Septic shock corticosteroids

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... 

Corticosteroids were shown in a metaanalysis to improve hemodynamics and survival and reduce the duration of vasopressor support in septic shock. 

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. 

Prompt intensive treatment with corticosteroids may be lifesaving when an excessive inflammatory reaction has resulted in septic shock. A massive infusion of corticosteroids can restore cardiac output and reverse hypotension by sensitizing the response of adrenoceptors in the heart and blood vessels to the stimulating action of catecholamines. This protective role of steroids may be due to a direct effect on vascular smooth muscle. The combination of glucocorticoids and dopamine therapy preserves renal blood flow during shock. 

Sprung CL, Caralis PV, Marcial EH, Pierce M, Gelbard MA, Long WM, Duncan RC, Tendler MD, Karpf M. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med 1984 11 (18) 1137—43. 

GRAPEFRUIT JUICE CORTICOSTEROIDS t adrenal suppressive effects of corticosteroids, which may t risk of infections and produce an inadequate response to stress scenarios (e.g. septic shock). However, studies have shown only moderate t plasma concentrations of methylprednisolone and minimal or no changes with prednisolone Due to inhibition of metabolism of corticosteroids Monitor cortisol levels and warn patients to report symptoms such as fever and sore throat... 

The use of corticosteroids in the treatment of septic shock has been a topic of controversy for many years. A meta-analysis of early studies of steroids in sepsis demonstrated a lack of benefit and potential harm in sepsis and septic shock. There is a renewed interest in corticosteroid use because of the increased awareness of adrenocortical insufficiency in critically ill patients with septic shock. Relative adrenal insufficiency has been defined as a poor adrenal response [<250 nmol/L (9 mcg/dL) irrespective of the initial serum cortisol level] to a dose of synthetic adrenocorticotropic hormone (ACTH), indicating a low fnnctional reserve of the adrenal cortex. Although absolute insufficiency is rare, relative adrenocortical insufficiency in the presence of normal or high cortisol concentrations at baseline is present in 30% to 50% of patients with septic shock and is associated with a poor outcome. ... 

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. ... 

Given the current data, corticosteroids may be administered to patients with septic shock on high doses of vasopressors for prolonged periods of time if (1) reversible causes of hypotension are eliminated, (2) relative/absolute corticosteroid deficiency is determined with corticotropin stimulation testing, and (3) corticosteroids are used for at least 5 to 7 days and then are reduced progressively. ... 

Recent data with moderate doses of corticosteroids (200 to 300 mg/day) infused over 5 to 7 days may reverse septic shock and dependency on vasopressor agents, particularly in patients with relative adrenal insufficiency. Data are still needed regarding optimal dosing and the effect on outcomes such as mortality. Initial uncontrolled studies with vasopressin suggest a potential role in the management of vasopressor-refractory septic shock patients, although further data are needed. 

Spijkstra JJ, Girbes AR. The continuing story of corticosteroids in the treatment of septic shock. Intensive Care Med 2000 26 496-500. 

Burry ED, Wax RS. Role of corticosteroids in septic shock. Ann Phar-... 

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. 

Advances in medical practice, including the aggressive use of catheters and other invasive equipment, the implantation of prosthetic devices, the administration of chemotherapy to cancer patients, and the administration of immunosuppressive agents and corticosteroids to patients with organ transplants, have increased the risk of sepsis, septic syndrome, and septic shock. 

Studies conducted in our laboratories examined the effects of such conjoint therapy with antibiotics on eicosanoid levels and survival in septic shock. In the rat faecal peritonitis model, improved survival time was observed with early treatment with steroids. However, this protection appears to be independent of inhibition of arachidonic acid metabolism. Corticosteroid pretreatment effected no more than a 30 and 40% inhibition of plasma levels of iTxB2 and i6-keto-PGFi3( respectively, compared with 100% inhibition with the cyclo-oxygenase inhibitors. Conjoint steroid and NSAID treatment improved survival time compared with each drug employed individually. The combination of steroid, NSAID and gentamicin produced the most significant effect on survival. 

Antibiotic therapy is generally only indicated for cases of secondary bacterial infection following primary viral pneumonia, especially in the case of late-onset pneumonia. Corticosteroids should not be used routinely, but may be considered for septic shock with demonstrable adrenal insufficiency. 

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