title: The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans.
abstract: Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline and repeated after a 4-h intravenous LPS infusion. The assessments of dCA were based on transfer function analysis of spontaneous oscillations between MAP and middle cerebral artery blood flow velocity measured by transcranial Doppler ultrasound in the low frequency range (0.07-0.20 Hz). Prior to LPS, noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P < 0.05) with no effect on phase (0.71 (0.93-0.66) vs 0.94 (0.81-1.10) radians; P = 0.58). After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional neuroprotective effect by enhancing dCA in patients with early sepsis.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, University Hospital Rigshospitalet, Copenhagen, Denmark.|Centre of Inflammation and Metabolism, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.affiliation: Intensive Care Unit 4131, University Hospital Rigshospitalet, Copenhagen, Denmark.|Department of Anaesthesiology, Køge Hospital, Køge, Denmark.
authors.forename: Ronni R
authors.initials: RR
authors.lastname: Plovsing
authors.affiliation: Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.affiliation: Renal and Vascular Research Section, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.affiliation: Centre of Inflammation and Metabolism, University Hospital Rigshospitalet, Copenhagen, Denmark.|Neurointensive Care Unit 2093, Department of Neuroanaesthesiology, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018805:Sepsis / Q000139:chemically induced / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D009638:Norepinephrine
keywords: cerebral blood flow; endotoxin; lipopolysac-charide; sepsis; sepsis-associated encephalopathy; vasopressor