28 Dec 08

D-Dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism

Posted in Anticoagulation at 0:00 by Laci

By M Verhovsek, J D Douketis, Q Yi, S Shrivastava, R Cl Tait, T Baglin, D Poli and W Lim

Ann Int Med 2008;149:481-490

The optimal duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) is uncertain. Methods for predicting risk for recurrence may identify low-risk patients who are less likely to benefit from prolonged anticoagulation.

To synthesize evidence evaluating the value of D-dimer as a predictor of recurrent disease in patients who have stopped anticoagulant therapy after a first unprovoked VTE.

Data sources
The MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched until March 2008 without language restrictions. The strategy was supplemented with manual review of reference lists and contact with content experts.

Study selection
Randomized, controlled trials or prospective cohort studies that measured D-dimer after anticoagulant therapy in patients who received at least 3 months of anticoagulant treatment of unprovoked VTE.

Data extraction
Two authors independently reviewed articles and extracted data.

Data synthesis
Seven studies, totaling 1888 patients with a first unprovoked VTE, were eligible for analysis. During 4500 person-years of follow up, annual rates of recurrent VTE differed statistically significantly: 8.9% (95% CI, 5.8% to 11.9%) in patients with positive D-dimer results and 3.5% (CI, 2.7% to 4.3%) in patients with negative D-dimer results.

The duration of anticoagulation, timing of D-dimer testing, and D-dimer assay varied across studies.

In patients who have completed at least 3 months of anticoagulation for a first episode of unprovoked VTE and after approximately 2 years of follow-up, a negative D-dimer result was associated with a 3.5% annual risk for recurrent disease, whereas a positive D-dimer result was associated with an 8.9% annual risk for recurrence. These rates should inform decisions about the balance of risks and benefits of prolonging anticoagulation.

25 Dec 08

Effect of evidence-based feeding guidelines on mortality of critically ill adults

Posted in Nutrition at 20:09 by Laci

By G S Doig, F Simpson, S Finfer, A Delaney, A R Davies, I Mitchell, G Dobb for the Nutrition Guidelines Investigators of the ANZICS Clinical Trials Group

JAMA. 2008;300:2731-2741

Evidence demonstrates that providing nutritional support to intensive care unit (ICU) patients within 24 hours of ICU admission reduces mortality. However, early feeding is not universally practiced. Changing practice in complex multidisciplinary environments is difficult. Evidence supporting whether guidelines can improve ICU feeding practices and patient outcomes is contradictory.

To determine whether evidence-based feeding guidelines, implemented using a multifaceted practice change strategy, improve feeding practices and reduce mortality in ICU patients.

Design, setting, and patients
Cluster randomized trial in ICUs of 27 community and tertiary hospitals in Australia and New Zealand. Between November 2003 and May 2004, 1118 critically ill adult patients expected to remain in the ICU longer than 2 days were enrolled. All participants completed the study.

Intensive care units were randomly assigned to guideline or control groups. Guideline ICUs developed an evidence-based guideline using Browman’s Clinical Practice Guideline Development Cycle. A practice-change strategy composed of 18 specific interventions, leveraged by educational outreach visits, was implemented in guideline ICUs.

Main outcome measures
Hospital discharge mortality. Secondary outcomes included ICU and hospital length of stay, organ dysfunction, and feeding process measures.


Guideline and control ICUs enrolled 561 and 557 patients, respectively. Guideline ICUs fed patients earlier (0.75 vs 1.37 mean days to enteral nutrition start; difference, ñ0.62 [95% confidence interval {CI}, ñ0.82 to ñ0.36]; P < .001 and 1.04 vs 1.40 mean days to parenteral nutrition start; difference, ñ0.35 [95% CI, ñ0.61 to ñ0.01]; P = .04) and achieved caloric goals more often (6.10 vs 5.02 mean days per 10 fed patient-days; difference, 1.07 [95% CI, 0.12 to 2.22]; P = .03). Guideline and control ICUs did not differ with regard to hospital discharge mortality (28.9% vs 27.4%; difference, 1.4% [95% CI, ñ6.3% to 12.0%]; P = .75) or to hospital length of stay (24.2 vs 24.3 days; difference, ñ0.08 [95% CI, ñ3.8 to 4.4]; P = .97) or ICU length of stay (9.1 vs 9.9 days; difference, ñ0.86 [95% CI, ñ2.6 to 1.3]; P = .42).

Using a multifaceted practice change strategy, ICUs successfully developed and introduced an evidence-based nutritional support guideline that promoted earlier feeding and greater nutritional adequacy. However, use of the guideline did not improve clinical outcomes.

23 Dec 08

Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?

Posted in Early goal directed therapy, ScvO2, Sepsis at 0:30 by Laci

By F Vallet, B Vallet, O Mathe, J Parraguette, A Mari et al

Intensive Care Med 2008:34;2218-2225

To test the hypothesis that, in resuscitated septic shock patients, central venous-to-arterial carbon dioxide difference [P(cv-a)CO2] may serve as a global index of tissue perfusion when the central venous oxygen saturation (ScvO2) goal value has already been reached.

Prospective observational study.

A 22-bed intensive care unit (ICU).

After early resuscitation in the emergency unit, 50 consecutive septic shock patients with ScvO2 > 70% were included immediately after their admission into the ICU (T0). Patients were separated in Low P(cv-a)CO2 group (Low gap; n = 26) and High P(cv-a)CO2 group (High gap; n = 24) according to a threshold of 6 mmHg at T0.

Measurements were performed every 6 h over 12 h (T0, T6, T12).

At T0, there was a significant difference between Low gap patients and High gap patients for cardiac index (CI) (4.3 ± 1.6 vs. 2.7 ± 0.8 l/min/m≤, P < 0.0001) but not for ScvO2 values (78 ± 5 vs. 75 ± 5%, P = 0.07). From T0 to T12, the clearance of lactate was significantly larger for the Low gap group than for the High gap group (P < 0.05) as well as the decrease of SOFA score at T24 (P < 0.01). At T0, T6 and T12, CI and P(cv-a)CO2 values were inversely correlated (P < 0.0001).

In ICU-resuscitated patients, targeting only ScvO2 may not be sufficient to guide therapy. When the 70% ScvO2 goal-value is reached, the presence of a P(cv-a)CO2 larger than 6 mmHg might be a useful tool to identify patients who still remain inadequately resuscitated.

20 Dec 08

Prone positioning in acute respiratory distress syndrome

Posted in ALI/ARDS, Mechanical ventilation at 0:21 by Laci

By R Fernandez, X Trenchs, J Klamburg, J Castedo, J M Serrano et al

Intensive Care Med 2008:34;1487-1491

We examined the effect on survival of prone positioning as an early and continuous treatment in ARDS patients already treated with protective ventilation.

Design and setting
Open randomized controlled trial in 17 medical-surgical ICUs.

Forty mechanically ventilated patients with early and refractory ARDS despite protective ventilation in the supine position.
Interventions  Patients were randomized to remain supine or be moved to early (within 48h) and continuous (=20h/day) prone position until recovery or death. The trial was prematurely stopped due to a low patient recruitment rate.

Measurements and results
Clinical characteristics, oxygenation, lung pressures, and hemodynamics were monitored. Need for sedation, complications, length of MV, ICU, and hospital stays, and outcome were recorded. PaO2/FIO2 tended to be higher in prone than in supine patients after 6h (202±78 vs. 165±70mmHg); this difference reached statistical significance on day 3 (234±85 vs. 159±78). Prone-related side effects were minimal and reversible. Sixty-day survival reached the targeted 15% absolute increase in prone patients (62% vs. 47%) but failed to reach significance due to the small sample.

Our study adds data that reinforce the suggestion of a beneficial effect of early continuous prone positioning on survival in ARDS patients.

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