Case Report: Congenital tuberculosis in a premature infant requiring extracorporeal membrane oxygenation.

Congenital tuberculosis is a rare infectious disease with less than 500 cases documented worldwide. Mortality is significant, ranging from 34 to 53%, and death without treatment is inevitable. Patients exhibit nonspecific symptoms such as fever, cough, respiratory distress, feeding intolerance, and irritability which can make appropriate diagnosis challenging in Peng et al. (2011) Pediatr Pulmonol 46(12), 1215-1224. Tuberculosis prevalence is particularly high in developing countries where access to resources can be limited in World Health Organization (2019) Global tuberculosis report 2019, Geneva. We present a 2.4-kg premature male infant with acute respiratory distress syndrome secondary to congenital tuberculosis caused by Mycobacterium bovis and tuberculosis-immune reconstitution inflammatory syndrome who was successfully supported with veno-arterial extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation in critically ill neonatal and pediatric patients with acute respiratory failure: a guide for the clinician.

Intro: Extracorporeal membrane oxygenation for neonatal and pediatric respiratory failure continues to demonstrate improving outcomes, largely due to advances in technology along with refined management strategies despite mounting patient acuity and complexity. Successful use of ECMO requires thoughtful initiation and candidacy strategies, along with reducing the risk of ventilator induced lung injury and the progression to multiorgan failure.Areas Covered: This review describes current ECMO management strategies for neonatal and pediatric patients with acute refractory respiratory failure and summarizes relevant published literature. ECMO initiation and candidacy, along with ventilator and sedation management, are highlighted. Additionally, rapidly expanding areas of interest such as anticoagulation strategies, transfusion thresholds, rehabilitation on ECMO, and drug pharmacokinetics are described.Expert Opinion: Over the last few decades, published studies supporting ECMO use for acute refractory respiratory failure, along with institutional experience, have resulted in increased utilization although more randomized-controlled trials are needed. Future research should focus on filling the knowledge gaps that remain regarding anticoagulation, transfusion thresholds, ventilator strategies, sedation, and approaches to rehabilitation to subsequently implement into clinical practice. Additionally, efforts should focus on well-designed trials, including population pharmacokinetic studies, to develop dosing recommendations.

Anticoagulation and Transfusion Management During Neonatal and Pediatric Extracorporeal Membrane Oxygenation: A Survey of Medical Directors in the United States.

OBJECTIVES: To compare current practices within the United States of anticoagulation management and blood transfusion in neonatal and pediatric extracorporeal membrane oxygenation patients with a 2013 international report. DESIGN: Cross-sectional survey distributed between August and December 2019. SETTING: Extracorporeal Life Support Organization-registered neonatal and pediatric extracorporeal membrane oxygenation centers in the United States. PARTICIPANTS: Extracorporeal membrane oxygenation medical directors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-three medical directors at 108 centers responded. After removing four duplicate responses, 79 surveys were analyzed. Seventy-nine percent (n = 62) report a written extracorporeal membrane oxygenation protocol for both anticoagulation and blood product management. Ninety-four percent (n = 74) report unfractionated heparin as their primary anticoagulant; the remaining use the direct thrombin inhibitor, bivalirudin. Ninety percent (n = 71) report measuring antifactor Xa levels. Most centers report using a combination of assays to monitor heparin therapy, either antifactor Xa and activated partial thromboplastin time (54%) or more commonly antifactor Xa and activated clotting time (68%). Forty-one percent use viscoelastic tests to aid management. Goal monitoring levels and interventions generated by out of range values are variable. Fifty-one percent will replace antithrombin. Platelet transfusion thresholds vary by age and center with ranges from 50,000 to 100,000 cells/µL. Eighty-two percent of respondents are willing to participate in a randomized controlled trial comparing anticoagulation strategies for patients receiving extracorporeal membrane oxygenation. CONCLUSIONS: Compared with the 2013 pediatric population, extracorporeal membrane oxygenation center anticoagulation and blood transfusion approaches continue to vary widely. Most report continued use of heparin as their primary anticoagulant and follow a combination of monitoring assays with the majority using the antifactor Xa assay in their practices, a significant shift from prior results. Antithrombin activity levels and viscoelastic tests are followed by a growing number of centers. Platelet transfusion thresholds continue to vary widely. Future research is needed to establish optimal anticoagulation and blood transfusion management.

Evaluation of effect of scheduled fresh frozen plasma on ECMO circuit life: A randomized pilot trial.

BACKGROUND: Factor consumption is common during ECMO complicating the balance of pro and anticoagulation factors. This study sought to determine whether transfusion of coagulation factors using fresh frozen plasma (FFP) increased ECMO circuit life and decreased blood product transfusion. Secondly, it analyzed the association between FFP transfusion and hemorrhagic and thrombotic complications. STUDY DESIGN AND METHODS: Thirty-one pediatric ECMO patients between October 2013 and January 2016 at a quaternary care institution were included. Patients were randomized to FFP every 48 hours or usual care. The primary outcome was ECMO circuit change. Secondary outcomes included blood product transfusion, survival to decannulation, hemorrhagic and thrombotic complications, and ECMO costs. RESULTS: Median (interquartile range [IQR]) number of circuit changes was 0 (0, 1). No difference was seen in percent days without a circuit change between intervention and control group, P = .53. Intervention group patients received median platelets of 15.5 mL/kg/d IQR (3.7, 26.8) vs 24.8 mL/kg/d (12.2, 30.8) for the control group (P = .16), and median packed red blood cells (pRBC) of 7.7 mL/kg/d (3.3, 16.3) vs 5.9 mL/kg/d (3.4, 18.7) for the control group, P = .60. FFP transfusions were similar with 10.2 mL/kg/d (5.0, 13.9) in the intervention group vs 8.8 (2.5, 17.7) for the control group, P = .98. CONCLUSION: In this pilot randomized study, scheduled FFP did not increase circuit life. There was no difference in blood product transfusion of platelets, pRBCs, and FFP between groups. Further studies are needed to examine the association of scheduled FFP with blood product transfusion.

Evaluation of Heparin Anti-Factor Xa Levels Following Antithrombin Supplementation in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation.

OBJECTIVE: Thrombotic events are potential complications in patients receiving extracorporeal membrane oxygenation (ECMO) necessitating the use of systemic anticoagulation with heparin. Heparin works by potentiating the effects of antithrombin (AT), which may be deficient in critically ill patients and can be replaced. The clinical benefits and risks of AT replacement in children on ECMO remain incompletely understood. METHODS: This single-center, retrospective study reviewed 28 neonatal and pediatric patients supported on ECMO at a tertiary care hospital between April 1, 2013, and October 31, 2014, who received at least 1 dose of AT during their ECMO course. The primary outcome of the study was the change in anti-factor Xa levels after pooled human AT supplementation. Secondary outcomes included the percentage of anti-factor Xa levels within the therapeutic range surrounding AT administration; survival to decannulation; 30 days after cannulation and discharge; time to first circuit change; and incidence of bleeding and thrombotic events. RESULTS: A total of 78 doses of AT were administered during the study period. The mean increase in anti-factor Xa level following AT administration in patients without a ≥10% concurrent change in heparin was 0.075 ± 0.13 international units/mL. A greater percentage of anti-factor Xa levels were therapeutic for the 48 hours following AT administration (64.2% vs 38.6%). Survival and adverse events were similar to Extracorporeal Life Support Organization averages, with the exception of a higher incidence of intracranial hemorrhage. CONCLUSIONS: Patients experienced a small but significant increase in anti-factor Xa level and a greater percentage of therapeutic anti-factor Xa levels following AT supplementation.

Correlation Among Antifactor Xa, Activated Partial Thromboplastin Time, and Heparin Dose and Association with Pediatric Extracorporeal Membrane Oxygenation Complications.

Anticoagulation is essential during extracorporeal membrane oxygenation (ECMO) to prevent catastrophic circuit clotting. Several assays exist to monitor unfractionated heparin (UFH), the most commonly used anticoagulant during ECMO, but no single test or combination of tests has consistently been proven to be superior. This retrospective observational study examines the correlation among antifactor Xa level, activated partial thromboplastin time (aPTT), and UFH dose and the association between antifactor Xa level and aPTT with survival and hemorrhagic and thrombotic complications. Sixty-nine consecutive neonatal and pediatric ECMO patients from September 2012 to December 2014 at a single institution were included. Spearman rank correlation was used to compare antifactor Xa level, aPTT, and UFH dose. Significant but poor correlation exists between antifactor Xa level and UFH dose ρ = 0.1 (p < 0.0001) and aPTT and UFH dose ρ = 0.26 (p < 0.0001). Antifactor Xa level and aPTT were weakly correlated to each other ρ = 0.38 (p < 0.0001). In an univariate analysis, there was no difference between survival and antifactor Xa level, aPTT, or UFH dose. Multiple anticoagulation tests may be superior to a single test during ECMO.

Histoplasmosis Myocarditis in an Immunocompetent Host After a Recreational Mud Run.

Mud runs are an increasingly popular recreational fitness activity across the United States, combining a running race through an obstacle course with submersion in mud. Recent reports estimate 4 million people have participated in these types of events over the last 5 years. We describe an atypical case of myocarditis and multiorgan failure from disseminated histoplasmosis in a previously healthy pediatric patient, likely acquired during participation in a mud run. Although cases of histoplasmosis-associated endocarditis and pericarditis have been reported in the literature, cases of histoplasmosis myocarditis are rare.

Transfusion-related biologic effects and free hemoglobin, heme, and iron.

BACKGROUND: Red blood cell (RBC) transfusion is common in intensive care unit (ICU) patients and is associated with complications that appear related to the duration of blood storage. We hypothesize that hemolysis of stored RBCs results in increases in the availability of non-heme-bound iron, which inhibits macrophage activation. STUDY DESIGN AND METHODS: RBCs were sampled at multiple time points to evaluate hemolysis and iron release. Activation of THP-1 monocytic cells was assessed in the presence of plasma from aged RBCs. Age of transfused blood in our pediatric intensive care unit (PICU) from 2001 to 2006 was analyzed to assess relevance to our patient population. RESULTS: Hemolysis increased significantly during storage time as demonstrated by increases in free heme and hemoglobin. While there was a trend toward elevated levels of non-heme-bound iron, this was not significant (p = 0.07). THP-1 cell activation was inhibited by exposures to both plasma and a ferric compound; the effect of plasma on macrophage activation was not reversed by the iron chelator desferroxamine. Thirty-one percent of our PICU patients received blood older than 2 weeks. CONCLUSION: Hemolysis products increased significantly over time in our stored RBCs. Ferric compounds and plasma from stored blood inhibit THP-1 cell activation. Plasma inhibition does not appear to be due primarily to increased iron. Further studies are needed to define the inhibitory effect of stored blood plasma on macrophage function. Complications related to blood storage are relevant to our PICU patients.

Extracorporeal membrane oxygenation for severe refractory respiratory failure secondary to 2009 H1N1 influenza A.

BACKGROUND: Respiratory failure and acute respiratory distress syndrome secondary to H1N1 influenza infection is a source of substantial morbidity and mortality, having caused over 265,000 hospitalizations in the United States in 2009. During the H1N1 pandemic, up to 31% of the H1N1 patients required intensive care unit admission, and many were refractory to maximal conventional therapies. These most critically ill patients may require extracorporeal membrane oxygenation (ECMO) for survival. METHODS: We retrospectively reviewed the medical records of the 7 patients with refractory hypoxemia due to H1N1 influenza who were treated with ECMO in our pediatric intensive care unit. RESULTS: Five of the 7 patients survived to hospital discharge. The cohort's mean age was 21 years, and 4 were female. At admission to the pediatric intensive care unit, 6 had at least one comorbid condition, 6 were mechanically ventilated, and one was in shock. All 7 patients were treated with oral oseltamivir, high-frequency oscillatory ventilation, and inhaled nitric oxide prior to ECMO. Five received intravenous steroids, and 2 were treated with compassionate-use intravenous zanamivir. The mean duration of pre-ECMO ventilation was 8.7 days (range 14 h to 25 d). Mean oxygenation index was 50 (range 26-73) at ECMO cannulation. Six received venovenous ECMO, and one received venoarterial ECMO. The mean duration of ECMO was 432 hours (range 192-890 h). CONCLUSIONS: This series suggests that ECMO is a viable treatment for refractory hypoxemia secondary to H1N1 influenza infection in both pediatric and adult patients.

Iron overload following red blood cell transfusion and its impact on disease severity.

Transfusion of red blood cells can be a life-saving therapy both for patients with chronic anemias and for those who are critically ill with acute blood loss. However, transfusion has been associated with significant morbidity. Chronic transfusion results in accumulation of excess iron that surpasses the binding capacity of the major iron transport protein, transferrin. The resulting non-transferrin bound iron (NTBI) can catalyze the production of highly reactive oxygen species (ROS) leading to significant and wide spread injury to the liver, heart, and endocrine organs as well as increases in infection. Acute transfusion of red blood cells in critically ill patients likewise has significant effects including increased mortality, prolonged hospital stays, and elevated risk of nosocomial infection. These effects appear to be more profound with increasing age of stored blood. The progressive release of free iron associated with storage time suggests that morbidity following acute transfusion, like that seen in chronic transfusion, may be due in part to elevated levels of NTBI. It is clear that transfusion is necessary in many instances; however, its risks and benefits must be carefully balanced before proceeding to avoid unnecessary iron toxicity.