Inhaled nitric oxide in acute respiratory failure in adults. Inhaled nitric oxide in acute respiratory distress syndrome. Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo. Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure. 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. Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome Inhaled nitric oxide in children with severe lung disease: results of acute and prolonged therapy with two concentrations. Short-term effects of inhaled nitric oxide and prone position in pulmonary and extrapulmonary acute respiratory distress syndrome. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Effects of inhaled nitric oxide compared with aspirin on platelet function in vivo in healthy subjects. Randomized, placebo-controlled, blinded and cross-matched study on the antiplatelet effect of inhaled nitric oxide in healthy volunteers. Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Combination of inhaled nitric oxide therapy and inverse ratio ventilation in patients with sepsis-associated acute respiratory distress syndrome. The adult respiratory distress syndrome. A report of survival and modifying factors. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study A randomized, controlled study of the 1-hour and 24-hour effects of inhaled nitric oxide therapy in children with acute hypoxemic respiratory failure. Inhaled nitric oxide in acute respiratory failure: Dose-response curves Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome Combined effects of inhaled nitric oxide and positive end-expiratory pressure during mechanical ventilation in acute respiratory distress syndrome. Prone positioning and inhaled nitric oxide: synergistic therapies for acute respiratory distress syndrome. Prolonged Inhalation of Low Concentrations of Nitric Oxide in Patients with Severe Adult Respiratory Distress Syndrome: Effects on Pulmonary Hemodynamics and Oxygenation Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Inhaled nitric oxide for the adult respiratory distress syndrome. Additive Effect of Nitric Oxide Inhalation on the Oxygenation Benefit of the Prone Position in the Adult Respiratory Distress Syndrome Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. Combined nitric oxide inhalation, prone positioning and almitrine infusion improve oxygenation in severe ARDS
We have assessed the acute effects of inhaled nitric oxide 8 , 32 and 128 volumes per million ( vpm ) on pulmonary haemodynamics and arterial oxygenation in patients with severe acute respiratory failure . Fourteen patients requiring artificial ventilation with mean pulmonary artery pressures greater than 30 mm Hg were given inhaled nitric oxide ; haemodynamic values and blood-gas tensions were measured before and after 10 min of inhalation of nitric oxide . Nitric oxide inhaled at 8 , 32 and 128 vpm decreased mean pulmonary artery pressure by 1.7 ( SD 2.2 ) , 3.2 ( 2.6 ) and 3.3 ( 3.3 ) mm Hg , pulmonary vascular resistance by 20 ( 64 ) , 53 ( 57 ) and 66 ( 54 ) dyn s cm-5 and increased arterial oxygen tension by 2.5 ( 3.6 ) , 3.0 ( 5.1 ) and 2.9 ( 3.9 ) kPa , respectively . All changes were significant ( P < 0.05 or less ) except for changes in pulmonary vascular resistance at 8 vpm . The improvement in arterial oxygenation with 128 vpm was related to pulmonary vascular resistance before commencing nitric oxide . The major beneficial effect of nitric oxide in acute respiratory failure would appear to be improvement in oxygenation rather than reduction in pulmonary artery pressure . The degree of improvement in arterial oxygenation with nitric oxide was related directly to pulmonary vascular resistance before treatment BACKGROUND Inhaled nitric oxide has been shown to improve oxygenation in select patients with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE The purpose of this study was to evaluate the clinical response to four concentrations of inhaled nitric oxide ( NO ) in 20 patients with ARDS . METHODS All patients with ARDS were eligible for the study . ARDS was defined as ( 1 ) the presence of a predisposing factor ; ( 2 ) a PaO2/FiO2 ratio < 200 ; ( 3 ) bilateral infiltrates on chest radiograph ; and ( 4 ) absence of evidence of congestive heart failure and pulmonary artery wedge pressure < 18 mm Hg . Patients received each of four doses ( 1 , 15 , 30 , and 60 ppm ) in r and om order , each for a 3-hour period . Cardiovascular variables were continuously monitored , and arterial and mixed venous blood gas measurements were obtained at 30 minutes and 3 hours . RESULTS Thirteen of the 20 patients demonstrated a significant increase in their PaO2/FiO2 ( > 20 % increase ) when treated with inhaled NO . The administration of inhaled NO was associated with an increase in oxygenation at doses of 1 , 15 , and 30 ppm , but not 60 ppm . Increasing NO dose to more than 1 ppm did not significantly improve response . Mean pulmonary artery pressure decreased with increasing NO concentration , but this did not reach statistical significance . Nine of the 13 responding patients and 2 of the 7 nonresponding patients survived . CONCLUSION Inhaled NO was successful in increasing PaO2/FiO2 by > 20 % in 65 % of the surgical patients in this trial . Response to NO could not be predicted by initial PaO2/FiO2 or pulmonary artery pressures . A trial of inhaled NO at a dose of < 10 ppm may be helpful in ARDS patients requiring increasing FiO2 and positive end-expiratory pressure BACKGROUND Recent data suggest that inhaled NO can inhibit platelet aggregation .  This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation . METHODS AND RESULTS In 30 healthy volunteers , platelet-rich plasma was incubated with an air/5 % CO2 mixture containing 0 , 100 , 450 , and 884 ppm inhaled NO . ADP- and collagen-induced platelet aggregation , the membrane expression of P-selectin , and the binding of fibrinogen to the platelet glycoprotein ( GP ) IIb/IIIa receptor were determined before ( t0 ) and during the 240 minutes of incubation . In addition , eight patients suffering from severe adult respiratory distress syndrome ( ARDS ) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO . In vitro , NO led to a dose-dependent inhibition of both ADP-induced ( 3+/-3 % at 884 ppm versus 70+/-6 % at 0 ppm after 240 minutes ; P<.001 ) and collagen-induced ( 13+/-5 % versus 62+/-5 % ; P<.01 ) platelet aggregation . Furthermore , P-selectin expression ( 36+/-7 % of t0 value ; P<.01 ) and fibrinogen binding ( 33+/-11 % ; P<.01 ) were inhibited . In patients with ARDS , after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded , an increase in plasma cGMP , prolongation of in vitro bleeding time , and inhibition of platelet aggregation and P-selectin expression were observed , and fibrinogen binding was also inhibited ( 19+/-7 % versus 30+/-8 % ; P<.05 ) . CONCLUSIONS NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor The aim of this prospect i ve study was to determine factors influencing effects of inhaled nitric oxide ( NO ) on the pulmonary circulation and on gas exchange in critically ill patients with acute lung injury . Twenty-one hypoxemic patients with acute respiratory failure ( PaO2 = 127 + /- 69 mm Hg during intermittent positive pressure ventilation , FiO2 = 1 ) , were mechanically ventilated with 2 ppm NO and pure oxygen . The effect of positive end-expiratory pressure ( PEEP ) on alveolar recruitment was assessed on an anatomic basis using a high-resolution and spiral thoracic computed tomographic ( CT ) scan . Four conditions were studied in r and om order : zero end-expiratory pressure ( ZEEP ) , ZEEP + 2 ppm NO , 10 cm H2O PEEP , 10 cm H2O PEEP + 2 ppm NO . During ZEEP and PEEP , NO significantly decreased pulmonary vascular resistance index ( PVRI ) , mean pulmonary arterial pressure ( MPAP ) , true pulmonary shunt ( Qs/QT ) , and alveolar dead space ( VDA/VT ) and significantly increased PaO2 ( p < 0.01 ) . During ZEEP , NO-induced decreases in PVRI ( delta PVRI ) and MPAP ( delta MPAP ) were significantly correlated to baseline PVRI and MPAP ( delta PVRI = -0.5 PVRI + 125 , r = 0.97 , p < 0.01 and delta MPAP = -0.28 MPAP + 4.8 , r = 0.69 , p < 0.05 ) . These changes were not potentiated by PEEP-induced alveolar recruitment . The NO-induced increase in PaO2 ( delta PaO2 ) was not significantly correlated with baseline PaO2 but was correlated with baseline PVRI ( delta PaO2 = 0.11 PVRI + 30 , r = 0.67 , p < 0.05 ) . In patients in whom PEEP was associated with alveolar recruitment , NO increased PaO2 by 66 + /- 24 mm Hg during ZEEP and by 104 + /- 26 mm Hg during PEEP ( p < 0.01 ) . In patients in whom PEEP did not induce alveolar recruitment , the NO-induced increase in PaO2 was similar during ZEEP and PEEP conditions ( + 70 + /- 15 mm Hg versus + 76 + /- 12 mm Hg , NS ) . In patients with adult respiratory distress syndrome , factors determining NO-induced improvement in arterial oxygenation and pulmonary vascular effects are PEEP-induced alveolar recruitment and the baseline level of pulmonary vascular resistance OBJECTIVES To evaluate the safety and physiologic response of inhaled nitric oxide ( NO ) in patients with acute respiratory distress syndrome ( ARDS ) . In addition , the effect of various doses of inhaled NO on clinical outcome parameters was assessed . DESIGN Prospect i ve , multicenter , r and omized , double-blind , placebo-controlled study . SETTING Intensive care units of 30 academic , teaching , and community hospitals in the United States . PATIENTS Patients with ARDS , as defined by the American-European Consensus Conference , were enrolled into the study if the onset of disease was within 72 hrs of r and omization . INTERVENTIONS Patients were r and omized to receive placebo ( nitrogen gas ) or inhaled NO at concentrations of 1.25 , 5 , 20 , 40 , or 80 ppm . MEASUREMENTS AND MAIN RESULTS Acute increases in PaO2 , decreases in mean pulmonary arterial pressure , intensity of mechanical ventilation , and oxygenation index were examined . Clinical outcomes examined were the dose effects of inhaled NO on mortality , the number of days alive and off mechanical ventilation , and the number of days alive after meeting oxygenation criteria for extubation . A total of 177 patients were enrolled over a 14-month period . An acute response to treatment gas , defined as a PaO2 increase > or = 20 % , was seen in 60 % of the patients receiving inhaled NO with no significant differences between dose groups . Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs . The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment , as measured by the oxygenation index . There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate , the number of days alive and off mechanical ventilation , or the number of days alive after meeting oxygenation criteria for extubation . However , patients receiving 5 ppm inhaled NO showed an improvement in these parameters . In this dose group , the percentage of patients alive and off mechanical ventilation at day 28 ( a post hoc analysis ) was higher ( 62 % vs. 44 % ) than the placebo group . There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo . Four patients had methemoglobin concentrations > 5 % . The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm . CONCLUSIONS From this placebo-controlled study , inhaled NO appears to be well tolerated in the population of ARDS patients studied . With mechanical ventilation held constant , inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment . An improvement in oxygenation index was observed over the first 4 days . Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome BACKGROUND Inhaled nitric oxide ( iNO ) is a potential therapeutic agent for the management of  acute respiratory distress syndrome ( ARDS ) . Concerns remain , however , regarding the potential toxicity from iNO and /or its oxidative derivatives and methaemoglobinaemia . AIMS To determine the risk of toxicity from iNO , which includes worsening of lung injury , a prospect i ve study evaluating the acute effects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit . INTERVENTION iNO was administered for one hour at three concentrations ( 1 , 10 , and 20 parts per million ( ppm ) ) in a r and om order of possible dosing schedules to avoid dose accumulation bias . Arterial blood gas , methaemoglobin concentrations , and haemodynamic parameters were obtained at baseline before commencement of iNO , at the end of each study hour , and after iNO was discontinued . Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study . RESULTS iNO significantly improved the oxygenation ratio ( Pao 2/Fio 2 ) from a mean ( SEM ) baseline of 11.9 ( 1.7 ) kPa to 20 ( 3.9 ) kPa , 24 ( 4.5 ) kPa , and 21.6 ( 3.9 ) kPa at 1 , 10 , and 20 ppm iNO , respectively . There was no significant difference in the improvement in oxygenation achieved between the three concentrations . Correspondingly , there was a significant improvement in oxygenation index ( pre-iNO 28.3 ( 5 ) v post-iNO 18 ( 3 ) ( 1 ppm ) , 15 ( 3 ) ( 10 ppm ) , 16 ( 3 ) ( 20 ppm ) ) . No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration . CONCLUSION The results show that a low concentration of iNO ( 1 ppm ) is as effective as higher concentrations ( 10 and 20 ppm ) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use OBJECTIVES To evaluate the acute effects of 11 and 60 parts per million ( ppm ) inhaled nitric oxide on the pulmonary vascular resistance and systemic oxygenation of children with severe lung disease , and to compare the outcome of prolonged therapy with approximately 10 and 40 ppm inhaled nitric oxide . DESIGN Prospect i ve , r and omized study . SETTING A 26-bed pediatric intensive care unit in a tertiary children 's hospital . PATIENTS Nineteen patients ( median age 11 yrs , range 7 months to 16 yrs ) with acute bilateral lung disease requiring a positive end-expiratory pressure ( PEEP ) of > 6 cm H2O and an FIO2 of > 0.5 for > 12 hrs were treated with inhaled nitric oxide .  One patient was treated twice during the same hospitalization . INTERVENTIONS Acute hemodynamic and blood gas effects of 11 and 60 ppm inhaled nitric oxide were studied , while delivering these concentrations in r and om order for intervals of 20 to 30 mins . Each interval was preceded by an interval of 20 to 30 mins without nitric oxide . Patients were then r and omized and treated for a prolonged period with approximately 10 or 40 ppm inhaled nitric oxide independent of their initial acute responses to 11 and 60 ppm . Nitric oxide was discontinued when ventilatory support was decreased to a PEEP of < or = 6 cm H2O and an FIO2 of < or = 0.5 . MEASUREMENTS AND MAIN RESULTS Inhaled nitric oxide selectively decreased pulmonary vascular resistance and improved systemic oxygenation . Acute hemodynamic and blood gas effects of 11 and 60 ppm nitric oxide were similar . Systemic oxygenation improved to a greater extent in patients with radiographic evidence of residual aerated lung regions than in patients with diffuse bilateral lung disease . Maximum methemoglobin concentrations were greater in patients treated for a prolonged period with 40 ppm nitric oxide . The mortality and duration of therapy were similar for patients treated with 10 and 40 ppm inhaled nitric oxide . CONCLUSIONS Pulmonary vascular resistance and systemic oxygenation are acutely improved to a similar extent by 11 and 60 ppm inhaled nitric oxide , and concentrations in excess of 10 ppm are probably not needed for prolonged therapy of children with severe lung disease Inhaled nitric oxide ( NO ) and prone position ( PP ) are frequently used in the treatment of acute respiratory distress syndrome ( ARDS ) . We compared the gas exchange and hemodynamic effects induced by the combination of NO inhalation and PP in patients with ARDS and analyzed whether or not pulmonary ( Pu ) and extrapulmonary ( Epu ) ARDS patients behave differently . Eight Pu and seven Epu ARDS patients were studied in four situations : supine position ( SP ) ; SP with NO inhalation at 5 ppm ( SP + NO ) ; PP ; and PP with NO inhalation ( PP + NO ) . In comparison with SP , NO inhalation and PP induced significant increases in Pa(O(2))/FI(O(2 ) ) ( from 106 + /- 58 in SP to 131 + /- 69 mm Hg in SP + NO , p = 0.01 , and to 184 + /- 67 mm Hg in PP , p < 0.001 ) . Pu and Epu ARDS showed a similar improvement in Pa(O(2))/FI(O2 ) with PP . Only Pu ARDS patients showed a significant increase ( p < 0.001 ) in oxygenation induced by NO inhalation from 81 + /- 45 to 100 + /- 50 mm Hg in SP , and from 146 + /- 53 to 197 + /- 98 mm Hg in PP . In conclusion , PP is associated with a marked improvement in oxygenation , irrespective of the causes of ARDS , and additive effects of NO inhalation are mainly seen in patients with Pu ARDS A r and omized , controlled clinical trial was performed with patients with acute respiratory distress syndrome ( ARDS ) to compare the effect of conventional therapy or inhaled nitric oxide ( iNO ) on oxygenation .  Patients were r and omized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses : ( 1 ) that iNO would improve oxygenation during the 72 h after r and omization , as compared with conventional therapy ; and ( 2 ) that iNO would increase the likelihood that patients would improve to the extent that the FI(O2 ) could be decreased by > or = 0.15 within 72 h after r and omization . There were two major findings . First , That iNO as compared with conventional therapy increased Pa(O2)/FI(O2 ) at 1 h , 12 h , and possibly 24 h. Beyond 24 h , the two groups had an equivalent improvement in Pa(O2)/FI(O2 ) . Second , that patients treated with iNO therapy were no more likely to improve so that they could be managed with a persistent decrease in FI(O2 ) > or = 0.15 during the 72 h following r and omization ( 11 of 20 patients with iNO versus 9 of 20 patients with conventional therapy , p = 0.55 ) . In patients with severe ARDS , our results indicate that iNO does not lead to a sustained improvement in oxygenation as compared with conventional therapy 1 . Nitric oxide has platelet-stabilizing effects . Inhaled nitric oxide is used to treat pulmonary disorders , and may prolong bleeding times , suggesting that it has effects on haemostasis . We therefore examined if inhaled nitric oxide influences platelet function in vivo in healthy subjects . 2 . Platelet aggregability ( filtragometry ex vivo , which reflects aggregability in vivo ) , bleeding time and platelet secretion products and cGMP in plasma were studied during inhalation of two different doses of nitric oxide ( 30 and 80 p.p.m . ; 15 min at each dose level ; n = 19 ) and during prolonged ( 55 min ; n = 18 ) inhalation of 30 p.p.m . nitric oxide . For comparison , studies were also performed before and after ingestion of 640 mg aspirin in 13 of the healthy subjects . 3 . Plasma cGMP increased dose dependently during nitric oxide inhalation , suggesting guanylate cyclase activation in vivo . Platelet aggregability was , however , little affected and platelet secretion was not attenuated by nitric oxide inhalation . Bleeding time tended to increase ( by 16 - 33 % ) , but was significantly increased only after prolonged inhalation of nitric oxide at 30 p.p.m . 4 . Aspirin ( 640 mg orally ) caused pronounced and significant prolongations of filtragometry readings and bleeding time . Thus , the methods used were able to reveal platelet stabilization . 5 . We conclude that nitric oxide inhalation causes only mild , if any , attenuation of platelet function  in healthy subjects with a normal endogenous nitric oxide production . The effects may be different in disease states The platelet inhibitory effect of 0 - 40 ppm inhaled nitric oxide ( NO ) was investigated in healthy men and women . In both groups , ADP- and collagen-induced platelet aggregation was significantly inhibited 20 ( T20 ) and 40 min ( T40 ) after the beginning of inhalation of 5 , 10 , and 40 ppm . Moreover , in both men and women , the in vitro bleeding time was significantly prolonged at T20 and T40 during inhalation of 40 ppm . Inhalation of NO also inhibited P-selectin expression at 5 , 10 , and 40 ppm and fibrinogen binding to the GPIIb/IIIa-receptor at 40 ppm . In conclusion , in healthy volunteers , the platelet inhibitory effect of inhaled NO was not dose-related , since it was significant at 5 and 10 ppm but did not increase during the administration of higher NO concentrations . In addition , gender-related differences were only observed in ADP-induced platelet aggregation at 10 ppm and in bleeding time prolongation at 40 ppm Objective To compare the effects of inhaled nitric oxide ( NO ) and an infusion of prostacyclin ( PGI2 ) on right ventricular function in patients with severe acute respiratory distress syndrome ( ARDS ) . Design R and omized prospect i ve short-term study . Setting : Post-surgical ICU in an university hospital . Patients 10 patients with severe ARDS referred to our hospital for intensive care . Interventions In r and om sequence the patients inhaled NO at a concentration of 18 parts per million ( ppm ) followed by 36 ppm , and received an intravenous infusion of PGI2 ( 4 ng·kg−1·min−1).Measurement and results Inhalation of 18 ppm NO reduced the means ( ±SE ) pulmonary artery pressure ( PAP ) from 33±2 to 28±1 mmHg ( p=0.008 ) , increased right ventricular ejection fraction ( RVEF ) , as assessed by thermodilution technique , from 28±2 to 32±2 % ( p=0.005 ) , decreased right ventricular end-diastolic volume index from 114±6 to 103±8 ml·m−2 ( p=0.005 ) and right ventricular end-systolic volume index from 82±4 to 70±5 ml·m−2 ( p=0.009 ) . Mean arterial pressure ( MAP ) and cardiac index ( CI ) did not change significantly . The effects of 36 ppm NO were not different from the effects of 18 ppm NO . Infusion of PGI2 reduced PAP from 34±2 to 30±2 mmHg ( p=0.02 ) , increased RVEF from 29±2 to 32±2 % ( p=0.02 ) . Right ventricular end-diastolic and end-systolic volume indices did not change significantly . MAP decreased from 80±4 to 70±5 mmHg ( p=0.03 ) , and CI increased from 4.0±0.5 to 4.5±0.5 l·min−1·m−2 ( p=0.02 ) . Conclusions Using a new approach to selective pulmonary vasodilation by inhalation of NO , we demonstrate in this groups of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI . The increase in CI during PGI2 infusion is probably related to the systemic effect of this substance This pilot r and omized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide ( inhNO ) on lung function , morbidity , and mortality .  Thirty patients with ARDS were r and omly allocated to usual care or usual care plus inhNO . The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily . All therapeutic interventions were st and ardized . ARDS result ed mainly from sepsis ( 25 of the 30 ) . During the first 24 h , the hypoxia score increased greatly in patients treated with inhNO + 70.4 mm Hg ( + 59 % ) versus + 14.2 mm Hg ( + 9.3 % ) for the control group ( p = 0.02 ) , venous admixture decreased from 25.7 to 15.2 % in the inhNO group , and from only 19.4 to 14.9 % in the control group ( p = 0.05 ) . After the first day of therapy no further beneficial effect of inhNO was detected . Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after r and omization compared with 33.3 % in the control group ( p = 0.83 ) . The 30-d mortality rate was similar in the two groups ; most deaths ( 11 of 17 ) were due to multiple organ dysfunction syndrome . This study shows that inhNO , in this population , may improve gas exchange but does not affect mortality Inverse ratio ventilation ( IRV ) is a ventilatory technique that uses an inspiratory to expiratory ratio ( I : E ) greater than 1:1 . We studied the effects of mechanical ventilation with an I : E of 1:3 , 1:1 , and 2:1 on arterial oxygenation in 10 patients with sepsis-associated acute respiratory distress syndrome ( ARDS ) . At each I : E , patients received 0 and 4 ppm of inhaled nitric oxide ( INO ) in r and om order for 30 min . Respiratory and cardiovascular parameters were measured . Of the 10 patients studied , 7 responded to IRV and 3 did not . An increase in the I : E and the addition of INO significantly improved arterial oxygenation in the responders ( p < 0 . 0001 and p < 0.006 , respectively ) . The combination of an increase in the I : E and INO had an additive effect on arterial oxygenation . The combined use of IRV and INO is a more effective method of avoiding hypoxemia than either INO or IRV alone The adult respiratory distress syndrome ( ARDS ) is a form of acute lung injury characterized by arterial hypoxemia , reduced thoracic compliance , normal pulmonary capillary wedge pressure , and diffuse infiltrates on chest roentgenograms . Mortality remains high and has been associated with sepsis , organ failure , age , and predisposing factors . We prospect ively identified 215 ARDS patients over 34 months to examine how these factors influence outcome . One hundred two ( 47 percent ) of 215 patients  survived . Age 65 years or older was associated with a survival of 34 percent , which was statistically different from the 53 percent survival of those patients younger than 65 years ( p = 0.02 ) . Aspiration pneumonia as a predisposing factor of ARDS was associated with a better survival ( p = 0.04 ) . Survivors had statistically less organ failure and sepsis than did nonsurvivors ( p less than 0.05 ) . Cause of death was determined using the criteria of Montgomery et al for irreversible organ dysfunction . Forty-five ( 40 percent ) of our patients died of respiratory failure ( not sepsis ) . We conclude the following : ( 1 ) survival in our ARDS patients is different from previous reports ; ( 2 ) the cause of death in our ARDS patients is different from that reported by Montgomery et al in 1985 ; and ( 3 ) multisystem organ failure , sepsis , age , and some predisposing factors of ARDS continue to be associated with decreased survival of ARDS patients 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 . Design : Prospect i ve , open , r and omised , multicentre , parallel group phase III trial . Setting : General ICUs in 43 university and regional hospitals in Europe . Patients : Two hundred and sixty-eight adult patients with early ALI . Interventions : NO responders were patients whose PaO2 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 r and omly 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 r and omised 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 STUDY OBJECTIVE To determine whether 24 h of inhaled nitric oxide improves oxygenation greater than conventional therapy alone in children with acute hypoxemic respiratory failure . DESIGN Prospect i ve , r and omized , controlled study . SETTING Twenty-six-bed pediatric ICU in a tertiary children 's hospital . PATIENTS Twenty-four patients with acute bilateral lung disease requiring a positive-end expiratory pressure > 6 cm H2O and a fraction of inspired oxygen > 0.5 for > 12 h. INTERVENTIONS Twelve patients were treated with 10 ppm inhaled nitric oxide from the onset of r and omization and 12 control patients were initially maintained on a regimen of conventional therapy alone . After a period of 24 h , control patients were also treated with 10 ppm inhaled nitric oxide .  Hemodynamic and blood gas measurements were performed at baseline , at 1 h after r and omization , and at 24-h intervals for 2 days . MEASUREMENTS AND RESULTS Inhaled nitric oxide decreased the ratio of pulmonary to systemic vascular resistance and improved oxygenation indexes during the initial hour following r and omization . However , 24 h after r and omization , the oxygenation indexes of 11 surviving treated patients were not improved in comparison to baseline or the oxygenation indexes of 10 surviving control patients . Oxygenation indexes acutely improved in control patients when inhaled nitric oxide was started after 24 h of conventional therapy .  Oxygenation indexes remained improved in the initial control patients after 24 h of inhaled nitric oxide . CONCLUSIONS Pulmonary vascular resistance and systemic oxygenation are acutely improved by 10 ppm inhaled nitric oxide in some children with severe lung disease . However , a sustained improvement in oxygenation may not occur during prolonged therapy . Thus , inhaled nitric oxide may have a limited therapeutic role in children with acute hypoxemic respiratory failure Objective To determine the dose-response curve of inhaled nitric oxide ( NO ) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure . Design Prospect i ve r and omized study . Setting A 14-bed ICU in a teaching hospital . Patients 6 critically ill patients with severe acute respiratory failure ( lung injury severity score ≥2.5 ) and pulmonary hypertension . Interventions 8 concentrations of inhaled NO were administered at r and om : 100 , 400 , 700 , 1000 , 1300 , 1600 , 1900 and 5000 parts per billion ( ppb ) . Control measurements were performed before NO inhalation and after the last concentration administered . After an NO exposure of 15–20 min , hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter , blood gases , methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide ( NO2 ) concentrations , continuously monitored using a bedside chemiluminescence apparatus , were recorded on a Gould ES 1000 recorder . In 2 patients end-tidal CO2 was also recorded . Results The administration of 100–2000 ppb of inhaled NO induced : i ) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance ( maximum decrease −25 % ) ; ii ) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt ; iii ) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space ; iv ) a dose-dependent increase in mixed venous oxygen saturation ( SVO2 ) . Systemic hemodynamic variables and methemoglobin blood concentrations did not change . Maximum NO2 concentrations never exceeded 165 ppb . In 2 patients , 91 % and 74 % of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb . Conclusion In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure , therapeutic inhaled NO concentrations are in the range 100–2000 ppb . The risk of toxicity related to NO inhalation is therefore markedly reduced . Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient Abstract Objective To evaluate the lowest dose of inhaled nitric oxide ( NO ) in patients with adult respiratory distress syndrome ( ARDS ) , which is able to improve arterial oxygenation more than 30 % compared to baseline data . Design Prospect i ve , clinical study . Setting Anesthesiological ICU in a university hospital . Patients 3 consecutive patients with severe ARDS according to clinical and radiological signs . Interventions Pressure-controlled ventilation with positive endexpiratory pressure of 8–12 cm H2O . Inhalation of NO was performed with a blender system and a Servo 300 ventilator . The lowest effective NO dose was defined by titrating the inspiratory NO dose until reaching a 30 % improvement of PaO2/FiO2 . This dose was used for the following continuous long-term NO inhalation ; controls of efficacy by investigation of hemodynamics and blood gas exchange were performed initially and 2 times per patient after intervals of 3–5 days . Measurements and results Initial NO concentrations were found to be effective at 60 , 100 , and 230 parts per billion ( ppb ) . In all measurements , arterial oxygenation was found to be elevated by NO inhalation with the initially evaluated dose compared to baseline data ; in parallel , the venous admixture $ $ \left ( { { { \dot Q_{va } } \mathord{\left/ { \vphantom { { \dot Q_{va } } { \dot Q_t } } } \right . \kern-\nulldelimiterspace } { \dot Q_t } } } \right)$$ was reduced . The O2 delivery increased , although O2 consumption and hemodynamics did not change . In 1 patient , interruption of NO inhalation caused remarkable increase of pulmonary resistance . Conclusions The improvement of oxygenation by NO inhalation in ARDS does not require reduction of pulmonary resistance and can be performed using low doses in the ppb range , which has to be considered as probably non-toxic We studied the combined effects of inhaled nitric oxide ( INO ) and positive end expiratory pressure ( PEEP ) during mechanical ventilation in patients with acute respiratory distress syndrome ( ARDS ) . Eleven patients received 0 and 4 parts per million of INO in r and om order for 30 min at PEEP levels of 0 , 5 , and 10 cm H2O . Respiratory and cardiovascular parameters were measured . The addition of INO and PEEP significantly improved arterial oxygenation ( p < 0.005 and p < 0.0001 , respectively ) . The combined effect of INO and PEEP  on arterial oxygenation was remarkable during 10 cm H2O PEEP . There was synergistic effect on arterial oxygenation by combining INO and 10 cm H2O PEEP . The present study showed that the combination of INO and 10 cm H2O PEEP enhanced arterial oxygenation in patients with ARDS BACKGROUND Inhaled nitric oxide ( INO ) and prone positioning have both been advocated as methods to improve oxygenation in patients with acute respiratory distress syndrome ( ARDS ) . This study was design ed to evaluate the relative contributions of INO and prone positioning alone and in combination on gas exchange in trauma patients with ARDS . METHODS Sixteen patients meeting the consensus definition of ARDS were studied . Patients received mechanical ventilation in the supine position , mechanical ventilation plus INO at 1 part per million in the supine position , mechanical ventilation in the PP , and mechanical ventilation in the prone positioning plus INO at 1 part per million . A stabilization period of 1 hour was allowed at each condition . After stabilization , hemodynamic and gas exchange variables were measured . RESULTS INO and prone positioning both increased PaO2/FIO2 compared with ventilation in the supine position . PaO2/FIO2 increased by 14 % during use of INO , and 10 of 16 patients ( 62 % ) responded to INO in the supine position . PaO2/FIO2 increased by 33 % , and 14 of 16 patients ( 87.5 % ) responded to the prone position . The combination of INO and prone positioning result ed in an improvement in PaO2/FIO2 in 15 of 16 patients ( 94 % ) , with a mean increase in PaO2/FIO2 of 59 % . Pulmonary vascular resistance was reduced during use of INO , with a greater reduction in pulmonary vascular resistance seen with INO plus prone positioning ( 175 + /- 36 dynes x s/cm5 vs. 134 + /- 28 dynes x s/cm5 ) compared with INO in the supine position ( 164 + /- 48 dynes x s/cm5 vs.138 + /- 44 dynes x s/cm5 ) . There were no significant hemodynamic effects of INO or prone positioning and no complications were seen during this relative short duration of study . CONCLUSIONS INO and prone positioning can contribute to improved oxygenation in patients with ARDS . The two therapies in combination are synergistic and may be important adjuncts to mechanical ventilation in the ARDS patient with refractory hypoxemia Background : Nitric oxide ( NO ) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome ( ARDS ) . In this study of patients with severe ARDS , we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response . Methods : Thirteen patients with severe ARDS ( hospital mortality 67 % )  inhaled 0 - 40 parts per million ( ppm ) NO . Seven of these patients continued to breathe 2 - 20 ppm NO for 2 - 27 days . Results : Inhaling 5 - 40 ppm NO  decreased mean pulmonary artery pressure in a dose-related fashion ( from 34 ± 7 to 30 ± 7 mmHg at 20 ppm NO ) . Systemic arterial pressure did not change . The ratio of arterial oxygen tension to inspired oxygen fraction increased ( from 126 ± 36 to 149 ± 38 mmHg ) and the venous admixture decreased ( from 31.2 ± 5.5 to 28.2 ± 5.2 % ) without a clear dose-response effect . During prolonged NO inhalation , 2 - 20 ppm NO effectively reduced mean pulmonary artery pressure ( 38 ± 7 vs. 31 ± 6 mmHg ) and increased arterial oxygen tension ( 79 ± 10 vs. 114 ± 27 mmHg ) without evidence of tachyphylaxis . The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO ( r=-0.72 ) . The reduction of venous admixture correlated with the level of venous admixture without NO ( r=-0.78 ) . Conclusions : Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS . The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP ) for acceptable oxygenation , with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels ( 35 to 38 mm Hg ) . Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve , a tidal volume of less than 6 ml per kilogram , driving pressures of less than 20 cm of water above the PEEP value , permissive hypercapnia , and preferential use of pressure-limited ventilatory modes . RESULTS After 28 days , 11 of 29 patients ( 38 percent ) in the protective-ventilation group had died , as compared with 17 of 24 ( 71 percent ) in the conventional-ventilation group ( P<0.001 ) . The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group ( P=0.005 ) : the rates of clinical barotrauma were 7 percent and 42 percent , respectively ( P=0.02 ) , despite the use of higher PEEP and mean airway pressures in the protective-ventilation group . The difference in survival to hospital discharge was not significant ; 13 of 29 patients ( 45 percent ) in the protective-ventilation group died in the hospital , as compared with 17 of 24 in the conventional-ventilation group ( 71 percent , P=0.37 ) . CONCLUSIONS As compared with conventional ventilation , the protective strategy was associated with improved survival at 28 days , a higher rate of weaning from mechanical ventilation , and a lower rate of barotrauma in patients with the acute respiratory distress syndrome .  Protective ventilation was not associated with a higher rate of survival to hospital discharge BACKGROUND The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood . We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions , thereby reducing pulmonary hypertension and improving gas exchange . METHODS Nine of 10 consecutive patients with severe adult respiratory distress syndrome  inhaled nitric oxide in two concentrations for 40 minutes each . Hemodynamic variables , gas exchange , and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation ; the results were compared with those obtained during intravenous infusion of prostacyclin .  Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million ( ppm ) for 3 to 53 days . RESULTS Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean ( + /- SE ) pulmonary-artery pressure from 37 + /- 3 mm Hg to 30 + /- 2 mm Hg ( P = 0.008 ) and decreased intrapulmonary shunting from 36 + /- 5 percent to 31 + /- 5 percent ( P = 0.028 ) . The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen ( PaO2/FiO2 ) , an index of the efficiency of arterial oxygenation , increased during nitric oxide administration from 152 + /- 15 mm Hg to 199 + /- 23 mm Hg ( P = 0.008 ) , although the mean arterial pressure and cardiac output were unchanged . Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure . Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days . CONCLUSIONS Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion , without producing systemic vasodilation . R and omized , blinded trials will be required to determine whether inhaled nitric oxide will improve outcome Background The response to inhaled nitric oxide and prone positioning was investigated in 47 patients with adult respiratory distress syndrome to test the hypothesis that inhalation of nitric oxide when in the prone position would result in additive improvement in oxygenation . Methods The authors prospect ively studied patients of both genders who were 15 to 75 yr old and had adult respiratory distress syndrome confirmed by computed tomography ( lung injury score , 3.1 + /− 1 ) . Results Compared with baseline values in the supine position ( T1 ) , inhalation of 10 ppm nitric oxide for 1 h ( T2 ) decreased the mean pulmonary artery pressure from 33 + /− 9 mmHg to 28 + /− 6 mmHg ( P < 0.05 ; T2 vs. T1 ) and increased the ratio of the partial pressure of oxygen in arterial blood ( Pa (O)(2 ) ) to inspired oxygen concentration ( FIO(2 ) ) from 115 ( median first quartile [ Q1 ] 97 , median third quartile [ Q3 ] 137 ) to 148 ( Q1 132 , Q3 196 ) ( P < 0.05 ; T2 vs. T1 ) . Cessation of nitric oxide brought the values back to baseline ( T3 ) . Two hours of prone positioning ( T4 ) significantly increased the PaO(2 ) : FIO(2 ) ratio ( T4 vs. T3 ) . However , after an additional hour of nitric oxide inhalation in the prone position ( T5 ) , a significant decrease of the venous admixture ( from 33 + /− 6 % to 25 + /− 6 % ; P < 0.05 ) and an increase of the PaO(2):FIO(2 ) ratio ( from 165 [ Q1 129 , Q3 216 ] to 199 [ Q1 178 , Q3 316 ] [ P < 0.05 ; T5 vs. T4 ] ) were observed . Conclusions In patients with isolated severe adult respiratory distress syndrome , inhalation of nitric oxide in the prone position significantly improved oxygenation compared with nitric oxide inhalation in the supine position or in the prone position without nitric oxide . The combination of the prone position with nitric oxide inhalation in the treatment of severe adult respiratory distress syndrome should be considered BACKGROUND Inhaled nitric oxide improves gas exchange in neonates , but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established . METHODS We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks ' gestation , were 4 days old or younger , required assisted ventilation , and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher . The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours , followed by 5 ppm for no more than 96 hours . The primary end point of the study was the use of extracorporeal membrane oxygenation . RESULTS Of 248 neonates enrolled , 126 were r and omly assigned to the nitric oxide group and 122 to the control group . Extracorporeal membrane oxygenation was used in 78 neonates in the control group ( 64 percent ) and in 48 neonates in the nitric oxide group ( 38 percent ) ( P=0.001 ) . The 30-day mortality rate in the two groups was similar ( 8 percent in the control group and 7 percent in the nitric oxide group ) . Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group ( 7 percent vs. 20 percent , P=0.02 ) . The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis . CONCLUSIONS Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension OBJECTIVES AND BACKGROUND To determine whether inhaled nitric oxide ( iNO ) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure , we performed a multicenter , r and omized , masked , controlled study of the effects of prolonged iNO therapy on oxygenation . We hypothesized that iNO therapy would improve oxygenation in an acute manner , slow the rate of decline in gas exchange , and decrease the number of patients who meet pre-established oxygenation failure criteria . STUDY DESIGN A total of 108 children ( median age 2.5 years ) with severe acute hypoxemic respiratory failure from 7 centers were enrolled . After consent was obtained , patients were r and omized to treatment with iNO ( 10 ppm ) or mechanical ventilation alone for at least 72 hours . Patients with an oxygenation index > /=40 for 3 hours or > /=25 for 6 hours were considered treatment failures and exited the study . RESULTS Patient age , primary diagnosis , pediatric risk of mortality score , mode of ventilation , and median oxygenation index ( 35 + /- 22 vs 30 + /- 15 ; iNO vs control ; mean + /- SEM ) were not different between groups at study entry . Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours ( -10.2 vs -2.7 , mean values ; P < .014 ) and at 12 hours ( -9.2 vs -2.8 ; P < .007 ) . At 12 hours 36 % of the control group met failure criteria in contrast with 16 % in the iNO group ( P < .05 ) . During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was > /=25 ( P < .04 ) and in immunocompromised patients ( P < .03 ) . CONCLUSIONS We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF . Two subgroups ( immunocompromised and an entry oxygen index > /=25 ) appear to have a more sustained improvement in oxygenation , and we speculate that these subgroups may benefit from prolonged therapy Purpose To determine the efficacy and side effects of prone positioning ( PP ) and nitric oxide ( NO ) inhalation , alone , associated , or combined withiv almitrine for the treatment of hypoxaemia in severe acute respiratory distress syndrome ( ARDS ) . Methods Over a period of 20 months , 27 consecutive critically ill patients with severe ARDS ( Murray score > 2.5 , PaO2/FiO2 < 170 after alveolar recruitment ) were prospect ively and r and omly included . They inhaled NO for two hours at concentrations of 5 and 10 ppm for one hour each ( H0–H2 ) . One hour later , they were returned to the prone position for four hours ( H3–H7 ) . During the last two hours in this position ( H5–H7 ) , they were assigned to further inhalation of 10 ppm NO ( Group B , n = 9 ) or to no further inhalation ( Group A , n = 9 ) . In group C ( n = 9 ) , the procedure for group B was combined with perfusion of 16 mg · kg−1 · min−1 almitrine throughout the study . Results Compared with control values , two hours NO inhalation improves PaO2/FiO2 and shunt effect by + 28 % and −9 % , PP by + 88 % and −27 % , PP + almitrine by + 132 % and −28 % , NO + almitrine by + 153 and −28 % , PP + NO by + 94 % and −29 % , NO + PP + almitrine by + 327 and −48 % . NO inhalation reduces pulmonary vascular resistance . Other haemodynamic parameters remain unchanged , whatever the treatment . NO inhalation improves PaO2/FiO2 by over 20 % in 50 % of the patients and PP is effective in 78 % of the cases . Conclusion Prone Position improves PaO2/FiO2 significantly more than NO alone but less than PP+ almitrine or NO+ almitrine . The best results are obtained with the association of NO + Prone position + Almitrine . RésuméObjectifApprécier et comparer l’intérêt du décubitus ventral ( DV ) , de l’inhalation de NO et de l’administration continue d’almitrine , seuls ou en association , dans le traitement de l’hypoxémie au cours du syndrome de détresse respiratoire aiguë (SDRA).MéthodeSur une période de 20 mois , 27 patients hospitalisés en réanimation avec un SDRA grave ( score de Murray > 2,5 , PaO2/FiO2 < 170 après recrutement alvéolaire ) ont été inclus prospect ivement et de manière r and omisée . Ils ont bénéficié de l’inhalation de NO pendant 2 heures à la posologie de 5ppm pendant une heure puis I0ppm ( H0–H2 ) . Après une heure d’arrêt , on les a retournés 4 heures en décubitus ventral ( H3–H7 ) . De H5 à H7 un groupe A ( n = 9 ) était traité par DV seul t and is que l’on ajoutait dans un groupe B ( n = 9 ) l’inhalation de NO à 10 ppm . Un troisième groupe C ( n = 9 ) bénéficiait d’une perfusion continue d’almitrine ( 16 mg · kg−1 · min−1 ) associée à cette même séquence thérapeutique . RésultatsPar rapport à H0 , 2 heures de NO améliorent le rapport PaO2/FiO2 et diminuent le shunt de + 28 % et −9 % , le DV de + 88 % et −27 % , les associations DV + almitrine de + 132 % et −28 % , NO + almitrine de + 153 et −28 % , DV + NO de + 94 % et −29 % , NO + PP + almitrine de + 327 et −48 % . L’inhalation de  NO diminue les resistances vasculaires pulmonaires . Les autres paramètres hémodynamiques restent inchangés quel que soit le traitement institué . L’inhalation de NO  améliore le rapport PaO2/FiO2 de plus de 20 % chez 50 % des patients t and is qu’avec le même critère d’efficacité , 78 % des malades sont répondeur au DV Conclusion Le DV s’avère plus efficace que le NO seul pour ce qui est d’améliorer le rapport PaO2/FiO2 , mais moins que les associations DV + almitrine ou NO + almitrine . Les meilleurs résultats sont obtenus avec latrithérapie  DV + NO + almitrine
BACKGROUND Acute hypoxemic respiratory failure affects all age groups and may result from a number of systemic diseases .
It continues to be associated with high mortality and morbidity .
Initial studies examining the effect of inhaled nitric oxide in respiratory failure demonstrated transient improvement in oxygenation but did not examine mortality or other significant morbidity outcomes .
OBJECTIVES To systematic ally examine r and omized controlled trials addressing the effect of inhaled nitric oxide , compared with placebo inhaled gas , on mortality and morbidity in patients with acute hypoxemic respiratory failure .