title: The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock.
abstract: OBJECTIVE
  To investigate the effect of escalating doses of norepinephrine, aimed at achieving incremental increases in mean arterial pressure (MAP), on microvascular flow and tissue oxygenation in patients with septic shock.
  
  
  METHODS
  Single-center interventional study.
  
  
  METHODS
  University hospital intensive care unit.
  
  
  METHODS
  Sixteen patients with established septic shock.
  
  
  METHODS
  The norepinephrine dose was escalated to achieve incremental increases in the MAP from 60 to 70, 80, and 90 mm Hg.
  
  
  RESULTS
  In addition to routine clinical measurements, cardiac output was determined using lithium dilution and arterial waveform analysis, cutaneous tissue Pto2 was measured using a Clark electrode, cutaneous red blood cell flux was assessed using laser Doppler flowmetry, and sublingual microvascular flow was evaluated using sidestream darkfield imaging. The mean (sd) norepinephrine dose increased from 0.18 (0.18) microg x kg(-1) x min(-1) at 60 mm Hg to 0.41 (0.26) microg x kg(-1) x min(-1) at 90 mm Hg (p < 0.0001). During this period, global oxygen delivery increased from 487 (418-642) to 662 (498-829) mL x min(-1) x m(-2) (p < 0.01), cutaneous Pto2 increased from 44 (11) to 54 (13) mm Hg (p < 0.0001) and cutaneous microvascular red blood cell flux increased from 26.1 (16.2-41.9) to 33.3 (20.3-46.7) perfusion units (p < 0.05). No changes in sublingual microvascular flow index, vessel density, the proportion of perfused vessels, perfused vessel density, or heterogeneity index were identified by sidestream darkfield imaging.
  
  
  CONCLUSIONS
  In patients with septic shock, targeting higher MAP by increasing the dose of norepinephrine resulted in an increase in global oxygen delivery, cutaneous microvascular flow, and tissue oxygenation. There were no changes in preexisting abnormalities of sublingual microvascular flow. Further research is required to clarify the optimal end points for vasopressor therapy in patients with septic shock.
authors.affiliation: Barts and The London School of Medicine and Dentistry, Queen Mary's University of London, London, United Kingdom.
authors.forename: Shaman
authors.initials: S
authors.lastname: Jhanji
authors.forename: Sarah
authors.initials: S
authors.lastname: Stirling
authors.forename: Nakul
authors.initials: N
authors.lastname: Patel
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Hinds
authors.forename: Rupert M
authors.initials: RM
authors.lastname: Pearse
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage* / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects*; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D010100:Oxygen; D009638:Norepinephrine