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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. [ABSTRACT FROM AUTHOR]

Introduction: Analgesia and sedation are integral to the care of critically ill children. However, the choice and dose of the analgesic or sedative drug is often empiric, and models predicting favorable responses are lacking. We aimed to compute models to predict a patient's response to intravenous morphine. Methods: We retrospectively analyzed data from consecutive patients admitted to the Cardiac Intensive Care Unit (January 2011–January 2020) who received at least one intravenous bolus of morphine. The primary outcome was a decrease in the State Behavioral Scale (SBS) ≥1 point; the secondary outcome was a decrease in the heart rate Z‐score (zHR) at 30 min. Effective doses were modeled using logistic regression, Lasso regression, and random forest modeling. Results: A total of 117,495 administrations of intravenous morphine among 8140 patients (median age 0.6 years [interquartile range [IQR] 0.19, 3.3]) were included. The median morphine dose was 0.051 mg/kg (IQR 0.048, 0.099) and the median 30‐day cumulative dose was 2.2 mg/kg (IQR 0.4, 15.3). SBS decreased following 30% of doses, did not change following 45%, and increased following 25%. The zHR significantly decreased after morphine administration (median delta‐zHR −0.34 [IQR−1.03, 0.00], p < 0.001). The following factors were associated with favorable response to morphine: A concomitant infusion of propofol, higher prior 30‐day cumulative dose, being invasively ventilated and/or on vasopressors. Higher morphine dose, higher zHR pre‐morphine, an additional analgosedation bolus ±30 min around the index bolus, a concomitant ketamine or dexmedetomidine infusion, and showing signs of withdrawal syndrome were associated with unfavorable response. Logistic regression (area under the receiver operating characteristic [ROC] curve [AUC] 0.900) and machine learning models (AUC 0.906) performed comparably, with a sensitivity of 95%, specificity of 71%, and negative predictive value of 97%. Conclusions: Statistical models identify 95% of effective intravenous morphine doses in pediatric critically ill cardiac patients, while incorrectly suggesting an effective dose in 29% of cases. This work represents an important step toward computer‐aided, personalized clinical decision support tool for sedation and analgesia in ICU patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]