Central Venous Pressure Estimation by Ultrasound Measurement of Inferior Vena Cava and Aorta Diameters in Pediatric Critical Patients: An Observational Study.

OBJECTIVES: To evaluate the ability to predict central venous pressure by ultrasound measured inferior vena cava and aortic diameters in a PICU population and to assess interoperator concordance. DESIGN: Noninterventional observational study. SETTING: PICU of a tertiary-care academic center. PATIENTS: Eighty-eight pediatric patients (0-16 yr old) with a central venous catheter in place were studied. Sixty-nine percent of the patients received positive-pressure ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An experienced and a nonexperienced operator used ultrasound to measure the maximal diameter of inferior vena cava and minimal diameter of the inferior vena cava and the maximum diameter of the abdominal aorta from the subxiphoid window. The inferior vena cava collapsibility index and the ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta were then derived. The central venous pressure was measured using a central venous catheter and recorded. Twenty-three patients had low central venous pressure values (≤ 4 mm Hg), 35 patients a value in the range of 5-9 mm Hg, and 30 patients high values (≥ 10 mm Hg). Both inferior vena cava collapsibility index and ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta were predictive of high (≥ 10 mm Hg) or low (≤ 4 mm Hg) central venous pressure. The test accuracy showed the best results in predicting low central venous pressure with an inferior vena cava collapsibility index greater than or equal to 35% and ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta less than or equal to 0.8, and in predicting high central venous pressure with an inferior vena cava collapsibility index less than or equal to 20% and ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta greater than or equal to 1.3. Inferior vena cava collapsibility index returned generally higher accuracy values than ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta. Lin's coefficient of concordance between the operators was 0.78 for inferior vena cava collapsibility index and 0.86 for ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta. CONCLUSIONS: Inferior vena cava collapsibility index and ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta correlate well with central venous pressure measurements in this PICU population, and specific inferior vena cava collapsibility index or ratio of maximal diameter of inferior vena cava/maximum diameter of the abdominal aorta thresholds appear to be able to differentiate children with high or low central venous pressure. However, the actual clinical application of these statistically significant results remains limited, especially by the intrinsic flaws of the procedure.

Acute Kidney Injury in Critically Ill Children: A Retrospective Analysis of Risk Factors.

INTRODUCTION: Children admitted to paediatric intensive care unit (PICU) are at risk of acute kidney injury (AKI). However, few paediatric studies have focused on the identification of factors potentially associated with the development of this condition. The aim of our study was to assess the incidence rate of AKI, identify risk factors, and evaluate clinical outcome in a large sample of critically ill children. METHODS: This retrospective observational study was conducted including patients admitted to our PICU from January 2014 to December 2016. AKI was defined according to Kidney Disease: Improving Global Outcome criteria. RESULTS: A total of 222 PICU patients out of 811 (27%) had AKI (stage I 39%, stage II 24%, stage III 37%). The most common PICU admission diagnoses in AKI cases were heart disease (38.6%), respiratory failure (16.8%) and postsurgical non-cardiac patients (11%). Hypoxic-ischaemic was the most frequent cause of AKI. Significant risk factors for AKI following multivariate analysis were age >2 months (OR 2.43; 95% CI 1.03-7.87; p = 0.05), serum creatinine at admission >44 µmol/L (OR 2.23; 95% CI 1.26-3.94; p = 0.006), presence of comorbidities (OR 1.84; 95% CI 1.03-3.30; p = 0.04), use of inotropes (OR 2.56; 95% CI 1.23-5.35; p= 0.012) and diuretics (OR 2.78; 95% CI 1.49-5.19; p = 0.001), exposure to nephrotoxic drugs (OR 1.66; 95% CI 1.01-2.91; p= 0.04), multiple organ dysfunction syndrome (OR 2.68; 95% CI 1.43-5.01; p = 0.002), and coagulopathy (OR 1.89; 95% CI 1.05-3.38, p = 0.03). AKI was associated with a significant longer PICU stay (median LOS of 8 days, interquartile range [IQR] 3-16, versus 4 days, IQR 2-8, in non-AKI patients; p < 0.001). The mortality rate resulted tenfold higher in AKI than non-AKI patients (12.6 vs. 1.2%; p < 0.001). CONCLUSIONS: The incidence of AKI in critically ill children is high, with an associated increased length of stay and risk of mortality. In the PICU setting, risk factors of AKI are multiple and mainly associated with illness severity.

Predictors of mortality after admission to pediatric intensive care unit in oncohematologic patients without history of hematopoietic stem cell transplantation: A single-center experience.

BACKGROUND: Pediatric oncohematologic patients are a high-risk population for clinical deterioration that might require pediatric intensive care unit (PICU) admission. Several studies have described outcomes and mortality predictors for patients post hematopoietic stem cell transplantation (HSCT), but fewer data exist regarding the category of non-HSCT patients. PROCEDURE: All oncohematologic non-HSCT patients ≤18 years requiring PICU admission from 1998 to 2015 in our tertiary-care academic hospital were retrospectively evaluated by means of the pediatric hematology-oncology unit database and the Italian PICUs data network database. We assessed the relation between demographic and clinical characteristics and 90-day mortality after PICU admission. RESULTS: Of 3750 hospitalized oncohematologic patients, 3238 were non-HSCT and 63 (2%) of them were admitted to the PICU. Patients were mainly affected by hematological malignancies (70%) and mostly were in the induction-therapy phase. The main reasons for admission were respiratory failure (40%), sepsis (25%), and seizures (16%). The median PICU stay was 5 days (range 1-107). The mortality rate at PICU discharge was 30%, and at 90 days it was 35%. Fifty-five percent of deaths happened in the first 2 days of the PICU stay. Cardiac arrest (P = .007), presence of disseminated intravascular coagulation (DIC, P = .007), and acute kidney injury (AKI) at PICU admission (P < .001) and during PICU stay (P = .021) were significant predictors of mortality in the multivariate analysis. Respiratory failure and mechanical ventilation were not associated with mortality. CONCLUSIONS: A relatively small percentage of non-HSCT patients required PICU admission, but the mortality rate was still high. Hemodynamic instability, DIC, and AKI, but not respiratory failure, were significant predictors of mortality.

The quality of life in extracorporeal life support survivors: single-center experience of a long-term follow-up.

OBJECTIVE: To evaluate the health-related quality of life on a very long-term follow-up in patients treated with extracorporeal membrane oxygenation (ECMO) during neonatal and pediatric age. DESIGN: Prospective follow-up study. SETTING: Pediatric Intensive Care Unit of a tertiary-care University-Hospital. PATIENTS: Out of 20 neonates and 21 children treated with ECMO in our center, 24 patients underwent short-term neurological follow-up. Twenty of them underwent long-term neurological follow-up. INTERVENTION: Short-term follow-up was performed at 18 months and consisted in clinical evaluation, electroencephalography, and neuroimaging. Long-term follow-up was performed in 2017, at the mean period 19.72 years from ECMO (median 20.75, range 11.50-24.08) and consisted in a standardized questionnaires self-evaluation (PedsQL 4.0 Generic Core Scale) of health-related quality of life and an interviewed about the presence of organ morbidity, school level, or work position. MEASUREMENTS AND MAIN RESULTS: Sixty-one percent (25/41) of the patients survived within 30 days after ECMO treatment. Short-term follow-up was performed in 24 patients (1 patient but died before the evaluation): 21 patients (87%) showed a normal neurological status, and 3 developed severe disability. Long-term follow-up was performed in 20 long-term survivors (3 patients were not possible to be contacted and considered lost to follow-up): mean age of patients at long-term follow-up was 21.23 (median 20.96, range 13.33-35.58) years; 90% (18/20) of them have no disability with a complete normal quality of life and 95% have no cognitive impairment. CONCLUSIONS: ECMO represents a life-saving treatment for infants and children with respiratory and/or heart failure; survivors show a good quality of life comparable to healthy peers.

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT.

Evolution of Noninvasive Mechanical Ventilation Use: A Cohort Study Among Italian PICUs.

OBJECTIVE: To assess how clinical practice of noninvasive ventilation has evolved in the Italian PICUs. DESIGN: National, multicentre, retrospective, observational cohort. SETTING: Thirteen Italian medical/surgical PICUs that participated in the Italian PICU Network. PATIENTS: Seven thousand one-hundred eleven admissions of children with 0-16 years old admitted from January 1, 2011, to December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cause of respiratory failure, length and mode of noninvasive ventilation, type of interfaces, incidence of treatment failure, and outcome were recorded. Data were compared with an historical cohort of children enrolled along 6 months from November 1, 2006, to April 30, 2007, over the viral respiratory season. Seven thousand one-hundred eleven PICU admissions were analyzed, and an overall noninvasive ventilation use of 8.8% (n = 630) was observed. Among children who were admitted in the PICU without mechanical ventilation (n = 3,819), noninvasive ventilation was used in 585 patients (15.3%) with a significant increment among the three study years (from 11.6% in 2006 to 18.2% in 2012). In the endotracheally intubated group, 17.2% children received noninvasive ventilation at the end of the weaning process to avoid reintubation: 11.9% in 2006, 15.3% in 2011, and 21.6% in 2012. Noninvasive ventilation failure rate raised from 10% in 2006 to 16.1% in 2012. CONCLUSIONS: Noninvasive ventilation is increasingly and successfully used as first respiratory approach in several, but not all, Italian PICUs. The current study shows that noninvasive ventilation represents a feasible and safe technique of ventilatory assistance for the treatment of mild acute respiratory failure. Noninvasive ventilation was used as primary mode of ventilation in children with low respiratory tract infection (mainly in bronchiolitis and pneumonia), in acute on chronic respiratory failure or to prevent reintubation.

Failure mode and effective analysis ameliorate awareness of medical errors: a 4-year prospective observational study in critically ill children.

BACKGROUND: Errors in are estimated to occur with an incidence of 3.7-16.6% in hospitalized patients. The application of systems for detection of adverse events is becoming a widespread reality in healthcare. Incident reporting (IR) and failure mode and effective analysis (FMEA) are strategies widely used to detect errors, but no studies have combined them in the setting of a pediatric intensive care unit (PICU). AIM: The aim of our study was to describe the trend of IR in a PICU and evaluate the effect of FMEA application on the number and severity of the errors detected. METHODS: With this prospective observational study, we evaluated the frequency IR documented in standard IR forms completed from January 2009 to December 2012 in the PICU of Woman's and Child's Health Department of Padova. On the basis of their severity, errors were classified as: without outcome (55%), with minor outcome (16%), with moderate outcome (10%), and with major outcome (3%); 16% of reported incidents were 'near misses'. We compared the data before and after the introduction of FMEA. RESULTS: Sixty-nine errors were registered, 59 (86%) concerning drug therapy (83% during prescription). Compared to 2009-2010, in 2011-2012, we noted an increase of reported errors (43 vs 26) with a reduction of their severity (21% vs 8% 'near misses' and 65% vs 38% errors with no outcome). CONCLUSION: With the introduction of FMEA, we obtained an increased awareness in error reporting. Application of these systems will improve the quality of healthcare services.

Near-infrared spectroscopy as continuous real-time monitoring for kidney graft perfusion.

BACKGROUND: Near-infrared spectroscopy (NIRS) is a non-invasive technique designed to study regional oxygenation (rSO(2)) by measuring the absorption of chromophores. This study investigated the role of NIRS in the real-time monitoring of kidney graft perfusion for 72 h post-transplantation. METHODS: Consecutive children undergoing living related donor (LRD) or deceased donor (DD) kidney transplantation (KTP) were prospectively enrolled between April 2010 and August 2011. Renal rSO(2) values were registered continuously for 3 days and correlated with hourly urine output, serum creatinine, and urinary neutrophil gelatinase-associated lipocalin (u-NGAL). RESULTS: Twenty-four children were included, 6 underwent LRD and 18 DD KTP. Median age was 12.5 years (interquartile range [IQR] 3.5-16.6) and median body weight was 37 kg (IQR 13-49.7). Four patients experienced delayed graft function (DGF). Renal Doppler ultrasound showed normal vascularization patterns in all children. Median basal renal rSO(2) value was 68.8 % (IQR 59.3-76.2), significantly lower than the end-of-period result (83.6 %; IQR 79.2-90.4; p < 0.0001). Renal rSO(2) values showed significant correlation with serum creatinine (rs = -0.62; p < 0.05) and estimated glomerular filtration rate (eGFR) (rs = 0.64; p < 0.05). No correlation was shown between rSO(2) and diuresis. Increased rSO(2) was also found in patients who experienced DGF. u-NGAL exhibited a trend toward a decrease from baseline in both DD and LRD KTPs, with a strong negative correlation with rSO(2). CONCLUSIONS: rSO(2) assessed by NIRS strongly correlates with common markers of kidney graft function and perfusion, allowing continuous real-time monitoring of blood flow in renal grafts.

High-flow nasal cannula oxygen for bronchiolitis in a pediatric ward: a pilot study.

UNLABELLED: High-flow nasal cannula (HFNC) is a widely used ventilatory support in children with bronchiolitis in the intensive care setting. No data is available on HFNC use in the general pediatric ward. The aim of this study was to evaluate the feasibility of HFNC oxygen therapy in infants hospitalized in a pediatric ward for moderate-severe bronchiolitis and to assess the changes in ventilatory parameters before and after starting HFNC support. This prospective observational pilot study was carried out during the bronchiolitis season 2011-2012 in a pediatric tertiary care academic center in Italy. Interruptions of HFNC therapy and possible side effects or escalation to other forms of respiratory support were recorded. Oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), and respiratory rate (RR), measured for a baseline period of 1 h before and at specific time intervals in 48 h after the start of HFNC were recorded. Twenty-seven infants were included (median age 1.3 months; absolute range 0.3-8.5). No adverse events, no premature HFNC therapy termination, and no escalation to other forms of respiratory support were recorded. Median SpO2 significantly increased by 1-2 points after changing from standard oxygen to HFNC (p <0.001). Median ETCO2 and RR rapidly decreased by 6-8 mmHg and 13-20 breaths per minute, respectively, in the first 3 h of HFNC therapy (p <0.001) and remained steady thereafter. CONCLUSIONS: Use of HFNC for oxygen administration is feasible for infants with moderate-severe bronchiolitis in a general pediatric ward. In these children, HFNC therapy improves oxygen saturation levels and seems to be associated with a decrease in both ETCO2 and RR.

Meningococcemia and heparin-induced thrombocytopenia: a dangerous combination.

We present a dramatic case of a patient presenting with disseminated intravascular coagulation related to meningococcal sepsis who developed heparin-induced thrombocytopenia following heparin administration during continuous renal replacement therapy. Association of these two prothrombotic conditions led to severe limbs ischemia and finally to bilateral legs amputation. We stress the importance of suspect heparin-induced thrombocytopenia in intensive care unit patients, especially when an improvement of other coagulation parameters is observed, and heparin therapy was started.

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy. CASE REPORT: A previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit. CONCLUSIONS: To our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.

Is ketamine infusion effective and safe as an adjuvant of sedation in the PICU? Results from the Ketamine Infusion Sedation Study (KISS).

STUDY OBJECTIVE: We aimed to evaluate the efficacy and safety of ketamine in ensuring comfort and sparing conventional drugs when used as an adjuvant for analgesia and sedation in the Pediatric Intensive Care Unit (PICU) as a continuous infusion (≥12 h). DESIGN: Observational prospective study. SETTING: Tertiary-care-center PICU. PATIENTS: All consecutive patients <18 years who received ketamine for ≥12 h between January 2019 and July 2021. INTERVENTIONS: ketamine infusion for ≥12 h. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients (median age 16 months, Interquartile Range (IQR) 7-43) were enrolled. Twenty-six percent of patients (n = 20) were paralyzed, while 74% (n = 57) were not. The median infusion duration was 90 h (IQR 39-193), with doses between 15 (IQR 15-20) and 30 µg/kg/min (IQR 20-50). At 24 h of ketamine infusion, values of COMFORT-B-Scale (CBS) were significantly lower compared with values pre-ketamine (p < 0.001). Simultaneously, doses/kg/h of opioids and benzodiazepines significantly decreased at 24 h (p < 0.001 and p = 0.002, respectively), while doses/kg/h of propofol (p = 0.500) and dexmedetomidine (p = 0.072) did not significantly change. Seventy-four percent of non-paralyzed patients (42/57) had a decrease in CBS ≥2 points with no increase of concomitant analgosedation drugs. Among paralyzed patients (n = 20), 13 (65%) had no increase of concomitant analgosedation within 24 h after ketamine initiation. Overall, 55/77 (71%) of patients responded to ketamine. The mean and maximum ketamine infusion dosages were significantly higher in the non-responders (p = 0.021 and 0.028, respectively). Eleven patients had adverse events potentially related to ketamine (hypersalivation, systemic hypertension, dystonia/dyskinesia, tachycardia, and agitation) and six patients required intervention (dose reduction, suspension, or pharmacologic therapy). None of the patients developed delirium during ketamine infusion. CONCLUSIONS: Ketamine used as a continuous infusion in the PICU might represent a valid strategy to ensure comfort and spare opioids and benzodiazepines in difficult-to-sedate PICU patients. Adverse events are minor and easily reversible. Future study will be needed to investigate long-term outcomes.

PICU Admission of Children for Status Epilepticus: Is There a Different Approach Between Referral and Second-Level Hospitals in an Italian Region?

Appropriate status epilepticus (SE) management is key to minimize admission to the pediatric intensive care unit (PICU). We retrospectively describe 115 children admitted to the PICU of the tertiary-care referral hospital of Padova for seizures, SE, and SE-related complications (59% from second-level hospitals, 41% from the referral hospital) and compare SE management among hospitals. Compared with the referral center, in second-level hospitals, anesthetics were more often administered as first/second drug (P < .001), and intubation was more frequent (P < .001). Intubation was significantly associated with SE onset at home (P = .045) and benzodiazepine-associated respiratory depression (P = .044). There was no association between intubation and SE duration, etiology, PICU length of stay, and morbidity at discharge. In conclusion, adherence to treatment protocols on SE management after the first-line drug differs between referral center and second-level hospitals. Lack of association with SE characteristics and patient's outcome suggests PICU admission could be due to inappropriate invasive management.

Corrigendum on: Ventilation weaning and extubation readiness in children in pediatric intensive care unit: A review.

[This corrects the article DOI: 10.3389/fped.2022.867739.].

Life-sustaining treatment decisions in pediatric intensive care: an Italian survey on ethical concerns.

OBJECTIVES: To investigate how life-sustaining treatment (LST) decisions are made and identify problematic ethical concerns confronted by physicians and nurses in pediatric intensive care within Italy. METHODS: An 88-question online survey was created, based on a previous qualitative study conducted by this team. The survey was designed to identify how LST decisions were managed; contrasting actual practices with what participants think practices should be. Replies from physicians and nurses were compared, to identify potential inter-professional ethical tensions. The study also identified participants' principal ethical concerns. Moreover, open-ended questions elicited qualitative perspectives on participants' views. The survey was pilot-tested and refined before initiation of the study. RESULTS: 31 physicians and 65 nurses participated in the study. Participants were recruited from pediatric intensive care units across five Italian cities; i.e., Florence, Milan, Padua, Rome, Verona. Statistically significant differences were identified for (a) virtually all questions contrasting actual practices with what participants think practices should be and (b) 14 questions contrasting physician replies with those of nurses. Physicians and nurses identified the absence of legislative standards for LST withdrawal as a highly problematic ethical concern. Physicians also identified bearing responsibility for LST decisions as a major concern. Qualitative descriptions further demonstrated that these Italian pediatric intensive care clinicians encounter significantly distressing ethical problems in their practice. CONCLUSIONS: The results of this study highlight a need for the development of (a) strategies for improving team processes regarding LST decisions, so they can be better aligned with how clinicians think decisions should be made, and (b) Italian LST decision-making standards that can help ensure optimal ethical practices.

Extracorporeal Membrane Oxygenation Support for Failure to Wean From Cardiopulmonary Bypass After Pediatric Cardiac Surgery: Analysis of Extracorporeal Life Support Organization Registry Data.

OBJECTIVES: Extracorporeal membrane oxygenation has been used to support children who fail to wean from cardiopulmonary bypass after pediatric cardiac surgery, but little is known about outcomes. We aimed to describe epidemiology and extracorporeal membrane oxygenation factors associated with inhospital mortality in these patients. DESIGN: Retrospective multicenter registry-based cohort study. SETTING: International pediatric extracorporeal membrane oxygenation centers. PATIENTS: Children less than 18 years old supported with extracorporeal membrane oxygenation for failure to wean from cardiopulmonary bypass after cardiac surgery during 2000-2016 and reported to Extracorporeal Life Support Organization's registry. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was inhospital mortality. Cardiac surgical procedural complexity was assigned using risk adjustment in congenital heart surgery-1. Multivariable logistic regression was used to identify factors independently associated with the primary outcome. We included 2,322 patients, with a median age of 26 days (interquartile range, 7-159); 47% underwent complex surgical procedures (risk adjustment in congenital heart surgery 4-6 categories). Inhospital mortality was 55%. The multivariable model evaluating associations with inhospital mortality showed noncardiac congenital anomalies (odds ratio, 1.78; CI, 1.36-2.32), comorbidities (odds ratio, 1.59; CI, 1.30-1.94), preoperative cardiac arrest (odds ratio, 1.67; CI, 1.20-2.34), preoperative mechanical ventilation greater than 24 hours (odds ratio, 1.49; CI, 1.21-1.84), preoperative bicarbonate administration (odds ratio, 1.42; CI, 1.08-1.86), longer cardiopulmonary bypass time (> 251 min; odds ratio, 1.50; CI, 1.13-1.99), complex surgical procedures (odds ratio, 1.43; CI, 1.13-1.81), longer extracorporeal membrane oxygenation duration (> 104 hr, odds ratio, 1.54; CI, 1.17-2.02), and extracorporeal membrane oxygenation complications increased the odds of inhospital mortality. Age greater than 26 days (odds ratio, 0.56; CI, 0.42-0.75) reduced the odds of mortality. CONCLUSIONS: Children supported with extracorporeal membrane oxygenation for failure to wean from cardiopulmonary bypass after cardiac surgery are at high risk of mortality (55%). Younger patients, those with congenital abnormalities and comorbidities, undergoing complex procedures, requiring longer cardiopulmonary bypass, and experiencing extracorporeal membrane oxygenation complications and longer extracorporeal membrane oxygenation duration have higher mortality risk. These data can help assessing prognosis in this high-risk population.

Case Report: Life-Threatening Macrophage Activation Syndrome With Fulminant Myocarditis Successfully Rescued by High Dose Intravenous Anakinra.

Macrophage activation syndrome (MAS) is a rare, potentially life-threatening, condition triggered by infections or flares in rheumatologic and neoplastic diseases. The mainstay of treatment includes high dose corticosteroids, intravenous immunoglobulins and immunosuppressive drugs although, more recently, a more targeted approach, based on the use of selective cytokines inhibitors, has been reported. We present the case of a two-year-old boy with 1-month history of high degree fever associated with limping gait, cervical lymphadenopathy and skin rash. Laboratory tests showed elevation of inflammatory markers and ferritin. By exclusion criteria, systemic onset Juvenile Idiopathic Arthritis (sJIA) was diagnosed and steroid therapy started. A couple of weeks later, fever relapsed and laboratory tests were consistent with MAS. He was promptly treated with high doses intravenous methylprednisolone pulses and oral cyclosporin A. One day later, he developed an acute myocarditis and a systemic capillary leak syndrome needing intensive care. Intravenous Immunoglobulin and subcutaneous IL-1-antagonists Anakinra were added. On day 4, after an episode of cardiac arrest, venous-arterial extracorporeal membrane oxygenation (VA-ECMO) was started. Considering the severe refractory clinical picture, we tried high dose intravenous Anakinra (HDIV-ANA, 2 mg/Kg q6h). This treatment brought immediate benefit: serial echocardiography showed progressive resolution of myocarditis, VA-ECMO was gradually decreased and definitively weaned off in 6 days and MAS laboratory markers improved. Our case underscores the importance of an early aggressive treatment in refractory life-threatening sJIA-related MAS and adds evidence on safety and efficacy of HDIV-ANA particularly in acute myocarditis needing VA-ECMO support.

Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): protocol for a multicentre, randomised, double-blind, controlled, non-profit trial.

INTRODUCTION: Some evidence indicates that exogenous surfactant therapy may be effective in infants with acute viral bronchiolitis, even though more confirmatory data are needed. To date, no large multicentre trials have evaluated the effectiveness and safety of exogenous surfactant in severe cases of bronchiolitis requiring invasive mechanical ventilation (IMV). METHODS AND ANALYSIS: This is a multicentre randomised, placebo-controlled, double-blind study, performed in 19 Italian paediatric intensive care units (PICUs). Eligible participants are infants under the age of 12 months hospitalised in a PICU, suffering from severe acute hypoxaemic bronchiolitis, requiring IMV. We adopted a more restrictive definition of bronchiolitis, including only infants below 12 months of age, to maintain the population as much homogeneous as possible. The primary outcome is to evaluate whether exogenous surfactant therapy (Curosurf, Chiesi Pharmaceuticals, Italy) is effective compared with placebo (air) in reducing the duration of IMV in the first 14 days of hospitalisation, in infants suffering from acute hypoxaemic viral bronchiolitis. Secondary outcomes are duration of non-invasive mechanical ventilation in the post-extubation phase, number of cases requiring new intubation after previous extubation within 14 days from randomisation, PICU and hospital length of stay (LOS), duration of oxygen dependency, effects on oxygenation and ventilatory parameters during invasive mechanical respiratory support, need for repeating treatment within 24 hours of first treatment, use of other interventions (eg, high-frequency oscillatory ventilation, nitric oxide, extracorporeal membrane oxygenation), mortality within the first 14 days of PICU stay and before hospital discharge, side effects and serious adverse events. ETHICS AND DISSEMINATION: The trial design and protocol have received approval by the Italian National Agency for Drugs (AIFA) and by the Regional Ethical Committee of Verona University Hospital (1494CESC). Findings will be disseminated through publication in peer-reviewed journals, conference/meeting presentations and media. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, issue date 22 May 2019. NCT03959384.

Efficacy and safety of dexmedetomidine for prevention of withdrawal syndrome in the pediatric intensive care unit: protocol for an adaptive, multicenter, randomized, double-blind, placebo-controlled, non-profit clinical trial.

BACKGROUND: Prolonged treatment with analgesic and sedative drugs in the pediatric intensive care unit (PICU) may lead to undesirable effects such as dependence and tolerance. Moreover, during analgosedation weaning, patients may develop clinical signs of withdrawal, known as withdrawal syndrome (WS). Some studies indicate that dexmedetomidine, a selective α2-adrenoceptor agonist, may be useful to prevent WS, but no clear evidence supports these data. The aims of the present study are to evaluate the efficacy of dexmedetomidine in reducing the occurrence of WS during analgosedation weaning, and to clearly assess its safety. METHODS: We will perform an adaptive, multicenter, randomized, double-blind, placebo-controlled trial. Patients aged < 18 years receiving continuous intravenous analgosedation treatment for at least 5 days and presenting with clinical conditions that allow analgosedation weaning will be randomly assigned to treatment A (dexmedetomidine) or treatment B (placebo). The treatment will be started 24 h before the analgosedation weaning at 0.4 µg/kg/h, increased by 0.2 µg/kg/h per hour up to 0.8 µg/kg/h (neonate: 0.2 µg/kg/h, increased by 0.1 µg/kg/h per hour up to 0.4 µg/kg/h) and continued throughout the whole weaning time. The primary endpoint is the efficacy of the treatment, defined by the reduction in the WS rate among patients treated with dexmedetomidine compared with patients treated with placebo. Safety will be assessed by collecting any potentially related adverse event. The sample size assuring a power of 90% is 77 patients for each group (total N = 154 patients). The study was approved by the Ethics Committee of the University-Hospital S.Orsola-Malpighi of Bologna on 22 March 2017. DISCUSSION: The present trial will allow us to clearly assess the efficacy of dexmedetomidine in reducing the occurrence of WS during weaning from analgosedation drugs. In addition, the study will provide a unique insight into the safety profile of dexmedetomidine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03645603. Registered on 24 August 2018. EudraCT, 2015-002114-80. Retrospectively registered on 2 January 2019.