Kinetics and characteristics of an acute phase response following cardiac arrest

Oppert, Michael; Gleiter, Christoph H.; Müller, Christian; Reinicke, Albrecht; Ahsen, Nicolas von; Frei, Ulrich; Eckardt, Kai‐Uwe

doi:10.1007/s001340051086

Cited by 19 publications

(10 citation statements)

References 22 publications

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“…An increase in CRP levels occurred irrespective to the cause of arrest, the estimated time of anoxia, the clinical course or patient's outcome and it was not different in patients with and without infectious complications within the first 2 days since hospital admission [90]. Similar findings were shown in a pediatric study, as CRP levels were elevated in all patients, survivors and nonsurvivors, within the first 24 h following arrest [91].…”

Section: Clinical Data On Inflammatory Biomarkerssupporting

confidence: 81%

Biomarkers as predictors of outcome after cardiac arrest

Scolletta

Donadello

Santonocito

et al. 2012

Expert Review of Clinical Pharmacology

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Cardiac arrest (CA) is a major health and economic problem. Management of patients resuscitated from CA is challenging for clinicians, and the mortality rate of those who achieve return of spontaneous circulation remains high. Hypoxic brain injury, cardiovascular abnormalities and systemic ischemia/reperfusion response characterize the so-called 'postcardiac arrest syndrome', which could lead to multiple organ failure and poor outcome after CA. The magnitude of these disorders differs in individual patients, mainly based on the cause and duration of CA and on the severity of the ischemic episode. Prognostication of outcome after CA is of importance because it could help physicians on triage decisions and readdress the overall management. A number of factors are thought to influence the prognosis of patients after CA, but due to the heterogeneity of CA population and scenarios no single factor has been identified as a reliable predictor of outcome and the timing and optimal approach to prognostication is still controversial. Biomarkers represent a growing area of interest in this field, as they may provide clinicians with early information on the severity of organ dysfunction to make a decision on clinical strategies and prognosticate outcome. In this article, the authors will focus on cardiac, neurological and inflammatory biomarkers as potential predictors of outcome after CA.

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Section: Clinical Data On Inflammatory Biomarkerssupporting

confidence: 81%

Biomarkers as predictors of outcome after cardiac arrest

Scolletta

Donadello

Santonocito

et al. 2012

Expert Review of Clinical Pharmacology

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“…These results are consistent with clinical studies that have described CA as a sepsis-like syndrome. (31, 32) IL-6 a mediator of the hepatic acute phase response and a potent inhibitor of CYPs. (33) Other ischemia models have shown that increased plasma IL-6 after injury is associated with decreased CYP activity.…”

Section: Discussionmentioning

confidence: 99%

Moderate hypothermia prevents cardiac arrest-mediated suppression of drug metabolism and induction of interleukin-6 in rats*

Tortorici

Mu²,

Kochanek³

et al. 2009

Critical Care Medicine

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Objective Therapeutic hypothermia is being clinically employed to reduce neurological deficits after cardiac arrest (CA). Patients receiving hypothermia after CA receive a wide-array of medications. During hypothermia, drug metabolism is markedly reduced. Little, however, is known about the impact of hypothermia on drug metabolism after re-warming. The objective of this study was to examine the effect of CA and hypothermia on the functional regulation of two major drug metabolizing cytochrome P450 (CYP) isoforms. Design Laboratory investigation. Setting University pharmacy school and animal research facility. Subjects Thirty-six male Sprague-Dawley rats. Interventions Hypothermia was induced via surface cooling in a rat CA model and maintained for 3h. Animals were sacrificed at 5 or 24h and liver was analyzed for hepatic activity and mRNA expression of CYP3A2 and CYP2E1. Plasma interleukin-6 (IL-6) concentrations were determined. The effect of IL-6 on PXR mediated transcription of the rat CYP3A2 promoter was evaluated via luciferace reporter in HepG2 cells. Measurements and Main Results At 24h after CA a decrease in CYP3A2 and CYP2E1 activity was observed, 55.7±12.8% and 46.8±29.7% of control, respectively (p<0.01). CA decreased CYP3A2 mRNA(p<0.05), but not CYP2E1 mRNA. Expression of other PXR target enzymes and transporter genes were similarly down-regulated. CA also produced a ∼10-fold increase in plasma IL-6. CA mediated inhibition of CYP3A2 and CYP2E1 was attenuated by hypothermia, as was the increase in IL-6. Furthermore, IL-6 attenuated PXR-mediated transcription of the CYP3A2 promoter. Conclusions CA produces CYP3A2 down-regulation at 24h, potentially via IL-6 effects on PXR-mediated transcription. Also, hypothermia attenuates the CA mediated down-regulation, thereby normalizing drug metabolism after re-warming.

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“…After ROSC, factors affecting survival are recurrence of CPA, persistent hypotension, shock or myocardial dysfunction [11], hyperthermia [30], hypoglycemia [31] or hyperglycemia [32], coma for more than 24 hours, and sepsis with multiorgan failure syndrome [33,34]. Use of therapeutic hypothermia is a relatively new post-arrest intervention.…”

Section: Post-arrest Variablesmentioning

confidence: 99%