CNS Inflammation as the First Sign of Complement Factor I Deficiency: A Severe Myelitis Treated With Intense Immunotherapy and Eculizumab

OBJECTIVES: Complement factor I (CFI) deficiency is a rare autosomal recessive inborn error of immunity. In this report, we highlight that complete CFI deficiency may present with isolated and severe CNS inflammation without associated systemic features nor prior non-CNS episodes. This inflammation may respond to complement blockade therapy. METHODS: This is a case description of a young girl with severe longitudinal transverse myelitis treated with aggressive immunotherapy that included eculizumab. Published cases of CFI-associated CNS inflammation were reviewed and discussed. RESULTS: A primary immunodeficiency panel revealed 2 germline pathogenic variants in the CFI gene. Further complement testing of the index case and her family confirmed complete CFI deficiency. DISCUSSION: We describe a unique case of severe spinal inflammation secondary to complete CFI deficiency. Although rare, isolated CNS inflammation may be the primary manifestation of complete CFI deficiency. To halt the uncontrolled complement-mediated inflammation associated with CFI deficiency, prompt targeted blockade of the complement pathway using eculizumab may be life changing in the acute phase. Long-lasting blockade of the complement pathway is also essential to prevent relapse in this subgroup of patients.

Strategies to Reduce Diagnostic Blood Loss and Anemia in Hospitalized Patients: A Scoping Review.

OBJECTIVES: Blood sampling is a recognized contributor to hospital-acquired anemia. We aimed to bundle all published neonatal, pediatric, and adult data regarding clinical interventions to reduce diagnostic blood loss. DATA SOURCES: Four electronic databases were searched for eligible studies from inception until May 2021. STUDY SELECTION: Two reviewers independently selected studies, using predefined criteria. DATA EXTRACTION: One author extracted data, including study design, population, period, intervention type and comparator, and outcome variables (diagnostic blood volume and frequency, anemia, and transfusion). DATA SYNTHESIS: Of 16,132 articles identified, we included 39 trials; 12 (31%) were randomized controlled trials. Among six types of interventions, 27 (69%) studies were conducted in adult patients, six (15%) in children, and six (15%) in neonates. Overall results were heterogeneous. Most studies targeted a transfusion reduction ( n = 28; 72%), followed by reduced blood loss ( n = 24; 62%) and test frequency ( n = 15; 38%). Small volume blood tubes ( n = 7) and blood conservation devices ( n = 9) lead to a significant reduction of blood loss in adults (8/9) and less transfusion of adults (5/8) and neonates (1/1). Point-of-care testing ( n = 6) effectively reduced blood loss (4/4) and transfusion (4/6) in neonates and adults. Bundles including staff education and protocols reduced blood test frequency and volume in adults (7/7) and children (5/5). CONCLUSIONS: Evidence on interventions to reduce diagnostic blood loss and associated complications is highly heterogeneous. Blood conservation devices and smaller tubes appear effective in adults, whereas point-of-care testing and bundled interventions including protocols and teaching seem promising in adults and children.

Prevention of submicron aerosolized particle dispersion: evaluation of an aerosol box using a pediatric simulation model.

Background and Aim: The SplashGuard CG (SG) is a barrier enclosure developed to protect healthcare workers from SARS-CoV-2 transmission during aerosol-generating procedures. Our objective was to evaluate the protection provided by the SG against aerosolized particles (AP), using a pediatric simulation model of spontaneous ventilation (SV) and noninvasive ventilation (NIV). Methods: An aerosol generator was connected to the airways of a pediatric high-fidelity manikin with a breathing simulator. AP concentrations were measured both in SV and NIV in the following conditions: with and without SG, inside and outside the SG, with and without suction applied to the device. Results: In the SV simulated setting, AP peaks were lower with SG: 0.1 × 105 particles/L compared to without: 1.6 × 105, only when the ports were closed and suction applied. In the NIV simulated setting, AP peaks outside the SG were lower than without SG (20.5 × 105 particles/L), whatever the situation, without suction (14.4 × 105particles/L), with suction and ports open or closed: 10.3 and 0.7 × 105 particles/L. In SV and NIV simulated settings, the AP peaks measured within the SG were much higher than the AP peaks measured without SG, even when suction was applied to the device. Conclusions: The SG seems to decrease peak AP exposure in the 2 ventilation contexts, but only with closed port and suction in SV. However, high concentrations of AP remain inside even with suction and SG should be used cautiously.

Impact of Blood Sampling on Anemia in the PICU: A Prospective Cohort Study.

OBJECTIVES: Fifty percent of children are anemic after a critical illness. Iatrogenic blood testing may be a contributor to this problem. The objectives of this study were to describe blood sampling practice in a PICU, determine patient factors associated with increased sampling, and examine the association among blood sampling volume, anemia at PICU discharge, and change in hemoglobin from PICU entry to PICU discharge. DESIGN: Prospective observational cohort study. SETTING: PICU of Sainte-Justine University Hospital. PATIENTS: All children consecutively admitted during a 4-month period. MEASUREMENTS AND MAIN RESULTS: Four hundred twenty-three children were enrolled. Mean blood volume sampled was 3.9 (±19) mL/kg/stay, of which 26% was discarded volume. Children with central venous or arterial access were sampled more than those without access (p < 0.05). Children with sepsis, shock, or cardiac surgery were most sampled, those with a primary respiratory diagnosis; the least (p < 0.001). We detected a strong association between blood sample volume and mechanical ventilation (H, 81.35; p < 0.0001), but no association with severity of illness (Worst Pediatric Logistic Organ Dysfunction score) (R, -0.044; p = 0.43). Multivariate analysis (n = 314) showed a significant association between the volume of blood sampled (as continuous variable) and anemia at discharge (adjusted OR, 1.63; 95% CI, 1.18-2.45; p = 0.003). We lacked power to detect an association between blood sampling and change in hemoglobin from PICU admission to PICU discharge. CONCLUSIONS: Diagnostic blood sampling in PICU is associated with anemia at discharge. Twenty-five percent of blood losses from sampling is wasted. Volumes are highest for patients with sepsis, shock, or cardiac surgery, and in patients with vascular access or ventilatory support.

Oxygenation Defects, Ventilatory Ratio, and Mechanical Power During Severe Pediatric Acute Respiratory Distress Syndrome: Longitudinal Time Sequence Analyses in a Single-Center Retrospective Cohort.

OBJECTIVES: Our understanding of pediatric acute respiratory distress syndrome is based on information from studies reporting intermittent, serial respiratory data. We have analyzed a high-resolution, longitudinal dataset that incorporates measures of hypoxemia severity, metrics of lung mechanics, ventilatory ratio, and mechanical power and examined associations with survival after the onset of pediatric acute respiratory distress syndrome. DESIGN: Single-center retrospective cohort, 2013-2018. SETTING: Tertiary surgical/medical PICU. PATIENTS: Seventy-six cases of severe pediatric acute respiratory distress syndrome, determined according to the Pediatric Acute Lung Injury Consensus Conference criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The high-resolution database included continuous monitoring of ventilatory data (0.03 Hz) for up to 14 days after the diagnosis of pediatric acute respiratory distress syndrome or until extubation or death (n = 26). In the 12,128 hours of data during conventional mechanical ventilation, we used generalized estimating equations to compare groups, accounting for any effect of time. We identified an association between survival and faster rate of improvement in delta pressure (peak inspiratory pressure minus positive end-expiratory pressure; p = 0.028). Nonsurvival was associated with higher daily Pediatric Logistic Organ Dysfunction-2 scores (p = 0.005) and more severe hypoxemia metrics (p = 0.005). Mortality was also associated with the following respiratory/pulmonary metrics (mean difference [95% CI]): positive end-expiratory pressure level (+2.0 cm H2O [0.8-3.2 cm H2O]; p = 0.001), peak inspiratory pressure level (+3.0 cm H2O [0.5-5.5 cm H2O]; p = 0.022), respiratory rate (z scores +2.2 [0.9-3.6]; p = 0.003], ventilatory ratio (+0.41 [0.28-0.55]; p = 0.0001], and mechanical power (+5 Joules/min [1-10 Joules/min]; p = 0.013). Based on generalized linear mixed modeling, mechanical power remained associated with mortality after adjustment for normal respiratory rate, age, and daily Pediatric Logistic Organ Dysfunction-2 score (+3 Joules/breath [1-6 Joules/breath]; p = 0.009). CONCLUSIONS: Mortality after severe pediatric acute respiratory distress syndrome is associated with the severity of organ dysfunction, oxygenation defects, and pulmonary metrics including dead space and theoretical mechanical energy load.

PICU Follow-Up Clinic: Patient and Family Outcomes 2 Months After Discharge.

OBJECTIVES: Hospitalization in a PICU is a life-altering experience for children and their families. Yet, little is known about the well-being of these children after their discharge. We are describing the outcome of PICU survivors at a PICU clinic 2 months after discharge. DESIGN: Prospective cohort study. SETTING: PICU and PICU clinic of CHU Sainte-Justine. PATIENTS: Prospective cohort study of children admitted for greater than or equal to 4 days, greater than or equal to 2 days of invasive ventilation, odds ratio greater than or equal to 4 days of noninvasive ventilation at Centre Hospitalier Universitaire Sainte-Justine. PATIENTS: Prospective cohort study of children admitted for greater than or equal to 4 days, greater than or equal to 2 days of invasive ventilation, or greater than or equal to 4 days of noninvasive ventilation at Centre Hospitalier Universitaire Sainte-Justine PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated by a pediatric intensivist 2 months after discharge at the follow-up clinic. They were asked to fill out validated questionnaires. One hundred thirty-two patients were followed from October 2018 to September 2020. The PICU diagnoses were respiratory illness (40.9%), head trauma, and septic shock (7.6%). Average length of PICU stay was 28.5 ± 84.2 days (median 7 d). Sixty-one percent were intubated. Symptoms reported by families were as follows: fatigue (9.9%), sleep disturbances (20.5%), feeding difficulties (12.1%), and voice change and/or stridor (9.8%). Twenty-one percent of school-aged children reported school delays. Twenty-seven children demonstrated communication delays, 45% gross motor function delays, 41% fine motor delays, 37% delays in problem-solving, and 49% delays in personal-social functioning. Quality of Life scores were 78.1 ± 20.5 and 80.0 ± 17.5 for physical and psychosocial aspects, respectively. Fourteen percent of parents reported financial difficulties, 42% reported symptoms of anxiety, 29% symptoms of depression. CONCLUSIONS: PICU survivors and their families experience significant physical and psychosocial morbidities after their critical illness. PICU follow-up is crucial to determine the outcome of these children and develop interventions.

Simulation-Based Rapid Development and Implementation of a Novel Barrier Enclosure for Use in COVID-19 Patients: The SplashGuard CG.

BACKGROUND: The current COVID-19 pandemic has resulted in over 54,800,000 SARS-CoV-2 infections worldwide with a mortality rate of around 2.5%. As observed in other airborne viral infections such as influenza and SARS-CoV-1, healthcare workers are at high risk for infection when performing aerosol-generating medical procedures (AGMP). Additionally, the threats of a global shortage of standard personal protective equipment (PPE) prompted many healthcare workers to explore alternative protective enclosures, such as the "aerosol box" invented by a Taiwanese anesthetist. Our study includes the design process of a protective barrier enclosure and its subsequent clinical implementation in the management of critically ill adults and children infected with SARS-CoV-2. METHODS AND RESULTS: The barrier enclosure was designed for use in our tertiary care facility and named "SplashGuard CG" (CG for Care Givers). The device has been adapted using a multi- and interdisciplinary approach, with collaboration between physicians, respiratory therapists, nurses, and biomechanical engineers. Computer-aided design and simulation sessions throughout the entire process facilitated the rapid and safe implementation of the SplashGuard CG in different settings (intensive care unit, emergency department, and the operating room) during AGMPs such as bag-valve-mask ventilation, nasopharyngeal suctioning, intubation and extubation, and noninvasive ventilation. Indications for use and anticipatory precautions were communicated to all healthcare workers using the SplashGuard CG. The entire process was completed within one month. CONCLUSION: The rapid design, development, and clinical implementation of a new barrier enclosure, the "SplashGuard CG," was feasible in this time of crisis thanks to close collaboration between medical and engineering teams and the use of recurring simulation sessions to test and improve the initial prototypes. Following this accelerated process, it is necessary to maintain team skills, monitor any undesirable effects, and evaluate and continuously improve this new device.

The New Trainee Effect in Tracheal Intubation Procedural Safety Across PICUs in North America: A Report From National Emergency Airway Registry for Children.

OBJECTIVES: Tracheal intubation carries a high risk of adverse events. The current literature is unclear regarding the "New Trainee Effect" on tracheal intubation safety in the PICU. We evaluated the effect of the timing of the PICU fellow academic cycle on tracheal intubation associated events. We hypothesize 1) PICUs with pediatric critical care medicine fellowship programs have more adverse tracheal intubation associated events during the first quarter (July-September) of the academic year compared with the rest of the year and 2) tracheal intubation associated event rates and first attempt success performed by pediatric critical care medicine fellows improve through the 3-year clinical fellowship. DESIGN: Retrospective cohort study. SETTING: Thirty-seven North American PICUs participating in National Emergency Airway Registry for Children. PATIENTS: All patients who underwent tracheal intubations in the PICU from July 2013 to June 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The occurrence of any tracheal intubation associated events during the first quarter of the academic year (July-September) was compared with the rest in four different types of PICUs: PICUs with fellows and residents, PICUs with fellows only, PICUs with residents only, and PICUs without trainees. For the second hypothesis, tracheal intubations by critical care medicine fellows were categorized by training level and quarter for 3 years of fellowship (i.e., July-September of 1st yr pediatric critical care medicine fellowship = first quarter, October-December of 1st yr pediatric critical care medicine fellowship = second quarter, and April-June during 3rd year = 12th quarter). A total of 9,774 tracheal intubations were reported. Seven-thousand forty-seven tracheal intubations (72%) were from PICUs with fellows and residents, 525 (5%) with fellows only, 1,201 (12%) with residents only, and 1,001 (10%) with no trainees. There was no difference in the occurrence of tracheal intubation associated events in the first quarter versus the rest of the year (all PICUs: July-September 14.9% vs October-June 15.2%; p = 0.76). There was no difference between these two periods in each type of PICUs (all p ≥ 0.19). For tracheal intubations by critical care medicine fellows (n = 3,836), tracheal intubation associated events significantly decreased over the fellowship: second quarter odds ratio 0.64 (95% CI, 0.45-0.91), third quarter odds ratio 0.58 (95% CI, 0.42-0.82), and 12th quarter odds ratio 0.40 (95% CI, 0.24-0.67) using the first quarter as reference after adjusting for patient and device characteristics. First attempt success significantly improved during fellowship: second quarter odds ratio 1.39 (95% CI, 1.04-1.85), third quarter odds ratio 1.59 (95% CI, 1.20-2.09), and 12th quarter odds ratio 2.11 (95% CI, 1.42-3.14). CONCLUSIONS: The New Trainee Effect in tracheal intubation safety outcomes was not observed in various types of PICUs. There was a significant improvement in pediatric critical care medicine fellows' first attempt success and a significant decline in tracheal intubation associated event rates, indicating substantial skills acquisition throughout pediatric critical care medicine fellowship.

Transfusion in children with acute respiratory distress syndrome.

Transfusion is a frequent treatment in pediatric patients with acute respiratory distress syndrome (PARDS) although evidence to support transfusion decision-making is lacking. The purpose of this review is to review the current state of knowledge on the issue of transfusion in children with PARDS and to detail the possible beneficial effects and potential deleterious impacts of transfusion in this patient population. Based on the current literature and recent guidelines, a restrictive red blood cell (RBC) transfusion strategy (avoidance of transfusion when the haemoglobin level is above 7 g/dL) is indicated in stable patients without severe PARDS, as these were excluded from the large trials. In children with severe PARDS, further research is needed to determine if factors other than the haemoglobin level might guide RBC transfusion decision-making by better characterizing the presence of low oxygen delivery (DO2). Additionally, appropriate indications for prophylactic transfusion of hemostatic products (plasma or platelets) in children with PARDS are lacking.

An Atypical Case of Atypical Hemolytic Uremic Syndrome.

We present the case of a 2-month-old infant presenting with pallor and laboratory results showing: hemoglobin 5.1 (10 to 1.5) g/dL, MCV 94.7 (75 to 105) fL, leukocytes 17.4 (7 to 15) ×10/µL, platelets 259 (150 to 450) ×10/µL, hyperbilirubinemia and renal dysfunction. A hemolytic anemia with tubular injury secondary to hemoglobinuria was suspected. Hyperhydration and packed cells were given but she deteriorated. Fluid overload with anuria further complicated the course necessating hemodialysis. Atypical hemolytic uremic syndrome was suspected and eculizumab was administered resulting in rapid improvement. Genetic analysis revealed a mutation in the gene encoding complement factor H and atypical hemolytic uremic syndrome was confirmed.