Randomized controlled trial of inhaled nitric oxide for the treatment of
microcirculatory dysfunction in patients with sepsis*.
Author(s): Trzeciak S(1), Glaspey LJ, Dellinger RP, Durflinger P, Anderson K, Dezfulian C,
Roberts BW, Chansky ME, Parrillo JE, Hollenberg SM.
Affiliation(s): Author information:
(1)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.
Publication date & source: 2014, Crit Care Med. , 42(12):2482-92
OBJECTIVES: 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.
DESIGN: Randomized, sham-controlled clinical trial.
SETTING: Single urban academic medical center.
PATIENTS: 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.
INTERVENTIONS: 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.
MEASUREMENTS AND MAIN 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.
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