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

Discussion

This study evaluated the efficacy of 1% chlorhexidine gel in reducing the incidence of VAP in a PICU. However, we failedto demonstrate any significant reduction in VAP rates, ICU stay, hospital stay, or mortality.

Although chlorhexidine has been shown to reduce VAP rates in cardiac[14–16] and trauma[10] ICUs, its role in mixed ICUs has not been substantiated in concentrations of <2%. The patients undergoing elective cardiac surgery are quite different from the patients seen in a medical pediatric ICU such as ours. Besides being intubated under controlled circumstances for an elective procedure, the previous group is also more likely to have shorter durations of ventilation. Grap and colleagues[10] studied the role of chlorhexidine in trauma victims for the prevention of nosocomial pneumonia at 48 and 72 hrs, and found significant reductions in both cases. However, in the patient population we studied, the mean duration of ventilation was 7.89 ± 5.7 days and 8.2 ± 10.3 days for chlorhexidine and placebo, respectively. We did not observe any significant difference in the day of development of VAP in the two groups.

Previous studies in mixed ICUs have revealed varying results. Groups[11–13] that used chlorhexidine concentrations varying from 0.1% to 0.2% failed to demonstrate significant reductions in VAP rates. Reductions in VAP rates in these settings were demonstrated in two randomized controlled trials, which used higher chlorhexidine concentrations of 2%.[18,19] A Dutch study by Koeman et al[18] demonstrated a 65% risk reduction with chlorhexidine vs. placebo (p = .012); while in Thailand, Tantipong and his colleagues[19] also showed a significant reduction in the number of VAP episodes/1000 ventilator days with there being seven with chlorhexidine and 21 with placebo (p = .04). Even in these studies, no reductions in mortality, duration of ventilation hospital stay, and ICU stay were reported.[18,19] We used 1% chlorhexidine in our study with the aim of providing increased efficacy while avoiding any potential side effects in the as yet untested population of children we had planned to study. It has been suggested that at lower concentrations, chlorhexidine has a bacteriostatic action, while at higher concentrations it is bactericidal with free chlorhexidine penetrating into cells and causing coagulation of cytoplasmic proteins;[28] it is possible that higher concentrations of chlorhexidine are required for a beneficial effect.

Another potential cause for the lack of efficacy of chlorhexidine that we observed could be the spectrum of organisms that we encountered. All but one of the bacterial isolates were gram-negative. Some earlier studies have shown chlorhexidine to have a better effect on gram-positive organisms than gram-negative.[28–30] In a recent study, Scannapieco et al[31] demonstrated a decrease in the number of Staphylococcus aureus with chlorhexidine application but not in the total number of enterics, Pseudomonas, and Acinetobacter in the dental plaque of tested subjects. In 2005, Fourrier et al[12] dididentify an overall decrease in dental plaque colonization, again this was not seen for Pseudomonas, Acinetobacter, and Enterobacter species. These were the type of organisms that were most common in our ICU with over 14 of 26 (53.84%) isolates being Acinetobacter and six of 26 (23.07%) being Pseudomonas.

There is a dose-response relationship described for chlorhexidine.[32,33] For Pseudomonas, 1 in 50,000 to 1 in 100,000 is the minimum inhibitory concentration for static effect, and for Staphylococcus, 1 in 500,000 to 1 in 2,000,000 was static. For Staphylococcus, a concentration of 1: 200,000 of chlorhexidine killed >99.9% of the bacteria present in 5 mins, but a concentration of 1: 20,000 did not completely kill in 10 mins.[32] For sub-gingival bacteria, Oosterwaal and colleagues[33] demonstrated that 128 μg/mL (0.1%) was bacteriostatic and 5 mg/mL (0.5%) was bactericidal.

Among the differences that our study had from previous ones on this aspect of VAP prevention was that this study was carried out in children. At the time of initiation of this study, there were no published studies evaluating the efficacy in children. In a recently published study, oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence ofnosocomial pneumonia and VAP in children undergoing cardiac surgery.[34] The pediatric population that we studied is inherently different from the adult subjects of the previous studies. Their oral cavities are smaller and less accessible as an adult's. Adults are also more likely to tolerate maneuvers such as cleansing of teeth, gingiva, tongue, and buccal mucosa. The safety of oropharyngeal cleansing with regards to accidents such as endotracheal tube displacement was considered before deciding to restrict the application of the allotted gel to the buccal mucosa and avoiding mechanical plaque removal. Another major difference in our population from previous studies was that nearly 85% of our patients had some form of infection, with 64% having preexisting pneumonia. Due to this large number of infected patients, our antibiotic prescription rates were much higher. All our patients were on some antibiotic with the most common being ceftriaxone (58.14%) and vancomycin (69.76%). Koeman et al reported antibiotic usage of 34.8% and Tantipong et al reported it to be 52.1% at admission, in contrast to our 100% usage rate.[18,19] The use of broad spectrum antibiotics has been linked to an increased incidence of VAP in mechanically ventilated patients; this finding holds true particularly for third generation cephalosporins among others.[35] In our study, we did not test the sensitivity of the organisms isolated to chlorhexidine, and doing so may have contributed to a better understanding of this issue.

The amount of chlorhexidine received was dependent on the duration of ventilation as chlorhexidine was only applied for that duration. There was no significant difference between the placebo and chlorhexidine group with respect to the amount of gel they received.

There were some limitations of our study. Our study was underpowered in view of the adequate sample size having not been achieved. However, as the trial was designed to be time driven and there was no trend toward a difference in any of the primary or secondary outcomes, the study was terminated at the planned date. We did not collect data regarding the numbers of suctioning and intubations; these may have an influence on incidenceof VAP.

This is the only study we know that evaluated the role of chlorhexidine in the prevention of VAP in children in a setting of a nonsurgical PICU. We were able to achieve effective randomization, blinding, and follow-up. We did not exclude patients with preexisting lung infections as they continue to be susceptible to new infections during ventilation and contribute to the burden of patients with nosocomial pneumonia. We used strict and objective criteria for the diagnosis of VAP. While we failed to demonstrate a role of 1% chlorhexidine gel in the prevention of VAP, more pediatric studies are required on this topic before this issue can be resolved.

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