10 Feb 06

High-dose antithrombin III in the treatment of severe sepsis in patients

Posted in Critical Care, Sepsis at 20:58 by Laci

By CJ Wiedermann, JN Hoffmann, M Juers, H Ostermann, J Kienast et al

Critical Care Medicine. 34(2):285-292

Objective
To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III.

Design
 Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study.

Setting
 Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial.

Patients
 We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II.

Interventions
 Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo.

Measurements and Main Results
 In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications.

Conclusions
 Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.

01 Feb 06

Statins and sepsis in patients with cardiovascular disease

Posted in Critical Care, Sepsis at 19:50 by Laci

Bz DG Hackam, M Mamdani, P Li and DA Redelmeier

The Lancet Early Online Publication 25 January 2006

Background
Atherosclerosis and sepsis share several pathophysiological similarities, including immune dysregulation, increased thrombogenesis, and systemic inflammation. The relation between statins and risk of sepsis in patients with atherosclerosis is unknown.

Methods
We did a population-based cohort analysis through linked administrative databases in Ontario, Canada, with accrual from 1997 to 2002. We identified 141?487 patients older than 65 years who had been hospitalised for an acute coronary syndrome, ischaemic stroke, or revascularisation, who survived for at least 3 months after discharge. 46?662 (33%) were prescribed a statin within 90 days of discharge, 94?825 (67%) were not. Propensity-based matching, which accounted for each individual’s likelihood of receiving a statin, yielded a cohort of 69?168 patients, of whom half (34?584) received a statin and half (34?584) did not.

Findings
Incidence of sepsis was lower in patients receiving statins than in controls (71·2 vs 88·0 events per 10?000 person-years; hazard ratio [HR] 0·81; 95% CI 0·72–0·91). Adjustment for demographic characteristics, sepsis risk factors, comorbidities, and health-care use gave similar results (HR 0·81; 95% CI 0·72–0·90). The protective association between statins and sepsis persisted in high-risk subgroups, including patients with diabetes mellitus, chronic renal failure, or a history of infections. Significant reductions in severe sepsis (HR 0·83; 95% CI 0·70–0·97) and fatal sepsis (0·75; 0·61–0·93) were also observed. No benefit was noted with non-statin lipid-lowering agents (0·95; 0·75–1·22).

Implications
Use of statins in patients with atherosclerosis is associated with a reduced risk of subsequent sepsis. Randomised trials of statins for prevention of sepsis are warranted.

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