Up until the 1980s, it was believed that maintenance of normal hemodynamic parameters was the key to resuscitation of critically ill patients. Shoemaker et al2,3 then published several papers about increasing patient survival by “supranormalizing” cardiac indices. They recommended increasing cardiac index, oxygen transport, and CVP to higher than normal. High-risk surgical patients had placement of a pulmonary artery catheter and were randomized into three groups: (1) normalization of CVP; (2) pulmonary artery catheter monitoring and normalization of CVP; or (3) a pulmonary artery catheter protocol based on increasing normal cardiac indices to supranormal values. The time to intervention was greater than 6 hours. The study demonstrated no mortality difference among the CVP and pulmonary artery control groups, but did demonstrate a significant mortality reduction in the pulmonary artery catheter protocol group where the hemodynamic markers were kept at values higher (supranormalization group) than normal.
Early Goal-Directed Therapy
The intervention time of 6 hours was questioned in a study by Rivers et al,4 who suggested this delay was too long. In this study, early goal-directed therapy (EGDT) was compared to standard therapy in the ED in severe sepsis and septic shock. A CVP catheter was used within the right atrium, and critically ill patients were randomized into the following two groups: (1) CVC with continuous central venous oxygen saturation (ScvO2) measurements; and (2) the standard therapy group which was treated at the clinician’s discretion according to standard ED care with the exception of placement of a CVC without ScvO2 monitoring. Both groups had targeted goals of CVP, 8 to 12 mm Hg; mean arterial pressure, greater than 65 mm Hg; and urine output, greater than 0.5 mL/kg/h. Both groups received an equal volume of crystalloid fluids, which exceeded the commonly given amount of fluid to patients. The EDGT group received 4981± 2984 mL compared to the standard group which received 3499 ± 2438 mL. The EGDT-targeted supranormalization of ScvO2 employs dobutamine to achieve a goal of ScvO2 level greater than 70% and uses transfusion to achieve hematocrit level greater than 30%. The study showed 21% overall reduction in mortality in the EGDT group. Aggressive care and early recognition of disease seemed critical to patient survival. The study supported the measurement of CVP as a guide in fluid resuscitation in protocol-driven therapy during the initial 6 hours for patients who had severe sepsis and septic shock.4 The 2012 Surviving Sepsis Campaign guidelines for the treatment of severe sepsis and septic shock recommend maintaining CVP at 8 to 12 mm Hg for nonventilated patients and higher for ventilated patients.5
Since the publication of the EGDT study,4 the use of protocolized “bundle” therapy as a guide for resuscitation in severe sepsis and septic shock has been brought into question. The debate begs to answer which intervention within the bundle (CVP, transfusions, ScvO2, serial lactate, blood transfusions) results in a mortality benefit.
Between 2014 and 2015, three trials were published with the goal of determining which bundle intervention of EGDT was important in decreasing mortality. These three randomized worldwide trials, the so-called “trilogy of EDGT,” were the Protocol-based Care for Early Septic Shock (PROCESS),6 Australasian Resuscitation in Sepsis Evaluation (ARISE),7 and Protocolised Management in Sepsis (ProMISe).8 The results of all three trials were consistent. From a population standpoint, if the comprehensive processes are in place for the early detection of sepsis, aggressive IV fluid administration, early antibiotic administration, and serial lactate measurement; the subsequent algorithm-driven EGDT (as defined by Rivers et al4), including continuous central venous oxygenation and CVP monitoring, did not lead to an improvement in outcomes. Patients in the usual care group received central-line and arterial-line placement at a much higher rate than expected.
A number of potential reasons for differences in results from the original study by Rivers et al4 exist—eg, randomization occurred later, patients appeared to be less ill at baseline, all patients received antibiotics prior to randomization (Table 1). It is important to bear in mind that usual care, as defined in the “trilogy” may in fact not have been the “usual” care back in the mid-1990s when Rivers et al4 were conducting his EGDT. In addition, due to the influences of the original paper, the Surviving Sepsis Guidelines publications, improvement in EMS, critical care improvement, what Rivers et al4 termed usual care was really a modification of EDGT. One can, however, conclude from the trilogy is that placing a CVP or an ScvO2 catheter just for the purpose of chasing a CVP is no longer recommended.