Adrenaline in pulp capping treatment of reversible pulpitis

Abstract

BACKGROUND

The role of epinephrine in the treatment of pulp capping in patients with reversible pulpitis is not clear.

AIM

To explore the role of epinephrine in the treatment of pulp capping in patients with reversible pulpitis.

METHODS

A total of 100 patients with reversible pulpitis who were treated in Anhui Jieshou People's Hospital from January 2020 to December 2021 were included in the study. They were categorized into an observation group (n = 50; treatment with adrenaline) and a control group (n = 50; treatment with zinc oxide eugenol paste). The 24-h postoperative pain, regression time of gingival congestion and redness, clinical efficacy, and incidence of adverse reactions were compared between the groups. Patients were further categorized into the ineffective and effective treatment groups based on clinical efficacy. Logistic multiple regression analysis explored factors affecting the efficacy of pulp capping treatment.

RESULTS

A significant difference in 24-h postoperative pain was observed between the groups (P < 0.05), with a higher proportion of grade I pain noted in the observation group than in the control group (P < 0.01). The regression time of gingival congestion and swelling was lower in the observation group (2.61 ± 1.44 d and 2.73 ± 1.36 d, respectively) than in the control group (3.85 ± 1.47 d and 4.28 ± 1.61 d, respectively) (P < 0.05). The 2-wk postoperative total effective rate was lower in the control group (80.00%) than in the observation group (94.00%) (P < 0.05). The incidence of adverse reactions was not significantly different between the control (14.00%) and observation (12.00%) groups (P > 0.05). The proportion of adrenaline usage was lower (P < 0.05) and that of anaerobic digestion by Streptococcus and Fusobacterium nucleatum was higher in the ineffective treatment group than in the effective treatment group (P < 0.05). Logistic multiple regression analysis revealed adrenaline as a protective factor (P < 0.05) and anaerobic digestion by Streptococcus and F. nucleatum as risk factors for pulp capping in reversible pulpitis (P < 0.05).

CONCLUSION

Adrenaline demonstrated therapeutic efficacy in pulp capping treatment for reversible pulpitis, reducing pain and improving clinical symptoms safely. It is a protective factor for pulp capping, whereas Streptococcus and F. nucleatum are risk factors. Targeted measures can be implemented to improve clinical efficacy.

Key Words: Adrenaline, Reversible pulpitis, Pulp capping, Efficacy, Safety

Core Tip: Reversible pulpitis is an inflammatory disease characterized by vasodilation and congestion of pulp tissue as the main pathological changes following infection and stimulation by cold and heat. It is speculated that adrenaline might improve the symptoms of congestion and swelling in the tissues surrounding the pulp in patients with reversible pulpitis. This study included 100 patients with reversible pulpitis to explore the role of adrenaline in pulp capping treatment in patients with reversible pulpitis and its analgesic and hemostatic effects and safety. Adrenaline demonstrated therapeutic efficacy in pulp capping treatment for reversible pulpitis, reducing pain and improving clinical symptoms safely.

INTRODUCTION

Reversible pulpitis is an inflammatory disease characterized by vasodilation and congestion of pulp tissue as the main pathological changes following infection and stimulation by cold and heat[1]. It is regarded as the early stage of pulpitis. Removing the pathogenic stimulus on the affected teeth and providing appropriate treatment to control inflammation can restore the pulp of the affected teeth to its original state[2]. Therefore, the primary principle of clinical treatment is to reduce inflammation, relieve pain, and preserve pulp vitality.

Pulp capping covers the near-pulp dentin or exposed pulp wound with a preparation that can recover the pulp from its diseased state, protecting the pulp and eliminate inflammation[3]. However, some patients do not experience improvements in congestion and swelling of the tissues around the pulp after pulp capping, considerably affecting their daily lives[4]. Adrenaline is a hormone and neurotransmitter released by the adrenal gland that increases heart contractility, dilates blood vessels of the heart, liver, and bones, and constricts blood vessels of the skin and mucous membranes. It has been shown to reduce the blood vessels of the skin and mucous membrane, and studies[5] have confirmed that adrenaline can reduce the blood flow and relieve the partial pressure of oxygen in the dental pulp.

It is speculated that adrenaline might improve the symptoms of congestion and swelling in the tissues surrounding the pulp in patients with reversible pulpitis; however, no relevant clinical research has been conducted. Therefore, in this study, adrenaline was applied for the pulp-capping treatment of reversible pulpitis to explore its analgesic and hemostatic effects and safety, aiming to find a more suitable pulp-capping agent for treating reversible pulpitis.

MATERIALS AND METHODS

Study population

This study included 100 patients with reversible pulpitis who were treated at Anhui Jieshou People's Hospital (Anhui, China) between January 2020 and December 2021. The inclusion criteria for participants in this study were as follows: (1) Meeting the diagnostic criteria of the American Association of Pulpopathy[6], confirmation by radiographic examination, and presence of clinical symptoms including immediate pain reaction to varying degrees of hot, cold, or chemical stimuli, without spontaneous pain and with cavities closer to the pulp chamber; (2) Maintaining good oral hygiene; and (3) Agreeing to provide a signed informed consent form for the study. The exclusion criteria were as follows: (1) Abnormal hematopoietic system, mental disease, or cardiac, renal and immune dysfunction; (2) Pregnancy or lactation; (3) Severe periodontal infection or periodontal pocket and occlusal trauma; (4) Allergic to the study drug; or (5) Chronic periodontitis, root furcation disease, cracked teeth, and oral mucosa disease. Using the random number table method, patients were categorized into an observation group and a control group, each including 50 patients. The observation group comprised 27 teeth of 27 male patients and 23 teeth of 23 female patients. The onset-to-treatment time ranged from 6 h to 5 mo, with an average of 2.22 ± 0.11 mo. Their ages ranged from 35 years to 60 years, with an average of 47.33 ± 4.11 years. The control group comprised 30 teeth of 30 male patients and 20 teeth of 20 female patients. The onset-to-treatment time ranged from 7 h to 5 mo, with an average of 2.33 ± 1.25 mo. Their ages ranged from 36 years to 60 years, with an average of 47.66 ± 4.28 years.

Therapeutic method

All patients underwent routine oral and radiographic examinations before treatment. After regional anesthesia with articaine, carious tissues or softened dentin was removed to the maximum extent possible. The cavity was rinsed with normal saline, eugenol was applied onto the dental pulp, and the tooth was dried and isolated from moisture contamination. Pulp capping was performed on teeth without exposed pulp or accidentally exposed pulp during treatment. In the control group, calcium hydroxide paste was placed on near-pulp dentine or exposed pulp, and the patients was monitored for 2 wk. If no symptom occurred, the cavity was permanently filled. In the observation group, cotton balls soaked in adrenaline were placed on near-pulp dentine or exposed pulp, removed after 30 min, replaced with the same cotton balls; the cavity was temporarily sealed with zinc polycarboxylate cement, and this process was repeated 1-2 times a week. If the patient had no symptoms after 1-2 wk of continuous treatment and pulp vitality was normal, most of the temporary filling was removed, a zinc phosphate cement base was applied, and the cavity was permanently filled with composite resin or silver mercury. If the patient exhibited sensitivity to temperature stimulation, the original temporary sealing agent was removed, pulp-capping agent was replaced, and the patient was monitored until the symptoms completely resolved. Thereafter, the cavity was permanently filled. During the treatment period, patients were instructed to avoid eating too cold, too hot, or hard food; avoid smoking or drinking; brush their teeth in the morning or evening; and maintain oral hygiene. For severe inflammation, appropriate anti-inflammatory drugs and glucocorticoid preparations were administered orally for 3 d. After symptom resolution, temporary sealing or permanently filling was performed.

Data collection

Data on sex, age, course of disease, tooth position, presence or absence of cold or hot stimulation pain, cold or hot stimulation delayed pain, nocturnal pain, percussion pain, microbial species in the affected teeth, and use of adrenaline for treatment were collected. The microbial strains in the affected teeth were identified using bacterial culture, performed before pulp capping. After opening the pulp chamber, the contents of the pulp cavity were collected using sterile probe-type cotton swabs, placed in sterile test tubes, and sent to the microbiological laboratory for testing. Cells from the samples were inoculated on a blood agar plate using the three-zone line-drawing method for bacterial culture. After a single bacterial colony grew, a single colony (with large colonies and clear edges) was selected for separation and purification. The morphology of the colony was observed, and preliminary identification was performed after Gram staining. Finally, the VITEK 2 Compact automated microbial identification instrument (bioMérieux, Inc., Durham, NC, United States) was used to identify the bacterial species.

Main adrenalines

(1) Comparison of the 24-h postoperative pain between the observation and control groups. Based on the relevant literature[7], pain levels were evaluated in grades within 24 h after the treatment, with grade I indicating no pain and a sense of well-being; grade II indicating slight pain without relief, and the pain disappearing within 24 h; and grade III indicating pain persisting beyond 24 h requiring further treatment.

(2) Comparison of the regression time of gingival congestion and swelling after treatment between the two groups.

(3) Comparison of the 2-wk postoperative clinical efficacy of the treatment in the two groups. Ineffective treatment for a patient was determined based on the inability to perform masticatory function and dental pain not improving or getting aggravated, whereas effective treatment for a patient was determined based on the partial improvement of masticatory function and relief from dental pain. Healers were defined as patients with resolution of dental pulp pain and restoration of masticatory function[8]. The total effective rate was calculated as follows: (number of effective cases + number of cured cases)/total number of cases × 100%.

(4) Comparison of the incidence of adverse reactions, including gastrointestinal discomfort, nausea, vomiting, dizziness, palpitations, and headache, between the two groups.

And (5) Exploration of factors affecting the curative effect of pulp capping for reversible pulpitis.

Statistical analyses

All data were analyzed using SPSS software version 18.0 (IBM, Armonk, NY, United States). Counting data are presented as n (%), and the t-test was used for comparisons. If any theoretical frequency was ≥ 1 but < 5, the χ² test was used. If any theoretical frequency was 0, Fisher's exact test was used. Measurement data are presented as the mean ± SD, and the independent samples t-test was used for comparisons. Logistic regression analysis was used to explore the factors influencing pulp capping therapy in patients with reversible pulpitis. Statistical significance was set at P < 0.05.

RESULTS

Comparison of the 24-h postoperative pain

As shown in Table 1, a statistically significant difference was observed between the observation group and control group (P < 0.05). The proportion of grade I pain was higher in the observation group than in the control group (90% vs 68%, respectively; P < 0.01).

Table 1 Grades of the 24-h postoperative pain, n (%).

Group	n	I	II	III
Control	50	34 (68.00)	11 (22.00)	5 (10.00)
Adrenaline	50	45 (90.00)a	3 (6.00)	2 (4.00)
Z value		7.389
P value		0.025

^aP < 0.01 vs control group.Data are n (%).

Comparison of the regression time of gingival congestion and gingival swelling after surgery

As shown in Table 2, in the observation group, gingival congestion, regression time of postoperative gingival congestion and swelling were 2.61 ± 1.44 d and 3.85 ± 1.47 d, respectively. In the control group, regression time of postoperative gingival congestion and swelling were 2.73 ± 1.36 d and 4.28 ± 1.61 d, respectively. The time taken for gingival congestion and swelling to subside was shorter in the observation group than in the control group (P < 0.05).

Table 2 Regression time of postoperative gingival congestion and swelling.

Group	n	Time of gingival congestion resolution	Time for gingival swelling to subside
Control	50	3.26 ± 1.36	4.28 ± 1.61
Adrenaline	50	3.12 ± 1.51	2.73 ± 1.36
t		4.261	5.200
P value		< 0.001	< 0.001

Comparison of the 2-wk postoperative clinical efficacy

As shown in Table 3, a statistically significant difference in 2-wk postoperative clinical efficacy of the treatment was observed between the observation and control (P < 0.05) groups, with a higher total effective rate noted in the observation group than in the control group (94% vs 80%, respectively; P < 0.05).

Table 3 Clinical efficacy between the two groups.

Group	Ineffective	Effective	Cured	Effective rate
Control	10 (20.00)	21 (42.00)	19 (38.00)	40 (80.00)
Adrenaline	3 (6.00)	18 (36.00)	29 (58.00)	47 (94.00)
Z/χ2	6.083			4.332
P value	0.048			0.037

Data are n (%).

Comparison of the incidence of adverse reactions

The incidence of adverse reactions in the control group was 14.00% (7/50), including 3 cases of gastrointestinal discomfort, 3 cases of nausea, and 1 case of vomiting. The incidence of adverse reactions was higher in the observation group at 12.00% (6/50), including 2 cases of gastrointestinal discomfort and 1 case each of nausea, dizziness, palpitation, and headache. No significant difference in the rate of adverse reactions was observed between the two groups (P > 0.05).

Analysis of the factors affecting pulp capping treatment in patients with reversible pulpitis

In this study, the treatment was ineffective for 13 patients and effective for 87 patients. A total of 188 strains were isolated from 100 samples, including 21 strains from the ineffective treatment group and 167 strains from the effective treatment group. The proportion of adrenaline usage was lower (P < 0.05) and that of anaerobic digestion by Streptococcus and Fusobacterium nucleatum was higher in the ineffective treatment group than in the effective treatment group (P < 0.05; Table 4). Logistic multiple regression analysis revealed adrenaline as a protective factor (P < 0.05) and anaerobic digestion by Streptococcus and F. nucleatum as risk factors (P < 0.05) for pulp capping treatment in reversible pulpitis (Table 5).

Table 4 Baseline characteristics of the study patients.

Variable	Ineffective, n = 13	Effective, n = 87	t/χ2	P value
Sex
Male	7 (53.85)	50 (57.47)	0.061	0.805
Female	6 (46.15)	37 (42.53)
Age in yr	47.92 ± 4.61	47.43 ± 4.13	0.393	0.695
Disease duration in mo	2.52 ± 1.38	2.24 ± 0.58	1.295	0.198
Site
Premolar	10 (76.92)	78 (89.66)	0.740	0.390
Molar tooth	3 (23.08)	9 (10.34)
Cold irritant pain
Yes	9 (69.23)	73 (83.91)	0.806	0.369
No	4 (30.77)	14 (16.09)
Heat tingling pain
Yes	10 (76.92)	74 (85.06)	0.116	0.733
No	3 (23.08)	13 (14.94)
Cold stimulation retards pain
Yes	7 (53.85)	38 (43.68)	0.151	0.698
No	6 (46.15)	49 (56.32)
Heat stimulation retards pain
Yes	8 (61.54)	42 (48.28)	0.796	0.372
No	5 (38.46)	45 (51.72)
Nocturnal pain
Yes	5 (38.46)	36 (41.38)	0.040	0.842
No	8 (61.54)	51 (58.62)
Percussion pain
Yes	7 (53.85)	38 (43.68)	0.472	0.492
No	6 (46.15)	49 (56.32)
Dental microorganisms
Lactobacillus	0 (0.00)	75 (86.21)	62.118	< 0.001
Streptococcus	7 (53.85)	7 (8.05)
Pseudomonas	4 (30.77)	3 (3.45)
other	2 (15.38)	2 (2.30)
Adrenaline use
Yes	2 (15.38)	48 (55.17)	5.659	0.017
No	11 (84.62)	39 (44.83)
Dental microorganisms, main Gram-positive aerobic bacteria
Staphylococcus aureus	2 (9.52)	37 (22.16)	1.124	0.289
Enterococcus mimicus	1 (4.76)	8 (4.79)	0.288	0.592
Colombian enterococcus	1 (4.76)	2 (1.20)	0.093	0.761
Main Gram-positive anaerobic bacteria
Peptostreptococcus anaerobius	4 (19.05)	5 (2.99)	7.319	0.007
Main Gram-negative anaerobic bacteria
Bacteroides fragilis	2 (9.52)	25 (14.97)	0.116	0.733
Prevotella melanogenes	2 (9.52)	36 (21.56)	1.012	0.314
Porphyromonas gingivalis	2 (9.52)	20 (11.98)	0.001	0.976
Fusobacterium nucleatum	5 (23.81)	10 (5.99)	8.069	0.005
Clostridium parvum	0 (0.00)	6 (3.59)	0.050	0.823

Table 5 Multivariate analysis of the curative effect of reversible pulpitis.

Variable	β	SE	Wald χ2	P value	OR	95%CI
Anaerobic Streptococcus	0.523	0.178	8.633	0.003	1.667	1.199-2.317
Fusobacterium nucleatum	0.589	0.201	8.587	0.004	1.761	1.216-2.551
Adrenaline use as yes	-0.742	0.299	6.158	0.013	0.491	0.279-0.864

CI: Confidence interval; OR: Odds ratio; SE: Standard error.

DISCUSSION

In reversible pulpitis the pulp exhibits congestion, vascular expansion, and tissue edema influenced by numerous inflammatory factors, all of which lead to irreversible necrosis of the pulp tissue, causing a serious impact on oral health[9]. Without timely clinical intervention, this condition can lead to periapical inflammation and eventually result in pulp necrosis[10]. Therefore, prompt and appropriate measures must be taken to provide active treatment, ensuring the vitality of dental pulp and preserving the normal physiological function of the affected teeth. Pulp capping is a widely used treatment method in clinical practice; however, the affected teeth are prone to repeated stimulation after pulp capping, leading to persistence of clinical symptoms, such as gingival congestion and edema that necessitates further clinical consideration.

The findings of this study revealed a significant difference in the 24-h postoperative pain between the observation and control groups, with a higher proportion of grade I pain noted in the former group. Additionally, the regression time of gingival congestion and redness was shorter and the clinical efficacy of the treatment was higher in the observation group than in the control group. These findings suggest that adrenaline as a pulp-capping agent can effectively relieve pain in patients with reversible pulpitis and help improve clinical symptoms of pulp tissue congestion, redness, and swelling. Such clinical improvements in symptoms are noteworthy. As the pulp tissue is located within the pulp cavity, characterized by weak elasticity and surrounded by rigid walls, it relies solely on blood circulation through small apical holes and lacks collateral circulation[11]. When the pulp undergoes an inflammatory reaction and the inflammatory exudates cannot be drained, the pressure within the pulp cavity increases, causing severe pain to the patient. Additionally, the permeability of the blood vessels of the affected pulp increases, leading to plasma exudation and subsequent redness and swelling of periodontal tissue; a small number of red blood cells extravasate around the blood vessels.

Zinc oxide clove oil paste is commonly used as a pulp-capping agent. It is weakly alkaline, minimally stimulating to the periodontal tissue, and becomes acidic before hardening. Furthermore, it exhibits antibacterial, soothing, and analgesic effects[12]. However, previous studies have revealed that[13], if zinc oxide eugenol paste is used in direct pulp capping treatment, it causes chronic inflammation of the dental pulp and surrounding tissues, thereby aggravate swelling and pain. Adrenaline is both an alpha and beta agonist of two types of receptors present on bronchial smooth muscle, capillaries, and the anterior sphincter of small arteries to relax bronchi and constrict blood vessels (alpha, beta type I effect) and is often used in clinics to relieve allergic reactions, prolong the action time of infiltration anesthesia, and improve hemostatic effects[14,15]. Additionally, it has important clinical application value. Given the abundance of alpha receptors in the smooth muscle of the blood vessels of the skin, oral mucosa, and other organs, adrenaline exerts a pronounced vasoconstrictive effect on these tissues[16]. A previous study showed that using adrenaline for the treatment of dental pulp disease can prolong anesthetic time, reduce allergic reactions, diminish toxic reactions, and constrict blood vessels[17]. A study also confirmed that adrenaline induces strong vasoconstriction at the mucosal gingival junction, which can diffuse to the gingival mucosal junction, thus exerting a diffusive vasoconstrictive effect[18]. This suggests that adrenaline can induce distal gingival vasoconstriction by locally generated vasoconstriction. Therefore, in this study, adrenaline was used for pulp capping treatment of carious teeth with reversible pulpitis for stimulating α receptors to induce vasoconstriction, reduce blood flow, accelerate the regression of symptoms such as gingival congestion and edema, reduce intramedullary pressure, relieve dental pain, and improve clinical efficacy. In addition, the results of this study showed that the incidence of adverse reactions was comparable in the observation and control groups, indicating that adrenaline does not increase the incidence of adverse reactions in pulp capping treatment for reversible pulpitis, thus affirming its safety and suitability for clinical use.

Through logistic multiple regression analysis, this study revealed adrenaline as a protective factor and anaerobic digestion by Streptococcus and F. nucleatum as risk factors for pulp capping treatment in patients with reversible pulpitis. This suggests that the application of adrenaline in pulp-capping treatment for reversible pulpitis can improve clinical efficacy and patient prognosis. The use of adrenaline can promote vasoconstriction of oral mucosal blood vessels and relaxation of the bronchial smooth muscles, thereby expanding the bronchi, reducing edema, slowing bleeding, improving patient symptoms, and enhancing therapeutic effects. Anaerobic Streptococcus is one of the primary pathogenic bacteria contributing to pulpitis. Its presence can cause dysbiosis of the dental pulp microbiota, accelerate bacterial infection, and promote disease progression. F. nucleatum mainly relies on amino acid decomposition metabolites for energy; among these metabolites, butyrate, ammonia, butyrate, and hydrogen sulfide have destructive effects on the periodontal tissue. Moreover, F. nucleatum can co-aggregate with Streptococcus, Actinobacteria, and Porphyromonas gingivalis, promoting the formation of plaque biofilms and increasing the difficulty of treatment[19,20]. Therefore, infections involving Streptococcus and F. nucleatum can exacerbate the severity of pulpitis and hinder the efficacy of pulp capping treatment.

Limits of the study

This study had some limitations. Only patients admitted to Anhui Jieshou People's Hospital were selected as the research subjects, and the sample size was not large, which may have led to a certain selectivity bias. Thus, future multicenter studies with large sample sizes are needed.

CONCLUSION

In conclusion, adrenaline demonstrates good clinical efficacy for treating reversible pulpitis with pulp capping, effectively alleviating pain, improving clinical symptoms, and demonstrating safety. Adrenaline acts as a protective factor in pulp capping for reversible pulpitis. Microorganisms of the affected teeth, including Streptococcus and F. nucleatum, are considered as risk factors affecting treatment outcomes.