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Corresponding author: Mavilde Luz Gonçalves Pedreira, Nursing School, Federal University of São Paulo, Rua Napoleão de Barros, 754 office 113, Vila Clementino-São Paulo-Capital, Brazil CEP 04024002 (e-mail: mpedreira{at}unifesp.br).
| Abstract |
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Objective To compare the oropharyngeal microbiological profile, duration of mechanical ventilation, and length of stay in the intensive care unit of children receiving mechanical ventilation who had pharmacological or nonpharmacological oral care.
Methods A randomized and controlled study was performed in a pediatric intensive unit in São Paulo, Brazil. A total of 56 children were randomly assigned to an experimental group (n=27, 48%) that received oral care with use of 0.12% chlorhexidine digluconate or a control group (n=29, 52%) that received oral care without an antiseptic. Oropharyngeal secretions were collected and cultured on days 0, 2, and 4, and at discharge.
Results The 2 groups had similar demographic characteristics, preexisting underlying diseases, and pharmacological, nutritional, and ventilatory support. Gram-negative bacteria were the predominant pathogens: Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enter-obacter species. The 2 groups did not differ significantly in the colonization of normal (P= .72) or pathogenic (P= .62) flora, in the duration of mechanical ventilation (P= .67), or in length of stay in the intensive care (P= .22).
Conclusion Use of chlorhexidine combined with nonpharmacological oral care did not decrease the colonization profile, duration of mechanical ventilation, or length of stay in critically ill children receiving mechanical ventilation.
Notice to CE enrollees:A closed-book, multiple-choice examination following this article tests your understanding of the following objectives:
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Patients receiving mechanical ventilation have decreased salivary secretion, and oral cavity hygiene worsens, resulting in bacteria overgrowth.10 Oropharyngeal colonization with potentially pathogenic microorganisms is crucial in the pathogenesis of VAP. Oral care regimens that improve oral health status and modulate bacterial overgrowth could reduce the development of nosocomial VAP.1–4,11–15
Grap et al16 investigated the relationship between VAP and oral health status in a sample of 34 adults receiving mechanical ventilation. Alterations in oral health status occurred during the first 7 days after intubation, with microbial colonization of the oropharynx and trachea. Dental plaque and oral organisms increased over time; potential pathogens were identified in cultures of oral samples before or at the same time as the appearance of these organisms in tracheal aspirates, and higher dental plaque scores correlated with an increased risk for VAP.
| Pneumonias account for 15% of all hospital-associated infections.
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The Centers for Disease Control and Prevention guidelines9 for preventing health care–associated pneumonia recommend the development and implementation of a comprehensive oral hygiene program for patients in acute care settings who are at high risk for this type of pneumonia. Essentially 2 techniques are described to remove dental plaque and associated microbes in critically ill patients: mechanical intervention and direct pharmacological intervention with antimicrobial agents.17 Although mechanical removal may be an effective method for eliminating oral pathogens, and oral hygiene is considered standard nursing care, oral care is often neglected in critically ill patients or is performed by quickly swabbing the patients mouth.18
In a study19 to determine the frequency of oral care performed by nurses, the majority of nurses reported that they provided oral care 5 or more times per day for any patient who was intubated, but oral care was documented only a mean of 1.2 times per patient. Toothbrushing was used significantly more often in nonintubated patients than in intubated patients (P < .001), whereas sponge toothette swabs were used significantly more often in intubated patients than in nonintubated patients (P < .001). Similarly, Hanneman and Gusick20 highlighted that the use of mouthwash, toothbrush, and toothpaste, as well as the frequency of oral care interventions, was lower in intubated patients than in nonintubated patients.
DeRiso et al21 showed that inexpensive and easily done oropharyngeal decontamination with a 0.12% chlorhexidine oral rinse significantly reduced the nosocomial respiratory infection rate and mortality in a comparatively homogeneous population of adults undergoing heart surgery.
Unfortunately, little is known about the effects of oral care interventions in critically ill children. Evidence-based protocols for oral care for these children are not available, and oral hygiene measures are generally directed toward a patients comfort rather than removal of microbes. Thus, the purpose of our study was to analyze the oropharyngeal microbiological colonization profile of children receiving mechanical ventilation. We used 2 methods of oral decontamination: mechanical intervention alone and mechanical intervention plus 0.12% chlorhexidine. We also evaluated the effect of these interventions on the duration of mechanical ventilation and length of PICU stay.
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The children were assigned randomly to 2 groups. For the experimental group, oral care included use of an oral gel containing chlorhexidine digluconate 0.12% as an active ingredient (chlorhexidine digluconate 0.12%; methylcellulose gel 2.12%, 25 g; gooseberry syrup, 4 drops; menthol solution 50%, 3 drops; and distilled water, to 30 g). The control group received the same oral care with the use of a similarly formulated gel without the antiseptic agent. The gel type was color coded and the nurses had no knowledge of the type of gel (with or without antiseptic) until the end of the study. Only the pharmacist was aware of the gel type used for each patient.
Procedures
Before the study, all PICU nurses were trained in oral care by a dentist who used a protocol designed to remove microorganisms from all mouth surfaces, including hard and soft tissues. The training included evaluation of a childs oral status, selection of oral care equipment according to the childs age, and a description of the desired outcome, preserving the integrity of oral and labial mucosa.
For each child, before oral care began, the child was placed in a lateral position to prevent pulmonary aspiration of secretions. The gel was applied on a toothbrush and the teeth were cleaned in quadrants; all teeth surfaces were cleaned (vestibular, lingual, occlusal, and incisal). After each quadrant was cleaned, 10 mL of water (dispensed via a syringe) was used to rinse the quadrant and continual aspiration was used to remove all the gel and debris. After all the teeth were cleaned, the ventral surface of the tongue was brushed with posterior-to-anterior movements. A sponge swab was then immersed in the gel and the gel was applied over all the oral mucosa. During the hygiene process and rinsing of each mouth quadrant, fluids and secretions were aspirated by using a vacuum aspirator. The protocol was used twice a day and took about 10 minutes to complete, depending on the childs acceptance and clinical conditions. Nurses compliance with the oral care protocol during the study period was evaluated by 2 trained researchers in a random fashion, and retraining was conducted when necessary.
| Little is known about the effects of oral care interventions in critically ill children.
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Measures
The dependent variables selected for the study were the profile of oropharyngeal colonization, duration of mechanical ventilation, and length of PICU stay. Oropharyngeal colonization was analyzed by using a qualitative microbiological culture assay of samples from the tonsillar area and the upper posterior part of the oropharynx. Samples were collected during the first 24 hours of PICU admission (day 0), at 48 hours (day 2), at 96 hours (day 4), and at the time of discharge from the PICU.
All the secretions were collected by 3 trained nurses 8 to 10 hours after oral care. A standard protocol was used for sample collection, storage, labeling, and transport to the laboratory. A sterile swab plastic stick 15 cm long with a cotton tip was pressed and rolled on the tonsillar area and the upper posterior part of the oropharynx to obtain oropharyngeal secretions. The swab with the sample secretions was immersed in a sterile tube containing 5 mL of Stuart agar. Then the tube was labeled and immediately transported to the laboratory.
| On study admission, 41% of oral samples were colonized with pathogenic bacteria.
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In the microbiological laboratory, the samples were cultured on blood agar, chocolate agar, eosin–methylene blue agar, and Sabouraud agar, and incubated according to controlled atmosphere, temperature, time, and humidity parameters for qualitative microbiological identification. After incubation, growth of colonies was evaluated by 2 microbiologists, and analyses of microbial resistance to antibiotics were done. The diffusion disk technique with Mueller-Hinton agar was used for qualitative analyses. Length of incubation, ionic concentration, temperature, nutritional characteristics of the plaque, incubation, and application of the antibiotics disks to be tested were done in accordance with the recommendations of the Clinical and Laboratory Standards Institute.22 Sensitivity and resistance were determined by comparing the size of the halos with the established standards.22
The following antibiotics were used in the sensitivity analyses, as determined by the pattern established in the hospital for the years 2005 and 2006: amikacin, tobramycin, gentamicin, cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem, piperacillin, disodium clavulanate, polymyxin, ceftriaxone, and sulfamethoxazole plus trimethoprim.
Duration of mechanical ventilation (in hours) and length of PICU stay (in days) were determined. Other data collected included each patients age; sex; nutritional status according to a Z score (normal, malnutrition, overweight); clinical evaluation of the condition of the oral mucosa (presence or absence of alterations such as moniliasis, gingivitis, and injuries); oral health status according to the DMFT (decayed, missing due to caries, and filled teeth) index, previous hospital length of stay; presence of infectious or chronic disease at admission; use of antibiotics; type of admission (elective or emergency); diagnoses (clinical or surgical); Nine Equivalents of Nursing Manpower Use Score; use of drugs that could affect oropharyngeal colonization (central nervous system suppressors, salivary secretion modifiers, immunological suppressors, gastric pH modifiers); characteristics of intubation, including indication (emergency and elective), type (oral or nasal), and type of endotracheal tube (cuffed or uncuffed); presence of enteral tubes; and outcome (discharge or death). All patients were followed up until discharge from the PICU.
Categorical variables were evaluated by using
2 and Fisher exact tests. Numerical variables were evaluated by using a t test or analysis of variance. Rejection of the null hypothesis was set at
= .05.
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During the first 48 hours of PICU admission, the number of children colonized with pathogenic microorganisms decreased in the experimental group and increased in the control group. Table 2
gives the number of children colonized and the microorganisms identified.
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A total of 26 samples contained pathogenic bacteria, and 24 (92%) of the 26 were antibiotic resistant, such as K pneumoniae strains resistant to β-lactamase, methicillin-resistant S aureus, carbapenem-resistant P aeruginosa and A baumannii, and cephalosporin-resistant Enterobacter species (Table 3
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| Discussion |
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| Pathogenic colonization decreased in the chlorhexidine group and increased in the control group.
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We found no difference between the control and experimental groups in colonization by pathogenic bacteria. Fewer children in the experimental group had an increase from day 0 to day 2 in the number of samples positive for growth of pathogenic microorganisms, but the difference was not significant. Similarly, colonization of the oral cavity by normal flora did not differ between the 2 groups.
In a systematic review and meta-analysis of the effect of oral decontamination, with antiseptics or antibiotics, on the incidence of VAP and mortality in adults receiving mechanical ventilation, Chan et al24 found that oral decontamination with antiseptics was associated with a lower risk for VAP. However, neither antiseptic nor antibiotic oral decontamination reduced mortality, duration of mechanical ventilation, or length of ICU stay.
Oropharyngeal Colonization
We found a high rate of oropharyngeal colonization in PICU patients. During the first 24 hours of PICU admission, the oropharynx was colonized by aerobic pathogens in 40% of the children. In addition, some of these children had colonization by multidrug-resistant pathogens. Four days after admission, more than 50% had colonization by bacterial pathogens. We found no significant differences between the 2 groups in colonization characteristics. These results were similar to those of Fourrier et al25 in a study of critically ill adults receiving mechanical ventilation. Approximately 50% of the patients had cultures positive for bacterial pathogens at admission, and 33% of these patients had aerobic pathogens, mainly gram-negative bacteria.25
In our study, the aerobic gram-negative bacteria identified most frequently were P aeruginosa, Escherichia coli, K pneumoniae, and various species of Acinetobacter. The number of infections caused by gram-positive bacteria is increasing rapidly in adult ICUs, particularly infections caused by methicillin-resistant strains of S aureus. The incidence of VAP related to multidrug-resistant pathogens has also increased, because of indiscriminate use of antibiotics, prolonged hospitalization, high frequency of antibiotic resistance in the community, and immunosuppression.2,3
Children in the experimental group had more species of Enterobacteriaceae, such as Enterobacter species (75%), E coli (100%), and K pneumoniae (71%), than did children in the control group. Similar findings were obtained in another study1 in which treatment with chlorhexidine caused a greater reduction in gram-positive bacteria than in gram-negative organisms.
Dental plaque is due to bacterial colonization of the surfaces of teeth, soft tissues, and dental prostheses via selective adherence mechanisms. Dental plaque is a biofilm, a dynamic and complex system that contains microorganisms embedded in an extracellular matrix. Plaque mass increases by cumulative addition of aerobic, anaerobic, and filamentous microorganisms. Numerous factors are involved in the development of plaque; however, poor oral hygiene and lack of mechanical elimination of microorganisms are the main factors leading to proliferation and accumulation of dental plaque and subsequent colonization.26
Adherent streptococci drench the salivary pellicle on binding sites during the first 2 to 8 hours of plaque deposition. This growth period is independent of personal characteristics, surface, and time and appears to depend on cell density. Initial colonization of enamel surfaces by bacteria occurs in 3 stages: saturation of pellicular binding sites, accumulation of organisms via a variety of mechanisms until a critical density is reached, and density-dependent growth.27
Several studies1,25,26 have suggested that oropharyngeal colonization plays an important role as a reservoir of nosocomial colonization and support the hypothesis that antiseptic decontamination of dental plaque might decrease the rate of acquired nosocomial infection in ICU adult patients. However, few data support this hypothesis for infants and children, and we found that in children in a PICU, the effects of oral care consisting of mechanical intervention plus chlorhexidine did not differ from the effects of oral care consisting of mechanical intervention alone.
Chlorhexidine
Chlorhexidine increases the permeability of bacterial cell walls in a dose-dependent manner by interacting with anionic receptors on the bacterial surface.15 Caton et al28 found that rinsing with chlorhexidine solution before mechanical cleaning had a profound and sustained effect on the aerobic and facultative flora of the oral cavity and may contribute to a variety of clinical benefits. A meta-analysis29 of the efficacy of topical chlorhexidine for prevention of VAP indicated that topical chlorhexidine is beneficial in preventing VAP and that the benefit is most marked in cardiac surgery patients.
| A total of 92.3% of the pathogenic bacteria were antibiotic-resistant strains.
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To document the effect of antiseptic decontamination of gingival and dental plaque on the rate of nosocomial bacteremias and respiratory infections acquired in the ICU, Fourrier et al26 carried out a prospective, multicenter, double-blind, placebo-controlled efficacy study. A total of 228 edentulous adults requiring endotracheal intubation and mechanical ventilation had 0.2% chlorhexidine gel or a placebo gel applied to gingival and alveolar processes 3 times a day. Compared with the control group, patients treated with chlorhexidine had fewer dental plaque cultures that remained negative for bacterial growth or became negative after 5 days, but the difference was not statistically significant. In our study, chlorhexidine influenced the growth of both normal flora and pathogenic flora, decreasing the number of microorganisms in cultures of oropharyngeal secretions mainly after 2 days of oral care, but the results were not significant.
| No difference was found in colonization between groups by pathogenic bacteria species.
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The number of chlorhexidine applications in our study (2/d) differed from the number in the study of Fourrier et al26 (3/d). Although this variation may be important, other investigators30 found no direct relationship between time interval and the development of biofilms. The characteristics of the microflora in children may be relevant for the chlorhexidine effect. Sharma et al31 concluded that in children 13 to 14 years old, a once-a-day unsupervised toothbrushing had the same effect on plaque formation as did a twice-daily mouth rinsing with 0.2% chlorhexidine. In our study, all treatments were performed twice a day in all children for several reasons, including better compliance with the protocol, lack of definitive evidence to determine the most appropriate method of oral hygiene, and lack of knowledge about the effects of chlorhexidine in young children.32,33
Studies21,25,26,34 on the effects of oral chlorhexidine have yielded conflicting results. In a meta-analysis, Pineda et al34 did not find any clinical benefits of regular oral application of chlorhexidine on the incidence of nosocomial pneumonia and mortality rate in critically ill patients requiring mechanical ventilation. Fourrier et al25 investigated the effect of antiseptic decontamination of dental plaque on plaque colonization by aerobic pathogens and nosocomial infections in 60 adult patients receiving mechanical ventilation. In that study, antiseptic decontamination with a 0.2% chlorhexidine gel decreased dental bacterial colonization on day 5 to 7 after admission, but the effect did not persist after 10 days.
In an in vitro model,35 the effect of chlorhexidine was time dependent, and exposure times of 30 seconds had little effect on the number of viable bacteria recovered from oral biofilms. Even at 0.2%, chlorhexidine was ineffective against dental plaque after 5 minutes of exposure and required 60 minutes to achieve an effective killing. Therefore, one reason for the lack of effect of our experimental protocol may be insufficient contact time with bacteria; increased contact times might be effective.
Another key point is microbial resistance. Irizarry et al36 reported that antibiotic-resistant microorganisms had a reduced susceptibility to antiseptic and disinfectant agents such as chlorhexidine. Biocide resistance among microorganisms has been considered an important clinical issue.37 In a study by Suller and Russell38 reported in 1999, the minimal inhibitory concentration of chlorhexidine for methicillin-resistant S aureus was 1.5- to 3-fold greater than that for methicillin-sensitive S aureus.
In a recent study, Vali et al39 observed reduction in susceptibility of pathogens to chlorhexidine, and therefore reduced microbial susceptibility to biocides may be a serious concern in clinical practice.
Clinical studies24,28,29 involving critically ill patients have shown that inadequate salivary flow promotes the development of pharyngeal mucositis and increased colonization by aerobic pathogens. The presence of endotracheal or feeding tubes contributes to the formation of biofilms strongly resistant to antiseptics or antibiotics. Isolates from the initial samples in our study had high indices of antibiotic resistance; therefore, these isolates may have been less susceptible to the effects of chlorhexidine than antibiotic-sensitive isolates would be.
Toothbrushing
The lack of significant differences in our study may be related to the mechanical intervention of toothbrushing. Use of a toothbrush is widely considered to be the only effective means to remove dental plaque, but toothbrushing is not widespread in orally intubated children. To the best of our knowledge, no investigators have evaluated the effect of oral care with pharmacological and mechanical interventions in critically ill children. Thus, comparisons of our results with results from adult populations are difficult. Furthermore, a direct comparison between adults and children may be difficult because of the lack of knowledge of differences in oropharyngeal colonization in these 2 groups.
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FINANCIAL DISCLOSURES
This research was supported by grant 04-13361-2, Fun-dação de Amparo a Pesquisa do Estado de São Paulo.
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C. Lizy, N. Brusselaers, S. Labeau, D. Vandijck, D. De Wandel, D. Vogelaers, and S. Blot Oral Care, Ventilator-Associated Pneumonia, and Counting Cultures Am. J. Crit. Care., November 1, 2009; 18(6): 507 - 509. [Full Text] [PDF] |
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