Pa o2 and Mortality in Neonatal Extracorporeal Membrane Oxygenation: Retrospective Analysis of the Extracorporeal Life Support Organization Registry, 2015-2020.

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pa o2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020. PATIENTS: Newborns supported by ECMO for respiratory indication were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045. CONCLUSIONS: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.

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.

Endothelial S1P1 Signaling Counteracts Infarct Expansion in Ischemic Stroke.

RATIONALE: Cerebrovascular function is critical for brain health, and endogenous vascular protective pathways may provide therapeutic targets for neurological disorders. S1P (Sphingosine 1-phosphate) signaling coordinates vascular functions in other organs, and S1P1 (S1P receptor-1) modulators including fingolimod show promise for the treatment of ischemic and hemorrhagic stroke. However, S1P1 also coordinates lymphocyte trafficking, and lymphocytes are currently viewed as the principal therapeutic target for S1P1 modulation in stroke. OBJECTIVE: To address roles and mechanisms of engagement of endothelial cell S1P1 in the naive and ischemic brain and its potential as a target for cerebrovascular therapy. METHODS AND RESULTS: Using spatial modulation of S1P provision and signaling, we demonstrate a critical vascular protective role for endothelial S1P1 in the mouse brain. With an S1P1 signaling reporter, we reveal that abluminal polarization shields S1P1 from circulating endogenous and synthetic ligands after maturation of the blood-neural barrier, restricting homeostatic signaling to a subset of arteriolar endothelial cells. S1P1 signaling sustains hallmark endothelial functions in the naive brain and expands during ischemia by engagement of cell-autonomous S1P provision. Disrupting this pathway by endothelial cell-selective deficiency in S1P production, export, or the S1P1 receptor substantially exacerbates brain injury in permanent and transient models of ischemic stroke. By contrast, profound lymphopenia induced by loss of lymphocyte S1P1 provides modest protection only in the context of reperfusion. In the ischemic brain, endothelial cell S1P1 supports blood-brain barrier function, microvascular patency, and the rerouting of blood to hypoperfused brain tissue through collateral anastomoses. Boosting these functions by supplemental pharmacological engagement of the endothelial receptor pool with a blood-brain barrier penetrating S1P1-selective agonist can further reduce cortical infarct expansion in a therapeutically relevant time frame and independent of reperfusion. CONCLUSIONS: This study provides genetic evidence to support a pivotal role for the endothelium in maintaining perfusion and microvascular patency in the ischemic penumbra that is coordinated by S1P signaling and can be harnessed for neuroprotection with blood-brain barrier-penetrating S1P1 agonists.

Association between pediatric intensive care mortality and mechanical ventilation settings during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome.

The main objective of this study was to describe the current mechanical ventilation (MV) settings during extracorporeal membrane oxygenation (ECMO) for pediatric acute respiratory distress syndrome (P-ARDS) in six European centers. This is a retrospective observational cohort study performed in six European centers from January 2009 to December 2019. Children > 1 month to 18 years supported with ECMO for refractory P-ARDS were included. Collected data were as follows: patients' pre-ECMO medical condition, pre-ECMO adjunctive therapies for P-ARDS, pre-ECMO and during ECMO MV settings on day (D) 1, D3, D7, and D14 of ECMO, use of adjunctive therapies during ECMO, duration of ECMO, pediatric intensive care unit length of stay, and survival. A total of 255 patients with P-ARDS were included. The multivariate analysis showed that PEEP on D1 (OR = 1.13, 95% CI [1.03-1.24], p = 0.01); D3 (OR = 1.17, 95% CI [1.06-1.29], p = 0.001); and D14 (OR = 1.21, 95% CI [1.05-1.43], p = 0.02) and DP on D7 were significantly associated with higher odds of mortality (OR = 0.82, 95% CI [0.71-0.92], p = 0.001). Moreover, DP on D1 above 15 cmH2O (OR 2.23, 95% CI (1.09-4.71), p = 0.03) and native lung FiO2 above 60% on D14 (OR 10.36, 95% CI (1.51-116.15), p = 0.03) were significantly associated with higher odds of mortality.   Conclusion: MV settings during ECMO for P-ARDS varied among centers; however, use of high PEEP levels during ECMO was associated with higher odds of mortality as well as a DP above 15 cmH2O and a native lung FiO2 above 60% on D14 of ECMO. What is Known: • Invasive ventilation settings are well defined for pediatric acute respiratory distress syndrome; however, once the children required an extracorporeal respiratory support, there is no recommendation how to set the mechanical ventilator. • Impact of invasive ventilator during extracorporeal respiratory support ad only been during the first days of this support but the effects of these settings later in the assistance are not described. What is New: • It seems to be essential to early decrease FiO2 on native lung once the ECMO flow allows an efficient oxygenation. • Tight control to limit the driving pressure at 15 cmH20 during ECMO run seems to be associated with better survival rate.

Diagnosis of mucormycosis using an intercalating dye-based quantitative PCR.

PCR-based methods applied to various body fluids emerged in recent years as a promising approach for the diagnosis of mucormycosis. In this study, we set up and assess the value of a qPCR to detect a wide variety of Mucorales species in a single tube. A pair of degenerated primers targeting the rDNA operon was used in a qPCR utilizing an intercalating fluorescent dye. Analytical assessment, using a wide variety of both Mucorales strains (8 genera, 11 species) and non-Mucorales strains (9 genera, 14 species), showed 100% sensitivity and specificity rates with a limit of detection at 3 rDNA copy/qPCR reaction. Subsequently, 364 clinical specimens from 166 at-risk patients were prospectively tested with the assay. All the seven patients classified as proven/probable mucormycosis using the EORTC-MSG criteria had a positive qPCR as well as a patient with a proven uncharacterized invasive mold infection. In addition, three out of seven patients with possible mold invasive infections had at least one positive qPCR test. Sensitivity was calculated between 73.33 and 100% and specificity between 98.10 and 100%. The qPCR method proposed showed excellent performances and would be an important adjunctive tool for the difficult diagnosis of mucormycosis diagnosis. LAY ABSTRACT: qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.

Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model. METHODS: Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC. RESULTS: Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC. CONCLUSIONS: During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.

Mortality and Neurologic Sequelae in Influenza-Associated Encephalopathy: Retrospective Multicenter PICU Cohort in France.

OBJECTIVES: To describe and estimate the mortality rate of severe influenza-associated encephalopathy/encephalitis among children admitted to PICUs. DESIGN: Multicenter retrospective study. SETTING: Twelve French PICUs. PATIENTS: All children admitted for influenza-associated encephalopathy/encephalitis between 2010 and 2018 with no severe preexisting chronic neurologic disorders and no coinfection potentially responsible for the disease. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We collected the clinical presentation; laboratory, electroencephalographic, and MRI findings; and treatments used in the PICU. The primary outcome was mortality. The secondary outcomes included sequelae at discharge and last follow-up. We included 41 patients with a median (interquartile range) age of 4.7 years (2.5-8.2 yr). The main reasons for admission were altered consciousness (59%) and status epilepticus (34%); 48% of patients had meningitis, and one third had acute necrotizing encephalopathy on MRI. Mechanical ventilation was required in 73% of patients and hemodynamic support in 24%. The use of specific treatments was variable; steroids were given to 49% of patients. Seven patients (17%) died in the PICU. Median (interquartile range) PICU stay length was 7 days (2-13 d), and total hospital length of stay was 23 days (7-33 d). On hospital discharge, 49% (n = 20) had neurologic sequelae, with 27% (n = 11) having severe disabilities defined by modified Rankin Score greater than or equal to 4. CONCLUSIONS: Children requiring PICU admission for influenza-associated encephalopathy/encephalitis have high mortality and morbidity rates. The management remains highly variable due to the lack of guidelines.

Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID-19 pandemic in France.

AIM: This study determined the influence of the COVID-19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS-C) and compared the main characteristics of MIS-C and Kawasaki disease (KD). METHODS: We included patients aged up to 18 years of age who were diagnosed with MIS-C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID-19 cases were correlated with MIS-C cases in our hospital. RESULTS: There were seven children with MIS-C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID-19, and 40 virus-negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C-reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS-C patients and COVID-19 cases. CONCLUSION: The rise and fall of COVID-19 first wave mirrored the MIS-C cases. There were important differences between MIS-C and KD.

Impact of Arterial Carbon Dioxide and Oxygen Content on Cerebral Autoregulation Monitoring Among Children Supported by ECMO.

BACKGROUND: Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO2 (PaCO2) and O2 (PaO2) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied. METHODS: Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO2) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox-MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO2, COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run. RESULTS: Thirty children (median age 4.8 months [Interquartile range (IQR) 0.7-39.1], median weight 5 kg [IQR 4-15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO2 was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO2 and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO2 was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO2 and nULA was observed within the whole ECMO run and on D1 of ECMO (R = -0.07 p = 0.04 and R = -0.135 p = <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO2 and negatively correlated with PaO2 (R = 0.224, p = 0.01 and R = -0.051, p = 0.004, respectively). CONCLUSIONS: We observed a complex relationship between PaCO2 and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO2, especially after ECMO start.

Continuous Monitoring of Cerebral Autoregulation in Children Supported by Extracorporeal Membrane Oxygenation: A Pilot Study.

OBJECTIVE: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome. DESIGN: Observational prospective study. PATIENTS AND SETTING: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy. MEASUREMENTS: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx-MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start. RESULTS: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3-93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02-0.15) vs. 0.01 (- 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE- patients [0.09 (0.01-0.23) vs. 0.04 (- 0.02 to 0.06), p = 0.04 and 33.3% (24.8-62.1) vs. 20.8% (17.3-23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5-32.9) vs. 5.6% (3.6-9.9), p = 0.02] and above ULA [13% (5.3-38.4) vs. 4.2% (2.7-7.4), p = 0.004], respectively. CONCLUSION: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

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.

Sevoflurane Sedation with AnaConDa-S Device for a Child Undergoing Extracorporeal Membrane Oxygenation.

BACKGROUND: Deep sedation in critically ill children undergoing extracorporeal membrane oxygenation (ECMO) can be challenging. Volatile anesthetics like sevoflurane can be a good alternative for patients hospitalized in pediatric intensive care units, in whom adequate sedation is difficult to obtain. CASE DESCRIPTION: We report here the first pediatric case of a patient under extracorporeal membrane oxygenation receiving sedation by sevoflurane using the AnaConDa-S device. This 2-year-old girl, suffering from congenital diaphragmatic hernia, was put on extracorporeal membrane oxygenation due to a persistent pulmonary hypertension following metapneumovirus infection. Despite high doses of drugs, neither satisfactory sedation nor analgesia could be reached. Sevoflurane allowed her to be released and we were able to wean her from certain drugs. Her physiological parameters and the indicators of pain and sedation improved. CONCLUSION: Anesthesia using sevoflurane with the AnaConDa-S device is efficient for children under ECMO. CLINICAL SIGNIFICANCE: This is the first pediatric report on anesthesia with sevoflurane under ECMO. HOW TO CITE THIS ARTICLE: Soreze Y, Piloquet J-E, Amblard A, Constan I, Rambaud J, Leger P-L. Sevoflurane Sedation with AnaConDa-S Device for a Child Undergoing Extracorporeal Membrane Oxygenation. Indian J Crit Care Med 2020;24(7):596-598.

Successful extracorporeal membrane oxygenation transport of a 4-month-old brain-dead infant for organ donation: A case report.

A 4-month-old infant was declared brain-dead 2 days after being initiated on venoarterial ECMO for a refractory septic shock. All brain death diagnostic criteria were fulfilled according to French law, and parental consent was given for organ donation. The hospital where ECMO was initiated had no authorization for organ procurement, and the donor was then transferred to the local referral center for child organ recovery with our mobile ECMO team to maintain organ perfusion. The kidneys were recovered and successfully transplanted to a child who is now well and alive. Although the transport elements of this case report are of limited relevance to an international audience as no other country, to our knowledge, has this particular organization, it does show excellent collaboration between teams to realize the goal of organ donation for this family. This is the first case describing a successful inter-hospital transport for organ procurement of a brain-dead infant on ECMO. Brain-dead pediatric patients undergoing ECMO can be considered as potential organ donors to expand the donor pool.

Nosocomial Infections in Neonates Supported by Extracorporeal Membrane Oxygenation: First French Retrospective Study.

How to cite this article: Rambaud J, Allioux C, Jean S, Guilbert J, Guellec I, Demoulin M, et al. Nosocomial Infections in Neonates Supported by Extracorporeal Membrane Oxygenation: First French Retrospective Study. Indian J Crit Care Med 2019;23(9):392-395.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. METHODS: This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.

Different response to antiepileptic drugs according to the type of epileptic events in a neonatal ischemia-reperfusion model.

Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care. It is currently unknown if treatment of the seizures modifies the outcome, and no clinical studies have focused on seizures during neonatal stroke. We studied the effect of phenobarbital and levetiracetam on an ischemic-reperfusion stroke model in P7 rats using prolonged electroencephalographic recordings and a histologic analysis of the brain (24h after injury). The following two types of epileptic events were observed: 1) bursts of high amplitude spikes during ischemia and the first hours of reperfusion and 2) organized seizures consisting in discharges of a 1-2Hz spike-and-wave. Both phenobarbital and levetiracetam decreased the total duration of the bursts of high amplitude spikes. Phenobarbital also delayed the start of seizures without changing the total duration of epileptic discharges. The markedly limited efficacy of the antiepileptic drugs studied in our neonatal stroke rat model is frequently observed in human neonatal seizures. Both drugs did not modify the stroke volume, which suggests that the modification of the quantity of bursts of high amplitude spikes does not influence the infarct size. In the absence of a reduction in seizure burden by the antiepileptic drugs, we increased the seizure burden and stroke volume by combining our neonatal stroke model with a lithium-pilocarpine-induced status epilepticus. Our data suggest that the reduction of burst of spikes did not influence the stroke volume. The presence of organized seizure with a pattern close to what is observed in human newborns seems related to the presence of the infarct. Further research is required to determine the relationship between seizure burden and infarct volume.

Do All Children Who Present With a Complex Febrile Seizure Need a Lumbar Puncture?

STUDY OBJECTIVE: We assess the prevalences of bacterial meningitis and herpes simplex virus meningoencephalitis (HSV-ME) in children with a complex febrile seizure and determine these prevalences in the subgroup of children with a clinical examination result not suggestive of meningitis or encephalitis. METHODS: This multicenter retrospective study was conducted in 7 pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 months to 5 years for a complex febrile seizure from January 2007 to December 2011 were analyzed. We defined a subgroup of patients whose clinical examination result was not suggestive of meningitis or encephalitis. Bacterial meningitis and HSV-ME were sequentially sought for by analyzing bacteriologic and viral data at the visit, looking for data from a second visit to the hospital after the index visit, and telephoning the child's parents. RESULTS: From a total of 1,183,487 visits in the 7 pediatric EDs, 839 patients presented for a complex febrile seizure, of whom 260 (31.0%) had a lumbar puncture. The outcomes bacterial meningitis and HSV-ME were ascertainable for 715 (85%) and 657 (78.3%) visits, respectively, and we found 5 cases of bacterial meningitis (0.7% [95% confidence interval [CI] 0.2% to 1.6%]) and no HSV-ME (0% [95% CI 0% to 0.6%]). Among the 630 visits of children with a clinical examination result not suggesting meningitis or encephalitis, we found no bacterial meningitis (0% [95% CI 0% to 0.7%]) and no HSV-ME (0% [95% CI 0% to 0.8%]). CONCLUSION: In children with a complex febrile seizure, bacterial meningitis and HSV-ME are unexpected events when the clinical examination after complex febrile seizure is not suggestive of meningitis or encephalitis.