human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    