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Inhaled NO in ARDS

Citation/s: Dellinger RP. Zimmerman JL. Taylor RW. Straube RC. Hauser DL. Criner GJ. Davis K Jr. Hyers TM. Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Critical Care Medicine 1998; 26(1):15-23.

Lead author's name and fax: Dellinger RP et al

Three-part Clinical Question:

1.      The patients- All-comers with ARDS

2.      The treatment- Inhaled NO therapy

3.      The outcome- Safety and efficacy

Search Terms: ARDS; Treatment; Inhaled NO

The Study:
Double-blinded concealed randomised controlled trial with intention-to-treat.

The Study Patients: ARDS according to American European Definitions within 72 hours (excluded patients with hypotension, vasopressor requirement and multi-organ failure)
Control group (N = 54; 54 analysed): Placebo, ventilatory mode not fully controlled

Experimental group (N = 120; 120 analysed): Inhaled NO at varying doses, ventilation mode not fully controlled

The Evidence:

Comments:
The study is a safety and efficacy study and does show safety and possible efficacy in the 5ppm dose group (significance of efficacy effect lost when allowance for multiple comparisons made). It is also the largest trial to date of inhaled NO and the only one that double blinds the therapy allocation.  

EBM summary questions:

1. Do the methods allow the adequate testing of the hypothesis? This is a safety and efficacy study and is designed the show efficacy and safety and not mortality based outcomes. It is a well-designed phase II study and demonstrates safety and efficacy of inhaled NO therapy especially at the 5ppm dose.
2. Do the statistical tests correctly test the results to allow differentiation of statistically significant result? Yes.
3. Are conclusions valid in light of results? Yes, although the 5ppm analysis was post-hoc but essentially acted as a hypothesis / dose generating analysis.
4. Did results get omitted, and why? Of the 177 patients recruited 56 patients had treatment gas discontinued before reaching trial end point but seem to have been analysed for mortality and gas exchange changes. 
5. Did they suggest areas of further research? “Additional studies ideally need to standardize concomitant therapies, ventilator management, and respiratory therapy (ventilators, patient positioning, NO delivery devices, etc.) as much as possible to clearly define the role of inhaled NO in the treatment of patients with ARDS”.
6. Did they make recommendations based on results and were they appropriate? “These findings need to be confirmed in other efficacy trials. These recommendations seem appropriate.
7. What level of evidence does this study represent? Level 1^-
8. What grade of recommendation can I make on this result alone? Grade B 
9. What grade of recommendation can I make when this study is considered along with other available evidence? Grade A
10. Should I change my practice because of these results? No, further evidence is required before using inhaled NO in current practice. It should also be noted that the trial excluded patients with hypotension, vasopressor requirement and multi-organ failure. As the majority of Scottish patients with ARDS have sepsis this makes the applicability of the study results to our patient limited.
11. Should I audit my current practice because of these results? If you are using inhaled NO you should audit your use and outcomes.

Appraised by: Dr Brian H Cuthbertson, Intensive Care Unit, Aberdeen Royal Infirmary; 07 July 2003.

Email: b.h.cuthbertson@abdn.ac.uk

Kill or Update By: July 2007

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