Evaluation of 0.12% chlorexidine in intensive care unit patients: a randomized clinical trial

Avaliação da clorexidina 0,12% em pacientes de unidade de terapia intensiva: ensaio clínico randomizado

ABSTRACT

Objective:  To evaluate the antimicrobial effect of 0.12% aqueous chlorhexidine solution on the oral microbiota of patients on mechanical ventilation in Intensive Care Units (ICUs) at 6, 8 and 12 hours after oral hygiene.

Methods:  This is a randomized clinical trial in which 30 patients admitted to the ICUs of a philanthropic hospital based in Aracaju-SE, selected by spontaneous demand over a period of 2 months according to inclusion criteria, were randomized and equally distributed into three groups. Oral hygiene followed the disinfection protocol adopted by the hospital, the same recommended by the Brazilian Association of Intensive Medical Care (AMIB). Saliva samples were collected before the application of 0.12% chlorhexidine, shortly after application of the solution, and then after 6 hours (TEST 1 Group), 8 hours (TEST 2 Group) and 12 hours (CONTROL Group), according to each group.

Results:  The material was sent to a clinical analysis laboratory for microbiological evaluation using the bacterioscopy technique, also called Gram stain. The results were tabulated in spreadsheets and analyzed using the Friedman test between groups and Kruskal Wallis test between groups.

Conclusion:  The study showed no statistical difference between groups and between groups.

Indexing terms Chlorhexidine; Intensive care units; Oral hygiene; Ventilator-associated pneumonia

RESUMO

Objetivo:  Avaliar o efeito antimicrobiano da solução aquosa de clorexidina 0,12% na microbiota oral de pacientes em ventilação mecânica em Unidades de Terapia Intensiva (UTI) 6, 8 e 12 horas após a higiene bucal.

Métodos:  Trata-se de um ensaio clínico randomizado no qual 30 pacientes internados nas UTIs de um hospital filantrópico de Aracaju-SE, selecionados por demanda espontânea durante um período de 2 meses conforme critérios de inclusão, foram randomizados e distribuídos igualmente em três grupos. A higiene bucal seguiu o protocolo de desinfecção adotado pelo hospital, o mesmo recomendado pela Associação Brasileira de Medicina Intensiva (AMIB). Amostras de saliva foram coletadas antes da aplicação de clorexidina 0,12%, logo após a aplicação da solução e após 6 horas (Grupo TESTE 1), 8 horas (Grupo TESTE 2) e 12 horas (Grupo CONTROLE), de acordo com cada grupo.

Resultados:  O material foi enviado para laboratório de análises clínicas para avaliação microbiológica pela técnica de bacterioscopia, também chamada de coloração de Gram. Os resultados foram tabulados em planilhas e analisados por meio do teste de Friedman entre grupos e teste de Kruskal Wallis entre grupos.

Conclusão:  O estudo não mostrou diferença estatística entre grupos.

Termos de indexação Clorexidina; Unidade de terapia intensiva; higiene Oral; Pneumonia associada ao ventilador

INTRODUÇÃO

Dental care in Intensive Care Units (ICUs) aims to prevent oral infections that may interfere with the clinical condition of critically ill patients and avoid the spread of pathogenic microorganisms present in the oral cavity to the lower respiratory tract.(1) Numerous infectious diseases of the mouth are prone to cause systemic changes [¹]. In this sense, ventilator-associated pneumonia (VAP) is one of the most common infections in ICUs and represents a major problem in hospitals due to its high incidence, affecting over 40% of critically ill or immunosuppressed patients, with mortality rates ranging from 20 to 60% [²]. This complication contributes to delayed recovery and increases the morbidity and mortality of patients, bed occupancy, length of stay, and hospital costs [³,⁴].

During hospitalization, the microbiota of the mouth undergoes changes according to time, invasive procedures and clinical conditions of the host [⁴]. Gram-negative rods and Staphylococcus spp. begin to colonize the oral cavity and oropharynx, and the level of infection varies according to the patient’s vulnerability and propensity for microorganism colonization in the inpatient unit [⁵]. In the first 48 hours of admission to the ICU, the oral flora of critically ill patients undergoes a change, especially the Gram-negative flora, which includes more virulent organisms [³,⁵]. In these immunosuppressed individuals, the oral microbiota is composed of a variety of microorganisms (Pseudomonas aeruginosa, Acinetobacter baumannii, Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus), which can colonize the dental biofilm, the tongue coating and the orotracheal tube [³].

Therefore, in this study the selected moments for microbiological evaluation were due to the alteration in the amount of biofilm that tends to grow with the time of hospitalization [⁶].

Fibronectin is present on cell surfaces and acts as a defense mechanism of the host, blocking the binding of pathogenic bacteria to the membranes of the buccal and tracheal mucosa [²,⁵]. The loss of fibronectin from cell surfaces causes cell receptor sites to replace the normal flora with virulent pathogens, that is, Gram-negative bacteria, such as Pseudomonas aeruginosa in oral and pharyngeal epithelial cells [⁴].

The study conducted by Teixeira, Santos, and Azambuja in 2019, made an analysis of the effectiveness of oral hygiene of ICU patients in a high-complexity hospital in southern Brazil used the bacterioscopy exam to classify the bacteria present in the saliva of these patients, which showed that such an exam is valid for a quick, presumptive diagnosis of an infectious agent.

Aspiration of oral microbiota has been identified as one of the main causes of VAP in ICUs [⁵,⁷]. The endotracheal tube acts as a carrier of microorganisms from the oropharynx to the lower respiratory tract, which are often identified as etiologic agents of nosocomial pneumonia [⁷]. Considering that the microbiota of the oral cavity plays an important role in the process of development of VAP, some studies indicate that the topical application of chlorhexidine, initiated before intubation, reduces nosocomial infections in patients [⁸,⁹].

Different strategies have been implemented to decrease the bacterial load by oral decontamination, including the use of local antiseptics, such as 0.12% aqueous chlorhexidine solution, which is used because it is a broad-spectrum antimicrobial capable of acting against antibacterial, antiviral and antifungal agents [⁸,¹⁰-¹³].

The aqueous chlorhexidine 0.12% has the ability to dissociate into positively charged molecules, its activity depends on the pH of the environment and is higher in alkaline pH, exhibits low irritability and demonstrates substantivity, i.e., has the ability to retain the dental surfaces and mucous membranes remaining in the oral cavity for a prolonged time. Regarding the mechanism of action, chlorhexidine alters the permeability of the membrane and can lead to cell death [¹⁰].

Oral hygiene in intensive care patients has been intensively studied and the findings call attention to the need to implement a bundle of measures of oral hygiene, including safe protocols and drugs that are effective and efficient in decolonizing the oropharynx, as well as continuing education for the nursing team [¹⁴]. However, to date, there are no studies on the best time interval for application of 0.12% chlorhexidine in ICU patients under mechanical ventilation.

The research conducted by Silva, Nascimento, and Salles in 2012 [¹⁵] that described a bundle for the prevention of ventilator-associated pneumonia mentioned the importance of sanitizing the oral cavity with 0.12% chlorhexidine in ICU patients to prevent VAP, but did not detail the application interval.

Thus, the purpose of this study was to evaluate the antimicrobial effect of 0.12% chlorhexidine aqueous solution in patients on mechanical ventilation at intervals of 6 hours, 8 hours, and 12 hours, considering the cost-benefit relationship. The study was conducted in the ICUs of the Hospital of Surgery Charity Foundation (FBHC), in which patients were selected by spontaneous demand in the period from December 2017 to January 2018. The research site is a philanthropic institution in great demand on the part of the public health sector, with 10 Cardiac ICU beds and 15 General ICU beds.

METHODS

Study population and ethical aspects

The research was carried out after the signing of an Informed Consent Form (ICF) by a family member responsible for the hospitalization of the patient, respecting all ethical aspects and complying with the recommendations of Resolution 466/12 of the National Health Council, and after approval by the Human Research Ethics Committee of Tiradentes University, under identification number 2.393.208.

Thirty-five patients admitted to the ICUs participated in the study, according to inclusion, non-inclusion, and exclusion criteria. The inclusion criteria were: hospitalized patients at the UCI, with any type of clinical systemic condition (except autoimmune diseases), who were on mechanical ventilation for more than 48 hours with no pre-determined length of stay in the ICU and whose participation was authorized through signing of the ICF. The non-inclusion criteria were: patients whose participation was not authorized by the person responsible for the hospitalization; patients who were not on mechanical ventilation; patients who were in contact isolation; patients who had autoimmune diseases; patients who were using antibiotic therapy for more than 24 hours (including patients diagnosed with VAP because of antibiotic use); and patients who had been admitted already under mechanical ventilation. Finally, the exclusion criteria were: patients who died; withdrawal from participation in the study; and patients who stopped using mechanical ventilation.

Of the 35 patients, 5 were excluded from the study: 2 had mechanical ventilation removed and 3 died. The 30 patients included were previously randomized through an electronic randomization system by an independent researcher and equally distributed into three groups as follows: 10 patients in the TEST 1 Group, who were treated with 0.12% chlorhexidine gluconate within an interval of 6 hours; 10 patients in the TEST 2 Group, who were treated with 0.12% Chlorhexidine Gluconate within an interval of 8 hours; 10 patients in the CONTROL Group, who were treated with 0.12% Chlorhexidine Gluconate within an interval of 12 hours. The methodological procedure is illustrated in figure 1.

Figure 1
Methodological illustration of the groups.

The patient, the operator and the evaluator did not know the treatment received, thus they were all blind, constituting a triple-blind study.

Mechanical ventilation

The patients had to be initially admitted to the ICU, on mechanical ventilation for more than 48 hours, either by orotracheal tube or tracheostomy.

Clinical oral procedures and sample collection

The biological material collected in the oral cavity was salivary secretion. The first collection of biological material in all groups was carried out at 7 am with a sterile cytology brush (Amies Medium Collection and Transport Swab - Sterile, model K41-0101 - OLEN, Brazil) using an exfoliative technique on the posterior dorsum of the tongue and external surface of the orotracheal tube (figure 2). Right after this collection, 15 ml of 0.12% Chlorhexidine Gluconate solution (Bellafarm - Pharmacy Manipulation with Ph between 5.0 and 7.0) measured using a 20 ml sterile graduated syringe (sterile LUER LOCK ANVISA registration 8002610002) was applied a across the mucosa, dental surfaces (when notched) and intraoral tube surface. This substance was introduced into the oral cavity with the aid of a 7.5cm x 7.5cm piece of sterile gauze wrapped in a wooden spatula, soaked in the solution. The swabbing time was 30 seconds, measured using a stopwatch (VOLLO model VLS510). Immediately after oral hygiene, a new collection of biological material analogous to the previous one was performed. The third and last collection was carried out at the time according to the selected group.

Figure 2
Illustration of the methodological steps performed in the study.

After collection of biological material, the swabs were smeared on clean and defatted glass slides, previously identified with the patient’s initials. Smears were made using a circular motion, starting from the center of the slide, homogeneously, not passing the swab twice in the same place. Then the smear was dried at room temperature and stored in a slide holder and immediately directed to the clinical analysis laboratory where the bacterioscopy exams were performed.

Microbiological evaluation

The colony samples were homogenized with a drop of distilled water. After drying by passing quickly through the flame, the slide was covered with crystal violet for one minute to stain the bacteria. The slide was then washed with distilled water and covered with lugol for one minute to fix the blue stain. Both types of bacteria are able to absorb the complex formed by the dye and the lugol, staining them blue. Next, the slide was washed with running water and 95% alcohol was applied for 30 seconds. The alcohol is responsible for dissolving the lipid membrane that forms gram-negative bacteria and thus removes the complex formed between the dye and the lugol, staining these bacteria. However, in the case of gram-positive bacteria, the alcohol dehydrates the cell wall of gram-positive bacteria, causing the pores to contract and making them impermeable. The slide was then washed again in distilled water and covered with the fuchsin for 30 seconds. Immediately afterwards, the slide was washed with distilled water and dried with a paper filter. After the slide was dry, a drop of immersion oil was applied to perform the microscopic analysis.

The bacterioscopic examination showed the presence of Gram-positive cocci, Gram-negative bacilli, and yeast-like fungi, classified according to their quantification as absent, rare, frequent, and abundant. They were considered absent when the mean number of bacteria per field was zero; rare when the mean was 1 to 5; frequent when the mean was 6 to 30; and abundant when the mean was greater than 30 [⁶,¹⁶].

Cases of patients in whom the microorganisms passed from frequent and abundant to rare and absent in the assessments were considered cases of significant reduction.

Statistical analyses

The results were tabulated in spreadsheets and analyzed using the Friedman test between groups and Kruskal Wallis test between groups, with program JAMOVI 1.6.23.

RESULTS

The volunteers, 15 were male and 15 were female, with a mean age of 66 (standard deviation of 13; maximum of 94 years and minimum of 39 years).

Table 1 presents a comparative analysis of the amounts of Gram-positive cocci between collection moments and groups (TEST 1 Group, TEST 2 Group and CONTROL Group). In test 1 group, which comprises patients receiving the solution at an interval of 6 hours, we observed that 90% of the group (9 patients) had a significant amount of Gram-positive cocci. Of these, 44.4% (4 patients) showed a decrease in Gram-positive cocci after the interval of 6 hours of application of 0.12% Chlorhexidine. In test 2 group, we observed that 80% (8 patients) initially had Gram-positive cocci classified as frequent and abundant. Of these, 37.5% (3 patients) showed a reduction after the interval of 8 hours of application of 0.12% chlorhexidine. In the Control group, we observed that 70% (7 patients) initially had a significant amount of Gram-positive cocci, classified as frequent and abundant. In only 14.28% (1 patient) of these patients there was a decrease in the amount of Gram-positive cocci after the 12-hour interval of 0.12% chlorhexidine application. Thus, the application of 0.12% chlorhexidine in shorter intervals (6 hours) showed no statistical difference in reducing Gram-positive cocci in the oral cavity.

Table 1
Comparative analysis of Gram-positive cocci between collections and groups.

		Collection
Gram-positive cocci		6h	8h	12h	p-value*
		n (%)	n (%)	n (%)
Group 1	Absent	1 (10)	1 (10)	1 (10)	1
	Rare	0 (0)	2 (20)	4 (40)
	Frequent	6 (60)	7 (70)	4 (40)
	Abundant	3 (30)	0 (0)	1 (10)
Group 2	Absent	2 (20)	1 (10)	3 (30)	0.62
	Rare	0 (0)	1 (10)	2 (20)
	Frequent	3 (30)	7 (70)	4 (40)
	Abundant	5 (50)	1 (10)	1 (10)
Control	Absent	2 (20)	1 (10)	1 (10)	0.93
	Rare	1 (10)	2 (20)	3 (30)
	Frequent	3 (30)	6 (60)	4 (40)
	Abundant	4 (40)	1 (10)	2 (20)
p-value £		0.98	0.96	1

• Note: Friedman test intergroups and Kruskal Wallis test between groups,
• ^*
  Intragroup comparison;
• ^£
  Intergroup comparison.

There was no significant presence of Gram-negative Cocci since the first collection, as shown in table 2, and statistical analyses were, therefore, not possible.

Table 2
Comparative analysis of Gram-negative cocci between collections and groups.

		Collection
Gram-negative cocci		6h	8h	12h	p-value*
		n (%)	n (%)	n (%)
Group 1	Absent	10 (100)	10 (100)	10 (100)	¥
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	0 (0)
	Abundant	0 (0)	0 (0)	0 (0)
Group 2	Absent	10 (100)	10 (100)	9 (90)	0.39
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	1 (10)
	Abundant	0 (0)	0 (0)	0 (0)
Control	Absent	10 (100)	10 (100)	10 (100)	¥
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	0 (0)
	Abundant	0 (0)	0 (0)	0 (0)
p-value£		1	1	1

• Note: Friedman test intergroups and Kruskal Wallis test between groups;
• ^¥
  Calculations for hypothesis testing were not possible.
• ^*
  Intragroup comparison;
• £Intergroup comparison.

Regarding Gram-positive bacilli, according to table 3, there was no significant presence of this group since the first collection. Therefore, statistical analyses were not possible.

Table 3
Comparative analysis of Gram-positive bacilli between collections and groups.

		Collection
Gram-positive bacilli		6h	8h	12h	p-value*
		n (%)	n (%)	n (%)
Group 1	Absent	10 (100)	10 (100)	10 (100)	¥
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	0 (0)
	Abundant	0 (0)	0 (0)	0 (0)
Group 2	Absent	10 (100)	10 (100)	9 (90)	0.39
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	1 (10)
	Abundant	0 (0)	0 (0)	0 (0)
Control	Absent	10 (100)	10 (100)	10 (100)	¥
	Rare	0 (0)	0 (0)	0 (0)
	Frequent	0 (0)	0 (0)	0 (0)
	Abundant	0 (0)	0 (0)	0 (0)
p-value£		1	1	1

• Note: Friedman test intergroups and Kruskal Wallis test between groups;
• ^¥
  Calculations for hypothesis testing were not possible.
• ^*
  Intragroup comparison;
• £Intergroup comparison.

Table 4 shows the comparative analysis of Gram-negative bacilli between collection moments and groups (TEST 1 Group, TEST 2 Group and CONTROL Group). In test 1 group, which comprises patients receiving the solution at an interval of 6 hours, we observed that 50% (5 patients) of the group had Gram-negative bacilli, with a significant reduction (60%) only in the number of patients in whom the amount of microorganisms was classified as abundant; however, there was no significant difference in the number of patients in whom the amounts of microorganisms remained as frequent and abundant. In test 2 group, we observed that 80% of the group (8 patients) had a significant amount of Gram-negative bacilli. Of these, 12.5% (1 patient) showed a reduction after 8 hours of application of 0.12% chlorhexidine. In the Control group, we observed that 80% of the group (8 patients) had a significant amount of Gram-negative bacilli. Of these, 25% (2 patients) showed a decreased after 12 hours of application of 0.12% chlorhexidine. Thus, the application of 0.12% chlorhexidine in longer intervals (12 hours) was no statistical difference in in reducing Gram-negative bacilli in the oral cavity.

Table 4
Comparative analysis of Gram-negative bacilli between collections and groups.

		Collection
Gram-negative bacilli		6h	8h	12h	p-value*
		n (%)	n (%)	n (%)
Group 1	Absent	4 (40)	5 (50)	4 (40)	0.39
	Rare	1 (10)	0 (0)	0 (0)
	Frequent	0 (0)	4 (40)	4 (40)
	Abundant	5 (50)	1 (10)	2 (20)
Group 2	Absent	2 (20)	4 (40)	2 (20)	0.62
	Rare	0 (0)	2 (20)	1 (10)
	Frequent	0 (0)	4 (40)	5 (50)
	Abundant	8 (80)	0 (0)	2 (20)
Control	Absent	2 (20)	4 (40)	2 (20)	0.64
	Rare	0 (0)	1 (10)	2 (20)
	Frequent	2 (20)	4 (40)	4 (40)
	Abundant	6 (60)	1 (10)	2 (20)
p-value £		0.93	0.99	0.98

• Note: Friedman test intergroups and Kruskal Wallis test between groups;
• ^*
  Intragroup comparison;
• ^£
  Intergroup comparison.

Table 5 presents a comparative analysis of yeast-like fungi between collection moments and groups (TEST 1 Group, TEST 2 Group and CONTROL Group). As for the findings in test 1 group, we observed that 60% of the group (6 patients) had yeast-like fungi. Of these, 33.33% (2 patients) showed a reduction. In test 2 group, 80% of the group (8 patients) had a significant amount of fungi. Of these, 25% (2 patients) showed a decreased after 8 hours of application of 0.12% chlorhexidine. In the Control group, 100% of the group (10 patients) had a significant amount of fungi. Of these, 20% (2 patients) showed a reduction after 12 hours of application of 0.12% chlorhexidine. Thus, the application of 0.12% chlorhexidine in the three times showed no statistical difference in effective in reducing fungi in the oral cavity.

Table 5
Comparative analysis of yeast-like fungi between collections and groups.

		Collection
	Yeast-like fungi	6h	8h	12h	p-value*
		n (%)	n (%)	n (%)
Group 1	Absent	2 (20)	3 (30)	2 (20)	0.62
	Rare	2 (20)	3 (30)	4 (40)
	Frequent	1 (10)	4 (40)	2 (20)
	Abundant	5 (50)	0 (0)	2 (20)
Group 2	Absent	1 (10)	1 (10)	2 (20)	0.62
	Rare	1 (10)	4 (40)	2 (20)
	Frequent	1 (10)	5 (50)	3 (30)
	Abundant	7 (70)	0 (0)	3 (30)
Control	Absent	0 (0)	4 (40)	2 (20)	0.82
	Rare	0 (0)	4 (40)	0 (0)
	Frequent	2 (20)	2 (20)	5 (50)
	Abundant	8 (80)	0 (0)	3 (30)
p-value £		0.72	0.95	0.96

• Note: Friedman test intergroups and Kruskal Wallis test between groups;
• ^*
  Intragroup comparison;
• ^£
  Intergroup comparison.

DISCUSSION

In this study we found that there was no statistical difference between the groups in the evaluation of the efficacy of chlorhexidine 0.12% in oral hygiene protocols. However, we know that the control of microorganisms in the oral cavity directly interferes in the high incidence of pneumonia in institutionalized and ventilator-associated patients, in the high mortality rates and in the costs that these patients represent to hospitals and governments. Thus, subtle differences between prevention protocols can have an important impact on public coffers [¹⁷-¹⁹]. The methodologies used are many and the centers where the studies are carried out are diverse, which makes it difficult to properly interpret and use the proposed intervention methodologies [²⁰-²³].

Studies have suggested the use of chlorhexidine and tooth brushing every 12 hours as part of an effective and safe oral care plan [²⁴,²⁵]. Some authors have evaluated the effectiveness of decontamination of the oral microbiota with 0.12% chlorhexidine, to reduce oral colonization by pathogens and avoid cases of nosocomial pneumonia. Pinto et al. [²⁶] reported in their meta-analysis a significant reduction in the incidence of VAP in the groups in which intervention with 0.12% chlorhexidine was performed. The authors used the strategy known as PICO. Where Population was adults in the UCI (≥ 18 years of age) on mechanical ventilation; Intervention was the different protocols involving oral hygiene combined with the use of chlorhexidine; Comparison was protocols involving the use of chlorhexidine alone; and Outcome was efficacy in reducing the incidence of VAP.

Fourrier et al. [²⁷] proved that the use of 0.2% chlorhexidine gel three times a day in ICU patients was effective in reducing bacterial colonization of the dental plaque and reduced the incidence of nosocomial infection in patients undergoing mechanical ventilation, decreasing the time under this treatment and, consequently, mortality rates.

Studies carried out by Anvisa, in 2013, proved the effectiveness of using 0.12% chlorhexidine in critically ill patients. Ventilator-associated pneumonia is mostly caused by the aspiration of fluids and bacteria hosted in the oral cavity, but VAP cases have been decreasing considerably with the use of 0.12% chlorhexidine. Other studies reported a majority of respondents indicating to perform oral hygiene two or three times a day in non-intubated patients and 5 times a day or more in intubated patients [⁸]. However, there are no publications of previously conducted studies comparing the efficacy of the time interval of the use of 0.12% chlorhexidine in intubated ICU patients.

In this study, in the case of Gram-positive cocci, there was no significant reduction of microorganisms in the three evaluation times. This is in contrast to the findings of Pineda et al. [²⁸], Wise et al. [²⁹], Scannapieco et al. [³⁰], Wip [²⁴] and Zhang et al. [²⁵].

There was no significant presence of Gram-negative cocci and Gram-positive bacilli in this trial; therefore, we could not evaluate the best time of application of the substance in the case of these microorganisms.

Gram-negative cocci present in the oral cavity include representatives of the genus Veillonella, which colonize mainly the dorsum of the tongue; of the genus Neisseria, which are present in low quantities in the oral cavity; and of the genus Moraxella, which can be detected in the oral cavity but with low frequency and in low levels.

The Gram-positive bacilli present in the oral mucosa include species of the genus Lactobacillus, colonizers mainly of the dorsum of the tongue, of the genus Actinomyces, which are part of the colonizers of dental surfaces and predominate both in the supragingival and subgingival biofilms. We also found the genus Corynebacterium, which is detected exclusively in the oral cavity, but at low levels. And the last genus present is Eubacterium, whose species have been identified in the presence of deep periodontal pocket [³¹].

Therefore, it is suggested that the absence of these microorganisms in the material collected from the oral cavity is related to their low frequency in the UCI environment, the method used, may presents some limitations to the detect the microorganisms and the 24 first hours of use of antibiotics, may change the oral microbiota.

The use of systemic antibiotics in oral decontamination leads to a significant reduction in VAP levels in treated patients, but this type of intervention has limitations due to bacterial resistance; thus, oral decontamination with 0.12% chlorhexidine is more effective [³²]. However, cross-sectional investigations and the assessment of patient outcomes are necessary to determine the most appropriate frequency of application to control these microorganisms.

In the present study, no significant reduction of Gram-negative bacilli was observed in group 1 (6 hours). In group 2, we found a reduction of microorganisms in 12.5% of the patients, after 8 hours of application of 0.12% chlorhexidine; and in the control group, a reduction of 25% of the microorganisms after 12 hours of application of the antimicrobial agent. Thus, as there was no difference between treatment times, thus thinking about cost-effectiveness, the best application time is 12 hours. It is noteworthy that in critically ill patients, the oral microbiota changes and becomes predominantly represented by gram-negative microorganisms. This microbiota can be composed of Staphylococcus aureus, Streptococcus pneumoniae, Acinetobacter baumannii, Haemophilus influenza, and Pseudomonas aeruginosa [³,³³]. Moreover, even though the bacteria usually responsible for the establishment of VAP such as P. aeruginosa, methicillin-resistant S. aureus, Acinetobacter spp., Escherichi coli, Klebsiella spp., Enterobacter spp., Proteus mirabilis, Klebsiella pneumonia, Streptococcus hemolyticus, and S. pneumonia are not common members of the oral and oropharyngeal microbiota, these organisms can colonize the oral cavity in some situations, such as in the case of ICU patients [³,³³]. In these cases, it is suggested that decontamination is more effective in the 12-hour period, maintaining its residual effect, preventing VAP, and reducing mortality, length of hospital stay, hospital costs, and consequently possible allergic reactions and side effects.

When assessing the presence of yeast-like fungi, we observed that there was a microbial reduction in 33.3% of patients in group 1, after 6 hours of application of 0.12% chlorhexidine. In group 2, there was a reduction in 25% of the patients after 8 hours of application of the solution, while in the control group, in 100% of the group, there was a reduction of 20% of microorganisms after 12 hours of application. Thus, the three time intervals evaluated were effective, but the greatest microbial reduction against yeast-like fungi occurred within 6 hours. The results obtained in this study, may suggest to be in line with other authors who proved the effectiveness of chlorhexidine as an antimicrobial agent, even outweighing the activity of other active principles. Chlorhexidine is considered a broad-spectrum antiseptic that effectively acts against Gram-positive, Gram-negative bacteria, yeast-like fungi, and viruses [³⁴-³⁶].

CONCLUSION

No Gram-negative cocci and Gram-positive bacilli were found in this study, confirming that the oral flora of ICU patients is changed. It was not possible to assess the best time of application in the case of these microorganisms.

The present evaluation of the efficacy of 0.12% chlorhexidine against Gram-negative bacilli causing VAP showed that there was no difference between the treatment times, thus thinking in cost-effectiveness, the best application time is 12 hours. The maintenance of the 12-hour protocol will act in the prevention of oral infections, causing fewer allergic reactions and consequent manipulation of the oral tissue, decreasing the length of hospital stay and accelerating bed turnover. However, cross-sectional investigations including patient outcomes are necessary to confirm the recommendations of use of 0.12% chlorhexidine and best time intervals in ICU patients on mechanical ventilation, aiming at the reduction of VAP and consequent morbidity, mortality, and hospital costs.

How to cite this article

• Melo HLFS, Nascimento YA, Cardoso MCAC, Couto GR, Amaral RC, Silva JAS, et al. Evaluation of 0.12% chlorexidine in intensive care unit patients: a randomized clinical trial. RGO, Rev Gaúch Odontol. 2024;72:e20240026. http://dx.doi.org/10.1590/1981-86372024002620230116

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Edited by

• Assistant editor: Luciana Butini Oliveira

Publication Dates

• Publication in this collection
  07 Oct 2024
• Date of issue
  2024

History

• Received
  14 Dec 2023
• Accepted
  27 June 2024