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Secondary insults such as hypotension or hemorrhagic shock (HS) can greatly worsen outcome after traumatic brain injury (TBI). We recently developed a mouse combined injury model of TBI and HS using a controlled cortical impact (CCI) model and showed that 90 minutes of HS can exacerbate neuronal death in hippocampus beneath the contusion. This combined injury model has three clinically relevant phases, a shock, pre hospital, and definitive care phases. Mice were randomly assigned to four groups, shams as well as a CCI only, an HS only, and a CCI+HS groups. The CCI and HS reduced cerebral blood flow (CBF) in multiple regions of interest (ROIs) in the hemisphere ipsilateral and contralateral to injury. Hemorrhagic shock to a level of ∼30 mm Hg exacerbated the CCI-induced CBF reductions in multiple ROIs ipsilateral to injury (hemisphere and thalamus) and in the hemisphere contralateral to injury (hemisphere, thalamus, hippocampus, and cortex, all P<0.05 versus CCI only, HS only or both). An important effect of HS duration was also seen after CCI with maximal CBF reduction seen at 90 minutes (P<0.0001 group-time effect in ipsilateral hippocampus). Given that neuronal death in hippocampus is exacerbated by 90 minutes of HS in this model, our data suggest an important role for exacerbation of posttraumatic ischemia in mediating the secondary injury in CCI plus HS. In conclusion, the serial, non invasive assessment of CBF using ASL-MRI (magnetic resonance imaging with arterial spin labeling) is feasible in mice even in the complex setting of combined CCI+HS. The impact of resuscitation therapies and various mutant mouse strains on CBF and other outcomes merits investigation in this model.

Objectives: With decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers. Design: National 2-day point prevalence study. Setting: Eighty-two PICUs in 65 hospitals across the United States. Patients: All patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day. Interventions: None. Measurements and Main Results: The primary outcome was prevalence of physical therapy– or occupational therapy–provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility–associated safety events, and barriers to mobility. The point prevalence of physical therapy– or occupational therapy–provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13–17 vs < 3 yr, 2.1; 95% CI, 1.5–3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61–0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1–0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1–0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1–6.6). Conclusions: Younger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.

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.

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately “reverse translate” critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care.

This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance. I.

Background Intensivists are increasingly attuned to the postdischarge outcomes experienced by families because patient recovery and family outcomes are interdependent after childhood critical illness. In this scoping review of international contemporary literature, we describe the evidence of family effects and functioning postpediatric intensive care unit (PICU) as well as outcome measures used to identify strengths and weaknesses in the literature. Methods We reviewed all articles published between 1970 and 2017 in PubMed, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), or the Cochrane Controlled Trials Registry. Our search used a combination of terms for the concept of “critical care/illness” combined with additional terms for the prespecified domains of social, cognitive, emotional, physical, health-related quality of life (HRQL), and family functioning. Results We identified 71 articles reporting on the postPICU experience of more than 2400 parents and 3600 families of PICU survivors in 8 countries. These articles used 101 different metrics to assess the various aspects of family outcomes; 34 articles also included open-ended interviews. Overall, most families experienced significant disruption in at least five out of six of our family outcomes subdomains, with themes of decline in mental health, physical health, family cohesion, and family finances identified. Almost all articles represented relatively small, single-center, or disease-specific observational studies. There was a disproportionate representation of families of higher socioeconomic status (SES) and Caucasian race, and there was much more data about mothers compared to fathers. There was also very limited information regarding outcomes for siblings and extended family members after a child's PICU stay. Conclusions Significant opportunities remain for research exploring family functioning after PICU discharge. We recommend that future work include more diverse populations with respect to the critically ill child as well as family characteristics, include more intervention studies, and enrich existing knowledge about outcomes for siblings and extended family.

Objective: To describe light and sound characteristics in the rooms of critically ill children. Design: Prospective observational cohort study, with continuously measured light and sound levels. Setting: Tertiary care pediatric intensive care unit (PICU), with a newly constructed expansion and an older, pre-existing section. Patients: Critically ill patients 0-18 years old, requiring respiratory or cardiovascular support. Patients with severe cognitive preconditions were excluded. Measurements and Main Results: One hundred patients were enrolled, totaling 602 patient-days. The twenty-four hour median illuminance was 16 (IQR 5-53) lux (lx). Daytime (07:00-21:00) median light level was 27 lx (IQR 13-82), compared with 4 lx (IQR 1-10) overnight (22:00-06:00). Peak light levels occurred midday between 11:00 and 14:00, with a median of 48 lx (IQR 24-119). Daytime median illuminance trended higher over the course of admission, whereas light levels overnight were consistent. Midday light levels were higher in newly constructed rooms: 78 lx (IQR 30-143) vs. 26 lx (IQR 20-40) in existing rooms. The twenty-four hour median equivalent sound level (LAeq) was 60 (IQR 55-64) decibels (dB). Median daytime LAeq was 62 dB (IQR 58-65) and 56 dB (IQR 52-61) overnight. On average, 35% of patients experienced at least one sound peak >80 dB every hour from 22:00 to 06:00. Overnight peaks, but not median sound levels nor daytime peaks, decreased over the course of admission. There was no difference in sound between new and pre-existing rooms. Conclusions: This study describes continuously measured light and sound in PICU rooms. Light levels were low even during daytime hours, while sound levels were consistently higher than World Health Organization hospital room recommendations of <35 dB. Given the relevance of light and sound to sleep/wake patterns, and evidence of post-intensive care syndromes, the clinical effects of light and sound on critically ill children should be further explored as potentially modifiable environmental factors.