Bioactive adrenomedullin dynamics and microcirculatory changes in a porcine model of hemorrhagic shock.

BACKGROUND

Hemorrhagic shock is a leading cause of preventable trauma death, marked by impaired oxygen delivery and endothelial dysfunction. Bioactive adrenomedullin (bio-ADM) regulates endothelial barrier integrity, but its dynamics during hemorrhagic shock and resuscitation remain unclear. This secondary analysis of a porcine hemorrhagic shock model investigated bio-ADM and its association with macro- and microcirculatory parameters during resuscitation. All animals received crystalloid infusion (10 mL/kg/h) from anesthesia induction onward. Shock was induced by blood withdrawal to maintain MAP at 40 ± 5 mmHg for 60 min (T5), before randomization to control (n = 7), fluid (n = 6), or noradrenaline (n = 7) groups, with intervention groups titrated to MAP targets of 65 then 90 mmHg (60 min each). Macrocirculation was assessed via vital signs and pulse contour analysis; microcirculation via hyperspectral imaging (tissue oxygenation, hemoglobin, water index).

RESULTS

Fluid resuscitation improved macrohemodynamics and microcirculatory oxygenation versus control and noradrenaline, which failed to sustain perfusion and impaired microcirculatory oxygenation. Bio-ADM increased after shock induction (p < 0.001), peaking at T9 (120 min of therapy). At T5, levels were comparable among control (16.8 [13.6-18.9] pg/ml), fluid (15.65 [15.43-16.55] pg/ml), and noradrenaline (14.3 [7.85-18.95] pg/ml). Thereafter, bio-ADM continued to rise in control (19.7 [17.4-32.6] pg/ml) and noradrenaline (21.2 [14.4-33.45] pg/ml), while stabilizing in the fluid group (12.05 [10.65-15.18] pg/ml); accordingly, the T5-T9 increase was smaller in the fluid group than in control (p = 0.022) or noradrenaline (p = 0.003). The fluid group received ~3-fold more fluid by T9. Higher bio-ADM correlated with lower MAP, higher lactate, and lower ScvO₂, but not oxygen delivery (DO₂); a higher tissue water index correlated with a smaller rise.

CONCLUSIONS

Bio-ADM increased during hemorrhagic shock, extending previous observations from cardiogenic and septic shock, and represents a comparatively non-specific marker of endothelial and microcirculatory stress rather than specific to any single shock etiology. Effective resuscitation was associated with stabilization, rather than a clear decrease, of bio-ADM levels, though this coincided with higher fluid administration, and dilution cannot be excluded. Whether bio-ADM offers therapeutic utility to guide resuscitation remains unclear, warranting further prospective evaluation in animal and human studies.