Seminal studies have demonstrated that tracheally intubated, mechanically ventilated patients, positioned in supine horizontal position, are at a high risk of developing ventilator-associated pneumonia, through aspiration of gastric pathogens. In the 1990s, innovative clinical findings promoted a radical change in practice, through the use of the semirecumbent position in all mechanically ventilated patients. Here, we critically review the main indications, pulmonary effects, and controversies on the use of the semirecumbent position. Also, we will depict potential roles of prone and lateral positions in the prevention of ventilator-associated pneumonia. Our review will span from preclinical experimental insights to clinical evidence, and we will discuss potential controversies on the use of the semirecumbent position as the standard of care. We will also detail potential alternatives to ultimately improve outcomes of tracheally intubated and mechanically ventilated patients.
Background
Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia.
Methods
We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers.
Results
The median (25–75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75–5.69), 0.72 (0.12–3.35), and 0.90 (0–4.55) log10 CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0.037). Adjunctive therapy also slightly affected interleukin-1β downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas.
Conclusions
In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.
Experienced intensive care clinicians who reminiscence with rosy nostalgia about the care provided to patients who were critically ill and mechanically ventilated decades ago often highlight the frequent monitoring and handling of almost any airway device for respiratory care. In those years, ventilator circuits, in-line suction catheters, heat and moisture exchangers, and even endotracheal tubes were
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