Vol. 14 •Issue 3 • Page 19
Pursuing a Panacea for Ventilator-associated Pneumonia
Respiratory infections are merely annoying inconveniences for otherwise healthy people. For the critically ill, though, bacteria threaten like invisible death squads.
When patients who require prolonged mechanical ventilation contract ventilator-associated pneumonia (VAP), half of them die. The rest linger in the ICU far longer than otherwise necessary, piling up costs.
Researchers have now added blood transfusions, the herpes virus and even dental plaque to the list of possible risk factors for VAP. But despite a mother lode of literature on the subject, clinicians have yet to devise an optimum strategy for diagnosing and treating VAP.
Diagnosing VAP reliably, for instance, could avoid needless administration of antibiotics, which creates multidrug-resistant pathogens and courts disaster.
Perhaps discovering a panacea for such a complex syndrome as VAP is unrealistic. But coming as close to one as possible would save lives, ease untold suffering, and slash hospital expenses.
Newly published research suggests a possible link between packed red blood cell transfusions and VAP.
Previous research has shown that transfusions alter the host’s immune system and are associated with surgical site infections, catheter-related infections and postoperative pneumonia.
In the new study, a cohort of 1,518 ICU patients received mechanical ventilation for at least 48 hours and didn’t have pre-existing pneumonia. Of these, 311 (20.4 percent) developed VAP. Most who developed late-onset VAP (71 percent) had had transfusions.1
“There was a dose-response relationship: The more blood you got, the worse the outcome,” explained lead author Andrew Shorr, MD, MPH, assistant professor of medicine and chief of the pulmonary clinic at Walter Reed Army Medical Center, Washington, D.C.
“We have seen a sea change in our approach to transfusion,” Dr. Shorr elaborated. “Our data is one more piece in the puzzle to suggest that it may not be as benign as we once thought. A lot of significant evidence over the last five years indicates that transfusion is not an optimal intervention in the ICU. And (VAP) is another kind of risk associated with it.”
Dr. Shorr said his study was greeted with some skepticism because of the methodology used; it wasn’t a prospective, randomized trial of transfusion practice. While that’s a legitimate critique, “in the absence of a randomized, larger trial, you still have to make a decision on how to best treat your patient,” he pointed out.
At least three well-done previous studies have demonstrated a relationship between transfusion and nosocomial infection, he said, adding: “How much noise must you hear before you conclude that it’s a signal and not noise?”
If the data demonstrate a risk, and if blood is expensive, “then not too many will object to a strategy that says give less blood and prevent fewer complications in patients,” Dr. Shorr reasoned.
Jean-Yves Fagon, MD, cited this study during a seminar on VAP at the 2004 American Thoracic Society conference in Orlando, Fla., and warned about transfusion-related immunosuppression. “Transfusion leads to increased cytokines such as interleukin-6,” Dr. Fagon said. “Avoid unnecessary red blood cell transfusions.”
HERPES, PLAQUE RISKS
ICU specialists also should watch for the herpes simplex virus (HSV) in mechanical ventilation patients, Dr. Fagon continued.
In a study of 764 patients admitted for at least three days in the ICU, HSV was detected via oropharyngeal swab in the upper respiratory tract of 169 of them (22 percent).2 Of the 764 patients, ARDS developed in 46, or 6 percent, Dr. Fagon said. Of them, 20 (44 percent) had HSV in the throat and 10 had the virus in the lower respiratory tract.
“HSV in the respiratory tract was associated with ARDS but it is unclear if HSV triggers ARDS,” noted Dr. Fagon, a pulmonologist in the medical ICU at Hopital European Georges Pompidou, Paris.
Germs found in dental plaque also can make their way into lungs and cause potentially fatal pneumonia in elderly nursing home patients, U.S. researchers reported recently.3
“This is the first study to establish unequivocally a link between dental hygiene and respiratory infection,” lead author Ali El-Solh, MD, of the University at Buffalo in New York, told Reuters.
Dr. El-Solh and colleagues tested 49 nursing home residents admitted to a nearby hospital with a high risk of pneumonia. Of them, 28 had germs known to cause respiratory disease in their dental plaque samples and 21 didn’t. Of the 14 who eventually developed pneumonia, eight of them — more than half — had plaque germs that were an identical DNA match to germs found in their bronchoalveolar lavage samples.
“These findings indicate that dental plaque is a reservoir of respiratory pathogens that can cause pneumonia in hospitalized, institutionalized elders,” Dr. El-Solh said.
No large studies have verified this finding, Dr. Shorr said. But what ICU director would object to purchasing so inexpensive a product as mouthwash to insure good oral hygiene in patients and potentially stave off pneumonia?
On the management side, a study by Dr. Fagon demonstrates that in treating VAP, doing less may be best. The researchers split 401 ICU patients with VAP into two groups, one receiving an eight-day regimen of antibiotics, the other, a 15-day regimen.4 Patients in the eight-day group had lower mortality and required fewer antibiotics — which meant multidrug-resistant pathogens were less of a threat to them than to members of the 15-day group.
Furthermore, except for infections involving nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, the eight-day group also had fewer recurrent pulmonary infections than the 15-day group.
Commenting on the study, Dr. Shorr said, “It’s probably one of the top five trials in changing antibiotic regimens in the ICU. It’s about the rational use of antibiotics, not more use.”
Meanwhile, a comprehensive study by a team led by David Ost, MD, evaluated 16 possible diagnostic and therapeutic approaches to VAP.
These researchers found that, of the 16 approaches examined, diagnostic testing for VAP using mini-bronchoalveolar lavage (mini-BAL), followed by an initial regimen of three antibiotics, did the best job of increasing survival, decreasing antibiotic use, and lowering cost-per-ventilated patient.5
“Initial coverage with three antibiotics was better than expectant management or one or two antibiotic approaches, leading to both improved survival (54 percent vs. 66 percent) and decreased cost ($55,447 vs. $41,483 per survivor),” Dr. Ost wrote. “Testing with mini-BAL didn’t improve survival but did decrease costs ($41,483 vs. $39,967) and antibiotic use (63 vs. 39 antibiotic days per survivor).
“From the perspective of minimizing cost, minimizing antibiotic use, and maximizing survival, the best strategy was three antibiotics with mini-BAL.”
Dr. Ost’s study “nicely showed that the strategy of creeping incrementalism, that is, starting with two drugs then adding a third as needed, is not cost-effective,” Dr. Shorr said. “You have to be narrow in your antibiotic choice, or else you invite resistant pathogens. But you must also acknowledge that resistance is out there, and if you don’t get the antibiotics right, the patient will do poorly.”
Dr. Shorr’s advice: Start with broad spectrum agents that cover pseudomonas and other common germs. Then, when the cultures come back, treat the patient with appropriate drugs. “You spend money up front, but in the end you make sure the patient gets the right drug,” he said.
NIDUS FOR INFECTION
In 2001, Dr. Shorr also demonstrated that an initial outlay pays dividends later. He and a colleague found that managing VAP with endotracheal tubes (ETs) capable of continuous subglottic suctioning saved money in the long run when pitted against less expensive management using standard ETs.6
Maybe clinicians should call ventilator-associated pneumonia “endotracheal tube-related pneumonia” instead, Dr. Shorr offered.
“It’s a disease of colonization of the upper airway,” he said. “When a patient is extubated, that tube coming out is not clean; it’s really quite disgusting. It’s a nidus for infection. Biofilm colonized with bacteria drips into the airway. Aspirating it leads to infection.”
As we move toward earlier weaning and more aggressive use of sedation protocols, we also have less infection, he said. So maybe VAP is a problem not just of process but of engineering.
In his study, special ETs with antibiotic-coated central venous catheters decreased the risk of nosocomial pneumonia. “So we modeled some strategies under the theory that more money up front will save money downstream,” Dr. Shorr explained. “We did some simple modeling and cost analysis. On average, we saved about $5,000 per patient.”
Today, however, he’s grown skeptical of the special ET he used. “The tube clogs and stops working, then it’s just like any other endotracheal tube,” he said. “So it’s not as optimal as it could be.”
There’s a silver lining here — literally. “What’s coming along now is a large, multicenter international clinical trial looking at a silver lining inside the catheter to prevent biofilm from building up,” he said. “There is good animal data to suggest that this is effective.”
Asked if a definitive treatment for VAP would ever appear, Dr. Shorr paused. “I’m not sure there is such a thing as an optimal strategy,” he said. “Strategies may have to be institution-specific and tailored to local populations and their specific risks.”
1. Shorr A, Duh M, Kelly K, et al. Red blood cell transfusion and ventilator-associated pneumonia: a potential link? Crit Care Med. 2004;32:666-74.
2. Brynseels P, Jorens P, Demey H, et al. Herpes simplex virus in the respiratory tract of critical care patients: a prospective study. Lancet. 2003;362:1536-41.
3. El-Solh A, Pietrantoni C, Bhat A, et al. Colonization of dental plaques: a reservoir of respiratory pathogens for hospital-acquired pneumonia in institutionalized elders. Chest. 2004;126:1575-82.
4. Chastre J, Wolff M, Fagon J, et al. Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults. JAMA. 2003;290:2588-98.
5. Ost D, Hall C, Gnanaraj J, et al. Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia. Am J Respir Crit Care Med. 2003;168:1060-7.
6. Shorr A, O’Malley P. Continuous subglottic suctioning for the prevention of ventilator-associated pneumonia. Chest. 2001;119:228-35.
Michael Gibbons is senior associate editor of ADVANCE. He can be reached at [email protected].