How to diagnose adrenal insufficiency in critical illness?

The concept of ‘relative’ adrenal insufficiency during critical illness remains a highly debated disease entity. Several studies have addressed how to diagnose or treat this condition but have often yielded conflicting results, which further fuelled the controversy. The main reason for the controversy is the fact that the pathophysiology is not completely understood. Recently, new insights in the pathophysiology of the hypothalamic–pituitary–adrenal axis response to critical illness were generated. It was revealed that high circulating levels of cortisol during critical illness are explained more by reduced cortisol breakdown than by elevated cortisol production. Cortisol production rate during critical illness is less than doubled during the day but lower than in healthy subjects during the night. High plasma cortisol concentrations due to reduced breakdown in turn reduce plasma ACTH concentrations via feedback inhibition, which with time may lead to an understimulation and hereby a dysfunction of the adrenal cortex. This could explain the high incidence of adrenal insufficiency in the prolonged phase of critical illness. These novel insights have created a new framework for the diagnosis and treatment of adrenal failure during critical illness that has redirected future research.

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Critical Illness-Related Corticosteroid Insufficiency (Previously Known as Relative Adrenal Insufficiency)

Clinical Endocrinology of Companion Animals ◽

10.1002/9781118997093.ch4 ◽

2014 ◽

pp. 36-42

Author(s):

Linda Martin

Keyword(s):

Critical Illness ◽

Adrenal Insufficiency ◽

Relative Adrenal Insufficiency ◽

Corticosteroid Insufficiency

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Adrenal insufficiency in critical illness Carrie A Sims and Vicente Gracias

Trauma, Critical Care and Surgical Emergencies ◽

10.3109/9781420021134-44 ◽

2016 ◽

pp. 382-385

Keyword(s):

Critical Illness ◽

Adrenal Insufficiency

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Etomidate, Adrenal Insufficiency and Mortality Associated With Severity of Illness: A Meta-Analysis

Journal of Intensive Care Medicine ◽

10.1177/0885066620957596 ◽

2020 ◽

pp. 088506662095759

Author(s):

Stewart G. Albert ◽

Sujata Sitaula

Keyword(s):

Critical Illness ◽

Mortality Rate ◽

Adrenal Insufficiency ◽

Absolute Risk ◽

Meta Analysis ◽

Severity Of Illness ◽

Mortality Rates ◽

Secondary Outcome ◽

Relative Mortality ◽

Cochrane Reviews

Purpose: Etomidate causes adrenal insufficiency. Yet in critically ill patients, it is controversial whether it increases mortality rates above that of comparator anesthetic induction agents. We postulated that etomidate would increase relative mortality rates correspondingly to the severity of illness as defined by SAPS or APACHE scores. Materials and Methods: A literature search was performed on Pub Med, SCOPUS, and Cochrane Reviews for human studies, regardless of language, between 1983 and February 2020. The search strategy used keywords, “etomidate,” “adrenal insufficiency,” “glucocorticoid,” and “intensive care.” Both authors reviewed electronic data search titles, abstracts and extracted data, which were checked by the other reviewer. Primary outcome was 28-day survival. Secondary outcome was adrenal insufficiency. Results: There were 29 trials of etomidate versus comparators in 8584 patients. Etomidate was associated with adrenal insufficiency (risk ratio (rr) = 1·54, 95% CI; 1·42, 1·67, p < 0.001) and increased overall relative mortality rates (rr = 1.09, CI;1.04,1.16, p = 0.001). Meta-regression showed that with etomidate there was a continuous progressive relative risk of mortality associated with increasing severity of illness (predefined in each article by standard critical illness scores). In those patients who had a predicted mortality rate > the median for this analysis (predicted mortality 44%) the relative mortality rate (rr) = 1.20, Ci;1.12,1.29, p < 0.001, the absolute risk difference (rd) = 0.08, CI;0.05,0.11, p < 0.0001 and the number needed to harm (1/rd) was 12.5. In those with a calculated predicted mortality <44% there was no increase in relative mortality rate. Conclusions: Whereas etomidate causes adrenal insufficiency, it was not shown to increase mortality in many analyzed here in ICU settings. However, etomidate associated relative mortality rates increased progressively and correlated with the severity of critical illness scores. Intensivists should anticipate the need for glucocorticoid supplementation after etomidate in those with severe critical illness and in those with acute deterioration of vital signs.

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