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Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

ABSTRACT: OBJECTIVES:Literature regarding appropriate use of inhaled nitric oxide for pediatric acute respiratory distress syndrome is sparse. This study aims to determine if positive response to inhaled nitric oxide is associated with decreased mortality and duration of mechanical ventilation in pediatric acute respiratory distress syndrome. DESIGN:Retrospective cohort study. SETTING:Large pediatric academic medical center. PATIENTS OR SUBJECTS:One hundred sixty-one children with pediatric acute respiratory distress syndrome and inhaled nitric oxide exposure for greater than or equal to 1 hour within 3 days of pediatric acute respiratory distress syndrome onset. INTERVENTIONS:Patients with greater than or equal to 20% improvement in oxygenation index or oxygen saturation index by 6 hours after inhaled nitric oxide initiation were classified as "responders." MEASUREMENTS AND MAIN RESULTS:Oxygenation index, oxygen saturation index, and ventilator settings were evaluated prior to inhaled nitric oxide initiation and 1, 6, 12, and 24 hours following inhaled nitric oxide initiation. Primary outcomes were mortality and duration of mechanical ventilation. Baseline characteristics, including severity of illness, were similar between responders and nonresponders. Univariate analysis showed no difference in mortality between responders and nonresponders (21% vs 21%; p = 0.999). Ventilator days were significantly lower in responders (10 vs 16; p < 0.001). Competing risk regression (competing risk of death) confirmed association between inhaled nitric oxide response and successful extubation (subdistribution hazard ratio = 2.11; 95% CI, 1.41-3.17; p < 0.001). Response to inhaled nitric oxide was associated with decreased utilization of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation and lower hospital charges (difference in medians of $424,000). CONCLUSIONS:Positive response to inhaled nitric oxide was associated with fewer ventilator days, without change in mortality, potentially via reduced use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Future studies of inhaled nitric oxide for pediatric acute respiratory distress syndrome should stratify based on oxygenation response, given the association with favorable outcomes.

SUBMITTER: Dowell JC

PROVIDER: S-EPMC5679068 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

Dowell Jasmine C JC Thomas Neal J NJ Yehya Nadir N

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20171101 11

<h4>Objectives</h4>Literature regarding appropriate use of inhaled nitric oxide for pediatric acute respiratory distress syndrome is sparse. This study aims to determine if positive response to inhaled nitric oxide is associated with decreased mortality and duration of mechanical ventilation in pediatric acute respiratory distress syndrome.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Large pediatric academic medical center.<h4>Patients or subjects</h4>One hundred sixty-one children ...[more]

PMID: 29099443

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Project description:To determine the frequency of low-tidal volume ventilation in pediatric acute respiratory distress syndrome and assess if any demographic or clinical factors improve low-tidal volume ventilation adherence.Descriptive post hoc analysis of four multicenter pediatric acute respiratory distress syndrome studies.Twenty-six academic PICU.Three hundred fifteen pediatric acute respiratory distress syndrome patients.All patients who received conventional mechanical ventilation at hours 0 and 24 of pediatric acute respiratory distress syndrome who had data to calculate ideal body weight were included. Two cutoff points for low-tidal volume ventilation were assessed: less than or equal to 6.5?mL/kg of ideal body weight and less than or equal to 8?mL/kg of ideal body weight. Of 555 patients, we excluded 240 for other respiratory support modes or missing data. The remaining 315 patients had a median PaO2-to-FIO2 ratio of 140 (interquartile range, 90-201), and there were no differences in demographics between those who did and did not receive low-tidal volume ventilation. With tidal volume cutoff of less than or equal to 6.5?mL/kg of ideal body weight, the adherence rate was 32% at hour 0 and 33% at hour 24. A low-tidal volume ventilation cutoff of tidal volume less than or equal to 8?mL/kg of ideal body weight resulted in an adherence rate of 58% at hour 0 and 60% at hour 24. Low-tidal volume ventilation use was no different by severity of pediatric acute respiratory distress syndrome nor did adherence improve over time. At hour 0, overweight children were less likely to receive low-tidal volume ventilation less than or equal to 6.5?mL/kg ideal body weight (11% overweight vs 38% nonoverweight; p = 0.02); no difference was noted by hour 24. Furthermore, in the overweight group, using admission weight instead of ideal body weight resulted in misclassification of up to 14% of patients as receiving low-tidal volume ventilation when they actually were not.Low-tidal volume ventilation is underused in the first 24 hours of pediatric acute respiratory distress syndrome. Age, Pediatric Risk of Mortality-III, and pediatric acute respiratory distress syndrome severity were not associated with improved low-tidal volume ventilation adherence nor did adherence improve over time. Overweight children were less likely to receive low-tidal volume ventilation strategies in the first day of illness.

Project description:ObjectivesTo characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes.DesignAn observational cohort study.SettingEight sites of the Collaborative Pediatric Critical Care Research Network.PatientsOne hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication.Measurements and main resultsClinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity.ConclusionsClinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

Project description:OBJECTIVES:Blood products are often transfused in critically ill children, although recent studies have recognized their potential for harm. Translatability to pediatric acute respiratory distress syndrome is unknown given that hypoxemia has excluded pediatric acute respiratory distress syndrome patients from clinical trials. We aimed to determine whether an association exists between blood product transfusion and survival or duration of ventilation in pediatric acute respiratory distress syndrome. DESIGN:Retrospective analysis of prospectively enrolled cohort. SETTING:Large, academic PICU. PATIENTS:Invasively ventilated children meeting Berlin Acute Respiratory Distress Syndrome and Pediatric Acute Lung Injury Consensus Conference Pediatric Acute Respiratory Distress Syndrome criteria from 2011 to 2015. INTERVENTIONS:We recorded transfusion of RBC, fresh frozen plasma, and platelets within the first 3 days of pediatric acute respiratory distress syndrome onset. Each product was tested for independent association with survival (Cox) and duration of mechanical ventilation (competing risk regression with extubation as primary outcome and death as competing risk). A sensitivity analysis using 1:1 propensity matching was also performed. MEASUREMENTS AND MAIN RESULTS:Of 357 pediatric acute respiratory distress syndrome patients, 155 (43%) received RBC, 82 (23%) received fresh frozen plasma, and 92 (26%) received platelets. Patients who received RBC, fresh frozen plasma, or platelets had higher severity of illness score, lower PaO2/FIO2, and were more often immunocompromised (all p < 0.05). Patients who received RBC, fresh frozen plasma, or platelets had worse survival and longer duration of ventilation by univariate analysis (all p < 0.05). After multivariate adjustment for above confounders, no blood product was associated with survival. After adjustment for the same confounders, RBC were associated with decreased probability of extubation (subdistribution hazard ratio, 0.65; 95% CI, 0.51-0.83). The association between RBC and prolonged ventilation was confirmed in propensity-matched subgroup analysis. CONCLUSIONS:RBC transfusion was independently associated with longer duration of mechanical ventilation in pediatric acute respiratory distress syndrome. Hemoglobin transfusion thresholds should be tested specifically within pediatric acute respiratory distress syndrome to establish whether a more restrictive transfusion strategy would improve outcomes.

Project description:PURPOSE:Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). METHODS:A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ? 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes. RESULTS:Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). CONCLUSIONS:Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.

Project description:OBJECTIVES:To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome. DESIGN:Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis. SETTING:Two quaternary care PICUs. PATIENTS:Children with pediatric acute respiratory distress syndrome. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ? 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.

Project description:IntroductionAssessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study.MethodsARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted.ResultsAt 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion.ConclusionsARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population.Trial registrationA Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.

Dataset Information

Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

Publications

Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

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