Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including therapeutic hypothermia (TH), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Patients remaining comatose following resuscitation from cardiac arrest and who are not bleeding are potential candidates for TH. This protocol will review induction, maintenance, and re-warming phases of TH, along with management of TH side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography imaging of the brain, continuous electroencephalography, monitoring, and correction of electrolyte, blood gas, and hematocrit changes are also necessary to optimize outcomes.     

Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest

Cardiac arrest is the most common cause of death in North America. An organized bundle of neurocritical care interventions can improve chances of survival and neurological recovery in patients who are successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Key aspects of successful early post-arrest management include: prevention of secondary brain injury; identification of treatable causes of arrest in need of emergent intervention; and, delayed neurological prognostication. Secondary brain injury can be attenuated through targeted temperature management (TTM), avoidance of hypoxia and hypotension, avoidance of hyperoxia, hyperventilation or hypoventilation, and treatment of seizures. Most patients remaining comatose after resuscitation from cardiac arrest should undergo TTM. Treatable precipitants of arrest that require emergent intervention include, but are not limited to, acute coronary syndrome, intracranial hemorrhage, pulmonary embolism and major trauma. Accurate neurological prognostication is generally not appropriate for several days after cardiac arrest, so early aggressive care should never be limited based on perceived poor neurological prognosis.     

Repetitive anodal transcranial direct current stimulation improves neurological recovery by preserving the neuroplasticity in an asphyxial rat model of cardiac arrest

BackgroundNon-shockable rhythms present an increasing proportion of out-of-hospital cardiac arrest (CA) patients, but are associated with poor prognosis and received limited therapeutic effect of targeted temperature management (TTM). Previous study showed repetitive anodal transcranial direct current stimulation (tDCS) improved neurological outcomes in animals with ventricular fibrillation. Here, we examine the effectiveness of tDCS on neurological recovery and the potential mechanisms in a rat model of asphyxial CA.MethodCardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial CA. Animals were randomized to three experimental groups immediately after successful resuscitation (n = 12/group, 6 males): no-treatment control (NTC) group, TTM group, and tDCS group. Post resuscitation hemodynamics, quantitative electroencephalogram (EEG), neurological deficit score, and 96-h survival were evaluated. Brain tissues of additional animals undergoing same experimental procedure was harvested for enzyme-linked immunoassay-based quantification assays of neuroplasticity-related biomarkers and compared with the sham-operated rats (n = 6/group).ResultsWe observed that after resuscitation tDCS-treated animals exhibited significantly higher mean arterial pressure and left ventricular ejection fraction than NTC group and showed greatly improved EEG characteristics including weighted-permutation entropy and gamma band power, and neurologic deficit scores and 96-h survival rates compared to NTC and TTM groups. Furthermore, neuroplastic biomarkers including microtubule-associated protein 2, growth-associated protein 43, postsynaptic density protein 95 and synaptophysin, were significantly higher in tDCS group when compared with NTC and TTM groups.ConclusionIn this rat model of asphyxial CA, repetitive anodal tDCS commenced after resuscitation improved neurological recovery, and it may exert a neuroprotective effect by preserving the neuroplasticity.     

Ethical issues in critical care and cardiac arrest: clinical research, brain death, and organ donation

Cardiac arrest results in global hypoxic-ischemic brain injury from which there is a range of possible neurological outcomes. In most cases, patients may require a surrogate to make decisions regarding end-of-life care, including the withdrawal of life-sustaining therapies. This article reviews ethical considerations that arise in the clinical care of patients following cardiac arrest, including decisions to continue or withdraw life-sustaining therapies; brain death determination; and organ donation in the context of brain death and cardiac death (so-called non-heart-beating donation). This article also discusses ethical concerns pertaining to the design and conduct of resuscitation research that is necessary for the development of effective therapies to prevent anoxic brain injury or promote neurological recovery.     

Cognitive and Functional Consequence of Cardiac Arrest

Cardiac arrest is associated with high morbidity and mortality. Better-quality bystander cardiopulmonary resuscitation training, cardiocerebral resuscitation principles, and intensive post-resuscitation hospital care have improved survival. However, cognitive and functional impairment after cardiac arrest remain areas of concern. Research focus has shifted beyond prognostication in the immediate post-arrest period to identification of mechanisms for long-term brain injury and implementation of promising protocols to reduce neuronal injury. These include therapeutic temperature management (TTM), as well as pharmacologic and psychological interventions which also improve overall neurological function. Comprehensive assessment of cognitive function post-arrest is hampered by heterogeneous measures among studies. However, the domains of attention, long-term memory, spatial memory, and executive function appear to be affected. As more patients survive cardiac arrest for longer periods of time, there needs to be a greater focus on interventions that can enhance cognitive and psychosocial function post-arrest.     

Targeted temperature management and early neuro-prognostication after cardiac arrest

Targeted temperature management (TTM) is a recommended neuroprotective intervention for coma after out-of-hospital cardiac arrest (OHCA). However, controversies exist concerning the proper implementation and overall efficacy of post-CA TTM, particularly related to optimal timing and depth of TTM and cooling methods. A review of the literature finds that optimizing and individualizing TTM remains an open question requiring further clinical investigation. This paper will summarize the preclinical and clinical trial data to-date, current recommendations, and future directions of this therapy, including new cooling methods under investigation. For now, early induction, maintenance for at least 24 hours, and slow rewarming utilizing endovascular methods may be preferred. Moreover, timely and accurate neuro-prognostication is valuable for guiding ethical and cost-effective management of post-CA coma. Current evidence for early neuro-prognostication after TTM suggests that a combination of initial prediction models, biomarkers, neuroimaging, and electrophysiological methods is the optimal strategy in predicting neurological functional outcomes.     

Repetitive anodal transcranial direct current stimulation improves neurological outcome and survival in a ventricular fibrillation cardiac arrest rat model

Background

Transcranial direct current stimulation (tDCS) modulates neuronal activity and is a potential therapeutic tool for many neurological diseases. However, its beneficial effects on post cardiac arrest syndrome remains uncertain.

Hypothermia for acute brain injury--mechanisms and practical aspects

Hypothermia is widely accepted as the gold-standard method by which the body can protect the brain. Therapeutic cooling--or targeted temperature management (TTM)--is increasingly being used to prevent secondary brain injury in patients admitted to the emergency department and intensive care unit. Rapid cooling to 33 °C for 24 h is considered the standard of care for minimizing neurological injury after cardiac arrest, mild-to-moderate hypothermia (33-35 °C) can be used as an effective component of multimodal therapy for patients with elevated intracranial pressure, and advanced cooling technology can control fever in patients who have experienced trauma, haemorrhagic stroke, or other forms of severe brain injury. However, the practical application of therapeutic hypothermia is not trivial, and the treatment carries risks. Development of clinical management protocols that focus on detection and control of shivering and minimize the risk of other potential complications of TTM will be essential to maximize the benefits of this emerging therapeutic modality. This Review provides an overview of the potential neuroprotective mechanisms of hypothermia, practical considerations for the application of TTM, and disease-specific evidence for the use of this therapy in patients with acute brain injuries.     

Cerebral Edema After Cardiopulmonary Resuscitation: A Therapeutic Target Following Cardiac Arrest?

We sought to review the role that cerebral edema plays in neurologic outcome following cardiac arrest, to understand whether cerebral edema might be an appropriate therapeutic target for neuroprotection in patients who survive cardiopulmonary resuscitation. Articles indexed in PubMed and written in English. Following cardiac arrest, cerebral edema is a cardinal feature of brain injury and is a powerful prognosticator of neurologic outcome. Like other conditions characterized by cerebral ischemia/reperfusion, neuroprotection after cardiac arrest has proven to be difficult to achieve. Neuroprotection after cardiac arrest generally has focused on protecting neurons, not the microvascular endothelium or blood–brain barrier. Limited preclinical data suggest that strategies to reduce cerebral edema may improve neurologic outcome. Ongoing research will be necessary to determine whether targeting cerebral edema will improve patient outcomes after cardiac arrest.     

Hypothermia and ERK activation after cardiac arrest

Mild hypothermia improves survival and neurological outcome after cardiac arrest, as well as increasing activation of the extracellular-signal-regulated kinase (ERK) in hippocampus. ERK signaling is involved in neuronal growth and survival. We tested the hypothesis that the beneficial effects of hypothermia required ERK activation. ERK activation was measured by immunoblotting with phosphorylation-specific antibodies. Rats (n = 8 per group) underwent 8 min of asphyxial cardiac arrest and were resuscitated with chest compressions, ventilation, epinephrine and bicarbonate. At 30 min after resuscitation, vehicle (50% saline:50% DMSO) or the ERK kinase inhibitor U0126 (100 microg) was infused into the lateral ventricle. Cranial temperature was kept at either 33 degrees C (hypothermia) or 37 degrees C (normothermia) between 1 and 24 h. Neurological function was assessed daily for 14 days. Surviving neurons were counted in the hippocampus. A dose of 100 mug U0126 inhibited ERK bilaterally for 12 to 24 h and decreased phosphorylation of the ERK substrates ATF-2 and CREB. As in previous studies, hypothermia improved survival, neurological and histological outcome after cardiac arrest. However, survival, neurological score and histology did not differ between U0126 and vehicle-treated rats after cardiac arrest. Therefore, a dose of U0126 sufficient to inhibit biochemical markers of ERK signaling in hippocampus does not alter the beneficial effects of hypothermia induced after resuscitation in rats and did not affect recovery of normothermia-treated rats. These results suggest that hypothermia-induced improvement in outcomes does not require ERK activation.     

Therapeutic hypothermia after cardiac arrest

The use of IH for 24 hours in patients who remain comatose following resuscitation from out-of-hospital cardiac arrest improves outcomes. How-ever, the induction of hypothermia has several physiologic effects that need to be considered. A protocol for the rapid induction of hypothermia is described. At present, the rapid infusion of a large volume (40 mL/kg) of ice-cold crystalloid (ie, lactated Ringer's solution) would appear to be an inexpensive, safe strategy for the induction of hypothermia after cardiac arrest. Hypothermia (33 degrees C) should be maintained for 24 hours, followed by rewarming over 12 hours. Particular attention must be paid to potassium and glucose levels during hypothermia.     

Hypothermia for neuroprotection after cardiac arrest: mechanisms, clinical trials and patient care

Therapeutic hypothermia is a proven part of cardio-cerebral resuscitation after cardiac arrest as it improves neurologic outcomes after hypoxic brain injury. This article reviews the mechanisms of hypothermic neuroprotection, the clinical trials that support its use after cardiac arrest, as well as the impact of hypothermia on patient management and prognosis. In caring for patients suffering hypoxic brain injury after cardiac arrest, the role of the neurologist is no longer limited to prognosis but is now to become actively involved in clinical management which includes the use of therapeutic hypothermia.     

Prehospital interventions to improve neurological outcome following cardiac arrest

As many cases of cardiac arrest occur outside of the health care setting, prehospital treatment may dramatically affect patient outcomes. The three major interventions that have been studied are chest compressions and ventilation, electrical defibrillation, and medications. Recent studies show that increasing the rate of cardiopulmonary resuscitation (CPR), decreasing the rate of ventilation, and initiation of CPR prior to defibrillation may result in improved survival. Biphasic defibrillators can restore perfusing rhythms while minimizing myocardial injury. Public access to automatic defibrillators has been shown to increase the survival of cardiac arrest patients. Medications such as amiodarone, vasopressin, and thrombolytics also may have a role in the prehospital treatment of cardiac arrest. Recent advances in these areas will be reviewed with a discussion of the effect of each intervention on the restoration of circulation and neurological outcomes.     

心脏骤停后全脑缺血犬内皮素和脑型肌酸激酶同功酶的变化

目的　脑复苏为心脏骤停后复苏成功与否的关键 ,本文对心脏骤停后全脑缺血犬损害的实验研究 ,旨在为临床心肺脑复苏工作提供一定的实验资料。方法　 16条成年健康杂种犬 ,随机分为两组 ,以同法诱颤后复苏 ,A组诱颤后 5分钟而B组诱颤后 10分钟开始复苏 ,复苏成功后 ,立即取血、脑脊液标本进行内皮素和脑型肌酸激酶同功酶 (CK BB)检查。结果　A组内皮素 (ET)和脑型肌酸激酶同功酶明显低于B组。结论　心脏骤停后脑复苏成功与否与时间密切相关 ,时间短则脑细胞坏死改变较轻     

Lessons in experimental ischemia for clinical stroke medicine

PURPOSE OF REVIEW: This review covers experimental developments in the laboratory and their translation to clinical stroke trials over the year from 3 August 2001 to 2002. RECENT FINDINGS: Recent findings include novel observations in the areas of excitotoxicity, free radical injury, neuro-inflammation and apoptosis. A key clinical finding this year has been the translation of the effects of hypothermia in global ischemia to two successful trials in cardiac arrest with patients cooled within 4-8 h following resuscitation achieving good neurological outcomes, as compared with their normothermic controls. An era of molecular imaging in stroke research is presaged by the first reports of enhanced magnetic resonance or labeling with supramagnetic contrast agents. SUMMARY: Although none of the drugs in focal ischemia has translated from experimental models, for the first time there is evidence of cytoprotection for the brain that has been translated from the laboratory to man.     

Adenosine treatment delays postischemic hippocampal CA1 loss after cardiac arrest and resuscitation in rats

Resuscitation from cardiac arrest results in reperfusion injury that leads to increased postresuscitation mortality and delayed neuronal death. One of the many consequences of resuscitation from cardiac arrest is a derangement of energy metabolism and the loss of adenylates, impairing the tissue's ability to regain proper energy balance. In this study, we investigated the effects of adenosine (ADO) on the recovery of the brain from 12 min of ischemia using a rat model of cardiac arrest and resuscitation. Compared to the untreated group, treatment with adenosine (7.2 mg/kg) initiated immediately after resuscitation increased the proportion of rats surviving to 4 days and significantly delayed hippocampal CA1 neuronal loss. Brain blood flow was increased significantly in the adenosine-treated rats 1 h after cardiac arrest and resuscitation. Adenosine-treated rats exhibited less edema in cortex, brainstem and hippocampus during the first 48 h of recovery. Adenosine treatment significantly lowered brain temperature during recovery, and a part of the neuroprotective effects of adenosine treatment could be ascribed to adenosine-induced hypothermia. With this dose, adenosine may have a delayed transient effect on the restoration of the adenylate pool (AXP = ATP + ADP + AMP) 24 h after cardiac arrest and resuscitation. Our findings suggested that improved postischemic brain blood flow and ADO-induced hypothermia, rather than adenylate supplementation, may be the two major contributors to the neuroprotective effects of adenosine following cardiac arrest and resuscitation. Although adenosine did not prevent eventual CA1 neuronal loss in the long term, it did delay neuronal loss and promoted long-term survival. Thus, adenosine or specific agonists of adenosine receptors should be evaluated as adjuncts to broaden the window of opportunity in the treatment of the reperfusion injury following cardiac arrest and resuscitation.     

Outcomes of Mild Therapeutic Hypothermia After In-Hospital Cardiac Arrest

Background

Although the benefits of mild therapeutic hypothermia (MTH) in selected patients after out-of-hospital cardiac arrest have been consistently demonstrated, no controlled trial of MTH in selected patients after in-hospital cardiac arrest (IHCA) has been published. We sought to assess the benefit of MTH after IHCA in patients meeting our institutions IHCA MTH inclusion criteria.

Methods

A retrospective, historical control study was performed. During the 3-year period before and after the 2006 MTH protocol implementation at our institution, we identified a total of 118 patients admitted to our Medical Intensive Care Unit after resuscitation from an IHCA. Two blinded investigators identified all patients meeting our institutions MTH protocol inclusion criteria and the patients in each time period were compared. The primary outcome was discharge with good neurological function.

Results

33 IHCA patients met MTH protocol inclusion criteria; 16 patients were admitted prior to MTH protocol implementation and thus were not treated with MTH post arrest while 17 patients were admitted after implementation and were all treated with MTH post arrest. 91% of patients had an arrest rhythm of asystole or pulseless electrical activity. Good neurological function at discharge was found in 24% of MTH patients and 31% of controls (P?=?.62).

Conclusions

No difference in neurological outcome at discharge was detected in predominantly non-shockable IHCA patients treated with MTH. This finding, if confirmed with further study, may define a population of patients for whom this costly and resource intensive therapy should be withheld.     

Emergency Neurological Life Support: Intracranial Hypertension and Herniation

Sustained intracranial hypertension and acute brain herniation are “brain codes,” signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, a brain code mandates the organized implementation of a stepwise management algorithm. The goal of this emergency neurological life support protocol is to implement an evidence-based, standardized approach to the evaluation and management of patients with intracranial hypertension and/or herniation.     

犬心脏骤停后脑缺血的病理变化

目的：本文旨在观察心肺脑复苏过程中脑缺血的病理变化。方法：16条成年健康杂种犬，随机分为两组，以同法诱颤后复苏，A组诱颤后5分钟而B组诱颤后10分钟开始复苏，复苏成功后，立即取血、脑脊液标本进行脑型肌酸激酶同功酶（CK－BB）检查，72小时后取脑组织标本进行光、电镜检查。结果：A组脑型肌酸激酶同功酶明显低于B组，且其病理改变也明显轻微。结论：心脏骤停后脑复苏成功与否与时间密切相关，时间短则脑病理改变较轻。     

Sexually Dimorphic Response of TRPM2 Inhibition Following Cardiac Arrest-Induced Global Cerebral Ischemia in Mice

Transient global cerebral ischemia due to cardiac arrest followed by resuscitation (CA/CPR) causes significant neurological damage in vulnerable neuron populations within the brain, such as hippocampal CA1 neurons. In recent years, we have implicated the transient receptor potential M2 (TRPM2) channel as a mediator of ischemic injury to neurons. We previously demonstrated that genetic and pharmacological strategies that reduce TRPM2 function preferentially protect male neurons in vitro and reduce infarct volume following experimental stroke. Due to the narrow therapeutic window for intervention following ischemic stroke, it is important to assess the role of TRPM2 in other models of cerebral ischemia. Therefore, this study utilized a modified mouse model of CA/CPR to mimic more accurately the clinical condition by maintaining body and head temperatures near the physiological range throughout. Here, we report that inhibition of TRPM2 activity with clotrimazole reduces hippocampal CA1 neuronal injury when administered 30 min after resuscitation from cardiac arrest. Consistent with our previous observations, neuroprotection was observed in male mice and no effect on injury was observed in the female. These findings provide further evidence for TRPM2 as a target for protection against cerebral ischemia in the male brain.