CIRCI Flashcards
Critically ill human patients with poor hypothalamic-pituitary-adrenal (HPA) axis function have decreased:
Low dosages of hydrocortisone improves:
The best method for diagnosing CIRCI is:
CIRCI likely occurs in a subpopulation of critically ill dogs and cats.
Appropriate methods for the diagnosis and management of CIRCI in dogs and cats are:
survival compared w those w normal HPA axis function
pressor responsiveness and may improve survival in human patients with pressor-resistant septic shock
unknown
unknown
CIRCI best decribed as:
improved pressor responsiveness and more rapid pressor weaning seen in some human patients with septic shock who are treated with low doses of hydrocortisone (usually 200 mg/day/adult)
why is relative adrenal insufficiency less accurate than CIRCI
rather than inadequate production of corticol - CIRCI patients appear to have:
studies suggest that some critically ill people benefit from corticosteroid therapy even if they are not adrenally “insufficient” based on plasma hormone tests (AcTH reveals normal levels)
impaired cellular response to cortisol
SSG recommends:
low-dose hydrocortisone in septic shock patients who remain hypotensive despite pressor therapy
even if still don’t fully understand the pathophysiology of CIRCI or how to identify patients with it
Once in circulation, most cortisol is bound to:
remaining “free cortisol” is:
free cortisol enters target cells and binds the glucocorticoid receptor (GR) in the cytoplasm
___ complex translocates into the nucleus, where it affects ___ and ultimately ____
corticosteroid-binding globulin (CBG)
biologically active cortisol
GR-cortisol complex translocates into the nucleus, where it affects gene transcription and ultimately cell function
underlying pathophysiology of CIRCI is unknown and is
likely a complex combination of:
altered hypothalamic pituitary adrenal hormonal enzymatic receptor function impaired cellular response to cortisol
potential causes:
systemic inflammation causes decreased:
Trauma, infarction, medications (e.g., etomidate or ketoconazole), hemorrhage from coagulopathy, or cytokines can impair adrenal synthesis of cortisol
CBG concentration and causes dissociation of cortisol from CBG, increasing % circulating cortisol that is biologically active
Intracellular enzymes and the GC Recep are also affected by cytokines = nonlinear relationship between plasma cortisol and cortisol’s tissue activity
a patient could appear corticosteroid sufficient with standard plasma tests and still have inadequate:
inadequate tissue cortisol activity because of cytokines’ effects on the GC Receptors
most common clinical abnormality associated with CIRCI in humans with septic shock is:
critically ill dogs with poor response to exogenous ACTH appear more likely to be:
pressor-resistant hypotension
to be hypotensive than those with more robust response
One study in septic dogs suggests that those with CIRCI are more likely to:
die than those with normal HPA function
At this time, the standard 250 mcg ACTH stimulation test is the method recommended to diagnose HPA axis abnormality in critically ill humans, but it fails to identify patients whose corticosteroid insufficiency stems from
tissue cortisol activity problems
CORTICUS is to date the largest published
investigation regarding the use of hydrocortisone in the treatment of septic shock found:
more rapid shock reversal in patients treated with hydrocortisone than in those treated with placebo
regardless of ACTH stimulation test results
no survival difference
steroid-treated group experienced more episodes of superinfection
SSG (2013):
The current recommendation in humans is to treat any:
suggest not using ACTH stimulation testing to identify which patients should be treated with hydrocortisone
pressor-resistant septic shock patient w low-dose hydrocortisone and monitor for decreased pressor
requirements
if improvement is seen, the implication seems
to be that the patient has CIRCI, regardless of plasma hormone concentrations
Burkitt JAVIM 2007 Relative adrenal insufficiency in sepsis:
Martin (Fletcher) et al, JAVMA 2008 HPA critically ill:
Peyton, Burkitt 2009 JVECC CIRCI in critically ill
- determine whether CIRCI occurs in dogs with sepsis -used standard 1-hour 250-mcg ACTH stim
- dogs with change (delta-) cortisol 3 mcg/dl or less were significantly more likely to be hypotensive and had significantly decreased survival compared with dogs with delta-cortisol greater than 3 mcg/dl
- *** decreased survival
-investigated HPA axis function in dogs with sepsis, severe trauma, or GDV
-1-hour ACTH stimulation tests using 5 mcg/kg cosyntropin and found that dogs with delta-
cortisol 3 mcg/dl or less were significantly more likely to receive vasopressors than dogs with delta-cortisol greater than 3 mcg/dl
**increased pressor requirement
Dx:
For all species, it is unclear whether plasma hormone concentrations or HPA axis testing are related to the improved pressor responsiveness seen when some individuals are treated with hydrocortisone.
It is possible, for example, that altered HPA axis function is a marker of disease severity and that the improved blood pressure seen with corticosteroid therapy is unrelated to HPA axis function.
For now, CIRCI seems to be a diagnosis made by:
gauging response to therapy
Tx:
currently two consensus statements available regarding CIRCI in humans both recommend:
against the use of hydrocortisone in septic shock patients unless they are poorly responsive to fluid therapy and vasopressor
both statements recommend hydrocortisone use in this patient set regardless of basal or stimulated plasma hormone concentrations
Marik et al recommends (dose):
2013 Surviving Sepsis Campaign
guidelines recommend:
50 mg/adult human every 6 hours, total 200 mg/adult/d
or as a dose of 100 mg followed by 10 mg/hr CRI
(240 mg/adult human/day)
200 mg hydrocortisone/adult human/day CRI
Both groups recommend tapering the hydrocortisone over a few days rather than stopping abruptly
Veterinary Medicine:
At the author’s hospital, dogs and cats with fluid-loaded, pressor-refractory septic shock are treated at the clinician’s discretion with:
what is “response to therapy”:
if yes response, continue for:
- 1-hour ACTH stimulation test
- 2.5 to 3 mg/kg/day of hydrocortisone CRI
- continue steroid therapy only IF patient shows significant improvement in CV status/BP within 24 hours of starting the drug
< pressor by 50% in 24 hrs
cortisol came back <3mcg/dl
5 days, taper over 2-3 days
