Mortality Decline With the Use of a Sepsis Treatment Bundle

Abstract & Commentary

Pulmonary and Critical Care Medicine, Northwest Permanente and Kaiser Sunnyside Medical Center, Portland

Financial Disclosure: Dr. Walter reports no financial relationships relevant to this field of study.

SYNOPSIS: This large, multicenter, quality improvement project showed a dramatic reduction in mortality among patients with severe sepsis or septic shock after implementation of a sepsis treatment bundle.

SOURCE: Miller RR, et al. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med 2013; 188:77-82.

Guidelines for the treatment of severe sepsis and septic shock over the last decade have focused on early recognition and rapid, aggressive resuscitative efforts. Implementation of these guidelines has consistently been shown to improve outcomes. However, the relative importance of different elements has been debated. As part of a multicenter quality improvement project, a sepsis treatment bundle was implemented for all patients admitted from the emergency department (ED) to the ICU in 11 hospitals within a single health care system (Intermountain Healthcare).

The sepsis treatment bundle was comprised of seven "resuscitative elements" and four "maintenance elements." The first three resuscitative elements — 1) measuring lactate, 2) blood cultures prior to antibiotic administration, and 3) administration of broad-spectrum antibiotics — had to be completed within 3 hours of ED arrival. The additional resuscitation elements were: 4) administration of fluids of 20-40 mL/kg for hypotension or lactate ≥ 4 mmol/L, 5) administration of vasopressors for hypotension despite appropriate fluid administration, 6) obtaining central venous pressure (CVP) and central venous oxygen saturation (ScVO2) at regular intervals with a goal CVP ≥ 8 cm H2O and ScVO2 ≥ 70%, and 7) administration of inotropes and/or packed red cells (if hematocrit < 30%) if ScVO2 was < 70% and CVP ≥ 8 cm H2O. All had to be accomplished within 6 hours of ED admission. The four maintenance elements consisted of 1) mean glucose ≤ 180 mg/dL between 12-24 hours following admission, 2) administration of glucocorticoids for persistent hypotension despite adequate fluid resuscitation, or a high dose of a single vasopressor or requiring more than 1 vasopressor, 3) assessment of drotrecogin alfa eligibility, and 4) use of low tidal volume ventilation (6 mL/kg predicted body weight) if mechanically ventilated.

From 2004-2010, 4329 subjects were diagnosed with severe sepsis or septic shock. All-or-none total bundle compliance increased from 4.9% to 73.4% over the study period, showing that a sepsis treatment bundle could be effectively implemented. Over the same time period, in-hospital mortality declined from 21.2% to 8.7%. Interestingly, the decline in mortality did not appear to be due to 100% bundle adherence, as the same decline in mortality was seen in subjects for whom not all bundle elements were implemented (21.7% to 9.7%). Throughout the study, however, the number of bundle elements successfully achieved per patient steadily increased.

The first three resuscitative elements were applied to all subjects. Additional elements were only applied if subjects were eligible (i.e., one could only be eligible for vasopressors, inotropes/red cell transfusion, glucocorticoids, or lung protective ventilation if one was hypotensive, had low ScVO2, or was intubated). A 100% compliance with the first three elements was associated with ineligibility for inotropes/red cell transfusions, glucocorticoids, and lung protective ventilation. Another way of saying this is that in subjects for whom lactate was measured, blood cultures were drawn prior to antibiotics, and broad-spectrum antibiotics were provided within the first 3 hours of ED arrival were less likely to have persistent hypotension, low ScVO2 or require mechanical ventilation. They were also less likely to die (P < 0.0001).


The authors should be commended on a tremendous amount of work put forth to implement this quality improvement project across 18 ICUs in 11 hospitals as well as to collate data from more than 4000 patients. The authors show that with an effective collaboration between the ED and ICU, a detailed sepsis treatment bundle can be effectively implemented. They also show that aggressive sepsis treatment should not be restricted to the first 6 hours; it should extend into comprehensive ICU care. The all-or-none measurement bar prevented providers from picking and choosing elements they felt were most beneficial. Supporters will argue that this demanding approach standardized care and led to the impressive decline in mortality. Detractors will argue the extensive bundle was "overkill" and not needed, as mortality declined equally among subjects in whom not all bundle elements were implemented. The truth probably lies somewhere in the middle. Like other pre-post studies evaluating practice changes, the outcome cannot be definitely attributed to the intervention. We may not definitely know what part or parts of the treatment bundle led to the mortality improvement, but clearly the implementation of this bundle achieved a very positive outcome.

The strong association between 100% compliance of the first three resuscitation bundle elements and subsequent severity of illness and death is intriguing. Simply asking physicians to consider sepsis and treat early is vital. Future studies will help delineate the added importance of invasive monitoring, vasopressors, inotropes, and transfusions. In the absence of such studies, these data argue that adherence to most, if not all, sepsis treatment guidelines should be the go-to approach.