Sepsis, severe sepsis, and septic shock are principal drivers of morbidity and mortality worldwide.1, 2, 3, 4 The seminal trial by Rivers et al5 in 2001 espoused the efficacy of early goal-directed therapy protocols, but 3 recent, multisite, randomized trials failed to demonstrate mortality benefit from such therapy compared with usual care.6, 7, 8 However, in all 3 trials, all patients in both study and control arms received early intravenous fluid resuscitation and intravenous antibiotic administration.Editor’s Capsule Summary
What is already known on this topic
There remains uncertainty in regard to how the timing of delivery of each component of standard sepsis care affects outcomes.
What question this study addressed
This observational study of 1,866 subjects examined the association between initiation of fluid resuscitation within 30 minutes of severe sepsis identification and hospital mortality and length of stay.
What this study adds to our knowledge
Initiation of fluids within 30 minutes of severe sepsis recognition was associated with lower inhospital mortality and length of stay.
How this is relevant to clinical practice
This article supports the importance of rapid identification and fluid administration for patients with severe sepsis. Studies are needed to measure the causal relationship of this association and the interaction with the timing of other therapeutic interventions.
Early intervention is critical in managing severe sepsis and septic shock. Current guidelines from the National Quality Forum and Surviving Sepsis Campaign recommend administration of crystalloid at 30 mL/kg and intravenous broad-spectrum antibiotics within 3 hours of a patient’s first meeting severe sepsis or septic shock criteria.9, 10 After the 2006 article by Kumar et al11 demonstrating substantially increased mortality with each hour of antibiotic delay in septic shock patients, the literature expansively explored the association between the timeliness of intravenous antimicrobial source-control administration and patient outcomes.12, 13, 14, 15, 16, 17 The importance of providing intravenous fluid resuscitation completed within 3 hours has also been established.6, 18, 19, 20 However, the tightly controlled environment of clinical trials starkly contrasts with the emergency department (ED) setting. Although consistent accounting of intravenous fluid completion times is available for patients enrolled in such studies, reliable documentation of these times in practice is another matter. Review of sepsis performance improvement data in the North Shore–LIJ health system, as well as anecdotal discussion with leadership at several New York hospitals, identified documentation of intravenous fluid bolus completion times as frequently inadequate or absent for ED patients at many sites, impeding assessment of provider adherence to current guidelines.
In 2009, based in part on Surviving Sepsis Campaign guidelines10 and in conjunction with the Institute for Healthcare Improvement, North Shore–LIJ developed an algorithm and basic 3-hour bundle for the early identification and treatment of patients on the sepsis continuum. This 3-hour bundle obligates initiation of a crystalloid intravenous fluid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification, rather than completion of a bolus within 3 hours. The rationale behind this approach was that any patient receiving intravenous fluid of appropriate volume administered as a bolus initiated within 30 minutes would have fluid resuscitation that not only adhered to 3-hour recommendations but also was likely completed considerably earlier.
As the primary objective, we attempt to determine the association of initiating intravenous fluid resuscitation within 30 minutes of severe sepsis or septic shock identification in the ED with inhospital mortality, controlling for demographic, acuity, and treatment factors. Secondary analysis sought to calibrate the 30-minute specification by assessing the relationship between whether intravenous fluid resuscitation initiated within 30 minutes, 31 to 60 minutes, 61 to 180 minutes, or greater than 180 minutes and in-hospital mortality in an adjusted model. In both analyses, we also attempt to determine the association of earlier intravenous fluid initiation with hospital length of stay.
Given the high incidence and mortality rate, even modest improvements in sepsis care translate to substantial absolute effect; eg, even with a conservative 25% mortality rate estimate, a mortality odds ratio (OR) of 0.75 would imply 5% absolute risk reduction and a number needed to treat of 20.1, 2 Considering this, as well as the difficulty in obtaining completion time data and the paucity of literature directly assessing fluid resuscitation and mortality in sepsis, we believe a mortality odds decrease on the order of 0.75 would support 30-minute intravenous fluid initiation as a feasible performance measure that is easier to operationalize in an ED practice environment than 3-hour intravenous fluid completion.