inclusion of a fewer number of patients who were in the age bracket 18-25 years. Amongst 30 patients from the spray anesthesia group, 04 were aged 18-25 years while 26 patients were aged 26-40 years. The range between 18-25 years is also smaller as opposed to 26-40 years.
The results from a study conducted by Hersh et al on intranasal tetracaine and oxymetazoline are in accordance with our study, who also concluded that there was no significant difference of age group on the efficacy of spray anesthesia.17 In another study performed by Ciancio et al. they also reported no significant difference of age on the efficacy of intranasal spray anesthesia.35 They compared the anesthetic success rates of three different intranasal mists for maxillary anterior & premolar teeth: tetracaine/oxymetazoline spray, tetracaine only spray and placebo.
EFFECT OF GENDER ON THE EFFICACY OF INTRANASAL SPRAY ANESTHESIA
In our study, the spray anesthesia group had 13 male patients while 17 female patients. Out of which 77% of the males and 65% females were successfully anesthetized by intranasal spray anesthesia (Table 4). Statistical analysis revealed that the gender had no statistically significant effect on the efficacy of intranasally delivered spray anesthesia (p=0.691). There is no literature available to compare gender variable on the success of intranasal spray anesthesia.
Although the difference between the two genders is not statistically significant, the difference in success rates, as evident from the percentages may be attributed to a number of reasons. Females have a lower pain threshold and greater dental anxiety than their male counterparts. Meechan et al47 in their study compared the differences between male and female regarding their attitudes with respect to dental local anesthesia amongst students at a dental institute in UK. They concluded that female students had greater dental anxiety when receiving or administering local anesthesia as compared to their male counterparts.
Wahid et al48 in their study also endorsed the fact that more female patients had severe dental anxiety as compared to male patients (9% vs. 5%). Thus the comparatively lower success rates of intranasal anesthesia in females may be attributed to this reason.
EFFECT OF TOOTH NUMBER ON THE EFFICACY OF INTRANASAL SPRAY ANESTHESIA
Another parameter of our study was to assess any difference of tooth number on the efficacy of intranasal spray anesthesia. Out of 30 patients who were administered spray anesthesia, 05 patients had a second premolar, 08 had a first premolar and 17 patients had either a canine or central/lateral incisor that had to be anesthetized by spray anesthesia. By spray anesthesia, 60% second premolars, 63% first premolars and 77% of the anterior teeth were anesthetized effectively. However data analysis revealed that there was no statistically significant effect of tooth number on the efficacy of intranasal spray anesthesia (p=0.637) as shown in Table 5, but the difference in success rates in terms of percentages is evident.
Ciancio et al35 in their study also reported lesser success rates for premolar teeth. Hersh et al17 also reported success rates of tetracaine oxymetazoline combination for second premolars in range of 60-66% as opposed to success rates of 88%17 for this product in maxillary premolars and anterior teeth combined. This variation in anesthetic efficacy may be attributed to the fact that the MSA nerve is present in only 72%49 of the population. When this is the scenario, the second premolars receive their innervation from the PSA and the first premolars are innervated via the ASA. Intranasal anesthetic delivery system is not as efficient in anesthetizing the PSA branch of the maxillary nerve owing to its farther distance from the maxillary sinus.
EFFECT OF ICDAS SCORE ON THE EFFICACY OF INTRANASAL SPRAY ANESTHESIA
In this study we also investigated whether the size of the cavity had any role on the efficacy of intranasal spray anesthesia. The spray anesthesia group had 11 patients who had a cavity with ICDAS score of ‘4’, 15 patients had cavities with ICDAS score ‘5’, whereas only 04 patients had cavities with ICDAS score of ‘6’. 91% patients with cavity classification ‘4’and 11% patients with cavity classification ‘5’ were successfully anesthetized by spray anesthesia. None of the patients with cavity sized ‘6’ were anesthetized by means of intranasal spray anesthesia. Statistical analysis also showed that there was a highly statistically significant difference of cavity classification on the effectiveness of intranasal spray anesthesia. The p-value computed was 0.002 (Table 6) which symbolizes that the result is significant at 1%. Hence, we conclude from the results, on the basis of frequency and percentages that the smaller sized cavities, i.e., ICDAS score 4 and 5 had a greater chance of getting anesthetized by intranasal spray anesthesia than larger sized cavity with ICDAS score 6.
None of the published literature on intranasal spray anesthesia has investigated any effect of cavity depth on the success of intranasal spray anesthesia.
Our study only had 04 patients with ICDAS cavity size ‘6’ thus reducing the number of larger sized cavities in the study to investigate its effects. Inclusion of fewer patients in this category may be due to our inclusion criteria that did not allow any patients with Irreversible pulpitis, since such large cavities usually invade the pulp space.
Failure of intranasal spray anesthesia in ICDAS ‘6’ cavities may be due to less remaining dentin thickness at the base of such cavities and during dentin instrumentation more of the odontoblastic processes are activated leading to dentin sensitivity and pain.50
EFFECT OF CAVITY CLASSIFICATION ON THE EFFICACY OF INTRANASAL SPRAY ANESTHESIA
The distribution of patients in different cavity classifications was homogenous apart from cavity classification V, which had none in the spray anesthesia group.
CLASS I CAVITY:
A total of 07 patients were administered intranasal spray anesthesia out of which 06 were successfully anesthetized yielding success rates of 86%. (Table 7)
CLASS II CAVITY:
A total of 06 patients were administered intranasal spray anesthesia out of which only 02 were successfully anesthetized yielding success rates of 33%. (Table 7)
CLASS III CAVITY:
A total of 09 patients were administered intranasal spray anesthesia out of which 08 were successfully anesthetized showing success rates of 89% for spray anesthesia
CLASS IV CAVITY:
A total 08 patients were given intranasal spray anesthesia out of which 05 (63%) were successfully anesthetized.
CLASS V CAVITY:
None of the patients with cavity classification V were part of the intranasal spray anesthesia group.
The higher success rates for intranasal spray anesthesia were reported in cavity classifications III with 89% and class I with success rates of 86%. This is the first study that has assessed the effect of cavity classification on the efficacy of intranasal spray anesthesia.
We assume that the higher success rates in class I and class III cavities may be due to the size of the lesion, restricting its proximity to the dental pulp thus increasing the prospects of successful achievement of local anesthesia by intranasal spray.
NUMBER OF INTRANASAL SPRAYS REQUIRED TO ACHIEVE LOCAL ANESTHESIA
In our study we administered two intranasal sprays spaced 4 minutes apart. Anesthesia was then assessed. If the anesthesia was found to be ineffective a third dose was given ten minutes after the administration of second dose. The results of our study revealed that out of 30 patients who were part of the study group, 11 patients were successfully anesthetized by two doses of spray anesthesia. The remaining 19 patients had to be given a third dose of spray anesthesia out of which 10 were successfully anesthetized while 09 had to be anesthetized by conventional injectable anesthesia. There was no statistically significant association of number of sprays on the efficacy of intranasal spray anesthesia (p=0.11).
No literature is currently available that has probed the effect of number of sprays and the efficacy of intranasal spray anesthesia.
From the results of this study we conclude that it is advisable to administer three doses of intranasal spray anesthesia to achieve adequate anesthetic effect since therapeutic dose of the drug is given in these three doses.
ADVERSE EFFECTS OF SPRAY LOCAL ANESTHESIA
The adverse effects of spray local anesthesia were also assessed in the study. Out of 30 patients who were part of the spray anesthesia group, only 04 patients experienced minor rhinorrhea after administration of spray anesthesia. Rhinorrhea was self-limiting and lasted only for a few minutes after spray dose administration. The vital signs in these patients remained within normal limits during and after the procedure. None of the patients from the injectable anesthesia group had any major complications. There was no statistically significant effect of either spray or injectable anesthesia group on occurrence of treatment emergent adverse effects (p=0.112) as depicted in Table 9.
In their study Hersh et al17 reported nasal discomfort as an adverse effect that also is a known adverse effect for oxymetazoline that is commonly used as an over the counter nasal decongestant at doses similar to the ones used in this study. Another adverse effect seen in the study was the occurrence of rebound nasal congestion. K305 caused a modest but overall non-significant change in the cardiovascular parameters in clinical setting. The variations in Systolic and Diastolic Blood Pressure are most likely linked to the oxymetazoline component of the formulation, since it causes a vaso constrictor effect owing to its postsynaptic alpha 2 receptor agonist effects.
In the study conducted by Ciancio et al35 they observed nasal discomfort, rhinorrhea, nasal congestion but fortunately, most of the effects were mild in nature. Most of the patients had regained their baseline parameters after 24 hours of drug administration. The mean deviation in blood pressure readings was significantly higher in the K305 group versus placebo. The differences may be linked to oxymetazoline’s mechanism of action which is a sympathomimetic drug and causes selective agonization of α1 & in part α2 adrenergic receptors leading to an episode of vasoconstriction.51
The last two studies reveal that Oxymetazoline, being an α-2 receptor agonist, has its own share of demerits. Therefore, in our study we have investigated the role of Xylometzoline in conjunction with Lidocaine, for anesthetizing maxillary teeth for restorative procedures.
This solution of combination intranasal spray seems promising for use to anesthetize maxillary anterior & premolar teeth for restorative procedures in patients having a stable medical history.
- The sample size could have been increased to further assess the efficacy of spray anesthesia agent.
- Blinding was not possible due to two different treatment modalities, i.e. intranasal spray and infiltration injection.
- Since the dental anesthetic effects of Lidocaine/ Xylometazoline intranasal spray combination have not been assessed before for restorative procedures, we have limited literature available to compare the results of our study with those of others.
STRENGTHS OF THE STUDY
- Our study is a randomized controlled trial where every possible step was taken to control confounders, e.g; Randomization was done between intervention and control groups.
- This is the first study that has used lidocaine xylometazoline combination intranasally for` anesthetizing maxillary teeth for restorative procedures.
- This study provides a needle less solution for anesthetizing maxillary incisors, canine and premolar teeth thus reducing dental anxiety in needle phobic patients.
- The results of our study may help us pave way for anesthetizing maxillary teeth for smaller carious lesions with much ease, alleviating the need for an infiltration anesthesia.
- This study has used intranasal spray containing lidocaine as key component, which is easily available, cost effective and besets the de merits of tetracaine (ester) that is a vital component of Kovanaze nasal spray anesthesia.
Lidocaine xylometazoline intranasal spray solution was fairly efficacious in anesthetizing maxillary anterior & premolar teeth for restorative procedures. The intranasal solution can be more predictably used for smaller carious lesions (ICDAS size 4 or 5) and for anterior teeth and premolars in patients with stable medical history. The combination spray of Lidocaine (amide) and xylometazoline was used in our study instead of tetracaine (ester) that yields fairly successful anesthetic rate, thus avoiding the harmful effects of esters. Intranasal spray solution can be promising for patients with needle phobia who avoid dental visits due to fear of getting an injection, and as a result deteriorate their oral health to a point of no return.
- The study can be done with a larger sample size to further assess the success rates of intranasal spray anesthesia.
- Further clinical trials should be performed to assess the anesthetic success rates of this intranasal solution
- Comparison of this intranasal spray may be done with Kovanaze as a control group.
- The study can be performed on pediatric patients since they are the subjects most vulnerable to needle phobia.
- Homogenous age and gender based groups may be formed so as to better assess any role of age group on the efficacy of intranasal spray anesthesia.
- Our study measured anesthetic efficacy on the basis of subjective assessment only (by means of VAS). Anesthetic efficacy in future studies may be assessed by means of an objective tool, e.g., an electric pulp tester.