Abstract
Background:
Inhaled nitric oxide (INO) improves arterial oxygen tension-to inspired oxygen fraction ratio (PaO2/FIO2) and reduces the intensity of ventilator therapy over 4 days without further improvements in PaO2/FIO2.1 This implies the presence of a therapeutic plateau versus diminished effect (although enhanced sensitivity paradoxically reduces INO effectiveness after 4 days). 2 Because AP improves PaO2/FIO2 through a similar pathway we inquired whether AP has a similar response profile.
Methods:
Using data from a previous study, 3 we examined 14 AP responders (defined as increased PaO2/FIO2 >10 mm Hg) with lung injury score of 3.2 ± 0.5 who had: 1) AP therapy > 48 h, 2) arterial blood gas and ventilator data available pre therapy: within 2.2 ± 2.0 h post initiation (H-0) and at 24, 36, 48 and 60 h (± 4.0 h) thereafter, 3) no recruitment maneuvers or prone positioning. AP was initiated at 50 ng/kg per min. Data were expressed as either mean (± SD) or median [IQR] for normally and non-normally distributed data respectively. Paired comparisons used Wilcoxon Signed Rank tests; multiple comparisons used either ANOVA: Tukey-Kramer post-tests or Kruskal-Wallis and Dunn's post-tests. Alpha was set 0.05.
Results:
AP initially increased PaO2/FIO2 by 34 mm Hg, (P < 0.001) and decreased oxygenation index (OI) by 8 (P = 0.001) at the same FIO2 and PEEP. After H-0, FIO2 decreased significantly without corresponding changes in PEEP, PaO2/FIO2 or oxygenation index (OI) (Table).
Conclusions:
The oxygenation profile of AP in ARDS was similar to that reported for INO, 1 suggesting the absence of tachyphylaxis within 60 h. Rather, a therapeutic plateau likely exists due to local endothelial receptor site saturation in limited aerated lung tissue.
1. Dellinger RP, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome. Crit Care Med 1998;26(1):15-23. 2. Gerlach H, et al. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2003;167:1008-1015. 3. Kallet RH, et al. Severity of hypoxemia and other factors that influence the response to aerosolized prostacyclin in ARDS. Respir Care 2017;62(8):1014-1022.
*P< 0.001 vs. FiO2 at 24,36,48 and 60h post therapy initiation View all access options for this article.
Post Rx or H-0
Post 24h
Post 36h
Post 48h
Post 60h
P
Dose (ng/kg per m
50 [50,50]
50 [50,50]
50 [50,50]
50 [50,50]
50 [50,50]
0.55
FiO2
1 [0.9,1]*
0.7 [0.6,0.8]
0.7 [0.6,0.8]
0.7 [0.6,0.9]
0.7 [0.6,0.8]
<0.001
PEEP (cmH2O)
15.7±3.8
15.2±3.5
14.9±4.0
14.6±4.1
15.0±3.6
0.95
PaO2/FiO2 (mmHg)
117 [95,123]
144 [131,258]
110 [93,310]
103 [91,198]
115 [90,138]
0.43
OI
20.3±7.7
15.6±7.7
18.3±7.8
19.0±6.3
19.8±5.6
0.43
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