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Steroids and Insulin for Patients with Severe Sepsis: Back to the Drawing Board

Neither of these interventions benefited patients with severe sepsis or septic shock.

Both corticosteroids and intensive insulin therapy have been advocated for use in critically ill patients, largely on the basis of older studies (e.g., JW Aug 30 2002, JW Nov 16 2001). But, results of clinical trials that were published in 2008 have cast doubt on the efficacy of these interventions for patients with severe sepsis or septic shock.

In the CORTICUS trial, about 500 patients with septic shock were randomized to receive physiologic doses of hydrocortisone (50 mg intravenously every 6 hours for 5 days, followed by tapering doses) or placebo for 11 days. No significant differences were found in 28-day mortality between the steroid and placebo groups among cosyntropin nonresponders (39% and 36%) or among cosyntropin responders (29% in both groups). Blood pressure improved more quickly with hydrocortisone than with placebo, but hydrocortisone recipients were more likely to develop superinfections (JW Jan 9 2008).

In the VISEP trial, investigators randomized 537 patients with severe sepsis to intensive insulin therapy (mean blood glucose level, 112 mg/dL) or conventional therapy (mean blood glucose level, 151 mg/dL). At 28 days, no significant differences were found in mortality between the two groups. The rate of severe hypoglycemia (blood glucose level, <40 mg/dL) was significantly higher in the intensive-therapy group (17% vs. 4%). The researchers also compared colloid (10% pentastarch) and crystalloid therapy (Ringer’s lactate). Colloid therapy was associated with higher rates of acute renal failure than was crystalloid therapy (JW Jan 24 2008).

The decision to administer corticosteroids to a patient in septic shock typically has been guided by response to adrenocorticotropic hormone (ACTH; e.g., cosyntropin) testing. However, the CORTICUS results suggest that hydrocortisone cannot be recommended as general adjuvant therapy in patients with septic shock, regardless of their responses to ACTH testing. Given previous data, a limited role for steroids might remain; however, steroids seem to be effective only very early in the course of septic shock in patients who do not respond to fluid resuscitation and vasopressor therapy (a weak recommendation for such intervention was made in recent guidelines; JW Infect Dis Feb 6 2008). Such decisions should be made on clinical grounds and not on the basis of cosyntropin testing. Tight glycemic control and pentastarch also failed to produce benefits in patients with severe sepsis, and data reveal that these treatments actually can be harmful and contribute to higher short-term morbidity.

— Neil H. Winawer, MD

Published in Journal Watch General Medicine December 29, 2008

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