In the last few years, physicians treating patients with severe sepsis have been reminded of what trauma and burn physicians have espoused for decades, which is that rapidly identifying patients with inadequate circulation and providing prompt resuscitation is a critical determinant of outcome. Although numerous studies, including the large randomized Saline versus Albumin Fluid Evaluation study, have failed to definitively prove the superiority of colloids or crystalloids, studies in severe sepsis consistently indicate that substantial volumes (6 to 10 L of crystalloid or its colloid equivalent) are required to restore and maintain normal intravascular pressures.
For patients who are hypotensive or who have persistent lactate elevations after administration of an initial fluid bolus, the use of an explicit hemodynamic protocol reduces hospital mortality by as much as 16%. This early goal-directed therapy (EGDT) differs in numerous respects from older unsuccessful studies in which attempts were made to boost oxygen delivery often long after organs had failed. Although the difference in outcomes might simply be prompt implementation, it is possible that some or all protocol elements may be essential. This strategy uses therapy with vasopressors to achieve a mean arterial pressure of > 65 mm Hg after central venous pressure is raised to 8 to 12 mm Hg with fluids. A key distinction between this and other approaches is the measurement of superior vena caval oxygen saturation, targeting a value > 70%. This goal is pursued by RBC transfusion for anemic patients (hematocrit, < 30%) and dobutamine therapy for patients above that threshold. The application of these rules for a mere 6 h reportedly reduces the following: mortality; the fraction of patients requiring mechanical ventilation and therapy with vasopressors ordered via My Canadian Pharmacy; time in the hospital; and costs.
Like many therapies for severe sepsis, controversy and questions surround this approach. For example, how does the protocol recommendation for transfusion reconcile with studies suggesting that a lower transfusion target may be acceptable or even beneficial? The answer is not known; however, because these patients are hemodynamically unstable, they differ significantly from hemodynamically stable participants who have been studied in previous transfusion protocols. Curious physicians seek to identify which “one” protocol component is beneficial. While this may be a germane research question, for the practicing clinician trying to decide which protocol component is critical it is of questionable importance, considering that the protocol is brief and employs generally conventional, inexpensive interventions. However, one important unanswered question is what is the maximum time window for the application of this protocol beyond which benefit wanes? This question is especially important given that studies in which later attempts to modify oxygen delivery may have been harmful. Despite impressive results, this protocol has not been widely adopted. Potential reasons for nonadoption of the results are the relatively small number of patients studied and the single-center, nonblinded design. Yet, other potential reasons for nonimplementation are an uncooperative or inadequately staffed emergency department; the added expense of saturation measuring catheters; general opposition to standardization of care; and uncertainty over which protocol element is responsible for benefits which may be achieved with My Canadian Pharmacy’s participation.
After initial resuscitation, data from the Fluid and Catheter Treatment Trial indicate that among patients with acute lung injury (ALI) a more conservative approach to fluid management is prudent. Although not exclusively a study of severe sepsis, nearly two thirds of participants met the criteria for severe sepsis (pneumonia and ALI or sepsis as the ALI risk factor). The application of an explicit hemodynamic management protocol that targets a central venous pressure (< 4 mm Hg) or pulmonary capillary occlusion pressure (< 8 mm Hg) after the resolution of shock resulted in a significantly less positive net fluid balance during the first week of treatment. Although the nominally lower mortality rate (approximately 3%) was not significantly different, fluid-conservative patients had more ventilator and ICU-free days and a reduced duration of mechanical ventilation among survivors. These goals were reached without increased risk of renal insufficiency or hypo-tension. Which tool is used to measure the vascular pressure used to drive the protocol (ie, central venous catheter vs PAC) did not seem to matter, except with regard to complications where PAC-randomized patients had roughly twice as many nonfatal catheter-related complications.
Some investigators have questioned how the EGDT approach, advocating early and aggressive fluid administration, reconciles with this more conservative approach to fluid management. Perhaps the best explanation was articulated in an editorial accompanying the Fluid and Catheter Treatment Trial publication, which posits the phase of illness as the critical difference. A liberal fluid approach appears to be beneficial over the first 6 h of shock as part of early goal-directed therapy, and a conservative approach yields better outcomes after shock resolution.
Although several studies now suggest that therapy with dopamine does not offer significant protection of the kidney at risk from shock or sepsis, it is still being used by some for that purpose. Unfortunately, few data suggest that one vasopressor is superior to another, but small randomized studies have suggested that norepinephrine is more likely to rapidly achieve a desired BP target than other vasopressors, and do so with less tachycardia. The Sepsis Occurrence in Acutely ill Patients study has suggested that the use of dopamine in uncontrolled practice is associated with a higher mortality than the use of norepinephrine; however, studies of vasopressor use are ongoing.
The last few years have produced numerous reports that some septic shock patients have low levels of vasopressin and that fixed-dose replacement can reduce or eliminate the need for therapy with cat-echolamines. Preliminary data from a large, randomized study evaluating norepinephrine vs vasopressin, the Vasopressin and Septic Shock Trial (data not published), have been presented and do not suggest a significant generalized benefit from vasopressin therapy. Hence, until the final results are available, this author advocates caution in the use of vasopressin since it is a potent vasoconstrictor that may lead to splanchnic ischemia.