Acute and Sustained Effects of Early Administration of Inhaled
Objective: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome.
Design: Observational study.
Setting: Pediatric intensive care unit at a university-affiliated hospital.
Patients: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs.
Interventions: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000.
Measurements and Main Results: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao2/Fio2 ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao2/Fio2 ratio was lower (CTG, 116.9 ± 34.5; iNOG, 62.5 ± 12.8, p < .0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p < .0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio2 and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p < .001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p > .05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p > .05).
Conclusions: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.
Since its first description, acute respiratory distress syndrome (ARDS) is still a therapeutic challenge in pediatric intensive care, and it has been associated with high mortality rate, despite better understanding of its pathophysiology and recent therapeutic advances.
The local effects of inhaled nitric oxide (iNO) on oxygenation, inflammation, pulmonary hypertension, edema, and capillary permeability may account for its use in ARDS. Rossaint et al. first demonstrated in adult ARDS patients that iNO decreases intrapulmonary shunting and improves arterial oxygenation. Abman et al., in 1994, described the beneficial effects of iNO on oxygenation, pulmonary hypertension, and cardiac index in children with ARDS. Afterward, many studies performed on adults and children, although confirming those effects, were not able to demonstrate a sustained response to iNO therapy. However, Dobyns et al. observed sustained response to iNO vs. placebo therapy in subgroups of pediatric patients (oxygenation index ≥25 and immunocompromised group). These authors explained that iNO therapy did not sustain oxygenation improvement in all patients because they were enrolled in the study in the later stages of the disease.
The hypothesis that the response to iNO therapy depends on its time of introduction had already been stated by others, supporting the idea that early iNO treatment may be more effective. Recently, starting iNO administration as early as 12 hrs after ARDS diagnosis, we demonstrated acute and sustained response of oxygenation indexes.
In 2002, The Cochrane Library published a systematic review on the effects of iNO in acute hypoxemic respiratory failure in children and adults. Five randomized controlled trails were evaluated, assessing 535 patients. The review concluded that iNO may be useful only as a rescue treatment in first 24 hrs of the disease. However, it is worth mentioning that of these five studies, only one was performed in children. Therefore, the question about the potential role of iNO therapy in ARDS is still open and remains to be defined, mainly in children.
The aims of this study were a) to determine the acute and sustained effects of early iNO on some oxygenation indexes and ventilator settings, to analyze the weaning process, and to assess the safety of nitric oxide inhalation; and b) to compare iNO administration plus conventional therapy with just conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation (MV) in children with ARDS.
Objective: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome.
Design: Observational study.
Setting: Pediatric intensive care unit at a university-affiliated hospital.
Patients: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs.
Interventions: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000.
Measurements and Main Results: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao2/Fio2 ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao2/Fio2 ratio was lower (CTG, 116.9 ± 34.5; iNOG, 62.5 ± 12.8, p < .0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p < .0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio2 and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p < .001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p > .05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p > .05).
Conclusions: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.
Since its first description, acute respiratory distress syndrome (ARDS) is still a therapeutic challenge in pediatric intensive care, and it has been associated with high mortality rate, despite better understanding of its pathophysiology and recent therapeutic advances.
The local effects of inhaled nitric oxide (iNO) on oxygenation, inflammation, pulmonary hypertension, edema, and capillary permeability may account for its use in ARDS. Rossaint et al. first demonstrated in adult ARDS patients that iNO decreases intrapulmonary shunting and improves arterial oxygenation. Abman et al., in 1994, described the beneficial effects of iNO on oxygenation, pulmonary hypertension, and cardiac index in children with ARDS. Afterward, many studies performed on adults and children, although confirming those effects, were not able to demonstrate a sustained response to iNO therapy. However, Dobyns et al. observed sustained response to iNO vs. placebo therapy in subgroups of pediatric patients (oxygenation index ≥25 and immunocompromised group). These authors explained that iNO therapy did not sustain oxygenation improvement in all patients because they were enrolled in the study in the later stages of the disease.
The hypothesis that the response to iNO therapy depends on its time of introduction had already been stated by others, supporting the idea that early iNO treatment may be more effective. Recently, starting iNO administration as early as 12 hrs after ARDS diagnosis, we demonstrated acute and sustained response of oxygenation indexes.
In 2002, The Cochrane Library published a systematic review on the effects of iNO in acute hypoxemic respiratory failure in children and adults. Five randomized controlled trails were evaluated, assessing 535 patients. The review concluded that iNO may be useful only as a rescue treatment in first 24 hrs of the disease. However, it is worth mentioning that of these five studies, only one was performed in children. Therefore, the question about the potential role of iNO therapy in ARDS is still open and remains to be defined, mainly in children.
The aims of this study were a) to determine the acute and sustained effects of early iNO on some oxygenation indexes and ventilator settings, to analyze the weaning process, and to assess the safety of nitric oxide inhalation; and b) to compare iNO administration plus conventional therapy with just conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation (MV) in children with ARDS.
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