Inhaled Nitric Oxide in Patients With Acute Respiratory Distress Syndrome: An End to the Debate?* Daniel J. Niven, MD, MSc, FRCPC Department of Critical Care Medicine University of Calgary and Alberta Health Services Calgary, AB, Canada; and Department of Community Health Sciences Institute for Public Health University of Calgary Calgary, AB, Canada
end-expiratory pressure, inverse-ratio ventilation, and highfrequency oscillation), optimizing delivery of positive pressure to the diseased, dependent lung units through prone ventilation, selective pulmonary vasodilation through inhaled nitric oxide, and extraeorporeal membrane oxygénation (3). Unfortunately, while many of these interventions result in improved arterial oxygénation, few are associated with a survival benefit. This includes the use of inhaled nitric oxide. Following the discovery of its role in vascular biology, Henry T. Stelfox, MD, PhD, FRCPC inhaled nitric oxide was rapidly adopted for the treatment of Department of Critical Care Medicine; ARDS due to the belief that selective pulmonary vasodilation Department of Medicine within ventilated lung units would improve gas exchange and University of Calgary and Alberta Health Services therefore outcomes (4). Its efficacy in ARDS was examined in Calgary, AB, Canada; and several randomized clinical trials and has been the subject of at Department of Community Health Sciences least five meta-analyses. Although it is clear that inhaled nitric Institute for Public Health oxide transiently improves arterial oxygénation (5-7), no study University of Calgary has demonstrated a clinically-relevant benefit in patients with Calgary, AB, Canada ARDS (e.g., survival and duration of mechanical ventilation). Furthermore, three meta-analyses demonstrate that nitric oxide is associated with an increased risk of renal impairment he acute respiratory distress syndrome (ARDS) is (5-7). In spite of this risk/benefit imbalance, nitric oxide condefined by an acute onset of hypoxemia (Pao,/Fio, ratio tinues to be used in up to 14% of patients with ARDS (6, 8). < 300 mm Hg) and bilateral pulmonary opacities that This is at least partially due to the belief among intensivists are not due to cardiac failure or hydrostatic edema (1). Recent that the greatest benefit resides with patients suffering from data suggest that the prevalence of ARDS may be decreasing severe hypoxemia, a subgroup that has been underrepresented due to a reduction in hospital-acquired cases (2); however, estiin clinical trials (9). mates of case fatality remain high (30-40%) (1,2). In this issue of Critical Care Medicine, Adhikari et al (10) Hypoxemia in ARDS occurs as a result of ventilation-perfiibuild upon the results of a previous systematic review and sion mismatch due to the accumulation of inflammatory debris meta-analysis (5) by obtaining patient-level data to examine within the alveolar space and consequential asymmetry in pulwhether inhaled nitric oxide improves survival in patients monary vascular reactivity (i.e., vasoconstriction within norwith severe hypoxemia (Pao^/Fio, < 100 mm Hg) compared mal lung parenchyma and vasodilation within diseased lung) with those with mild to moderate hypoxemia (Pao^/Fio, > (1). It is generally categorized as mild (200 mm Hg < Pao^/Fio^ < 100 mm Hg). Among the nine clinical trials that met the crite300mm Hg), moderate (100 mm Hg < Pao/Fio^
end-expiratory pressure, inverse-ratio ventilation, and highfrequency oscillation), optimizing delivery of positive pressure to the diseased, dependent lung units through prone ventilation, selective pulmonary vasodilation through inhaled nitric oxide, and extraeorporeal membrane oxygénation (3). Unfortunately, while many of these interventions result in improved arterial oxygénation, few are associated with a survival benefit. This includes the use of inhaled nitric oxide. Following the discovery of its role in vascular biology, Henry T. Stelfox, MD, PhD, FRCPC inhaled nitric oxide was rapidly adopted for the treatment of Department of Critical Care Medicine; ARDS due to the belief that selective pulmonary vasodilation Department of Medicine within ventilated lung units would improve gas exchange and University of Calgary and Alberta Health Services therefore outcomes (4). Its efficacy in ARDS was examined in Calgary, AB, Canada; and several randomized clinical trials and has been the subject of at Department of Community Health Sciences least five meta-analyses. Although it is clear that inhaled nitric Institute for Public Health oxide transiently improves arterial oxygénation (5-7), no study University of Calgary has demonstrated a clinically-relevant benefit in patients with Calgary, AB, Canada ARDS (e.g., survival and duration of mechanical ventilation). Furthermore, three meta-analyses demonstrate that nitric oxide is associated with an increased risk of renal impairment he acute respiratory distress syndrome (ARDS) is (5-7). In spite of this risk/benefit imbalance, nitric oxide condefined by an acute onset of hypoxemia (Pao,/Fio, ratio tinues to be used in up to 14% of patients with ARDS (6, 8). < 300 mm Hg) and bilateral pulmonary opacities that This is at least partially due to the belief among intensivists are not due to cardiac failure or hydrostatic edema (1). Recent that the greatest benefit resides with patients suffering from data suggest that the prevalence of ARDS may be decreasing severe hypoxemia, a subgroup that has been underrepresented due to a reduction in hospital-acquired cases (2); however, estiin clinical trials (9). mates of case fatality remain high (30-40%) (1,2). In this issue of Critical Care Medicine, Adhikari et al (10) Hypoxemia in ARDS occurs as a result of ventilation-perfiibuild upon the results of a previous systematic review and sion mismatch due to the accumulation of inflammatory debris meta-analysis (5) by obtaining patient-level data to examine within the alveolar space and consequential asymmetry in pulwhether inhaled nitric oxide improves survival in patients monary vascular reactivity (i.e., vasoconstriction within norwith severe hypoxemia (Pao^/Fio, < 100 mm Hg) compared mal lung parenchyma and vasodilation within diseased lung) with those with mild to moderate hypoxemia (Pao^/Fio, > (1). It is generally categorized as mild (200 mm Hg < Pao^/Fio^ < 100 mm Hg). Among the nine clinical trials that met the crite300mm Hg), moderate (100 mm Hg < Pao/Fio^
