Chapter 72 - CIRCI

Question 1

why is relative adrenal insufficiency a possible misnomer?

Answer 1

some patients have adequate cortisol production but impaired cellular responses

Question 2

Findings of the CORTICUS study?

Answer 2

499 human septic shock patients, more rapid shock reversal in patients treated with hydrocortisone regardless of ACTH stim results. no survival difference between treatment groups. steroid group experienced more superinfection.

Question 3

Criticisms of the CORTICUS study?

Answer 3

possible selection bias (clinicians reluctant to enrol septic shock patients to ensure they received steroids), under-enrolled - underpowered to detect a difference, differences in illness severity, timing of subject enrollment, some patients received etomidate, hydrocortisone treatment regimen

Question 4

Findings of the French study?

Answer 4

300 people with septic shock, people with a blunted response to corticotropin treated with 200mg/d hydrocortisone and 50mcg/d fludrocortisone had improved survival, those with an adequate response to corticotropin did not benefit from steroids

Question 5

Criticisms of the French study?

Answer 5

differences in illness severity, timing of subject enrolment, percent of subjects receiving etomidate, hydrocortisone treatment regimen

Question 6

describe the HPA axis

Answer 6

when serum cortisol concentration drops, negative feedback stimulates the hypothalamus to produce corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH), which stimulates the adrenals to produce cortisol. Rising cortisol levels inhibits release of more CRH and ACTH

Question 7

how is cortisol transported and how does it exert its effect in cells?

Answer 7

most is bound to corticosteroid binding globulin (CBG), unbound or free cortisol is biologically active and can enter target cells and bind to the glucocorticoid receptor in the cytoplasm. the GR cortisol complex translocates into the nucleus where it affects gene transcription and ultimately cell function

Question 8

pathophysiology of CIRCI?

Answer 8

unknown - likely a combination of altered hypothalamic, pituitary, adrenal, hormonal, enzymatic and receptor function

Question 9

how does systemic inflammation affect the levels of free cortisol?

Answer 9

decreases cortisol binding globulin, increasing the percentage of free cortisol that is biologically active

Question 10

how does systemic inflammation affect the glucocorticoid receptor?

Answer 10

decreases tissue reactivity at the glucocorticoid receptor

Question 11

list two medications that can impair adrenal synthesis of cortisol

Answer 11

etomidate, ketoconazole

Question 12

most common clinical manifestation of CIRCI in humans with septic shock?

Answer 12

pressor-resistant hypotension

Question 13

what was the correlation between presence of CIRCI and outcome in dogs with septic shock in one study?

Answer 13

associated with non-survival

Question 14

what do the 2013 surviving sepsis campaign guidelines for identification and treatment of CIRCI?

Answer 14

dont rely on ACTH stim testing to identify which patients to treat, treat any pressor-resistant septic shock patient with low-dose hydrocortisone (200mg/adult/day as a CRI) and monitor for decreased pressor requirements

Question 15

in a study of septic dogs undergoing ACTH stim testing, what cut-off change in cortisol was significantly associated with hypotension and decreased survival?

Answer 15

3mcg/dL

Question 16

in studies of septic cats undergoing ACTH stim testing, what cut-off change in cortisol was significantly associated with hypotension and decreased survival?

Answer 16

no cut-off proposed, significant overlap between CIRCI and non-CIRCI, though CIRCI cats had significantly lower results overall

Question 17

suggested treatment regimen for fluid-loaded, pressor-refractory septic shock patients

Answer 17

2.5-3mcg/kg/d hydrocortisone CRI after standard ACTH stim test, continue only if showing cardiovascular improvement with 24 hours of starting hydrocortisone

Question 18

prognosis for human patients with CIRCI?

Answer 18

worse than those without, may have the same prognosis with hydrocortisone therapy

Question 19

prognosis for return of normal HPA axis function following illness?

Answer 19

good

Question 20

in dogs and cats with septic shock, hypotension resistant to fluid loading despite moderate pressor dose, on hydrocortisone for 24h, what action should be taken if ACTH stim test delta cortisol >3?

Answer 20

stop corticosteroids (based on guidelines from the French study)