Hydrocortisone septic shock

The recent CORTICUS trial (hydrocortisone vs placebo) does not support the routine use of corticosteroids in the management of septic shock. No difference in 28-d mortality was observed between groups, regardless of baseline relative adrenal insufficiency. Duration of shock was shorter in the hydrocortisone group however, an increased incidence of hyperglycemia, sepsis, and recurrent septic shock was observed. This section reflects the 2004 consensus guidelines... 

Hydrocortisone 50 mg IV q6h or 100 mg IV q8h for 7 d in patients with septic shock requiring vasopressor support if relative adrenal insufficiency present... 

Hydrocortisone for septic shock patients refractory to resuscitation and vasopressors, with adrenal insufficiency. 

Stress-induced adrenal insufficiency complicates 9% to 24% of septic patients and is associated with increased mortality. Adrenal-insuffident patients are identified by a adrenocorticotropic hormone (ACTH) stimulation test. Patients are given 250 meg ACTH and a cortisol level is checked within 30 to 60 minutes. Responders are defined as a greater than 9-mcg/dL increase in cortisol and non-responders as a less than 9-mcg/dL increase in cortisol. Septic shock patients refractory to resuscitation and vasopressors, and with adrenal insufifidency (non-responders to the ACTH test) should be administered intravenous hydrocortisone 200 to 300 mg per day in three divided doses for 7 days.24,44... 

Corticosteroids can be initiated in septic shock when adrenal insufficiency is present or when weaning of vasopressor therapy proves futile. A daily dose equivalent to 200 to 300 mg hydrocortisone should be continued for 7 days. Adverse events are few because of the short duration of therapy. 

One of most compelling lines of evidence supporting the hypothesis that lower cortisol levels may be an important pathway to the development of PTSD symptoms involves results of studies by Schelling et al. (2001) who administered stress doses of hydrocortisone during septic shock and evaluated the... 

Keh, D., et al. (2003) Immunologic and hemodynamic effects of low-dose hydrocortisone in septic shock a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 167, 512-20. 

The value of intravenous hydrocortisone 200-300 mg/day for 7 days in three or four C divided doses in patients with septic shock is not clear. 

Since the two meta-analyses in 1995, five prospective, randomized, controlled trials of low-dose corticosteroids in vasopressor-dependent septic shock patients (n = 505) have been published. " These smdies used moderate physiologic doses (200 to 300 mg/day) of hydrocortisone. A meta-analysis of these studies showed that steroid therapy was associated with an overall improvement in survival rate (odds ratio [OR] 1.52, 95% confidence interval [Cl] 1.03-2.27 p =. 036) and shock reversal (OR 4.79, 95% Cl 2.07-11.11 p =. 001). These effects were beneficial in both responders and nonresponders to corticotrophin stimulation testing (p =. 63 and p =. 75, respectively). These smdies also showed that low-dose corticosteroid administration improves hemodynamics and reduces the duration of vasopressor support. " All these studies differ from earlier smdies in that steroids were admimstered later in septic shock (23 hours versus less than 2 hours p =. 02). In these studies, steroids were administered longer (6 days versus 1 day p =. 004), doses were tapered, lower doses were used (hydrocortisone eqmvalents 1209 mg versus 23,975 mg p =. 01), aU patients received high doses of catecholamine vasopressors, and control groups had higher mortality rates (mean 57% versus 34% p =. 03). Since only one of the five studies showed a mortality benefit of low-dose steroids in septic shock, further research is required to confirm this finding. ... 

Briegel J, Eorst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock A prospective, randomized, double-blind, single-center study. Crit Care Med 1999 27 723-732. 

Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002 288 862-871. 

Bellissant E, Annane D. Effect of hydrocortisone on phenylephrine Mean arterial pressure dose-response relationship in septic shock. Clin Pharmacol Ther 2000 68 293-303. 

The corticosteroids have been the subject of much controversy in the management of septic patients. Corticosteroids suppress the activation of polymorphonuclear leukocytes, complement activation, release of TNF, and activation of the coagulation system involved in the cascades of sepsis. A recent study demonstrated a decrease in mortality (absolute reduction of 10%) with lower doses of hydrocortisone and fludrocortisone in patients with adrenal insufficiency requiring high-dose or increasing vasopressor therapy within the first 8 hours of septic shock. There was no benefit for those patients without adrenal insufficiency. In summary, routine use of corticosteroids in patients with sepsis or septic shock is not recommended until further study. 

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