Prevalence and determinants of anemia at discharge in pediatric intensive care survivors.

BACKGROUND: Restrictive transfusion practices are increasingly being followed in pediatric intensive care units (PICU); consequently, more patients are discharged anemic from PICU. Given the possible impact of anemia on long-term neurodevelopmental outcomes, we aim to describe the epidemiology of anemia at PICU discharge in a mixed (pediatric and cardiac) cohort of PICU survivors and to characterize risk factors for anemia. STUDY DESIGN AND METHODS: We performed a retrospective cohort study in the PICU of a multidisciplinary tertiary-care university-affiliated center. All consecutive PICU survivors for whom a hemoglobin level was available at PICU discharge were included. Baseline characteristics and hemoglobin levels were extracted from an electronic medical records database. RESULTS: From January 2013 to January 2018, 4750 patients were admitted to the PICU (97.1% survival); discharge hemoglobin levels were available for 4124 patients. Overall, 50.9% (n = 2100) were anemic at PICU discharge. Anemia at PICU discharge was also common in the cardiac surgery population (53.3%), mainly in acyanotic patients; only 24.6% of cyanotic patients were anemic according to standard definitions of anemia. Cardiac surgery patients were transfused more often and at higher hemoglobin levels than medical and non-cardiac surgery patients. Anemia at admission was the strongest predictor of anemia at discharge (odds ratios (OR): 6.51, 95% confidence interval (CI:5.40;7.85)). DISCUSSION: Half of PICU survivors are anemic at discharge. Further studies are required to determine the course of anemia after discharge and to ascertain whether anemia is associated with adverse long-term outcomes.

Strategies to Reduce Diagnostic Blood Loss and Anemia in Hospitalized Patients: A Scoping Review.

OBJECTIVES: Blood sampling is a recognized contributor to hospital-acquired anemia. We aimed to bundle all published neonatal, pediatric, and adult data regarding clinical interventions to reduce diagnostic blood loss. DATA SOURCES: Four electronic databases were searched for eligible studies from inception until May 2021. STUDY SELECTION: Two reviewers independently selected studies, using predefined criteria. DATA EXTRACTION: One author extracted data, including study design, population, period, intervention type and comparator, and outcome variables (diagnostic blood volume and frequency, anemia, and transfusion). DATA SYNTHESIS: Of 16,132 articles identified, we included 39 trials; 12 (31%) were randomized controlled trials. Among six types of interventions, 27 (69%) studies were conducted in adult patients, six (15%) in children, and six (15%) in neonates. Overall results were heterogeneous. Most studies targeted a transfusion reduction ( n = 28; 72%), followed by reduced blood loss ( n = 24; 62%) and test frequency ( n = 15; 38%). Small volume blood tubes ( n = 7) and blood conservation devices ( n = 9) lead to a significant reduction of blood loss in adults (8/9) and less transfusion of adults (5/8) and neonates (1/1). Point-of-care testing ( n = 6) effectively reduced blood loss (4/4) and transfusion (4/6) in neonates and adults. Bundles including staff education and protocols reduced blood test frequency and volume in adults (7/7) and children (5/5). CONCLUSIONS: Evidence on interventions to reduce diagnostic blood loss and associated complications is highly heterogeneous. Blood conservation devices and smaller tubes appear effective in adults, whereas point-of-care testing and bundled interventions including protocols and teaching seem promising in adults and children.

The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial.

OBJECTIVES: Guidelines recommend against RBC transfusion in hemodynamically stable (HDS) children without cardiac disease, if hemoglobin is greater than or equal to 7 g/dL. We sought to assess the clinical and economic impact of compliance with RBC transfusion guidelines. DESIGN: A nonprespecified secondary analysis of noncardiac, HDS patients in the randomized trial Age of Blood in Children (NCT01977547) in PICUs. Costs analyzed included ICU stay and physician fees. Stabilized inverse propensity for treatment weighting was used to create a cohort balanced with respect to potential confounding variables. Weighted regression models were fit to evaluate outcomes based on guideline compliance. SETTING: Fifty international tertiary care centers. PATIENTS: Critically ill children 3 days to 16 years old transfused RBCs at less than or equal to 7 days of ICU admission. Six-hundred eighty-seven subjects who met eligibility criteria were included in the analysis. INTERVENTIONS: Initial RBC transfusions administered when hemoglobin was less than 7 g/dL were considered "compliant" or "non-compliant" if hemoglobin was greater than or equal to 7 g/dL. MEASUREMENTS AND MAIN RESULTS: Frequency of new or progressive multiple organ system dysfunction (NPMODS), ICU survival, and associated costs. The hypothesis was formulated after data collection but exposure groups were masked until completion of planned analyses. Forty-nine percent of patients (338/687) received a noncompliant initial transfusion. Weighted cohorts were balanced with respect to confounding variables (absolute standardized differences < 0.1). No differences were noted in NPMODS frequency (relative risk, 0.86; 95% CI, 0.61-1.22; p = 0.4). Patients receiving compliant transfusions had more ICU-free days (mean difference, 1.73; 95% CI, 0.57-2.88; p = 0.003). Compliance reduced mean costs in ICU by $38,845 U.S. dollars per patient (95% CI, $65,048-$12,641). CONCLUSIONS: Deferring transfusion until hemoglobin is less than 7 g/dL is not associated with increased organ dysfunction in this population but is independently associated with increased likelihood of live ICU discharge and lower ICU costs.

Transfusion-Associated Delirium in Children: No Difference Between Short Storage Versus Standard Issue RBCs.

OBJECTIVES: Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN: This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING: Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS: Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS: Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001). CONCLUSIONS: RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Noncardiac Surgery and Critically Ill Children Undergoing Invasive Procedures Outside the Operating Room: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room. CONCLUSIONS: Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations.

Impact of Blood Sampling on Anemia in the PICU: A Prospective Cohort Study.

OBJECTIVES: Fifty percent of children are anemic after a critical illness. Iatrogenic blood testing may be a contributor to this problem. The objectives of this study were to describe blood sampling practice in a PICU, determine patient factors associated with increased sampling, and examine the association among blood sampling volume, anemia at PICU discharge, and change in hemoglobin from PICU entry to PICU discharge. DESIGN: Prospective observational cohort study. SETTING: PICU of Sainte-Justine University Hospital. PATIENTS: All children consecutively admitted during a 4-month period. MEASUREMENTS AND MAIN RESULTS: Four hundred twenty-three children were enrolled. Mean blood volume sampled was 3.9 (±19) mL/kg/stay, of which 26% was discarded volume. Children with central venous or arterial access were sampled more than those without access (p < 0.05). Children with sepsis, shock, or cardiac surgery were most sampled, those with a primary respiratory diagnosis; the least (p < 0.001). We detected a strong association between blood sample volume and mechanical ventilation (H, 81.35; p < 0.0001), but no association with severity of illness (Worst Pediatric Logistic Organ Dysfunction score) (R, -0.044; p = 0.43). Multivariate analysis (n = 314) showed a significant association between the volume of blood sampled (as continuous variable) and anemia at discharge (adjusted OR, 1.63; 95% CI, 1.18-2.45; p = 0.003). We lacked power to detect an association between blood sampling and change in hemoglobin from PICU admission to PICU discharge. CONCLUSIONS: Diagnostic blood sampling in PICU is associated with anemia at discharge. Twenty-five percent of blood losses from sampling is wasted. Volumes are highest for patients with sepsis, shock, or cardiac surgery, and in patients with vascular access or ventilatory support.

Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an Investigator-Initiated Research Network.

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022.

Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).

OBJECTIVES: Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients. DESIGN: Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]). SETTING: Not applicable. PATIENTS: Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients. CONCLUSIONS: The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.

Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study).

BACKGROUND: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). STUDY DESIGN AND METHODS: This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). RESULTS: No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. CONCLUSION: While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

Neonatal red blood cell transfusion.

Transfusions are more common in premature infants with approximately 40% of low birth weight infants and up to 90% of extremely low birth weight infants requiring red blood cell transfusion. Although red blood cell transfusion can be life-saving in these preterm infants, it has been associated with higher rates of complications including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and possibly abnormal neurodevelopment. The main objective of this review is to assess current red blood cell transfusion practices in the neonatal intensive care unit, to summarize available neonatal transfusion guidelines published in different countries and to emphasize the wide variation in transfusion thresholds that exists for red blood cell transfusion. This review also addresses certain issues specific to red blood cell processing for the neonatal population including storage time, irradiation, cytomegalovirus (CMV) prevention strategies and patient blood management. Future research avenues are proposed to better define optimal transfusion practice in neonatal intensive care units.

Risk factors for post-transplant Epstein-Barr virus events in pediatric recipients of hematopoietic stem cell transplants.

BACKGROUND: Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. METHODS: We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. RESULTS: Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). CONCLUSION: This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.

Intravenous Immunoglobulin Use In Critically Ill Children.

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population. Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018. Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations. Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children.

The safety of platelet (PLT) concentrates with longer storage duration has been questioned due to biochemical and functional changes that occur during blood collection and storage. Some studies have suggested that transfusion efficacy is decreased and immune system dysfunction is worsened with increased storage age. We sought to describe the effect of PLT storage age on laboratory and clinical outcomes in critically ill children receiving PLT transfusions. STUDY DESIGN AND METHODS: We performed a secondary analysis of a prospective, observational point-prevalence study. Children (3 days to 16 years of age) from 82 pediatric intensive care units in 16 countries were enrolled if they received a PLT transfusion during one of the predefined screening weeks. Outcomes (including PLT count increments, organ dysfunction, and transfusion reactions) were evaluated by PLT storage age. RESULTS: Data from 497 patients were analyzed. The age of the PLT transfusions ranged from 1 to 7 days but the majority were 4 (24%) or 5 (36%) days of age. Nearly two-thirds of PLT concentrates were transfused to prevent bleeding. The indication for transfusion did not differ between storage age groups (P = .610). After patient and product variables were adjusted for, there was no association between storage age and incremental change in total PLT count or organ dysfunction scoring. A significant association between fresher storage age and febrile transfusion reactions (P = .002) was observed. CONCLUSION: The results in a large, diverse cohort of critically ill children raise questions about the impact of storage age on transfusion and clinical outcomes which require further prospective evaluation.

Pediatric Plasma and Platelet Transfusions on Extracorporeal Membrane Oxygenation: A Subgroup Analysis of Two Large International Point-Prevalence Studies and the Role of Local Guidelines.

OBJECTIVES: To describe the indications and thresholds for plasma and platelet transfusions for pediatric extracorporeal membrane oxygenation, to compare responses to these transfusions and to describe institutional protocols directing their administration. DESIGN: Subgroup analysis of two prospective, observational studies paired with survey of sites who enrolled subjects into this cohort. SETTING: Fifty-one PICUs in 13 countries. PATIENTS: Children (3 d to 16 yr old) were enrolled if they received a plasma or platelet transfusion while on extracorporeal membrane oxygenation during one of the predefined screening weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-eight children on extracorporeal membrane oxygenation received plasma transfusions and 90 received platelet transfusions. Sixty percent of plasma transfusions (29/48) and 79% of the platelet transfusions (71/90) were given for prophylaxis of bleeding. The median (interquartile range) international normalized ratio prior to transfusion, known in 75% of the patients (36/48), was 1.45 (1.20-1.85). The median (interquartile range) total platelet count prior to transfusion, known in all of the patients, was 70 × 10/L (52-90 × 10/L). The international normalized ratio and total platelet count values prior to transfusion did not vary based on bleeding versus nonbleeding indications. The median (interquartile range) reduction in international normalized ratio for mild coagulopathies (international normalized ratio ≤ 2.0) was 0.1 (0.4-0), median (interquartile range) increase in fibrinogen was 0.2 g/L (0.1-0.4 g/L) and median increase in total platelet count was 34 × 10/L (10-74 × 10/L). Through the course of their admission, children supported by extracorporeal membrane oxygenation received a total median (interquartile range) dose of 75 mL/kg (36-159 mL/kg) of plasma transfusions and 92 mL/kg (42-239 mL/kg) of platelet transfusions. Institutional protocols varied but provided guidance for platelet transfusions more commonly. CONCLUSIONS: Children supported by extracorporeal membrane oxygenation receive large volumes of plasma and platelet transfusions with some institutional guidance in the form of protocols, but significant variation in practice. Interventional studies are necessary to provide evidence to direct the transfusion of hemostatic products in children supported by extracorporeal membrane oxygenation.

How 217 Pediatric Intensivists Manage Anemia at PICU Discharge: Online Responses to an International Survey.

OBJECTIVE: To describe the management of anemia at PICU discharge by pediatric intensivists. DESIGN: Self-administered, online, scenario-based survey. SETTING: PICUs in Australia/New Zealand, Europe, and North America. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respondents were asked to report their decisions regarding RBC transfusions, iron, and erythropoietin prescription to children ready to be discharged from PICU, who had been admitted for hemorrhagic shock, cardiac surgery, craniofacial surgery, and polytrauma. Clinical and biological variables were altered separately in order to assess their effect on the management of anemia. Two-hundred seventeen responses were analyzed. They reported that the mean (± SEM) transfusion threshold was a hemoglobin level of 6.9 ± 0.09 g/dL after hemorrhagic shock, 7.6 ± 0.10 g/dL after cardiac surgery, 7.0 ± 0.10 g/dL after craniofacial surgery, and 7.0 ± 0.10 g/dL after polytrauma (p < 0.001). The most important increase in transfusion threshold was observed in the presence of a cyanotic heart disease (mean increase ranging from 1.80 to 2.30 g/dL when compared with baseline scenario) or left ventricular dysfunction (mean increase, 1.41-2.15 g/dL). One third of respondents stated that they would not prescribe iron at PICU discharge, regardless of the hemoglobin level or the baseline scenario. Most respondents (69.4-75.0%, depending on the scenario) did not prescribe erythropoietin. CONCLUSIONS: Pediatric intensivists state that they use restrictive transfusion strategies at PICU discharge similar to those they use during the acute phase of critical illness. Supplemental iron is less frequently prescribed than RBCs, and prescription of erythropoietin is uncommon. Optimal management of post-PICU anemia is currently unknown. Further studies are required to highlight the consequences of this anemia and to determine appropriate management.

Bleeding Assessment Scale in Critically Ill Children (BASIC): Physician-Driven Diagnostic Criteria for Bleeding Severity.

OBJECTIVE: Although bleeding frequently occurs in critical illness, no published definition to date describes the severity of bleeding accurately in critically ill children. We sought to develop diagnostic criteria for bleeding severity in critically ill children. DESIGN: Delphi consensus process of multidisciplinary experts in bleeding/hemostasis in critically ill children, followed by prospective cohort study to test internal validity. SETTING: PICU. PATIENTS: Children at risk of bleeding in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-four physicians worldwide (10 on a steering committee and 14 on an expert committee) from disciplines related to bleeding participated in development of a definition for clinically relevant bleeding. A provisional definition was created from 35 descriptors of bleeding. Using a modified online Delphi process and conference calls, the final definition resulted after seven rounds of voting. The Bleeding Assessment Scale in Critically Ill Children definition categorizes bleeding into severe, moderate, and minimal, using organ dysfunction, proportional changes in vital signs, anemia, and quantifiable bleeding. The criteria do not include treatments such as red cell transfusion or surgical interventions performed in response to the bleed. The definition was prospectively applied to 40 critically ill children with 46 distinct bleeding episodes. The kappa statistic between the two observers was 0.74 (95% CI, 0.57-0.91) representing substantial inter-rater reliability. CONCLUSIONS: The Bleeding Assessment Scale in Critically Ill Children definition of clinically relevant bleeding severity is the first physician-driven definition applicable for bleeding in critically ill children derived via international expert consensus. The Bleeding Assessment Scale in Critically Ill Children definition includes clear criteria for bleeding severity in critically ill children. We anticipate that it will facilitate clinical communication among pediatric intensivists pertaining to bleeding and serve in the design of future epidemiologic studies if it is validated with patient outcomes.

International Study of the Epidemiology of Platelet Transfusions in Critically Ill Children With an Underlying Oncologic Diagnosis.

OBJECTIVES: To describe the epidemiology of platelet transfusions in critically ill children with an underlying oncologic diagnosis and to examine effects of prophylactic versus therapeutic transfusions. DESIGN: Subgroup analysis of a prospective, observational study. SETTING: Eighty-two PICUs in 16 countries. PATIENTS: All children (3 d to 16 yr old) who received a platelet transfusion during one of the six predefined screening weeks and had received chemotherapy in the previous 6 months or had undergone hematopoietic stem cell transplantation in the last year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 548 patients enrolled in the parent study, 237 (43%) had an underlying oncologic diagnosis. In this population, 71% (168/237) of transfusions were given prophylactically, and 59% (139/237) of transfusions were given at a total platelet count greater than 20 × 10/L, higher than the current recommendations. Those with an underlying oncologic diagnosis were significantly older, and received less support including less mechanical ventilation, fewer medications that affect platelet function, and less use of extracorporeal life support than those without an underlying oncologic diagnosis. In this subpopulation, there were no statistically significant differences in median (interquartile range) platelet transfusion thresholds when comparing bleeding or nonbleeding patients (50 × 10/L [10-50 × 10/L] and 30 × 10/L [10-50 × 10/L], respectively [p = 0.166]). The median (interquartile range) interval transfusion increment in children with an underlying oncologic diagnosis was 17 × 10/L (6-52 × 10/L). The presence of an underlying oncologic diagnosis was associated with a poor platelet increment response to platelet transfusion in this cohort (adjusted odds ratio, 0.46; 95% CI, 0.22-0.95; p = 0.035). CONCLUSIONS: Children with an underlying oncologic diagnosis receive nearly half of platelet transfusions prescribed by pediatric intensivists. Over half of these transfusions are prescribed at total platelet count greater than current recommendations. Studies must be done to clarify appropriate indications for platelet transfusions in this vulnerable population.

Effects of ABO Matching of Platelet Transfusions in Critically Ill Children.

OBJECTIVES: To determine if transfusing ABO compatible platelets has a greater effect on incremental change in platelet count as compared to ABO incompatible platelets in critically ill children. DESIGN: Secondary analysis of a prospective, observational study. Transfusions were classified as either ABO compatible, major incompatibility, or minor incompatibility. The primary outcome was the incremental change in platelet count. Transfusion reactions were analyzed as a secondary outcome. SETTING: Eighty-two PICUs in 16 countries. PATIENTS: Children (3 d to 16 yr old) were enrolled if they received a platelet transfusion during one of the predefined screening weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five-hundred three children were enrolled and had complete ABO information for both donor and recipient, as well as laboratory data. Three-hundred forty-two (68%) received ABO-identical platelets, 133 (26%) received platelets with major incompatibility, and 28 (6%) received platelets with minor incompatibility. Age, weight, proportion with mechanical ventilation or underlying oncologic diagnosis did not differ between the groups. After adjustment for transfusion dose, there was no difference in the incremental change in platelet count between the groups; the median (interquartile range) change for ABO-identical transfusions was 28 × 10 cells/L (8-68 × 10 cells/L), for transfusions with major incompatibility 26 × 10 cells/L (7-74 × 10 cells/L), and for transfusions with minor incompatibility 54 × 10 cells/L (14-81 × 10 cells/L) (p = 0.37). No differences in count increment between the groups were noted for bleeding (p = 0.92) and nonbleeding patients (p = 0.29). There were also no differences observed between the groups for any transfusion reaction (p = 0.07). CONCLUSIONS: No differences were seen in the incremental change in platelet count nor in transfusion reactions when comparing major ABO incompatible platelet transfusions with ABO compatible transfusions in a large study of critically ill children. Studies in larger, prospectively enrolled cohorts should be performed to validate whether ABO matching for platelet transfusions in critically ill children is necessary.

Anemia at Discharge From the PICU: A Bicenter Descriptive Study.

OBJECTIVE: To determine the prevalence and risk markers of anemia at PICU discharge. DESIGN: Bicenter retrospective cohort study. SETTING: Two multidisciplinary French PICUs. PATIENTS: All children admitted during a 5-year period, staying in the PICU for at least 2 days, and for whom a hemoglobin was available at PICU discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient, admission, and PICU stay characteristics were retrospectively collected in the electronic medical records of each participating PICU. Anemia was defined according to the World Health Organization criteria. Among the 3,170 patients included for analysis, 1,868 (58.9%) were anemic at discharge from PICU. The proportion of anemic children differed between age categories, whereas the median hemoglobin level did not exhibit significant variations according to age. After multivariate adjustment, anemia at PICU admission was the strongest predictor of anemia at PICU discharge, and the strength of this association varied according to age (interaction). Children anemic at PICU admission had a reduced risk of anemia at PICU discharge if transfused with RBCs during the PICU stay, if less than 6 months old, or if creatinine level at PICU admission was low. Children not anemic at PICU admission had an increased risk of anemia at PICU discharge if they were thrombocytopenic at PICU admission, if they had higher C-reactive protein levels, and if they received plasma transfusion, inotropic/vasopressor support, or mechanical ventilation during the PICU stay. CONCLUSIONS: Anemia is frequent after pediatric critical illness. Anemia status at PICU admission defines different subgroups of critically ill children with specific prevalence and risk markers of anemia at PICU discharge. Further studies are required to confirm our results, to better define anemia during pediatric critical illness, and to highlight the causes of post-PICU stay anemia, its course, and its association with post-PICU outcomes.

Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients: A Randomized Clinical Trial.

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial. Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. Design, Setting, and Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded. Interventions: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. Main Outcomes and Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death. Results: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34). Conclusions and Relevance: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells. Trial Registration: ClinicalTrials.gov Identifier: NCT01977547.