Monday, May 19, 2008

Monday May 19, 2008
Hydrocortisone in septic shock - controversy continues


Controversy over use of Hydrocortisone in septic shock has been hot particularly after recent publication and criticism of CORTICUS trial. Just few days ago, we posted a concise commentary on this issue from Dr. Jean-Louis Vincent (
here). One very recent study (from Annane group) now looked into relationship between cardiovascular autonomic modulation and adrenal function during sepsis.

Patients and Method: Cardiovascular variability was assessed by spectral analysis of heart rate and diastolic blood pressure signals, which included computation of normalized low (LFnu) and high frequency (HFnu) components.

In study phase 1, the spectral analysis of heart rate and diastolic blood pressure was obtained in five septic shock and six healthy volunteers before and 60 min after a single intravenous bolus of 50 mg of hydrocortisone.

In study phase 2, the spectral analysis of heart rate and diastolic blood pressure was obtained in 47 consecutive patients with septic shock immediately before a 250 μg adrenocarticotropic hormone (ACTH) stimulation test and before initiation of corticosteroids. Spectral components were compared between patients with adrenal insufficiency and those with presumed normal adrenal function. Adrenal insufficiency was defined as a basal cortisol of less than 15 μg/dl or a maximal cortisol increment after 250 μg of ACTH of less than 9 μg/dl.

Study phase 3 focused on 23 consecutive patients with septic shock and adrenal insufficiency. Spectral components were obtained immediately before and at day 3 after initiation of 50 mg every 6 hrs of hydrocortisone and 50 μg daily of fludrocortisone, or their respective placebos in a double blind manner.

Results:
  • As compared to healthy volunteers, patients had decreased LFnu-HR and LFnu-DBP and, after hydrocortisone, they had a greater increase in LFnu-DBP (p = .01)
  • As compared to patients with normal adrenal function, those with adrenal failure had decreased LFnu-HR and LFnu-DBP
  • In patients with adrenal failure, as compared to placebos, hydrocortisone plus fludrocortisone increased significantly LFnu-DBP (p = .02) and low frequency/high volume ratio (p = .009)

Conclusion: In septic shock, the loss in cardiovascular variability is more marked in patients with adrenal insufficiency and is partly restored by exogenous administration of corticosteroids.



Reference: click to get abstract

Hydrocortisone effects on cardiovascular variability in septic shock: A spectral analysis approach - Critical Care Medicine. 36(5):1481-1486, May 2008.