The Effects of Expectation Setting and Bundle Consent on Acute Caregiver Stress in the PICU: A Randomized Controlled Trial.

OBJECTIVES: Having a child admitted to the PICU is a stressful experience for parents and can have long-term negative mental health consequences. The objective was to determine if formalized expectation setting and bundled consent for invasive procedures upon admission impacts the acute stress burden on parents. DESIGN: Prospective cluster randomized controlled trial. SETTING: Single-center, tertiary PICU. SUBJECTS: Parents/guardians of patients, 0-18 years old, admitted to PICU. INTERVENTIONS: During experimental weeks, all patients admitted to PICU were bundled-consented for common procedures and given a novel unit introductory letter and "Common Procedures Explained" document. During control weeks, all patients were consented for invasive procedures with separate consents for each procedure. Parents then completed a demographic survey and Stress Overload Scale-Short (SOS-S) 48-72 hours after their child's admission. For each participant, the SOS-S generates a Personal Vulnerability (PV) score and an Event Load (EL) score. Parents' perception of the life-threatening nature of their child's condition was also evaluated. MEASUREMENTS AND MAIN RESULTS: Over 73 weeks, 1,882 patients were screened and 261 consented to the SOS-S. Median PV score was 10.4 in the control group and 9.1 in the experimental group ( p = 0.15). Median EL score was 11.3 for the control group and 10.5 in the experimental group ( p = 0.42). Adjusting for demographic variables and severity of illness, there was no independent association between either PV or EL and bundled consent. However, a parent's perception of threat-to-life was significantly related to the allocated group ( p = 0.036), which resulted in a decreased percentage of parents who rated their child's illness as "Extremely" life-threatening (experimental group, 17% vs control group, 26%). CONCLUSIONS: This study did not demonstrate a decrease in stress when bundled consent was obtained. However, this intervention decreased the parents' perceived severity of illness. Further multicenter studies are needed to evaluate the effects of bundled consent on parents.

Comparison of Intracranial Pressure Measurements Before and After Hypertonic Saline or Mannitol Treatment in Children With Severe Traumatic Brain Injury.

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP). Design, Setting, and Participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021. Interventions: Boluses of HTS and mannitol were administered. Main Outcomes and Measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments. Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted ß, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted ß, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted ß, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted ß, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted ß, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis. Conclusions and Relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

Potential Neurodevelopmental Effects of Pediatric Intensive Care Sedation and Analgesia: Repetitive Benzodiazepine and Opioid Exposure Alters Expression of Glial and Synaptic Proteins in Juvenile Rats.

Sedatives are suspected contributors to neurologic dysfunction in PICU patients, to whom they are administered during sensitive neurodevelopment. Relevant preclinical modeling has largely used comparatively brief anesthesia in infant age-approximate animals, with insufficient study of repetitive combined drug administration during childhood. We hypothesized that childhood neurodevelopment is selectively vulnerable to repeated treatment with benzodiazepine and opioid. We report a preclinical model of combined midazolam and morphine in early childhood age-approximate rats. DESIGN: Animal model. SETTING: Basic science laboratory. SUBJECTS: Male and female Long-Evans rats. INTERVENTIONS: Injections of morphine + midazolam were administered twice daily from postnatal days 18-22, tapering on postnatal days 23 and 24. Control groups included saline, morphine, or midazolam. To screen for acute neurodevelopmental effects, brain homogenates were analyzed by western blot for synaptophysin, drebrin, glial fibrillary acidic protein, S100 calcium-binding protein B, ionized calcium-binding adaptor molecule 1, and myelin basic proteins. Data analysis used Kruskal-Wallis with Dunn posttest, with a p value of less than 0.05 significance. MEASUREMENTS AND MAIN RESULTS: Morphine + midazolam and morphine animals gained less weight than saline or midazolam (p ≤ 0.01). Compared with saline, morphine + midazolam expressed significantly higher drebrin levels (p = 0.01), with numerically but not statistically decreased glial fibrillary acidic protein. Similarly, morphine animals exhibited less glial fibrillary acidic protein and more S100 calcium-binding protein B and synaptophysin. Midazolam animals expressed significantly more S100 calcium-binding protein B (p < 0.001) and 17-18.5 kDa myelin basic protein splicing isoform (p = 0.01), with numerically increased synaptophysin, ionized calcium-binding adaptor molecule 1, and 21.5 kDa myelin basic protein, and decreased glial fibrillary acidic protein. CONCLUSIONS: Analysis of brain tissue in this novel rodent model of repetitive morphine and midazolam administration showed effects on synaptic, astrocytic, microglial, and myelin proteins. These findings warrant further investigation because they may have implications for critically ill children requiring sedation and analgesia.

Advances and Future Directions of Diagnosis and Management of Pediatric Abusive Head Trauma: A Review of the Literature.

Abusive head trauma (AHT) is broadly defined as injury of the skull and intracranial contents as a result of perpetrator-inflicted force and represents a persistent and significant disease burden in children under the age of 4 years. When compared to age-matched controls with typically single occurrence accidental traumatic brain injury (TBI), mortality after AHT is disproportionately high and likely attributable to key differences between injury phenotypes. This article aims to review the epidemiology of AHT, summarize the current state of AHT diagnosis, treatment, and prevention as well as areas for future directions of study. Despite neuroimaging advances and an evolved understanding of AHT, early identification remains a challenge for contemporary clinicians. As such, the reported incidence of 10-30 per 100,000 infants per year may be a considerable underestimate that has not significantly decreased over the past several decades despite social campaigns for public education such as "Never Shake a Baby." This may reflect caregivers in crisis for whom education is not sufficient without support and intervention, or dangerous environments in which other family members are at risk in addition to the child. Acute management specific to AHT has not advanced beyond usual supportive care for childhood TBI, and prevention and early recognition remain crucial. Moreover, AHT is frequently excluded from studies of childhood TBI, which limits the precise translation of important brain injury research to this population. Repeated injury, antecedent abuse or neglect, delayed medical attention, and high rates of apnea and seizures on presentation are important variables to be considered. More research, including AHT inclusion in childhood TBI studies with comparisons to age-matched controls, and translational models with clinical fidelity are needed to better elucidate the pathophysiology of AHT and inform both clinical care and the development of targeted therapies. Clinical prediction rules, biomarkers, and imaging modalities hold promise, though these have largely been developed and validated in patients after clinically evident AHT has already occurred. Nevertheless, recognition of warning signs and intervention before irreversible harm occurs remains the current best strategy for medical professionals to protect vulnerable infants and toddlers.

Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury.

OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design. SETTING: PICUs in tertiary children's hospitals in United States and abroad. PATIENTS: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). CONCLUSIONS: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines.

Intracranial Hypertension and Cerebral Hypoperfusion in Children With Severe Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults.

OBJECTIVES: The evidence to guide therapy in pediatric traumatic brain injury is lacking, including insight into the intracranial pressure/cerebral perfusion pressure thresholds in abusive head trauma. We examined intracranial pressure/cerebral perfusion pressure thresholds and indices of intracranial pressure and cerebral perfusion pressure burden in relationship with outcome in severe traumatic brain injury and in accidental and abusive head trauma cohorts. DESIGN: A prospective observational study. SETTING: PICU in a tertiary children's hospital. PATIENTS: Children less than18 years old admitted to a PICU with severe traumatic brain injury and who had intracranial pressure monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A pediatric traumatic brain injury database was interrogated with 85 patients (18 abusive head trauma) enrolled. Hourly intracranial pressure and cerebral perfusion pressure (in mm Hg) were collated and compared with various thresholds. C-statistics for intracranial pressure and cerebral perfusion pressure data in the entire population were determined. Intracranial hypertension and cerebral hypoperfusion indices were formulated based on the number of hours with intracranial pressure more than 20 mm Hg and cerebral perfusion pressure less than 50 mm Hg, respectively. A secondary analysis was performed on accidental and abusive head trauma cohorts. All of these were compared with dichotomized 6-month Glasgow Outcome Scale scores. The models with the number of hours with intracranial pressure more than 20 mm Hg (C = 0.641; 95% CI, 0.523-0.762) and cerebral perfusion pressure less than 45 mm Hg (C = 0.702; 95% CI, 0.586-0.805) had the best fits to discriminate outcome. Two factors were independently associated with a poor outcome, the number of hours with intracranial pressure more than 20 mm Hg and abusive head trauma (odds ratio = 5.101; 95% CI, 1.571-16.563). As the number of hours with intracranial pressure more than 20 mm Hg increases by 1, the odds of a poor outcome increased by 4.6% (odds ratio = 1.046; 95% CI, 1.012-1.082). Thresholds did not differ between accidental versus abusive head trauma. The intracranial hypertension and cerebral hypoperfusion indices were both associated with outcomes. CONCLUSIONS: The duration of hours of intracranial pressure more than 20 mm Hg and cerebral perfusion pressure less than 45 mm Hg best discriminated poor outcome. As the number of hours with intracranial pressure more than 20 mm Hg increases by 1, the odds of a poor outcome increased by 4.6%. Although abusive head trauma was strongly associated with unfavorable outcome, intracranial pressure/cerebral perfusion pressure thresholds did not differ between accidental and abusive head trauma.