Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature

INTRODUCTION: Patients with sepsis suffer high morbidity and mortality. We sought to conduct a systematic review of the literature to evaluate the association between hemodynamic goals of therapy and patient outcomes. METHODS: We conducted a comprehensive search of the literature to systematically review hemodynamic goals used in clinical trials in patients with sepsis. We searched the literature using the Pubmed (1965–June 2006), Embase (1974–June 2006), CINAHL (1982–June 2006), pre-CINAHL, and Cochrane Library (2006, issue 3) electronic databases on 1 August 2006 for the following terms: sepsis, septic shock, severe sepsis, human clinical trials. We also hand-searched references and our personal files. Studies were selected if they met all of the following criteria: randomized, controlled trial study design; enrollment of adult patients with sepsis; presence of a hemodynamic goal for patient management; > 24-hour follow-up; and survival included as an outcome. Studies were independently selected and reviewed by two investigators. RESULTS: A total of 6,006 citations were retrieved, and 13 eligible articles were reviewed. Mean arterial pressure was a treatment goal in nine studies, and systolic blood pressure was a treatment goal in three studies. A goal for pulmonary artery occlusion pressure, central venous pressure, and cardiac index was given in four, three, and five studies, respectively. The range of hemodynamic goals used in the trials were: mean arterial pressure 60–100 mmHg, central venous pressure 6–13 mmHg, pulmonary artery occlusion pressure 13–17 mmHg, and cardiac index 3–6 l/min/m(2). All trials that used a systolic blood pressure goal used 90 mmHg as the aim. CONCLUSION: For those trials that specify hemodynamic goals, the wide range of treatment targets suggest a lack of agreement on blood pressure and filling pressure goals for management of patients with sepsis. There was also inconsistency between trials in which measures were targeted. Further research is necessary to determine whether this lack of consistency in hemodynamic goals may contribute to heterogeneity in treatment effects for clinical trials of novel sepsis therapies.