Early depletion of contact system in patients with sepsis: a prospective matched control observational study

Activation of the contact system generates bradykinin from high‐molecular‐weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high‐molecular‐weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis‐3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90‐day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to controls (130 [86–255] pg/ml, p < 0.025) and did not correlate with mortality or severity of circulatory derangement. High‐molecular‐weight kininogen levels were lower in sepsis patients (1.6 [0.8–4.8] densitometry units) compared to controls (4.4 [2.9–7.7] densitometry units, p < 0.001), suggesting previous contact system activation. High‐molecular‐weight kininogen levels were lower in non‐survivors than survivors (p = 0.003) and negatively correlated to severity of circulatory derangement. We conclude that a role for bradykinin in later stages of severe sepsis must be challenged. Low high‐molecular‐weight kininogen concentrations suggest that the decrease in bradykinin is due to substrate depletion.