15 Jun 08

Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome

Posted in ALI/ARDS, Mechanical ventilation at 10:04 by Laci

By A Mercat, J-C Richard, B Vielle, S Jaber, D Osman, J-L Diehl, J-Y Lefrant et al for the Expiratory Pressure (Express) Study Group

JAMA. 2008;299:646-655

The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.

Objective
To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.

Design, setting and patients
A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.

Intervention
Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385).

Main outcome measures
The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. RESULTS: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.

Conclusions
A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.

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Sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment

Posted in General at 9:58 by Laci

By N S Jafri, C A Hornung and C W Howden

Ann Int Med 2008;148,xxx

Standard proton-pump inhibitor–based therapy for Helicobacter pylori infection fails in up to one quarter of patients. Sequential therapy may be more efficacious.

Purpose
To compare sequential therapy with standard triple therapy for H. pylori infection.

Data Sources
MEDLINE, EMBASE (1981 to October 2007), the Cochrane Central Register of Controlled Trials, and Google Scholar. PubMed and Ovid were the search engines used.

Study Selection
Randomized, controlled trials (RCTs) comparing sequential and standard triple therapies in treatment-naive patients with documented H. pylori infection.

Data Extraction
3 reviewers independently assessed trial eligibility and quality and extracted data on eradication.

Data Synthesis
The crude rates of H. pylori eradication in 10 RCTs involving 2747 patients were 93.4% (95% CI, 91.3% to 95.5%) for sequential therapy (n = 1363) and 76.9% (CI, 71.0% to 82.8%) for standard triple therapy (n = 1384) (relative risk reduction, 71% [CI, 64% to 77%]; absolute risk reduction, 16 percentage points [CI, 14 to 19 percentage points]). The median rates of adherence were 97.4% (range, 90.0% to 98.9%) for sequential therapy and 96.8% (range, 93.0% to 100%) for standard therapy. Sequential therapy appeared superior in prespecified sensitivity (subgroup) analyses stratified by trial quality; smoking status; diagnosis (ulcer disease or nonulcer dyspepsia); resistance to clarithromycin, imidazoles, or both; duration of triple therapy; and method of diagnosis. Both treatments had similar side effect profiles.

Limitations
Only 1 study was double-blinded. Most patients were from Italy. There was clear evidence of publication bias.

Conclusions
Sequential therapy appears superior to standard triple therapy for eradication of H. pylori infection. If RCTs in other countries confirm these findings, 10-day sequential therapy could become a standard treatment for H. pylori infection in treatment-naive patients.

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