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Inhaled NO in ALI / ARDS

(European inhaled NO in ALI study)

Citation/s: Lundin S. Mang H. Smithies M. Stenqvist O. Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Medicine 1999 25(9):911-9.

 
Lead author's name: Lundin S et al

Three-part Clinical Question:

1.      Patients-Acute lung injury with PaO₂/ F_IO₂ ratio of < 22kPa (165mmHg) ventilated for 18-96 hours from the development of ALI.

2.      The treatment- Inhaled NO.

3.      The outcome- Reversal of ALI and mortality.

Search Terms: ARDS; treatment nitric oxide; inhaled

The Study: Non-blinded randomised controlled trial without intention-to-treat.

The Study Patients: ALI using PaO₂ / FiO₂ <22kPa (165mmHg) criteria (which would now be considered ARDS) for 19-96 hours. PAOP <18mmHg, PEEP > 5mmHg, mean airway pressure >10cmH₂O, I:E 2:1 to 1:2
Control group (N = 87; ?87 analysed): "Conventional ventilation" as above. Ventilatory mode not fully controlled. Patients were required to have a significant response to dose titration before trial enrolment.
Experimental group (N = 93; ?93 analysed): "Conventional ventilation" as above plus dose titration for inhaled NO. Patients were required to have a significant response to dose titration before trial enrolment.

The Evidence:

Comments:
Study was stopped early due to slow recruitment and had a major protocol change after recruitment of 140 patients. Patient who did not respond to inhaled NO dose titration were not included in trial and were not analysed with outcome data. It thus was not well designed and was not powered to detect a change in mortality although the trend was towards a worse outcome in the treatment group.

EBM questions:

1. Do the methods allow the adequate testing of the hypothesis? No, inadequate patient number and change in trial protocol make methods inadequate to test this hypothesis
2. Do the statistical tests correctly test the results to allow differentiation of statistically significant result? Stats are correct but are testing inadequate data.
3. Are conclusions valid in light of results? No.
4. Did results get omitted, and why? Patients who did not respond to inhaled NO test dose were excluded from main analysis.
5. Did they suggest areas of further research? “Metabolism and uptake of inhaled NO in ALI, sepsis and MODS. Study the relationship between inhaled NO and renal replacement therapy requirement”.
6. Did they make recommendations based on results and were they appropriate? Further research required as stated above.
7. Is this study relevant to my clinical practice? Yes, subject and patients are relevant.
8. What level of evidence does this study represent? Level 1^-.
9. What grade of recommendation can I make on this result alone? Grade B
10. What grade of recommendation can I make when this study is considered along with other available evidence? Grade A
11. Should I change my practice because of these results? No, this study suggests that inhaled NO should not be used in all-comers with ALI / ARDS without further evidence. Compassionate use of inhaled NO in severe respiratory failure could be justified on grounds of improved oxygenation result in this and Dellinger study.
12. Should I audit my current practice because of these results? If you use inhaled NO you should audit your results and outcomes.

Appraised by: Dr Brian H Cuthbertson, ICU, Aberdeen Royal Infirmary, ARI. ; 23 February 2004

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

Kill or Update By: February 2006

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