25 Jun 06
Posted in rhAPC at 11:56 by Laci
By JO Friedrich, NKJ Adhikari and MO Meade
Critical Care 2006, 10:145
Two international multicentre randomised controlled trials of drotrecogin alfa (activated) (DrotAA), the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials, have produced inconsistent results. When 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random-effects meta-analysis technique, there is no statistically significant survival benefit (for patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more), or a borderline significant benefit (for patients with multi-organ failure). We argue that two important methodological issues might explain the disparate results between the two trials. These issues centre on early trial stopping, which exaggerates treatment effects, and reliance on subgroup analyses, which for DrotAA yields inconsistent results across different definitions of high risk. These concerns call into question the effectiveness of DrotAA in any patients with severe sepsis. Consequently, further randomised trials of this agent in prospectively defined high-risk patients are required to clarify its role in the management of severe sepsis.
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Posted in rhAPC at 11:54 by Laci
By JO Friedrich
N Engl J Med 2006;354:94-95
To the Editor: In the article by Abraham et al., the ADDRESS trial showed no benefit of drotrecogin alfa (activated) (DrotAA) in patients with severe sepsis and a low risk of death (defined by single-organ failure or an Acute Physiology and Chronic Health Evaluation [APACHE II] score <25). In contrast to the prematurely terminated PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial, the ADDRESS study showed higher mortality in its subgroup of patients treated with DrotAA who had an APACHE II score of 25 or more. … No further text is available due to copyright restrictions
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16 Jun 06
Posted in Inotropic support, PA catheter at 20:30 by Laci
By SM Lobo, FR Lobo, CA Polachini, DS Patini, AE Yamamoto, NE de Oliveira et al
Critical Care 2006, 10:R72
Preventing perioperative tissue oxygen debt contributes to a better postoperative recovery. Whether the beneficial effects of fluids and inotropes during optimization of the oxygen delivery index (DO2I) in high-risk patients submitted to major surgeries are due to fluids, to inotropes, or to the combination of the two is not known. We aimed to investigate the effect of DO2I optimization with fluids or with fluids and dobutamine on the 60-day hospital mortality and incidence of complications.
Methods
A randomized and controlled trial was performed in 50 high-risk patients (elderly with coexistent pathologies) undergoing major elective surgery. Therapy consisted of pulmonary artery catheter-guided hemodynamic optimization during the operation and 24 hours postoperatively using either fluids alone (n = 25) or fluids and dobutamine (n = 25), aiming to achieve supranormal values (DO2I > 600 ml/minute/m2).
Results
The cardiovascular depression was an important component in the perioperative period in this group of patients. Cardiovascular complications in the postoperative period occurred significantly more frequently in the volume group (13/25, 52%) than in the dobutamine group (4/25, 16%) (relative risk, 3.25; 95% confidence interval, 1.22–8.60; P < 0.05). The 60-day mortality rates were 28% in the volume group and 8% in the dobutamine group (relative risk, 3.00; 95% confidence interval, 0.67–13.46; not significant).
Conclusion
In patients with high risk of perioperative death, pulmonary artery catheter-guided hemodynamic optimization using dobutamine determines better outcomes, whereas fluids alone increase the incidence of postoperative complications.
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Posted in Sedation at 20:20 by Laci
By B Muellejans, T Matthey, J Scholpp and M Schill
Critical Care 2006, 10:R91
Remifentanil is an opioid with a unique pharmacokinetic profile. Its organ-independent elimination and short context-sensitive half time of 3 to 4 minutes lead to a highly predictable offset of action. We tested the hypothesis that with an analgesia-based sedation regimen with remifentanil and propofol, patients after cardiac surgery reach predefined criteria for discharge from the intensive care unit (ICU) sooner, resulting in shorter duration of time spent in the ICU, compared to a conventional regimen consisting of midazolam and fentanyl. In addition, the two regimens were compared regarding their costs.
Methods
In this prospective, open-label, randomised, single-centre study, a total of 80 patients (18 to 75 years old), who had undergone cardiac surgery, were postoperatively assigned to one of two treatment regimens for sedation in the ICU for 12 to 72 hours. Patients in the remifentanil/propofol group received remifentanil (6- max. 60 µg kg-1 h-1; dose exceeds recommended labelling). Propofol (0.5 to 4.0 mg kg-1 h-1) was supplemented only in the case of insufficient sedation at maximal remifentanil dose. Patients in the midazolam/fentanyl group received midazolam (0.02 to 0.2 mg kg-1 h-1) and fentanyl (1.0 to 7.0 µg kg-1 h-1). For treatment of pain after extubation, both groups received morphine and/or non-opioid analgesics.
Results
The time intervals (mean values ± standard deviation) from arrival at the ICU until extubation (20.7 ± 5.2 hours versus 24.2 h ± 7.0 hours) and from arrival until eligible discharge from the ICU (46.1 ± 22.0 hours versus 62.4 ± 27.2 hours) were significantly (p < 0.05) shorter in the remifentanil/propofol group. Overall costs of the ICU stay per patient were equal (approximately €1,700 on average).
Conclusion
Compared with midazolam/fentanyl, a remifentanil-based regimen for analgesia and sedation supplemented with propofol significantly reduced the time on mechanical ventilation and allowed earlier discharge from the ICU, at equal overall costs.
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