Clinical Use of Mild Hypothermia for Brain Protection

Milde, Leslie Newberg

doi:10.1097/00008506-199207000-00012

Cited by 70 publications

(37 citation statements)

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“…It is known that altered neurometabolic dynamics can occur in each of the conditions associated with burst suppression: in general anesthesia, through a reduction in neural activity and subsequent reductions in CMRO (25,36); in hypoxic/ischemic injury, through aberrant reductions in metabolic regulation due to diffuse injury or through direct oxidative stress (6,22); in hypothermia, through direct reductions in metabolic rate (3,35); and in developmental encephalopathy, through neural and metabolic dysfunction (23). Implicating brain metabolism in the neural mechanisms of burst suppression establishes a unifying physiologic connection between the main etiologies of the phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…The parameter J ATP is the production rate of ATP that is known to be directly coupled to the cerebral metabolic rate (32). As a surrogate for the metabolic rate, we directly manipulate J ATP over a range of 30−50% of baseline, consistent with studies of anesthetic and hypothermic effects on cerebral metabolism (35,36). Complete details of the model and simulation parameters are found in SI Methods.…”

Section: Methodsmentioning

confidence: 99%

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A neurophysiological–metabolic model for burst suppression

Ching

Purdon

Vijayan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

259

326

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Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia, hypothermia, and in pathological conditions such as coma and early infantile encephalopathy. We propose a unifying mechanism for burst suppression that accounts for all of these conditions. By constructing a biophysical computational model, we show how the prevailing features of burst suppression may arise through the interaction between neuronal dynamics and brain metabolism. In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression. Consequently, the model makes a number of specific predictions of experimental and clinical relevance.B urst suppression-an electroencephalogram (EEG) pattern in which high voltage activity (burst) and flatline (suppression) periods alternate systematically but quasiperiodically (almost periodic but with variations in inter-and intra-burst duration) (1)-is a state of profound brain inactivation. It is frequently observed in deep general anesthesia (2). It is also observed in a range of pathological conditions including hypothermia (3-5), hypoxic-ischemic trauma/coma (6), and the so-called Ohtahara syndrome (7,8), a type of early infantile encephalopathy. These etiologies indicate that the burst suppression pattern represents a low-order dynamic mechanism that persists in the absence of higher-level brain activity. Indeed, the fact that many different conditions produce similar brain activity suggests that there may be a common pathway to the state of brain inactivation and may indicate fundamental properties of the brain's arousal circuits (2).The basic features of the burst suppression phenomenon have been established through a variety of EEG studies that are reviewed in ref. 9. The two most notable of these features are the spatial homogeneity of bursts and the quasi-periodic nature of the suppression. Later research has been directed at describing the phenomenon in vivo and in the specific context of general anesthesia. In particular, the early work of Steriade et al. (10) helped establish the neural correlates of burst suppression, including the differential participation of cortical and subcortical cell types. More recent studies (11,12) have suggested that burst suppression is associated with enhanced excitability in cortical networks. These studies implicate extracellular calcium as a correlate for the switches between burst and suppression.Despite the findings of these studies, a unifying mechanism for burst suppression-one that explains its prevailing features and also accounts for its range of etiologies-has not been proposed. Indeed, the existing characterizations of burst suppression in pathological situations are highly limited. Computational models offer a means of synthesizing the availabl...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A neurophysiological–metabolic model for burst suppression

Ching

Purdon

Vijayan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

259

326

View full text Add to dashboard Cite

show abstract

“…24 However, maintenance of body temperature at this level may be difficult at times and undesirable in those instances where mild hypothermia may be preferable. 29,30 In summary, this study demonstrates that localized hypothermia in the monitored extremity can influence the assessment of recovery from vecuronium-induced neuromuscular blockade. This has important clinical implications, insofar as the patient's level of neuromuscular blockade is usually monitored in an exposed, accessible arm which may be significantly colder than the rest of the body.…”

Section: Discussionmentioning

confidence: 77%

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade

et al. 1994

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“…Reduced oxygen demand does not fully explain the positive effects of hypothermia and several additive tissue protective effects have been suggested [24]. It has been shown that mild hypothermia can prevent ischemic cells from entering apoptosis through prevention of mitochondrial dysfunction and inhibition of caspase release [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…In an experimental setting, mild hypothermia has a positive effect on contractility, but deep hypothermia has been associated with deterioration in cardiac function [19,20]. The tissue-protective mechanism of action is multi-factorial and partly unknown [20][21][22][23][24][25][26][27]. We recently found that hypothermia reduces ischemia related coronary t-PA release, suggesting a possible role for t-PA as a mechanism for reperfusion injury that may be affected by hypothermia [28].…”

Section: Introductionmentioning

confidence: 99%