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Background: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events., Methods: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted., Results: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528)., Conclusions: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children., Design/setting: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020., Patients: Critically ill children, 0 to 17 years old, undergoing TI in PICUs., Interventions: None., Measurements and Main Results: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002)., Conclusions: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events., Competing Interests: Ms. Napolitano’s, Dr. Shults’s, Dr. Nadkarni’s, and Dr. Nishisaki’s institution received funding from the Agency for Healthcare Research and Quality (R18HS024511). Ms. Napolitano’s institution received funding from Dräger, Actuated Medical, and Philips Respironics; they received support for article research from Timpel and VERO-Biotech. Dr. Krawiec received funding from New England Journal of Medicine Healer Cases and Carle Illinois School of Medicine Admissions Committee. Dr. Polikoff received funding from Novavax. Dr. Lee’s institution received funding from National Research Medical Council, Singapore. Dr. Shenoi is an elected member of the Society of Critical Care Medicine (SCCM) Council of the SCCM. Dr. Peihl disclosed that he is founder and Chief Medical Officer of 410 Medical; his institution received funding the Department of Defense (grants: USSOCOM W81XWH-22-C-0002, USAF SBIR AF212-CSO1 Phase II, F2-15653 USAF, SBIR AF211-CSO1 Phase II, F2-15254). Dr. Hasegawa disclosed work for hire. Dr. Nishisaki’s institution received funding from Chiesi USA, AHRA, and the National Institute of Child Health and Human Development. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families., Design: A modified Delphi consensus process., Setting: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators., Subjects: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered., Interventions: None., Measurements and Main Results: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures., Conclusions: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness., Competing Interests: Dr. Maddux’s institution received funding from the National Institute of Child Health and Human Development (NICHD) (K23HD096018) and the Francis Family Foundation, Parker B Francis Fellowship. Drs. Maddux, Jarvis, Killien, Meert, Olson, and Fink received support for article research from the National Institutes of Health (NIH). Drs. Jarvis, Michelson, Beers, Meert, and Fink’s institutions received funding from the NIH. Dr. Jarvis received funding from the NIH (T32 HD040686). Dr. Killien and Olson’s institutions received funding from the NICHD. Dr. Choong’s institution received funding from the AFP Innovation Fund; she received funding from McMaster University. Dr. Michelson’s institution received funding from The National Palliative Care Research Center, and the Greenwall Foundation. Dr. Lee’s institution received funding from the National Medical Research Council, Singapore. Dr. Slomine received funding from the National Academy of Neuropsychology and Cambridge University Press. Dr. Beers’ institution received funding from the National Football League Brain Health Study. Dr. Morrow received funding from EduPro, Imperial College Press, the University of Cape Town, and the South African Society of Physiotherapy. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the Child Nervous Society and the American Board of Pediatrics CCM Subsection member. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Assessing outcomes after pediatric critical illness is imperative to evaluate practice and improve recovery of patients and their families. We conducted a scoping review of the literature to identify domains and instruments previously used to evaluate these outcomes., Design: Scoping review., Setting: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials Registry for studies evaluating pediatric critical care survivors or their families published between 1970 and 2017. We identified articles using key words related to pediatric critical illness and outcome domains. We excluded articles if the majority of patients were greater than 18 years old or less than 1 month old, mortality was the sole outcome, or only instrument psychometrics or procedural outcomes were reported. We used dual review for article selection and data extraction and categorized outcomes by domain (overall health, emotional, physical, cognitive, health-related quality of life, social, family)., Subjects: Manuscripts evaluating outcomes after pediatric critical illness., Interventions: None., Measurements and Main Results: Of 60,349 citations, 407 articles met inclusion criteria; 87% were published after 2000. Study designs included observational (85%), interventional (7%), qualitative (5%), and mixed methods (3%). Populations most frequently evaluated were traumatic brain injury (n = 96), general pediatric critical illness (n = 87), and congenital heart disease (n = 72). Family members were evaluated in 74 studies (18%). Studies used a median of 2 instruments (interquartile range 1-4 instruments) and evaluated a median of 2 domains (interquartile range 2-3 domains). Social (n = 223), cognitive (n = 183), and overall health (n = 161) domains were most frequently studied. Across studies, 366 unique instruments were used, most frequently the Wechsler and Glasgow Outcome Scales. Individual domains were evaluated using a median of 77 instruments (interquartile range 39-87 instruments)., Conclusions: A comprehensive, generalizable understanding of outcomes after pediatric critical illness is limited by heterogeneity in methodology, populations, domains, and instruments. Developing assessment standards may improve understanding of postdischarge outcomes and support development of interventions after pediatric critical illness.

IntroductionChildren with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.Materials and methodsWe sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation., Results: A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease., Conclusions: The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.

Objectives: Evaluate differences in tracheal intubation-associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in children with underlying cardiac disease., Design: Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children)., Setting: Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016., Patients: Children with medical or surgical cardiac disease who underwent intubation in an ICU., Interventions: None., Measurements and Main Results: Our primary outcome was the rate of any adverse tracheal intubation-associated event. Secondary outcomes were severe tracheal intubation-associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo [interquartile range, 0-6 mo]) compared with noncardiac ICUs (median 3 mo [interquartile range, 1-11 mo]; p < 0.001). Tracheal intubation-associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54-1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52-0.97; p = 0.033). Rates of severe tracheal intubation-associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04-1.15; p = 0.002)., Conclusions: In children with underlying cardiac disease, rates of adverse tracheal intubation-associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models.

Objectives: To describe promoters and barriers to implementation of an airway safety quality improvement bundle from the perspective of interdisciplinary frontline clinicians and ICU quality improvement leaders., Design: Mixed methods., Setting: Thirteen PICUs of the National Emergency Airway Registry for Children network., Intervention: Remote or on-site focus groups with interdisciplinary ICU staff. Two semistructured interviews with ICU quality improvement leaders with quantitative and qualitative data-based feedbacks., Measurements and Main Results: Bundle implementation success (compliance) was defined as greater than or equal to 80% use for tracheal intubations for 3 consecutive months. ICUs were classified as early or late adopters. Focus group discussions concentrated on safety concerns and promoters and barriers to bundle implementation. Initial semistructured quality improvement leader interviews assessed implementation tactics and provided recommendations. Follow-up interviews assessed degree of acceptance and changes made after initial interview. Transcripts were thematically analyzed and contrasted by early versus late adopters. Median duration to achieve success was 502 days (interquartile range, 182-781). Five sites were early (median, 153 d; interquartile range, 146-267) and eight sites were late adopters (median, 783 d; interquartile range, 773-845). Focus groups identified common "promoter" themes-interdisciplinary approach, influential champions, and quality improvement bundle customization-and "barrier" themes-time constraints, competing paperwork and quality improvement activities, and poor engagement. Semistructured interviews with quality improvement leaders identified effective and ineffective tactics implemented by early and late adopters. Effective tactics included interdisciplinary quality improvement team involvement (early adopter: 5/5, 100% vs late adopter: 3/8, 38%; p = 0.08); ineffective tactics included physician-only rollouts, lack of interdisciplinary education, lack of data feedback to frontline clinicians, and misconception of bundle as research instead of quality improvement intervention., Conclusions: Implementation of an airway safety quality improvement bundle with high compliance takes a long time across diverse ICUs. Both early and late adopters identified similar promoter and barrier themes. Early adopter sites customized the quality improvement bundle and had an interdisciplinary quality improvement team approach.

Objective: Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality., Study Design: Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%., Setting: PICUs participating in NEAR4KIDS., Patients: All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed., Measurements and Main Results: Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58-229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1-7 yr and 18% for 8-17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p < 0.001) and longer PICU stay (14 vs 11 d; p < 0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p < 0.003), longer PICU stay (15 vs 12 d; p < 0.035), and PICU mortality (19.9% vs 9.6%; p < 0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4-21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24-2.60; p = 0.002), after adjusted for patient confounders., Conclusions: Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.

The Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study investigates the potential neurotoxicity of anesthetics in the pediatric population. At a recent symposium, a panel of nonsurgical physicians from the disciplines of radiology, neurology, cardiology, and critical care discussed the role anesthesia plays in their respective practices. To execute diagnostic studies and/or therapeutic interventions in each of these disciplines, general anesthesia is oftentimes required for pediatric patients. Given recent publications in the literature suggesting the potential for neurotoxicity following anesthesia in pediatric patients, physicians, parents, and other stakeholders are now challenged to continue to balance safety with efficacy in caring for children. This paper summarizes the panelist presentations and the ensuing discussion at the 2014 PANDA symposium.

Background: Chlorhexidine gluconate-impregnated dressings have become widely adopted as a means to reduce the risk for catheter-associated bloodstream infections. These dressings release antiseptic under occlusion onto the skin surrounding catheter insertion sites. Although chlorhexidine gluconate is a known cause of contact dermatitis, the phenotypic range of this adverse effect of chlorhexidine gluconate–impregnated dressings in critically ill patients has not been described., Observations: We report 7 cases of erosive irritant contact dermatitis due to chlorhexidine gluconate-impregnated transparent dressings. Six of these patients were children (age range, 4 months to 2 years); the adult was a critically ill 62-year-old man. Four patients were immunosuppressed after solid organ transplant and all were receiving blood pressure support at the time of this reaction. The insertion sites of femoral catheters were involved in all but 1 case; 3 catheter sites were involved in the adult patient. Results of extensive infectious workups were negative. All lesions resolved with discontinuation of the chlorhexidine gluconate-containing dressings, local wound care, and alternative antimicrobial dressings., Conclusions: Erosive contact dermatitis is an under-recognized complication of chlorhexidine gluconate-impregnated dressings. Health care providers should be aware of this risk, particularly in young children and immunosuppressed and/or critically ill patients, who may be more susceptible to the irritant effects of these dressings. When the dressings are used, patients should be monitored closely for skin breakdown.

Objective: Simulation training has been used to integrate didactic knowledge, technical skills, and crisis resource management for effective orientation and patient safety. We hypothesize multi-institutional simulation-based training for first year pediatric critical care (PCC) fellows is feasible and effective., Design: Descriptive, educational intervention study., Setting: The simulation facility at the host institution., Interventions: A multicentered simulation-based orientation training "boot camp" for first year PCC fellows was held at a large simulation center. Immediate posttraining evaluation and 6-month follow-up surveys were distributed to participants., Measurements and Main Results: A novel simulation-based orientation training for first year PCC fellows was facilitated by volunteer faculty from seven institutions. The two and a half day course was organized to cover common PCC crises. High-fidelity simulation was integrated into each session (airway management, vascular access, resuscitation, sepsis, trauma/traumatic brain injury, delivering bad news). Twenty-two first year PCC fellows from nine fellowship programs attended, and 13 faculty facilitated, for a total of 15.5 hours (369 person-hours) of training. This consisted of 2.75 hours for whole group didactic sessions (17.7%), 1.08 hours for a small group interactive session (7.0%), 4.67 hours for task training (30.1%), and 7 hours for training (45.2%) with high-fidelity simulation and crisis resource management. A "train to success" approach with repetitive practice of critical assessment and interventional skills yielded higher scores in training effectiveness in the end-of-course evaluation. A follow-up survey revealed this training was highly effective in improving clinical performance and self-confidence., Conclusions: The first PCC orientation training integrated with simulation was effective and logistically feasible. The train to success concept with repetitive practice was highly valued by participants. Continuation and expansion of this novel multi-institutional training is planned.

Hypoxic-ischemic brain injury occurs frequently in infancy and childhood. Events such as perinatal asphyxia, near drowning, respiratory arrest, and near sudden infant death syndrome cause significant mortality and morbidity. Despite current critical care practices, the outcomes from such injuries may be life-long neurologic deficits. This review discusses findings from laboratory investigations into such injuries--in particular the roles of excitotoxic amino acids, proteolytic enzymes, free radicals, nitric oxide, and leukocytes. Understanding of the two distinct forms of neuronal death, necrosis and apoptosis, provides additional insights into mechanisms of injury. The development of new therapies for hypoxic-ischemic brain injury depends on such understanding. To date, the results of preclinical therapeutic trials have not demonstrated a "magic bullet." Nevertheless, the understanding of injury mechanisms has uncovered potential avenues for new therapies, particularly combination therapies or single interventions that have multiple effects. Clinical trials, using these strategies, are planned or have been recently begun and offer hope for advancements in treatment.

Despite increasing understanding of the cellular and molecular mechanisms that cause pathology in children who suffer traumatic brain injury, few advances have been made in developing new effective therapies for such injury. In the past, clinicians treated some neurologically injured patients with the sustained application of systemic hypothermia. This practice was largely abandoned when patients experienced complications; however, interest has been renewed in treatment with milder forms of hypothermia. This review focuses on the clinical and laboratory evidence concerning this therapy. Promising results from two clinical trials are presented. Moreover, evidence is discussed in support of the notion that some children with traumatic brain injury, more so than adults, may benefit from hypothermic therapy. Lastly, putative mechanisms for the effects of hypothermia, including attenuation of injury caused by inflammation, excitotoxic amino acids, nitric oxide, and free radicals, are discussed.

Clinical studies suggest that increased cerebral blood flow (CBF), or hyperemia, after traumatic brain injury (TBI) is commonly found in children and young adults, but is less often found in adults older than 40 years. However, whether posttraumatic cerebral hyperemia is truly an age-related phenomenon has not been proven. Using a model of focal percussive TBI, we hypothesized that (1) local CBF (ICBF) is increased by 24 after injury, and (2) the magnitude of the ICBF increase is age-related and is greatest in immature rats. Wistar rats that were immature (3.5-4.5 weeks), mature (2-3 months), and aged (14.5-15.5 months) were anesthetized and ventilated. TBI was produced by dropping a weight on the exposed right parietal cortex. LCBF was determined by [(14)C]iodoan-tipyrine autoradiography at 24 h posttrauma in all three age groups, at 48 h posttrauma in immature and mature rats, and at 7 days posttrauma in mature rats. In all age groups, low ICBF (<50 mL 100 g(-1) min(-1)) was present in the area of impact at all times studied. At 24 h, hyperemia was observed (vs. corresponding regions of age-matched control rats) in immature and mature rats (7/17 and 5/17 regions, respectively, both p < 0.05), but not in aged rats. Comparisons of ICBF between the three age groups revealed a hyperemic response in the peritrauma region in immature rats. Hyperemia persisted to 48 h in both immature and mature rats (2 and 7 of 17 structures with increased ICBF in immature and mature rats, respectively, both p < .05). By 7 days posttrauma no regions of increased ICBF were found. Posttraumatic hyperemia appears to be an age-dependent phenomenon. These results suggest possible age-related differences in vasoreactivity or regional metabolism after TBI.

Neutrophils accumulate during the acute inflammatory response to brain injury, but their role in the injury process remains controversial. We tested the hypothesis that neutrophils contribute to cerebral edema, tissue injury, and disturbed cerebral blood flow (CBF) (hyperemia or ischemia) during the first 24 h after traumatic brain injury. Wistar rats (n = 51) were injected with either vinblastine sulfate to induce neutropenia or the saline vehicle. Five days later, under halothane anesthesia, right hemispheric trauma was produced by weight drop (10 g x 5 cm) onto exposed dura. At 24 h after trauma, brain water (wet-dry weight), traumatic infarct size (percent of hemispheric section infarcted), or local CBF (lCBF, 14C-iodoantipyrine autoradiography) was assessed. Vinblastine treatment produced profound neutropenia on the day of trauma (absolute neutrophil count 0.024 +/- 0.008 x 10(9)/L vs 1.471 +/- 0.322 x 10(9)/L, p < 0.05 in neutropenic vs saline, respectively, mean +/- SEM). Neutropenia did not reduce the development of brain edema in the injured hemisphere (brain water 82.38 +/- 0.29% vs 82.73 +/- 0.37% in neutropenic and saline, respectively, mean +/- SEM) or traumatic infarct size (34.5 +/- 3.3% vs 33.2 +/- 2.1% in neutropenic vs saline respectively). In contrast, neutropenic rats exhibited 52%, 41%, and 57% reductions in lCBF in the frontal cortex, parietal cortex, and amygdala, respectively, of the injured hemisphere 24 h after trauma (all p < 0.05 vs nonneutropenic controls). These data suggest that neutrophils and the acute inflammatory process contribute to the level of CBF observed 24 h after trauma, but effects on edema or early posttraumatic infarct size could not be demonstrated.

Clinical studies suggest that children respond to head injury with more pronounced cerebral edema and hyperemia than do adults. We hypothesized that these age-related differences could be demonstrated in an animal model. Anesthetized and ventilated mature (2-3 months) and immature (3.5-4.5 weeks) male Wistar rats were traumatized by weight drop onto the exposed right parietal cortex. Trauma severity was adjusted to keep the ratio of force to brain weight constant. This resulted in an energy delivered to the brain of about 9 x 10(3) ergs.mm-2.g-1 brain in both age groups. Percent right hemispheric brain water (%RBW) was measured at 2, 24, 48, and 168 h posttrauma. Infarct area, intracranial pressure (ICP), and 14C-iodoantipyrine autoradiographic local cerebral blood flow (ICBF) were measured at 2 h or 24 h posttrauma. In mature rats, %RBW was unchanged at 2 h, but increased at 24 and 48 h (both p < 0.05). In immature rats, %RBW increased at 2 h and remained elevated at 24 and 48 h (all p < 0.05). Traumatic infarct area as a percent of hemispheric area at 24 h did not differ between age groups. In mature rats, at 2 h posttrauma ICBF was reduced (p < 0.05) in 16 of 17 regions but in only 4 of 17 regions in immature rats. ICBF as a percent of age-matched control values showed a greater reduction in mature vs immature rats in 9 of 16 regions (p < 0.05). ICP increased at 24 h posttrauma in both age groups. In immature rats posttrauma, brain water increased earlier and cerebral hypoperfusion was less marked than in mature rats.

Polymorphonuclear leukocytes (PMN) are implicated in the pathogenesis of traumatic brain injury. We tested the following hypotheses: (1) leukocyte accumulation is present in brain tissue 24 h posttrauma, (2) leukocyte accumulation represents PMN, and (3) prior systemic PMN depletion attenuates brain tissue PMN accumulation. Trauma was induced in exposed right parietal cortex by weightdrop in anesthetized Wistar rats (n = 24). Of the traumatized rats, 12 were PMN-depleted with vinblastine sulfate i.v. Controls were 12 normal rats and 5 sham-operated rats (craniotomy). Sections of traumatized and contralateral hemispheres were analyzed for myeloperoxidase (MPO) activity. Brain MPO activity was increased fivefold at 24 h posttrauma, but only in the traumatized hemisphere (0.448 +/- 0.133 U/g vs 0.090 +/- 0.022 U/g in trauma vs normal, respectively, p < 0.05, mean +/- SEM). PMN depletion attenuated this increase in MPO activity and decreased circulating PMN counts (0.07 +/- 0.032 x 10(9)/L vs 0.894 +/- 0.294 x 10(9)/L PMN-depleted-trauma vs trauma rats, respectively, p < 0.05). Leukocyte accumulation in the brain posttrauma was confirmed by MPO assay. Inhibition of MPO activity in the PMN-depleted group and the specificity of vinblastine treatment for depletion of circulating PMN suggest that leukocyte accumulation in the brain at 24 h posttrauma is largely due to PMN.