14 Nov 06
Posted in Sepsis, rhAPC at 19:01 by Laci
By GR Bernard, J-L Vincent, P-F Laterre, SP LaRosa, J-F Dhainaut, A Lopez-Rodriguez, JS Steingrub, GE Garber, JD Helterbrand, EW Ely, CJ Fisher, for The Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group
N Engl J Med 2001;344:699-709
Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis.
Methods
We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 µg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C.
Results
A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06).
Conclusions
Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.
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Posted in Inotropic support at 18:54 by Laci
By F Kerbaul, B Rondelet, J-P Demester, P Fesler, S Huez, R Naeije, Se Brimioulle
Critical Care Medicine 2006;34:2814-2819
A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure.
Design
Prospective, controlled, randomized animal study.
Setting
University research laboratory.
Subjects
Fifteen anesthetized dogs.
Interventions
Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 µg/kg/min or levosimendan 12 µg/kg for 10 mins followed by 0.1 and 0.2 µg/kg/min.
Measurements and Main Results
We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 ± 0.07 to 3.01 ± 0.28 mm Hg/mL, decreased Ees from 1.17 ± 0.09 to 0.58 ± 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 ± 0.09 to 0.22 ± 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state.
Conclusions
A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.
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13 Nov 06
Posted in ALI/ARDS, Mechanical ventilation at 19:40 by Laci
By L Gattinoni, P Caironi, M Cressoni, D Chiumello, M Ranieri, M Quintel et al
N Engl J Med 2006; 354:1775-1786
In the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed. Since the effects of PEEP probably depend on the recruitability of lung tissue, we conducted a study to examine the relationship between the percentage of potentially recruitable lung, as indicated by computed tomography (CT), and the clinical and physiological effects of PEEP.
Methods
Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5, 15, and 45 cm of water. The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water.
Results
The percentage of potentially recruitable lung varied widely in the population, accounting for a mean (±SD) of 13±11 percent of the lung weight, and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP (r2=0.72, P<0.001). On average, 24 percent of the lung could not be recruited. Patients with a higher percentage of potentially recruitable lung (greater than the median value of 9 percent) had greater total lung weights (P<0.001), poorer oxygenation (defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen) (P<0.001) and respiratory-system compliance (P=0.002), higher levels of dead space (P=0.002), and higher rates of death (P=0.02) than patients with a lower percentage of potentially recruitable lung. The combined physiological variables predicted, with a sensitivity of 71 percent and a specificity of 59 percent, whether a patient's proportion of potentially recruitable lung was higher or lower than the median.
Conclusions
In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.
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Posted in ScvO2 at 19:05 by Laci
By SM Jakob and The Collaborative study group on peri-operative ScvO2 monitoring
Critical Care 2006, 10:R158
Low central venous oxygen saturation (ScvO2) has been associated with increased risk of postoperative complications in high-risk surgery. Whether this association is center-specific or more generalizable is not known. The aim of this study was to assess the association between peri- and postoperative ScvO2 and outcome in high-risk surgical patients in a multi-center setting.
Methods
Three large European university hospitals (two in Finland, one in Switzerland) participated. In 60 patients with intra-abdominal surgery lasting >90 minutes, the presence of >/=2 Shoemaker criteria, and American Society of Anesthesiologists (ASA) class >2, ScvO2 was determined preoperatively and at 2-hour intervals during the operation until 12 hours postoperatively. Hospital length of stay (LOS), mortality and predefined postoperative complications were recorded.
Results
The age of the patients was 72 +/-10 years (mean +/-SD), and simplified acute physiology score (SAPS II) was 32 +/-12. Overall LOS was 10.5 (8-14) days, and 28-day hospital mortality was 10.0%. Preoperative ScvO2 decreased from 77 +/-10% to 70 +/-11% (p<0.001) immediately after surgery and remained unchanged 12 hours later. A total of 67 postoperative complications were recorded in 32 patients. After multivariate analysis, mean ScvO2 value (odds ratio [OR] 1.23 [95% confidence interval 1.01 to 1.50]; p = 0.037), length of hospital stay (OR 0.75 [0.59 to 0.94]; p = 0.012) and SAPS II (OR 0.90 [0.82 to 0.99]; p = 0.029) were independently associated with postoperative complications. The optimal value of mean ScvO2 to discriminate between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%).
Conclusions
Low central venous oxygen saturation perioperatively is related to increased risk of postoperative complications in high-risk surgery. This warrants trials with goal-directed therapy using ScvO2 as a target in high-risk surgery patients.
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