Predictive value of microcirculation for pediatric extracorporeal membrane oxygenation weaning test: A monocentric prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for children treated for refractory respiratory failures or refractory cardiogenic shock. Its duration depends on organ functions recovery. Weaning is decided using macro-circulatory tools, but microcirculation is not well evaluated. Sidestream dark-field video imaging is used to assess the perfusion of the sublingual microvascular vessels. The aim of this study was to assess the predictive value of microcirculatory indices in ECMO weaning. METHODS: This prospective monocentric study examined pediatric patients at Trousseau Hospital between March 2017 and December 2020. The study included all patients from 35 weeks of gestational age to 18 years old who were treated with ECMO. Children were divided into two groups: one with stability after weaning and the other with instability after weaning. We collected clinical and biological data, ventilation parameters, extracorporeal membrane oxygenation parameters, and drugs used at admission and after the weaning test. Microcirculations videos were taken after weaning trials with echocardiography and blood gas monitoring. RESULTS: The study included 30 patients with a median age of 29 days (range: 1-770 days) at admission, including 18 patients who received venoarterial ECMO (60%). There were 19 children in the stability group and 11 in the instability group. Macrocirculatory and microcirculatory indices showed no differences between groups. The microvascular flow index was subnormal in both groups (2.3 (1.8-2.4) and 2.3 (2.3-2.6), respectively; p = 0.24). The microvascular indices were similar between cases of venovenous and venoarterial ECMO and between age groups. CONCLUSION: Microcirculation monitoring at the weaning phase did not predict the failure of ECMO weaning.

Usefulness of implementation of a protective mechanical ventilation bundle during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome.

OBJECTIVE: Defining the best ventilatory settings under ECMO remains a challenging question. Despite a well-defined ARDS treatment before ECMO initiation, there is no recommendation on how to ventilate a patient under ECMO for P-ARDS. Only a few descriptive studies are available on ventilatory settings during respiratory ECMO. We aim at evaluating the usefulness of a protective ventilation bundle under ECMO and its capacity to reduce the ventilatory pressure in our ECMO center. METHODS: We performed a monocentric retrospective study from January 2007 to December 2018. All children aged from 1 month to 18 years old and requiring an extracorporeal membrane oxygenation for a refractory acute respiratory distress syndrome were included. A protective mechanical ventilation under ECMO bundle has been developed in 2014. We compare the period 1 (before 2014) to the period 2 (after 2014). RESULTS: Eighty-three patient had been included during the study. We reported a significant increase of PEEP and mean pressure respectively at day 3, day 7 and day 14 of ECMO during the period 2. Conversely, the driving pressure were significantly lower in the period 2 at day 3 (p: 0.009), day 7 (p:0.001) and day 14 (p: 0.001). We also shown a strong increase in the use of prone positioning during ECMO in the period 2 (p: 0.01). There was no significant effect of our bundle on the length of mechanical ventilation, of hospitalization and on the survival rate. CONCLUSIONS: The implementation of a protective mechanical ventilation bundle during ECMO is usefulness to apply for lower ventilatory pressure and higher use of prone positioning. Nonetheless, the lack of power of our study prevents us from showing its efficacy on outcome criteria.

Extracorporeal membrane oxygenation for immunocompromised children with acute respiratory distress syndrome: a French referral center cohort.

BACKGROUND: Immunocompromised children are likely to develop a refractory acute respiratory distress syndrome (ARDS). The usefulness of providing extracorporeal life support (ECLS) to these patients is a subject of debate. The aim of our study was to report the outcomes and to compare factors associated with mortality between immunocompromised and non-immunocompromised children supported with veno-venous ECMO. METHODS: We performed a retrospective monocentric study in the French pediatric ECMO center of Armand Trousseau Hospital, including all pediatric patients aged from 1 month to 18 years requiring ECLS for ARDS. RESULTS: Between 2007 and 2018, one hundred and eleven (111) patients underwent ECMO for respiratory failure; among them twenty-five (25) were immunocompromised. Survival rate at 6 months after intensive care discharge was significantly lower for immunocompromised patients compared to non-immunocompromised ones (41.7% vs. 62.8%; P=0.0.04). ARDS severity was similar between the 2 groups. Fungal pneumonias were reported only in immunocompromised patients (12.5% versus 0% in the control group; P=0.0.001). Bleeding complications were significantly more frequent in the immunocompromised group and blood product transfusions were also more frequently required in this group. CONCLUSIONS: Six months after intensive care discharge, survival rate of immunocompromised children supported with ECMO for pediatric ARDS is lower than for non-immunocompromised patients. But the expectation for a favorable outcome is real and it is worth it if their condition is likely to be compatible with a good long-term quality of life.

Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.

BACKGROUND: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. RESULTS: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. CONCLUSIONS: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

Mobile Extracorporeal Membrane Oxygenation: 5-Year Experience of a French Pediatric and Neonatal Center.

OBJECTIVES: Extracorporeal membrane oxygenation is an established therapy for refractory cardiac and/or pulmonary failure that is not available in all centers. When infants and children require extracorporeal membrane oxygenation, they are sometimes placed on extracorporeal membrane oxygenation support in peripheral centers where extracorporeal membrane oxygenation is not available and then transferred on extracorporeal membrane oxygenation to specialized centers. The objective of this study is to first describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation. DESIGN: We undertook a single-center retrospective study that included patients transported while on extracorporeal membrane oxygenation between November 1, 2014, and May 31, 2019. PATIENTS: All patients transported by our mobile extracorporeal membrane oxygenation unit during the study period were included. Computerized data collection was approved by the French Data Protection Authority (Commission nationale de l'informatique et des libertés n° 2121127V0). MAIN RESULTS: Over the study period, our extracorporeal membrane oxygenation mobile team transported 80 patients on extracorporeal membrane oxygenation among which 20 were newborns (25%) and 60 were children of 1 month to 17 years old (75%); 57 patients were on venoarterial-extracorporeal membrane oxygenation (71%) and 23 on venovenous-extracorporeal membrane oxygenation (29%). The average duration of transport was 8.4 hours with a median of 8 hours; the average distance travelled was 189 ± 140 km. Transport was by air and then ground for 50% of the patients and by ground for 42%. We observed a significant decrease in the Vasoactive-Inotropic Score (125 vs 99; p = 0.005) and PaCO2 levels (67 vs 49 mm Hg; p = 0.0005) after arrival in our unit. Survival rate 6 months after PICU discharge was 46% (37). There was a statistically significant relationship between initial lactate level and mortality (p = 0.02). We observed minor adverse events in 39% of the transports and had no mortality during transport. CONCLUSIONS: We describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation. Our findings confirm that it is safe to start extracorporeal membrane oxygenation in a referring center and to transport patients using an extracorporeal membrane oxygenation mobile team. The only risk factor associated with higher mortality was an initially elevated lactate level.

Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model.

Septic patients often die in a context of multiple organ dysfunction syndrome (MODS), despite the macro-hemodynamic parameters being normalized and after the onset of antibiotic therapy. Microcirculation injury during sepsis affects capillary permeability and leukocyte-endothelium interactions and is thought to be instrumental in organ injury. Several studies have demonstrated a beneficial effect of mesenchymal stromal cells (MSCs) injection on survival and organ dysfunctions in sepsis models. In vivo activity of MSCs also appears to be very much dependent on the information provided before injection. Indeed preconditioning by interferon γ (IFNγ; MSC-IFNγ) increases immunosuppressive capacity of MSCs in vitro and in vivo. Therefore, the objective was to evaluate the effect of MSC naive or IFNγ preconditioned on leukocyte-endothelium interactions in a polymicrobial sepsis model by intraperitoneal feces injection. Six hours (H6) after this induction, we used intravital microscopy in mice cremaster muscle venules to study the flow behavior of leukocytes. Plasmas were harvested to evaluate inflammation level and endothelial activation. We showed that MSC-IFNγ have a beneficial effect on microcirculation, by increasing the flow of white blood cells (WBCs) and the percentage of venules containing flowing WBCs, by significantly reducing the adhesion of WBCs and by increasing the average red blood cell velocity (VRBC). In conclusion, our results suggest that intravenous injection of preconditioned MSC-IFNγ improves microvascular hemodynamics in early phases of sepsis.