The HPA axis response to critical illness: New study results with diagnostic and therapeutic implications

Peeters, Bram; Boonen, Eva; Langouche, Lies; Berghe, Greet Van den

doi:10.1016/j.mce.2014.11.012

Cited by 38 publications

(34 citation statements)

References 48 publications

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“…There is a negative feedback loop of cortisol to the pituitary that is dependent on the cortisol concentration [35] . Therefore, reduced ACTH levels in CF children may be a sign of both hyperand hypocortisolaemia associated with the abnormal driving of the hypothalamic-pituitary-adrenal (HPA) axis by repeated lung disease exacerbations and chronic systemic low-grade inflammation [36] .…”

Section: Discussionmentioning

confidence: 99%

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Shmarina

Pukhalsky²,

Avakian³

et al. 2017

Int Arch Allergy Immunol

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Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ₁ concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.

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Section: Discussionmentioning

confidence: 99%

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Shmarina

Pukhalsky²,

Avakian³

et al. 2017

Int Arch Allergy Immunol

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“…However, the adaptive changes to the hypothalamic-pituitary-adrenal (HPA) axis in other critical illnesses, including all-cause septic shock and pediatric ARDS, may be quite different. An ACTH-cortisol “disassociation” has been described in critical illness (37). In such cases, increased cortisol reflected impaired cortisol clearance rather than increased ACTH release (38).…”

Section: Discussionmentioning

confidence: 99%

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome

Yehya

Vogiatzi

Thomas

et al. 2016

The Journal of Pediatrics

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Objective To test the association between random cortisol and severity of illness in a “real-world” application of current guidelines. Study design We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels prior to potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 μg/dL and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Results Of 357 children with ARDS, 155 (15 non-survivors, 10%) had vasopressors initiated with cortisol drawn prior to possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum p < 0.05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. Conclusions In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function.

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“…In this phenomenon, the ACTH concentration falls below the normal control values, whereas plasma cortisol levels remain elevated. 6 Increased cortisol levels were thought to be a result of reduced cortisol breakdown in critical illnesses. 7 Chronic exposure to IL-6, IL-1â and TNFá may result in decreased ACTH and CRH production.…”

Section: Figure-1: Schematic Diagram Of Cellular Responses To Sepsis mentioning

confidence: 99%

Does Low Dose Steroids Confer Benefits in Sepsis and Septic Shock?

Nazim

2017

Birdem Med J

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Over the last 40 years, the use of corticosteroids in sepsis and septic shock has evolved from the initial use of high-dose, short-duration steroid therapy in the 1980s, to the recent recommendation of using low-dose longerduration steroid therapy in refractory septic shock patients. A recent, prospective, open-label, randomized, controlled pilot trial of patients in four adult intensive care units in London-teaching hospitals showed that hydrocortisone decreased vasopressin requirements, reduced the duration and reduced the required dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. The optimal dosing of hydrocortisone, about 300 mg/day, was agreed uniformly. As this dose also provides sufficient mineralocorticoid effects, the additional use of mineralocorticoid is not needed. Despite the fact that severely ill septic shock patients are given treatment, according to the current guidelines, the survival benefit is unproven. The benefits of steroids on less severely ill septic patients are still questionable. More research is highly recommended to successfully identify the benefits of steroids in septic shock.Birdem Med J 2017; 7(1): 48-59

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The HPA axis response to critical illness: New study results with diagnostic and therapeutic implications

Cited by 38 publications

References 48 publications

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome

Does Low Dose Steroids Confer Benefits in Sepsis and Septic Shock?

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