Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide.
OBJECTIVE
To determine whether inhalation of nitric oxide (INO) can increase the frequency of reversal of acute lung injury (ALI) in nitric oxide (NO) responders.


METHODS
Prospective, open, randomised, multicentre, parallel group phase III trial.


METHODS
General ICUs in 43 university and regional hospitals in Europe.


METHODS
Two hundred and sixty-eight adult patients with early ALI.


METHODS
NO responders were patients whose PaO(2) increased by more than 20 % when receiving 0, 2, 10 and 40 ppm of INO for 10 min within 96 h of study entry. Responders were randomly allocated to conventional treatment with or without INO. INO, 1-40 ppm, was given at the lowest effective dose for up to 30 days or until an end point was reached. The primary end point was reversal of ALI. Clinical outcome parameters and safety were assessed in all patients.


RESULTS
Two hundred and sixty-eight patients were recruited, of which 180 were randomised NO responders. Frequency of reversal of ALI was no different in INO patients (61 %) and controls (54 %; p > 0.2). Development of severe respiratory failure was lower in the INO (2.2 % ) than controls (10.3 %; p < 0.05). The mortality at 30 days was 44 % for INO patients, 40 % for control patients (p > 0.2 vs INO) and 45 % in non-responders.


CONCLUSIONS
Improvement of oxygenation by INO did not increase the frequency of reversal of ALI. Use of inhaled NO in early ALI did not alter mortality although it did reduce the frequency of severe respiratory failure in patients developing severe hypoxaemia.
Lundin
S
S
Department of Anaesthesia and Intensive Care, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. stefan.lundin@medfak.gu.se
Mang
H
H
Smithies
M
M
Stenqvist
O
O
Frostell
C
C
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008708:Methemoglobinemia / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D014665:Vasodilator Agents; D009569:Nitric Oxide