Synopsis: Seventeen randomized controlled trials and three quasi-randomized controlled trials of 3,384 patients were selected for statistical analysis. Overall, corticosteroids did not improve 28-day, all-cause mortality in severe sepsis and septic shock. There was a statistically significant reduction in 28-day mortality only for the subgroup of patients receiving prolonged low-dose steroid treatment (37.5% vs. 44% in the control group).
There was no increased risk of gastrointestinal hemorrhage, superinfection, or neuromuscular weakness seen in treated patients.
The trials differed in the types of corticosteroid used, the time to institution of therapy, bolus versus continuous administration, duration of therapy, and abrupt versus gradual interruption of treatment. All of these factors make the clinical application of the data challenging.
Bottom line: Many questions remain about the optimal dose, timing, and duration of corticosteroids in patients with vasopressor-dependent sepsis and septic shock, but there appears to be a modest mortality benefit with prolonged low-dose corticosteroid therapy.
Citation: Annane D, Bellissant E, Bollaert P, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301(22): 2362-2375.
8) Testing for FVL Mutation but Not 20210A Predicts Recurrent VTE Risk
Clinical question: Are the rates of recurrent VTE higher in adults with VTE who possess either the factor V Leiden (FVL) or Prothrombin G20210A mutation, and what are the rates of VTE among family members?
Background: Clinicians commonly test for genetic mutations when treating patients who have a thrombotic event. However, the utility of such tests on predicting the risk for recurrent events and on outcomes needs review.
Study design: Meta-analysis.
Setting: Literature search of MEDLINE, EMBASE, the Cochrane Library, CINAHL, and PsycInfo.
Synopsis: Forty-six articles were selected for statistical analysis. The presence of either homozygous or heterozygous FVL mutation increased the risk of recurrent VTE compared with individuals without the FVL mutation (OR 2.65 and 1.56, respectively).
Compared with family members of adults without the FVL mutation, the presence of either homozygous or heterozygous FVL mutation predicts VTE in family members (OR 18 and 3.5, respectively).
The presence of G20210A is not predictive of recurrent VTE compared with individuals without this mutation. There is not sufficient evidence regarding the predictive value of the G20210A mutation on the risk of VTE in family members.
No studies directly address the effect of testing on outcomes other than recurrent VTE. In family members who were tested, there did not seem to be any impact on daily behavior, recognition of VTE risk factors, or perceived stress from testing.
Bottom line: FVL mutation increases the risk of recurrent VTE and predicts VTE in family members. The benefits of testing family members remain unclear.
Citation: Segal J, Brotman, D, Necochea, A, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301 (23):2472-2485. TH