Cerebral autoregulation in paediatric and neonatal intensive care: A scoping review.

Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care.

Procedural sedation and analgesia in pediatric diagnostic and interventional radiology: An expert DELPHI consensus document developed by the ITALIAN scientific society of anesthesia, analgesia, resuscitation and intensive care (SIAARTI).

BACKGROUND: Children undergoing diagnostic and interventional radiology procedures often require sedation to achieve immobility and analgesia if the procedure is painful. In the past decades, leading scientific organizations have developed evidence-based guidelines for procedural sedation and analgesia in children outside of the operating room. Their recommendations are being applied to procedural sedation in radiology. However, some questions remain open regarding specific aspects contextualized to the radiology setting, such as elective prone sedation, the urgency of the procedure, when venous access or airway protection is required, and others. AIMS: To address the unresolved issues of procedural sedation and analgesia in pediatric diagnostic and interventional radiology. METHODS: An expert panel of pediatricians, pediatric anesthesiologists, intensivists, and neuroradiologists selected topics representative of current controversies and formulated research questions. Statements were developed by reviewing the literature for new evidence, comparing expertise and experience, and expressing opinions. Panelists' agreement with the statements was collected anonymously using the DELPHI method. RESULTS: Twelve evidence-based or expert opinion incorporate are presented, considering risks, benefits, and applicability. CONCLUSIONS: This consensus document, developed by a multidisciplinary panel of experts involved in the field, provides statements to improve the quality of decision-making practice in procedural sedation and analgesia in pediatric radiology.

Visualization of the Intracranial Pressure and Time Burden in Childhood Brain Trauma: What We Have Learned One Decade on With KidsBrainIT.

To validate the intracranial pressure (ICP) dose-response visualization plot for the first time in a novel prospectively collected pediatric traumatic brain injury (pTBI) data set from the multi-center, multi-national KidsBrainIT consortium. Prospectively collected minute-by-minute ICP and mean arterial blood pressure time series of 104 pTBI patients were categorized in ICP intensity-duration episodes. These episodes were correlated with the 6-month Glasgow Outcome Score (GOS) and displayed in a color-coded ICP dose-response plot. The influence of cerebrovascular reactivity and cerebral perfusion pressure (CPP) were investigated. The generated ICP dose-response plot on the novel data set was similar to the previously published pediatric plot. This study confirmed that higher ICP episodes were tolerated for a shorter duration of time, with an approximately exponential decay curve delineating the positive and negative association zones. ICP above 20 mm Hg for any duration in time was associated with poor outcome in our patients. Cerebrovascular reactivity state did not influence their respective transition curves above 10 mm Hg ICP. CPP below 50 mm Hg was not tolerated, regardless of ICP and duration, and was associated with worse outcome. The ICP dose-response plot was reproduced in a novel and independent pTBI data set. ICP above 20 mm Hg and CPP below 50 mm Hg for any duration in time were associated with worse outcome. This highlighted a pressing need to reduce pediatric ICP therapeutic thresholds used at the bedside.

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.

Cerebral autoregulation monitoring using the cerebral oximetry index after neonatal cardiac surgery: A single-center retrospective cohort study.

OBJECTIVE: To investigate whether cerebral autoregulation is impaired after neonatal cardiac surgery and whether changes in autoregulation metrics are associated with different congenital heart defects or the incidence of postoperative neurologic events. METHODS: This is a retrospective observational study of neonates undergoing monitoring during the first 72 hours after cardiac surgery. Archived data were processed to calculate the cerebral oximetry index (COx) and derived metrics. Acute neurologic events were identified by an electronic medical record review. The Skillings-Mack test and the Wilcoxon signed-rank test were used to analyze the evolution of autoregulation metrics over time; the Mann-Whitney U test was used for comparison between groups. RESULTS: We included 28 neonates, 7 (25%) with hypoplastic left heart syndrome and 21 (75%) with transposition of the great arteries. Overall, the median percentage of time spent with impaired autoregulation, defined as percentage of time with a COx >0.3, was 31.6% (interquartile range, 21.1%-38.3%). No differences in autoregulation metrics between different cardiac defects subgroups were observed. Seven patients (25%) experienced a postoperative acute neurologic event. Compared to the neonates without an acute neurologic event, those with an acute neurologic event had a higher COx (0.16 vs 0.07; P = .035), a higher percentage of time with a COx >0.3 (39.4% vs 29.2%; P = .017), and a higher percentage of time with a mean arterial pressure below the lower limit of autoregulation (13.3% vs 6.9%; P = .048). CONCLUSIONS: COx monitoring after cardiac surgery allowed for the detection of impaired cerebral autoregulation, which was more frequent in neonates with postoperative acute neurologic events.

Association Between Early Change in Arterial Carbon Dioxide Tension and Outcomes in Neonates Treated by Extracorporeal Membrane Oxygenation.

The primary objective was to investigate the association between partial pressure of carbon dioxide (PaCO 2 ) change after extracorporeal membrane oxygenation (ECMO) initiation and neurologic outcome in neonates treated for respiratory failure. A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) database including newborns supported by ECMO for respiratory indication during 2015-2020. The closest Pre-ECMO (Pre-ECMO PaCO 2 ) and at 24 hours after ECMO initiation (H24 PaCO 2 ) PaCO 2 values allowed to calculate the relative change in PaCO 2 (Rel Δ PaCO 2 = [H24 PaCO 2 - Pre-ECMO PaCO 2 ]/Pre-ECMO PaCO 2 ). The primary outcome was the onset of any acute neurologic event (ANE), defined as cerebral bleeding, ischemic stroke, clinical or electrical seizure, or brain death during ECMO. We included 3,583 newborns (median age 1 day [interquartile range {IQR}, 1-3], median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers. The median Rel Δ PaCO 2 value was -29.9% [IQR, -46.2 to -8.5]. Six hundred nine (17%) of them had ANE (405 cerebral bleedings, 111 ischemic strokes, 225 seizures, and 6 brain deaths). Patients with a decrease of PaCO 2 > 50% were more likely to develop ANE than others (odds ratio [OR] 1.78, 95% confidence interval [CI], 1.31-2.42, p < 0.001). This was still observed after adjustment for all clinically relevant confounding factors (adjusted OR 1.94, 95% CI, 1.29-2.92, p = 0.001). A significant decrease in PaCO 2 after ECMO start is associated with ANE among neonates requiring ECMO for respiratory failure. Cautious PaCO 2 decrease should be considered after start of ECMO therapy.

Sudden Onset of Severe Pulmonary Hypertension in a Preterm Infant: A Case Report on the Role of Maternal Use of Serotonin Re-Uptake Inhibitors During Pregnancy and Concurrent Risk Factors.

Persistent pulmonary hypertension of the newborn (PPHN) is a severe condition caused by failed circulatory adaptation at birth. Pulmonary hypertension is most common in full-term infants and rare in preterms, although it is increasingly diagnosed also in extremely preterm infants. Previous studies demonstrated the association between maternal use of selective serotonin re-uptake inhibitors during gestation and pulmonary hypertension. This brief report describes the complex physiopathological correlations that were identified in a case of severe pulmonary hypertension in a fetal growth restricted (FGR) preterm infant, with a history of maternal use of antidepressants during pregnancy. Perinatal factors, triggers and aggravating mechanisms caused a dramatic clinical course. Maternal history of escitalopram therapy throughout pregnancy was noted. Uteroplacental insufficiency, fetal hypoxia, FGR, preeclampsia, preterm delivery, antenatal steroids, and cesarean section were documented as concurrent risk factors. Myocardial immaturity and dysfunction, secondary to FGR and prematurity aggravated the hemodynamic compromise. The short time gap between pharmacological ductal closure and the onset of PPHN may suggest a cause-effect relationship, as observed in previous reports. Placental histopathologic findings are reported.

Optic Nerve Sheath Diameter Ultrasound: A Non-Invasive Approach to Evaluate Increased Intracranial Pressure in Critically Ill Pediatric Patients.

Early diagnosis of increased intracranial pressure (ICP) is crucial for prompt diagnosis and treatment of intracranial hypertension in critically ill pediatric patients, preventing secondary brain damage and mortality. Although the placement of an external ventricular drain coupled to an external fluid-filled transducer remains the gold standard for continuous ICP monitoring, other non-invasive approaches are constantly being improved and can provide reliable estimates. The use of point-of-care ultrasound (POCUS) for the assessment of ICP has recently become widespread in pediatric emergency and critical care settings, representing a valuable extension of the physical examination. The aim of this manuscript is to review and discuss the basic principles of ultra-sound measurement of the optic nerve sheath diameter (ONSD) and summarize current evidence on its diagnostic value in pediatric patients with ICP. There is increasing evidence that POCUS measurement of the ONSD correlates with ICP, thus appearing as a useful extension of the physical examination in pediatrics, especially in emergency medicine and critical care settings for the initial non-invasive assessment of patients with suspected raised ICP. Its role could be of value even to assess the response to therapy and in the follow-up of patients with diagnosed intracranial hypertension if invasive ICP monitoring is not available. Further studies on more homogeneous and extensive study populations should be performed to establish ONSD reference ranges in the different pediatric ages and to define cut-off values in predicting elevated ICP compared to invasive ICP measurement.

COVID-19 Pneumomediastinum: Possible Role of Transesophageal Echo in Bedside Percutaneous Bicaval Double-Lumen ECMO Cannulation in Children. A Case Report.

COVID-19 is generally uneventful in children. Only 8% of severe acute respiratory distress syndrome corona virus 2 pediatric patients require intensive care; of these, 1% may need extracorporeal membrane oxygenation. Preexisting medical conditions are an independent risk factor for pediatric intensive care unit admission. We describe the case of an 11-year-old girl with adenosine deaminase 2 deficiency who presented severe COVID-19 acute respiratory distress syndrome, complicated by a massive air leak syndrome. The respiratory failure, refractory to conventional support, required veno-venous extracorporeal membrane oxygenation. To prevent viral diffusion, bicaval double-lumen cannulation was performed percutaneously at the bedside under exclusive echo guidance. Because of pneumomediastinum, pneumothorax, and subcutaneous emphysema, ultrasound visualization of the heart was possible only with transesophageal echo. To our knowledge, this is the first description of a transesophageal echo guided bedside percutaneous bicaval double-lumen extracorporeal membrane oxygenation cannulation in a pediatric patient. Pitfalls of the technique are highlighted.

Working as a team in airway surgery: History, present and perspectives.

Teamwork is one of the most important trend in modern medicine. Airway team were created in many places to respond in a multidisciplinary and coordinated way to challenging clinical problems which were beyond the possibility of an individual management. In this chapter, we illustrate the historical steps leading to the development of an airway team in a pediatric referral hospital, describe the present teamwork activity defining the key points for the creation of a team and discussing different organization models; finally we delineate possible future directions for the airway teams in the globalized world.

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.

Ultrasound non-invasive intracranial pressure assessment in paediatric neurocritical care: a pilot study.

BACKGROUND: The assessment of intracranial pressure (ICP) is essential in the management of neurocritical care paediatric patients. The gold standard for invasive ICP is an intraventricular catheter or intraparenchymal microsensor but is invasive and carries some risks. Therefore, a non-invasive method for measuring ICP (nICP) would be desirable especially in the paediatric population. The aim of this study is to assess the relationship between ICP and different ultrasound-based methods in neurocritical care paediatric patients. METHODS: Children aged < 16 years with indication for invasive ICP monitoring were prospectively enrolled. The following non-invasive methods were compared with the invasive gold standard: optic nerve sheath diameter ultrasound (ONSD)-derived nICP (nICPONSD); arterial TCD-derived pulsatility index (PIa) and a method based on the diastolic component of the TCD cerebral blood flow velocity and mean arterial blood pressure (nICPFVd). RESULTS: We analysed 107 measurements from 10 paediatric patients. Results from linear regression demonstrated that, among the nICP methods, ONSD has the best correlation with ICP (r = 0.852 (p < 0.0001)). Results from receiving operator curve analysis demonstrated that using a threshold of 15 mmHg, ONSD has and area under the curve (AUC) of 0.94 (95% CI = 0.892-0.989), with best threshold at 3.85 mm (sensitivity = 0.811; specificity = 0.939). CONCLUSIONS: Our preliminary results suggested that ONSD ultrasonography presents the best accuracy to assess ICP among the methods studied. Given its non-invasiveness, repeatability and safety, this technique has the potential of representing a valid option as non-invasive tool to assess the risk of intracranial hypertension in the paediatric population.

Intensivists Performed Percutaneous Bicaval Double-Lumen Echo-Guided Extracorporeal Membrane Oxygenation Cannulation at Bedside in Newborns and Children: A Retrospective Analysis.

OBJECTIVES: To describe a single institution experience on echo-guided percutaneous bicaval double lumen extracorporeal membrane oxygenation cannulation performed at the bedside by intensivists. DESIGN: Retrospective observational study. SETTING: Extracorporeal membrane oxygenation team of a tertiary care children's hospital. PATIENTS: All patients 0-14 years old undergoing venovenous extracorporeal membrane oxygenation from January 1, 2013, to January 1, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty children underwent 32 extracorporeal membrane oxygenation runs. Median age at enrollment was 2 months (interquartile range, 0-20.5 mo), 65.6% of the runs (21 patients) were performed in newborns (n = 13, 40.6%) or infants (n = 8, 25%). Median preextracorporeal membrane oxygenation index was 66.9 (interquartile range, 50-85.6). Major comorbidities were present in 50% of patients. All patients were cannulated percutaneously. In two cases cannulation occurred from the left internal jugular vein. Extracorporeal membrane oxygenation was effective in increasing pH, arterial oxygen saturation, PaO2, and lowering PaCO2. The overall differences in pre and postextracorporeal membrane oxygenation values were statistically significant, while stratifying patients according to the cannula diameter (mm)/major diameter of the cannulated internal jugular vein (mm) ratio (> 0.67 or ≤ 0.67), statistical significance was reached only for the highest ratio. Complications were observed in three runs: two cannula tip dislocations in the right atrium and one limited flow in the only case in which an Avalon cannula was not used. In 20 cases (62.5% of 32 runs), the cannulated vessel was patent at follow-up or autopsy. A ratio less than or equal to 0.67 or greater than 0.67 did not influence the occurrence rate of complications, nonpatency of the internal jugular vein, death for intracranial bleeding and death at 30 days from extracorporeal membrane oxygenation discontinuation. Overall cumulative survival at 30 days from extracorporeal membrane oxygenation discontinuation was 60% (95% CI, 40-75), with a survival advantage in the case of ratio greater than 0.67 (65%; 95% CI, 44-80 vs 25%; 95% CI, 0-60). CONCLUSIONS: The described technique proved to be feasible, safe, and effective. Further investigation is needed.

Epidemiology of Infectious Complications During Extracorporeal Membrane Oxygenation in Children: A Single-Center Experience in 46 Runs.

BACKGROUND: Infections represent a severe complication of extracorporeal membrane oxygenation (ECMO). Aim of the present study was to describe the epidemiology of infections acquired during ECMO in a tertiary care children's hospital. METHODS: Retrospective analysis of clinical records of patients undergoing ECMO between January 2009 and December 2016. For each patient, data were collected on clinical characteristics, modality of ECMO support, site and etiology of documented infections, survival within 1 week after ECMO weaning and/or at pediatric intensive care unit discharge. These data were employed to evaluate overall infection prevalence, infection rate expressed as episodes/1000 days of support and cumulative risk estimates of infections occurring during ECMO. RESULTS: During the study period, a total of 46 ECMO procedures were performed. The overall prevalence of documented infections was 33%, with an infection rate of 27.22 and a cumulative risk of 55%. Bloodstream infection represented the most frequently documented (53%), followed by pneumonia (40%). Coagulase-negative staphylococci and Pseudomonas aeruginosa prevailed as isolated pathogens. Overall survival was 59%, and 46% among those developing infections during ECMO. CONCLUSIONS: ECMO is a procedure at high risk for infections. Our data, limited to 1 center, represent a recent benchmark for further investigations.

Venovenous ECMO for Congenital Diaphragmatic Hernia: Role of Ductal Patency and Lung Recruitment.

We report a case of antenatally diagnosed left-sided congenital diaphragmatic hernia, managed on venovenous extracorporeal membrane oxygenation with an hemodynamic and ventilation strategy aimed at preventing left and right ventricular dysfunction. Keeping the ductus arteriosus open with prostaglandin infusion and optimizing lung recruitment were effective in achieving hemodynamic stabilization and an ideal systemic oxygen delivery. The patient was discharged from the hospital and had normal development at 1 year of age. The combination of ductal patency and lung recruitment has not been previously reported as a strategy to stabilize congenital diaphragmatic hernia patients undergoing venovenous extracorporeal membrane oxygenation. We believe that this approach may deserve further evaluation in prospective studies.