Controversies surrounding critical illness-related corticosteroid insufficiency in animals. Burkitt

Question 1

What are the findings of the CORTICUS trial?
What are its limitations?

Answer 1

• hydrocortisone administration lead to faster vasopressor weaning - regardless of ACTH stim test
• hydrocortisone administration did not improve mortality
• hydrocortisone administration was associated with more superinfections

Limitations:
* underpoweder
* less severely ill patient population
* etomidate administration

Question 2

Explain the HPA axis

Answer 2

hypothalamus produces CRH (corticotropin-releasing hormone) –> CRH binds receptors in the anterior pituitary –> ACTH (adrenocorticotropin hormone) release –> stimulates adrenal cortices to produce cortisol –> cortisol causes negative feedback on CRH and ACTH production/release

Question 3

How is most of cortisol carried in the plasma?

Answer 3

CSG - corticosteroid-binding globulin

unbound/free corticosteroid is the biologically active form

Question 4

How does cortisol cross the cell membrane?

Answer 4

diffuses freely

Question 5

What enzyme can up- or downregulate to active form of cortisol?
What is the inactive form of cortisol?

Answer 5

11-beta-hydroxysteroid dehydrogenase (11betaHSD)
cortisone is the inactive form of cortisol

Question 6

List different proposed mechanisms of the pathophysiology of CIRCI

Answer 6

• damage of the hypothalamus/pituitary/adrenal glands - from cytokines, ROS, hemorrhage
• corticosteroid-binding globulin damaged by neutrophil elastase
• 11-beta-hydroxysteroid dehydrogenase stimulation
• inhibition of GR-cortisol binding

Question 7

What is the current recommendation for CIRCI diagnosis in human medicine?

Answer 7

NOTE: NEW CIRCI GUIDELINES RECOMMEND ACTH STIM/CORTISOL LEVELS OVER HEMODYNAMIC/CLINICAL RESPONSE (THIS PAPER IS OLD)
* identified by assessing response to hydrocortisone treatment
* SSC and CIRCI recommendations do not recommend ACTH stim for diagnosis
* CIRCI recommendations do not recommend cortisol measurements to guide tx as there is no established reference range for patients with sepsis
* Marik et al recommends identifying CIRCI with low cortisol, but that cortisol level shouldn’t be used to decide whether to treat with hydrocortisone

Question 8

Why does the american college of critical care medicne recommend against the use of dexamethasone in CIRCI?

Answer 8

• because of its profound HPA axis suppression and subsequent inability to use ACTH stim as a diagnostic tool
• structurally altered from cortisol - may cause more profound immunosuppression and have less mineralocorticoid effects

Question 9

What is the currently recommended hydrocortisone dose for dogs and cats?

Answer 9

1 to 4.3 mg/kg/day
4 equal IV doses or constant rate infusion

4.3 mg/kg is the equivalent to the maximum dose in people of 300 mg/kg