Oral Mucosal Decontamination With Chlorhexidine for the Prevention of Ventilator-Associated Pneumonia in Children

A Randomized, Controlled Trial

Meghna Raju Sebastian, MD; Rakesh Lodha, MD; Arti Kapil, MD; Sushil K. Kabra, MD

Disclosures

Pediatr Crit Care Med. 2012;13(5):E305-310. 

In This Article

Abstract and Introduction

Abstract

Objective: To study the efficacy of oral mucosal decontamination with chlorhexidine gel for the prevention of ventilator-associated pneumonia in children between 3 months and 15 yrs.
Design: Double blind randomized placebo controlled trial.
Setting: Pediatric intensive care unit of a tertiary care hospital in North India.
Patients: Eligible participants were patients aged 3 months to 15 yrs who required orotracheal or nasotracheal intubation and mechanical ventilation. Two hundred eighty-three children admitted to the pediatric intensive care unit between November 2007 and April 2009 were screened. Eighty-six patients fulfilled the study requirements.
Intervention: Either 1% chlorhexidine or placebo gel was applied on the buccal mucosa at 8-hr intervals for the entire duration of ventilation, subject to a maximum of 21 days. Patients were followed up for the development of ventilator-associated pneumonia, diagnosed using the Centers for Disease Control and Prevention criteria.
Main Outcome Measures: Incidence of ventilator-associated pneumonia, duration of hospital stay, duration of intensive care unit stay, mortality, and characteristics of organisms isolated.
Results: Fourty-one children received 1% chlorhexidine, whereas 45 received placebo application. Patients of both groups were comparable with respect to baseline characteristics. Incidence of ventilator-associated pneumonia was 39.6/1,000 ventilator days with 1% chlorhexidine and 38.1/1,000 ventilator days with placebo (relative risk 1.03, confidence interval 0.44–2.42, p = .46). The duration of intensive care unit stay and hospital stay was a mean of 8.4 ± 5.8 vs. 9.6 ± 11.4 days (p = .58) and 16.1 ± 10.2 days vs. 15.1 ± 14.3 days (p = .19) with chlorhexidine and placebo, respectively. The mortality rates were similar in the two groups (p = .81). All but two isolates causing ventilator-associated pneumonia were gram-negative, with Acinetobacter species being the most common (14 of 26). No side effects of the applied gel were seen in either group.
Conclusion: Oral mucosal application on 1% chlorhexidine gel did not prevent the development of ventilator-associated pneumonia in children 3 months to 15 yrs age.

Introduction

Over the last 50 yrs, mechanical ventilation has undoubtedly represented an advance in the treatment of respiratory insufficiency. However, nosocomial pneumonia has emerged as a leading complication of ventilation—increasing morbidity, mortality, and healthcare costs. Ventilator-associated pneumonia (VAP) has been found to have varying rates in different studies based on the population studied and the type of diagnostic techniques used. While the incidence of VAP in children, according to the data from hospitals enrolled in the National Care and Safety Network, has been found to be as low as 2.3 per 1,000 ventilator days in pediatric medical intensive care units (ICUs) in the United States, VAP continues to be the second most common healthcare-associated infection even in developed countries.[1] Two studies from India have shown contrastingly high VAP rates of 32.5%[2] and 20%[3] in children ventilated in pediatric ICUs (PICUs). In view of its relative frequency and associated high morbidity and mortality,[4] the prevention of VAP is the need of the hour.

Oropharyngeal microflora has been implicated in the pathogenesis of VAP. Oropharyngeal colonization by aerobic pathogens occurs very rapidly in ICU patients because of mucosal desiccation, decreased salivary content of IgA, reduced salivary secretion, and mechanical injury induced by nasogastric and endotracheal tubes.[5,6] In a systematic review, Scannapieco et al[7] identified 11 clinical studies that demonstrated a significant association between periodontal disease and the occurrence of nosocomial pneumonia. These findings suggest that decontamination of the oral mucosa could potentially prevent oropharyngeal colonization by nosocomial pathogens and subsequent infections.

Owing to its promise, chlorhexidine, an antiseptic agent with topical antibacterial activity, has been evaluated as an agent to decrease VAP. The evidence provided is conflicting. Although the Centers for Disease Control and Prevention guidelines recommend regular oral care with antiseptics, these highlight the lack of pediatric studies on strategies to prevent VAP and the lack of a consensus on the methodology of oral care.[8] In a meta-analysis of seven studies, chlorhexidine use was associated with reduction in risk of VAP relative risk 0.74, 95% confidence interval 0.56–0.96, p = .03).[9] It was observed that the beneficial effects were demonstrated maximally in two of the seven trials that were limited to cardiac surgery patients.[9] A recent study demonstrated that even a single application of chlorhexidine could reduce clinically assessed VAP at 48 hrs and 72 hrs in trauma victims.[10] On the other hand, studies such as MacNaughton et al[11] in 2004 and Fourrier et al[12] in 2005 failed to demonstrate a reduction in VAP rates in adult patients of medical and surgical ICUs with chlorhexidine. A similar observation was made in an adult medical ICU through a large, open-label, randomized control trial of 512 patients in Mumbai.[13]

Varying concentrations of chlorhexidine have been used in various studies for the prevention of VAP. Studies that used concentrations of <0.2% and have demonstrated efficacy have been mostly conducted in cardiac and surgical ICUs.[14–16] In medical ICUs like ours, or mixed ICUs, the results with lower (0.2%) chlorhexidine concentrations[12,17] have not been as encouraging. In two studies that used 2% chlorhexidine—both of which were in mixed ICUs—a reduction in VAP rates was demonstrated.[18,19] Hence, we decided to choose a higher concentration of chlorhexidine. As there are reports of transient superficial mucosal desquamations and dental staining,[20] as well as increased enamel diffusion in deciduous compared to permanent teeth;[21] this was considered before choosing a concentration of 1%. Whereas the study by Tantipong and colleagues[19] has shown a higher incidence of mucosal irritation with increasing concentrations, this report was not available at the time of conception of the study and did not influence our decision on the chlorhexidine concentration.

We used a gel preparation of chlorhexidine as application of gel was more feasible than use of a rinse solution (specific disposables for use of the same were not available). Other studies have used both the gel and rinse formulations and the results have been variable, possibly not influenced by the formulation.[10,11,14,15,18,19,22]

The mixed results observed in these trials and the lack of any available studies on the use of chlorhexidine for the prevention of VAP in children prompted us to test the hypothesis that oral mucosal decontamination with 1% chlorhexidine gel would reduce the incidence of VAP in mechanically ventilated children aged 3 months to 15 yrs admitted in PICUs.

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