BACKGROUND

Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control.

OBJECTIVE

This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock.

METHODS

This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patient's hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol.

RESULTS

A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004).

CONCLUSION

Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution.