In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for early goal-directed therapy that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. During the first 6 hrs of resuscitation of sepsis-induced hypoperfusion, specific levels of central venous pressure, mean arterial pressure, urine output, central venous (or mixed venous) oxygen saturation should be targeted. When central venous oxygen saturation remains low, despite achieving central venous pressure and mean arterial pressure targets, packed red blood cells or dobutamine should be considered. Increasing cardiac index to achieve an arbitrarily predefined elevated level is not recommended.?