Delayed Management of Severe Sepsis, Septic Shock Increases Mortality

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Study demonstrated a new approach to incorporate time ("delay") when analyzing the effect on outcomes and provided new evidence for clinical practice and research of severe sepsis or septic shock.

Delays in implementing evidence-based recommendations for severe sepsis or septic shock, even within the advised time frame, increases the risk for adverse outcomes, according to a retrospective cohort study published in Critical Care Medicine.

The Surviving Sepsis Campaign offers 4 recommendations for severe sepsis or septic shock management that must be completed within 3 hours of diagnosis: collect blood cultures before initiating antibiotics, measure lactate levels, administer broad-spectrum antibiotics, and administer 30 mL/kg crystalloid fluid if patient is hypotensive (mean arterial pressure, <65 mm Hg) or lactate levels are >4.

Previous studies have been inadequate in indicating how outcomes may be affected by the amount of time delay within the 3-hour period.

Investigators collected data on hospitalized, adult patients with either severe sepsis or septic shock (n=5072). Patients were selected from a health system comprising 6 hospitals and 45 clinics in the Midwest. Onset of sepsis was defined by the earliest time and date during the hospital visit that the patient met standard diagnostic criteria.

The effect of t minutes of delay in administering each recommendation was measured, focusing on the probability of in-house mortality. Sequential propensity score matching was performed between “exposed” and “control” patients, defined as patients who received a specific intervention in less than t minutes vs greater than t minutes, respectively.

Of the patients studied, 27.8% (n=1412) died in the hospital. The following time delays in implementation of each guideline increased the risk for death: lactate, 20 minutes; blood culture, 50 minutes; crystalloids, 100 minutes; and antibiotic therapy, 125 minutes.

The study had multiple limitations. For example, time of delay was based on time of in-hospital diagnosis, but sepsis may have been present before admission. Further, the data only represent cases of in-house mortality; long-term outcomes or out-of-hospital mortality were not addressed.

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“The guideline recommendations showed that shorter delays indicates better outcomes. There was no evidence that 3 hours is safe; even very short delays adversely impact outcomes,” the authors commented. “Findings demonstrated a new approach to incorporate time t when analyzing the impact on outcomes and provide new evidence for clinical practice and research.”


Pruinelli L, Westra BL, Yadav P, et al. Delay within the 3-hour surviving sepsis campaign guideline on mortality for patients with severe sepsis and septic shock. Crit Care Med. 2018;46(4):500-505.