title: Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study.
abstract: BACKGROUND
  Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation.
  
  
  METHODS
  Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (DeltaPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated.
  
  
  RESULTS
  Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and DeltaPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001).
  
  
  CONCLUSIONS
  Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.
authors.affiliation: Servicio de Terapia Intensiva, Sanatorio Otamendi y Miroli, Buenos Aires C1115AAB, Argentina. arnaldodubin@speedy.com.ar
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Dubin
authors.forename: Mario O
authors.initials: MO
authors.lastname: Pozo
authors.forename: Christian A
authors.initials: CA
authors.lastname: Casabella
authors.forename: Fernando
authors.initials: F
authors.lastname: Pálizas
authors.forename: Gastón
authors.initials: G
authors.lastname: Murias
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Moseinco
authors.forename: Vanina S
authors.initials: VS
authors.lastname: Kanoore Edul
authors.forename: Fernando
authors.initials: F
authors.lastname: Pálizas
authors.forename: Elisa
authors.initials: E
authors.lastname: Estenssoro
authors.forename: Can
authors.initials: C
authors.lastname: Ince
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000368:Aged; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009060:Mouth Floor / Q000098:blood supply*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D009638:Norepinephrine