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Neurologic morbidity is highly prevalent in pediatric critical illness, and the use of benzodiazepines and/or opioids is a risk factor for delirium and post-discharge sequelae. However, little is known about how multidrug sedation with these medications interacts with inflammation in the developing brain, a frequent condition during childhood critical illness that has not been extensively studied. In weanling rats, mild-moderate inflammation was induced with lipopolysaccharide (LPS) on postnatal day (P)18 and combined with 3 days repeated opioid and benzodiazepine sedation using morphine and midazolam (MorMdz) between P19-21. Delirium-like behaviors including abnormal response to whisker stimulation, wet dog shakes, and delay in finding buried food were induced in male and female rat pups treated with LPS, MorMdz, or LPS/MorMdz (n ≥ 17/group) and were compared using a z-score composite. Composite behavior scores were significantly increased in LPS, MorMdz, and LPS/MorMdz groups compared to saline control (F 3,78  = 38.1, p < 0.0001). Additionally, expression of glial-associated neuroinflammatory markers ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) in western blots of P22 brain homogenate were significantly higher after LPS than after LPS/MorMdz (Iba1, p < 0.0001; GFAP, p < 0.001). Likewise, proinflammatory cytokines were increased in brains of LPS-treated pups versus Saline (p = 0.002), but not LPS/MorMdz-treated pups (p = 0.16). These results are of potential interest during pediatric critical illness, as inflammation is ubiquitous and the effects of multidrug sedation on homeostatic neuroimmune responses need to be considered along with neurodevelopmental effects., Competing Interests: Declaration of Competing Interest The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although most US emergency medical services (EMS) systems collect time-to-treatment data in their electronic prehospital patient care reports (PCRs), analysis of these data seldom appears in publications. We believe EMS agencies should routinely analyze the initial time-to-treatment data for various potentially life-threatening conditions. This not only assures that protocol-required treatments have been provided but can discover avoidable delays and drive protocol/treatment priority change. Our study purpose was to analyze the interval from 9-1-1 call receipt until the first administration of naloxone to adult opioid overdose victims to demonstrate the quality assurance importance of analyzing time-to-treatment data., Methods: Retrospective analysis of intervals from 9-1-1 call receipt to initial naloxone treatment in adult opioid overdose victims. We excluded victims <18 years of age and cases where a bystander, police, or a health care worker gave naloxone before EMS arrival. We compared data collected before and during the COVID-19 pandemic to determine its effect on the analysis., Results: The mean patient age of 582 opioid overdose victims was 40.7 years [95% CI 39.6, 41.8] with 405 males (69.6%). EMS units' scene arrival was 6.7 minutes from the 9-1-1 call receipt. It took 1.8 minutes to reach the victim, and 8.6 additional minutes to administer the first naloxone regardless of administration route (70.4% intravenous, 26.1% intranasal, 2.7% intraosseous, 0.7% intramuscular). EMS personnel administered the first naloxone 17.1 minutes after the 9-1-1 call receipt, with 50.3% of the delay occurring after patient contact. There was no statistically significant difference in the times-to-treatment before vs. during the pandemic., Conclusion: The prepandemic interval from 9-1-1 call receipt until initial EMS administration of naloxone was substantial and did not change significantly during COVID-19. Our findings exemplify why EMS agencies should analyze initial time-to-treatment data, especially for life-threatening conditions, beyond assuring that protocol-required treatments have been provided. Based on our analysis, fire department crews now carry intranasal naloxone, and intranasal naloxone is given to "impaired" opioid overdose victims the first-arriving fire department or EMS personnel. We continue to collect data on intervals-to-treatment prospectively and monitor our critical process/treatment intervals using the plan-do-study-act model to improve our process/carry out change, and publish our results in a future publication.