Respiratory pathogens associated with intubated pediatric patients following hematopoietic cell transplant.

BACKGROUND: We describe organisms found in the respiratory tracts of a multicenter cohort of pediatric hematopoietic cell transplant (HCT) recipients with respiratory failure. METHODS: Twelve centers contributed up to 25 pediatric allogeneic HCT recipients requiring mechanical ventilation for respiratory failure to a retrospective database. Positive respiratory pathogens and method of obtaining sample were recorded. Outcomes were assessed using Mann-Whitney U test or chi-squared analysis. RESULTS: Of the 222 patients in the database, ages 1 month through 21 years, 34.6% had a positive respiratory culture. 105 pathogens were identified in 77 patients; of those, 48.6% were viral, 34.3% bacterial, 16.2% fungal, and 1% parasitic. PICU mortality with a respiratory pathogen was 68.8% compared to 54.9% for those without a respiratory pathogen (P = .045). Those with a positive respiratory pathogen had longer PICU length of stay, 20 days (IQR 14.0, 36.8) vs 15 (IQR 6.5, 32.0), P = .002, and a longer course of mechanical ventilation, 17 days (IQR 10, 29.5) vs 8 (3, 17), P < .0001. Method of pathogen identification, type of pathogen, and the presence of multiple pathogens were not associated with changes in PICU outcomes. CONCLUSIONS: In this multicenter retrospective cohort of intubated pediatric post-HCT patients, there was high variability in the respiratory pathogens identified. Type of pathogen and method of detection did not affect PICU mortality. The presence of any organism leads to increased PICU mortality, longer PICU stay, and increased duration of mechanical ventilation suggesting that early detection and treatment of pathogens may be beneficial in this population.

Acute Respiratory Failure in Pediatric Hematopoietic Cell Transplantation: A Multicenter Study.

OBJECTIVES: Acute respiratory failure is common in pediatric hematopoietic cell transplant recipients and has a high mortality. However, respiratory prognostic markers have not been adequately evaluated for this population. Our objectives are to assess respiratory support strategies and indices of oxygenation and ventilation in pediatric allogeneic hematopoietic cell transplant patients receiving invasive mechanical ventilation and investigate how these strategies are associated with mortality. DESIGN: Retrospective, multicenter investigation. SETTING: Twelve U.S. pediatric centers. PATIENTS: Pediatric allogeneic hematopoietic cell transplant recipients with respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred twenty-two subjects were identified. PICU mortality was 60.4%. Nonsurvivors had higher peak oxygenation index (38.3 [21.3-57.6] vs 15.0 [7.0-30.7]; p < 0.0001) and oxygen saturation index (24.7 [13.8-38.7] vs 10.3 [4.6-21.6]; p < 0.0001), greater days with FIO2 greater than or equal to 0.6 (2.4 [1.0-8.5] vs 0.8 [0.3-1.6]; p < 0.0001), and more days with oxygenation index greater than 18 (1.4 [0-6.0] vs 0 [0-0.3]; p < 0.0001) and oxygen saturation index greater than 11 (2.0 [0.5-8.8] vs 0 [0-1.0]; p < 0.0001). Nonsurvivors had higher maximum peak inspiratory pressures (36.0 cm H2O [32.0-41.0 cm H2O] vs 30.0 cm H2O [27.0-35.0 cm H2O]; p < 0.0001) and more days with peak inspiratory pressure greater than 31 cm H2O (1.0 d [0-4.0 d] vs 0 d [0-1.0 d]; p < 0.0001). Tidal volume per kilogram was not different between survivors and nonsurvivors. CONCLUSIONS: In this cohort of pediatric hematopoietic cell transplant recipients with respiratory failure in the PICU, impaired oxygenation and use of elevated ventilator pressures were common and associated with increased mortality.

High-Frequency Oscillatory Ventilation Use and Severe Pediatric ARDS in the Pediatric Hematopoietic Cell Transplant Recipient.

INTRODUCTION: The effectiveness of high-frequency oscillatory ventilation (HFOV) in the pediatric hematopoietic cell transplant patient has not been established. We sought to identify current practice patterns of HFOV, investigate parameters during HFOV and their association with mortality, and compare the use of HFOV to conventional mechanical ventilation in severe pediatric ARDS. METHODS: This is a retrospective analysis of a multi-center database of pediatric and young adult allogeneic hematopoietic cell transplant subjects requiring invasive mechanical ventilation for critical illness from 2009 through 2014. Twelve United States pediatric centers contributed data. Continuous variables were compared using a Wilcoxon rank-sum test or a Kruskal-Wallis analysis. For categorical variables, univariate analysis with logistic regression was performed. RESULTS: The database contains 222 patients, of which 85 subjects were managed with HFOV. Of this HFOV cohort, the overall pediatric ICU survival was 23.5% (n = 20). HFOV survivors were transitioned to HFOV at a lower oxygenation index than nonsurvivors (25.6, interquartile range 21.1-36.8, vs 37.2, interquartile range 26.5-52.2, P = .046). Survivors were transitioned to HFOV earlier in the course of mechanical ventilation, (day 0 vs day 2, P = .002). No subject survived who was transitioned to HFOV after 1 week of invasive mechanical ventilation. We compared subjects with severe pediatric ARDS treated only with conventional mechanical ventilation versus early HFOV (within 2 d of invasive mechanical ventilation) versus late HFOV. There was a trend toward difference in survival (conventional mechanical ventilation 24%, early HFOV 30%, and late HFOV 9%, P = .08). CONCLUSIONS: In this large database of pediatric allogeneic hematopoietic cell transplant subjects who had acute respiratory failure requiring invasive mechanical ventilation for critical illness with severe pediatric ARDS, early use of HFOV was associated with improved survival compared to late implementation of HFOV, and the subjects had outcomes similar to those treated only with conventional mechanical ventilation.

Pediatric Acute Respiratory Distress Syndrome in Pediatric Allogeneic Hematopoietic Stem Cell Transplants: A Multicenter Study.

OBJECTIVE: Immunodeficiency is both a preexisting condition and a risk factor for mortality in pediatric acute respiratory distress syndrome. We describe a series of pediatric allogeneic hematopoietic stem cell transplant patients with pediatric acute respiratory distress syndrome based on the recent Pediatric Acute Lung Injury Consensus Conference guidelines with the objective to better define survival of this population. DESIGN: Secondary analysis of a retrospective database. SETTING: Twelve U.S. pediatric centers. PATIENTS: Pediatric allogeneic hematopoietic stem cell transplant recipients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the first week of mechanical ventilation, patients were categorized as: no pediatric acute respiratory distress syndrome or mild, moderate, or severe pediatric acute respiratory distress syndrome based on oxygenation index or oxygen saturation index. Univariable logistic regression evaluated the association between pediatric acute respiratory distress syndrome and PICU mortality. A total of 91.5% of the 211 patients met criteria for pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition: 61.1% were severe, 27.5% moderate, and 11.4% mild. Overall survival was 39.3%. Survival decreased with worsening pediatric acute respiratory distress syndrome: no pediatric acute respiratory distress syndrome 66.7%, mild 63.6%, odds ratio = 1.1 (95% CI, 0.3-4.2; p = 0.84), moderate 52.8%, odds ratio = 1.8 (95% CI, 0.6-5.5; p = 0.31), and severe 24.6%, odds ratio = 6.1 (95% CI, 2.1-17.8; p < 0.001). Nonsurvivors were more likely to have multiple consecutive days at moderate and severe pediatric acute respiratory distress syndrome (p < 0.001). Moderate and severe patients had longer PICU length of stay (p = 0.01) and longer mechanical ventilation course (p = 0.02) when compared with those with mild or no pediatric acute respiratory distress syndrome. Nonsurvivors had a higher median maximum oxygenation index than survivors at 28.6 (interquartile range, 15.5-49.9) versus 15.0 (interquartile range, 8.4-29.6) (p < 0.0001). CONCLUSION: In this multicenter cohort, the majority of pediatric allogeneic hematopoietic stem cell transplant patients with respiratory failure met oxygenation criteria for pediatric acute respiratory distress syndrome based on the Pediatric Acute Lung Injury Consensus Conference definition within the first week of invasive mechanical ventilation. Length of invasive mechanical ventilation, length of PICU stay, and mortality increased as the severity of pediatric acute respiratory distress syndrome worsened.

Invasive Mechanical Ventilation and Mortality in Pediatric Hematopoietic Stem Cell Transplantation: A Multicenter Study.

OBJECTIVE: To establish the current respiratory practice patterns in pediatric hematopoietic stem cell transplant patients and investigate their associations with mortality across multiple centers. DESIGN: Retrospective cohort between 2009 and 2014. SETTING: Twelve children's hospitals in the United States. PATIENTS: Two hundred twenty-two pediatric allogeneic hematopoietic stem cell transplant recipients with acute respiratory failure using invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU mortality of our cohort was 60.4%. Mortality at 180 days post PICU discharge was 74%. Length of PICU stay prior to initiation of invasive mechanical ventilation was significantly lower in survivors, and the odds of mortality increased for longer length of PICU stay prior to intubation. A total of 91 patients (41%) received noninvasive ventilation at some point during their PICU stay prior to intubation. Noninvasive ventilation use preintubation was associated with increased mortality (odds ratio, 2.1; 95% CI, 1.2-3.6; p = 0.010). Patients ventilated longer than 15 days had higher odds of death (odds ratio, 2.4; 95% CI, 1.3-4.2; p = 0.004). Almost 40% of patients (n = 85) were placed on high-frequency oscillatory ventilation with a mortality of 76.5% (odds ratio, 3.3; 95% CI, 1.7-6.5; p = 0.0004). Of the 20 patients who survived high-frequency oscillatory ventilation, 18 were placed on high-frequency oscillatory ventilation no later than the third day of invasive mechanical ventilation. In this subset of 85 patients, transition to high-frequency oscillatory ventilation within 2 days of the start of invasive mechanical ventilation resulted in a 76% decrease in the odds of death compared with those who transitioned to high-frequency oscillatory ventilation later in the invasive mechanical ventilation course. CONCLUSIONS: This study suggests that perhaps earlier more aggressive critical care interventions in the pediatric hematopoietic stem cell transplant patient with respiratory failure requiring invasive mechanical ventilation may offer an opportunity to improve outcomes.