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. 2018 Fall;65(3):156–161. doi: 10.2344/anpr-65-02-08

Effect of Nitrous Oxide on Pulpal Anesthesia: A Preliminary Study

Papimon Chompu-inwai *,✉, Sophon Simprasert †, Patchanee Chuveera ‡, Areerat Nirunsittirat ‡, Thanapat Sastraruji §, Tanida Srisuwan ||
PMCID: PMC6148698  PMID: 30235437

Abstract

To compare the success of perceived pulpal anesthesia between groups using nitrous oxide/oxygen (N2O/O2) and oxygen (O2) in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. Thirty-three children (mean age 10.4 ± 1.9 years) with 33 symptomatic irreversible pulpitis permanent teeth were included in this preliminary study. All children were premedicated with ibuprofen and randomly assigned to receive either N2O/O2 (17 participants) or O2 (16 participants). Four percent articaine with epinephrine 1:100,000 was administered, and vital pulp therapy was performed. Children used the Wong-Baker FACES Pain Rating Scale (WBFPS) to report their pain at baseline as well as during carious dentin removal, pulpal exposure, and pulpal tissue removal steps. The success was determined when the reported WBFPS score was ≤4. The chi-square test was used to compare the success between both groups. The success of pulpal anesthesia was 71% (12/17) and 19% (3/16) in the N2O/O2 and O2 groups, respectively. The success in the N2O/O2 group was 52% higher than that in the O2 group (confidence interval = 22.9% to 80.7%; significant difference p = .003). From the result of this preliminary study, N2O/O2 significantly increased the success of perceived pulpal anesthesia in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. However, further study with a larger sample is required to confirm this result.

Key Words: Pulpal anesthesia, Symptomatic irreversible pulpitis, Nitrous oxide, Ibuprofen

Achieving profound pulpal anesthesia in permanent teeth diagnosed with irreversible pulpitis has always been problematic, with the limited success ranging between 60 and 80% with maxillary infiltration1,2 to between 13 and 65% with inferior alveolar nerve block.3–6 Researchers have been continuously searching for adjunctive therapies, such as supplementary injection, preemptive analgesia, and sedation, to improve the success of perceived pulpal anesthesia in these teeth. Ibuprofen, a nonsteroidal anti-inflammatory drug, has previously been shown to provide a success rate of pulpal anesthesia from 27 to 78%.5–13 Nitrous oxide/oxygen (N2O/O2) inhalation sedation, in one study, significantly enhanced the success of perceived pulpal anesthesia in teeth with symptomatic irreversible pulpitis up to 50%.14 However, these studies have clearly shown that the use of either ibuprofen or N2O/O2 alone was insufficient to provide complete pulpal anesthesia in teeth with symptomatic irreversible pulpitis. Moreover, all previous studies have evaluated pulpal anesthesia only in patients who were at least 18 years of age,5–14 and there are limited studies on pulpal anesthesia in younger patients.

In pediatric patients, preventing pain by administering preemptive analgesia and/or sedation should be greatly beneficial because inadequate pain control, especially in this group of patients, could lead to a failure in behavior management, a negative experience for the patient, and a poor treatment outcome. Moreover, fear and anxiety may also be major factors that cause the failure of pulpal anesthesia in this group of patients. In addition, young permanent teeth have a larger pulp that possesses a more extensive blood and nerve supply than do older teeth15,16; these specific characteristics of the young pulp may, consequently, lead to more response to noxious stimuli. To achieve the greatest possible success of pulpal anesthesia in pediatric patients, the combination of methods previously reported in adults is therefore worth investigating. Ibuprofen is one of the most common drugs used to reduce pain and inflammation in pediatric patients with minimal side effects. N2O/O2 has also been commonly used in children with mild to moderate anxiety levels. Besides its anxiolytic properties, N2O also has an analgesic effect and has been recommended for patients in whom profound local anesthesia cannot be obtained.17

At present, there is no clinical study on the combination of preemptive ibuprofen and N2O/O2 inhalation sedation in pediatric patients with symptomatic irreversible pulpitis permanent teeth. Therefore, the aim of this preliminary study was to compare the success rates of pulpal anesthesia between using N2O/O2 and O2 in patients younger than 18 years who had symptomatic irreversible pulpitis permanent teeth and were premedicated with ibuprofen.

METHODS

This single-blind randomized clinical trial was approved by the Human Experimentation Committee of the Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Children and their legal guardians were informed about the study procedure. The legal guardians were asked to sign the informed consent on behalf of the eligible participants if both agreed to participate in the study.

Study Population

The participants were recruited from pediatric patients attending the Pediatric Dentistry Clinic, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand, during September 2014 to June 2015. The inclusion criteria included American Society of Anesthesiologists class I and II patients aged 6 to 18 years for whom there was no contraindication to ibuprofen or N2O/O2 sedation. Patients had a deep carious lesion in a permanent molar with a diagnosis of symptomatic irreversible pulpitis, judged by the patient's having pain on the day of treatment and prolonged pain response to cold test with Green Endo-Ice (Coltene Whaledent, Cuyahoga Falls, Ohio) even after the cold stimulus had been removed. The periapical radiographs showed extension of the dental caries having penetrated three-fourths or more of the entire dentin thickness without any prominent periapical pathosis. Condensing osteitis and/or widened periodontal ligament space was not considered as an excluding criterion in this study. If the patient had more than 1 tooth that met the inclusion criteria, only the first treated tooth as requested by the patient was included in the study. Other teeth also received the treatment but were not included in the study.

Sample Size Calculation

Sample size was calculated for a superiority trial. In a previous study, the success of pulpal anesthesia with ibuprofen was 27%.8 In this trial, in view of the findings of Stanley et al,14 we expected 22% greater success in the N2O/O2 group than in the O2 group. To detect a significant difference of success between both groups, 73 participants in each group would be required for a trial with a 5% type I error and 90% precision. However, we were able to include only 16 and 17 samples for each group; therefore, we intended to primarily report a preliminary result of this study.

Study Procedure

One unblinded postgraduate student in pediatric dentistry performed all procedures. The initial preoperative subjective pain was evaluated using the Wong-Baker FACES Pain Rating Scale (WBFPS). The WBFPS is a 6-face pictures scale with fixed scores from 0 to 10, ranging from does not hurt to hurts the worst.18 This scale is preferred by both children and health care providers because it is quick and easy to use.19,20 Then, all patients received 10 mg/kg (maximum of 600 mg per dose) of ibuprofen syrup (Bunofen; The Government Pharmaceutical Organization, Bangkok, Thailand) immediately after a meal, 1 hour before a treatment procedure. Immediately before the beginning of the procedure, the operator evaluated the preoperative fear and anxiety level of the participants using the Facial Image Scale (FIS). The FIS consists of pictures of 5 different facial expressions ranging from very happy to very unhappy. This scale is easy for children to understand and rate their anxiety level through pictures with fixed numbers, and it takes only a short time interval for assessment.21 Then, all patients were divided into 4 strata by a combination of FIS (1–3 in one group and 4–5 in a second group) and tooth type (maxillary or mandibular) and then further randomly assigned into 2 treatment groups (N2O/O2 or O2) using a block randomization. A computing program22 was used to generate the randomized table with a block size of 4. Both groups of patients were blinded to the treatment they received. Vital signs, including pulse rate and oxygen saturation, were recorded before and during the procedure. A properly sized nasal hood was placed over each patient's nose at an appropriate flow rate of 100% oxygen for 5 minutes.

For the N2O/O2 group, the range of N2O concentration administered was between 30 and 50%. Patients received N2O via nasal hood by the slow titration or rapid induction method, as appropriate for each patient, until the patient reached a good stage of sedation, defined as feeling comfortable and relaxed as assessed by the operator with eyes becoming less active and having a glazed-like appearance. After 5 minutes, the operator began the treatment, and the concentration of N2O/O2 was maintained throughout the procedure.

For the O2 group, the operator pretended to adjust the N2O machine, but the patient received 100% oxygen. Similar to the N2O/O2 group, the operator began the treatment after 5 minutes, and 100% oxygen concentration was maintained throughout the procedure.

All patients then received an inferior alveolar nerve block with long buccal nerve block for a permanent mandibular molar or a buccal and palatal infiltration for a permanent maxillary molar, using a gauge-27 13/16-in.-long needle (Terumo Dental Needle, Terumo Corporation, Tokyo, Japan). One cartridge of 1.7 mL of 4% articaine with 1:100,000 epinephrine (Septanest SP, Septodont, Saint-Maur-des-Fasses, France) was administered. The operator tested soft-tissue numbness by asking the patient about the numbness of surrounding tissue or by probing with an explorer at the surrounding gingiva for a permanent maxillary molar or the ipsilateral cheek and lip for a permanent mandibular molar. Tissue numbness was evaluated every 5 minutes after injection. If a patient did not experience soft-tissue numbness within 5 minutes in maxillary molars and 15 minutes in mandibular molars, the patient was then excluded from the study. After soft-tissue numbness was confirmed, treatment was then started, and patients were instructed to indicate their pain level using the WBFPS during the steps of carious dentin removal, pulpal exposure, and pulpal tissue removal. Pulpal anesthesia was considered as a success if the WBFPS score was less than or equal to 4 in all steps of treatment. Pulpal anesthesia was considered as a failure if the WBFPS score was more than 4 in any step of treatment. In cases of failure, supplementary injections, such as intraligamentary and/or intrapulpal injection, were added before continuing on with treatment.

The baseline variables were compared using the chi-square test, Fisher exact test, or the 2-sample t test. The data obtained were analyzed using the chi-square test with 95% confidence level to compare the success rates between both groups. The software used for these analyses was SPSS 17.0 (SPSS Science, Chicago, IL).

RESULTS

Thirty-three children with 33 teeth were included and randomly assigned to the N2O/O2 (17 children) and the O2 (16 children) groups, respectively. All children reported soft-tissue anesthesia after primary injection with inferior alveolar nerve block or infiltration, resulting in no exclusion from this study. The participants consisted of 22 girls and 11 boys, aged between 8 and 16.8 years, with a mean age of 10.4 ± 1.9 years. Forty-nine percent of participants rated the initial WBFPS at 6 and 70% of participants rated the FIS scores of 1 to 3. The mandibular first permanent molar was the most studied tooth (70%), followed by the maxillary first permanent molar (30%). The baseline variables, including gender, age, initial WBFPS, FIS, and tooth type, are shown in Table 1. Baseline variables between the N2O/O2 and O2 groups were not significantly different. The mean concentration of N2O administered was 40.0 ± 7.1%.

Table 1.

Baseline Variables of the N2O/O2 and O2 Groups

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The success rates of pulpal anesthesia are shown in Table 2. The success rate was 71% in the N2O/O2 and 19% in the O2 groups, respectively. The success rate in the N2O/O2 group was 52% higher than that in the O2 group, with statistical significance (Confidence interval 22.9% to 80.7%; p = .003).

Table 2.

Success Rates of Pulpal Anesthesia of Each Group*

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DISCUSSION

In this study, all patients were premedicated with ibuprofen; the success rate of pulpal anesthesia in the O2 group was significantly lower than that in the N2O/O2 group (19% vs 71%; p = 0.003). Moreover, it was also much lower than that in previous studies with ibuprofen alone (27-78%).5–13 The reason for this lower success rate may be the younger group of patients in this study. Young patients may have more fear and anxiety that consequently decreases their pain threshold.23,24 However, most patients (70%) in this study reported FIS scores of 1 to 3, which indicated mild to moderate anxiety. Moreover, when compared with older pulp, young pulp is larger and has more blood supply and more innervation.15,16 These factors may lead to a higher degree of difficulty in achieving pulpal anesthesia. Consequently, only 1 intervention, such as premedication with ibuprofen alone, may become inadequate in managing pulpal anesthesia in this group of patients. Ibuprofen is a nonspecific cyclooxygenase enzyme inhibitor. Cyclooxygenase-1 and cyclooxygenase-2 enzymes are important enzymes involved in the synthesis of prostaglandin, a mediator of inflammation, fever, gastroprotection, and pain. Theoretically, reducing the inflammatory mediator prostaglandin E2 (PGE2) in pulp would be advantageous in both decreasing pulpal nociceptor sensitization and elimination of prostanoid-induced stimulation of tetrodotoxin0resistant sodium channel activity.25 However, this study and previous studies5–13 similarly reported insufficient pulpal anesthesia of preemptive ibuprofen. Thus, the search for other approaches for adequate pulpal anesthesia is highly recommended.

Since the mechanisms of ibuprofen and N2O work through different targets and pathways, the authors hypothesized that the combination of both would increase the success rate of pulpal anesthesia in teeth of young patients with symptomatic irreversible pulpitis. The success of pulpal anesthesia in the N2O/O2 group (71%) in this study was higher than that in the previous study by Stanley et al,14 who reported a 50% success rate of pulpal anesthesia when only N2O/O2 was used, without any preemptive drugs. In this study, after premedication with ibuprofen, N2O/O2 could provide an additional success of 52% (95% confidence interval 22.9 to 80.7%). At subanesthetic concentration, N2O has anxiolytic and analgesic properties, both of which are highly desirable for young, anxious patients with symptomatic irreversible pulpitis teeth. The anxiolytic effect of N2O likely involves interactions with the gamma-amino-butyric acid (GABA) receptor.26 The analgesic effect of N2O seems to involve primarily N-methyl-D-aspartate glutamate receptor antagonism.27 Although the combination of ibuprofen and N2O has shown a promising result, approximately one-third of the patients (29%) still experienced pulpal anesthetic failures during the procedure, making supplementary injections unavoidable. Therefore, other combinations should be further investigated to increase the success of pulpal anesthesia.

In this single-blind randomized clinical trial, efforts were made to meet the requirements of the CONSORT 2010 statement.28 All patients were randomly allocated, which resulted in baseline variables that were equally distributed in both groups. The limitation, however, was that the operator could not be blinded to the procedure performed; nevertheless, all the patients were blinded to the treatment received, and the pain was self-reported by the patients themselves, using the WBFPS. The WBFPS can be used effectively in children, by themselves, as young as 3 years old18 and has been found to be more sensitive than a visual analogue scale.29 At the beginning of this study, the most rated WBFPS was 6 (hurts even more; 49%), and all patients rated initial WBFPS between 4 (hurts a little more) and 10 (hurts the worst), which corresponded with the diagnosis of symptomatic irreversible pulpitis. Another limitation of this study lies in its sample size. We were able to include a lower number of patients than the number we estimated. For this reason, we reported our results as a preliminary study. However, in this study, we observed 52% of difference of the additional effect. With 16 and 17 samples in each group, this study seems to have adequate power to detect the difference of success of at least 35% or more. However, a larger sample size should be considered in further studies.

CONCLUSIONS

Based on the findings of this preliminary study, the following conclusions can be made:

  1. The success rate of pulpal anesthesia after inferior alveolar nerve block as a primary injection is quite low in permanent teeth with symptomatic irreversible pulpitis of pediatric patients premedicated with ibuprofen.

  2. N2O/O2 inhalation sedation can increase the success rate of pulpal anesthesia in permanent teeth with symptomatic irreversible pulpitis of pediatric patients premedicated with ibuprofen. However, a further study with a larger sample is required.

ACKNOWLEDGMENTS

This research was supported by the Research Fund for Postgraduate Student from the Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. The authors also wish to thank Dr M. Kevin O. Carroll, Professor Emeritus of the School of Dentistry, University of Mississippi, Jackson, and faculty consultant with the Faculty of Dentistry, Chiang Mai University, for his assistance in the preparation of the article.

REFERENCES

  • 1.Atasoy Ulusoy OI, Alacam T. Efficacy of single buccal infiltrations for maxillary first molars in patients with irreversible pulpitis: a randomized controlled clinical trial. Int Endod J. 2014;47:222–227. doi: 10.1111/iej.12129. [DOI] [PubMed] [Google Scholar]
  • 2.Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. J Endod. 1998;24:487–491. doi: 10.1016/S0099-2399(98)80053-8. [DOI] [PubMed] [Google Scholar]
  • 3.Claffey E, Reader A, Nusstein J, Beck M, Weaver J. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis. J Endod. 2004;30:568–571. doi: 10.1097/01.don.0000125317.21892.8f. [DOI] [PubMed] [Google Scholar]
  • 4.Tortamano IP, Siviero M, Costa CG, Buscariolo IA, Armonia PL. A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis. J Endod. 2009;35:165–168. doi: 10.1016/j.joen.2008.10.020. [DOI] [PubMed] [Google Scholar]
  • 5.Reader A, Nusstein J, Drum M. Successful Local Anesthesia for Restorative Dentistry and Endodontics Vol 1. Hanover Park, IL: Quintessence;; 2011. [Google Scholar]
  • 6.Shahi S, Mokhtari H, Rahimi S, et al. Effect of premedication with ibuprofen and dexamethasone on success rate of inferior alveolar nerve block for teeth with asymptomatic irreversible pulpitis: a randomized clinical trial. J Endod. 2013;39:160–162. doi: 10.1016/j.joen.2012.10.011. [DOI] [PubMed] [Google Scholar]
  • 7.Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2011;37:593–597. doi: 10.1016/j.joen.2011.02.015. [DOI] [PubMed] [Google Scholar]
  • 8.Aggarwal V, Singla M, Kabi D. Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial. J Endod. 2010;36:375378. doi: 10.1016/j.joen.2009.11.010. [DOI] [PubMed] [Google Scholar]
  • 9.Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients with irreversible pulpitis. J Endod. 2010;36:379–382. doi: 10.1016/j.joen.2009.12.030. [DOI] [PubMed] [Google Scholar]
  • 10.Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal anti-inflammatory drugs for the success of the inferior alveolar nerve block in irreversible pulpitis treatment: a systematic review and meta-analysis based on randomized controlled trials. Quintessence Int. 2012;43:209–219. [PubMed] [Google Scholar]
  • 11.Nusstein JM, Reader A, Drum M. Local anesthesia strategies for the patient with a “hot” tooth. Dent Clin North Am. 2010;54:237–247. doi: 10.1016/j.cden.2009.12.003. [DOI] [PubMed] [Google Scholar]
  • 12.Parirokh M, Ashouri R, Rekabi AR, et al. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2010;36:1450–1454. doi: 10.1016/j.joen.2010.05.007. [DOI] [PubMed] [Google Scholar]
  • 13.Modaresi J, Dianat O, Mozayeni MA. The efficacy comparison of ibuprofen, acetaminophen-codeine, and placebo premedication therapy on the depth of anesthesia during treatment of inflamed teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2006;102:399–403. doi: 10.1016/j.tripleo.2005.10.053. [DOI] [PubMed] [Google Scholar]
  • 14.Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38:565–569. doi: 10.1016/j.joen.2012.02.010. [DOI] [PubMed] [Google Scholar]
  • 15.Bernick S. Effect of aging on the nerve supply to human teeth. J Dent Res. 1967;46:694–699. doi: 10.1177/00220345670460041101. [DOI] [PubMed] [Google Scholar]
  • 16.Bernick S, Nedelman C. Effect of aging on the human pulp. J Endod. 1975;1:88–94. doi: 10.1016/S0099-2399(75)80024-0. [DOI] [PubMed] [Google Scholar]
  • 17.American Academy of Pediatric Dentistry. Guideline on use of nitrous oxide for pediatric dental patients. Pediatr Dent. 2013;35:E174–E178. [PubMed] [Google Scholar]
  • 18.Tomlinson D, von Baeyer CL, Stinson JN, Sung L. A systematic review of faces scales for the self-report of pain intensity in children. Pediatrics. 2010;126:e1168–e1198. doi: 10.1542/peds.2010-1609. [DOI] [PubMed] [Google Scholar]
  • 19.Chambers CT, Giesbrecht K, Craig KD, Bennett SM, Huntsman E. A comparison of faces scales for the measurement of pediatric pain: children's and parents' ratings. Pain. 1999;83:25–35. doi: 10.1016/s0304-3959(99)00086-x. [DOI] [PubMed] [Google Scholar]
  • 20.Chambers CT, Hardial J, Craig KD, Court C, Montgomery C. Faces scales for the measurement of postoperative pain intensity in children following minor surgery. Clin J Pain. 2005;21:277–285. doi: 10.1097/00002508-200505000-00011. [DOI] [PubMed] [Google Scholar]
  • 21.Buchanan H, Niven N. Validation of a Facial Image Scale to assess child dental anxiety. Int J Paediatr Dent. 2002;12:47–52. [PubMed] [Google Scholar]
  • 22.Sealed Envelope Ltd. Create a blocked randomisation list. 2014 Available at: https://www.sealedenvelope.com/simple-randomiser/v1/lists Accessed May 10,
  • 23.van Wijk AJ, Makkes PC. Highly anxious dental patients report more pain during dental injections. Br Dent J. 2008;205(3):E7. doi: 10.1038/sj.bdj.2008.583. [DOI] [PubMed] [Google Scholar]
  • 24.Clark MS, Brunick AL. Handbook of Nitrous Oxide and Oxygen Sedation. St Louis, MO: Mosby, Elsevier;; 2008. [Google Scholar]
  • 25.Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs) BMJ. 2013. 346:f3195. [DOI] [PubMed]
  • 26.Emmanouil DE, Quock RM. Advances in understanding the actions of nitrous oxide. Anesth Prog. 2007;54:9–18. doi: 10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Ben Boujema M, Laboureyras E, Pype J, Bessiere B, Simonnet G. Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: a dose-dependent effect. Pain Res Manage. 2015;20:309–315. doi: 10.1155/2015/809059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Schulz KF, Altman DG, Moher D. Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2011;9:672–677. doi: 10.1016/j.ijsu.2011.09.004. [DOI] [PubMed] [Google Scholar]
  • 29.Khatri A, Kalra N. A comparison of two pain scales in the assessment of dental pain in East delhi children. ISRN Dent. 2012;2012:247–351. doi: 10.5402/2012/247351. [DOI] [PMC free article] [PubMed] [Google Scholar]

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