Sepsis is frequently complicated by brain dysfunction, which may be associated with disturbances in cerebral autoregulation rendering the brain susceptible to hypo- and hyperperfusion. The purpose of the present study was to assess static and dynamic cerebral autoregulation (i) in a human-experimental model of the systemic inflammatory response during early sepsis, and (ii) in patients with advanced clinical sepsis. Cerebral autoregulation was tested using transcranial Doppler ultrasonography (i) before and after lipopolysaccharide (LPS) infusion in healthy volunteers (n=9), and (ii) in patients with sepsis (n=16). Static autoregulation was tested by norepinephrine infusion and dynamic autoregulation by transfer function analysis (TFA) of spontaneous oscillations between mean arterial blood pressure and middle cerebral artery blood flow velocity in the low frequency range (0.07-0.20 Hz). Static autoregulatory performance after LPS infusion and in patients with sepsis was similar to values in healthy volunteers at baseline. In contrast, TFA showed decreased gain and an increased phase difference between blood pressure and cerebral artery blood flow velocity after LPS (both p <0.01 vs. baseline); patients exhibited similar gain but lower phase difference values (p <0.01 vs. baseline and LPS), indicating a slower dynamic autoregulatory response. Our findings imply that static and dynamic cerebral autoregulatory performance may disassociate in sepsis; thus static autoregulation was maintained both after LPS and in patients with sepsis, whereas dynamic autoregulation was enhanced after LPS and impaired with a prolonged response time in patients. Hence, acute surges in blood pressure may adversely affect cerebral perfusion in patients with sepsis.
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2012, Vol 120/9