Current Concepts in Cerebral Protection

doi:10.1378/chest.103.4.1246

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Volume 103, Issue 4, April 1993, Pages 1246-1254

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In the past, physicians viewed ischemic injury as an irreversible event. Modern science has shown that this view is incorrect and that ischemic neuronal damage is an ongoing, active process that might be amenable to various therapies. Figure 2 illustrates some of the possible sites where these therapies might be active. Pending evidence of their effectiveness, cerebral protection can best be achieved by maintaining adequate CPP and CBF during periods when patients are at risk for cerebral ischemia, restoring perfusion after ischemia occurs, and optimizing the metabolic milieu of the ischemic penumbra.

Section snippets

DETERMINANTS OF CEREBRAL METABOLISM AND BLOOD FLOW

Central nervous system tissue has a high metabolic rate for oxygen (CMRo₂) and uses predominantly glucose as a substrate. Local cerebral metabolic needs are coupled with local increases in cerebral blood flow (CBF) through autoregulation. Hence, factors that increase the CMRo₂ increase CBF. Temperature has a dramatic effect on CMRo₂, increasing it approximately 6 to 7 percent for every rise in temperature of 1°C. Conversely, hypothermia reduces CMRo₂ by the same percentage. Seizures increase

MECHANISMS OF BRAIN ISCHEMIA

When CBF fails to meet the critical metabolic needs of the neurons and their supporting parenchymal cells, brain ischemia results. Ischemia may be focal, as in the case of a stroke, or global, as in the hypoxic-ischemic state that results after cardiac arrest. Permanent cell death (brain infarction) occurs if CBF is not quickly reestablished; such death is due to a complex series of interactions that results in the disruption of cellular membrane integrity and the destruction of the basic

Improving Cerebral Metabolism and Blood Flow

Since CBF is intimately related to tissue survival, adequate CPP must be maintained. This can be done by means of maneuvers that raise the MAP to reduce ICE It is imperative in all brain-injured patients that hypotension be avoided. Oxygen should be administered, and factors that increase CMRo₂ (and thereby require an increased CBF) should be corrected. To this end, seizures should be rapidly identified and treated. Fever should be aggressively corrected with antipyretics and cooling blankets

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Cited by (18)

Neurologic Evaluation and Management
2012, Oral and Maxillofacial Trauma
Anti-epileptic drugs as possible neuroprotectants in cerebral ischemia
2003, Brain Research Reviews
Many similarities exist between cerebral ischemia and epilepsy regarding brain-damaging and auto-protective mechanisms that are activated following the injurious insult. Therefore, drugs that are effective in minimizing seizure-induced brain damage may also be useful in minimizing ischemic injury. Use of such drugs in stroke victims may have important clinical and financial advantages. Therefore, the authors conducted a Medline search of studies involving the use of anti-epileptic drugs (AEDs) as possible neuroprotectants and summarize the data. Most AEDs have been tested in animal models of focal or global ischemia and some were already tested in humans, for a possible neuroprotective effect. The existing data is rather scant and insufficient but it appears that only drugs that have multiple mechanisms of action seem to have some potential in conferring a degree of neuroprotection that could be clinically applicable to stroke patients. In conclusion, some of the newer AEDs show promise as possible neuroprotectants in the setup of acute ischemic stroke but more studies are needed before clinical trials in humans could be undertaken.
Neurological lesions during extracorporeal circulation: Physiopathology, monitoring and neurological protection
2002, Medicina Intensiva
La incidencia de lesiones neurológicas graves tras la cirugía cardíaca se ha establecido en un 6,1%: un 3,1% de lesiones focales y un 3% de lesiones difusas. Parece que su causa es multifactorial. Se ha conjeturado que ciertos factores preoperatorios, como la presencia de hipertensión, diabetes insulinodependiente, la edad avanzada y la presencia de enfermedad cerebrovascular previa, se asociarían con la aparición de estas lesiones. Sin embargo, también se relaciona con factores intraoperatorios: el tipo de manejo ácido- base, el flujo sistémico durante la circulación extracorpórea (CEC), la presión de perfusión cerebral, el hematócrito durante la CEC, la duración de ésta, el control de las glucemias y la liberación de mediadores inflamatorios.
Aunque se han utilizado diversos métodos de protección neurológica durante la CEC, ninguno ha demostrado evitar completamente la aparición de estas lesiones. Habitualmente se emplea la hipotermia, la prevención del desprendimiento de placas de ateroma con ecocardiografía, la prevención de microembolismos con filtros y la hemodilución. últimamente se han ensayado diversos fármacos con resultados dispares
The incidence of severe neurological injury after cardiac surgery is 6.1%: focal lesions account for 3.1% and diffuse lesions for 3%. The cause of these lesions is multifactorial. It has been speculated that certain preoperative factors such as hypertension, insulin-dependent diabetes, advanced age and previous cardiovascular disease could be associated with the development of neurological injury. However, intraoperative factors also play a role: the type of acid-base management, systemic flow during extracorporeal circulation (ECC), cerebral perfusion pressure, hematocrit during ECC, duration of ECC, glycemia regulation and release of inflammatory mediators.
Although several methods of neurological protection have been used during ECC, none of them completely prevents neurological injury. Usually, the methods employed are hypothermia, prevention of the release of atheroma plaques with echocardiography, prevention of microemboli with filters, and hemodilution. Several drugs have recently been tried with differing results.
Management of head trauma
2002, Chest
Citation Excerpt :
However, as a result of autoregulation, CBF remains relatively constant when CPP is between 40 mm Hg and 140 mm Hg (Fig 4).34 This phenomenon is due to changes in cerebrovascular resistance probably brought about by a local effect of hydrogen ions on cerebral vessels.34 Thus, low flow states leading to hypoxia or hypercapnia result in an acidosis that causes cerebral vasodilation and increased blood flow.
Traumatic brain injury (TBI) is a major cause of disability and death in most Western nations and consumes an estimated $100 billion annually in the United States alone. In the last 2 decades, the management of TBI has evolved dramatically, as a result of a more thorough understanding of the physiologic events leading to secondary neuronal injury as well as advances in the care of critically ill patients. However, it is likely that many patients with TBI are not treated according to current treatment principles. This article presents an overview of the current management of patients with TBI.
Hypothermia as an adjunctive treatment for severe bacterial meningitis
2000, Brain Research
Citation Excerpt :
Current management of brain injury emphasizes the maintenance of adequate physiologic substrate and attenuation of the inflammatory response in an attempt to prevent secondary brain injury. This approach applies the principles of improved cerebral perfusion and oxygen delivery in all patients with techniques to decrease oxygen consumption in the most severely affected [30]. Current recommendations include lowering intracranial pressure (ICP), maintaining an adequate cerebral perfusion pressure and avoiding hyperventilation [43,49].
Brain injury due to bacterial meningitis results in a high mortality rate and significant neurologic sequelae in survivors. The objective of this study was to determine if the application of moderate hypothermia shortly after the administration of antibiotics would attenuate the inflammatory response and increase in intracranial pressure that occurs in meningitis. For this study we used a rabbit model of severe Group B streptococcal meningitis. The first component of this study evaluated the effects of hypothermia on blood–brain barrier function and markers of inflammation in meningitic animals. The second part of the study evaluated the effects of hypothermia on intracranial pressure, cerebral perfusion pressure and brain edema. This study demonstrates that the use of hypothermia preserves CSF/serum glucose ratio, decreases CSF protein and nitric oxide and attenuates myeloperoxidase activity in brain tissue. In the second part of this study we show a decrease in intracranial pressure, an improvement in cerebral perfusion pressure and a decrease in cerebral edema in hypothermic meningitic animals. We conclude that in the treatment of severe bacterial meningitis, the application of moderate hypothermia initiated shortly after antibiotic therapy improves short-term physiologic measures associated with brain injury.
A paradox of cerebral hyperperfusion in the face of cerebral hypotension: The effect of perfusion pressure on cerebral blood flow and metabolism during normothermic cardiopulmonary bypass
1998, Journal of Surgical Research
Background.The purpose of this study was to determine the impact of perfusion pressure on cerebral blood flow (CBF) and metabolism during normothermic cardiopulmonary bypass (CPB) and after weaning.
Materials and methods.Two groups of mongrel dogs were studied (Group A, CPB perfusion at 50 mm Hg,n= 6; and Group B, CPB perfusion at 100 mm Hg,n= 6). All animals underwent 2 h of normothermic bypass at cardiac indexes >2.1 L/min/m²and were weaned from pump, maintained at pressures >75 mm Hg, and followed for an additional 2 h.
Results.In both groups CBF increased over 85% from baseline, in proportion to the hemodilution during the initiation of CPB. Intracranial pressure increased moderately in both groups during CPB, compromising CBF at 1 h in Group A, but not in Group B. The Group A cerebral metabolic rate for oxygen (CMRO₂), however, remained unchanged as the percentage of oxygen extraction increased to compensate for the decreased CBF. During recovery, temperature, mean arterial pressure, and cerebral perfusion pressure were not significantly different between the two groups. However, the CBF, percentage of oxygen extracted, and CMRO₂were significantly lower in Group A.
Conclusions.Normothermic CPB initiated with a crystalloid prime and performed at the lower end of a 50–70 mm Hg perfusion window resulted in a highly significant increase in CBF in order to compensate for hemodilution, while at the same time reduced the perfusion pressure available to supply the increased CBF. Together, these two events create a hemodynamic paradox of hyperperfusion in the face of hypotension. The reduction in CMRO₂in Group A is yet to be explained but seems to remain coupled to CBF and could represent a previously undescribed protective mechanism of hibernating cerebral tissue, similar to the phenomena of ischemic preconditioning in the heart, where cerebral tissue is stimulated to lower metabolism in response to inadequate CBF.

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: The opinions and assertions contained herein are those of the authors and are not to be construed as official or reflecting the views of the Navy Department or the Naval Service at large.

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Critical CareCurrent Concepts in Cerebral Protection

Section snippets

DETERMINANTS OF CEREBRAL METABOLISM AND BLOOD FLOW

MECHANISMS OF BRAIN ISCHEMIA

Improving Cerebral Metabolism and Blood Flow

Critical Care
Current Concepts in Cerebral Protection