Individualized Numeric Rating Scale to Assess Pain in Critically Ill Children With Neurodevelopmental Disabilities.

BACKGROUND: Pain is a significant burden for children with neurodevelopmental disabilities but is difficult for clinicians to identify. No pain assessment tools for children with neurodevelopmental disabilities have been validated for use in pediatric intensive care units. The Individualized Numeric Rating Scale (INRS) is an adapted 0-to-10 rating that includes parents' input on their child's pain indicators. OBJECTIVES: To evaluate the reliability, validity, and feasibility and acceptability of use of the INRS for assessing pain in critically ill children with neurodevelopmental disabilities. METHODS: This observational study enrolled critically ill patients with neurodevelopmental disabilities aged 3 to 17 years in 2 pediatric intensive care units at a children's hospital using a prospective repeated-measures cohort design. Structured parent interviews were used to populate each patient's INRS. Bedside nurses assessed pain using the INRS throughout the study. The research team completed independent INRS ratings using video clips. Participating parents and nurses completed feasibility and acceptability surveys. Psychometric properties of the INRS and survey responses were evaluated with appropriate statistical methods. RESULTS: For 481 paired INRS pain ratings in 34 patients, interrater reliability between nurse and research team ratings was moderate (weighted κ = 0.56). Parents said that creating the INRS was easy, made them feel more involved in care, and helped them communicate with nurses. CONCLUSIONS: The INRS has adequate measurement properties for assessing pain in critically ill children with neurodevelopmental disabilities. It furthers goals of patient- and family-centered care but may have implementation barriers.

Endogenous Opioid Dynorphin Is a Potential Link between Traumatic Brain Injury, Chronic Pain, and Substance Use Disorder.

Traumatic brain injury (TBI) is a serious public health problem associated with numerous physical and neuropsychiatric comorbidities. Chronic pain is prevalent and interferes with post-injury functioning and quality of life, whereas substance use disorder (SUD) is the third most common neuropsychiatric diagnosis after TBI. Neither of these conditions has a clear mechanistic explanation based on the known pathophysiology of TBI. Dynorphin is an endogenous opioid neuropeptide that is significantly dysregulated after TBI. Both dynorphin and its primary receptor, the ĸ-opioid receptor (KOR), are implicated in the neuropathology of chronic pain and SUD. Here, we review the known roles of dynorphin and KORs in chronic pain and SUDs. We synthesize this information with our current understanding of TBI and highlight potential mechanistic parallels between and across conditions that suggest a role for dynorphin in long-term sequelae after TBI. In pain studies, dynorphin/KOR activation has either antinociceptive or pro-nociceptive effects, and there are similarities between the signaling pathways influenced by dynorphin and those underlying development of chronic pain. Moreover, the dynorphin/KOR system is considered a key regulator of the negative affective state that characterizes drug withdrawal and protracted abstinence in SUD, and molecular and neurochemical changes observed during the development of SUD are mirrored by the pathophysiology of TBI. We conclude by proposing hypotheses and directions for future research aimed at elucidating the potential role of dynorphin/KOR in chronic pain and/or SUD after TBI.

Traumatic Brain Injury Diminishes Feedforward Activation of Parvalbumin-Expressing Interneurons in the Dentate Gyrus.

Traumatic brain injury (TBI) is associated with aberrant network hyperexcitability in the dentate gyrus (DG). GABAAergic parvalbumin-expressing interneurons (PV-INs) in the DG regulate network excitability with strong, perisomatic inhibition, although the posttraumatic effects on PV-IN function after TBI are not well understood. In this study, we investigated physiological alterations in PV-INs one week after mild lateral fluid percussion injury (LFPI) in mice. PV-IN cell loss was observed in the dentate hilus after LFPI, with surviving PV-INs showing no change in intrinsic membrane properties. Whole-cell voltage clamp recordings in PV-INs revealed alterations in both EPSCs and IPSCs (EPSCs/IPSCs). Evoked EPSCs (eEPSCs) in PV-INs from perforant path electrical stimulation were diminished after injury but could be recovered with application of a GABAA-receptor antagonist. Furthermore, current-clamp recordings using minimal perforant path stimulation demonstrated a decrease in evoked PV-IN action potentials (APs) after LFPI, which could be restored by blocking GABAAergic inhibition. Together, these findings suggest that injury alters synaptic input onto PV-INs, resulting in a net inhibitory effect that reduces feedforward PV-IN activation in the DG. Decreased PV-IN activation suggests a potential mechanism of DG network hyperexcitability contributing to hippocampal dysfunction after TBI.

Sedation Management for Critically Ill Children with Pre-Existing Cognitive Impairment.

OBJECTIVE: To compare current analgesia and sedation management practices between critically ill children with pre-existing cognitive impairment and critically ill neurotypical children, including possible indicators of therapeutic efficacy. STUDY DESIGN: This study used secondary analysis of prospective data from the RESTORE clinical trial, with 2449 children admitted to the pediatric intensive care unit and receiving mechanical ventilation for acute respiratory failure. Subjects with a baseline Pediatric Cerebral Performance Category ≥3 were defined as subjects with cognitive impairment, and differences between groups were explored using regression methods accounting for pediatric intensive care unit as a cluster variable. RESULTS: This study identified 412 subjects (17%) with cognitive impairment. Compared with neurotypical subjects, subjects with cognitive impairment were older (median, years, 6.2 vs 1.4; P < .001) with more severe pediatric acute respiratory distress syndrome (40% vs 33%; P = .009). They received significantly lower cumulative doses of opioids (median, mg/kg, 14.2 vs 16.2; P < .001) and benzodiazepines (10.6 vs 14.4; P < .001). Three nonverbal subjects with cognitive impairment received no analgesia or sedation. Subjects with cognitive impairment were assessed as having more study days awake and calm and fewer study days with an episode of pain. They were less likely to be assessed as having inadequate pain/sedation management or unplanned endotracheal/invasive tube removal. Subjects with cognitive impairment had more documented iatrogenic withdrawal symptoms than neurotypical subjects. CONCLUSIONS: Subjects with cognitive impairment in this study received less medication, but it is unclear whether they have authentically lower analgesic and/or sedative requirements or are vulnerable to inadequate assessment of discomfort because of the lack of validated assessment tools. We recommend the development of pain and sedation assessment tools specific to this patient population.

Patient, Process, and System Predictors of Iatrogenic Withdrawal Syndrome in Critically Ill Children.

OBJECTIVE: To generate a multidimensional predictive model of risk factors for iatrogenic withdrawal syndrome in critically ill children. DESIGN: Secondary analysis of prospective data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: PICU. PATIENTS: Children who received greater than or equal to 5 days of sedation during mechanical ventilation for acute respiratory failure. INTERVENTIONS: The Randomized Evaluation of Sedation Titration for Respiratory Failure study tested the effect of a nurse-led, goal-directed sedation protocol on clinical outcomes. There was no additional intervention in this secondary analysis. MEASUREMENTS AND MAIN RESULTS: Data included 1,157 children from 31 PICUs. Iatrogenic withdrawal syndrome was defined as having at least two Withdrawal Assessment Tool-Version 1 scores greater than or equal to 3 after the start of opioid weaning. Logistic regression with generalized estimating equations to account for clustering by site was used to evaluate patient, process, and healthcare system risk factors for iatrogenic withdrawal syndrome. Subjects with iatrogenic withdrawal syndrome (544/1,157; 47%) were younger and more likely to have preexisting cognitive or functional impairment. They also received higher sedative doses and longer exposure periods. In multivariable analyses, significant predictors of iatrogenic withdrawal syndrome included younger age, preexisting cognitive impairment, higher preweaning mean daily opioid dose, longer duration of sedation, receipt of three or more preweaning sedative classes, higher nursing workload, and more one-to-one nurse staffing. CONCLUSIONS: Iatrogenic withdrawal syndrome is common in children recovering from critical illness, and several risk factors are predictive, including patient characteristics, sedative exposure, additional sedative agents, and system-level factors. High-risk patients could be identified before weaning to better prevent iatrogenic withdrawal syndrome among at-risk patients.

Patterns of Sedation Weaning in Critically Ill Children Recovering From Acute Respiratory Failure.

OBJECTIVE: To characterize sedation weaning patterns in typical practice settings among children recovering from critical illness. DESIGN: A descriptive secondary analysis of data that were prospectively collected during the prerandomization phase (January to July 2009) of a clinical trial of sedation management. SETTING: Twenty-two PICUs across the United States. PATIENTS: The sample included 145 patients, aged 2 weeks to 17 years, mechanically ventilated for acute respiratory failure who received at least five consecutive days of opioid exposure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Group comparisons were made between patients with an intermittent weaning pattern, defined as a 20% or greater increase in daily opioid dose after the start of weaning, and the remaining patients defined as having a steady weaning pattern. Demographic and clinical characteristics, tolerance to sedatives, and iatrogenic withdrawal symptoms were evaluated. Sixty-six patients (46%) were intermittently weaned; 79 patients were steadily weaned. Prior to weaning, intermittently weaned patients received higher peak and cumulative doses and longer exposures to opioids and benzodiazepines, demonstrated more sedative tolerance (58% vs 41%), and received more chloral hydrate and barbiturates compared with steadily weaned patients. During weaning, intermittently weaned patients assessed for withdrawal had a higher incidence of Withdrawal Assessment Tool-version 1 scores of greater than or equal to 3 (85% vs 46%) and received more sedative classes compared with steadily weaned patients. CONCLUSIONS: This study characterizes sedative administration practices for pediatric patients prior to and during weaning from sedation after critical illness. It provides a novel methodology for describing weaning in an at-risk pediatric population that may be helpful in future research on weaning strategies to prevent iatrogenic withdrawal syndrome.

Innovation in creating a strategic plan for research within an academic community.

Strategic planning for research priorities in schools of nursing requires consensus building and engagement of key stakeholders. However, traditional approaches to strategic planning using work groups and committees sometimes result in low rates of faculty participation and fail to engage other important stakeholders. The purpose of this article is to describe the unique low-cost, high-yield processes that contributed to the rapid development of our school's strategic research plan over the course of 1 month. Using the name recognition of the National Collegiate Athletic Association's annual basketball tournament, we were able to encourage high levels of participation by faculty, doctoral students, and postdoctoral fellows in not only developing a consensus around eight broad lines of inquiry but also offering tangible recommendations for accomplishing those goals within the next 5 years. Other schools of nursing seeking to evaluate their research enterprise and align their science with national priorities could easily replicate this approach.

Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model.

OBJECTIVES: Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients. DATA SOURCES: Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014. STUDY SELECTION: Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported. DATA EXTRACTION: In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome. FINDINGS: Most articles were prospective observational or interventional studies. CONCLUSIONS: Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the construction of a conceptual model of iatrogenic withdrawal syndrome risk that, if supported, could be useful in guiding future research.