NT-proBNP course during MIS-C post-COVID-19: an observational study.

Multisystem inflammatory syndrome in children (MIS-C or PIMS-TS) is a severe disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. However, contrasting cut-offs have been suggested. The aims of the present study were to compare NT-proBNP values depending on the time of measurement and to describe the NT-proBNP course during the MIS-C episode. The data from a single-centre cohort observational study on the impact of time to diagnosis, defined as the time from first symptom to diagnosis of MIS-C, were used for the purpose of this study, with an extended period of inclusion from May 2020 to April 2023. The timing and level of all NT-proBNP samples available for each patient were retrospectively collected. Thirty-seven children (18 (49%) females, median age 8.8 years, 14 (38%) with shock) were included. Until diagnosis, NT-proBNP increased with time and was significantly higher at 6 days from first symptoms than at 3 days (median (interquartile range) 32,933 (7773-61,592) versus 1994 (1291-4190) pg/mL, respectively, p = 0.031). From diagnosis, NT-proBNP decreased by at least 50% after 3.0 (2.1-5.3) days (n = 12) when NT-proBNP at diagnosis was low ≤ 11,000 pg/mL versus 1.8 (0.7-3.4) days (n = 16) when NT-proBNP at diagnosis was high (p = 0.040), and after 3.6 (2.4-5.9) days (n = 7) when fever persisted after 48 h versus 1.8 (0.8-3.0) days (n = 21) when fever resolved before 48 h (p = 0.004).  Conclusions: During the MIS-C episode, NT-proBNP increased over time until diagnosis and treatment. It dropped faster thereafter in children with high NT-proBNP at diagnosis > 11,000 pg/mL and slower in case of persistent fever. What is Known: • NT-proBNP is useful in MIS-C for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. • Contrasting cut-offs for differential diagnosis and severity assessment have been suggested. What is New: • Before diagnosis, NT-proBNP increases with time and is significantly higher at 6 days from first symptoms than at 3 days suggesting different cut-offs depending on the timing of measurement. • From diagnosis and treatment initiation, the 50% NT-proBNP drop occurs earlier in children with high NT-proBNP at diagnosis > 11,000 pg/mL and later in children with persistent fever.

Visiting Policies and Parental Presence During PICU Admission: A Survey in French Units.

OBJECTIVES: To describe the policies about parent visiting and involvement in care during admission to French PICUs. DESIGN: A structured questionnaire was emailed to the chief of each of 35 French PICUs. Data about visiting policies, involvement in care, evolution of policies, and general characteristics were collected from April 2021 to May 2021. A descriptive analysis was conducted. SETTING: Thirty-five PICUs in France. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-nine of 35 (83%) PICUs replied. Twenty-four-hour access for parents was reported for all PICUs responding. Other allowed visitors were grandparents (21/29, 72%) and siblings (19/29, 66%) with professional support. Simultaneous visits were restricted to two visitors in 83% (24/29) of PICUs. Family presence was always permitted during medical rounds for 20 of 29 (69%) PICUs. Most of the units rarely or never allowed parental presence during the most invasive procedures, such as central venous catheter placement (18/29, 62%) and intubation (22/29, 76%). CONCLUSIONS: Unrestricted access to the PICU, for both parents, was available in all responding French units. There were, however, restrictions on the number of visitors and the presence of other family members at the bedside. Moreover, permission for parental presence during care procedures was heterogenous, and mainly restricted. National guidelines and educational programs are needed to support family wishes and promote acceptance by healthcare providers in French PICUs.

Impact of puberty as threshold to differentiate outcome of out-of-hospital cardiac arrest care groups: a nationwide observational study in France.

BACKGROUND: Since 2005, the international guidelines for out-of-hospital cardiac arrest (OHCA) use puberty to differentiate paediatric and adult care. This threshold is mainly relied on the more frequent respiratory aetiologies in children. Hitherto, to the best of our knowledge, no study has compared the characteristics and outcomes of non-pubescent children, adolescents and adult patients with OHCA. In this study, we intended to describe the characteristics, outcome and factors associated with survival of patients who experienced OHCA in the three groups: children, adolescents (pubescent<18 years) and adults (<65 years), to assess the pertinence of the guidelines. METHODS: Data from the French national cardiac arrest registry (2012-2017) were used in this nationwide observational study. Victims of OHCA who were <65 years old were included. The characteristics and outcomes of children and adolescents, and adolescents and adults were compared. Logistic regression was performed in each group to identify factors associated with survival at day 30. RESULTS: We included 934 children, 433 adolescents and 26 952 adults. Respiratory aetiology was more frequent and shockable rhythm less frequent in children compared with adolescents (25.5% vs 17.2%, p=0.025 and 2.4% vs 6.8%, p<0.001, respectively). However, these differences were not observed between adolescents and adults (17.2% vs 14.1%, p=0.266 and 6.8% vs 10%, p=0.055, respectively). Between children and adolescents, and adolescents and adults, there was no significant difference in survival at day 30 (8.6%vs 9.8% and 9.8% vs 8.5%, respectively). For all groups, shockable initial rhythm was a factor of survival. CONCLUSION: Frequency of respiratory aetiologies and shockable rhythm were common in adolescents and adults and different between children and adolescents. These results indicate that puberty as a threshold in international guidelines seems to be relevant.

Intraosseous or Peripheral IV Access in Pediatric Cardiac Arrest? Results From the French National Cardiac Arrest Registry.

OBJECTIVES: Despite the evolving recommendations that favor the use of intraosseous access in pediatric resuscitation, the impact of vascular access type on survival in young children has not been demonstrated. The aim of this study was to assess the impact of the intravascular injection route on the return on spontaneous circulation, survival to hospital admission (0 day), and 30 days or survival to hospital discharge, by comparing survival rates in young children having intraosseous and peripheral IV access. The second aim was to compare the rates of favorable neurologic outcome after 30 days or survival to hospital discharge. DESIGN: This was a multicenter retrospective comparative study between July 2011 and October 2018. SETTING: Based on the French cardiac arrest registry data. PATIENTS: All prepubescent (males < 12 yr old, females < 10 yr old) victims of an out-of-hospital cardiac arrest. INTERVENTIONS: Patients with adrenaline administration by intraosseous versus peripheral venous technique were compared, using propensity score matching. MEASUREMENTS AND MAIN RESULTS: The analysis included 603 prepubescent patients, 351 (58%) in the intraosseous group and 252 (42%) in the peripheral IV group. Intraosseous group patients were younger, lighter, with more medical cause for arrest. The intraosseous group had lower survival rates at 30 days or hospital discharge (n = 6; 1.7%) than the peripheral IV group (n = 12; 4.8%) (p = 0.030). After matching, 101 pairs of patients were created. No difference was observed on return of spontaneous circulation or 0-day survival rates (odds ratio = 1.000 [95% CI, 0.518-1.930]; odds ratio = 0.946 [95% CI, 0.492-1.817], respectively) and on 30 days or hospital discharge survival (n = 3 in both groups) (odds ratio = 1.000 [95% CI, 0.197-5.076]). Meaningful statistical evaluation of neurologic status among survivors was precluded by inadequate numbers. CONCLUSIONS: The type of injection route (intraosseous or peripheral venous access) does not appear to have an impact on survival of out-of-hospital cardiac arrest in a prepubescent population, but limitations of propensity matching limit a definitive conclusion.

The newborn infant parasympathetic evaluation in pediatric and neonatology: a literature review.

PURPOSE: The Newborn Infant Parasympathetic Evaluation (NIPE) is a heart rate variability-based technology for assessing pain and comfort in neonates and infants under 2-years-old. This review aims to investigate the clinical utility of the NIPE. METHODS: Two investigators screened Pubmed/Medline and Google Scholar for relevant studies, independently. One investigator extracted data, which were reviewed by a second investigator. RESULTS: The NIPE was used during/after painful stimuli (6 studies), in the context of general anaesthesia (2 studies), and for comfort assessment (6 studies). A) Evaluation of procedural pain/distress: 2 studies reported that the mean-NIPE could be used for reliable monitoring of prolonged pain, and one study reported the association between instant-NIPE and pain after a stimulus but the instant-NIPE represents the NIPE average over 3 min. Two studies found no correlation between the NIPE and comfort behavior/pain scales, but they mainly differed in patients' gestational age and evaluation methodology. B) There are only 2 studies for the evaluation of nociception during surgery under general anaesthesia with contradictory results. C) Studies assessing neonates' comfort reported increased NIPE scores during skin-to-skin contact and during facilitated tucking associated with a human voice. No effect on NIPE scores of facilitated tucking during echocardiography was reported in preterm infants. One study reported significantly different NIPE scores with 2 surfactant therapy protocols. Overall, study populations were small and heterogeneous. CONCLUSION: The results regarding NIPE's performances differ between studies. Given the limited number of studies and the heterogeneous outcomes, more studies are required to confirm the NIPE usefulness in the different clinical settings.

Comparison of the Automated Pediatric Logistic Organ Dysfunction-2 Versus Manual Pediatric Logistic Organ Dysfunction-2 Score for Critically Ill Children.

OBJECTIVES: The Pediatric Logistic Organ Dysfunction-2 is a validated score that quantifies organ dysfunction severity and requires complex data collection that is time-consuming and subject to errors. We hypothesized that a computer algorithm that automatically collects and calculates the Pediatric Logistic Organ Dysfunction-2 (aPELOD-2) score would be valid, fast and at least as accurate as a manual approach (mPELOD-2). DESIGN: Retrospective cohort study. SETTING: Single center tertiary medical and surgical pediatric critical care unit (Sainte-Justine Hospital, Montreal, Canada). PATIENTS: Critically ill children participating in four clinical studies between January 2013 and August 2018, a period during which mPELOD-2 data were manually collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The aPELOD-2 was calculated for all consecutive admissions between 2013 and 2018 (n = 5,279) and had a good survival discrimination with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.81-0.88). We also collected data from four single-center studies in which mPELOD-2 was calculated (n = 796, 57% medical, 43% surgical) and compared these measurements to those of the aPELOD-2. For those patients, median age was 15 months (interquartile range, 3-73 mo), median ICU stay was 5 days (interquartile range, 3-9 d), mortality was 3.9% (n = 28). The intraclass correlation coefficient between mPELOD-2 and aPELOD-2 was 0.75 (95% CI, 0.73-0.77). The Bland-Altman showed a bias of 1.9 (95% CI, 1.7-2) and limits of agreement of -3.1 (95% CI, -3.4 to -2.8) to 6.8 (95% CI, 6.5-7.2). The highest agreement (Cohen's Kappa) of the Pediatric Logistic Organ Dysfunction-2 components was noted for lactate level (0.88), invasive ventilation (0.86), and creatinine level (0.82) and the lowest for the Glasgow Coma Scale (0.52). The proportion of patients with multiple organ dysfunction syndrome was higher for aPELOD-2 (78%) than mPELOD-2 (72%; p = 0.002). The aPELOD-2 had a better survival discrimination (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.72-0.90) over mPELOD-2 (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.82; p = 0.01). CONCLUSIONS: We successfully created a freely available automatic algorithm to calculate the Pediatric Logistic Organ Dysfunction-2 score that is less labor intensive and has better survival discrimination than the manual calculation. Use of an automated system could greatly facilitate integration of the Pediatric Logistic Organ Dysfunction-2 score at the bedside and within clinical decision support systems.

Assessment of Procedural Distress in Sedated/Intubated Children Under 3 Years Old Using the Newborn Infant Parasympathetic Evaluation: A Diagnostic Accuracy Pilot Study.

OBJECTIVES: Newborn infant parasympathetic evaluation index is based on heart rate variability and is related to the autonomic response to pain or stress. The Comfort Behavior Scale is used to assess distress intensity in sedated intubated children. The objective of this study was to assess the validity and performance of newborn infant parasympathetic evaluation as a distress indicator during procedural distress. DESIGN: Monocentric, prospective, noninterventional pilot study of diagnostic accuracy between October 1, 2017, and April 30, 2019. SETTING: PICU in a tertiary care university hospital. PATIENTS: Sedated intubated children under 3 years old. INTERVENTIONS: We continuously obtained mean newborn infant parasympathetic evaluation and instantaneous newborn infant parasympathetic evaluation scores and compared them to Comfort Behavior scores obtained before (T1 period), during (T2 period), and after (T3 period) care procedures. MEASUREMENTS AND MAIN RESULTS: We obtained 54 measurements from 32 patients. The median age was 4 months (23 d to 31 mo). Between T1 and T2, there was a significant decrease in the instantaneous newborn infant parasympathetic evaluation and mean newborn infant parasympathetic evaluation scores (64 ± 2 to 42 ± 1 [p 0.0001] and 64 ± 1 to 59 ± 1 [p = 0.007], respectively) and a significant increase in the Comfort Behavior scores (from 12 ± 0 to 16 ± 1; p 0.0001). Comfort Behavior scores and instantaneous newborn infant parasympathetic evaluation and mean newborn infant parasympathetic evaluation scores were significantly inversely correlated (r = -0.44, p 0.0001 and r = -0.19, p = 0.01, respectively). With a instantaneous newborn infant parasympathetic evaluation score threshold of 53, the sensitivity, specificity, positive predictive, and negative predictive values to predict a Comfort Behavior Scale up to 17 were 80.0%, 73.5%, 43.8%, and 93.5%, respectively. CONCLUSIONS: Instantaneous newborn infant parasympathetic evaluation is valid for assessing distress in sedated/intubated children in the PICU. Further studies are needed to confirm these results and for newborn infant parasympathetic evaluation-based comparisons of sedation-analgesia protocols.

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.

International Survey on Determinants of Antibiotic Duration and Discontinuation in Pediatric Critically Ill Patients.

OBJECTIVES: We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries. DESIGN: Cross-sectional survey. SETTING: PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries. CONCLUSIONS: Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.

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.

Anaphylaxis admissions in pediatric intensive care units: Follow-up and risk of recurrence.

BACKGROUND: Data about the risk of anaphylaxis recurrence in children are lacking. We assessed anaphylaxis recurrence and medical follow-up in a cohort of children previously hospitalized in a French pediatric intensive care unit (PICU) for anaphylaxis. METHODS: We conducted a telephone survey of 166 children (≤18 years) hospitalized from 2003 to 2013. RESULTS: In all, 106 (64%) completed the survey (boys, 59%; mean age [SD]: 15.3 years [5.5]). The main index triggers were drugs (45%) and foods (37%). The mean duration follow-up was of 7.7 years (SD: 2.4). Thirty-eight (36%) children experienced 399 new allergic reactions during a follow-up period of 282 patient-years (incidence rate: 1.4/100 patients/y; 95% CI: 0.64-2.04). Twelve children experienced 19 anaphylaxis reactions including five requiring PICU admission (anaphylaxis recurrence rate: 0.20/100 patients/y; 95% CI non-calculable). Food was the trigger for 79% of recurrent reactions and drugs for 8%. The food trigger was previously known in 83%, the same as the index trigger in 69%. Overall, 1.5% of the recurrent reactions were treated with adrenaline injection and 8% an emergency hospital admission. Patients with recurrence had more likely a history of food allergy (P < 10-4 ), asthma (P < 0.005), atopic dermatitis (P < 0.05) than those without. 31% of the 50 children with food allergy did not see an allergist, 23% had no adrenaline auto-injector, and 26% lacked a school individual healthcare plan. CONCLUSIONS: Following a PICU admission for anaphylaxis, recurrence is high in children with food allergy compared with drug allergy. Allergic comorbidities increase the risk. Medical follow-up has to be improved for these at-risk children.

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.

Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?

OBJECTIVE: A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection. DESIGN: Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2. SETTINGS: Nine university-affiliated PICUs in Europe. PATIENTS: Only children with hypotension-low systolic blood pressure or low mean blood pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were considered in shock. MEASUREMENTS AND MAIN RESULTS: We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96) in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure. CONCLUSION: Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.

Outcomes Related to the Use of Frozen Plasma or Pooled Solvent/Detergent-Treated Plasma in Critically Ill Children.

OBJECTIVE: To determine if the use of fresh frozen plasma/frozen plasma 24 hours compared to solvent detergent plasma is associated with international normalized ratio reduction or ICU mortality in critically ill children. DESIGN: This is an a priori secondary analysis of a prospective, observational study. Study groups were defined as those transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma. Outcomes were international normalized ratio reduction and ICU mortality. Multivariable logistic regression was used to determine independent associations. SETTING: One hundred one PICUs in 21 countries. PATIENTS: All critically ill children admitted to a participating unit were included if they received at least one plasma unit during six predefined 1-week (Monday to Friday) periods. All children were exclusively transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 443 patients enrolled in the study. Twenty-four patients (5%) were excluded because no plasma type was recorded; the remaining 419 patients were analyzed. Fresh frozen plasma/frozen plasma 24 hours group included 357 patients, and the solvent detergent plasma group included 62 patients. The median (interquartile range) age and weight were 1 year (0.2-6.4) and 9.4 kg (4.0-21.1), respectively. There was no difference in reason for admission, severity of illness score, pretransfusion international normalized ratio, or lactate values; however, there was a difference in primary indication for plasma transfusion (p < 0.001). There was no difference in median (interquartile range) international normalized ratio reduction, between fresh frozen plasma/frozen plasma 24 hours and solvent detergent plasma study groups, -0.2 (-0.4 to 0) and -0.2 (-0.3 to 0), respectively (p = 0.80). ICU mortality was lower in the solvent detergent plasma versus fresh frozen plasma/frozen plasma 24 hours groups, 14.5% versus 29.1%%, respectively (p = 0.02). Upon adjusted analysis, solvent detergent plasma transfusion was independently associated with reduced ICU mortality (odds ratio, 0.40; 95% CI, 0.16-0.99; p = 0.05). CONCLUSIONS: Solvent detergent plasma use in critically ill children may be associated with improved survival. This hypothesis-generating data support a randomized controlled trial comparing solvent detergent plasma to fresh frozen plasma/frozen plasma 24 hours.

Indications and Effects of Plasma Transfusions in Critically Ill Children.

RATIONALE: Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES: To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. METHODS: Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS: During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. CONCLUSIONS: One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.