Kahoud, Robert J.

Introduction As part of the Society of Critical Care Medicine's Pediatric ICU Liberation Campaign Collaborative, Mayo Clinic developed a daily physician-led rounding checklist to promote timely de-escalation of ICU support and proactive measures to prevent iatrogenic conditions. We hypothesized that implementing this checklist would be feasible and would reduce missed opportunities to optimize care through both de-escalation and initiation of key preventive tasks. Methods We conducted a prospective study in a 16-bed medical/surgical PICU at a quaternary academic center over a 300-day period from May 2017 to March 2018. A 15-task daily rounding checklist was integrated into standard patient-centered rounds for every admitted patient to prompt physicians to address common de-escalation and preventive care tasks. For each task, physicians documented whether it had already been addressed during rounds, was not applicable to the patient, or the checklist directly prompted a plan modification. Trends in checklist compliance and the frequency/type of plan modifications were assessed in 60-day intervals to evaluate sustainability over time. Results 1,710 rounding checklists were completed across 2,424 patient-days (71% compliance). The checklist prompted 198 documented plan modifications from 9% of all completed checklists. The most frequent modifications involved initiating a bowel regimen ( n = 47), converting intravenous to enteral medications ( n = 32), initiating gastrointestinal prophylaxis ( n = 30), consulting rehabilitation services ( n = 18), and restarting home medications ( n = 18), which together accounted for 73% (145/198) of all modifications. Discussion Implementation of a daily rounding checklist was feasible, achieved acceptable compliance, and identified 198 opportunities for timely de-escalation and proactive care in a complex PICU environment. Although overall compliance did not meet the a priori >75% target across the entire study period, early adoption exceeded this threshold and later decline highlighted sustainability challenges. This initiative demonstrates the potential of structured physician-led checklists to standardize care and reduce iatrogenic risk in pediatric critical care.

Objective: The Society of Critical Care Medicine PICU Liberation ABCDEF (A–F) Campaign Collaborative aimed to implement best practices for analgesia (A), breathing (B), comfort/consciousness (C), delirium (D), early mobilization (E), and family engagement and empowerment (F). Our post hoc study of Mayo Clinic data sought to compare the pre-implementation rounding process, which used a nursing script organized by organ systems, with a novel, liberation-focused rounding process emphasizing A–F bundle elements. Design: Secondary analysis of pre- vs. post-implementation surveys collected by independent observers during rounds. Setting: Medical/surgical PICU in a quaternary-care, academic medical center during April to July 2017. Subjects: The observed participants included PICU physicians, nurses, respiratory therapists, pharmacists, and dietitians. Interventions: None. Measurements and Main Results: Survey responses from 145 team members pre-implementation and 67 post-implementation showed improved team satisfaction, communication, and understanding of daily plans (all p < 0.05). Respondents reported an increased frequency of discussions on bundle components A–E (all p < 0.01). Observations of 41 pre-implementation and 46 post-implementation rounds showed an increase in the frequency of discussion of all components of the bundle (all p < 0.01). However, this finding was not at the expense of increased duration of individual rounds since we failed to find a difference in pre- vs. post-implementation duration per patient (480 vs. 544 s per patient, p = 0.20). Conclusions: In 2017, around the time of introducing the nurse-led PICU Liberation rounding process to our practice, we found that after implementation, there was an associated increase in discussions about bundle elements and improved communications and satisfaction in team members.

Importance Neurological manifestations during acute SARS-CoV-2–related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective To assess the association of severe neurological manifestations during a SARS-CoV-2–related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2–related condition. Results Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P &amp;lt; .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations ( P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Abstract Objective This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non‐BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). Methods This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non‐BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non‐BZD ASM. Results We included 293 patients with a median (interquartile range) age of 3.8 (1.3–9.3) years. Thirty‐six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997–.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out‐of‐hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73–3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40–6.03, p < .0001) compared to patients with in‐hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01–2.06, p = .04). Forty‐seven percent of patients ( n = 94) with out‐of‐hospital onset did not receive treatment before hospital arrival. Among patients with out‐of‐hospital onset who received at least two BZDs before hospital arrival ( n = 54), 48.1% received additional BZDs at hospital arrival. Significance Failure to escalate from BZDs to non‐BZD ASMs occurs mainly in out‐of‐hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non‐BZD ASMs after two BZD doses during handoffs between prehospital and in‐hospital settings.

AbstractObjectiveThis study was undertaken to describe long‐term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE.MethodsWe performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients.ResultsFollow‐up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow‐up duration was 1.6 (.9–2.7) years. The in‐hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty‐six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1–134.5] h vs. 4 [1.6–16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008–1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale‐Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion.SignificanceAbout one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow‐up, with longer electroclinical RSE duration as a predictor.

ObjectiveWe recently reported successful treatment of a child with febrile infection‐related epilepsy syndrome (FIRES), a subtype of new onset refractory status epilepticus, with the recombinant interleukin‐1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.MethodsLevels of IL1β and IL1RA were measured in serum and cerebrospinal fluid (CSF). The inhibitory activity of endogenous IL1RA was assessed using a cell‐based reporter assay. IL1RN gene variants were identified by sequencing. Expression levels for the secreted and intracellular isoforms of IL1RA were measured in patient and control cells by real‐time polymerase chain reaction.ResultsLevels of endogenous IL1RA and IL1β were elevated in the serum and CSF of patients with FIRES (n = 7) relative to healthy controls (n = 10). Serum from FIRES patients drove IL1R signaling activity and potentiated IL1R signaling in response to exogenous IL1β in a cell‐based reporter assay. Functional assessment of endogenous IL1RA activity in 3 FIRES patients revealed attenuated inhibition of IL1R signaling. Sequencing of IL1RN in our index patient revealed multiple variants. This was accompanied by reduced expression of intracellular but not secreted isoforms of IL1RA in the patient's peripheral blood mononuclear cells.InterpretationOur findings suggest that FIRES is associated with reduced expression of intracellular IL1RA isoforms and a functional deficiency in IL1RA inhibitory activity. These observations may provide insight into disease pathogenesis for FIRES and other inflammatory seizure disorders and may provide a valuable biomarker for therapeutic decision‐making. Ann Neurol 2019;85:526–537

BACKGROUNDDelirium is associated with poor outcomes in adults but is less extensively studied in children.OBJECTIVESTo describe a quality improvement initiative to implement delirium assessment in a pediatric intensive care unit and to identify barriers to delirium screening completion.METHODSA survey identified perceived barriers to delirium assessment. Failure modes and effects analysis characterized factors likely to impede assessment. A randomized case-control study evaluated factors affecting assessment by comparing patients always assessed with patients never assessed.RESULTSDelirium assessment was completed in 57% of opportunities over 1 year, with 2% positive screen results. Education improved screening completion by 20%. Barriers to assessment identified by survey (n = 25) included remembering to complete assessments, documentation outside workflow, and “busy patient.” Factors with high risk prediction numbers were lack of time and paper charting. Patients always assessed had more severe illness (median Pediatric Index of Mortality 2 score, 0.90 vs 0.36; P &lt; .001), more developmental disabilities (moderate to severe pediatric cerebral performance category score, 54% vs 32%; P = .007), and admission during lower pediatric intensive care unit census (median [interquartile range], 10 [9–12] vs 12 [10–13]; P &lt; .001) than did those never assessed (each group, n = 80). Patients receiving mechanical ventilation were less likely to be assessed (41.0% vs 51.2%, P &lt; .001).CONCLUSIONSSuccessful implementation of pediatric delirium screening may be associated with early use of quality improvement tools to identify assessment barriers, comprehensive education, monitoring system with feedback, multidisciplinary team involvement, and incorporation into nursing workflow models.