1. Kuznar, Wayne


Researchers weigh measuring tissue oxygen, controlling blood glucose.


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Two recent studies examined the management of adults with severe sepsis-an inflammatory response to infection that affects more than 750,000 people in the United States each year. In one study, intensive insulin therapy was used in an effort to mitigate the effects of corticosteroid-associated hyperglycemia and lower the risk of death from septic shock, the most severe form of sepsis. The second study examined two methods to determine tissue oxygen delivery in early goal-directed therapy in patients admitted to the ED with severe sepsis.


Corticosteroid therapy and glucose control in septic shock. Although low-dose corticosteroid therapy has regained favor as a treatment for septic shock, it may cause hyperglycemia, which has led to debate over the optimal means of controlling blood glucose in patients treated with hydrocortisone. To help resolve the controversy, investigators randomized 509 adults with septic shock who were being treated with low-dose hydrocortisone to receive either intensive or conventional insulin therapy. The blood glucose target range in the intensive group was 80 to 110 mg/dL, whereas in the conventional group it was 150 mg/dL or lower. The intensive therapy and control patients were further randomized to receive either hydrocortisone alone or with fludrocortisone.


In-hospital mortality (the primary outcome) was 45.9% in the patients receiving intensive insulin therapy, compared with 42.9% in those assigned to conventional insulin therapy. Similarly, the addition of fludrocortisone had no significant effect on in-hospital mortality. There was no evidence that an interaction between fludrocortisone treatment and insulin therapy lowered the risk of death. And intensive insulin therapy appeared to double the risk of severe hypoglycemia (16.4% in the intensive therapy group, compared with 7.8% in the control group).


An earlier study had found a survival advantage to intensive insulin therapy in surgical ICU patients, but that finding may have been extrapolated prematurely to patients with severe sepsis, said Mary Pat Aust, clinical practice specialist at the American Association of Critical-Care Nurses. "We're finding out that you do want to control the glucose, but perhaps intensive insulin therapy is not the best way," she said, adding that institution-specific outcomes in very specific patient populations need to be examined before the best glucose control strategy can be determined.


Measuring ScvO2 versus lactate levels. In 2008, guidelines from the Surviving Sepsis Campaign recommended the use of a quantitative protocol that "targets predefined physiological or laboratory goals to be achieved within the first several hours" after the identification of sepsis or septic shock. The guidelines suggested using the normalization of ScvO2-a recommendation that came under fire because it was based on one single-center study. Because ScvO2 monitoring requires the use of a specialized central venous catheter as well as specific training, Jones and colleagues sought a more easily measured alternative and in the present study compared the attainment of ScvO2 goals with attaining appropriate serum lactate values. Substituting the serum lactate clearance targets for attaining ScvO2 goals, they theorized, could permit wider use of early goal-directed therapy if the two strategies were associated with comparable outcomes. Researchers compared both strategies in 300 patients with severe sepsis or septic shock.


Attaining serum lactate clearance goals was found to be "noninferior" to targeting ScvO2 measurements, in terms of both the primary outcome, in-hospital mortality (the rate was actually lower in the serum lactate than in the ScvO2 group: 17% versus 23%, respectively), and the secondary outcomes (length of stay and serious complications and adverse events). The authors concluded that their findings "justify the use of lactate clearance instead of continuous ScvO2 monitoring."


Wayne Kuznar


COIITSS Study Investigators. JAMA 2010; 303(4):341-8;


Jones AE, et al. JAMA 2010; 303(8):739-46.