INTRODUCTION

Bacterial infections are a common problem in the intensive care unit (ICU), especially ventilator-associated pneumonia (VAP). Early-onset VAP refers to pneumonia occurring in individuals who have been mechanically ventilated for at least 48 h, while late-onset VAP occurs after 96 h of endotracheal intubation. The prevalence of VAP in ICUs has been reported to be 36% in Thailand, 28% in Pakistan, 81% in India, and 47% in Lebanon. Risk factors for VAP include the duration of intubation and mechanical ventilation, comorbidities, and antimicrobial usage. Prevention methods for VAP include keeping the head of the bed elevated to 30-45 degrees, oral care with chlorhexidine gluconate (CHG), continuous subglottic suctioning, stress ulcer prophylaxis, and chlorhexidine oral rinse. Within 48 h of ICU admission, the oral flora shows gram-negative organisms, accompanied by dental plaque formation, which creates an environment for microorganisms contributing to VAP. Oral hygiene is a crucial component in VAP prevention, significantly reducing respiratory infections. Adequate oral care for intubated patients is a vital nursing intervention in the ICU, promoting patient comfort and peace. Many reports indicate a relationship between pneumonia and inadequate oral hygiene in the ICU, as intubated individuals not receiving oral care encounter various oral microorganisms, ultimately leading to the microaspiration of pharyngeal secretions and VAP. ICU nurses play a significant role in VAP prevention. Proper mouth and dental care reduces discomfort in the mouth and lips and prevents bacterial stomatitis, gingivitis, and periodontitis, ensuring oral and dental health. Researchers have identified oral hygiene as the primary approach to VAP prevention, with mechanical and pharmacological methods being effective in eliminating dental plaque and associated microorganisms. Pharmacological methods for controlling bacterial plaque through CHG mouthwash have been widely accepted among healthcare professionals. CHG mouthwashes are effective antimicrobials against a broad spectrum of bacteria, fungi, and viruses.

This study discusses the importance of oral hygiene in preventing VAP in the ICU. Risk factors for VAP include the duration of intubation, mechanical ventilation, comorbidities, and antibiotic usage. Prevention methods include keeping the patient’s head elevated to 30-45 degrees, oral care with CHG, continuous subglottic suctioning, stress ulcer prophylaxis, and chlorhexidine oral rinse. Oral hygiene plays a crucial role in reducing respiratory infections, and proper oral care for intubated patients is the primary nursing intervention in the ICU.

This mouthwash prevents bacterial adherence to teeth and oral mucosa by increasing bacterial wall permeability and altering osmotic balance, leading to their elimination. Several studies have focused on the use of CHG in preventing bacterial colonization and VAP, with no reported microbial resistance or carcinogenic effects. However, some studies suggest that, compared to placebo, CHG does not significantly differ in preventing bacterial colonization or VAP. Potential adverse effects of CHG on oral mucosa and bacterial sensitivity, as well as a potential concerning link between CHG mouthwash and increased mortality, have been reported. Therefore, there is a tendency to search for mouthwashes as effective as CHG but with fewer side effects. Herbal mouthwashes may serve as a good and cost-effective alternative for oral hygiene in ICU patients. Aloe vera contains active ingredients, such as anthraquinones, aloesin, aloin, aloemodin, anthraquinones, saponins, sterols, amino acids, minerals, aminoglycosides, and beneficial enzymes. Aloe vera’s antibacterial activity inhibits the growth of both gram-positive and gram-negative bacteria. It has antimicrobial power against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Enterococcus faecalis, and Micrococcus luteus. Aloe vera is widely used in managing health issues, with approximately 99% of the gel inside its leaves being water, giving it significant moisturizing effects. Due to the presence of glucomannan and anthraquinones, aloe vera activates macrophages and stimulates the immune system, giving it antibacterial and antiviral effects. Miswak, or Salvadora persica, is another effective substance for oral hygiene, recommended by the World Health Organization. Some important natural substances found in this plant include chloride, silica, bicarbonate, resin, vitamin C, sitosterol, trimethylamine, tannic acid, and sulfur. Besides mechanically removing bacterial plaque, miswak inhibits oral microbial growth and dental plaque, and also has anti-inflammatory, antioxidant, wound-healing, and soothing effects. Given the antibacterial and anti-inflammatory effects of aloe vera and the antibacterial and anti-plaque effects of miswak, their combination has been recognized as effective in maintaining oral health and hygiene. The most effective way to eliminate bacterial colonies and oral plaques is through mechanical methods, especially tooth brushing, which is only contraindicated in patients with coagulation disorders. Considering the anti-plaque properties of miswak and the anti-inflammatory, softening, and moisturizing effects of aloe vera, along with their lack of serious and dangerous side effects and the advantages of herbal compounds over chemical ones, and also considering that the effects of these plants have not been studied in patients with tracheostomy tubes and the absence of specific guidelines for mouthwash use in ICU patients, we conducted this study with the aim of comparing the effectiveness of miswak+aloe vera mouthwash with that of CHG mouthwash in preventing VAP in patients with tracheostomy tubes admitted to the ICU.

METHODS

The present study is a single-blind randomized clinical trial registered at the Iranian Registry of Clinical Trials with the code 4N201610140
30294IRCT. All patients admitted to the ICUs of Valiasr Teaching Hospital, Arak, were systematically recruited and, upon meeting the inclusion criteria and providing informed consent, were enrolled in the study. The sample size was estimated to be 35 patients per group using a two-sample comparison of proportions formula, with a 95% confidence level (α=0.05), 80% power, 0.25 type I error, and 0.05 type II error. Patients were randomly assigned to either the intervention or control group using simple randomization (random number table). The inclusion criteria were age range of 18-65 years, the presence of an oral endotracheal tube, mechanical ventilation for at least 72 h, the absence of pneumonia, sepsis, pulmonary thromboembolism, atelectasis, inflammatory gastrointestinal, liver, or biliary tract diseases, and no history of allergy to herbal compounds as assessed by an anesthesiologist. Patients who were transferred from the ICU for any reason, died before completing the study, refused to continue participation, experienced adverse events, such as vomiting, itching, skin rash, sudden changes in clinical status, or respiratory pattern, were excluded from the study. To ensure proper suctioning, each time before oral care, the suction pressure was adjusted using a manometer (20 mmHg), and all oral areas were examined using a flashlight for ulcers, red tissues, and bleeding, and any lesions were reported to the physician for appropriate action. Ultimately, oral care in the intervention group was performed using a mouthwash containing a combination of 10% miswak (Salvadora persica) extract and 94% aloe vera extract, manufactured by Barij Essence Kashan, while in the control group, CHG 0.2% mouthwash manufactured by Shahrdaru Pharmaceutical Company was used.

Oral care was performed twice daily (every 12 h) using a soft children’s toothbrush to brush all oral areas, including the inner and outer surfaces of teeth (with circular motions), gums, and tongue (with backward-to-forward motions). Before and after brushing each oral area, the mouthwash solution was poured into the same area using a 20 cc syringe, and within less than 30 sec, it was suctioned out, cleaned, and reinserted into the mouth if the patient had an endotracheal tube in place. All patients received oral rinsing with normal saline and suctioning of secretions every four hours. On the fifth day, VAP was assessed based on the modified Clinical Pulmonary Infection Score (MCPIS), conducted by an anesthesiologist. This questionnaire included five criteria: temperature, white blood cell count, appearance and purulence of endotracheal tube secretions, oxygenation, and chest radiography, with scores ranging from 0 to 2 for each criterion, with a maximum score of 10. A score equal to or greater than 6 indicated pneumonia.

Sampling took six months, and precautions were taken to prevent sampling errors by having all interventions performed by a trained nurse colleague according to the existing protocol. Data analysis was performed using SPSS software (version 20). Descriptive statistics and measures of central tendency and dispersion were used to analyze demographic characteristics (age and gender) and baseline data (GCS, invasive interventions, history of chronic diseases, and prescribed antibiotics). Independent t-test, Mann-Whitney U test, and McNemar test were used to compare the incidence of VAP between the intervention and control groups. A significance level of P<0.05 was considered for all tests.

RESULTS

This study was conducted on 70 intubated patients in two groups of 35. During the study, no adverse events were observed in any of the patients, and none were excluded from the study. Comparison of the two groups in terms of demographic characteristics and disease profiles showed no statistically significant difference between them (P>0.05).

The results of the study showed that the number of individuals with early-onset VAP in the miswak+aloe vera mouthwash group was 10 (28.6%) and in the CHG mouthwash group was 4 (11.4%), but the difference was not statistically significant (P>0.07). Similarly, the number of individuals with late-onset VAP in the miswak+aloe vera mouthwash group was 8 (22.9%), while in the CHG mouthwash group, it was 14 (40%), which was also not statistically significant (P>0.13). Although there was a slight decrease in the percentage of early-onset and late-onset VAP in the miswak+aloe vera mouthwash group, it was not significant (P>0.64), while there was a significant increase in the percentage of early-onset and late-onset VAP in the CHG mouthwash group (P<0.02).

This study aimed to compare the effectiveness of a mouthwash containing a combination of miswak+aloe vera extract with that of the CHG mouthwash in preventing VAP in patients with intubation. Our study results indicated that CHG mouthwash does not have superiority over miswak+aloe vera mouthwash in the early onset of VAP prevalence. However, the late-onset VAP prevalence increased significantly in the CHG mouthwash group compared to the early-onset VAP prevalence in the same group, while the late-onset VAP prevalence decreased in the miswak+aloe vera mouthwash group compared to the early-onset VAP prevalence, suggesting the potentially greater impact of miswak+aloe vera mouthwash in reducing late-onset VAP. Several studies have been conducted on the effect of miswak extract, CHG, and other mouthwash solutions on VAP occurrence and oral hygiene in ICU patients. Some of these reports have findings consistent with our study, while others have contradictory findings. Consistent with our study results, another review article showed that the use of persica extract is associated with a significant reduction in plaque score and cariogenic bacteria. In another study, CHG mouthwash did not show superiority over cinnamon and echinacea mouthwashes in preventing VAP and improving oral health among hospitalized ICU patients. Another study showed that Salvador persica is more effective than CHG mouthwash in promoting oral health.

Ethical Considerations

Compliance with ethical guidelines

The study protocol has been approved by the Ethics Committee of Arak University of Medical Sciences (Ethical ID: IR.ARAKMU.REC.1398.082) and registered in the Iranian Registry of Clinical Trials (IRCT registration number: IRCT201610140302
94N4). Initially, the study objectives were explained to all participants, and written informed consent was obtained. All patients participated in the study voluntarily.

Funding

The above article is the result of the research project number 3122, and the Research and Technology Vice-Chancellor of Arak University of Medical Sciences has financially supported this study.

Authors’ Contributions

The authors contributed equally to the concept-ualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest

The authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Acknowledgments

The researcher would like to express her gratitude to the respected lecturers and vice-chancellor of Arak Paramedical Faculty and all the respected staff of Valiasr University Hospital (AS) who helped the researcher.