Great study. While disappointing not to have a mortality benefit, the secondary outcomes are of clinical significance and are likely to increase the use of hydrocortisone in our ICU. At the moment we use bolus dosing, which has been shownpreviously to be non-inferior to continuous infusions, but with more hyperglycaemia and less need for additional lines (Hoang H, Wang S, Islam S, Hanna A, Axelrad A, Brathwaite C. Evaluation of hydrocortisone continuous infusion versus intermittent boluses in resolution of septic shock. P T. 2017; 42 (4): 252-255.). We tend to initiate hydrocortisone once noradrenaline infusion rate goes beyond 10mcg/min and we have variation in practice in terms of tapering or stopping hydrocortisone once vasopressor support is off. The timing of hydrocortisone initiation would be an interesting future study to guide practice.
Catecholamines are produced in chromaffin cells in the medulla of the adrenal gland, from tyrosine , a non-essential amino acid derived from food or produced from phenylalanine in the liver. The enzyme tyrosine hydroxylase converts tyrosine to L-DOPA in the first step of catecholamine synthesis. L-DOPA is then converted to dopamine before it can be turned into noradrenaline. In the cytosol , noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT.