Efficacy of ketamine in refractory convulsive status epilepticus in children: A protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Introduction: Status epilepticus (SE) is a lifethreatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-D-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/ hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Sensory phenotype assessment in a young girl affected by congenital insensitivity to pain (CIPA)

Sensory phenotype was assessed in a young girl affected by congenital insensitivity to pain (CIPA) scheduled for an open surgical drainage. The sensory profile showed that only the Abeta fibers were functioning normally, whereas Adelta and C fibers did not respond to nociceptive stimuli. On the basis of these findings and the results of cardiovascular reflexes, she was submitted to abscess incision and debridement under midazolam sedation alone. She did not report pain or other discomfort during surgery. The sensory (and sympathetic) assessment may have a high potential value in planning anesthesia and analgesia in children with CIPA. This psychophysical procedure could be introduced as standard component of clinical evaluation before surgery

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

Cannabidiol in the acute phase of febrile infection‐related epilepsy syndrome (FIRES)

Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long‐term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure‐free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add‐on treatment in the acute phase of FIRES

Tick-borne encephalitis in North-East Italy: A 14-year retrospective study, January 2000 to December 2013

Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases\u2019 median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (> 10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto- Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600 m was greater (2.41/100,000) than at other altitudes (p< 0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considere

KETASER01 protocol: What went right and what went wrong

To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies

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.</p

Parental presence in Italian pediatric intensive care units: a reappraisal of current visiting policies

Parental presence in Italian pediatric intensive care units: a reappraisal of current visiting policie