Background
Dysphagia is a symptom of swallowing dysfunction that is caused by a variety of conditions such as cerebrovascular disorder [
1]. Dysphagia was observed in 55% of elderly patients admitted with care-associated pneumonia (CAP) [
2]. Loeb et al. [
3] conducted a case–control study and demonstrated that dysphagia was observed in 14.3% of elderly patients hospitalized for pneumonia. Oral hygiene is critical for the prevention of aspiration. Oral bacteria may be an important reservoir for CAP in institutionalized elders who are on parenteral nutrition and are at high risk for developing aspiration pneumonia [
4]. Although oral care is important for the prevention of aspiration pneumonia, there are many cases in which it is difficult to clean smooth tissues or teeth surfaces. The oral cavities of patients on parenteral nutrition are dry, and their care is time-consuming due to the risk of bleeding. Moreover, special care has to be taken because of the risk of aspiration. Such patients are more likely to develop severe diseases or complications after infection. Adequate oral care using a safe method is important for preventing dysphagia and reducing the risk of aspiration. Oral care for the elderly is different from that for healthy people, and it is necessary to manage oral hygiene, including moisturizing, in addition to brushing the teeth. In these cases, membranous substances may be observed in the oral cavity of patients receiving Ryle’s tube-feeding. All membranous substances were composed of keratinous material derived from the stratified squamous epithelium of the oral mucosa. It has been reported that parenteral intake and dryness of the oral mucosa are important factors for its formation [
5]. Despite the fact that a lot of bacteria are present in membranous substances, it is not clear whether intraoral bacteria decrease on temporarily cleaning membranous substances.
A common method of oral care in high-risk patients is using gels [
6]. Oral care gels are also effective in patients with xerostomia [
7]. In practice, xerostomia can impair swallowing, speech, and oral hygiene; if left unchecked, symptoms such as dysphagia and dysarthria can diminish patients’ quality of life (QOL). Xerostomia is one of the factors contributing to dysphagia [
8]. The principal idea of these salivary substitutes is to provide a long-continuous coat over oral soft tissues using an oral care gel [
9]. Xerostomia is often observed in hospitalized or older adults requiring long-term care [
10]. Tube-feeding and mechanical airways decrease the auto-purification of saliva. In cases of xerostomia, membranous substances observed on the tongue and palate are risk factors for halitosis and aspiration pneumonia.
In this study, we evaluated the effectiveness of oral care gel using a matching transformation system (MA-T). MA-T is an on-demand aqueous chlorine dioxide solution with the generation of aqueous radicals controlled by a catalyst [
11]. MA-T exhibits excellent safety and various antimicrobial effects [
12]. MA-T showed sufficient antimicrobial effects at 100 ppm in all the media. Additionally, MA-T is not inflammable, volatile, or corrosive; therefore, it is widely used in medical care. In this study, we focused on the effects of MA-T in high-risk patients. Based on the hypothesis that MA-T is effective for improving oral hygiene, we prospectively tested its efficacy against these pathogens.
This study aimed to investigate the effect of MA-T gel on patients who were on parenteral nutrition. The effectiveness of oral care provided by the gel was examined at the bedside and in the laboratory side by assessing oral bacterial counts and oral moisture.
Methods
Study design
This interventional study assessed the efficacy of MA-T gel. Patients included in the study were hospitalized in Okayama Prefecture, Japan. This study was conducted between April and June 2022. Patients who underwent medical examination and treatment and were put on parenteral nutrition were included in the study. The exclusion criteria were as follows: patients who could not provide consent and those with a relatively good oral environment. The oral environment was assessed using the Oral Assessment Guide score [
13]. A flowchart of the patient selection process is shown in Additional file
1: Figure S1. All patients required nursing care and underwent medical examination and treatment. The patients were managed by tube feeding and assisted respiration using a mechanical ventilator. They had been receiving nasal feeding for at least 1 year. They were followed up for several years, so their dental treatment had been completed, and they continued to receive professional care prior to the study. Five participants were included in the study. However, two patients died during this study, as a consequence of a critical underlying disease. Three patients were included in the study
. All sampling was repeated three times using the same method. None of the patients developed severe pneumonia during the study period. Informed consent was obtained from the relatives for inclusion of the patients in the study. The clinical characteristics of the patients are presented in Table
1.
Table 1
Participant characteristics
A | 64 | Female | NG | TR | Cerebral hemorrhage |
B | 71 | Male | NG | TR | Cerebral infarction Diabetes |
C | 87 | male | NG | NPPV | Cerebral hemorrhage Cerebral infarction Diabetes Chronic hepatitis |
Study protocol for the research participants
The two phases of MA-T gel and control were compared in the same patient during the investigation period. Pure water was used as a control instead of the MA-T gel. Continuous professional care was provided during the investigation period. The first intervention was performed with pure water and without any oral care products. The next period of investigation involved care with MA-T gel. During the MA-T gel investigation, the gel was placed at the bedside and used for daily care. Before each investigation period, a month reset periods was set up. During the reset period, the patients did not receive professional care. Daily care was consistently provided throughout the reset and study period. Daily care was done using the same type of oral swab sponge and toothbrush, and that was provided by ward nurses three times a day, between 6:00 and 10:00, 12:00 and 16:00, and 18:00 and 20:00. During investigation periods, daily care was not provided at noon. Instead, dental hygienists with more than 20 years of experience in dentistry cleaned the oral cavity with 2.0 g pure water or MA-T gel. The duration of the oral care was not limited. Because the patient’s position was limited owing to contractures and pressure ulcers, oral care was provided keeping the patient’s comfort in mind. The same types of new oral swab sponges, toothbrushes, tufts, and interdental brushes were used. The following basic information was extracted from medical records: age, sex, nutritional intake, type of ventilation, and primary disease. In all cases, physical conditions were checked before the investigation. Body temperature was measured using a thermometer, and blood oxygen saturation was measured using a pulse oximeter. In addition, blood pressure was measured to check for any changes in the daily status.
Oral care gel
MA-T gel; N.act oral removal gel® is available from Earth Corporation (Tokyo, Japan). The chief ingredient of MA-T gel is chlorous acid ion. Other ingredients included solvent, water, viscosity conditioner, hydroxypropyl methylcellulose, flavoring materials, xylitol, pH conditioner, sodium phosphate, disodium phosphate, and sodium hydroxide; cleaning materials, sodium chlorite; and preservative, benzalkonium chloride. The mouth gel contained 100 ppm MA-T. The control gel for the cultural experience was provided by the Earth Corporation. The control gel consisted of a base material in the MA-T gel and did not contain MA-T. Although water was used as a control in the patient surveys, we used similar quantities of water and the MA-T gel. MA-T mouthwash; A2Care mouthwash® (Earth Corporation and a2care Corporation, Tokyo, Japan) has been commercially available without any adverse events for 7 years since 2016. There have been no reports of harmful effects caused by the use of MA-T gels since the beginning of 2022.
Study methods
The research was conducted at the bedside and laboratory-side. Bacterial count measurements, oral moisture tests, and opportunistic bacterial count measurements were performed in the bedside study. Histological and bacterial culture analyses were performed in the laboratory.
Bacterial count measurement
Bacterial counts were performed using an oral bacterial counter
Ⓡ (Panasonic, Tokyo, Japan). The bacteria counter measures all the living bacteria. It collects bacteria in the liquid by dielectrophoretic on the electrode, measures the impedance change, and converts it into the bacterial concentration (CFU) in 1.0 mL of the sample, thus quantitatively measuring the number of bacteria. Samples were collected from the oral mucosa using cotton swabs. The number of bacteria is affected by intraoral humidity [
14]. The oral cavity was wiped using a sponge brush soaked in a small amount of water before professional care. The samples were measured before swabbing, after swabbing, and after professional care a total of three times.
Oral moisture test using Mucus®
Moisture levels of the oral mucosa were measured using an oral moisture-checking device (Mucus
®, LIFE Co., Saitama, Japan). The device analyzes water maintenance of the mucous membrane [
15]. The oral moisture score of the buccal mucosa was repeated thrice, and the median value was selected. Scores ≤ 27.9 were categorized as xerostomia. Scores between 28.0 and 29.5 are considered borderline between normal and xerostomia, and a score ≥ 29.6 is considered normal.
Opportunistic bacterial count measurement
Opportunistic bacterial infections were corrected prior to swabbing and professional care. All opportunistic bacterial counts were measured by BML, Inc. (Tokyo, Japan). Nutrient medium with the samples was cultured at 35.0 ± 1.0°C for 18–24 h under 5.0% CO2. Colonies of the desired bacteria were identified using a confirmation nutrient medium and an identification kit. For opportunistic infection analysis, we assessed 10 types of pathogens: methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), Haemophilus influenzae (H. influenzaw), Streptococcus agalactiae (S. agalactiae), Pseudomonas aeruginosa (P. aeruginosa), Streptococcus pneumoniae (S. pneumoniae), Klebsiella pneumoniae (K. pneumoniae), Serratia marcescens (S. marcescens), Moraxella catarrhalis (M. catarrhalis), and Candida species. The opportunistic infection bacterial score was set as follows: (—): No growth of bacteria, (1+): The growth of bacteria accepted to be one-third of the nutrient medium (approximately 1.0 × 103 CFU/mL), (2+): The growth of bacteria accepted to be two-thirds of the nutrient medium (approximately 1.0 × 104 CFU/mL), (3+): The growth of bacteria accepted by the whole nutrient medium (above 1.0 × 105 CFU/mL).
Histological analysis
Histological analysis was performed to confirm the structures of the membranes. The membranes used in the laboratory study were samples obtained after the reset period and before the intervention began. Samples were obtained from the patients’ palates by dental hygienists. The membranes were blindly selected as a sample of middle softness and sectioned by the technical staff. After intraoral photographs were taken, the adherent material of the palate was collected and immersed in 4.0% neutral buffered formalin solution. Paraffin sections of the collected membranous material were prepared according to the standard method, and hematoxylin and eosin staining was performed [
16].
Bacterial culture analysis
The control gel and MA-T gel were used to compare reactivity to bacteria. Most gram-positive and gram-negative bacteria were cultured on cetrimide agar (Nissui, Tokyo, Japan). MRSA and P. aeruginosa-selective media were used for culture of the respective organisms. Oral film of 0.5 g and 1.0 mL of sterilized distilled pure water were mixed by vortex for 1 min after being left for 10 min at 28 °C. Half of the liquid part of the mixed oral epithelium was mixed with gel and spread in the culture medium prepared in 9-cm diameter plates. Three experiments were performed. After culturing the cells for 24 h, the number of bacteria was evaluated.
Ethical approval and consent
The Institutional Ethical Review Board of Osaka University Graduate School of Dentistry approved the study protocol (Approval Number: R2-E40-4). All methods were performed in accordance with relevant guidelines and regulations. Informed consent was provided by the patients’ families because all the patients were unable to communicate. We confirmed that informed consent described the conditions of donation of materials for this research, such as oral membranous substances.
Statistical analysis
Data are presented as mean values and standard deviations. We used the paired t test to compare the MA-T gel and water. The Bonferroni correction was used for multiple comparisons (Before, Swab, and Care). Spearman rank correlation coefficients were used to determine the relationship between the moisture score and bacterial count. Fisher’s exact test was used for opportunistic infection bacterial score analyses.
Discussion
None of the patients in this study could take oral feeds and breathing was by mechanical ventilation, due to cerebrovascular disease. High-quality care is necessary because of the difficulties in communicating with such patients. Additionally, daily care should be simple and safe. Oral care must be performed several times a day to protect the oral cavity from bacterial invasion. Although oral care of the elderly is important, physical and mental burdens occur owing to changes in posture and breathing patterns and choking due to aspiration and mental stress [
17]. Moreover, aspiration should be prevented during oral care in high-risk patients. Silent aspiration easily occurs when oral hygiene is poor and infected saliva causes aspiration-related pneumonia [
18]. Therefore, oral care can prevent aspiration-related pneumonia in older receiving nursing care. Although it is well known that oral care is important, challenges in hospitals and facilities exist because there are fewer staff members. Oral care gels are often used for ease of care and moisturization. This study showed that the use of MA-T gel not only improved moisture retention but also reduced the total bacteria in the oral cavity. Bacterial culture experiments showed that the gel was effective against opportunistic bacteria. This study focused on the membrane substances of high-risk patients who were not taking oral medication. Membranous substances were always detected in patients who did not ingest them orally if their oral cavity were regularly cared for. A previous study showed that membranous substances consist of secretory mucins (Muc5B) from the palatine gland, dried viscous liquid, and bacteria [
19]. Tearing a film from the oral mucosa is challenging. The MA-T gel consisted of MA-T and base material. MA-T directly reduced the total bacterial count in the oral cavity by inactivating bacteria, including opportunistic organisms that cause pneumonia. In addition, the base material of the gel was shown to improve the oral humidity. The improvement in intraoral humidity makes it easier to remove dirt, which indirectly reduces the number of intraoral bacteria. Furthermore, the formation of the epithelial film is caused by interference in the turnover of the mucosa [
20]. The improvement in oral humidity leads to normal turnover of the oral mucosa and prevents the formation of membrane substances, which are the breeding grounds for bacteria.
Therefore, it is necessary to reduce intraoral bacteria while maintaining high oral humidity. Moreover, oral moisture was high with few bacteria when daily care was continued using the MA-T gel. Our results showed that oral care using MA-T gel was ideal in terms of humidity and hygiene. In this study, we evaluated several bacterial species by using various methods. Many bacteria may exist, even if there is no overt evidence of infection. The medical staff should objectively evaluate the oral cavity of the patient by measuring the number of bacteria. Dentists can recognize changes in general health conditions by evaluating the intraoral state of patients.
It should be noted that MA-T is effective against a variety of bacteria without side effects. This study confirmed the efficacy of the MA-T gel in targeting opportunistic infectious bacteria that cause pneumonia. Pneumonia is the leading cause of death among the elderly [
21]. According to data released by the World Health Organization, pneumonia was the third leading cause of death in 2019, causing 2.5 million deaths worldwide [
22]. The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic [
23]. Pneumonia caused by opportunistic bacteria presents symptoms similar to those caused by SARS-CoV-2 [
23]. It is important to provide an agent for the treatment and prevention of fungal infections such as opportunistic infections and SARS-CoV-2. Several transmission routes for SARS-CoV-2 have been proposed, including direct and contact transmission. Importantly, recent studies have proposed that saliva is a potential reservoir for COVID-19, a symptomatic infection [
25,
26]. MA-T also has a high bacterial killing ability against SARS-CoV-2 virus [
12]. MA-T has the potential to prevent xerostomia with candidiasis and Sjögren syndrome. MA-T gel could be useful for the maintenance of the oral mucosa in patients whose dentures need removal.
The main component of MA-T is chlorine acid. Sodium chlorite is used as a water disinfectant in Europe and the USA as well as in the food industry [
27]. In an aqueous solution containing acid (H+), sodium chlorite forms a semi-stable chlorous acid that exhibits disinfectant properties against bacteria and viruses. Although alcohol degrades bacteria, it is difficult to volatilize. Chlorine dioxide is widely used as a disinfectant in laboratories, hospitals, and public spaces because it does not produce toxic by-products unlike chlorine [
28]. Noguchi et al. [
29] investigated the safety of MA-T ingestion in mice. Mice that were provided drinking water containing 0–3000 μg/mL MA-T for 7 days did not show any changes. Recent studies have indicated the safety of MA-T. This study also demonstrated that MA-T gel is effective and safe for oral care.
Therefore, it is necessary to reduce intraoral bacteria while maintaining high oral humidity. Moreover, oral moisture is high with a few bacteria when daily care was continued using MA-T gel. Our results showed that oral care using the MA-T gel maintains an ideal state in terms of humidity and hygiene. In this study, we evaluated several bacterial species by using various methods. Many bacteria may exist, even if it appears visually clean. It is thought that care from the medical staff should objectively evaluate the oral cavity of the patient by measuring the number of bacteria. Dentists can recognize changes in general health conditions by evaluatively their intraoral state extensively.
This study has some limitations. First, the sample size was extremely small. At the beginning of the study, we tried to recruit more patients; however, some patients could not complete the study because they died. During the COVID-19 pandemic, it was critical to conduct research on high-risk patients. For studies with small sample sizes, cross-sectional studies are common and require examination of the effects of appliances. We had to complete this study within the shortest possible time because high-risk patients were being studied. A 1-month blank was established before the period of professional care with water and MA-T gel. Second, the base material of MA-T was used as the control in the laboratory, but the control gel was not used on the patients to investigate the effect of MA-T. Our ethical committee and patients could not accept that we used unknown gels that are not commercially available for the purpose of oral care. Although water was used as a control in the patient surveys, we used similar quantities of water and the MA-T gel. Glycerin is used for xerostomia because it is included in various oral care gels [
30]. Glycerin was also used in cosmetics for skincare products, hair conditioning agents, and body creams [
31]. However, glycerin was not used in this study. The molecular weight of glycerin (92.1 g/mol) is higher than water (18.0 g/mol). Glycerin has a high ability to absorb oral moisture; however, it remains in the oral cavity when dried because it has a large molecular weight. Most tube-feeding patients experience oral dryness [
32] and glycerin is easily retained in the oral cavity when dried. The MA-T gel did not include Glycerin to keep humidity and is able to avoid membrane substances or oral infection. Thus, MA-T gel could be an ideal product for oral hygiene.
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