Bioactive adrenomedullin, or bio-ADM, rose as pigs went through controlled hemorrhagic shock and resuscitation, reaching a median 17.55 pg/ml at the final measurement. Across all animals, concentrations ranged from 2.2 to 98.2 pg/ml, and the rise from the first measurement to the last was statistically significant (p<0.001). The authors interpret the pattern as evidence that bio-ADM tracks hemodynamic and microcirculatory compromise, although the result is an association rather than proof that the marker itself causes poor circulation.
The most distinct treatment pattern appeared in the fluid group. Bio-ADM continued rising in animals given noradrenaline, plateaued after early treatment in controls, and remained stable during treatment in fluid-treated animals. At the final time point, the reported values were 19.70 ± 15.20 pg/ml in controls, 21.20 ± 19.05 pg/ml in the noradrenaline group and 12.05 ± 4.52 pg/ml in the fluid group. The fluid group's increase from T5 to T9 was smaller than the increase in the noradrenaline group (p=0.003) and controls (p=0.022).
A controlled test in pigs
This was a secondary analysis of a porcine hemorrhagic-shock experiment. It included 20 pigs, divided into control, noradrenaline and fluid groups of 7, 7 and 6 animals. The animals were among 27 in the original experiment: three died, two were excluded because baseline hemodynamics had changed, and two had no blood samples. All received background crystalloid at 10 mL/kg/h. Researchers then withdrew blood to hold mean arterial pressure, or MAP, at 40±5 mmHg for 60 minutes before randomly assigning the animals to no further intervention, fluid or noradrenaline strategies. Treatment targets were 65 mmHg and then 90 mmHg.
The circulation pattern
At the final time point, the fluid group showed partial hemodynamic stabilization, with higher MAP than the noradrenaline and control groups and a lower heart rate. Its ear tissue-oxygenation reading, StO2, increased, while StO2 Ear declined in the noradrenaline group. ScvO2 recovered with fluid treatment but declined in the control and noradrenaline groups, whereas DO2 declined similarly across the groups.
The same pattern appeared in comparisons of individual measurements. Higher MAP was associated with a smaller increase in bio-ADM between T5 and T9. A total fluid volume above 3,000 mL was also associated with a smaller increase. Higher lactate and ScvO2 below 51% were associated with larger increases, while DO2 showed no relationship. These findings describe measurements that moved together; they do not establish that one caused the other.
An exploratory regression sharpened the signal but also shows how narrow the evidence is. In the 14 animals in the control and noradrenaline groups with complete data, each doubling of bio-ADM at T7 was associated with 4.62 mmHg lower MAP at T9 after adjustment for fluid volume and treatment group. The 95% confidence interval spanned 2.35 to 6.90 mmHg lower MAP, with a model p-value of 0.0069 and an adjusted R-squared of 0.594. The analysis was exploratory and involved only those two treatment groups.
Signals from the tissue
Hyperspectral imaging, used in the study to assess microcirculatory measures, added a similar signal. Lower StO2 and NIR readings in both the ear and kidney were associated with larger bio-ADM increases. Higher tissue-water index, or TWI, was associated with smaller increases, while THI showed no significant trajectory differences. Significant associations were reported for StO2 Ear, StO2 Kidney, NIR Ear, NIR Kidney, TWI Ear and TWI Kidney.
Why the finding remains preliminary
The authors describe bio-ADM as a comparatively nonspecific signal of stress in the lining of blood vessels, associated with reduced blood flow rather than tied to one particular cause of shock. They say further prospective studies are needed before its therapeutic value can be assessed.
The fluid group's stabilization also needs careful interpretation. Incomplete hematocrit sampling meant the analysis could not reliably separate dilution of the blood from a biological change in bio-ADM. The study had a small sample and restricted sampling, and it included no anesthesia-and-surgery-only control, no direct endothelial or glycocalyx injury markers, and no renal or mortality endpoints.
Because this was a secondary analysis in pigs, its applicability to human patients is limited. The findings establish a pattern within this experimental model, while whether bio-ADM can provide useful information for human shock care remains unresolved and requires prospective study.
Paper data and sources
Original title: Bioactive adrenomedullin dynamics and microcirculatory changes in a porcine model of hemorrhagic shock
Authors: Vekla C, Hartmann O, Decker S et al.
Journal/Repository: Intensive care medicine experimental
Status: Peer-reviewed
First online: 2026-10-13
DOI: Not available
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