Effect of Inhaled Nitric Oxide on Outcomes in Children With Acute Lung Injury: Propensity Matched Analysis From a Linked Database. (Chaudhary)

Gupta P, Richardson T, Hall M, Bertoch D, Hebbar KB, Fortenberry JD, Wetzel
RC. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. Crit Care Med. 2016 Oct;44(10):1901-9.

OBJECTIVES: To evaluate the effect of inhaled nitric oxide on outcomes in children with acute lung injury.

DESIGN: Retrospective study with a secondary data analysis of linked data from two national databases. Propensity score matching was performed to adjust for potential confounding variables between patients who received at least 24 hours of inhaled nitric oxide (inhaled nitric oxide group) and those who did not receive inhaled nitric oxide (no inhaled nitric oxide group).

SETTING: Linked data from Virtual Pediatric Systems (LLC) database and Pediatric Health Information System.

PATIENTS: Patients less than 18 years old receiving mechanical ventilation for acute lung injury at nine participating hospitals were included (2009-2014).


MEASUREMENTS AND MAIN RESULTS: A total of 20,106 patients from nine hospitals were included. Of these, 859 patients (4.3%) received inhaled nitric oxide for at least 24 hours during their hospital stay. Prior to matching, patients in the inhaled nitric oxide group were younger, with more comorbidities, greater severity of illness scores, higher prevalence of cardiopulmonary resuscitation, and greater resource utilization. Before matching, unadjusted outcomes, including mortality, were worse in the inhaled nitric oxide group (inhaled nitric oxide vs no inhaled nitric oxide; 25.7% vs 7.9%; p < 0.001; standardized mortality ratio, 2.6 [2.3-3.1] vs 1.1 [1.0-1.2]; p < 0.001). Propensity score matching of 521 patient pairs revealed no difference in mortality in the two groups (22.3% vs 20.2%; p = 0.40; standardized mortality ratio, 2.5 [2.1-3.0] vs 2.3 [1.9-2.8]; p = 0.53). However, the other outcomes such as ventilation free days (10.1 vs 13.6 d; p < 0.001), duration of mechanical ventilation (13.8 vs 10.1 d; p < 0.001), duration of ICU and hospital stay (15.5 vs 12.2 d; p < 0.001 and 28.0 vs 24.1 d; p < 0.001), and hospital costs ($150,569 vs $102,823; p < 0.001) were significantly worse in the inhaled nitric oxide group.

CONCLUSIONS: This large observational study demonstrated that inhaled nitric oxide administration in children with acute lung injury was not associated with improved mortality. Rather, it was associated with increased hospital utilization and hospital costs.

Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis. (Dugan)

Trzeciak S, Glaspey LJ, Dellinger RP, et al. Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*. Crit Care Med. 2014 Dec;42(12):2482-92.

Full-text for Children’s and Emory users.

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.

Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients. (Stockwell)

J Crit Care. 2013 May 14. pii: S0883-9441(13)00067-1. PMID: 23683572

PURPOSE: The purpose of this is to compare efficacy, safety, and cost outcomes inpatients who have received either inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) for hypoxic respiratory failure.

MATERIALS AND METHODS: This is a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iNO or iEPO for improvement in oxygenation.

RESULTS: We evaluated 105 mechanically ventilated patients who received iEPO (52patients) or iNO (53 patients) between January 2009 and October 2010. Most patientsreceived therapy for acute respiratory distress syndrome (iNO 58.5% vs iEPO 61.5%; P = .84). There was no difference in the change in the partial pressure of arterial O2/fraction of inspired O2 ratio after 1 hour of therapy (20.58 ± 91.54 vs 33.04 ± 36.19 [P = .36]) in the iNO and iEPO groups, respectively. No difference was observed in duration of therapy (P = .63), mechanical ventilation (P = .07), intensive care unit (P = .67), and hospital lengths of stay (P = .26) comparing the iNO and iEPO groups. No adverse events were attributed to either therapy. Inhaled nitric oxide was 4.5 to 17 times more expensive than iEPO depending on contract pricing.

CONCLUSIONS: We found no difference in efficacy and safety outcomes when comparing iNO and iEPO in hypoxic, critically ill patients. Inhaled epoprostenol is associated with less drug expenditure than iNO.

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