Septic shock

Septic shock is a condition in medicine in which sepsis is "associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status."

Vasopressors
Among the choices for pressors, a randomized controlled trial concluded that there was no difference between the biogenic amines norepinephrine (plus dobutamine as needed for cardiac output) versus epinephrine. Similarly, another randomized controlled trial found no difference between vasopressin and norepinephrine.

Corticosteroids
Clinical practice guidelines by American College of Critical Care Medicine conclude "hydrocortisone should be considered in the management strategy of patients with septic shock, particularly those patients who have responded poorly to fluid resuscitation and vasopressor agents."
 * Practice guidelines and meta-analysis

In a meta-analysis that was included with the guidelines found greater shock reversal (at day 7) with hydrocortisone and a (insignficant) trend towards benefit in mortality".

Prior meta-analyses have concluded that steroids are beneficial but these analyses did not include the CORICUS trial published in 2008.

Regarding whether the use of steroids should be confined to patients with relative adrenal insufficiency, the guidelines state "ACTH stimulation test should not be used to identify those patients with septic shock or ARDS who should receive GC". The recommendation is based on the similar impact of steroids on shock reversal at seven days regardless of adrenal status. However, mortality data in the French study by Annane only found benefit in the patients with relative adrenal insufficiency. Although the CORTICUS study by Sprung found no mortality benefit, these patients were not as ill. In a post hoc analysis of the CORTICUS study, the sickest patients ("systolic blood pressure persisting at less than 90 mm Hg within 30 hours") had better outcomes when given corticosteroids. Thus, confining steroids to the sickest patients who also have relative adrenal insufficiency is supported by mortality data.

Corticosteroids, perhaps if combined with a mineralocorticoid, may reduce mortality among selected patients who have relative adrenal insufficiency It is unclear whether the corticosteroids should be combined with mineralocorticoids and whether the medications should be reserved for the sickest patients (those with persistent hypotension).
 * Details of individual trials

Although the largest and most recent randomized controlled trial was negative, its patients were less sick (as evidenced by less stringent inclusion criteria and less mortality in the control group) and mineralcorticoids were not given as a co-treatment. In a post hoc analysis of the CORTICUS study, the sickest patients ("systolic blood pressure persisting at less than 90 mm Hg within 30 hours") had better outcomes when given corticosteroids.

The lack of mineralocorticoid in the new study may not be important. In the new trial, the total hydrocortisone per day in the new trial is 200 mg. This equates to 200/250 or 0.8 mg (800 microgram) fludrocortisone (see relative potency table for corticosteroids). The French study by Annane used 50 microgram daily of fludrocortisone.

Activated protein C
Recombinant human activated protein C, also called drotrecogin alpha, has been shown in a randomized clinical trial to be associated with reduced mortality (Number needed to treat (NNT) of 16) in patients with multi-organ failure If this is given, heparin should probably be continued.

Tissue factor pathway inhibitor
Recombinant human tissue factor (thromboplastin) pathway inhibitor, also called tifacogin, was found not to be effective in a randomized controlled trial.