SACCM 81: Critical Illness-Related Corticosteroid Insufficiency Flashcards
What is the definition of CIRCI
inadequate cellular corticosteroid activity for the severity of the patient’s disease
What were the results of the “French Study”
in septic shock:
* patients with failed ACTH stim test had improved survival with hydrocortisone and fludrocortisone administration
* patients with adequate ACTH stim test response did not show this improved survival
What were the results of the CORTICUS trial
regardless of ACTH stim test results, patients with septic shock receiving hydrocortisone showed:
* more rapid pressor weaning
* improved SOFA scores
* more superinfections
sutdy was underpowered
What were the results of the APROCCHSS trial?
in septic shock regardless of ACTH stim test:
* hydrocortisone + fludrocortisone improved 90-day all-cause mortality
* improved number of vasopressor-free and organ failure-free days
* no more serious adverse events compared to placebo
What were the results of the ADRENAL trial?
patients with septic shock:
* hydrocortisone did not improve 90-day survival
* hydrocortisone group had more rapid shock reversal
* hydrocortisone group had more adverse events compared with placebo
List the functions of cortisol
- regulation of carbohydrate, lipid, and protein metabolism
- immune-system modulation
- ensures proper catecholamine production and function of adrenergic receptors
- stabilizes cell membranes
What carries cortisol in the circulation
corticosteroid-binding globulin (CBG)
small amount albumin
free cortisol is the biologically active form
How does the ACTH and cortisol cc typically change in CIRCI?
low ACTH
high cortisol
List mechanisms that may impair the HPA axis
- trauma
- hemorrhage
- cytokine influence
List medications that are known to decrease cortisol production
- ketoconazole
- etomidate
- propofol
- opiates
List the main causes for the dissociation between ACTH and cortisol in CIRCI
- stimulation of adrenal cortisol production by cytokines, lipopolysaccharide-bound TLR, endothelin (independent of ACTH)
- decreased CBG –> more free cortisol –> negative feedback on ACTH release
- impaired cortisol metabolism by the kidneys and liver
List mechanisms leading to an increased proportion of free cortisol
- systemic inflammation decreased hepatic synthesis of CBG and albumin
- acidemia, hyperthermia, increased neutrophil activation –> structural CBG change –> less affinity for cortisol
How do you test for CIRCI in people?
- current clinical guidelines (SCCM guideline) recommend either resting cortisol or stim with 250 mcg cosyntropin (human dose!)
- two other large clinical trials showed no relationship between testing and clinical response to hydrocortison - may not be useful
- SSC does not mention testing ACTH stim/cortisol levels but to just treat refractory shock patients
- buttom line - no agreement, unclear
What is the current evidence on identifying CIRCI in dogs and cats?
Dogs:
* Burkitt et al. 2007: stim test in dogs with sepsis using 250 mcg cosyntropin –> dogs with delta cortisol <3 more likely to be hypotensive and decreased survival compared to dogs with cortisol >3
* Martin et al. 2008: dogs with sepsis, trauma, GDV using 5 mcg/kg cosyntropin –> delta cortisol <3 more likely to receive vasopressors
cats:
* Castello et al. 2006: mean delta cortisol in septic cats 2.3 and normal cats 4.6 BUT SD made the values overlap
* case report corticosteroid responsive pressor-refractory hypotensive critically ill cat - baseline cortisol after stim 3.2
Bottom line: cannot make a recommendation at this time
What is the theory behind fludrocortisone not being beneficial when added to hydrocortisone therapy?
hydrocortisone will already occupy all aldosterone receptors
