Background and Aims

Potential adverse impact of spontaneous effort in patient with lung injury is an emerging concept in adults described as patient self-inflicted lung injury (p-SILI). High spontaneous effort may participate in the alveolar injury in infant with severe bronchiolitis. We hypothesize that nCPAP may prevent the risk of p-SILI by decreasing the lung stress.

Methods

We conducted a secondary analysis (ethics approval CE SRLF 20-19) of a prospective physiological study including infants with severe bronchiolitis < 3 months. Esophageal (Peso), gastric (Pga), and airway (Paw) pressures, electrical activity of the diaphragm (Edi), and Flow were recorded in spontaneous breathing (SB) and in n-CPAP 7 cmH₂O, applied for 1 hour. Inspiratory transpulmonary pressure (TPP) was estimated as Paw-Peso at the minimal Peso Swing.

Results

Twelve children (median [IQR] age 30 [22-49] days, mWCAS 4.5 [4.5-5.0]) were included. Delta Edi and Peso swing were significantly lower in CPAP than in SB (Table 1). The TPP was not different between the 2 modes. The change in TPP was negatively correlated with TPP in SB (r=-0.72, p=0.002), indicating a decrease in TPP in infants with higher effort at baseline (Fig.1)

Conclusions

In infants with severe bronchiolitis, the application of a nCPAP may help to decrease the risk of p-SILI but only in infants with high TPP in spontaneous breathing.

Background and Aims

Multisystem Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of SARS-CoV-2 infection, but the optimal therapeutic strategy remains unknown. Our aim was to compare intravenous immunoglobulins (IVIG) plus methylprednisolone versus IVIG alone as initial therapy.

Methods

Retrospective cohort study, comparing IVIG plus methylprednisolone and IVIG alone, with propensity score matching analysis based on a national surveillance system. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the WHO definition were included.
The primary outcome was persistence of fever 2 days or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, and acute left ventricular dysfunction after first-line therapy. The primary analysis involved propensity score matching with a minimum caliper of 0.1

Results

We have included 111 children. Overall, 3/34 (9%) children in the IVIG and methylprednisolone group and 37/72 (51%) in the IVIG alone group failed treatment. Treatment with IVIG and methylprednisolone was associated with lower risk of treatment failure (absolute risk difference -0.28, 95% CI -0.48 to -0.08, p=.008). IVIG and methylprednisolone therapy was also significantly associated with less use of second-line therapy (absolute risk difference -0.22, 95% CI -0.40 to -0.04, p=.004], hemodynamic support (absolute risk difference -0.17, 95% CI -0.34 to -0.004) and acute left ventricular dysfunction occurring after initial therapy (absolute risk difference -0.18, 95% CI -0.35 to -0.01).

Conclusions

Combined treatment with methylprednisolone vs IVIG alone was associated with better course of fever in children with MIS-C.

Background and Aims

In France, Claeys-Leonetti Law of 2016 authorizes deep and continuous sedation maintained until death (DCSUD). There are no French pediatric studies evaluating practice in pediatric intensive care unit (PICU) since then. We seek to highlight differences in practice since the passing of the law.

Methods

Our study is monocentric and retrospective. It was conducted in the PICU of Children’s Hospital of Lyon between 2010 and 2019. We included all children for whom it has been discussed to withdraw a treatment.

Results

82 patients with a withdrawing treatment decision were included : 51 patients before and 31 after the law. At the time of discontinuation, sedative doses were more frequently increased (18.4% vs 37%, p = 0.044) without changing the scale of doses increase. The most common sedative drug, Midazolam, remains administrated at 2.26 mg.kg^-1.h^-1 on average. Moreover, symptom assessment is performed for more patients (68% vs 90.3%, p = 0.023), at least 3 times a day almost systematically (74.3% vs 96.4%, p < 0.001). There is still a lack of traceability of procedures, particularly with regard to the sedative use. Nevertheless, the participation of an external consultant and a nurse in the decision-making meetings becomes systematic.

Conclusions

There has been little changes in sedative practice since the Claeys-Leonetti Law in PICU for withdrawing treatment. Whether it is due to the practice of deep sedation prior to the law or to a lack of knowledge of the law calls for further investigation.

Background and Aims

Background and aims: Superantigen toxins synthesized by Staphylococcus aureus and Streptococcus pyogenes are responsible for toxic shock syndromes (TSS), which lethality can reach 28% in children. In vitro, high concentration of Intravenous Immunoglobulins (IVIG) neutralize their toxicity. No randomized controlled trial (RCT) on IVIG efficacy in TSS has been conducted in children.

Before launching such a prospective RCT, a pilot study is required, with objective to assess the feasibility including inclusion rate, protocol deviations, and missing data.

Methods

We performed a multicenter, double-blind, pilot RCT. We planned to recruit, over 24 months, 20 patients with suspicion of TSS and criteria of septic shock, aged from 1 month to 18 years, admitted within 9 French paediatric intensive care units. The experimental group received IVIG10% (2g/kg) and the control group Albumin4% (0,8g/kg). There were 12 months of follow-up.

Results

79 children with TSS were assessed for eligibility, including 49 eligible, among which 30 (61%) were recruited within 38 months. Median Pelod 2 score at inclusion was 6 (0-11). 29 patients received allocated treatment (97%) and 9 patients (30%) had at least one protocol deviation. There were no missing data on key data for primary endpoint. 9 patients (30%) presented serious adverse events (no death)

Conclusions

This first RCT in paediatric TSS shows the feasibility of such a trial with only a few adjustments. As recommended by the Data Safety Monitoring Board, an international multicentre efficacy study is required to perform this trial.

Background and Aims

Multiple Inflammatory Syndrome in Children (MIS-C) is the most frequent severe form of COVID19 in children. MIS-C combines features of Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) but its pathophysiology is unknown. The aim of this study was to investigate the immunological profile of MIS-C cases in comparison with KD and TSS cases.

Methods

Blood samples were collected from MIS-C cases during PICU stay. HLA-DR, lymphocytes subsets and Vbeta repertoire of lymphocytes were measured by flow cytometry. Serum levels of cytokines were measured by automated Elisa, interferon response (ISGs with Nanostring technology, IFN-alpha with Simoa technology, IFN-gamma with Elisa) and a biocollection were performed.

Results

Twenty four MIS-C cases were compared to 4 KD and 4 TSS cases. Similarly to TSS, an increase of inflammatory cytokines (IL1RA, IL18, TNFalpha, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR. Analysis of T-cell receptor beta chain variable region (TCR-Vb) repertoire showed a specific expansion of Vb 21.3+ T-cells occurring in both CD4 and CD8 subsets in 40% of cases. TCR sequencing uncovered the polyclonality nature of the Vb21.3+ population. In one child with Vb21.3+ expansion, the combination of SARS-CoV2 with autologous serum induced patient T cells in vitro proliferation, suggesting that SARS-CoV2 complexed to immunoglobulins could act as superantigen structure in MIS-C.

Conclusions

This study suggests that MIS-C is mediated by a superantigen activity that may explain the observed efficacy of high dose immunoglobulins.This is consistent with the delayed onset of PIM-S, explained by the time required for antibodies appearance.

Background and Aims

Raised Intracranial Pressure (ICP) is a life-threatening complication of brain injuries. Optic Nerve Sheath Diameter (ONSD) appears to be an interesting, non-invasive tool for detecting raised ICP. The primary aim is to study the predictive value of ONSD for diagnostic of raised ICP in children with brain injuries.

Methods

ONSD was measured in children with ICP invasive monitoring: before monitoring insertion and daily during 3 days. ONSD was also measured in a control group of children, with mechanical ventilation and intravenous sedation, without brain injury and invasive ICP monitoring.

Results

97 patients were included with a median (IQR) age respectively of 8.7 (2.3-13.6) years. The median (IQR) PIM 2 was 6.6 (4.4-9.7) and the median (IQR) PELOD was 21 (12-22). Etiologies were traumatic brain injuries (n=72), infections (n=17) and cerebrovascular accidents (n=8). Raised ICP occurred in 65 children. 31 controls were included, with a median age of 3.7 (1.2-8.8) years. Mean ONSD (measured within 15 min preceding insertion of ICP probe) are illustrated in Figure. ONSD performance to predict raised ICP occurrence was poor (area under the curve, 0.57; 95%CI 0.45-0.7). OSND did not differ significantly during the 3 days study period. Age, etiology or raised ICP level did not change the results.

Conclusions

In a paediatric severe brain injuries population, ONSD measurement could not predict the occurrence of raised ICP. Severity of patients, timing and conditions of measurements may explain these results.

Background and Aims

Multiple Inflammatory Syndrome in Children (MIS-C) is the most frequent severe form of COVID19 in children. MIS-C combines features of Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) but its pathophysiology is unknown. The aim of this study was to investigate the immunological profile of MIS-C cases in comparison with KD and TSS cases.

Methods

Blood samples were collected from MIS-C cases during PICU stay. HLA-DR, lymphocytes subsets and Vbeta repertoire of lymphocytes were measured by flow cytometry. Serum levels of cytokines were measured by automated Elisa, interferon response (ISGs with Nanostring technology, IFN-alpha with Simoa technology, IFN-gamma with Elisa) and a biocollection were performed.

Results

Twenty four MIS-C cases were compared to 4 KD and 4 TSS cases. Similarly to TSS, an increase of inflammatory cytokines (IL1RA, IL18, TNFalpha, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR. Analysis of T-cell receptor beta chain variable region (TCR-Vb) repertoire showed a specific expansion of Vb 21.3+ T-cells occurring in both CD4 and CD8 subsets in 40% of cases. TCR sequencing uncovered the polyclonality nature of the Vb21.3+ population. In one child with Vb21.3+ expansion, the combination of SARS-CoV2 with autologous serum induced patient T cells in vitro proliferation, suggesting that SARS-CoV2 complexed to immunoglobulins could act as superantigen structure in MIS-C.

Conclusions

This study suggests that MIS-C is mediated by a superantigen activity that may explain the observed efficacy of high dose immunoglobulins.This is consistent with the delayed onset of PIM-S, explained by the time required for antibodies appearance.

Background and Aims

Background and aims: Superantigen toxins synthesized by Staphylococcus aureus and Streptococcus pyogenes are responsible for toxic shock syndromes (TSS), which lethality can reach 28% in children. In vitro, high concentration of Intravenous Immunoglobulins (IVIG) neutralize their toxicity. No randomized controlled trial (RCT) on IVIG efficacy in TSS has been conducted in children.

Before launching such a prospective RCT, a pilot study is required, with objective to assess the feasibility including inclusion rate, protocol deviations, and missing data.

Methods

We performed a multicenter, double-blind, pilot RCT. We planned to recruit, over 24 months, 20 patients with suspicion of TSS and criteria of septic shock, aged from 1 month to 18 years, admitted within 9 French paediatric intensive care units. The experimental group received IVIG10% (2g/kg) and the control group Albumin4% (0,8g/kg). There were 12 months of follow-up.

Results

79 children with TSS were assessed for eligibility, including 49 eligible, among which 30 (61%) were recruited within 38 months. Median Pelod 2 score at inclusion was 6 (0-11). 29 patients received allocated treatment (97%) and 9 patients (30%) had at least one protocol deviation. There were no missing data on key data for primary endpoint. 9 patients (30%) presented serious adverse events (no death)

Conclusions

This first RCT in paediatric TSS shows the feasibility of such a trial with only a few adjustments. As recommended by the Data Safety Monitoring Board, an international multicentre efficacy study is required to perform this trial.

Background and Aims

Multisystem Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of SARS-CoV-2 infection, but the optimal therapeutic strategy remains unknown. Our aim was to compare intravenous immunoglobulins (IVIG) plus methylprednisolone versus IVIG alone as initial therapy.

Methods

Retrospective cohort study, comparing IVIG plus methylprednisolone and IVIG alone, with propensity score matching analysis based on a national surveillance system. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the WHO definition were included.
The primary outcome was persistence of fever 2 days or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, and acute left ventricular dysfunction after first-line therapy. The primary analysis involved propensity score matching with a minimum caliper of 0.1

Results

We have included 111 children. Overall, 3/34 (9%) children in the IVIG and methylprednisolone group and 37/72 (51%) in the IVIG alone group failed treatment. Treatment with IVIG and methylprednisolone was associated with lower risk of treatment failure (absolute risk difference -0.28, 95% CI -0.48 to -0.08, p=.008). IVIG and methylprednisolone therapy was also significantly associated with less use of second-line therapy (absolute risk difference -0.22, 95% CI -0.40 to -0.04, p=.004], hemodynamic support (absolute risk difference -0.17, 95% CI -0.34 to -0.004) and acute left ventricular dysfunction occurring after initial therapy (absolute risk difference -0.18, 95% CI -0.35 to -0.01).

Conclusions

Combined treatment with methylprednisolone vs IVIG alone was associated with better course of fever in children with MIS-C.