The results appeared in the second issue for June 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Mirelle Koeman, M.D., Ph.D., of the Department of Emergency Medicine and Infectious Diseases at the University Medical Center Utrecht in the Netherlands, and 13 associates used chlorhexidine as an oral decontaminant paste to treat 127 intubated ventilated patients. The investigators treated a separate group of 128 ventilated patients with a paste composed of chlorhexidine and the antibiotic colistin. A third group of 130 ventilated patients were given a placebo paste.
In comparison to the placebo, the chlorhexidine paste reduced the risk of ventilator-associated pneumonia by 65 percent and the chlorhexidine/colistin combination cut the risk by 55 percent.
All 385 patients who were enrolled consecutively in the study needed mechanical ventilation for 48 hours or more at two university hospitals and three general hospitals in the Netherlands.
According to the authors, ventilator-associated pneumonia is second only to urinary infection as a hospital-acquired illness. The disease affects 27 percent of all critically-ill ventilated patients. Crude mortality rates from ventilator-associated pneumonia range from 20 to 60 percent, and resulting health care costs can be anywhere from $12,000 to $40,000 per patient.
The bacteria that cause ventilator-associated pneumonia usually originate in the mouth and throat. Mechanically ventilated patients have a catheter called an endotracheal tube inserted through either their nose or mouth into the windpipe (trachea) to maintain an open airway, to deliver oxygen, and to suction mucus. The endotracheal tube raises the risk of ventilator-associated pneumonia up to 20 times by allowing bacteria access to the lungs.
The trial medication in the form of a paste was applied every 6 hours inside the mouth at the cheeks (or the buccal cavity). Oropharyngeal swabs were taken daily to determine the level of gram-positive and gram-negative microorganisms.
Of the 385 patients in the study cohort, 52 were diagnosed with ventilator-associated pneumonia: 23 in the placebo group (18 percent); 13 in the chlorhexidine group (10 percent); and 16 in the combination group (13 percent).
"The interventions tested cost less than $100 per patient, making them extremely cost effective," said Dr. Koeman.
However, the researchers noted that the experimental treatments made no difference in how long patients required mechanical ventilation or how long they had to stay intensive care unit. They also reported no change in intensive care unit survival rates.
In an editorial on the research in the same issue of the journal, Donald E. Craven, M.D., of Lahey Clinic Medical Center in Burlington, Massachusetts, and Robert A. Duncan, M.D., M.P.H., of Tufts University School of Medicine in Boston, called the findings an "impressive result for an inexpensive, non-toxic modality" that "warrants further attention."
At the same time, they argued that the study raised several important concerns. They wrote: "The use of 'sequential analysis' is an intriguing concept and offers the promise of more efficient study design, but the small number may have limited power and increased the possibility of an erroneous conclusion. For example, there appear to be significantly more males and patients with infections in the placebo group, which questions the effectiveness of randomization. Second, it is difficult to reconcile significant reductions in ventilator-associated pneumonia with an absence of effect on ventilator days, length stay and mortality."
They continued: "Why wasn't chlorhexidine ultimately more effective and why did some patients fail prophylaxis? Data is limited on how best to apply chlorhexidine paste and its pharmacokinetics, in vitro efficacy, impact on biofilm formation, or possible bacterial resistance, as reported for other topical agents. Furthermore, it is important to understand how the use of chlorhexidine and combined chlorhexidine and colistin will complement other recommended prevention strategies and health care improvement projects for ventilator-associated pneumonia."
To demonstrate the need for clear instructions for use, the editorial authors compared the risk of death from medical error (1 in 300) to that from airline travel (1 in 10 million). They also noted the growing interest in applying the principles of industrial safety to the prevention of health-care associated infections.
Although the authors called the response to date "notably slow," they pointed out that the Institute for Healthcare Improvement, through its "100,000 Lives Campaign," has successfully enlisted 3,000 hospitals in establishing safety programs that include a "ventilator-associated pneumonia prevention bundle." Recommendations for using the bundle include elevating the head of the bed by 30 degrees to prevent inhaling unwanted substances (aspiration), vacations from sedation to allow earlier tube removal, and prophylactic agents to reduce stress bleeding and deep vein thrombosis.
The authors indicated that the prevention of ventilator-associated pneumonia is a multi-disciplinary team effort in which nurses, respiratory therapists, physicians and administrators "play a vital role."
They concluded that, with the right cooperation, "zero tolerance" is an achievable goal for this deadly problem.
Contact for study: Mirelle Koeman, M.D., Ph.D., University Medical Center Utrecht, Department of Emergency Medicine and Infectious Diseases (FO2.126), Heidelberglaan 100, 3884CX, Utrecht, The Netherlands
Phone: +31 70 390 7035
Contact for editorial: Donald E. Craven, M.D., Professor of Medicine, Tufts University School of Medicine, Chair, Department of Infectious Diseases, Lahey Clinic Medical Center,41 Mall Road, Burlington, Massachusetts 01805
Phone: (781) 744-8608
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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