Continuous renal replacement therapy in neonates and children: what does the pediatrician need to know? An overview from the Critical Care Nephrology Section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion: In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes. • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT. What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality. • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes.

Impact of the first 24 h of continuous kidney replacement therapy on hemodynamics, ventilation, and analgo-sedation in critically ill children.

BACKGROUND: In a group of children admitted to the paediatric intensive care unit (PICU) receiving continuous kidney replacement therapy (CKRT), we aim to evaluate the data about their hemodynamic, ventilation and analgo-sedation profile in the first 24 h of treatment and possible associations with mortality. METHODS: Retrospective cohort study of children admitted to the PICU of the University Hospital of Padova undergoing CKRT between January 2011 and March 2021. Data was collected at baseline (T0), after 1 h (T1) and 24 h (T24) of CKRT treatment. The differences in outcome measures were compared between these time points, and between survivors and non-survivors. RESULTS: Sixty-nine patients received CKRT, of whom 38 (55%) died during the PICU stay. Overall, the vasoactive inotropic score and the adrenaline dose increased at T1 compared to T0 (p = 0.012 and p = 0.022, respectively). Compared to T0, at T24 patients showed an improvement in the following ventilatory parameters: Oxygenation Index (p = 0.005), Oxygenation Saturation Index (p = 0.013) PaO2/FiO2 ratio (p = 0.005), SpO2/FiO2 ratio (p = 0.002) and Mean Airway Pressure (p = 0.016). These improvements remained significant in survivors (p = 0.01, p = 0.027, p = 0.01 and p = 0.015, respectively) but not in non-survivors. No changes in analgo-sedative drugs have been described. CONCLUSIONS: CKRT showed a significant impact on hemodynamics and ventilation in the first 24 h of treatment. We observed a significant rise in the inotropic/vasoactive support required after 1 h of treatment in the overall population, and an improvement in the ventilation parameters at 24 h only in survivors.

Pediatric COVID-19 extracorporeal membrane oxygenation transport during the pandemic.

INTRODUCTION: ExtraCorporeal Membrane Oxygenation (ECMO) in pediatric patients with COVID-19 has a survival rate similar to adults. Occasionally, patients may need to be cannulated by an ECMO team in a referring hospital and transported to an ECMO center. The ECMO transport of a COVID-19 patient has additional risks than normal pediatric ECMO transport for the possible COVID-19 transmissibility to the ECMO team and the reduction of the ECMO team performance due to the need of wearing full personal protective equipment. Since pediatric data on ECMO transport of COVID-19 patients are lacking, we explored the outcomes of the pediatric COVID-19 ECMO transports collected in the EuroECMO COVID_Neo/Ped Survey. METHODS: We reported five European consecutive ECMO transports of COVID-19 pediatric patients collected in the EuroECMO COVID_Neo/Ped Survey including 52 European neonatal and/or pediatric ECMO centers and endorsed by the EuroELSO from March 2020 till September 2021. RESULTS: The ECMO transports were performed for two indications, pediatric ARDS and myocarditis associated to the multisystem inflammatory syndrome related to COVID-19. Cannulation strategies differed among patients according to the age of the patients, transport distance varied between 8 and 390 km with a total transport duration between 5 to 15 h. In all five cases, the ECMO transports were successfully performed without major adverse events. One patient reported a harlequin syndrome and another patient a cannula displacement both without major clinical consequences. Hospital survival was 60% with one patient reporting neurological sequelae. No ECMO team member developed COVID-19 symptoms after the transport. CONCLUSION: Five transports of pediatric patients with COVID-19 supported with ECMO were reported in the EuroECMO COVID_Neo/Ped Survey. All transports were performed by an experienced multidisciplinary ECMO team and were feasible and safe for both the patient and the ECMO team. Further experiences are needed to better characterize these transports and draw insightful conclusions.

Sepsis Prognostic Scores Accuracy in Predicting Adverse Outcomes in Children With Sepsis Admitted to the Pediatric Intensive Care Unit From the Emergency Department: A 10-Year Single-Center Experience.

OBJECTIVE: To compare the performance of several prognostic scores calculated in the first 24 hours of admission (day 1) in predicting mortality and morbidity among critically ill children with sepsis presenting to the pediatric emergency department (PED) and then admitted to the pediatric intensive care unit (PICU). METHODS: Single-center, retrospective cohort study in children with a diagnosis of sepsis visiting the PED and then admitted to the PICU from January 1, 2010 to December 31, 2019. Sepsis organ dysfunction scores-pediatric Sequential Organ Failure Assessment (pSOFA) (Schlapbach, Matics, Shime), quickSOFA, quickSOFA-L, Pediatric Logistic Organ Dysfunction (PELOD)-2, quickPELOD-2, and Pediatric Multiple Organ Dysfunction score-were calculated during the first 24 hours of admission (day 1) and their performance compared with systemic inflammatory response syndrome (SIRS) and severe sepsis-International Consensus Conference on Pediatric Sepsis(ICCPS)-derived criteria-using the area under the receiver operating characteristic curve. Primary outcome was PICU mortality. Secondary outcomes were: a composite of death and new disability (ie, change from baseline Pediatric Overall Performance Category score ≥1); prolonged PICU length of stay (>5 d); prolonged invasive mechanical ventilation (MV) (>3 d). RESULTS: Among 60 patients with sepsis, 4 (6.7%) died, 7 (11.7%) developed new disability, 26 (43.3%) experienced prolonged length of stay, and 21 (35%) prolonged invasive MV. The prognostic ability in mortality discrimination was significantly higher for organ dysfunction scores, with PELOD-2 showing the best performance (area under the receiver operating characteristic curve, 0.924; 95% confidence interval, 0.837-1.000), significantly better than SIRS 3 criteria (0.924 vs 0.509, P = 0.009), SIRS 4 criteria (0.924 vs 0.509, P < 0.001), and severe sepsis (0.924 vs 0.527, P < 0.001). Among secondary outcomes, PELOD-2 performed significantly better than SIRS criteria and severe sepsis to predict prolonged duration of invasive MV, whereas better than severe sepsis to predict "poor outcome" (mortality or new disability). CONCLUSIONS: Day 1 organ dysfunction scores performed better in predicting mortality and morbidity outcomes than ICCPS-derived criteria. The PELOD-2 was the organ dysfunction score with the best performance for all outcomes.

Assessment and management of iatrogenic withdrawal syndrome and delirium in pediatric intensive care units across Europe: An ESPNIC survey.

INTRODUCTION: Analgesia and sedation are essential for the care of children in the pediatric intensive care unit (PICU); however, when prolonged, they may be associated with iatrogenic withdrawal syndrome (IWS) and delirium. We sought to evaluate current practices on IWS and delirium assessment and management (including non-pharmacologic strategies as early mobilization) and to investigate associations between the presence of an analgosedation protocol and IWS and delirium monitoring, analgosedation weaning, and early mobilization. METHODS: We conducted a multicenter cross-sectional survey-based study collecting data from one experienced physician or nurse per PICU in Europe from January to April 2021. We then investigated differences among PICUs that did or did not follow an analgosedation protocol. RESULTS: Among 357 PICUs, 215 (60%) responded across 27 countries. IWS was systematically monitored with a validated scale in 62% of PICUs, mostly using the Withdrawal Assessment Tool-1 (53%). The main first-line treatment for IWS was a rescue bolus with interruption of weaning (41%). Delirium was systematically monitored in 58% of PICUs, mostly with the Cornell Assessment of Pediatric Delirium scale (48%) and the Sophia Observation Scale for Pediatric Delirium (34%). The main reported first-line treatment for delirium was dexmedetomidine (45%) or antipsychotic drugs (40%). Seventy-one percent of PICUs reported to follow an analgosedation protocol. Multivariate analyses adjusted for PICU characteristics showed that PICUs using a protocol were significantly more likely to systematically monitor IWS (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.01-3.67) and delirium (OR 2.00, 95% CI 1.07-3.72), use a protocol for analgosedation weaning (OR 6.38, 95% CI 3.20-12.71) and promote mobilization (OR 3.38, 95% CI 1.63-7.03). CONCLUSIONS: Monitoring and management of IWS and delirium are highly variable among European PICUs. The use of an analgosedation protocol was associated with an increased likelihood of monitoring IWS and delirium, performing a structured analgosedation weaning and promoting mobilization. Education on this topic and interprofessional collaborations are highly needed to help reduce the burden of analgosedation-associated adverse outcomes.

Apneas requiring respiratory support in young infants with COVID-19: a case series and literature review.

The objective of this study is to describe the clinical features of young infants with apneas as a clinical sign of COVID-19. We reported the cases of 4 infants who needed respiratory support in our PICU for a severe course of COVID-19 complicated with recurrent apneas. Moreover, we conducted a review of the literature about COVID-19 and apneas in infants ≤ 2 months of corrected age. A total of 17 young infants were included. Overall, in most of the cases (88%), apnea was an initial symptom of COVID-19, and in two cases, it recurred after 3-4 weeks. Regarding neurological workup, most children underwent a cranial ultrasound, while a minority underwent electroencephalography registration, neuroimaging, and lumbar punctures. One child showed signs of encephalopathy on electroencephalogram, with further neurological workup resulting normal. SARS-CoV-2 was never found in the cerebrospinal fluid. Ten children required intensive care unit admission, with five of them needing intubation and three non-invasive ventilation. A less invasive respiratory support was sufficient for the remaining children. Eight children were treated with caffeine. All patients had a complete recovery.  Conclusion: Young infants with recurrent apneas during COVID-19 usually need respiratory support and undergo a wide clinical work-up. They usually show complete recovery even when admitted to the intensive care unit. Further studies are needed to better define diagnostic and therapeutic strategies for these patients. What is Known: • Although the course of COVID-19 in infants is usually mild, some of them may develop a more severe disease needing intensive care support. Apneas may be a clinical sign in COVID-19. What is New: • Infants with apneas during COVID-19 may require intensive care support, but they usually show a benign course of the disease and full recovery.

Analgesia and sedation in critically ill pediatric patients: an update from the recent guidelines and point of view.

In the last decades, the advancement of knowledge in analgesia and sedation for critically ill pediatric patients has been conspicuous and relevant. Many recommendations have changed to ensure patients' comfort during their intensive care unit (ICU) stay and prevent and treat sedation-related complications, as well as improve functional recovery and clinical outcomes. The key aspects of the analgosedation management in pediatrics have been recently reviewed in two consensus-based documents. However, there remains a lot to be researched and understood. With this narrative review and authors' point of view, we aimed to summarize the new insights presented in these two documents to facilitate their interpretation and application in clinical practice, as well as to outline research priorities in the field.    Conclusion: With this narrative review and authors' point of view, we aimed to summarize the new insights presented in these two documents to facilitate their interpretation and application in clinical practice, as well as to outline research priorities in the field. What is Known: • Critically ill pediatric patients receiving intensive care required analgesia and sedation to attenuate painful and stressful stimuli. •Optimal management of analgosedation is a challenge often burdened with complications such as tolerance, iatrogenic withdrawal syndrome, delirium, and possible adverse outcomes. What is New: •The new insights on the analgosedation treatment for critically ill pediatric patients delineated in the recent guidelines are summarized to identify strategies for changes in clinical practice. •Research gaps and potential for quality improvement projects are also highlighted.

Trends in In-Hospital Cardiac Arrest and Mortality Among Children With Cardiac Disease in the Intensive Care Unit: A Systematic Review and Meta-analysis.

Importance: Data on trends in incidence and mortality for in-hospital cardiac arrest (IHCA) in children with cardiac disease in the intensive care unit (ICU) are lacking. Additionally, there is limited information on factors associated with IHCA and mortality in this population. Objective: To investigate incidence, trends, and factors associated with IHCA and mortality in children with cardiac disease in the ICU. Data Sources: A systematic review was conducted using PubMed, Web of Science, EMBASE, and CINAHL, from inception to September 2021. Study Selection: Observational studies on IHCA in pediatric ICU patients with cardiac disease were selected (age cutoffs in studies varied from age ≤18 y to age ≤21 y). Data Extraction and Synthesis: Quality of studies was assessed using the National Institutes of Health Quality Assessment Tools. Data on incidence, mortality, and factors associated with IHCA or mortality were extracted by 2 independent observers. Random-effects meta-analysis was used to compute pooled proportions and pooled ORs. Metaregression, adjusted for type of study and diagnostic category, was used to evaluate trends in incidence and mortality. Main Outcomes and Measures: Primary outcomes were incidence of IHCA and in-hospital mortality. Secondary outcomes were proportions of patients who underwent extracorporeal membrane oxygenation (ECMO) cardiopulmonary resuscitation (ECPR) and those who did not achieve return of spontaneous circulation (ROSC). Results: Of the 2574 studies identified, 25 were included in the systematic review (131 724 patients) and 18 in the meta-analysis. Five percent (95% CI, 4%-6%) of children with cardiac disease in the ICU experienced IHCA. The pooled in-hospital mortality among children who experienced IHCA was 51% (95% CI, 42%-59%). Thirty-nine percent (95% CI, 29%-51%) did not achieve ROSC; in centers with ECMO, 22% (95% CI, 14%-33%) underwent ECPR, whereas 22% (95% CI, 12%-38%) were unable to be resuscitated. Both incidence of IHCA and associated in-hospital mortality decreased significantly in the last 20 years (both P for trend < .001), whereas the proportion of patients not achieving ROSC did not significantly change (P for trend = .90). Neonatal age, prematurity, comorbidities, univentricular physiology, arrhythmias, prearrest mechanical ventilation or ECMO, and higher surgical complexity were associated with increased incidence of IHCA and mortality odds. Conclusions and Relevance: This systematic review and meta-analysis found that 5% of children with cardiac disease in the ICU experienced IHCA. Decreasing trends in IHCA incidence and mortality suggest that education on preventive interventions, use of ECMO, and post-arrest care may have been effective; however, there remains a crucial need for developing resuscitation strategies specific to children with cardiac disease.

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.

Continuous Kidney Replacement Therapy Practices in Pediatric Intensive Care Units Across Europe.

Importance: Continuous kidney replacement therapy (CKRT) is the preferred method of kidney support for children with critical illness in pediatric intensive care units (PICUs). However, there are no data on the current CKRT management practices in European PICUs. Objective: To describe current CKRT practices across European PICUs. Design, Setting, and Participants: This cross-sectional survey of PICUs in 20 European countries was conducted by the Critical Care Nephrology Section of the European Society of Pediatric and Neonatal Intensive Care from April 1, 2020, to May 31, 2022. Participants included intensivists and nurses working in European PICUs. The survey was developed in English and distributed using SurveyMonkey. One response from each PICU that provided CKRT was included in the analysis. Data were analyzed from June 1 to June 30, 2022. Main Outcome and Measures: Demographic characteristics of European PICUs along with organizational and delivery aspects of CKRT (including prescription, liberation from CKRT, and training and education) were assessed. Results: Of 283 survey responses received, 161 were included in the analysis (response rate, 76%). The attending PICU consultant (70%) and the PICU team (77%) were mainly responsible for CKRT prescription, whereas the PICU nurses were responsible for circuit setup (49%) and bedside machine running (67%). Sixty-one percent of permanent nurses received training to use CKRT, with no need for certification or recertification in 36% of PICUs. Continuous venovenous hemodiafiltration was the preferred dialytic modality (51%). Circuit priming was performed with normal saline (67%) and blood priming in children weighing less than 10 kg (56%). Median (IQR) CKRT dose was 35 (30-50) mL/kg/h in neonates and 30 (30-40) mL/kg/h in children aged 1 month to 18 years. Forty-one percent of PICUs used regional unfractionated heparin infusion, whereas 35% used citrate-based regional anticoagulation. Filters were changed for filter clotting (53%) and increased transmembrane pressure (47%). For routine circuit changes, 72 hours was the cutoff in 62% of PICUs. Some PICUs (34%) monitored fluid removal goals every 4 hours, with variation from 12 hours (17%) to 24 hours (13%). Fluid removal goals ranged from 1 to 3 mL/kg/h. Liberation from CKRT was performed with a diuretic bolus followed by an infusion (32%) or a diuretic bolus alone (19%). Conclusions and Relevance: This survey study found a wide variation in current CKRT practice, including organizational aspects, education and training, prescription, and liberation from CKRT, in European PICUs. This finding calls for concerted efforts on the part of the pediatric critical care and nephrology communities to streamline CKRT education and training, research, and guidelines to reduce variation in practice.

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.].

Italian Version of the Cornell Assessment of Pediatric Delirium: Evaluation of the Scale Reliability and Ability to Detect Delirium Compared to Pediatric Intensive Care Unit Physicians Clinical Evaluation.

Background: Delirium is an acute brain dysfunction associated with increased length of hospitalization, mortality, and high healthcare costs especially in patients admitted to the pediatric intensive care unit (PICU). The Cornell Assessment of Pediatric Delirium (CAPD) is a screening tool for evaluating delirium in pediatric patients. This tool has already been used and validated in other languages but not in Italian. Objectives: To test the reliability of the Italian version of the CAPD to screen PICU patients for delirium and to assess the agreement between CAPD score and PICU physician clinical evaluation of delirium. Methods: Prospective double-blinded observational cohort study of patients admitted to a tertiary academic center PICU for at least 48 h from January 2020 to August 2021. We evaluated intra- and inter-rater agreement using the Intraclass Correlation Coefficient (ICC). The ability of the scale to detect delirium was evaluated by comparing the nurses' CAPD assessments with the clinical evaluation of a PICU physician with expertise in analgosedation using the area under the ROC curve (AUC). Measurements and Main Results: Seventy patients were included in the study. The prevalence of pediatric delirium was 54% (38/70) when reported by a positive CAPD score and 21% (15/70) when diagnosed by the PICU physician. The CAPD showed high agreement levels both for the intra-rater (ICC 1 0.98, 95% CI: 0.97-0.99) and the inter-rater (ICC 2 0.93, 95% CI: 0.89-0.96) assessments. In patients with suspected delirium according to the CAPD scale, the observed sensitivity and specificity of the scale were 0.93 (95% CI: 0.68-1.00) and 0.56 (95% CI: 0.42-0.70), respectively. The AUC observed was 0.75 (95% CI: 0.66-0.8490). Conclusion: The Italian version of the CAPD seems a reliable tool for the identification of patients at high risk of developing delirium in pediatric critical care settings. Compared to the clinical evaluation of the PICU physician, the use of the CAPD scale avoids a possible underestimation of delirium in the pediatric population.

A Single Dose of Oral Sucrose Is Enough to Control Pain During Venipuncture: A Randomized Controlled Trial.

Sucrose is effective in reducing pain during minor procedures in neonates. We evaluated whether a second dose of sucrose was more effective than a single dose during venipuncture. We performed a randomised, double-blind, controlled trial at the NICU of Padua Hospital (August 2016-October 2017). We randomised 72 preterm infants undergoing venipuncture for routine test to a control group, which received a single standard dose of sucrose 2' before the procedure and a placebo 30″ after the venipuncture, and an experimental group in which they received two doses of 24% sucrose 2' before and 30″ after the venipuncture. No difference in pain perception was found between the groups at 30″, 60″ and 120″. In conclusion, we do not recommend a second dose of sucrose during venipuncture in prematures.

Pain and sedation management and monitoring in pediatric intensive care units across Europe: an ESPNIC survey.

BACKGROUND: Management and monitoring of pain and sedation to reduce discomfort as well as side effects, such as over- and under-sedation, withdrawal syndrome and delirium, is an integral part of pediatric intensive care practice. However, the current state of management and monitoring of analgosedation across European pediatric intensive care units (PICUs) remains unknown. The aim of this survey was to describe current practices across European PICUs regarding the management and monitoring of pain and sedation. METHODS: An online survey was distributed among 357 European PICUs assessing demographic features, drug choices and dosing, as well as usage of instruments for monitoring pain and sedation. We also compared low- and high-volume PICUs practices. Responses were collected from January to April 2021. RESULTS: A total of 215 (60% response rate) PICUs from 27 European countries responded. Seventy-one percent of PICUs stated to use protocols for analgosedation management, more frequently in high-volume PICUs (77% vs 63%, p = 0.028). First-choice drug combination was an opioid with a benzodiazepine, namely fentanyl (51%) and midazolam (71%) being the preferred drugs. The starting doses differed between PICUs from 0.1 to 5 mcg/kg/h for fentanyl, and 0.01 to 0.5 mg/kg/h for midazolam. Daily assessment and documentation for pain (81%) and sedation (87%) was reported by most of the PICUs, using the preferred validated FLACC scale (54%) and the COMFORT Behavioural scale (48%), respectively. Both analgesia and sedation were mainly monitored by nurses (92% and 84%, respectively). Eighty-six percent of the responding PICUs stated to use neuromuscular blocking agents in some scenarios. Monitoring of paralysed patients was preferably done by observation of vital signs with electronic devices support. CONCLUSIONS: This survey provides an overview of current analgosedation practices among European PICUs. Drugs of choice, dosing and assessment strategies were shown to differ widely. Further research and development of evidence-based guidelines for optimal drug dosing and analgosedation assessment are needed.

Adherence to guideline recommendations in the management of pediatric cardiac arrest: a multicentre observational simulation-based study.

BACKGROUND AND IMPORTANCE: Pediatric cardiac arrest is a rare emergency with associated high mortality. Its management is challenging and deviations from guidelines can affect clinical outcomes. OBJECTIVES: To evaluate the adherence to guideline recommendations in the management of a pediatric cardiac arrest scenario by teams of pediatric residents. Secondarily, the association between the use of the Pediatric Advanced Life Support-2015 (PALS-2015) pocket card, and the teams' adherence to international guidelines, were explored. DESIGN, SETTINGS AND PARTICIPANTS: Multicentre observational simulation-based study at three Italian University Hospitals in 2018, including PALS-2015 certified pediatric residents in their 3rd-5th year of residency program, divided in teams of three. INTERVENTION OR EXPOSURE: Each team conducted a standard nonshockable pediatric cardiac arrest scenario and independently decided whether to use the PALS-2015 pocket card. OUTCOME MEASURE AND ANALYSIS: The primary outcome was the overall number and frequency of individual deviations from the PALS-2015 guidelines, measured by the novel c-DEV15plus score (range 0-15). Secondarily, the performance on the validated Clinical Performance Tool for asystole scenarios, the time to perform resuscitation tasks and cardiopulmonary resuscitation (CPR) quality metrics were compared between the teams that used and did not use the PALS-2015 pocket card. MAIN RESULTS: Twenty-seven teams (81 residents) were included. Overall, the median number of deviations per scenario was 7 out of 15 [interquartile range (IQR), 6-8]. The most frequent deviations were delays in positioning of a CPR board (92.6%), calling for adrenaline (92.6%), calling for help (88.9%) and incorrect/delayed administration of adrenaline (88.9%). The median Clinical Performance Tool score was 9 out of 13 (IQR, 7-10). The comparison between teams that used ( n = 13) and did not use ( n = 14) the PALS-2015 pocket card showed only significantly higher Clinical Performance Tool scores in the former group [9 (IQR 9-10) vs. 7 (IQR 6-8); P = 0.002]. CONCLUSIONS: Deviations from guidelines, although measured by means of a nonvalidated tool, were frequent in the management of a pediatric cardiac arrest scenario by pediatric residents. The use of the PALS-2015 pocket card was associated with better Clinical Performance Tool scores but was not associated with less deviations or shorter times to resuscitation tasks.

Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial.

STUDY OBJECTIVE: Withdrawal syndrome (WS) may be a critical drawback of opioid/benzodiazepine weaning in children. The most effective intervention to reduce WS prevalence is yet to be determined. Dexmedetomidine (DEX) was estimated to be effective in reducing WS-related symptoms, but no randomized trial has been conducted to prove its efficacy so far. We aimed to evaluate the efficacy and safety of DEX in reducing the occurrence of WS. DESIGN AND SETTING: This was an adaptive randomized double-blind placebo-controlled trial conducted at three Italian Pediatric Intensive Care Units (PICUs). PATIENTS: It included children admitted to PICU, undergoing at least five days of opioids/benzodiazepines continuous infusion, and ready to start the analgosedation weaning. INTERVENTION: Twenty-four hours before the start of weaning, an infusion of DEX/placebo was started. WS symptoms were monitored using the Withdrawal-Assessment-Tool-version-1 (WAT-1). In case of WS symptoms (WAT-1 ≥ 3) an opioid/benzodiazepine bolus was given and the DEX/placebo infusion-rate was increased. MEASUREMENTS: The primary outcome measure was the prevalence of WS. Secondary outcomes were the trend of WAT-1 over time, number of rescue doses, length of weaning and PICU-stay, and onset of adverse events (AEs). MAIN RESULTS: Forty-five patients were enrolled, of whom 5 dropped-out and 40 entered the interim analysis. There were no significant baseline differences between groups. WS prevalence did not significantly differ between groups (77.8% DEX vs 90.9% placebo, p = 0.381). By generalized linear mixed modeling, the WAT-1 trend showed a significant increase per unit of time in the DEX arm (estimate 0.27, CI 0.07-0.47, p = 0.009) compared to placebo. Most frequent AEs were hemodynamic, and all of them happened in the DEX arm. CONCLUSIONS: A continuous infusion of DEX, started 24 h before the analgosedation weaning and increased based on WS signs, was not able to significantly modify the prevalence of WS in children who received at least five days of opioids/benzodiazepines treatment compared to placebo.

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score-Weighted Analysis.

OBJECTIVES: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality. DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING: Seventeen PICUs in Italy. PATIENTS: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis.

OBJECTIVE: Ketamine is commonly used as an anesthetic and analgesic agent for procedural sedation, but there is little evidence on its current use as a prolonged continuous infusion in the PICU. We sought to analyze the use of ketamine as a prolonged infusion in critically ill children, its indications, dosages, efficacy, and safety. METHODS: We retrospectively reviewed the clinical charts of patients receiving ketamine for ≥24 hours in the period 2017-2018 in our tertiary care center. Data on concomitant treatments pre and 24 hours post ketamine introduction and adverse events were also collected. RESULTS: Of the 60 patients included, 78% received ketamine as an adjuvant of analgosedation, 18% as an adjuvant of bronchospasm therapy, and 4% as an antiepileptic treatment. The median infusion duration was 103 hours (interquartile range [IQR], 58-159; range, 24-287), with median dosages between 15 (IQR, 10-20; range, 5-47) and 30 (IQR, 20-50; range, 10-100) mcg/kg/min. At 24 hours of ketamine infusion, dosages/kg/hr of opioids significantly decreased (p < 0.001), and 81% of patients had no increases in dosages of concomitant analgosedation. For 27% of patients with bronchospasm, the salbutamol infusions were lowered at 24 hours after ketamine introduction. Electroencephalograms of epileptic patients (n = 2) showed resolution of status epilepticus after ketamine administration. Adverse events most likely related to ketamine were hypertension (n = 1), hypersalivation (n = 1), and delirium (n = 1). CONCLUSIONS: Ketamine can be considered a worthy strategy for the analgosedation of difficult-to-sedate patients. Its use for prolonged sedation allows the sparing of opioids. Its efficacy in patients with bronchospasm or status epilepticus still needs to be investigated.