Hydrocortisone treatment in septic shock promotes shock reversal and reduces mortality. We hypothesised the doses that used (200300 mg/2 h) would result in plasma cortisol levels sufficient to saturate the 11 beta-hydroxysteroid dehydrogenase 2 enzyme (11 beta-HSD 2) with cortisol inactivation overload. Consequently cortisol would access the mineralocorticoid receptor producing mineralocorticoid effects. Hypertensive metabolic alkalotic effects would tend to counteract the prevailing hypotension and metabolic acidosis.
An index of 11 beta-HSD 2 enzyme activity can be obtained from the ratio of urinary cortisol to cortisone metabolites, being raised when saturated.
We studied 10 patients (mean age 68.6 years, range 1786) with septic shock who received hydrocortisone 200 mg/24 h. Plasma cortisol, urinary tetrahydrocortisol (THF), 5-alpha tetrahydrocortisol (5-alphaTHF) and tetrahydrocortisone (THE) were measured pre and post hydrocortisone infusion.
Results: Plasma cortisol 899.6±843.8 nmol/l (pre), 2922.7±2227.4 nmol/l (post). Urinary THF 5662.9±4815.7 μg/l (pre), 8922.1±7680.1 μg/l (post). Controls 853±358.5 μg/l. THE 2470.1±2107.7 μg/l (pre), 3859.2±4183.6 μg/l (post). Controls 2539±1033 μg/l. THF+5-alpha THF/ THE 4.6±3.1 (pre), 4.5±2.7 (post). Controls 0.8±0.21.
The results confirm that the hydrocortisone dose used resulted in saturation of 11 beta-HSD 2. However, they also suggest the enzyme was saturated prior to hydrocortisone treatment. In both situations mineralocorticoid effects that possibly contribute to shock reversal would be expected. The pre treatment situation could be regarded as a shock induced homeostatic mechanism and the post treatment as an exaggeration of this.