ABSTRACT Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Ventilator-associated pneumonia (VAP) has been described in humans and in experimental animals. The most severe lesions are located in dependent lung segments along a sterno-vertebral axis, however the cephalocaudal distribution of lung infection remains unknown. We used an experimental model to evaluate the distribution of lung infection, considering its anteroposterior and cephalocaudal gradient, and its impact on lung aeration. Ten healthy domestic piglets were anesthetized, paralyzed and mechanically ventilated for 59 hours in the prone position. At the end of the experiment they were sacrificed and their lungs were fixed. Six segments were analyzed: a non-dependant (ND) and a dependant (D) segment of the upper (UL), middle (ML) and lower (LL) lobes. The presence of healthy lung or of histological infectious lesions was analyzed with a semi-quantitative method. The regional distribution of lung infection was compared between upper, middle and lower lobes, as well as between dependant and non-dependant regions. The presence of infectious lesions was correlated with measurements of lung aeration. Nine of the ten piglets developed VAP. Infectious lesions were distributed along a sterno-vertebral and a cephalocaudal gradient; the lower and middle lobes were more frequently infected than the upper lobes. There was an inverse correlation (R= - 0.902) between the development of lung lesions and lung aeration. In conclusion, VAP was a frequent complication in healthy mechanically ventilated piglets, showing an anteroposterior as well as a cephalocaudal gradient. As expected, development of lung infection was accompanied by a corresponding loss of aeration.