1.
Albumin replacement in patients with severe sepsis or septic shock
Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, et al
New England Journal of Medicine. 2014;370((15):):1412-21.
Abstract
BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).
2.
Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock
Dhainaut JF, Antonelli M, Wright P, Desachy A, Reignier J, Lavoue S, Charpentier J, Belger M, Cobas-Meyer M, Maier C, et al
Intensive Care Medicine. 2009;35((7):):1187-95.
Abstract
OBJECTIVE To determine the efficacy and safety of extended drotrecogin alfa (activated) (DAA) therapy. DESIGN Multicentre, randomised, double-blind, placebo-controlled study. SETTING Sixty-four intensive care units in nine countries. PATIENTS Adults with severe sepsis and vasopressor-dependent hypotension after a 96-h infusion of standard DAA. INTERVENTIONS A total of 193 patients received an intravenous infusion of extended DAA 24 microg/kg/h or sodium chloride placebo for a maximum of 72 h. MEASUREMENTS AND RESULTS At extended therapy initiation (baseline), DAA-group patients had lower protein C levels (P = 0. 23) and higher vasopressor requirements, particularly for the primary vasopressor used, norepinephrine (P = 0. 03), compared with placebo-group patients. DAA treatment did not result in a difference in the primary outcome of time to resolution of vasopressor-dependent hypotension versus placebo (P = 0. 419). However, few patients reached resolution (DAA 34%, placebo 40%) as most continued to require vasopressor support after 72 additional hours of treatment. Treatment did not reduce 28-day all-cause mortality and in-hospital mortality or improve organ function compared with placebo, although there was a lower percentage change in D-dimers (P < 0. 001) and increases in protein C levels were numerically greater on extended infusion. There was no difference in serious adverse events including bleeding events. CONCLUSIONS Extended DAA treatment did not result in more rapid resolution of vasopressor-dependent hypotension, despite demonstrating anticipated biological effects on D-dimer and protein C levels. A reduced planned sample size combined with baseline imbalances in protein C levels and vasopressor requirements may have limited the ability to demonstrate a clinical benefit.
3.
Effect of intravenous immunoglobulin on opsonic activity and TNF production in patients at high risk for sepsis syndrome
Nazzari C, Gaeta A, Lun MT, Raponi G, Antonelli M, Mancini C, Filadoro F
New Microbiologica. 1993;16((3):):251-8.
Abstract
In a randomized double blind study, we analyzed the efficacy of IVIG in the infectious complications in patients at high risk of developing sepsis syndrome. Two groups of twenty patients were enrolled, one receiving 250 mg/Kg of IVIG on the first and seventh day after admission and the other receiving sterile saline as placebo. Serum samples were drawn before IVIG administration and 24, 48 and 72 hours afterwards. The same schedule was used for patients treated with placebo. Sera pooled from healthy donors served as controls. On all the samples, opsonic and bactericidal activity as well as C3, total IgG and serum TNF content were tested. IVIG did not significantly affect total IgG and C3 content. Similarly, opsonic and bactericidal activity tested against E. coli 06 :K-, E. coli 0111 and SAC I was not modified ranging within HPS values. Furthermore, IVIG administration did not change the TNF level. A lower incidence of bacteremia in IVIG treated patients was observed.