Adrenomedullin plays a central role in both the early beneficial vasodilation and the late dangerous cardiovascular collapse of sepsis, making it both a therapeutic target and a biomarker for sepsis progression.
Dual-phase roleADM helps in early sepsis but kills in late sepsis — the same peptide goes from friend to foe as clearance fails and accumulation grows
What the researchers found
Adrenomedullin contributes to both phases of sepsis: beneficial vasodilation during early compensation and harmful cardiovascular collapse during late decompensation, driven by progressive ADM accumulation from reduced clearance and increased tissue production.
Why it matters
Understanding the dual role of ADM in sepsis — helpful early, harmful late — could guide timing of potential ADM-modulating therapies to preserve early benefits while preventing late collapse.
How the study worked
Review synthesizing data on adrenomedullin dynamics during experimental sepsis, covering tissue production, pulmonary clearance, receptor regulation, and hemodynamic effects across both sepsis phases.
What this study cannot tell us
Review based largely on animal sepsis models. The exact tipping point where ADM shifts from beneficial to harmful is not precisely defined.
How to read the evidence
Moderate evidence from a review integrating multiple experimental sepsis studies with coherent mechanistic framework.
When this study was published
Published in 2001. ADM-targeting therapies (adrecizumab) are now in clinical trials for sepsis, and MR-proADM is a clinical sepsis biomarker.
The bigger picture
Sepsis kills more people than many cancers. Understanding which peptide changes drive the transition from compensated to decompensated shock could enable therapies that prevent this deadly transition.
Questions still open
- Can ADM levels be used to time therapeutic intervention in sepsis?
- Would ADM receptor antagonists help in late sepsis without harming early compensation?
- Could monitoring ADM predict which sepsis patients will decompensate?
Common questions
Why does sepsis worsen suddenly?
Can this be treated?
Read the original research
The role of adrenomedullin in producing differential hemodynamic responses during sepsis.
The Journal of surgical research, 95(2), 207-18
Citation
Koo, D J; Zhou, M; Chaudry, I H; Wang, P. (2001). The role of adrenomedullin in producing differential hemodynamic responses during sepsis.. The Journal of surgical research, 95(2), 207-18.