title: Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*.
abstract: OBJECTIVE
  Sepsis treatment guidelines recommend macrocirculatory hemodynamic optimization; however, microcirculatory dysfunction is integral to sepsis pathogenesis. We aimed to test the hypothesis that following macrocirculatory optimization, inhaled nitric oxide would improve microcirculation in patients with sepsis and that improved microcirculation would improve lactate clearance and multiple organ dysfunction.
  
  
  METHODS
  Randomized, sham-controlled clinical trial.
  
  
  METHODS
  Single urban academic medical center.
  
  
  METHODS
  Adult patients with severe sepsis and systolic blood pressure less than 90 mm Hg despite intravascular volume expansion and/or serum lactate greater than or equal to 4.0 mmol/L.
  
  
  METHODS
  After achievement of macrocirculatory resuscitation goals, we randomized patients to 6 hours of inhaled nitric oxide (40 ppm) or sham inhaled nitric oxide administration. We administered study drug via a specialized delivery device that concealed treatment allocation so that investigators and clinical staff remained blinded.
  
  
  RESULTS
  We performed sidestream dark-field videomicroscopy of the sublingual microcirculation prior to and 2 hours after study drug initiation. The primary outcome measure was the change in microcirculatory flow index. Secondary outcomes were lactate clearance and change in Sequential Organ Failure Assessment score. We enrolled 50 patients (28 of 50 [56%] requiring vasopressor agents; 15 of 50 [30%] died). Although inhaled nitric oxide significantly raised plasma nitrite levels, it did not improve microcirculatory flow, lactate clearance, or organ dysfunction. In contrast to previous studies conducted during the earliest phase of resuscitation, we found no association between changes in microcirculatory flow and lactate clearance or organ dysfunction.
  
  
  CONCLUSIONS
  Following macrocirculatory optimization, inhaled nitric oxide at 40 ppm did not augment microcirculatory perfusion in patients with sepsis. Further, we found no association between microcirculatory perfusion and multiple organ dysfunction after initial resuscitation.
authors: 1Division of Critical Care Medicine, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ. 2Department of Critical Care Medicine and The Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA. 3Department of Emergency Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ. 4Division of Cardiovascular Disease, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ.
authors: Stephen
authors: S
authors: Trzeciak
authors: Lindsey J
authors: LJ
authors: Glaspey
authors: R Phillip
authors: RP
authors: Dellinger
authors: Paige
authors: P
authors: Durflinger
authors: Keith
authors: K
authors: Anderson
authors: Cameron
authors: C
authors: Dezfulian
authors: Brian W
authors: BW
authors: Roberts
authors: Michael E
authors: ME
authors: Chansky
authors: Joseph E
authors: JE
authors: Parrillo
authors: Steven M
authors: SM
authors: Hollenberg
mesh_terms: D000046:Academic Medical Centers; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D019344:Lactic Acid / Q000097:blood; D007902:Length of Stay; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009060:Mouth Floor / Q000098:blood supply; D009102:Multiple Organ Failure / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology*; D012121:Respiration, Artificial; D012151:Resuscitation; D018805:Sepsis / Q000097:blood / Q000628:therapy*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019344:Lactic Acid