Joan Daniel Marti

Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is an iatrogenic pulmonary infection that develops in tracheally intubated patients on mechanical ventilation for at least 48 hours. VAP is the nosocomial infection with the greatest impact on patient outcomes and health care costs. Endogenous colonization by aerobic gram-negative pathogens, that is, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus play a pivotal role in the pathogenesis of VAP. Several preventive strategies have shown efficacy in decreasing VAP incidence and are often implemented altogether as a prevention bundle. In patients with clinical suspicion of VAP, respiratory samples should be promptly collected. The empiric treatment should be based on the local prevalence of pathogens, duration of hospital stay, and prior antimicrobial therapy. The antibiotics can be stopped or adjusted to more narrow-spectrum once cultures and susceptibilities are available.

A Novel Porcine Model of Ventilator-associated Pneumonia Caused by Oropharyngeal Challenge with pseudomonas aeruginosa

Background: Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. Methods: Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. Results: In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P < 0.001). VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). Conclusions: The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors’ model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.

Effects of manual rib cage compressions on expiratory flow and mucus clearance during mechanical ventilation.

Objectives:We investigated the effects of two different types of manual rib cage compression on expiratory flow and mucus clearance during prolonged mechanical ventilation in pigs. Design:Prospective randomized animal study. Setting:Animal research facility, University of Barcelona, Spain. Subjects:Nine healthy pigs. Measurement and Main Results:Pigs were tracheally intubated, sedated, paralyzed, and mechanically ventilated. The animals were prone on a surgical bed in the anti-Trendelenburg position. The experiments were carried out at approximately 60 and 80 hrs from the beginning of mechanical ventilation. Two types of manual rib cage compressions were tested: Hard and brief rib cage compressions synchronized with early expiratory phase (hard manual rib cage compression) and soft and gradual rib cage compressions applied during the late expiratory phase (soft manual rib cage compression). The interventions were randomly applied for 15min with a 15-min interval between treatments. Respiratory flow and mucus movement were assessed during the interventions. Respiratory mechanics and hemodynamics were assessed prior to and after the interventions. Peak expiratory flow increased to 60.1±7.1L/min in comparison to 51.2±4.6L/min without treatment (p < 0.0015) and 48.7±4.3L/min with soft manual rib cage compression (p = 0.0002). Similarly, mean expiratory flow increased to 28.4±5.2L/min during hard manual rib cage compression vs. 15.9±2.2 and 16.6±2.8L/min without treatment and soft manual rib cage compression, respectively (p = 0.0006). During hard manual rib cage compression, mucus moved toward the glottis (1.01 ± 2.37mm/min); conversely, mucus moved toward the lungs during no treatment and soft manual rib cage compression, –0.28 ± 0.61 and –0.15±0.95mm/min, respectively (p = 0.0283). Soft manual rib cage compression slightly worsened static lung elastance and cardiac output (p = 0.0391). Conclusions:Hard manual rib cage compression improved mucus clearance in animals positioned in the anti-Trendelenburg position. The technique appeared to be safe. Conversely, soft manual rib cage compression was not effective and potentially unsafe. These findings corroborate the predominant role of peak expiratory flow on mucus clearance.

Gravity predominates over ventilatory pattern in the prevention of ventilator-associated pneumonia.

Objective:In the semirecumbent position, gravity-dependent dissemination of pathogens has been implicated in the pathogenesis of ventilator-associated pneumonia. We compared the preventive effects of a ventilatory strategy, aimed at decreasing pulmonary aspiration and enhancing mucus clearance versus the Trendelenburg position. Design:Prospective randomized animal study. Setting:Animal research facility, University of Barcelona, Spain. Subjects:Twenty-four Large White–Landrace pigs. Interventions:Pigs were intubated and on mechanical ventilation for 72 hours. Following surgical preparation, pigs were randomized to be positioned: 1) in semirecumbent/prone position, ventilated with a duty cycle (TITTOT) of 0.33 and without positive end-expiratory pressure (control); 2) as in the control group, positive end-expiratory pressure of 5 cm H2O and TITTOT to achieve a mean expiratory-inspiratory flow bias of 10 L/min (treatment); 3) in Trendelenburg/prone position and ventilated as in the control group (Trendelenburg). Following randomization, Pseudomonas aeruginosa was instilled into the oropharynx. Measurements and Main Results:Mucus clearance rate was measured through fluoroscopic tracking of tracheal markers. Microspheres were instilled into the subglottic trachea to assess pulmonary aspiration. Ventilator-associated pneumonia was confirmed by histological/microbiological studies. The mean expiratory-inspiratory flow in the treatment, control, and Trendelenburg groups were 10.7 ± 1.7, 1.8 ± 3.7 and 4.3 ± 2.8 L/min, respectively (p < 0.001). Mucus clearance rate was 11.3 ± 9.9 mm/min in the Trendelenburg group versus 0.1 ± 1.0 in the control and 0.2 ± 1.0 in the treatment groups (p = 0.002). In the control group, we recovered 1.35% ± 1.24% of the instilled microspheres per gram of tracheal secretions, whereas 0.22% ± 0.25% and 0.97% ± 1.44% were recovered in the treatment and Trendelenburg groups, respectively (p = 0.031). Ventilator-associated pneumonia developed in 66.67%, 85.71%, and 0% of the animals in the control, treatment, and Trendelenburg groups (p < 0.001). Conclusions:The Trendelenburg position predominates over expiratory flow bias and positive end-expiratory pressure in the prevention of gravity-dependent translocation of oropharyngeal pathogens and development of ventilator-associated pneumonia. These findings further substantiate the primary role of gravity in the pathogenesis of ventilator-associated pneumonia.

Endotracheal Tubes for Critically Ill Patients: An In Vivo Analysis of Associated Tracheal Injury, Mucociliary Clearance, and Sealing Efficacy

BACKGROUND Improvements in the design of the endotracheal tube (ETT) have been achieved in recent years. We evaluated tracheal injury associated with ETTs with novel high-volume low-pressure (HVLP) cuffs and subglottic secretions aspiration (SSA) and the effects on mucociliary clearance (MCC). METHODS Twenty-nine pigs were intubated with ETTs comprising cylindrical or tapered cuffs and made of polyvinylchloride (PVC) or polyurethane. In specific ETTs, SSA was performed every 2 h. Following 76 h of mechanical ventilation, pigs were weaned and extubated. Images of the tracheal wall were recorded before intubation, at extubation, and 24 and 96 h thereafter through a fluorescence bronchoscope. We calculated the red-to-green intensity ratio (R/G), an index of tracheal injury, and the green-plus-blue (G+B) intensity, an index of normalcy, of the most injured tracheal regions. MCC was assessed through fluoroscopic tracking of radiopaque markers. After 96 h from extubation, pigs were killed, and a pathologist scored injury. RESULTS Cylindrical cuffs presented a smaller increase in R/G vs tapered cuffs (P = .011). Additionally, cuffs made of polyurethane produced a minor increase in R/G (P = .012) and less G+B intensity decline (P = .022) vs PVC cuffs. Particularly, a cuff made of polyurethane and with a smaller outer diameter outperformed all cuffs. SSA-related histologic injury ranged from cilia loss to subepithelial inflammation. MCC was 0.9 ± 1.8 and 0.4 ± 0.9 mm/min for polyurethane and PVC cuffs, respectively (P < .001). CONCLUSIONS HVLP cuffs and SSA produce tracheal injury, and the recovery is incomplete up to 96 h following extubation. Small, cylindrical-shaped cuffs made of polyurethane cause less injury. MCC decline is reduced with polyurethane cuffs.

Oropharyngeal decontamination with antiseptics to prevent ventilator-associated pneumonia: rethinking the benefits of povidone-iodine.

The colonization of the oropharynx plays a pivotal role in the pathogenesis of ventilator-associated pneumonia (VAP). Analysis of the oropharyngeal microbiota of healthy humans, using real-time PCR, demonstrated an extensive bacterial diversity comprising species of Streptococcus, Gemella, Eubacterium, Selenomonas, Veillonella, Actinomyces, Atopobium, Rothia, Neisseria, Eikenella, Campylobacter, Porphyromonas, Prevotella, Capnocytophaga, Fusobacterium, and Leptotrichia{\). Oropharyngeal colonization with respiratory pathogens is prevented by the physical-chemical properties of the oral mucosa surface, the salivary enzymatic content, and specific proteases and immunoglobulins. Conversely, in the critically ill tracheally intubated patient, the oral flora shifts to a predominance of Gram-negative and Gram-positive aerobic pathogens, that is, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (2). The main reasons for such overgrowth of pathogens are difficulties in oral hygiene, changes in salivary properties during critical illness, and antibiotic therapy (2, 3). Once the oropharynx becomes colonized, microbes translocate into the airways because of endotracheal tubes (ETTs) comprising high-volume lowpressure cuffs. These cuffs are not leak-proof and promote a continuous seepage of bacteria-laden oropharyngeal contents into the airways (4). Heo et al (5) compared genetic features of microbes obtained from oral, trachea!, and bronchoalveolar