Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

Prophylactic Transfusion Strategies in Children Supported by Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021. STUDY SELECTION: Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Thirty-three references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. MEASUREMENTS AND MAIN RESULTS: The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-informed recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for prophylactic transfusion strategies for children supported with ECMO. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. We developed two good practice statements, 4 weak recommendations, and three expert consensus statements. CONCLUSIONS: Despite the frequency with which pediatric ECMO patients are transfused, there is insufficient evidence to formulate evidence-based prophylactic transfusion strategies.

Priorities for Clinical Research in Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From the Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Clinical outcomes in critically ill children on extracorporeal membrane oxygenation with severe thrombocytopenia.

INTRODUCTION: As international guidelines suggest keeping the platelet count between 50 and 100 × 109 cells/L in children on extracorporeal membrane oxygenation (ECMO), platelet transfusions are administered to two-thirds of ECMO days, and up to 70% of these patients still bleed. We aim to describe outcomes in critically ill children who develop severe thrombocytopenia on ECMO. METHODS: Single-center retrospective study, enrolling critically ill children on ECMO admitted at Children's Memorial Hermann, TX, between 1/2018 and 12/2022, with at least one platelet count below 50 × 109 cells/L (severe thrombocytopenia). Platelet counts were measured four times a day. We report platelet transfusion, bleeding, hemolysis, and clotting events within 6 h after transfusion, as well as ECMO duration and mortality. RESULTS: We enrolled 54 patients representing 337 ECMO days and 1190 platelet counts. Median weight was 3.7 kg and 54% were male. Severe thrombocytopenia was observed in 56% of platelet counts. Severe thrombocytopenia was not associated with bleeding in the subsequent 6 h (18% vs 20%, p = .95), but was associated with more frequent platelet transfusions (18% vs 11%, p = .001). There was no correlation between time spent with severe thrombocytopenia and the duration of ECMO (R2 = 0.03). While the time spent with severe thrombocytopenia was not associated with on-ECMO mortality rate (p = .36), there was an association with in-hospital mortality rate (p = .003). CONCLUSIONS: Our results indicate a restrictive platelet transfusion strategy is not associated with higher proportions of subsequent bleeding, duration of ECMO, or on-ECMO mortality rate. Multicenter studies are needed to evaluate further the appropriateness of this strategy.

Epidemiology of anticoagulation for children supported by extracorporeal membrane oxygenation in the United States: A Pediatric Hospital Information System database study.

INTRODUCTION: Due to the risk of thrombosis, nearly all children supported by extracorporeal membrane oxygenation (ECMO) receive systemic anticoagulation. While heparin has traditionally been used, there are reports of increased use of direct thrombin inhibitors. We sought to describe the use of anticoagulation in children supported by ECMO in the United States using a large administrative database. METHODS: We performed a retrospective cohort study of children supported by ECMO within the Pediatric Health Information System (PHIS) database. Pediatric encounters involving ECMO from 2012 to 2020 were identified. Data regarding demographics, diagnoses, anticoagulation, complications, and outcomes were extracted for eligible encounters. RESULTS: Eleven thousand five hundred ninety-five encounters that involved ECMO were identified. Fifty-four percent were male with an age range of 0-17 years and a median (IQR) age of 0 (0-2) years. Unfractionated heparin (UFH) only was used in 94% (95% CI: 93.6-94.5%) of encounters and UFH followed by bivalirudin in 5% (95% CI: 4.3-5.1%) of cases. There was a significant difference in the use of bivalirudin from 2012 to 2020 (p < 0.001). Differences in anticoagulation regimens were observed between infants and children (p = 0.004) and between those with and without cardiac indications for ECMO (p < 0.001). Four percent (95% CI: 4.1-4.8%) of encounters were associated with diagnostic coding for thrombosis and differences in occurrence of thrombosis were observed between different anticoagulant regimens (p < 0.001). CONCLUSIONS: Though the majority of children on ECMO in the United States receive heparin anticoagulation, there is an increase in use of direct thrombin inhibitors. Prospective studies must evaluate the efficacy of different anticoagulants in this patient population.

Scenario Decision-Making About Plasma and Platelet Transfusion for Intracranial Monitor Placement: Cross-Sectional Survey of Pediatric Intensivists and Neurosurgeons.

OBJECTIVES: To report pediatric intensivists' and pediatric neurosurgeons' responses to case-based scenarios about plasma and platelet transfusions before intracranial pressure (ICP) monitor placement in children with severe traumatic brain injury (TBI). DESIGN: Cross-sectional, electronic survey to evaluate reported plasma and platelet transfusion decisions in eight scenarios of TBI in which ICP monitor placement was indicated. SETTING: Survey administered through the Pediatric Acute Lung Injury and Sepsis Investigators and the American Association of Neurologic Surgeons. SUBJECTS: Pediatric intensivists and pediatric neurosurgeons. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 184 participants responded (85 identified as pediatric intensivists and 54 as pediatric neurosurgeons). In all eight scenarios, the majority of respondents reported that they would base their decision-making about plasma transfusion on international normalized ratio (INR) alone (60-69%), or platelet transfusion on platelet count alone (83-86%). Pediatric intensivists, as opposed to pediatric neurosurgeons, more frequently reported that they would have used viscoelastic testing in their consideration of plasma transfusion (32% vs. 7%, p < 0.001), as well as to guide platelet transfusions (29 vs. 8%, p < 0.001), for the case-based scenarios. For all relevant case-based scenarios, pediatric neurosurgeons in comparison with pediatric reported that they would use a lower median (interquartile range [IQR]) INR threshold for plasma transfusion (1.5 [IQR 1.4-1.7] vs. 2.0 [IQR 1.5-2.0], p < 0.001). Overall, in all respondents, the reported median platelet count threshold for platelet transfusion in the case-based scenario was 100 (IQR 50-100) ×10 9 /L, with no difference between specialties. CONCLUSIONS: Despite little evidence showing efficacy, when we tested specialists' decision-making, we found that they reported using INR and platelet count in pediatric case-based scenarios of TBI undergoing ICP monitor placement. We also found that pediatric intensivists and pediatric neurosurgeons had differences in decision-making about the scenarios.

Bleeding in Critically Ill Children With Malignancy or Hematopoietic Cell Transplant: A Single-Center Prospective Cohort Study.

OBJECTIVES: To determine the incidence of bleeding in critically ill children with malignancy and to describe associated patient characteristics, interventions, and clinical outcomes. DESIGN: Prospective cohort study. SETTING: PICU in a specialized cancer hospital. PATIENTS: Children with malignancy or hematopoietic cell transplant 0-18 years of age were admitted to the PICU from November 2020 to November 2021. INTERVENTIONS: None. MEASUREMENTS: Patient demographic data, laboratory values, and PICU outcome data were collected. Bleeding was classified according to the Bleeding Assessment Scale in Critically Ill Children. MAIN RESULTS: Ninety-three bleeding patients were enrolled, and a total of 322 bleeding days were recorded. The median (interquartile range [IQR]) age was 5.8 (2.9-11.8) years and 56% (52/93) of the patients were male. There were 121 new bleeding episodes, in 593 at-risk person-days, translating into a 20% incidence rate per day (95% CI, 17-24%). The incidence of severe, moderate, and minimal bleeding was 2% (95% CI, 1-3), 4% (95% CI, 3-6), and 14% (95% CI, 12-17), respectively. Of the new bleeding episodes, 9% were severe, 25% were moderate and 66% were minimal. Thrombocytopenia was the only laboratory value independently associated with severe bleeding ( p = 0.009), as compared to minimal and moderate bleeding episodes. History of radiation therapy was independently associated with severe bleeding ( p = 0.04). We failed to identify an association between a history of stem cell transplant ( p = 0.49) or tumor type ( p = 0.76), and bleeding severity. Patients were transfused any blood product on 28% (95% CI, 22-34) of the bleeding days. Severe bleeding was associated with increased length of mechanical ventilation ( p = 0.003), longer PICU stays ( p = 0.03), and higher PICU mortality ( p = 0.004). CONCLUSIONS: In this prospective cohort of children with malignancy, the incidence rate of bleeding was 20%. Most events were classified as minimal bleeding. Low platelet count and radiation therapy were variables independently associated with severe bleeding episodes.

Performance of Platelet Mass Index as a Marker of Severity for Sepsis and Septic Shock in Children.

Platelet mass index (PMI) as a prognostic indicator in pediatric sepsis has not been previously reported. In this retrospective observational study, we evaluated PMI's performance as a prognostic indicator in children aged younger than 18 years with sepsis and septic shock in relationship with survival. Over 5 years, we collected data from 122 children admitted to our pediatric intensive care unit (PICU). PMI accuracy was assessed with sensitivity and specificity and its discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Median PMI values on days 1 and 3 of PICU admission were lower among nonsurvivors. On day 1 of PICU admission, a cutoff PMI value of 1,450 fL/nL resulted in a sensitivity of 72% and a specificity of 69%, and the AUC was 0.70 (95% confidence interval [CI]: 0.55-0.86). Similarly, on day 3, a cutoff of 900 fL/nL resulted in a sensitivity of 71% and a specificity of 70%, and the AUC was 0.76 (95% CI: 0.59-0.92). Our exploratory study suggests that low PMI in children with septic shock is associated with increased mortality. Considering the PMI's fair performance, further studies should be performed to assess its clinical value.

Efficacy of Prostacyclin Anticoagulation in Critically Ill Patients Requiring Extracorporeal Support: A Systematic Review and Meta-Analysis.

Extracorporeal support modalities are highly prothrombotic. Anticoagulation is frequently used for patients receiving Continuous Renal Replacement Therapy (CRRT), Molecular Adsorbent Recirculating System (MARS), and Extracorporeal Membrane Oxygenation (ECMO). The objective of this systematic review and meta-analysis is to determine if prostacyclin-based anticoagulation strategies are effective compared to other anticoagulation strategies, in critically ill children and adults who needs extracorporeal support, such as continuous renal replacement therapy. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to June 1, 2022. Circuit lifespan, proportion of bleeding, thrombotic, and hypotensive events, and mortality were evaluated. Out of 2,078 studies that were screened, 17 studies (1,333 patients) were included. The mean circuit lifespan was 29.7 hours in the patients in the prostacyclin-based anticoagulation series and 27.3 hours in the patients in the heparin- or citrate-based anticoagulation series, with a mean difference of 2.5 hours (95%CI -12.0;16.9, p=0.74, I2=0.99, n=4,003 circuits). Bleeding occurred in 9.5% of the patients in the prostacyclin-based anticoagulation series and in 17.1% of the patients in the control series, which was a statistically significant decrease (LogOR -1.14 (95%CI -1.91;-0.37), p<0.001, I2=0.19, n=470). Thrombotic events occurred in 3.6% of the patients in the prostacyclin-based anticoagulation series and in 2.2% of the patients in the control series, which was not statistically different (LogOR 0.97 (95%CI -1.09;3.04), p=0.35, I2=0.0, n=115). Hypotensive events occurred in 13.4% of the patients in the prostacyclin-based anticoagulation series and in 11.0% of the patients in the control series, which was not statistically different (LogOR -0.56 (95%CI -1.87;0.74), p=0.40, I2=0.35, n=299). The mortality rate was 26.3% in the prostacyclin-based anticoagulation series, and 32.7% in the control series, which was not statistically different (LogOR -0.40 (95%CI -0.87;0.08), p=0.10, I2=0.00, n=390). The overall risk of bias was low to moderate. In this systematic review and meta-analysis of 17 studies, prostacyclin-based anticoagulation was associated with fewer bleeding events, but with similar circuit lifespans, thrombotic events, hypotensive events, and mortality rates. The potential benefits of prostacyclin-based anticoagulation should be explored in large randomized controlled trials.

The Effects of Expectation Setting and Bundle Consent on Acute Caregiver Stress in the PICU: A Randomized Controlled Trial.

OBJECTIVES: Having a child admitted to the PICU is a stressful experience for parents and can have long-term negative mental health consequences. The objective was to determine if formalized expectation setting and bundled consent for invasive procedures upon admission impacts the acute stress burden on parents. DESIGN: Prospective cluster randomized controlled trial. SETTING: Single-center, tertiary PICU. SUBJECTS: Parents/guardians of patients, 0-18 years old, admitted to PICU. INTERVENTIONS: During experimental weeks, all patients admitted to PICU were bundled-consented for common procedures and given a novel unit introductory letter and "Common Procedures Explained" document. During control weeks, all patients were consented for invasive procedures with separate consents for each procedure. Parents then completed a demographic survey and Stress Overload Scale-Short (SOS-S) 48-72 hours after their child's admission. For each participant, the SOS-S generates a Personal Vulnerability (PV) score and an Event Load (EL) score. Parents' perception of the life-threatening nature of their child's condition was also evaluated. MEASUREMENTS AND MAIN RESULTS: Over 73 weeks, 1,882 patients were screened and 261 consented to the SOS-S. Median PV score was 10.4 in the control group and 9.1 in the experimental group ( p = 0.15). Median EL score was 11.3 for the control group and 10.5 in the experimental group ( p = 0.42). Adjusting for demographic variables and severity of illness, there was no independent association between either PV or EL and bundled consent. However, a parent's perception of threat-to-life was significantly related to the allocated group ( p = 0.036), which resulted in a decreased percentage of parents who rated their child's illness as "Extremely" life-threatening (experimental group, 17% vs control group, 26%). CONCLUSIONS: This study did not demonstrate a decrease in stress when bundled consent was obtained. However, this intervention decreased the parents' perceived severity of illness. Further multicenter studies are needed to evaluate the effects of bundled consent on parents.

Pediatric firearm injury related emergency department visits and hospitalizations: a population-based study in the United States.

Background: Firearm injury (FI) is the leading cause of death in children and adolescents in the United States (US). We describe the epidemiology of pediatric FI-associated emergency department (ED) visits and hospitalizations in the US stratified by race and ethnicity. Methods: Data on pediatric (0-17-year-olds) FI were analyzed using the 2019 Nationwide Emergency Department Sample (NEDS) and Kids' Inpatient Database (KID), the largest all-payer databases in the US for ED visits and pediatric hospitalizations, respectively. FI encounters were stratified by race and ethnicity. Poisson regression was used to identify factors associated with in-hospital mortality. Sampling weights were applied to generate nationally representative estimates. Findings: There were 7017 pediatric ED visits with FI (NEDS); 85.0% (5961/7017) were male and 73.0% (5125/7017) were adolescents (15-17 years). Overall, 5.5% (384/7017) died in the ED; 53.1% (3727/7017) of ED encounters did not result in hospitalization. There were 2817 pediatric FI hospitalizations (KID); 84.1% (2369/2817) were male and 71.6% (2018/2817) were adolescents; 51.4% (1447/2817) of FI were unintentional, 42.8% (1207/2817) were assault-related, and 5.8% (163/2817) were self-inflicted. Black children had the highest proportion (52.6%; 1481/2817) of hospitalizations among all race and ethnicities (p < 0.0001 vs. White). White children had the highest proportion of hospitalizations for self-inflicted injuries (16.6% [91/551] vs. 4.9% [25/504; p < 0.0001] in Hispanics and 1.7% [24/1481] in Blacks; p < 0.0001). The majority (56.5%; 1591/2817) of hospitalizations were patients from low-income zip codes (median annual-household-income <$44,000); 70% (1971/2817) had Medicaid as the primary insurance payer. Overall, 8.0% (225/2817) died during FI-associated hospitalizations. Self-inflicted injuries had the highest in-hospital mortality (prevalence ratio = 8.20, 95% CI = 6.06-11.10 vs. unintentional). Interpretation: Black children and children with lower household incomes were disproportionately impacted by FI resulting from assaults and accidents, while White children had the highest proportion of self-inflicted FI injuries. Public health and legal policy interventions are needed to prevent pediatric FI. Funding: US National Institutes of Health.

Anticoagulation and hemostasis on extracorporeal membrane oxygenation.

PURPOSE OF REVIEW: The purpose of this review is to describe the hemostatic changes induced by extracorporeal membrane oxygenation (ECMO), the need to balance the risks of bleeding and clotting with anticoagulation and hemostatic transfusions, and the inherent risks to these interventions. RECENT FINDINGS: Both bleeding and clotting are frequent complications of ECMO. To prevent clotting events, virtually, all children are anticoagulated. However, the optimal anticoagulation strategy is unknown. A recent systematic review of observational studies showed that anti-Xa-guided strategies were associated with a two-fold decrease in bleeding and no increase in clotting complications. These results need to be tested in randomized controlled trials. To avoid bleeding events, platelet transfusions are frequently prescribed to children on ECMO. However, platelet transfusions have recently been shown to be independently associated with increased bleeding and clotting. Therefore, the optimal platelet transfusion strategy must be evaluated appropriately. SUMMARY: Most patients on ECMO will develop either a hemorrhagic or thrombotic complication. Balancing these risks involves careful titration of anticoagulation to prevent clotting and hemostatic transfusions to prevent bleeding. As the current level of evidence is low, prospective randomized trials are needed.

Transfusion Strategies in the 21st Century: A Case-Based Narrative Report.

The transfusion of all blood components (red blood cells, plasma, and platelets) has been associated with increased morbidity and mortality in children. It is essential that pediatric providers weigh the risks and benefits before transfusing a critically ill child. A growing body of evidence has demonstrated the safety of restrictive transfusion practices in critically ill children.

First nosocomial infections in children supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

BACKGROUND: Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a standard procedure for patient with refractory shock in Pediatric Intensive Care Unit (PICU). There is a paucity of data on the time relationship between VA-ECMO support, nosocomial infection occurrence, and PICU length of stay (LOS). The aim of this study was to determine the characteristics and impact of ECMO-related infections. METHODS: This is a retrospective study from 01/2008 to 12/2014, enrolling children with a VA-ECMO support for > 6 h. We recorded the first PICU infection during the VA-ECMO run, defined as a positive microbiological sample with clinical signs of infection or clinical signs of severe infection without positive sample. RESULTS: During the study period, 41 patients (25/41 male) were included, with a median age of 41.2 months (IQR 12.9-89.9) and a 53% mortality rate. Median time on VA-ECMO was 4.2 d (IQR 2-7.1), median PICU LOS was 14.7 d (IQR 4,7-26,9). Overall, 34% patients developed an infection, with an incidence of 60/1000 VA-ECMO days. Median time to first infection was 4 d (IQR 3-5), with Pseudomonas spp. being the most commonly detected microorganism (42%). Infected sites were ventilator-associated pneumonia (9/14), sternotomy infection (2/14), bloodstream (2/14) and urinary tract infections (1/14). Longer VA-ECMO support (> 5 d) (OR 5.9 (CI 95% 1.4-24.6; p = 0.01) and longer PICU stay (> 14 d) (OR 12 (95% CI 2.2-65.5; p = 0.004) were associated with infection. CONCLUSION: In this single-center study, we underlined the high proportion and early occurrence of infections in patient on VA-ECMO, mostly in the first week. As infection was an early event, it may prolong the duration of VA-ECMO support and PICU LOS. Further research is needed to better understand the impact of infections on VA-ECMO and develop prevention strategies.

Cardiac manifestations of multisystem inflammatory syndrome of children after SARS-CoV-2 infection: a systematic review and meta-analysis.

This systematic review and meta-analysis were conducted to evaluate the prevalence of cardiac manifestations associated with multisystem inflammatory syndrome in children worldwide. We conducted electronic searches in Ovid MEDLINE, Ovid EMBASE, and the World Health Organization COVID-19 Literature Database from the inception of the SARS-CoV-2 pandemic to 1 January, 2022. Three authors independently screened the abstracts to determine eligibility, assessed methodology in the full texts, and extracted the data.We identified 2848 citations; 94 studies (14,932 patients) were included. The prevalence of vasopressors was 48.2% (95% CI 45.1%, 51.3%), left ventricular systolic dysfunction occurred in 37.2% (95% CI 34.1%, 40.3%), myocarditis in 34.1% (95% CI 30.5%, 37.8%), electrocardiographic dysrhythmias and abnormalities detected in 23.1% (95% CI 18.8%, 27.6%), coronary abnormalities identified in 18% (95% CI 16%, 20%), extracorporeal membrane oxygenation deployed in 2.2% (95% CI 1.7%, 2.8%), and mortality rate of 2.2% (95% CI 1.7%, 2.7%). A sensitivity analysis was performed after removing eleven studies with high bias, and the adjusted prevalence was not different than the original evaluation.In this meta-analysis of the largest cohort of multisystem inflammatory syndrome in children patients to date, we established the most accurate prevalence of the most common cardiac manifestations. Providers will subsequently have more precise data to anticipate patient outcomes and approach discussions concerning the frequency of monitoring outside the acute hospital period.

Lung Ultrasound versus Chest X-Ray for the Detection of Fluid Overload in Critically Ill Children: A Systematic Review.

Fluid overload is a common complication of critical illness, associated with increased morbidity and mortality. Pulmonary fluid status is difficult to evaluate clinically and many clinicians utilize chest X-ray (CXR) to identify fluid overload. Adult data have shown lung ultrasound (LUS) to be a more sensitive modality. Our objective was to determine the performance of LUS for detecting fluid overload, with comparison to CXR, in critically ill children. We conducted a systematic review using multiple electronic databases and included studies from inception to November 15, 2020. The sensitivity and specificity of each test were evaluated. Out of 1,209 studies screened, 4 met eligibility criteria. Overall, CXR is reported to have low sensitivity (44-58%) and moderate specificity (52-94%) to detect fluid overload, while LUS is reported to have high sensitivity (90-100%) and specificity (94-100%). Overall, the quality of evidence was moderate, and the gold standard was different in each study. Our systematic review suggests LUS is more sensitive and specific than CXR to identify pulmonary fluid overload in critically ill children. Considering the clinical burden of fluid overload and the relative ease of obtaining LUS, further evaluation of LUS to diagnose volume overload is warranted.

Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES: Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION: Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION: A standardized data extraction tool was used. DATA SYNTHESIS: Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2 =72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS: Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.

Anticoagulation strategies and recurrence of venous thromboembolic events in patients with sickle cell disease: a systematic review and meta-analysis.

Sickle cell disease (SCD) results in many complications including an increased risk of developing venous thromboembolic events (VTEs) and an increased risk of mortality as a result. We conducted a systematic review using multiple databases to compare the efficacy of different anticoagulation in preventing recurrence, development of bleeding, progression of thrombus, and mortality in patients with SCD and a venous thrombotic event. Eight hundred seventy-one studies were screened and six studies were included. Among patients with SCD who experienced a VTE and were anticoagulated, the overall recurrence of VTE was 27.6% (95%CI 23.5-31.9). The overall progression to pulmonary embolism (PE) was 11.7% (95%CI 4.3-22.1). The overall bleeding rate was 14.1% (95%CI 7.8-21.9) and the overall mortality was 3.7% (95%CI 0.8-8.5). Based on observational studies, there did not appear to be differences between anticoagulant classes for the above adverse outcomes. Significant heterogeneity in the patient population and outcome measures limited the interpretation of the results. More studies, specifically randomized trials, are needed to help direct appropriate management of VTE's in patients with sickle cell disease (PROSPERO ID: 236,208).

Ketamine Boluses Are Associated with a Reduction in Intracranial Pressure and an Increase in Cerebral Perfusion Pressure: A Retrospective Observational Study of Patients with Severe Traumatic Brain Injury.

Background: Increased intracranial pressure (ICP) and hypotension have long been shown to lead to worse outcomes in the severe traumatic brain injury (TBI) population. Adequate sedation is a fundamental principle in TBI care, and ketamine is an attractive option for sedation since it does not commonly cause systemic hypotension, whereas most other sedative medications do. We evaluated the effects of ketamine boluses on both ICP and cerebral perfusion pressure (CPP) in patients with severe TBI and refractory ICP. Methods: We conducted a retrospective review of all patients admitted to the neurointensive care unit at a single tertiary referral center who had a severe traumatic brain injury with indwelling intracranial pressure monitors. We identified those patients with refractory intracranial pressure who received boluses of ketamine. We defined refractory as any sustained ICP greater than 20 mmHg after the patient was adequately sedated, serum Na was at goal, and CO2 was maintained between 35 and 40 mmHg. The primary outcome was a reduction in ICP with a subsequent increase in CPP. Results: The patient cohort consisted of 44 patients with a median age of 30 years and a median presenting Glasgow Coma Scale (GCS) of 5. The median reduction in ICP after administration of a ketamine bolus was -3.5 mmHg (IQR -9 to +1), and the postketamine ICP was significantly different from baseline (p < 0.001). Ketamine boluses led to an increase in CPP by 2 mmHg (IQR -5 to +12), which was also significantly different from baseline (p < 0.001). Conclusion: In this single-institution study of patients with severe traumatic brain injury, ketamine boluses were associated with a reduction in ICP and an increase in CPP. This was a retrospective review of 43 patients and is therefore limited in nature, but further randomized controlled trials should be performed to confirm the findings.