Critical care medicine
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Critical care medicine · Apr 2012
Rewarming after hypothermia after cardiac arrest shifts the inflammatory balance.
The aim of this study was to simultaneously analyze the key components of the cerebral and systemic inflammatory response over time in cardiac arrest patients during mild therapeutic hypothermia and rewarming. ⋯ Complement activation occurs during rewarming from mild therapeutic hypothermia after cardiac arrest. Interleukin-6 increased already from 12 to 24 hrs, concomitantly with a significant increase in the temperature seen during this period of mild therapeutic hypothermia. The optimal rate of rewarming is unknown. Additional clinical studies are needed to determine the optimal rewarming rate and strategy.
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Critical care medicine · Apr 2012
Combining xenon and mild therapeutic hypothermia preserves neurological function after prolonged cardiac arrest in pigs.
Despite the introduction of mild therapeutic hypothermia into postcardiac arrest care, cerebral and myocardial injuries represent the limiting factors for survival after cardiac arrest. Administering xenon may confer an additional neuroprotective effect after successful cardiopulmonary resuscitation due to its ability to stabilize cellular calcium homeostasis via N-methyl-D-aspartate-receptor antagonism. ⋯ These results demonstrate that even a short exposure to xenon during induction of mild therapeutic hypothermia results in significant improvements in functional recovery and ameliorated myocardial dysfunction.
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Critical care medicine · Apr 2012
Mild hypothermia decreases fentanyl and midazolam steady-state clearance in a rat model of cardiac arrest.
Therapeutic hypothermia is widely employed for neuroprotection after cardiac arrest. However, concern regarding elevated drug concentrations during hypothermia and increased adverse drug reaction risk complicates concurrent pharmacotherapy. Many commonly used medications in critically ill patients rely on the cytochrome P450 3A isoform for their elimination. Therefore, our study objectives were to determine the effect of mild hypothermia on the in vivo pharmacokinetics of fentanyl and midazolam, two clinically relevant cytochrome P450 3A substrates, after cardiac arrest and to investigate the mechanisms of these alterations. ⋯ Mild hypothermia reduces the systemic clearances of fentanyl and midazolam in rats after cardiac arrest through alterations in cytochrome P450 3a2 metabolic capacity rather than enzyme affinity as observed with other cytochrome P450s. Contrasting effects on blood and brain levels further complicates drug dosing. Consideration of the impact of hypothermia on medications whose clearance is dependent on P450 3A metabolism is warranted.
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Critical care medicine · Apr 2012
Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon.
Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses. ⋯ Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.