Thermoregulate, autoregulate and ventilate: brain-directed critical care for pediatric cardiac arrest.

PURPOSE OF REVIEW: Cardiac arrest in childhood is associated with a high risk for mortality and poor long-term functional outcome. This review discusses the current evidence for neuroprotective therapies and goals for postarrest care in the context of the pathophysiology of hypoxic-ischemic injury, modalities for neurologic prognostication in these children and potential future monitoring paradigms for maximizing cerebral perfusion in the postarrest period. RECENT FINDINGS: The recent publication of the in-hospital and out-of-hospital Therapeutic Hypothermia After Cardiac Arrest trials demonstrated a lack of statistically significant benefit for the use of postarrest therapeutic hypothermia. As a result, targeted normothermic temperature management has become standard of care. Continuous electroencephalographic monitoring during the acute postarrest period provides useful additional data for neurologic prognostication, in addition to its value for detection of seizures. Ongoing research into noninvasive monitoring of cerebrovascular autoregulation has the potential to individualize blood pressure goals in the postarrest period, maximizing cerebral perfusion in these patients. SUMMARY: Therapeutic strategies after cardiac arrest seek to maximize cerebral perfusion while mitigating the effects of secondary brain injury and loss of autoregulation. Future research into new monitoring strategies and better long-term outcome measures may allow more precise targeting of therapies to these goals.

Methylmalonic and propionic acidemias: clinical management update.

PURPOSE OF REVIEW: Recent clinical studies and management guidelines for the treatment of the organic acidopathies methylmalonic acidemia (MMA) and propionic acidemia address the scope of interventions to maximize health and quality of life. Unfortunately, these disorders continue to cause significant morbidity and mortality due to acute and chronic systemic and end-organ injury. RECENT FINDINGS: Dietary management with medical foods has been a mainstay of therapy for decades, yet well controlled patients can manifest growth, development, cardiac, ophthalmological, renal, and neurological complications. Patients with organic acidopathies suffer metabolic brain injury that targets specific regions of the basal ganglia in a distinctive pattern, and these injuries may occur even with optimal management during metabolic stress. Liver transplantation has improved quality of life and metabolic stability, yet transplantation in this population does not entirely prevent brain injury or the development of optic neuropathy and cardiac disease. SUMMARY: Management guidelines should identify necessary screening for patients with methylmalonic acidemia and propionic acidemia, and improve anticipatory management of progressive end-organ disease. Liver transplantation improves overall metabolic control, but injury to nonregenerative tissues may not be mitigated. Continued use of medical foods in these patients requires prospective studies to demonstrate evidence of benefit in a controlled manner.

Ice Hockey Summit II: zero tolerance for head hits and fighting.

OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.

Rugby contact and collisions--clinical challenges of a global game.

Rugby Union (rugby) is a sport that evolved from and resembles other forms of football but is unique in many respects and presents distinctive clinical challenges. This article discusses those aspects of rugby that are different from other sports and those injuries that have specific significance to the game as a result of it being a global collision sport with an increasing focus on serious injury prevention. Injury screening and intervention programs, neck injuries, rugby's contribution to evolving concussion protocols, contact and travel-related illnesses, and rugby's drug intervention protocols are discussed.

Huanglian-Jie-Du-Tang extract protects against chronic brain injury after focal cerebral ischemia via hypoxia-inducible-factor-1α-regulated vascular endothelial growth factor signaling in mice.

Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula which is widely used clinically. In this study, we investigated the effects of an aqueous (HJDTaq) and an ethanolic (HJDTet) extract of HJDT on chronic brain injury after focal cerebral ischemia in mice. The ischemia was induced by occlusion of the right middle cerebral artery for 30 min. HJDTaq (4 g/kg) and HJDTet (200, 400, 800 mg/kg) were orally administered for 21 d from day 7 before ischemia to day 14 after ischemia. The survival rate decreased to less than 50% at 35 d after ischemia. HJDTet at 400 mg/kg increased the survival rate. HJDTaq (4 g/kg) and HJDTet (400, 800 mg/kg) significantly attenuated the neurological dysfunction, brain atrophy and infarct volume after ischemia. There were few cells positive for CD31, hypoxia-inducible-factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and Flk-1 in the sham control. After ischemia, the number increased. HJDTaq (4 g/kg) and HJDTet (400 or 800 mg/kg) further increased the numbers of CD31, HIF-1α, VEGF and Flk-1-positive cells in the ischemic hemisphere. We conclude that HJDTaq and HJDTet have neuroprotective effects on chronic brain injury after focal cerebral ischemia and lead to accelerated angiogenesis by HIF-1α-regulated VEGF signaling.

Sports concussion and the risk of chronic neurological impairment.

Intense recent media focus on long-term outcomes from sports concussion has highlighted concerns on both cognitive deterioration and mental health issues, such as depression and suicide. At this time, the scientific evidence to support these views is limited, with only a handful of cases thus far reported. Based on the literature on this topic that extends back over 50 years, it is clear that only a small percentage of athletes suffer such sequelae presumably due to recurrent concussive or subconcussive head impacts. At this stage, determining which athletes are at future risk is not possible; however, following existing concussion guidelines (eg, Zurich guidelines) is likely to be the safest option based on current evidence.

A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors.

We face a profound and emerging public health problem in the form of acute and chronic brain dysfunction. This affects both young and elderly intensive care unit survivors and is altering the landscape of society. Two-thirds of intensive care unit patients develop delirium, and this is associated with longer stays, increased costs, and excess mortality. In addition, over half of intensive care unit survivors suffer a dementia-like illness that impacts their physical and cognitive functional abilities and which appears to be related to the duration of their intensive care unit delirium. A new paradigm of how intensivists handle the brain is required. We propose a three-step approach to address this emerging epidemic, which includes Screening, Prevention, and Restoration of brain function (SPR). Screening combines risk factor identification and delirium assessment using validated instruments. Prevention of acute and chronic brain dysfunction requires implementation of a core model of care that combines evidence-based practices: awakening and breathing, coordination with target-based sedation, delirium monitoring, and exercise/early mobility (ABCDE). Restoration introduces strategies of ongoing screening and treatment for intensive care unit survivors at high risk of ongoing brain dysfunction. This practical system applying many evidence-based concepts incorporates personalized medicine, systems-based practice, and continuing research and development toward improving acute and chronic cognitive outcomes.

Perioperative neuroprotective strategies.

Long-term neurodevelopmental impairment is common in newborns and infants undergoing corrective or palliative congenital heart surgery. The etiologies of neurodevelopmental morbidity in these children are multifactorial and include prenatal, preoperative, intraoperative, and postoperative factors. Perioperative neurologic monitoring is thought to be integral to prevention or rescue from adverse neurologic events. Recent advances in perfusion techniques for congenital heart surgery now ensure adequate cerebral O(2) delivery during all phases of cardiopulmonary bypass. Periventricular leukomalacia and other serious neurologic injury can be minimized by an optimized perfusion strategy of continuous high-flow, high hematocrit cardiopulmonary bypass, minimal use of deep hypothermic circulatory arrest, antegrade cerebral perfusion during aortic arch reconstruction, pH-stat blood gas strategy, and cerebral monitoring with NIRS and trans-cranial Doppler. Because there is evidence that brain injury can also occur in the prenatal, preoperative, and postoperative periods, improved strategies to prevent injury in these arenas are much needed. Extensive further clinical investigation is warranted to identify neuroprotective management strategies for the operating room and intensive care unit to preserve neurologic function and optimize long-term neurodevelopmental outcomes in children with congenital heart disease.

Routine continuous perfusion for aortic arch reconstruction in the neonate.

Continuous perfusion has evolved over the past 15 years as a viable cerebral protection strategy for neonatal aortic arch reconstruction. It presents an attractive alternative to deep hypothermic circulatory arrest. However, because of its relatively recent development, a standardized technique for its application is lacking. Here we describe our approach for continuous perfusion for repairs of the aortic arch based on experience with over 700 cases.

Peripheral administration of a novel diketopiperazine, NNZ 2591, prevents brain injury and improves somatosensory-motor function following hypoxia-ischemia in adult rats.

The current study describes the neuroprotective effects of an endogenous diketopiperazine, cyclo-glycyl-proline (cyclic GP), in rats with hypoxic-ischemic brain injury and the pre-clinical development of an analogue, cyclo-L-glycyl-L-2-allylproline (NNZ 2591), modified for improved bioavailability. The compounds were given either intracerebroventricularly or subcutaneously 2h after hypoxia-ischemia. Histology, immunohistochemistry and behavior were used to evaluate treatment effects. The central uptake of NNZ 2591 was also examined in normal and hypoxic-ischemic injured rats by HPLC-mass spectrometry. Central administration of cyclic GP or NNZ 2591 reduced the extent of brain damage in the lateral cortex, the hippocampus and the striatum (p<0.001), with NNZ 2591 being more potent. NNZ 2591 was stable in the plasma and crossed the blood-brain barrier independent of hypoxic-ischemic injury. The level of NNZ 2591 in the CSF was maintained for 2 h after a single subcutaneous dose, and modest neuroprotection was seen after a bolus subcutaneous administration (overall p<0.001). Treatment with NNZ 2591 for 5 d subcutaneously improved somatosensory-motor function (p<0.05) and long-term histological outcome (overall p<0.0001). NNZ 2591 treatment not only reduced both caspase-3 mediated apoptosis and microglial activation but also enhanced astrocytic reactivity, which may mediate its protective effect. The pharmacokinetic profile and potent long-term protective effects of NNZ 2591 suggests its utility for the treatment of ischemic brain injury and other neurological conditions requiring chronic intervention.

Brain monitoring and protection during pediatric cardiac surgery.

With advances in medical care, survival after cardiac surgery for congenital heart disease has dramatically improved, and attention is increasingly focused on long-term functional morbidities, especially neurodevelopmental outcomes, with their profound consequences to patients and society. There are multiple reasons for concern about brain injury. Some cardiac defects are associated with brain anomalies and altered cerebral blood flow regulation. Brain imaging studies have demonstrated that injury to gray and white matter is quite frequent before heart surgery in neonates. Cardiopulmonary bypass and deep hypothermic circulatory arrest are associated with short- and longer-term adverse neurologic outcome. Additional brain injury can occur during the patient's recovery from surgery. Strategies to optimize neurologic outcome continue to evolve. With new technological developments, perioperative neurologic monitoring of small children has become easier, and data suggest these modalities usefully identify adverse neurologic events and might predict outcome. Monitoring methods to be discussed include processed electroencephalography, near infrared spectroscopy, and transcranial Doppler ultrasound. Alternative perfusion techniques to deep hypothermic circulatory arrest have been developed, such as regional antegrade cerebral perfusion during cardiopulmonary bypass. Other neuroprotective strategies employed during open-heart surgery include temperature regulation, acid-base management, degree of hemodilution, blood glucose control and anti-inflammatory therapies. Evidence of the impact of these measures on neurologic outcome is examined, and deficiencies in our current understanding of neurologic function in children with congenital heart disease are identified.

Is Heading in Youth Soccer Dangerous Play?

BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.

Ectopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity.

The catalytic subunit of telomerase reverse transcriptase (TERT) protects dividing cells from replicative senescence in vitro. Here, we show that expression of TERT mRNA is induced in the ipsilateral cortical neurons after occlusion of the middle cerebral artery in adult mice. Transgenic mice that overexpress TERT showed significant resistance to ischemic brain injury. Among excitotoxicity, oxidative stress, and apoptosis comprising of routes of ischemic neuronal death, NMDA receptor-mediated excitotoxicity was reduced in forebrain cell cultures overexpressing TERT. NMDA-induced accumulation of cytosolic free Ca2+ ([Ca2+]c) was reduced in forebrain neurons from TERT transgenic mice, which was attributable to the rapid flow of [Ca2+]c into the mitochondria from the cytosol without change in Ca2+ influx and efflux through the plasma membrane. The present study provides evidence that TERT is inducible in postmitotic neurons after ischemic brain injury and prevents NMDA neurotoxicity through shift of the cytosolic free Ca2+ into the mitochondria, and thus plays a protective role in ameliorating ischemic neuronal cell death.

Determining brain fitness to fight: Has the time come?

Professional boxing is associated with a risk of chronic neurological injury, with up to 20-50% of former boxers exhibiting symptoms of chronic brain injury. Chronic traumatic brain injury encompasses a spectrum of disorders that are associated with long-term consequences of brain injury and remains the most difficult safety challenge in modern-day boxing. Despite these concerns, traditional guidelines used for return to sport participation after concussion are inconsistently applied in boxing. Furthermore, few athletic commissions require either formal consultation with a neurological specialist (i.e. neurologist, neurosurgeon, or neuropsychologist) or formal neuropsychological testing prior to return to fight. In order to protect the health of boxers and maintain the long-term viability of a sport associated with exposure to repetitive head trauma, we propose a set of specific requirements for brain safety that all state athletic commissions would implement.

Should boxing be banned?

Should boxing be banned? Do the ever-so-obvious risks outweigh everyone's freedom to choose whether to expose oneself to these risks by taking up the sport? On an official level, the RCN in the UK has taken its stand--it does not! So has also the British Medical Association (BMA)--it does! With few exceptions, the responding nurses from Europe, America, and Australia in this month's column seem to agree with the official nursing standpoint in the UK, also emphasizing the importance that any person's choice not only should be free, but also informed. In the United States, where boxing perhaps has its strongest tradition and deepest roots, the whole issue hardly seems to be one of much realistic debate at all. In Australia, however, the debate seems to be similar to that in the UK. What would a total ban on boxing lead to? No more boxing and no more neurological consequences due to boxing? Doubtfully, boxing would probably continue anywhere where there is an interest for it, and a ban might actually increase the attraction to the sport for some people. In this scenario there is also a risk that the safety precautions would be seriously compromised. This month's question exemplifies an area in which it is very important for nurses to make a stand, on a personal as well as on a collective level. As indicated by several of this month's replies, the issue is probably not merely about boxing but also about to what extent people's choices should be controlled by bans and where the line should be drawn. To what extent are people competent to make their own decisions and where/when/how should "big brother" (in this case as represented by, among others, nursing as a profession) be allowed to step in? Anyone who has any further contributions or comments on this issue is welcome to contact me!