Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion.

Background: To clarify whether propofol (PROP) and dexmedetomidine (DEX) differentially affect preload dependency in an endotoxemic model based on evaluations of the systemic vascular system and cardiac function.

Methods: Animals were prepared under PiCCO monitoring (BL), and endotoxemic shock was induced using an intravenous bolus of lipopolysaccharide (055:B5) in 16 New Zealand ketamine-anesthetized rabbits. After fluid resuscitation and norepinephrine infusion (SD0), the animals were randomized to PROP (n = 8) or DEX (n = 8) sedation at two incremental doses (SD1 and SD2). The mean arterial pressure and the central venous pressure were monitored. Pulse pressure variation (PPV) was assessed to evaluate preload dependency. Global end-diastolic volume, vascular resistance, mean systemic filling pressure, and cardiac function index were assessed at each time point.

Results: PPV progressively and significantly increased with increasing infusion rates of PROP (SD1 versus SD0, P < 0.01; SD2 versus SD0, P < 0.001; and SD2 versus SD1, P = 0.024) but not DEX. PPV was higher at SD1 and SD2 in the PROP group than in the DEX group (P < 0.001). PROP increased the heart rate without affecting cardiac contractility or vascular resistance. In contrast, DEX decreased heart contractility and increased vascular resistance at the highest dose. However, neither drug affected mean arterial pressure, central venous pressure, mean systemic filling pressure, global end-diastolic volume, or venous return.

Conclusions: PROP more effectively increased PPV than DEX in an endotoxemic shock model after fluid resuscitation during norepinephrine infusion. DEX, but not PROP, at the highest dose influenced vascular resistance and heart contractility.