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1.
Acute Respiratory Failure in Pediatric Hematopoietic Cell Transplantation-A Multicenter Study
Rowan, C. M., McArthur, J., Hsing, D. D., Gertz, S. J., Smith, L. S., Loomis, A., Fitzgerald, J. C., Nitu, M. E., Moser, E. A. S., Duncan, C. N., et al
Critical care medicine. 2018
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Editor's Choice
Abstract
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.
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Characteristics and Outcome of Patients After Allogeneic Hematopoietic Stem Cell Transplantation Treated With Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome
Wohlfarth, P., Beutel, G., Lebiedz, P., Stemmler, H. J., Staudinger, T., Schmidt, M., Kochanek, M., Liebregts, T., Taccone, F. S., Azoulay, E., et al
Critical Care Medicine. 2017;45(5):e500-e507
Abstract
OBJECTIVES The acute respiratory distress syndrome is a frequent condition following allogeneic hematopoietic stem cell transplantation. Extracorporeal membrane oxygenation may serve as rescue therapy in refractory acute respiratory distress syndrome but has not been assessed in allogeneic hematopoietic stem cell transplantation recipients. DESIGN Multicenter, retrospective, observational study. SETTING ICUs in 12 European tertiary care centers (Austria, Germany, France, and Belgium). PATIENTS All allogeneic hematopoietic stem cell transplantation recipients treated with venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome between 2010 and 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thirty-seven patients, nine of whom underwent noninvasive ventilation at the time of extracorporeal membrane oxygenation initiation, were analyzed. ICU admission occurred at a median of 146 (interquartile range, 27-321) days after allogeneic hematopoietic stem cell transplantation. The main reason for acute respiratory distress syndrome was pneumonia in 81% of patients. All but one patient undergoing noninvasive ventilation at extracorporeal membrane oxygenation initiation had to be intubated thereafter. Overall, seven patients (19%) survived to hospital discharge and were alive and in remission of their hematologic disease after a follow-up of 18 (range, 5-30) months. Only one of 24 patients (4%) initiated on extracorporeal membrane oxygenation within 240 days after allogeneic hematopoietic stem cell transplantation survived compared to six of 13 (46%) of those treated thereafter (p < 0.01). Fourteen patients (38%) experienced bleeding events, of which six (16%) were associated with fatal outcomes. CONCLUSIONS Discouraging survival rates in patients treated early after allogeneic hematopoietic stem cell transplantation do not support the use of extracorporeal membrane oxygenation for acute respiratory distress syndrome in this group. On the contrary, long-term allogeneic hematopoietic stem cell transplantation recipients otherwise eligible for full-code ICU management may be potential candidates for extracorporeal membrane oxygenation therapy in case of severe acute respiratory distress syndrome failing conventional measures.
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Weight gain and supplemental O2 : Risk factors during the hematopoietic cell transplant admission in pediatric patients
Rowan, C. M., Nitu, M. E., Moser, E. A. S., Swigonski, N. L., Renbarger, J. L.
Pediatric Blood & Cancer. 2017
Abstract
BACKGROUND Respiratory failure in the pediatric hematopoietic cell transplant (HCT) recipient is the leading cause for admission to the intensive care unit and carries a high mortality rate. The objective of this study is to investigate the association of clinical risk factors with the development of respiratory failure in the pediatric allogeneic HCT recipient. PROCEDURES This is a single-center, retrospective review of allogeneic pediatric HCT from 2008 to 2014. Multiple variables were examined. The primary outcome was respiratory failure. Percent weight gain was investigated at multiple time points. Bivariate and multivariate regression was used. RESULTS Of the 87 allogeneic HCT recipients, 22 (25%) developed respiratory failure. Mortality for entire cohort was 13.8%. All who died were intubated prior to death. The group with respiratory failure had significantly higher percent weight gain increase at multiple time points: peak weight prior to discharge or intubation (P = 0.008), weight at discharge or intubation (P = .001), and weight at day 43 (median day for intubation) (P = 0.02). Odds ratio (OR) for respiratory failure increased with increasing percentage peak weight gain: 10% increase (3.1 [1.1, 9.0]), 15% increase (4.1 [1.5, 11.2]), and 20% (8.3 [2.4. 28.9]). Fifty percent of all patients required supplemental O2 . OR for respiratory failure in patients requiring more than 1 l supplemental O2 is 25.3 (6.5, 98.7). CONCLUSION Percent weight gain and need for supplemental oxygen is highly associated with the development of respiratory failure in pediatric HCT recipients, representing predictors of acute respiratory failure in pediatric HCT. These data could be incorporated into an algorithm that should be developed, implemented, and validated in a prospective, multicenter fashion.Copyright © 2017 Wiley Periodicals, Inc.
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Pediatric Acute Respiratory Distress Syndrome in Pediatric Allogeneic Hematopoietic Stem Cell Transplants: A Multicenter Study
Rowan, C. M., Smith, L. S., Loomis, A., McArthur, J., Gertz, S. J., Fitzgerald, J. C., Nitu, M. E., Moser, E. A., Hsing, D. D., Duncan, C. N., et al
Pediatric Critical Care Medicine. 2017;18(4):304-309
Abstract
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.
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Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality
Zinter, M. S., Spicer, A., Orwoll, B. O., Alkhouli, M., Dvorak, C. C., Calfee, C. S., Matthay, M. A., Sapru, A.
American Journal of Physiology - Lung Cellular & Molecular Physiology. 2016;310(3):L224-31
Abstract
Angiopoietin-2 (Ang-2) is a key mediator of pulmonary vascular permeability. This study tested the association between plasma Ang-2 and mortality in pediatric acute respiratory distress syndrome (ARDS), with stratification for prior hematopoietic cellular transplantation (HCT), given the severe, yet poorly understood, ARDS phenotype of this subgroup. We enrolled 259 children <18 years of age with ARDS; 25 had prior HCT. Plasma Ang-2, von Willebrand Factor antigen (vWF), and vascular endothelial growth factor (VEGF) were measured on ARDS days 1 and 3 and correlated with patient outcomes. Day 1 and day 3 Ang-2 levels were associated with mortality independent of age, sex, race, and P/F ratio [odds ratio (OR) 3.7, 95% CI 1.1-11.5, P = 0.027; and OR 10.2, 95% confidence interval (CI) 2.2-46.5, P = 0.003, for each log10 increase in Ang-2]. vWF was associated with mortality (P = 0.027), but VEGF was not. The association between day 1 Ang-2 and mortality was independent of levels of both vWF and VEGF (OR 3.6, 95% CI 1.1-12.1, P = 0.039, for each log10 increase in Ang-2). 45% of the cohort had a rising Ang-2 between ARDS day 1 and 3 (adjusted mortality OR 3.3, 95% CI 1.2-9.2, P = 0.026). HCT patients with a rising Ang-2 had 70% mortality compared with 13% mortality for those without (OR 16.3, 95% CI 1.3-197.8, P = 0.028). Elevated plasma levels of Ang-2 were associated with mortality independent of vWF and VEGF. A rising Ang-2 between days 1 and 3 was strongly associated with mortality, particularly in pediatric HCT patients, suggesting vulnerability to ongoing endothelial damage. Copyright © 2016 the American Physiological Society.
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Prognostic factors and outcome of patients undergoing hematopoietic stem cell transplantation who are admitted to pediatric intensive care unit
An, K., Wang, Y., Li, B., Luo, C., Wang, J., Luo, C., Chen, J.
BMC Pediatrics. 2016;16(1):138
Abstract
BACKGROUND There are many studies about the prognosis and possible predictive factors of mortality for pediatric allogeneic hematopoietic stem cell transplantation (HSCT) recipients requiring pediatric intensive care unit (PICU) treatment, but the related study in China is lacking. This study investigates the data of these special patients in our center. METHODS This retrospective analysis is based on data from bone marrow center and PICU of our hospital. A total of 302 patients received allogeneic HSCT from January 2000 to December 2012, 29 of them were admitted to PICU because of various complications developed after transplantation. We collected the clinical data, identified the reasons why the patients to PICU, analyzed the mortality of these patients in PICU, and the prognostic factors of these patients. RESULTS The main reasons for admission were: respiratory failure (62.07 %), neurological abnormities (13.79 %), renal failure (13.79 %) and others (10.35 %). Twenty-one cases (72.41 %) died. Compared with survivors, the deaths cases had lower pediatric critical illness score (77 vs. 88, p=0.004); higher levels of lactic acid and serum urea nitrogen (4.02 vs. 1.19 mmol/L, P=0.008;11.56 vs. 7.13 m moll /L, P=0.045); more organs damaged (2.05 vs. 1.38, P=0.01), and required more supportive treatments (1.52 vs. 0.63, P=0.02). Univariate analysis identified pediatric critical illness score, use of mechanical ventilation, and the number of supportive treatment as the significant predictors to prognosis. Multivariate analysis by regression showed that pediatric critical illness score was the only independent prognostic factor (P=0.035). CONCLUSIONS In our study, pediatric allogeneic HSCT recipients who had PICU care had a high rate of mortality. Pediatric critical illness score was the independent prognostic factor for these patients.
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Respiratory failure in patients undergoing allogeneic hematopoietic SCT--a randomized trial on early non-invasive ventilation based on standard care hematology wards
Wermke, M., Schiemanck, S., Hoffken, G., Ehninger, G., Bornhauser, M., Illmer, T.
Bone Marrow Transplant. 2012;47(4):574-80
Abstract
The prognosis of patients suffering from respiratory failure (RF) after allogeneic hematopoietic SCT (HSCT) is poor. However, early treatment for using non-invasive ventilation (NIV) may be of benefit. We conducted a randomized trial to prove the impact of early NIV in patients in the early post-transplant period. A total of 526 patients undergoing HSCT in a single center were monitored for signs of RF. Patients with RF were enrolled into either treatment arm A (oxygen supply only) or treatment arm B (oxygen+intermittent NIV). RF had to be diagnosed in 86 patients (16%). RF was an independent risk factor for both short-term (100 day mortality/ OR 2.76; P<0.001) and long-term survival (OR 1.57; P<0.01). Although early RF treatment with NIV was associated with a decreased rate of failure to achieve sufficient oxygenation (39% in arm A vs 24% in arm B, P=0.17), neither intensive care unit admission rate, nor need for intubation or survival parameters were affected by the treatment strategy. An early interventional strategy using NIV was not associated with improvement of the prognosis of the patients. The limited influence of NIV may be related to the study design allowing for switching of treatment in case of unsatisfactory efficacy.