Acute respiratory failure in intensive care units. FINNALI: a prospective cohort study 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. Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality. Incidence and Outcomes of Pediatric Acute Lung Injury Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. 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. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome Inhaled nitric oxide does not prevent pulmonary edema after lung transplantation measured by lung water content: a randomized clinical study. Influence of inhaled nitric oxide on plasma nitrate concentrations in patients with adult respiratory distress syndrome and sepsis: results of a pilot study. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. 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. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study Effect of inhaled nitric oxide on right ventricular function in adult respiratory distress syndrome. 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 Healthcare costs and long-term outcomes after acute respiratory distress syndrome: A phase III trial of inhaled nitric oxide* Incidence and outcomes of acute lung injury. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. A randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation. Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics Inhaled nitric oxide for the adult respiratory distress syndrome. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury
Objective To evaluate the incidence , treatment and mortality of  acute respiratory failure ( ARF ) in Finnish intensive care units ( ICUs ) . Study design Prospect i ve multicentre cohort study . Methods All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period . Patients needing ventilatory support for more than 6 h were included and defined as ARF patients . Risk factors for ARF and details of prior chronic health status were assessed .  Ventilatory and concomitant treatments  were evaluated and recorded daily throughout the ICU stay . ICU and 90-day mortalities were assessed . Results A total of 958 ( 39 % ) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF , acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) was 149.5 , 10.6 and 5.0/100,000 per year , respectively . Ventilatory support was started with non-invasive interfaces in 183 of 958 ( 19 % ) patients . Ventilatory modes allowing triggering of spontaneous breaths were preferred ( 81 % ) . Median tidal volume/predicted body weight was 8.7 ( 7.6–9.9 ) ml/kg and plateau pressure 19 ( 16–23 ) cmH2O . The 90-day mortality of ARF was 31 % . Conclusions While the incidence of ARF requiring ventilatory support is higher , the incidence of ALI and ARDS seems to be lower in Finl and than previously reported in other countries . Tidal volumes are higher than recommended in the concept of lung protective strategy . However , restriction of peak airway pressure was used in the majority of ARF patients 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 RATIONALE The 1994 American European Consensus Committee definitions of acute lung injury ( ALI ) and the acute respiratory distress syndrome ( ARDS ) have not been applied systematic ally in the pediatric population . OBJECTIVES The purpose of this study was to evaluate prospect ively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large , pediatric intensive care units with ALI/ARDS using Consensus criteria . METHODS All pediatric patients meeting Consensus Committee definitions for ALI were prospect ively identified and included in a relational data base . MEASUREMENTS AND MAIN RESULTS There were 328 admissions for ALI/ARDS with a mortality of 22 % . Multivariate logistic regression analyses revealed ( 1 ) the initial severity of oxygenation defect , as measured by the Pa(O2)/FI(O2 ) ratio ; ( 2 ) the presence of nonpulmonary and non- central nervous system ( CNS ) organ dysfunction ; and ( 3 ) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation . A substantial fraction of patients ( 28 % ) did not require mechanical ventilation at the onset of ALI ; 46 % of these patients eventually required intubation for worsening ALI . CONCLUSIONS Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value . In contrast to ALI/ARDS in adults , the initial severity of arterial hypoxemia in children correlates well with mortality . A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required . These patients provide a valuable group in whom new therapies can be tested OBJECTIVE : This population -based , prospect i ve , cohort study was design ed to determine the population incidence and outcomes of pediatric acute lung injury . METHODS : Between 1999 and 2000 , 1 year of screening was performed at all hospitals admitting critically ill children in King County , Washington . County residents 0.5 to 15 years of age who required invasive ( through endotracheal tube or tracheostomy ) or noninvasive ( through full face mask ) mechanical ventilation , regardless of the duration of mechanical ventilation , were screened . From this population , children meeting North American-European Consensus Conference acute lung injury criteria were eligible for enrollment . Postoperative patients who received mechanical ventilation for < 24 hours were excluded . Data collected included the presence of predefined cardiac conditions , demographic and physiological data , duration of mechanical ventilation , and deaths . US Census population figures were used to estimate incidence . Associations between outcomes and subgroups identified a priori were assessed . RESULTS : Thirty-nine children met the criteria for acute lung injury , result ing in a calculated incidence of 12.8 cases per 100000 person-years . Severe sepsis ( with pneumonia as the infection focus ) was the most common risk factor . The median 24-hour Pediatric Risk of Mortality III score was 9.0 , and the mean ± SD was 11.7 ± 7.5 . The hospital mortality rate was 18 % , lower than that reported previously for pediatric acute lung injury . There were no statistically significant associations between age , gender , or risk factors and outcomes . CONCLUSIONS : We present the first population -based estimate of pediatric acute lung injury incidence in the United States . Population incidence and mortality rates are lower than those for adult acute lung injury . Low mortality rates in pediatric acute lung injury may necessitate clinical trial outcome measures other than death BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use 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 Inhaled nitric oxide ( NO ) improves systemic oxygenation ( PaO2/FIO2 ) in adult patients with acute respiratory distress syndrome ( ARDS ) . However , individual response varies , and previous trials demonstrated no outcome benefit . This prospect i ve , r and omized study in 40 ARDS patients analyzed dose-response ( DR ) characteristics  during long-term inhaled NO .  Patients were r and omized for conventional therapy ( control ) or continuous treatment with 10 parts per million ( ppm ) inhaled NO until weaning was initiated . We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals . Before treatment ( Day 0 ) , peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients . After 4 days , the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm . At higher doses ( 10 and 100 ppm ) , oxygenation deteriorated , and the response to inhaled NO disappeared in several patients . This effect was not observed in the control group . There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit . In conclusion , long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters . Hence , previous trials on therapy with inhaled NO in ARDS should be carefully interpreted , as they used constant NO concentrations , which may have become overdoses leading to deterioration of oxygenation after several days CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion 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 STUDY OBJECTIVE In order to assess the effects of inhaled nitric oxide ( iNO ) in preventing early-onset lung edema from occurring after lung transplantation , we measured extravascular lung water ( EVLW ) in a group of lung transplant recipients who were at high risk for developing ischemia-reperfusion-induced lung injury . DESIGN Prospect i ve , r and omized study . SETTING S Surgical ICU in a teaching hospital . PATIENTS Thirty double-lung transplant recipients . INTERVENTIONS Patients were r and omized to receive or not receive 20 ppm iNO at the time of reperfusion ( ie , before any occurrence of lung edema ) . In the NO group , iNO was then administered for a 12-h period . A double-dilution technique was used for the serial assessment of EVLW , intrathoracic blood volume , and cardiac index . St and ard hemodynamic and pulmonary parameters were also recorded during the first 3 postoperative days . MEASUREMENTS AND RESULTS Patients who received iNO did not have a different lung water content compared to control subjects ( p = 0.61 [ by analysis of variance ( ANOVA ) ] ) . Blood oxygenation ( ie , Pao(2)/fraction of inspired oxygen [ Fio(2 ) ] ratio ) did not differ between the two groups ( p = 0.61 [ by ANOVA ] ) . In both groups , EVLW and Pao(2)/Fio(2 ) ratio dropped significantly over time , regardless of the use of iNO ( p < 0.01 [ by ANOVA ] ) . CONCLUSIONS In the population studied , prophylactic iNO that was administered at 20 ppm had no effect on pulmonary edema formation and resolution following lung transplantation STUDY OBJECTIVE To measure plasma nitrate concentrations after inhalation of nitric oxide for treatment of adult respiratory distress syndrome ( ARDS ) and sepsis . DESIGN Prospect i ve pilot study . SETTING Intensive care unit at a university-affiliated hospital . PATIENTS Nine consecutive medical intensive care unit patients with ARDS and sepsis . INTERVENTIONS After diagnosis of ARDS , all patients received a balloon-tipped triple-lumen thermodilution pulmonary artery catheter ( Baxter Healthcare Corp , Irvine , CA ) . Inhaled nitric oxide was initiated starting at a dose of one part per million and titrated according to the maximal achievable increase in arterial oxygenation . Hemodynamic measurements including intrapulmonary shunt fraction and blood as analyses were performed before nitric oxide application , as well as 1 and 24 hours after starting nitric oxide , respectively . Plasma sample s for determination of nitrate were taken from the arterial line and from the pulmonary thermodilution catheter and analyzed using high-performance liquid chromatography . MEASUREMENTS AND MAIN RESULTS Eight of 9 patients were  nitric oxide responders ( intrapulmonary shunt decrease > 5 % ) . There was no statistically significant increase in nitrate plasma concentration measured both in peripheral arterial and in mixed venous blood with inhaled nitric oxide up to a concentration of 40 parts per million . CONCLUSION Inhalation of nitric oxide in patients with ARDS and sepsis does not result in increased plasma nitrate concentrations 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 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 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 To determine whether inhaled nitric oxide ( NO ) affects pulmonary circulation , thereby improving right ventricular ( RV ) function in adult respiratory distress syndrome ( ARDS ) , we studied 13 patients with both a lung injury severity score of 2.5 or more and a mean pulmonary artery pressure higher than 30 mm Hg . RV function was assessed by a thermodilution technique using a pulmonary artery catheter equipped with a rapid response thermistor before and 15 min after initiation of inhalation of NO ( 5 ppm ) . At baseline , stroke volumes were in a normal range ( 46 + /- 14 ml/m2 ) , with a RV dilation ( end-diastolic volume = 142 + /- 36 ml/m2 ) . Inhaled NO was followed by an improvement in arterial oxygenation ( PaO2/FIO2 = 103 + /- 47 versus 142 + /- 63 , p < 0.05 ) and a drop in pulmonary artery pressure ( 36.1 + /- 4.5 versus 31.3 + /- 6.1 mm Hg , p < 0.01 ) ; stroke volumes and heart rates did not change . The result ing fall in pulmonary vascular resistance ( 211 + /- 43 versus 180 + /- 59 dyn-s/cm5 , p < 0.05 ) was associated with an increase in RV , ejection fractions ( 32 + /- 5 versus 36 + /- 6 % , p < 0.05 ) , a trend toward decreased RV end-systolic ( 96 + /- 25 versus 85 + /- 19 ml/m2 , NS ) and end-diastolic ( 142 + /- 36 versus 131 + /- 27 ml/m2 , NS ) volumes , and a decrease in right atrial pressures ( 10.9 + /- 2.9 versus 9.6 + /- 3.2 mm Hg , p < 0.05 ) . No relationship was seen between the improvement in arterial oxygenation and the decrease in pulmonary vascular resistance . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Objective : To determine the costs and long-term outcomes of acute respiratory distress syndrome ( ARDS ) in previously healthy adults . To determine whether treatment with inhaled nitric oxide affects these costs and outcomes . Design : One-year follow-up of a r and omized trial of inhaled nitric oxide . Hospital bills were collected , and follow-up was performed at hospital discharge , 6 months , and 1 year . Setting : Forty-six U.S. centers . Patients : Three hundred and eighty-five previously healthy adults with ARDS . Interventions : Subjects were r and omized to 5 ppm inhaled nitric oxide or placebo gas . Measurements and Main Results : One-year survival was 67.8 % , with no difference by treatment arm ( 67.3 % vs. 68.3 % for inhaled nitric oxide vs. placebo , p = .71 ) . Hospital costs from enrollment to discharge were high and similar in the inhaled nitric oxide and placebo arms ( $ 48,500 vs. $ 47,800 , p = 0.8 ) . There were also no differences in length of stay or Therapeutic Intervention Scoring System points . Almost half ( 43.4 % ) of subjects were discharged to another healthcare facility or to home with professional help , and 24.1 % were readmitted in 6 months , with no differences between groups . At 1 year , survivors reported low quality of life with no differences by treatment arm ( Quality of Well-Being score [ range 0–1 ] , 0.61 vs. 0.64 for inhaled nitric oxide vs. placebo , p = .11 ) and poor function with no differences by treatment arm ( 32.5 % returned to ≤5 points of baseline Activities of Daily Living [ range 0–100 ] , 63.3 % returned to ≤10 points , and the remaining 36.7 % suffered a mean decrement of 27 points ) . Conclusions : ARDS , even in previously healthy adults , not only is followed by poor survival , quality of life , and function but also is associated with high costs of care and postdischarge re source use .  Inhaled nitric oxide at 5 ppm had no effect on these outcomes BACKGROUND Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension . Despite recent advances in our underst and ing of the mechanism and treatment of acute lung injury , its incidence and outcomes in the United States have been unclear . METHODS We conducted a prospect i ve , population -based , cohort study in 21 hospitals in and around King County , Washington , from April 1999 through July 2000 , using a vali date d screening protocol to identify patients who met the consensus criteria for acute lung injury . RESULTS A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older . On the basis of this figure , the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years . The in-hospital mortality rate was 38.5 percent . The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age . Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older ( P<0.001 ) . We estimate that each year in the United States there are 190,600 cases of acute lung injury , which are associated with 74,500 deaths and 3.6 million hospital days . CONCLUSIONS Acute lung injury has a substantial impact on public health , with an incidence in the United States that is considerably higher than previous reports have suggested CONTEXT Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury . OBJECTIVE To evaluate the clinical efficacy of low-dose ( 5-ppm ) inhaled nitric oxide in patients with acute lung injury . DESIGN AND SETTING Multicenter , r and omized , placebo-controlled study , with blinding of patients , caregivers , data collectors , assessors of outcomes , and data analysts ( triple blind ) , conducted in the intensive care units of 46 hospitals in the United States . Patients were enrolled between March 1996 and September 1999 . PATIENTS Patients ( n = 385 ) with moderately severe acute lung injury , a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome ( ARDS ) using a ratio of PaO2 to FiO2 of < or = 250 , were enrolled if the onset was within 72 hours of r and omization , sepsis was not the cause of the lung injury , and the patient had no significant nonpulmonary organ system dysfunction at r and omization . INTERVENTIONS Patients were r and omly assigned to placebo ( nitrogen gas ) or inhaled nitric oxide at 5 ppm until 28 days , discontinuation of assisted breathing , or death . MAIN OUTCOME MEASURES The primary end point was days alive and off assisted breathing . Secondary outcomes included mortality , days alive and meeting oxygenation criteria for extubation , and days patients were alive following a successful unassisted ventilation test . RESULTS An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing ( mean [ SD ] , 10.6 [ 9.8 ] days in the placebo group and 10.7 [ 9.7 ] days in the inhaled nitric oxide group ; P = .97 ; difference , -0.1 day [ 95 % confidence interval , -2.0 to 1.9 days ] ) . This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO2 that resolved by 48 hours . Mortality was similar between groups ( 20 % placebo vs 23 % nitric oxide ; P = .54 ) . Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean ( SD ) of 11.9 ( 9.9 ) for placebo and 11.4 ( 9.8 ) for nitric oxide patients ( P = .54 ) . Days alive and meeting criteria for extubation were also similar : 17.0 placebo vs 16.7 nitric oxide ( P = .89 ) . CONCLUSION Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality Inhalation of nitric oxide ( NO ) has been advocated as a method to prevent ischemia-reperfusion injury after lung transplantation . We enrolled 84 patients into a concealed , r and omized , placebo-controlled trial to evaluate the effect of inhaled NO ( 20 ppm NO or nitrogen ) initiated 10 minutes after reperfusion on outcomes after lung transplantation . The groups ( n = 42 ) were balanced with respect to age , sex , lung disease , procedure , and total ischemic times . PaO2/FIO2 ratios were similar on admission to the intensive care unit ( ICU ) ( NO 361 + /- 134 ; control patients 357 + /- 132 ) , and over the duration of the study . There were no differences in hemodynamics between the two groups . Severe reperfusion injury ( PaO2/FIO2 < 150 ) was present at the time of admission to the ICU in 14.6 % NO patients versus 9.5 % of control patients ( p = 0.48 ) . The groups had similar median times to first successful trial of unassisted breathing ( 25 vs. 27 hours ; p = 0.76 ) , successful extubation ( 32 vs. 34 hours ; p = 0.65 ) , ICU discharge ( 3.0 days for both groups ) , and hospital discharge ( 27 vs. 29 days ; p = 0.563 ) . Five NO versus six control patients died during their hospital stay . Adjusting for age , sex , lung disease etiology , presence of pulmonary hypertension , and total ischemic time did not alter these results . In conclusion , we did not detect a significant effect of inhaled NO administered 10 minutes after reperfusion on physiologic variables or outcomes in lung transplant patients Objective High-frequency oscillatory ventilation ( HFOV ) and inhaled nitric oxide ( iNO ) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure ( AHRF ) , but their roles in the treatment of AHRF remains unknown . The use of HFOV improves oxygenation by increasing lung recruitment . iNO can improve oxygenation in AHRF , but it may have limited efficacy in patients with poor lung inflation . Based on these findings , we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation ( CMV ) or either treatment alone . Setting Tertiary pediatric intensive care units at seven academic centers . Design Post hoc analysis of data from children enrolled in a multicenter , r and omized , masked study of the use of iNO in the treatment of AHRF . Patients A total of 108 pediatric patients with AHRF defined as an oxygenation index of > 15 twice within 6 hrs . Mode of  ventilation ( HFOV or CMV ) was determined by the patient ’s physician based on guidelines to maximize oxygenation . The patient was then r and omized to treatment with or without iNO . Comparisons were made between patients who were treated with HFOV plus iNO ( n = 14 ) , HFOV alone ( n = 12 ) , CMV plus iNO ( n = 35 ) , and CMV alone ( n = 38 ) . Interventions Ventilation with CMV or HFOV with or without iNO . Measurements and Main Results We found that the change in Pao2/Fio2 ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs ( p = .02 ) and 12 hrs ( p = .01 ) . After 24 hrs of treatment , both HFOV plus iNO and HFOV alone result ed in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO ( p = .005 ) . After 72 hrs , treatment with HFOV alone result ed in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO ( p = .03 ) . There was no difference in predefined treatment failures between treatment groups . Conclusions We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF . We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange 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 OBJECTIVE Inhaled nitric oxide has been shown to reduce pulmonary vascular resistance in patients undergoing cardiothoracic surgery , but it is limited by toxicity , the need for special monitoring , and cost . Inhaled prostacyclin also decreases pulmonary artery pressure , is relatively free of toxicity , requires no specific monitoring , and is less expensive . The objective of this study was to compare nitric oxide and prostacyclin in the treatment of pulmonary hypertension , refractory hypoxemia , and right ventricular dysfunction in thoracic transplant recipients in a prospect i ve , r and omized , crossover pilot trial . METHODS Heart transplant and lung transplant recipients were r and omized to  nitric oxide or prostacyclin  as initial treatment , followed by a crossover to the other agent after 6 hours . Pulmonary vasodilators were initiated in the operating room for pulmonary hypertension , refractory hypoxemia , or right ventricular dysfunction . Nitric oxide was administered at 20 ppm , and prostacyclin was administered at 20,000 ng/mL. Hemodynamic and oxygenation parameters were recorded before and after initiation of pulmonary vasodilator therapy . At 6 hours , the hemodynamic and oxygenation parameters were recorded again , just before discontinuing the initial agent . Crossover baseline parameters were measured 30 minutes after the initial agent had been stopped . The crossover agent was then started , and the hemodynamic and oxygenation parameters were measured again 30 minutes later . RESULTS Heart transplant and lung transplant recipients ( n = 25 ) were r and omized by initial treatment ( nitric oxide , n = 14 ; prostacyclin , n = 11 ) . Nitric oxide and prostacyclin both reduced pulmonary artery pressure and central venous pressure , and improved cardiac index and mixed venous oxygen saturation on initiation of therapy . More importantly , at the 6-hour crossover trial , there were no significant differences between nitric oxide and prostacyclin in the reduction of pulmonary artery pressures or central venous pressure , or in improvement in cardiac index or mixed venous oxygen saturation . Nitric oxide and prostacyclin did not affect the oxygenation index or systemic blood pressure . There were no complications associated with nitric oxide or prostacyclin . CONCLUSION In heart transplant and lung transplant recipients , nitric oxide and prostacyclin similarly reduce pulmonary artery pressures and central venous pressure , and improve cardiac index and mixed venous oxygen saturation . Inhaled prostacyclin may offer an alternative to nitric oxide in the treatment of pulmonary hypertension in thoracic transplantation 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 Objective Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury . Endogenous nitric oxide regulates inflammatory responses , but the effect of inhaled nitric oxide therapy is unknown . We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity . Design A r and omized , prospect i ve interventional study . Setting A university hospital ’s general intensive care unit . Patients Thirty-two patients with acute lung injury . Interventions Patients who responded to test doses of nitric oxide were r and omized to ventilator therapy with and without inhaled nitric oxide . The inhaled concentration of nitric oxide was determined by dose titration at 0 , 2 , 10 , and 40 ppm and the minimum concentration used , which result ed in an increase in the Pao2/Fio2 ratio of at least 25 % . Measurements and Main Results Patients were followed up for 30 days or until death , and bronchoalveolar lavage ( BAL ) was performed at 0 , 24 , and 72 hrs . Nitric oxide synthase activity was measured spectrophotometrically , and myeloperoxidase , elastase , interleukin-8 , and leukotrienes were measured in BAL fluid by enzyme immunoassay . Total nitrite and lipid peroxides in serum were measured colorimetrically . Nitric oxide synthase activity decreased ( p = .01 ) and total nitrite increased ( p = .02 ) in patients receiving inhaled nitric oxide . Other markers of inflammation in BAL fluid did not change . Lipid peroxide concentrations also did not alter . Conclusions The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme . This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress
BACKGROUND Acute hypoxaemic respiratory failure ( AHRF ) , defined as acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) , are critical conditions .
AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages .
Inhaled nitric oxide ( INO ) has been used to improve oxygenation but its role remains controversial .
OBJECTIVES To systematic ally assess the benefits and harms of INO in critically ill patients with AHRF .