ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The development of modern cardiopulmonary-cerebral resuscitation (CPCR) has given every person the ability to challenge death anywhere. Despite sparks of knowledge and occasional applications of possibly effective lifesaving efforts since antiquity, the possibility to reverse acute terminal states or clinical death by modern, physiologically sound, and effective measures did not come about until around 1900 inside hospitals, and around 1960 outside hospitals. Additional potentially effective cerebral resuscitation, researched since around 1970, may be taken to clinical trials before the year 2000. The history of resuscitation medicine around 1900, when many opportunities to assemble existing bits of knowledge into an effective system were missed, should be a warning for those individuals who will lead CPCR beyond the year 2000. History has shown the need for continuing communication and collaboration among investigators of different countries, and between laboratory researchers, clinicians of various disciplines, and prehospital rescuers.The lessons learned from history, for research challenges in the near future, include:a) the development of ultra-advanced life support to be initiated outside the hospital, to bridge cardiopulmonary resuscitation (CPR)-resistant cases to definitive cardiac procedures in the hospital; and b) cerebral resuscitation to complete recovery after 10 to 15 mins of normothermic cardiac arrest without blood flow. Both challenges above will require research projects at multiple levels--from the molecular and cellular levels, to the use of small and large animal models (with organs' and organisms' process and outcome evaluations), to studies of patients and communities. Beyond the year 2000, resuscitation research might become more challenging and cost-effective in the area of multiple trauma, which concerns the young and fit. Research challenges concerning brain trauma, uncontrolled hemorrhagic shock, and ``suspended animation'' for delayed resuscitation have their own histories, and are not covered here.The author apologizes for not having recognized many important contributors to the history of CPCR because of space constraints or lack of knowledge about such contributions.Input on this subject from readers of this paper is hereby invited.(Crit Care Med 1996; 24(Suppl):S3-S11)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The potential to be successfully resuscitated from severe traumatic hemorrhagic shock is not only limited by the ``golden 1 hr,'' but also by the ``brass (or platinum) 10 mins'' for combat casualties and civilian trauma victims with traumatic exsanguination.One research challenge is to determine how best to prevent cardiac arrest during severe hemorrhage, before control of bleeding is possible. Another research challenge is to determine the critical limits of, and optimal treatments for, protracted hemorrhagic hypotension, in order to prevent ``delayed'' multiple organ failure after hemostasis and all-out resuscitation. Animal research is shifting from the use of unrealistic, pressure-controlled, hemorrhagic shock models and partially realistic, volume-controlled hemorrhagic shock models to more realistic, uncontrolled hemorrhagic shock outcome models. Animal outcome models of combined trauma and shock are needed; a challenge is to find a humane and clinically realistic long-term method for analgesia that does not interfere with cardiovascular responses.Clinical potentials in need of research are shifting from normotensive to hypotensive (limited) fluid resuscitation with plasma substitutes.Topics include optimal temperature, fluid composition, analgesia, and pharmacotherapy. Hypotensive fluid resuscitation in uncontrolled hemorrhagic shock with the addition of moderate resuscitative (28 degrees to 32 degrees C) hypothermia looks promising in the laboratory. Regarding the composition of the resuscitation fluid, despite encouraging results with new preparations of stroma-free hemoglobin and hypertonic salt solutions with colloid, searches for the optimal combination of oxygen-carrying blood substitute, colloid, and electrolyte solution for limited fluid resuscitation with the smallest volume should continue. For titrating treatment of shock, blood lactate concentrations are of questionable value, although metabolic acidemia seems helpful for prognostication. Development of devices for early noninvasive monitoring of multiple parameters in the field is indicated. Molecular research applies more to protracted hypovolemic shock followed by the systemic inflammatory response syndrome or septic shock, which were not the major topics of this discussion.(Crit Care Med 1996; 24(Suppl):S12-S23)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Suspended animation is defined as the therapeutic induction of a state of tolerance to temporary complete systemic ischemia, i.e., protection-preservation of the whole organism during prolonged circulatory arrest (more than equals 1 hr), followed by resuscitation to survival without brain damage. The objectives of suspended animation include: a) helping to save victims of temporarily uncontrollable (internal) traumatic (e.g., combat casualties) or nontraumatic (e.g., ruptured aortic aneurysm) exsanguination, without severe brain trauma, by enabling evacuation and resuscitative surgery during circulatory arrest, followed by delayed resuscitation; b) helping to save some nontraumatic cases of sudden death, seemingly unresuscitable before definitive repair; and c) enabling selected (elective) surgical procedures to be performed which are only feasible during a state of no blood flow. In the discussion session, investigators with suspended animation-relevant research interests brainstorm on present knowledge, future research potentials, and the advisability of a major research effort concerning this subject. The following topics are addressed: the epidemiologic facts of sudden death in combat casualties, which require a totally new resuscitative approach; the limits and potentials of reanimation research; complete reversibility of circulatory arrest of 1 hr in dogs under profound hypothermia (less than 10 degrees C), induced and reversed by portable cardiopulmonary bypass; the need for a still elusive pharmacologic or chemical induction of suspended animation in the field; asanguinous profound hypothermic low-flow with cardiopulmonary bypass; electric anesthesia; opiate therapy; lessons learned from hypoxia tolerant vertebrate animals, hibernators, and freeze-tolerant animals (cryobiology); myocardial preservation during open-heart surgery; organ preservation for transplantation; and reperfusion-reoxygenation injury in vital organs, including the roles of nitric oxide and free radicals; and how cells (particularly cerebral neurons) die after transient prolonged ischemia and reperfusion. The majority of authors believe that seeking a break-through in suspended animation is not utopian, that ongoing communication between relevant research groups is indicated, and that a coordinated multicenter research effort, basic and applied, on suspended animation is justified.(Crit Care Med 1996; 24(Suppl):S24-S47)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Severe traumatic brain injuries are extremely heterogeneous.At least seven of the secondary derangements in the brain that have been identified as occurring after most traumatic brain injuries also occur after cardiac arrest. These secondary derangements include posttraumatic brain ischemia. In addition, traumatic brain injury causes insults not present after cardiac arrest, i.e., mechanical tissue injury (including axonal injury and hemorrhages), followed by inflammation, brain swelling, and brain herniation. Brain herniation, in the absence of a mass lesion, is due to a still-to-be-clarified mix of edema and increased cerebral blood flow and blood volume. Glutamate release immediately after traumatic brain injury is proven. Late excitotoxicity needs exploration. Inflammation is a trigger for repair mechanisms.In the 1950s and 1960s, traumatic brain injury with coma was treated empirically with prolonged moderate hypothermia and intracranial pressure monitoring and control.Moderate hypothermia (30 degrees to 32 degrees C), but not mild hypothermia, can help prevent increases in intracranial pressure. How to achieve optimized hypothermia and rewarming without delayed brain herniation remains a challenge for research. Deoxyribonucleic acid (DNA) damage and triggering of programmed cell death (apoptosis) by trauma deserve exploration.Rodent models of cortical contusion are being used effectively to clarify the molecular and cellular responses of brain tissue to trauma and to study axonal and dendritic injury.However, in order to optimize therapeutic manipulations of posttraumatic intracranial dynamics and solve the problem of brain herniation, it may be necessary to use traumatic brain injury models in large animals (e.g., the dog), with long-term intensive care. Stepwise measures to prevent lethal brain swelling after traumatic brain injury need experimental exploration, based on the multifactorial mechanisms of brain swelling. Novel treatments have so far influenced primarily healthy tissue; future explorations should benefit damaged tissue in the penumbra zones and in remote brain regions. The prehospital arena is unexplored territory for traumatic brain injury research.(Crit Care Med 1996; 24(Suppl):S48-S56)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction?For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.(Crit Care Med 1996; 24(Suppl):S57-S68)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In 1961, in Pittsburgh, PA, ``cerebral'' was added to the cardiopulmonary resuscitation system (CPR right arrow CPCR).Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.(Crit Care Med 1996; 24(Suppl):S69-S80)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Resuscitative (postinsult) hypothermia is less well studied than protective-preservative (pre- and intra-arrest) hypothermia. The latter is in wide clinical use, particularly for protecting the brain during cardiac surgery. Resuscitative hypothermia was explored in the 1950s and then lay dormant until the 1980s when it was revived. This change occurred through the discoveries of brain damage mitigating effects after cardiac arrest in dogs, and after forebrain ischemia in rats, of mild (34 degrees C) hypothermia (which is safe), and of benefits derived from moderate hypothermia (30 degrees C) after traumatic brain injury or focal brain ischemia in various species. The idea that protection-preservation or resuscitation by hypothermia is mainly explained by its ability to reduce cerebral oxygen demand has been replaced by an increasingly documented synergism of many beneficial mechanisms. Deleterious chemical cascades during and after these insults are suppressed even by mild hypothermia. Prolonged moderate hypothermia carries some risks, e.g., arrhythmias, infection and coagulopathies. These side effects need further study. In global brain ischemia, protective-preservative mild hypothermia provides lasting mitigation of brain damage. Resuscitative mild hypothermia, however, may be beneficial in terms of long-term outcome or may merely delay the inevitable loss of selectively vulnerable neurons. Even if the latter is true, mild hypothermia may extend the therapeutic window for other interventions. This extension of the therapeutic window requires further documentation. After normothermic cardiac arrest of 11 mins in dogs, mild resuscitative hypothermia from 15 mins to 12 hrs after reperfusion plus cerebral blood flow promotion normalized functional recovery with the least histologic damage seen thus far. Optimal duration of, and rewarming methods from, resuscitative hypothermia need clarification. The earliest possible induction of mild hypothermia after cardiac arrest seems desirable. Head-neck surface cooling alone is too slow. Among many clinically feasible rapid cooling methods, carotid cold flush and peritoneal cooling look promising. After traumatic brain injury or focal brain ischemia, which seem to still benefit from even later cooling, surface cooling methods may be adequate. Resuscitative hypothermia after cardiac arrest, traumatic brain injury, or focal brain ischemia should be considered for clinical trials.(Crit Care Med 1996; 24(Suppl):S81-S89)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The present trend in managed care has meant downsizing expectations concerning the availability of support for resuscitation research.This trend applies to funding possibilities from industry, governmental agencies, and nongovernmental agenciesTable 1. There will be increasing barriers to making innovations. Truth, science, and good patient care alone will not make potential donors give grants. Investigators must also understand the potential donors' expectations and be persuasive. ``Delight your donor.'' Industries' concerns include intellectual property rights and publications. The National Institutes of Health, recently favoring molecular biology over lifesaving therapies or integrated physiologic research, is an anomaly. The current peer review system propagates itself without having advocates for resuscitation research. This system has become a self-fulfilling prophecy. The American Heart Association is only recently, after 30 yrs of educational activities concerning cardiopulmonary resuscitation, considering putting some basic research money into resuscitation research. In university hospitals, where clinical departments have made significant contributions to innovative, clinically relevant life-support research, funded with incomes from patient care, the sky is beginning to fall. Resuscitation researchers need persuasive advocates with clout and hard data to convince funding agencies to give support to multilevel research and development in areas of pathophysiology and reversibility of terminal states and clinical death--to give these topics a higher priority than is currently available.(Crit Care Med 1996; 24(Suppl):S90-S94)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID