Biomarkers for Early Complications After Hematopoietic Stem Cell Transplantation

The advancement in technology, particularly in the field of omics, has led to numerous discoveries of biomarkers for early post-HSCT complications. Future research must include the testing of newly discovered biomarkers against existing, validated biomarkers. Work also needs to be done to implement the promising, validated biomarkers into clinical practice in a time-efficient and cost-effective manner. The prognostic biomarkers should be incorporated into clinical trials so that the effect of early recognition on the outcomes of HSCT recipients can be assessed. Diagnostic biomarkers can help to differentiate the complex variety of diseases that can be present in this population. Finally, biomarkers that can serve as therapeutic targets should be further studied. Many of these post-HSCT complications have limited or nonspecific therapeutic options. For example, corticosteroids are the first-line therapy for aGVHD. Using biomarkers to help identify underlying biologic pathways may open new therapeutic avenues that deserve investigation. This major advancement in technology allows for early diagnosis of complications, risk stratification for complications, and potential new therapeutic targets. All of these strides can improve the utilization of life-saving allogeneic HSCT while minimizing complications and mortality

Modification and Assessment of the Bedside Pediatric Early Warning Score in the Pediatric Allogeneic Hematopoietic Cell Transplant Population

OBJECTIVES: To determine the validity of the Bedside Pediatric Early Warning Score system in the hematopoietic cell transplant population, and to determine if the addition of weight gain further strengthens the association with need for PICU admission. DESIGN: Retrospective cohort study of pediatric allogeneic hematopoietic cell transplant patients from 2009 to 2016. Daily Pediatric Early Warning Score and weights were collected during hospitalization. Logistic regression was used to identify associations between maximum Pediatric Early Warning Score or Pediatric Early Warning Score plus weight gain and the need for PICU intervention. The primary outcome was need for PICU intervention; secondary outcomes included mortality and intubation. SETTING: A large quaternary free-standing children's hospital. PATIENTS: One-hundred two pediatric allogeneic hematopoietic cell transplant recipients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 102 hematopoietic cell transplant patients included in the study, 29 were admitted to the PICU. The median peak Pediatric Early Warning Score was 11 (interquartile range, 8-13) in the PICU admission cohort, compared with 4 (interquartile range, 3-5) in the cohort without a PICU admission (p < 0.0001). Pediatric Early Warning Score greater than or equal to 8 had a sensitivity of 76% and a specificity of 90%. The area under the receiver operating characteristics curve was 0.83. There was a high negative predictive value at this Pediatric Early Warning Score of 90%. When Pediatric Early Warning Score greater than or equal to 8 and weight gain greater than or equal to 7% were compared together, the area under the receiver operating characteristic curve increased to 0.88. CONCLUSIONS: In this study, a Pediatric Early Warning Score greater than or equal to 8 was associated with PICU admission, having a moderately high sensitivity and high specificity. This study adds to literature supporting Pediatric Early Warning Score monitoring for hematopoietic cell transplant patients. Combining weight gain with Pediatric Early Warning Score improved the discriminative ability of the model to predict the need for critical care, suggesting that incorporation of weight gain into Pediatric Early Warning Score may be beneficial for monitoring of hematopoietic cell transplant patients

Pediatric asthma severity score is associated with critical care interventions

AIM: To determine if a standardized asthma severity scoring system (PASS) was associated with the time spent on continuous albuterol and length of stay in the pediatric intensive care unit (PICU). METHODS: This is a single center, retrospective chart review study at a major children's hospital in an urban location. To qualify for this study, participants must have been admitted to the PICU with a diagnosis of status asthmaticus. There were a total of 188 participants between the ages of two and nineteen, excluding patients receiving antibiotics for pneumonia. PASS was calculated upon PICU admission. Subjects were put into one of three categories based on PASS: ≤ 7 (mild), 8-11 (moderate), and ≥ 12 (severe). The groups were compared based on different variables, including length of continuous albuterol and PICU stay. RESULTS: The age distribution across all groups was similar. The median length of continuous albuterol was longest in the severe group with a duration of 21.5 h (11.5-27.5), compared to 15 (7.75-23.75) and 10 (5-15) in the moderate and mild groups, respectively (P = 0.001). The length of stay was longest in the severe group, with a stay of 35.6 h (22-49) compared to 26.5 (17-30) and 17.6 (12-29) in the moderate and mild groups, respectively (P = 0.001). CONCLUSION: A higher PASS is associated with a longer time on continuous albuterol, an increased likelihood to require noninvasive ventilation, and a longer stay in the ICU. This may help safely distribute asthmatics to lower and higher levels of care in the future

Implementation of Continuous Capnography Is Associated With a Decreased Utilization of Blood Gases

Background Capnography provides a continuous, non-invasive monitoring of the CO2 to assess adequacy of ventilation and provide added safety features in mechanically ventilated patients by allowing for quick identification of unplanned extubation. These monitors may allow for decreased utilization of blood gases. The objective was to determine if implementation of continuous capnography monitoring decreases the utilization of blood gases resulting in decreased charges. Methods This is a retrospective review of a quality improvement project that compares the utilization of blood gases before and after the implementation of standard continuous capnography. The time period of April 2010 to September 2010 was compared to April 2011 to September 2011. Parameters collected included total number of blood gases analyzed, cost of blood gas analysis, ventilator and patient days. Results The total number of blood gases after the institution of end tidal CO2 monitoring decreased from 12,937 in 2009 and 13,171 in 2010 to 8,070 in 2011. The average number of blood gases per encounter decreased from 20.8 in 2009 and 21.6 in 2010 to 13.8 post intervention. The blood gases per ventilator day decreased from 4.94 in 2009 and 4.76 in 2010 to 3.30 post intervention. The total charge savings over a 6-month period was $880,496. Conclusions Continuous capnography resulted in a significant savings over a 6-month period by decreasing the utilization of blood gas measurements

Pulmonary Specific Ancillary Treatment for Pediatric Acute Respiratory Distress Syndrome:From the Second Pediatric Acute Lung Injury Consensus Conference

OBJECTIVES: We conducted an updated review of the literature on pulmonary-specific ancillary therapies for pediatric acute respiratory distress syndrome (PARDS) to provide an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: Searches were limited to children, PARDS or hypoxic respiratory failure and overlap with pulmonary-specific ancillary therapies DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-six studies were identified for full-text extraction. Four clinical recommendations were generated, related to use of inhaled nitric oxide, surfactant, prone positioning, and corticosteroids. Two good practice statements were generated on the use of routine endotracheal suctioning and installation of isotonic saline prior to endotracheal suctioning. Three research statements were generated related to: the use of open versus closed suctioning, specific methods of airway clearance, and various other ancillary therapies. CONCLUSIONS: The evidence to support or refute any of the specific ancillary therapies in children with PARDS remains low. Further investigation, including a focus on specific subpopulations, is needed to better understand the role, if any, of these various ancillary therapies in PARDS.</p

Nurse practitioner coverage is associated with a decrease in length of stay in a pediatric chronic ventilator dependent unit

AIM: To hypothesize a dedicated critical care nurse practitioner (NP) is associated with a decreased length of stay (LOS) from a pediatric chronic ventilator dependent unit (PCVDU). METHODS: We retrospectively reviewed patients requiring care in the PCVDU from May 2001 through May 2011 comparing the 5 years prior to the 5 years post implementation of the critical care NP in 2005. LOS and room charges were obtained. RESULTS: The average LOS decreased from a median of 55 d [interquartile range (IQR): 9.8-108.3] to a median of 12 (IQR: 4.0-41.0) with the implementation of a dedicated critical care NP (P < 1.0001). Post implementation of a dedicated NP, a savings of 25738049 in room charges was noted over 5 years. CONCLUSION: Our data demonstrates a critical care NP coverage model in a PCVDU is associated with a significantly reduced LOS demonstrating that the NP is an efficient and likely cost-effective addition to a medically comprehensive service

Clinical Features of Critical Coronavirus Disease 2019 in Children

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objectives: We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and comparisons between critically ill and noncritical hospitalized pediatric patients. Design: Observational cohort study. Setting: Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic. Patients: All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included. Interventions: Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation. Measurements and Main Results: Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15–18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died. Conclusions: Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047); and by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637). Drs. Bhumbra, Malin, Khaitan, John, Rowan, and Enane disclosed off-label use of remdesivir, convalescent plasma, hydroxychloroquine, and tocilizumab. Drs. Kirkpatrick and Enane are supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047). Dr. Bhumbra is supported by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637)

Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality

Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period. We performed a 5-year retrospective study of pediatric patients who underwent allogeneic HCT for any indication. Patients were categorized based on albumin level. Hypoalbuminemia was defined as <3.1 g/dL. A total of 73 patients were included, with a median age of 7.4 years (IQR 3.3, 13.2). Patients with hypoalbuminemia had higher needs for critical care interventions including non-invasive ventilation (44% vs 8%, P=.01), mechanical ventilation (67% vs 17%, P<.01), and vasoactive therapy (56% vs 16%, P=.01). Patients with hypoalbuminemia also had a higher 6-month mortality (56% vs 17%, P=.02). Our data demonstrate that children undergoing allogeneic HCT with hypoalbuminemia in the pretransplant period are more likely to require critical care interventions and have higher 6-month mortality. These findings identify an at-risk population in which nutritional improvements may be instituted prior to HCT in hopes of improving outcomes

The Use of a Kinetic Therapy Rotational Bed in Pediatric Acute Respiratory Distress Syndrome: A Case Series

Patients with acute respiratory distress syndrome (ARDS) commonly have dependent atelectasis and heterogeneous lung disease. Due to the heterogenous lung volumes seen, the application of positive end expiratory pressure (PEEP) can have both beneficial and deleterious effects. Alternating supine and prone positioning may be beneficial in ARDS by providing more homogenous distribution of PEEP and decreasing intrapulmonary shunt. In pediatrics, the pediatric acute lung injury and consensus conference (PALICC) recommended to consider it in severe pediatric ARDS (PARDS). Manually prone positioning patients can be burdensome in larger patients. In adults, the use of rotational beds has eased care of these patients. There is little published data about rotational bed therapy in children. Therefore, we sought to describe the use of a rotational bed in children with PARDS. We performed a retrospective case series of children who utilized a rotational bed as an adjunctive therapy for their PARDS. Patient data were collected and analyzed. Descriptive statistical analyses were performed and reported. Oxygenation indices (OI) pre- and post-prone positioning were analyzed. Twelve patients with PARDS were treated with a rotational bed with minimal adverse events. There were no complications noted. Three patients had malfunctioning of their arterial line while on the rotational bed. Oxygenation indices improved over time in 11 of the 12 patients included in the study while on the rotational bed. Rotational beds can be safely utilized in pediatric patients. In larger children with PARDS, where it may be more difficult to perform a manual prone position, use of a rotational bed can be considered a safe alternative