Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including targeted temperature management (TTM), 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 should be considered for TTM. This protocol will review induction, maintenance, and re-warming phases of TTM, along with management of TTM side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography and/or magnetic resonance imaging of the brain, continuous electroencephalography monitoring, and correction of electrolyte, blood gas, and hematocrit changes, are also necessary to optimize outcomes.     

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.     

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.     

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.     

Therapeutic Hypothermia for Acute Neurological Injuries

Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.     

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.     

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     

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.     

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。     

Frequency and Timing of Nonconvulsive Status Epilepticus in Comatose Post-Cardiac Arrest Subjects Treated with Hypothermia

Background  

Therapeutic hypothermia (TH) improves outcomes in comatose patients resuscitated from cardiac arrest. However, nonconvulsive status epilepticus (NCSE) may cause persistent coma. The frequency and timing of NCSE after cardiac arrest is unknown.     

Post-cardiorespiratory arrest beta-alpha coma: an unusual electroencephalographic phenomenon

The presence of frontally-dominant alpha pattern in the EEG is common in patients with coma due to trauma, toxic-metabolic causes and following cardiorespiratory arrest. Diffuse beta activity following resuscitation after a cardiac arrest is not well recognized. We report a case of coma in a 3-year-old girl who had a cardiac arrest from which she was revived. Initial EEG showed diffuse beta activity, which later evolved to predominantly alpha activity. The possible mechanisms involved in the generation of such rhythms are discussed. Transition of EEG activity from faster to slower frequencies is suggested as an adverse prognostic factor in post-cardiorespiratory arrest coma.     

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.     

Clinical Outcome After a Reactive Hypothermic EEG Following Cardiac Arrest

Background

Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA.

Methods

We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses.

Results

A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG (p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak (p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ.

Conclusions

A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease.     

Cerebral resuscitation: state of the art, experimental approaches and clinical perspectives

Neuronal injury following global cerebral ischemia continues to bea central problem of patients in the postresuscitation phase following cardiocirculatory arrest. In addition to measures focusing on rapid restoration of spontaneous circulation, the most effective treatment after cardiac arrest, as shown by large randomized trials,is the use of therapeutic mild hypothermia. Current guidelines of the International Liaison Committee on Resuscitation (ILCOR)are recommending the use of therapeutic mild hypothermia for all unconscious patients after cardiac arrest. At present there is no specific neuroprotective treatment available. Promising animal experimental data concerning the use of thrombolytic agents during cardiopulmonary resuscitation have led to a large European multicenter trial (TROICA trial) that will provide its data in 2006.     

CHANGES IN CISTERNAL FLUID POTASSIUM CONCENTRATION FOLLOWING CARDIAC ARREST

The purpose of this study was to measure the changes in potassium concentration in human cisternal Cerebrospinal fluid following successful resuscitation after cardiac arrest. We also wished to examine whether or not changes in potassium concentration in the cisternal cerebrospinal fluid could be correlated to the ability to regain normal cerebral function. 41 patients were studied, of whom 20 regained consciousness and 21 did not. In those who did not regain consciousness there mas a significant increase in the potassium concentration found in samples obtained between 40 and 50 min, and between 50 and 60 min after cardiac arrest. The potassium Concentration decreased to normal values during the following hours. Lumbar spinal fluid did not reflect the changes in cisternal fluid. The results suggest that the potassium concentration of cisternal cerebrospinal fluid, obtained soon after cardiac arrest, might give an indication of the degree of cerebral damage caused by cardiac arrest.     

Early processing of Bid and caspase-6, -8, -10, -14 in the canine brain during cardiac arrest and resuscitation

A clinically relevant model of transient global brain ischemia involving cardiac arrest followed by resuscitation in dogs was utilized to study the expression and proteolytic processing of apoptosis-regulatory proteins. In the hippocampus, an increase in pro-apoptotic Bcl-2 family proteins Bcl-XS and Bak was detected, concomitant with proteolysis of Bcl-XL and Bcl-2, following ischemia-reperfusion injury. Also, biphasic cleavage of Bid was found in this region of the brain, with early generation of tBid-p11 within 10 min of cardiac arrest, followed by generation of tBid-p15 within 30-min reperfusion, consistent with activation of this pro-apoptotic protein. In addition, cardiac arrest and resuscitation induced early, reperfusion-dependent proteolytic processing of pro-caspase-6, -8, -10, and -14, which preceded caspase-3 activation. Immunohistochemical analysis using antibodies, which preferentially recognize processed caspase-3, -6, -8, and -10, provided evidence of time-dependent activation of these proteases in both neurons and glia in ischemia-sensitive regions of the brain. In conclusion, extremely rapid, cell-selective processing of apoptosis-regulatory proteins occurs in a clinically relevant model of ischemic brain injury caused by cardiac arrest and resuscitation. The early cleavage of Bid and rapid depletion of 32-kDa pro-caspase-14 from the canine hippocampus after induction of ischemia suggests the involvement of calpains in the processing of these proteins. Demonstration of in vitro cleavage of recombinant mouse caspase-14 by calpain I in the present study lends support to this hypothesis, further implicating cross-talk between different protease families in the pathophysiology of ischemic neural cell death.     

Prolonged Retention of Awareness During Cardiopulmonary Resuscitation for Asystolic Cardiac Arrest

Objective  To describe high level of awareness in a patient undergoing cardiopulmonary resuscitation for an asystolic cardiac arrest and review the literature regarding this phenomenon. Methods  This is a case report of a patient admitted to the Intensive Care Unit who suffered an asystolic cardiac arrest. We reviewed MEDLINE using the terms “awareness,” “consciousness,” “cerebral perfusion,” “sedation,” “analgesia,” “termination,” “cessation,” and “cardiopulmonary resuscitation.” Results  A 57-year-old man with renal failure suffered asystolic cardiac arrest. He was awake and alert during cardiopulmonary resuscitation (CPR). Cardiac arrest was confirmed by echocardiogram and invasive arterial monitoring. He briskly localized and consistently followed simple commands while chest compressions were in progress before becoming unresponsive and dying after a 3-h resuscitative effort. No sedation/analgesia was used. There are few reports in the literature describing similar events. Conclusion  It is possible to retain a high level of awareness following cardiac arrest, particularly with effective CPR. Recognition of this situation when it occurs allows appropriate decisions to be made regarding the use of sedation and the length of resuscitative efforts. This case report was approved by the Ethics Committee of Apollo Hospitals, Chennai.     

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.     

Therapeutic hypothermia for cardiac arrest: A practical approach

Therapeutic hypothermia (TH), which prevents and ameliorates the cascade of secondary neurologic injury after the return of spontaneous circulation, is the most effective neuroprotective therapy for encephalopathic survivors of cardiac arrest. Acute management of patients with severe hypoxic-ischemic encephalopathy requires rapid and well-coordinated efforts involving emergency medicine, neurology, cardiology, critical care medicine, and palliative care. This effort is complex, and broad implementation of TH has been slow in the United States and Europe. This review summarizes recent developments in the practical application of TH, reviews the role of the neurologist, and suggests an algorithm for coordination of care of cardiac arrest survivors by physicians of divergent subspecialties, with the goals of maximizing neurologic and cardiac recovery.