Hypercortisolism in septic shock is not suppressible by dexamethasone infusion

Perrot, D.; Bonneton, A.; Déchaud, H.; Motin, J; Pugeat, Michel

doi:10.1097/00003246-199303000-00018

Cited by 65 publications

(39 citation statements)

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“…In addition, levels of cortisol-binding protein decrease rapid- ly, 13,31 leading to an increase in the circulating plasma levels of free cortisol, which is the active component of the system. 35 During acute illness, the negative feedback of cortisol on the release of corticotropin-releasing hormone and corticotrophin is depressed, 13,33,36 and this is important to keep a sustained activation of the hypothalamicpituitary-adrenal axis. Finally, cytokines increase the affinity of cortisol to glucocorticoid receptors.…”

Section: Discussionmentioning

confidence: 99%

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

et al. 2006

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Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P ‫؍‬ .08). Resolution of septic shock (96% vs. 58%, P ‫؍‬ .001), survival in the intensive care unit (68% vs. 38%, P ‫؍‬ .03), and hospital survival (64% vs. 32%, P ‫؍‬ .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion, relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate. (HEPATOLOGY 2006;44:1288-1295 B acterial infections are a frequent complication and an important cause of death in patients with advanced cirrhosis. 1-3 The mortality rate for patients admitted to the hospital with severe bacterial infections but without septic shock is approximately 30%, 4-6 although it may decrease to 10% if circulatory support with intravenous albumin is given at infection diagnosis. 7 The development of a complex syndrome characterized by acute deterioration of circulatory, hepatic, and renal function and hepatic encephalopathy is the main cause of death in these patients. 6,7 Prognosis of patients with cirrhosis admitted with septic shock is even worse. Hospital mortality in these patients ranges between 60% and 100%, 8,9 which is higher than that reported in the general population of patients with septic shock (25%-70%). [10][11][12] In our experience, survival of patients with cirrhosis in septic shock has not improved greatly during the past decades despite important advances in antibiotic treatment and general supportive measures.During the last few years, several studies have shown that septic shock is frequently associated with relative adrenal insufficiency, a condition characterized by an inadequate production of cortisol with respect to the peripheral demands. [11][12][13][14][15][16][17][18] It also has been reported that patients with septic shock and relative adrenal insufficiency sho...

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Section: Discussionmentioning

confidence: 99%

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

et al. 2006

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“…In the first case, well-established doses of glucocorticoids exert their inhibitory effect on cortisol levels, but in the latter, they could fail in doing so. In a case-study on patients with hypercortisolism evoked by the state of circulatory (septic or non-septic) shock, intravenous infusion of dexamethasone failed to suppress cortisol concentration elevated due to circulatory shock, in contrast with the control group of healthy subjects, where dexamethasone infusion exerted its common behavior -the complete suppression of cortisol [58]. Presumably, the circulatory shock induced alteration of the HPA axis dynamics, shifting the axis to a novel non-basal dynamical state, so when the therapy with dexamethasone had been administered, the axis was unable to exert the same effect (suppression) as it does in basal conditions.…”

Section: Significance Of the Initial State Of The Hpa Axismentioning

confidence: 97%

Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress

et al. 2011

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OSCILLATORY dynamics appears to be essential for self-organization and self-regulation in living systems. Oscillations with different periodicity, from millisecond to annual range, are implemented at all levels of organization of living organisms, from the molecular to the biosphere level, occurring in processes as diverse as gene transcription in the cell nuclei to seasonal migrations of species between ecosystems [1, 2]. The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system involved in maintaining homeostasis in mammalian organisms under physiological conditions and stress [3][4][5], is no exception to that rule. Cortisol, the HPA axis principal hormone in humans, exhibits complex dynamic behavior with two char- Abstract. Detailed dynamics of the hypothalamic-pituitary-adrenal (HPA) axis is complex, depending on the individual metabolic load of an organism, its current status (healthy/ill, circadian phase (day/night), ultradian phase) and environmental impact. Therefore, it is difficult to compare the HPA axis activity between different individuals or draw unequivocal conclusions about the overall status of the HPA axis in an individual using single time-point measurements of cortisol levels. The aim of this study is to identify parameters that enable us to compare different dynamic states of the HPA axis and use them to investigate self-regulation mechanisms in the HPA axis under acute and chronic stress. In this regard, a fourdimensional stoichiometric model of the HPA axis was used. Acute stress was modeled by inducing an abrupt change in cortisol level during the course of numerical integration, whereas chronic stress was modeled by changing the mean stationary state concentrations of CRH. Effects of acute stress intensity, duration and time of onset with respect to the ultradian amplitude, ultradian phase and the circadian phase of the perturbed oscillation were studied in detail. Bifurcation analysis was used to predict the response of the HPA axis to chronic stress. Model predictions were compared with experimental findings reported in the literature and relevance for pharmacotherapy with glucocorticoids was discussed.Key words: HPA axis, Stress, Cortisol, Predictive modeling, Circadian and ultradian rhythmicity acteristic frequencies: ultradian oscillations, with a period of 20-120 min [4-6] superimposed on circadian oscillations, with a period of about 24 h. The importance of circadian rhythms for adequate functioning of the HPA axis has been recognized for years [7, 8]; in addition, new experimental [9-15] and theoretical [16][17][18][19][20][21][22][23][24][25][26][27] results offer enough evidence to support the indispensable roles of ultradian oscillatory dynamics of HPA hormones levels for normal physiology. Since ultradian and circadian oscillations operate on different time scales, their effects are manifested in different biological realms. However, being coupled they seem to contribute synergistically to better integration and adaptation of an organism to the unpredictable ...

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“…Furthermore, the degree of cortisolaemia frequently correlates with severity of illness and mortality rate [193,194] and is associated with an altered response of the HPA axis to suppression by dexamethasone and stimulation by corticotrophin-releasing hormone (CRH) and ACTH [194]. Cortisol elevation is achieved by several mechanisms including: 1) activation of the HPA axis; 2) GC resistance resulting from alterations in GCR binding; 3) failure of pituitary and hypothalamus glucocorticoid negative feedback; 4) decreased binding to CBG [195][196][197]; and 5) decreased cortisol extraction from the blood [192,193].…”

Section: Relationship Between Exaggerated Host Defence Response and Ementioning

confidence: 99%

The role of the host defence response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment

Gu¹

1996

Eur Respir J

114

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T Th he e r ro ol le e o of f t th he e h ho os st t d de ef fe en nc ce e r re es sp po on ns se e i in n t th he e p pr ro og gr re es ss si io on n a an nd d o ou ut tc co om me e o of f A AR RD DS S: : p pa at th ho op ph hy ys si io ol lo og gi ic ca al l c co or rr re el la at ti io on ns s a an nd d r re es sp po on ns se e t to o g gl lu uc co oc co or rt ti ic co oi id d t tr re ea at tm me en nt t

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Hypercortisolism in septic shock is not suppressible by dexamethasone infusion

Cited by 65 publications

References 0 publications

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Predictive modeling of the hypothalamic-pituitary-adrenal (HPA) axis response to acute and chronic stress

The role of the host defence response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment

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